2024

Jump to: 2023, 2022, 2021

15 pages, 1275 KiB

Open AccessReview

Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy

by Erwen Kou, Xiaobei Zhang, Baiping Dong, Bo Wang and Yuanjie Zhu

Life 2024, 14(2), 164; https://doi.org/10.3390/life14020164 - 23 Jan 2024

Viewed by 3586

Abstract

Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for [...] Read more.

Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for numerous allergic diseases and acid-related disorders, respectively. Historically, the combination of H1 and H2 receptor antagonists has been considered a classic treatment strategy, demonstrating relatively superior efficacy compared with single-drug therapies in the treatment of diverse histamine-mediated diseases. The latest emerging studies have additionally suggested the underlying roles of histamine and H1R and H2R in the development of anxiety disorders, arthritic diseases, and postexercise hypotension. Nevertheless, there is still a lack of systematic reviews on the clinical efficacy of combination therapy, greatly limiting our understanding of its clinical application. Here, we present a comprehensive overview of the current knowledge and perspectives regarding the combination of H1 and H2 histamine receptor antagonists in various histamine-mediated disorders. Furthermore, we critically analyze the adverse effects and limitations associated with combination therapy while suggesting potential solutions. Our review can offer a systematic summary and promising insights into the in-depth and effective application of the combination of H1 and H2 receptor antagonists. Full article

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2023

Jump to: 2024, 2022, 2021

11 pages, 2316 KiB

Open AccessReview

From Dormant Collections to Repositories for the Study of Habitat Changes: The Importance of Herbaria in Modern Life Sciences

by Mauro Mandrioli

Life 2023, 13(12), 2310; https://doi.org/10.3390/life13122310 - 08 Dec 2023

Cited by 2 | Viewed by 1155

Abstract

In recent decades, the advent of new technologies for massive and automatized digitization, together with the availability of new methods for DNA sequencing, strongly increased the interest and relevance of herbarium collections for the study of plant biodiversity and evolution. These new approaches [...] Read more.

In recent decades, the advent of new technologies for massive and automatized digitization, together with the availability of new methods for DNA sequencing, strongly increased the interest and relevance of herbarium collections for the study of plant biodiversity and evolution. These new approaches prompted new projects aimed at the creation of a large dataset of molecular and phenological data. This review discusses new challenges and opportunities for herbaria in the context of the numerous national projects that are currently ongoing, prompting the study of herbarium specimens for the understanding of biodiversity loss and habitat shifts as a consequence of climate changes and habitat destruction due to human activities. With regard to this, the National Biodiversity Future Center (active in Italy since 2022) started a large-scale digitization project of the Herbarium Centrale Italicum in Florence (Italy), which is the most important Italian botanical collection, consisting of more than 4 million samples at present. Full article

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35 pages, 593 KiB

Open AccessReview

Domestic Animal Models of Central Nervous System Tumors: Focus on Meningiomas

by Michele Tomanelli, Tullio Florio, Gabriela Coronel Vargas, Aldo Pagano and Paola Modesto

Life 2023, 13(12), 2284; https://doi.org/10.3390/life13122284 - 30 Nov 2023

Viewed by 1289

Abstract

Intracranial primary tumors (IPTs) are aggressive forms of malignancies that cause high mortality in both humans and domestic animals. Meningiomas are frequent adult IPTs in humans, dogs, and cats, and both benign and malignant forms cause a decrease in life quality and survival. [...] Read more.

Intracranial primary tumors (IPTs) are aggressive forms of malignancies that cause high mortality in both humans and domestic animals. Meningiomas are frequent adult IPTs in humans, dogs, and cats, and both benign and malignant forms cause a decrease in life quality and survival. Surgery is the primary therapeutic approach to treat meningiomas, but, in many cases, it is not resolutive. The chemotherapy and targeted therapy used to treat meningiomas also display low efficacy and many side effects. Therefore, it is essential to find novel pharmacological approaches to increase the spectrum of therapeutic options for meningiomas. This review analyzes the similarities between human and domestic animal (dogs and cats) meningiomas by evaluating the molecular and histological characteristics, diagnosis criteria, and treatment options and highlighting possible research areas to identify novel targets and pharmacological approaches, which are useful for the diagnosis and therapy of this neoplasia to be used in human and veterinary medicine. Full article

18 pages, 1312 KiB

Open AccessReview

Review of Predicting Synergistic Drug Combinations

by Yichen Pan, Haotian Ren, Liang Lan, Yixue Li and Tao Huang

Life 2023, 13(9), 1878; https://doi.org/10.3390/life13091878 - 07 Sep 2023

Cited by 2 | Viewed by 2290

Abstract

The prediction of drug combinations is of great clinical significance. In many diseases, such as high blood pressure, diabetes, and stomach ulcers, the simultaneous use of two or more drugs has shown clear efficacy. It has greatly reduced the progression of drug resistance. [...] Read more.

The prediction of drug combinations is of great clinical significance. In many diseases, such as high blood pressure, diabetes, and stomach ulcers, the simultaneous use of two or more drugs has shown clear efficacy. It has greatly reduced the progression of drug resistance. This review presents the latest applications of methods for predicting the effects of drug combinations and the bioactivity databases commonly used in drug combination prediction. These studies have played a significant role in developing precision therapy. We first describe the concept of synergy. we study various publicly available databases for drug combination prediction tasks. Next, we introduce five algorithms applied to drug combinatorial prediction, which include traditional machine learning methods, deep learning methods, mathematical methods, systems biology methods and search algorithms. In the end, we sum up the difficulties encountered in prediction models. Full article

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25 pages, 1591 KiB

Open AccessReview

Regulatory miRNAs and lncRNAs in Skin Cancer: A Narrative Review

by Nicole Natarelli, Aleena Boby, Shaliz Aflatooni, Jasmine Thuy Tran, Michael Joseph Diaz, Kamil Taneja and Mahtab Forouzandeh

Life 2023, 13(8), 1696; https://doi.org/10.3390/life13081696 - 06 Aug 2023

Cited by 2 | Viewed by 1372

Abstract

Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs [...] Read more.

Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the current review with an eye toward potential therapeutic treatments. LncRNAs are remarkably adaptable, acting as scaffolding, guides, or decoys to modify key signaling pathways (i.e., the Wnt/β-catenin pathway) and gene expression. As post-transcriptional gatekeepers, miRNAs control gene expression by attaching to messenger RNAs and causing their degradation or suppression during translation. Cell cycle regulation, cellular differentiation, and immunological responses are all affected by the dysregulation of miRNAs observed in skin cancer. NcRNAs also show promise as diagnostic biomarkers and prognostic indicators. Unraveling the complexity of the regulatory networks governed by ncRNAs in skin cancer offers unprecedented opportunities for groundbreaking targeted therapies, revolutionizing the landscape of dermatologic care. Full article

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14 pages, 839 KiB

Open AccessReview

Trends on Human Norovirus Virus-like Particles (HuNoV-VLPs) and Strategies for the Construction of Infectious Viral Clones toward In Vitro Replication

by Emilly Sion, Sharaniza Ab-Rahim and Mudiana Muhamad

Life 2023, 13(7), 1447; https://doi.org/10.3390/life13071447 - 26 Jun 2023

Cited by 1 | Viewed by 1616

Abstract

Most acute gastroenteritis (AGE) outbreaks and sporadic cases in developing countries are attributable to infection by human norovirus (HuNoV), the enteric virus mainly transmitted via fecal-contaminated water. However, it has been challenging to study HuNoV due to the lack of suitable systems to [...] Read more.

Most acute gastroenteritis (AGE) outbreaks and sporadic cases in developing countries are attributable to infection by human norovirus (HuNoV), the enteric virus mainly transmitted via fecal-contaminated water. However, it has been challenging to study HuNoV due to the lack of suitable systems to cultivate and replicate the virus, hindering the development of treatments and vaccines. Researchers have been using virus-like particles (VLPs) and infectious viral clones to overcome this challenge as alternatives to fresh virus isolates in various in vitro and ex vivo models. VLPs are multiprotein structures that mimic the wild-type virus but cannot replicate in host cells due to the lack of genetic materials for replication, limiting downstream analysis of the virus life cycle and pathogenesis. The development of in vitro cloning systems has shown promise for HuNoV replication studies. This review discusses the approaches for constructing HuNoV-VLPs and infectious viral clones, the techniques involved, and the challenges faced. It also highlights the relationship between viral genes and their protein products and provides a perspective on technical considerations for producing efficient HuNoV-VLPs and infectious viral clones, which could substitute for native human noroviruses in future studies. Full article

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13 pages, 2407 KiB

Open AccessReview

Research Trends in C-Terminal Domain Nuclear Envelope Phosphatase 1

by Harikrishna Reddy Rallabandi, Haewon Choi, Hyunseung Cha and Young Jun Kim

Life 2023, 13(6), 1338; https://doi.org/10.3390/life13061338 - 07 Jun 2023

Cited by 2 | Viewed by 1194

Abstract

C-terminal domain nuclear envelope phosphatase 1 (CTDNEP1, formerly Dullard) is a member of the newly emerging protein phosphatases and has been recognized in neuronal cell tissues in amphibians. It contains the phosphatase domain in the C-terminal, and the sequences are conserved in various [...] Read more.

C-terminal domain nuclear envelope phosphatase 1 (CTDNEP1, formerly Dullard) is a member of the newly emerging protein phosphatases and has been recognized in neuronal cell tissues in amphibians. It contains the phosphatase domain in the C-terminal, and the sequences are conserved in various taxa of organisms. CTDNEP1 has several roles in novel biological activities such as neural tube development in embryos, nuclear membrane biogenesis, regulation of bone morphogenetic protein signaling, and suppression of aggressive medulloblastoma. The three-dimensional structure of CTDNEP1 and the detailed action mechanisms of CTDNEP1’s functions have yet to be determined for several reasons. Therefore, CTDNEP1 is a protein phosphatase of interest due to recent exciting and essential works. In this short review, we summarize the presented biological roles, possible substrates, interacting proteins, and research prospects of CTDNEP1. Full article

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13 pages, 2153 KiB

Open AccessReview

Tensins in Kidney Function and Diseases

by Chien-Wei Huang and Su Hao Lo

Life 2023, 13(6), 1244; https://doi.org/10.3390/life13061244 - 24 May 2023

Viewed by 1203

Abstract

Tensins are focal adhesion proteins that regulate various biological processes, such as mechanical sensing, cell adhesion, migration, invasion, and proliferation, through their multiple binding activities that transduce critical signals across the plasma membrane. When these molecular interactions and/or mediated signaling are disrupted, cellular [...] Read more.

Tensins are focal adhesion proteins that regulate various biological processes, such as mechanical sensing, cell adhesion, migration, invasion, and proliferation, through their multiple binding activities that transduce critical signals across the plasma membrane. When these molecular interactions and/or mediated signaling are disrupted, cellular activities and tissue functions are compromised, leading to disease development. Here, we focus on the significance of the tensin family in renal function and diseases. The expression pattern of each tensin in the kidney, their roles in chronic kidney diseases, renal cell carcinoma, and their potentials as prognostic markers and/or therapeutic targets are discussed in this review. Full article

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36 pages, 1080 KiB

Open AccessReview

A Comprehensive Review on Weight Loss Associated with Anti-Diabetic Medications

by Fatma Haddad, Ghadeer Dokmak, Maryam Bader and Rafik Karaman

Life 2023, 13(4), 1012; https://doi.org/10.3390/life13041012 - 14 Apr 2023

Cited by 5 | Viewed by 8188

Abstract

Obesity is a complex metabolic condition that can have a negative impact on one’s health and even result in mortality. The management of obesity has been addressed in a number of ways, including lifestyle changes, medication using appetite suppressants and thermogenics, and bariatric [...] Read more.

Obesity is a complex metabolic condition that can have a negative impact on one’s health and even result in mortality. The management of obesity has been addressed in a number of ways, including lifestyle changes, medication using appetite suppressants and thermogenics, and bariatric surgery for individuals who are severely obese. Liraglutide and semaglutide are two of the five Food and Drug Administration (FDA)-approved anti-obesity drugs that are FDA-approved agents for the treatment of type 2 diabetes mellitus (T2DM) patients. In order to highlight the positive effects of these drugs as anti-obesity treatments, we analyzed the weight loss effects of T2DM agents that have demonstrated weight loss effects in this study by evaluating clinical studies that were published for each agent. Many clinical studies have revealed that some antihyperglycemic medications can help people lose weight, while others either cause weight gain or neutral results. Acarbose has mild weight loss effects and metformin and sodium-dependent glucose cotransporter proteins-2 (SGLT-2) inhibitors have modest weight loss effects; however, some glucagon-like peptide-1 (GLP-1) receptor agonists had the greatest impact on weight loss. Dipeptidyl peptidase 4 (DPP-4) inhibitors showed a neutral or mild weight loss effect. To sum up, some of the GLP-1 agonist drugs show promise as weight-loss treatments. Full article

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18 pages, 2024 KiB

Open AccessReview

Current Views on Infective Endocarditis: Changing Epidemiology, Improving Diagnostic Tools and Centering the Patient for Up-to-Date Management

by Giovanni Cimmino, Roberta Bottino, Tiziana Formisano, Massimiliano Orlandi, Daniele Molinari, Simona Sperlongano, Pasquale Castaldo, Saverio D’Elia, Andreina Carbone, Alberto Palladino, Lavinia Forte, Francesco Coppolino, Michele Torella and Nicola Coppola

Life 2023, 13(2), 377; https://doi.org/10.3390/life13020377 - 30 Jan 2023

Cited by 8 | Viewed by 6461

Abstract

Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number [...] Read more.

Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number of intravascular and intracardiac procedures associated with device implantation, the number of patients at risk is growing too. If bacteremia develops, infected vegetation on the native/prosthetic valve or any intracardiac/intravascular device may occur as the final result of invading microorganisms/host immune system interaction. In the case of IE suspicion, all efforts must be focused on the diagnosis as IE can spread to almost any organ in the body. Unfortunately, the diagnosis of IE might be difficult and require a combination of clinical examination, microbiological assessment and echocardiographic evaluation. There is a need of novel microbiological and imaging techniques, especially in cases of blood culture-negative. In the last few years, the management of IE has changed. A multidisciplinary care team, including experts in infectious diseases, cardiology and cardiac surgery, namely, the Endocarditis Team, is highly recommended by the current guidelines. Full article

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22 pages, 691 KiB

Open AccessReview

A Synopsis of Current Theories on Drug-Induced Nephrotoxicity

by Lukasz Dobrek

Life 2023, 13(2), 325; https://doi.org/10.3390/life13020325 - 24 Jan 2023

Cited by 6 | Viewed by 5627

Abstract

The overriding goal of the treatment of patients is its effectiveness and safety. However, all medications currently being used also exert some adverse pharmaceutical reactions, which may be regarded as an unintended but inevitable cost of pharmacotherapy. The kidney, as the main organ [...] Read more.

The overriding goal of the treatment of patients is its effectiveness and safety. However, all medications currently being used also exert some adverse pharmaceutical reactions, which may be regarded as an unintended but inevitable cost of pharmacotherapy. The kidney, as the main organ that eliminates xenobiotics, is an organ especially predisposed and vulnerable to the toxic effects of drugs and their metabolites during their excretion from the body. Moreover, some drugs (e.g., aminoglycosides, cyclosporin A, cisplatin, amphotericin B, and others) have a “preferential” nephrotoxicity potential, and their use is associated with an increased risk of kidney damage. Drug nephrotoxicity is, therefore, both a significant problem and a complication of pharmacotherapy. It should be noted that, currently, there is no generally recognized definition of drug-induced nephrotoxicity and no clear criteria for its diagnosis. This review briefly describes the epidemiology and diagnosis of drug-induced nephrotoxicity and characterizes its pathomechanisms, including immunological and inflammatory disturbances, altered kidney blood flow, tubulointerstitial injury, increased lithogenesis–crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. The study also lists the basic drugs with nephrotoxicity potential and provides a short overview of the preventive methods for reducing the risk of drug-related kidney damage developing. Full article

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2022

Jump to: 2024, 2023, 2021

10 pages, 230 KiB

Open AccessReview

Infectious Risks Related to Umbilical Venous Catheter Dwell Time and Its Replacement in Newborns: A Narrative Review of Current Evidence

by Lucia Corso, Martina Buttera, Francesco Candia, Francesca Sforza, Katia Rossi, Licia Lugli, Francesca Miselli, Luca Bedetti, Cecilia Baraldi, Laura Lucaccioni, Lorenzo Iughetti and Alberto Berardi

Life 2023, 13(1), 123; https://doi.org/10.3390/life13010123 - 31 Dec 2022

Cited by 3 | Viewed by 2392

Abstract

The use of umbilical venous catheters (UVCs) has become the standard of care in the neonatal intensive care unit (NICU) to administer fluids, medications and parenteral nutrition. However, it is well known that UVCs can lead to some serious complications, both mechanical and [...] Read more.

The use of umbilical venous catheters (UVCs) has become the standard of care in the neonatal intensive care unit (NICU) to administer fluids, medications and parenteral nutrition. However, it is well known that UVCs can lead to some serious complications, both mechanical and infective, including CLABSI (Central Line-Associated Bloodstream Infections). Most authors recommend removing UVC within a maximum of 14 days from its placement. However, the last Infusion Therapy Standards of Practice (INS) guidelines recommends limiting the UVC dwell time to 7 to 10 days, to reduce risks of infectious and thrombotic complications. These guidelines also suggest as an infection prevention strategy to remove UVC after 4 days, followed by the insertion of a PICC if a central line is still needed. Nevertheless, the maximum UVC dwell time to reduce the risk of CLABSI is still controversial, as well as the time of its replacement with a PICC. In this study we reviewed a total of 177 articles, found by using the PubMed database with the following search strings: “UVC AND neonates”, “(neonate* OR newborn*) AND (UVC OR central catheter*) AND (infection*)”. We also analyze the INS guidelines to provide the reader an updated overview on this topic. The purpose of this review is to give updated information on CVCs infectious risks by examining the literature in this field. These data could help clinicians in deciding the best time to remove or to replace the UVC with a PICC, to reduce CLABSIs risk. Despite the lack of strong evidence, the risk of CLABSI seems to be minimized when UVC is removed/replaced within 7 days from insertion and this indication is emerging from more recent and larger studies. Full article

22 pages, 3371 KiB

Open AccessReview

Application of Nanoparticles: Diagnosis, Therapeutics, and Delivery of Insulin/Anti-Diabetic Drugs to Enhance the Therapeutic Efficacy of Diabetes Mellitus

by Tilahun Ayane Debele and Yoonjee Park

Life 2022, 12(12), 2078; https://doi.org/10.3390/life12122078 - 11 Dec 2022

Cited by 5 | Viewed by 3796

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder of carbohydrates, lipids, and proteins due to a deficiency of insulin secretion or failure to respond to insulin secreted from pancreatic cells, which leads to high blood glucose levels. DM is one of the top [...] Read more.

Diabetes mellitus (DM) is a chronic metabolic disorder of carbohydrates, lipids, and proteins due to a deficiency of insulin secretion or failure to respond to insulin secreted from pancreatic cells, which leads to high blood glucose levels. DM is one of the top four noncommunicable diseases and causes of death worldwide. Even though great achievements were made in the management and treatment of DM, there are still certain limitations, mainly related to the early diagnosis, and lack of appropriate delivery of insulin and other anti-diabetic agents. Nanotechnology is an emerging field in the area of nanomedicine and NP based anti-diabetic agent delivery is reported to enhance efficacy by increasing bioavailability and target site accumulation. Moreover, theranostic NPs can be used as diagnostic tools for the early detection and prevention of diseases owing to their unique biological, physiochemical, and magnetic properties. NPs have been synthesized from a variety of organic and inorganic materials including polysaccharides, dendrimers, proteins, lipids, DNA, carbon nanotubes, quantum dots, and mesoporous materials within the nanoscale size. This review focuses on the role of NPs, derived from organic and inorganic materials, in the diagnosis and treatment of DM. Full article

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12 pages, 263 KiB

Open AccessReview

Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue—A Scoping Review

by Yohama Caraballo-Arias, Carlotta Zunarelli, Paola Caffaro, Francesco Roccuzzo, Mattia Roberto Nocilla, Maria Chiara Imperiale, Clara Romano, Paolo Boffetta and Francesco Saverio Violante

Life 2022, 12(12), 1969; https://doi.org/10.3390/life12121969 - 24 Nov 2022

Cited by 2 | Viewed by 1459

Abstract

Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both [...] Read more.

Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both in neoplastic and non-neoplastic tissue. The 9 studies selected comprised 62 cases, out of whom 100 samples were analyzed. Asbestos fibers were detected in 58 samples (58%). In addition, 28 cases had diagnosis of peritoneal mesothelioma. For 32 cases, a lung tumor sample was available: 28/32 samples analyzed presented asbestos fibers; 18/32 reported amphiboles with a range from not detected to 14.2 million fibers per gram of dry tissue (mfgdt); 18/32 reported chrysotile, with a range of 0 to 90 mfgdt. The studies were heterogeneous for type of samples, analytical technology, and circumstances of exposure to asbestos. To evaluate asbestos fibers in the peritoneum and to better understand the association between asbestos exposure and malignant peritoneal mesothelioma, it is desirable that the search for asbestos fibers becomes a routine process every time peritoneal tissue is accessible. Full article

11 pages, 1144 KiB

Open AccessReview

Effectiveness of CPR in Hypogravity Conditions—A Systematic Review

by Remco Overbeek, Jan Schmitz, Lucas Rehnberg, Yacine Benyoucef, Fabian Dusse, Thais Russomano and Jochen Hinkelbein

Life 2022, 12(12), 1958; https://doi.org/10.3390/life12121958 - 23 Nov 2022

Cited by 1 | Viewed by 1775

Abstract

(1) Background: Cardiopulmonary resuscitation (CPR), as a form of basic life support, is critical for maintaining cardiac and cerebral perfusion during cardiac arrest, a medical condition with high expected mortality. Current guidelines emphasize the importance of rapid recognition and prompt initiation of high-quality [...] Read more.

(1) Background: Cardiopulmonary resuscitation (CPR), as a form of basic life support, is critical for maintaining cardiac and cerebral perfusion during cardiac arrest, a medical condition with high expected mortality. Current guidelines emphasize the importance of rapid recognition and prompt initiation of high-quality CPR, including appropriate cardiac compression depth and rate. As space agencies plan missions to the Moon or even to explore Mars, the duration of missions will increase and with it the chance of life-threatening conditions requiring CPR. The objective of this review was to examine the effectiveness and feasibility of chest compressions as part of CPR following current terrestrial guidelines under hypogravity conditions such as those encountered on planetary or lunar surfaces; (2) Methods: A systematic literature search was conducted by two independent reviewers (PubMed, Cochrane Register of Controlled Trials, ResearchGate, National Aeronautics and Space Administration (NASA)). Only controlled trials conducting CPR following guidelines from 2010 and after with advised compression depths of 50 mm and above were included; (3) Results: Four different publications were identified. All studies examined CPR feasibility in 0.38 G simulating the gravitational force on Mars. Two studies also simulated hypogravity on the Moon with a force of 0.17 G/0,16 G. All CPR protocols consisted of chest compressions only without ventilation. A compression rate above 100/s could be maintained in all studies and hypogravity conditions. Two studies showed a significant reduction of compression depth in 0.38 G (−7.2 mm/−8.71 mm) and 0.17 G (−12.6 mm/−9.85 mm), respectively, with nearly similar heart rates, compared to 1 G conditions. In the other two studies, participants with higher body weight could maintain a nearly adequate mean depth while effort measured by heart rate (+23/+13.85 bpm) and VO_2max (+5.4 mL·kg⁻¹·min⁻¹) increased significantly; (4) Conclusions: Adequate CPR quality in hypogravity can only be achieved under increased physical stress to compensate for functional weight loss. Without this extra effort, the depth of compression quickly falls below the guideline level, especially for light-weight rescuers. This means faster fatigue during resuscitation and the need for more frequent changes of the resuscitator than advised in terrestrial guidelines. Alternative techniques in the straddling position should be further investigated in hypogravity. Full article

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28 pages, 1657 KiB

Open AccessReview

The Innovative Informatics Approaches of High-Throughput Technologies in Livestock: Spearheading the Sustainability and Resiliency of Agrigenomics Research

by Godagama Gamaarachchige Dinesh Suminda, Mrinmoy Ghosh and Young-Ok Son

Life 2022, 12(11), 1893; https://doi.org/10.3390/life12111893 - 15 Nov 2022

Cited by 1 | Viewed by 2526

Abstract

For more than a decade, next-generation sequencing (NGS) has been emerging as the mainstay of agrigenomics research. High-throughput technologies have made it feasible to facilitate research at the scale and cost required for using this data in livestock research. Scale frameworks of sequencing [...] Read more.

For more than a decade, next-generation sequencing (NGS) has been emerging as the mainstay of agrigenomics research. High-throughput technologies have made it feasible to facilitate research at the scale and cost required for using this data in livestock research. Scale frameworks of sequencing for agricultural and livestock improvement, management, and conservation are partly attributable to innovative informatics methodologies and advancements in sequencing practices. Genome-wide sequence-based investigations are often conducted worldwide, and several databases have been created to discover the connections between worldwide scientific accomplishments. Such studies are beginning to provide revolutionary insights into a new era of genomic prediction and selection capabilities of various domesticated livestock species. In this concise review, we provide selected examples of the current state of sequencing methods, many of which are already being used in animal genomic studies, and summarize the state of the positive attributes of genome-based research for cattle (Bos taurus), sheep (Ovis aries), pigs (Sus scrofa domesticus), horses (Equus caballus), chickens (Gallus gallus domesticus), and ducks (Anas platyrhyncos). This review also emphasizes the advantageous features of sequencing technologies in monitoring and detecting infectious zoonotic diseases. In the coming years, the continued advancement of sequencing technologies in livestock agrigenomics will significantly influence the sustained momentum toward regulatory approaches that encourage innovation to ensure continued access to a safe, abundant, and affordable food supplies for future generations. Full article

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21 pages, 2398 KiB

Open AccessReview

M. tuberculosis Transcription Machinery: A Review on the Mycobacterial RNA Polymerase and Drug Discovery Efforts

by Filia Stephanie, Usman Sumo Friend Tambunan and Teruna J. Siahaan

Life 2022, 12(11), 1774; https://doi.org/10.3390/life12111774 - 03 Nov 2022

Cited by 6 | Viewed by 3636

Abstract

Mycobacterium tuberculosis (MTB) is the main source of tuberculosis (TB), one of the oldest known diseases in the human population. Despite the drug discovery efforts of past decades, TB is still one of the leading causes of mortality and claimed more than 1.5 [...] Read more.

Mycobacterium tuberculosis (MTB) is the main source of tuberculosis (TB), one of the oldest known diseases in the human population. Despite the drug discovery efforts of past decades, TB is still one of the leading causes of mortality and claimed more than 1.5 million lives worldwide in 2020. Due to the emergence of drug-resistant strains and patient non-compliance during treatments, there is a pressing need to find alternative therapeutic agents for TB. One of the important areas for developing new treatments is in the inhibition of the transcription step of gene expression; it is the first step to synthesize a copy of the genetic material in the form of mRNA. This further translates to functional protein synthesis, which is crucial for the bacteria living processes. MTB contains a bacterial DNA-dependent RNA polymerase (RNAP), which is the key enzyme for the transcription process. MTB RNAP has been targeted for designing and developing antitubercular agents because gene transcription is essential for the mycobacteria survival. Initiation, elongation, and termination are the three important sequential steps in the transcription process. Each step is complex and highly regulated, involving multiple transcription factors. This review is focused on the MTB transcription machinery, especially in the nature of MTB RNAP as the main enzyme that is regulated by transcription factors. The mechanism and conformational dynamics that occur during transcription are discussed and summarized. Finally, the current progress on MTB transcription inhibition and possible drug target in mycobacterial RNAP are also described to provide insight for future antitubercular drug design and development. Full article

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36 pages, 1059 KiB

Open AccessReview

A Comprehensive Review on the Efficacy of Several Pharmacologic Agents for the Treatment of COVID-19

by Fatma Haddad, Ghadeer Dokmak and Rafik Karaman

Life 2022, 12(11), 1758; https://doi.org/10.3390/life12111758 - 01 Nov 2022

Cited by 8 | Viewed by 3647

Abstract

SARS-CoV-2, the coronavirus disease-2019 (COVID-19), and the cause of the pandemic is extremely contagious among people and has spread around the world. Antivirals, immunomodulators, and other medications, such as antibiotics, stem cells, and plasma therapy, have all been utilized in the treatment of [...] Read more.

SARS-CoV-2, the coronavirus disease-2019 (COVID-19), and the cause of the pandemic is extremely contagious among people and has spread around the world. Antivirals, immunomodulators, and other medications, such as antibiotics, stem cells, and plasma therapy, have all been utilized in the treatment of COVID-19. To better understand the clinical efficacy of these agents and to aid in the selection of effective COVID-19 therapies in various countries, this study reviewed the effectiveness of the various pharmacologic agents that have been used for COVID-19 therapy globally by summarizing the clinical outcomes that have been obtained from the clinical trials published on each drug related to COVID-19 infection. The Food and Drug Administration (FDA) has authorized the use of remdesivir, paxlovid, molnupiravir, baricitinib, tixagevimab–cilgavimab, and bebtelovimab for the management of COVID-19. On the other hand, most research advises against using chloroquine and hydroxychloroquine to treat COVID-19 patients because they are not beneficial. Although the FDA has given emergency use authorization for some monoclonal antibodies, including bamlanivimab, etesevimab, casirivimab, and imdevimab for managing COVID-19, they are not currently approved for use because the Omicron variant has significantly reduced their in vitro susceptibility. In this study, we also included a wide range of alternative therapy strategies that effectively treat COVID-19 patients, although further randomized studies are necessary to support and assess their applicability. Full article

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17 pages, 1360 KiB

Open AccessReview

Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Wound Healing

by Arulkumar Nallakumarasamy, Madhan Jeyaraman, Nicola Maffulli, Naveen Jeyaraman, Veerasivabalan Suresh, Srinath Ravichandran, Manu Gupta, Anish G. Potty, Saadiq F. El-Amin III, Manish Khanna and Ashim Gupta

Life 2022, 12(11), 1733; https://doi.org/10.3390/life12111733 - 28 Oct 2022

Cited by 8 | Viewed by 2728

Abstract

The well-orchestrated process of wound healing may be negatively impacted from interrupted or incomplete tissue regenerative processes. The healing potential is further compromised in patients with diabetes mellitus, chronic venous insufficiency, critical limb ischemia, and immunocompromised conditions, with a high health care burden [...] Read more.

The well-orchestrated process of wound healing may be negatively impacted from interrupted or incomplete tissue regenerative processes. The healing potential is further compromised in patients with diabetes mellitus, chronic venous insufficiency, critical limb ischemia, and immunocompromised conditions, with a high health care burden and expenditure. Stem cell-based therapy has shown promising results in clinical studies. Mesenchymal stem cell-derived exosomes (MSC Exos) may favorably impact intercellular signaling and immunomodulation, promoting neoangiogenesis, collagen synthesis, and neoepithelization. This article gives an outline of the biogenesis and mechanism of extracellular vesicles (EVs), particularly exosomes, in the process of tissue regeneration and discusses the use of preconditioned exosomes, platelet-rich plasma-derived exosomes, and engineered exosomes in three-dimensional bioscaffolds such as hydrogels (collagen and chitosan) to prolong the contact time of exosomes at the recipient site within the target tissue. An appropriate antibiotic therapy based on culture-specific guidance coupled with the knowledge of biopolymers helps to fabricate nanotherapeutic materials loaded with MSC Exos to effectively deliver drugs locally and promote novel approaches for the management of chronic wounds. Full article

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19 pages, 2589 KiB

Open AccessReview

Single Cell in a Gravity Field

by Irina V. Ogneva

Life 2022, 12(10), 1601; https://doi.org/10.3390/life12101601 - 14 Oct 2022

Cited by 5 | Viewed by 1898

Abstract

The exploration of deep space or other bodies of the solar system, associated with a long stay in microgravity or altered gravity, requires the development of fundamentally new methods of protecting the human body. Most of the negative changes in micro- or hypergravity [...] Read more.

The exploration of deep space or other bodies of the solar system, associated with a long stay in microgravity or altered gravity, requires the development of fundamentally new methods of protecting the human body. Most of the negative changes in micro- or hypergravity occur at the cellular level; however, the mechanism of reception of the altered gravity and transduction of this signal, leading to the formation of an adaptive pattern of the cell, is still poorly understood. At the same time, most of the negative changes that occur in early embryos when the force of gravity changes almost disappear by the time the new organism is born. This review is devoted to the responses of early embryos and stem cells, as well as terminally differentiated germ cells, to changes in gravity. An attempt was made to generalize the data presented in the literature and propose a possible unified mechanism for the reception by a single cell of an increase and decrease in gravity based on various deformations of the cortical cytoskeleton. Full article

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21 pages, 991 KiB

Open AccessSystematic Review

Phosphatidylethanol in Maternal or Neonatal Blood to Detect Alcohol Exposure during Pregnancy: A Systematic Review

by Lisa Franceschetto, Matteo Perilli, Alessandro Cinquetti, Chiara Giraudo, Mario Gardi, Giovanni Cecchetto and Guido Viel

Life 2022, 12(10), 1528; https://doi.org/10.3390/life12101528 - 30 Sep 2022

Cited by 1 | Viewed by 1764

Abstract

Background: Alcohol consumption during pregnancy, even at low doses, may damage the fetus. Pregnant women tend to underreport their alcohol consumption generating the need for sensitive and specific biomarkers, among which PEth has emerged due to its high specificity and possibility to be [...] Read more.

Background: Alcohol consumption during pregnancy, even at low doses, may damage the fetus. Pregnant women tend to underreport their alcohol consumption generating the need for sensitive and specific biomarkers, among which PEth has emerged due to its high specificity and possibility to be measured in both maternal and neonatal blood. The aim of this study is to systematically review the latest 20 years of literature for depicting the state of the art, the limitations, and the prospects of PEth for estimating alcohol consumption during pregnancy. Materials and methods: A systematic search, adhering to PRISMA guidelines, of the latest 20 years of literature through “MeSH” and “free-text” protocols in the databases PubMed, SCOPUS, and Web of Science, with time limits 1 January 2002–1 March 2022, was performed. The inclusion criteria were as follows: PEth used for detecting alcohol consumption during pregnancy, quantified in blood through liquid chromatography coupled to mass spectrometry, and full texts in the English language. Opinion papers, editorials, and narrative reviews were excluded. Results: Sixteen (16) papers were included in the present review (0.81% of total retrieved records). All the included records were original articles, of which there were seven prospective cohort/longitudinal studies, six cross-sectional studies, two observational-descriptive studies, and one retrospective study. All studies assayed PEth in at least one biological matrix; seven (7) studies quantified PEth in maternal blood, seven studies in newborn blood, and only two studies in both maternal and neonatal blood. In several included papers, PEth proved more sensitive than self-reports for identifying pregnant women with an active alcohol intake with the diagnostic efficiency improving with the increase of the maternal alcohol intake. Conclusions: Further studies, performed on wider and well-stratified populations, are needed to drive any definitive conclusion. PEth is a promising marker for monitoring alcohol use in pregnancy; however, at the present time, its use is still limited mainly by the absence of a globally agreed interpretative cut-off, the paucity of data regarding its specificity/sensitivity, and the lack of standardization on the diagnostic efficiency of the different isoforms. Full article

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18 pages, 2124 KiB

Open AccessReview

Recent Advances in the Study of Gas Vesicle Proteins and Application of Gas Vesicles in Biomedical Research

by Felicitas Pfeifer

Life 2022, 12(9), 1455; https://doi.org/10.3390/life12091455 - 19 Sep 2022

Cited by 8 | Viewed by 3132

Abstract

The formation of gas vesicles has been investigated in bacteria and haloarchaea for more than 50 years. These air-filled nanostructures allow cells to stay at a certain height optimal for growth in their watery environment. Several gvp genes are involved and have been [...] Read more.

The formation of gas vesicles has been investigated in bacteria and haloarchaea for more than 50 years. These air-filled nanostructures allow cells to stay at a certain height optimal for growth in their watery environment. Several gvp genes are involved and have been studied in Halobacterium salinarum, cyanobacteria, Bacillus megaterium, and Serratia sp. ATCC39006 in more detail. GvpA and GvpC form the gas vesicle shell, and additional Gvp are required as minor structural proteins, chaperones, an ATP-hydrolyzing enzyme, or as gene regulators. We analyzed the Gvp proteins of Hbt. salinarum with respect to their protein–protein interactions, and developed a model for the formation of these nanostructures. Gas vesicles are also used in biomedical research. Since they scatter waves and produce ultrasound contrast, they could serve as novel contrast agent for ultrasound or magnetic resonance imaging. Additionally, gas vesicles were engineered as acoustic biosensors to determine enzyme activities in cells. These applications are based on modifications of the surface protein GvpC that alter the mechanical properties of the gas vesicles. In addition, gas vesicles have been decorated with GvpC proteins fused to peptides of bacterial or viral pathogens and are used as tools for vaccine development. Full article

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15 pages, 687 KiB

Open AccessReview

Characteristic Sleep Patterns and Associated Obesity in Adolescents

by Ahreum Kwon, Youngha Choi, Sujin Kim, Kyungchul Song, Junghwan Suh, Hyun Wook Chae and Ho-Seong Kim

Life 2022, 12(9), 1316; https://doi.org/10.3390/life12091316 - 26 Aug 2022

Cited by 1 | Viewed by 2367

Abstract

Poor sleep adversely affects health and may cause obesity. Poor sleep includes short sleep duration, low quality of sleep, and sleep discrepancy. Although most studies have focused on the association between sleep duration and obesity, poor sleep is a significant risk factor for [...] Read more.

Poor sleep adversely affects health and may cause obesity. Poor sleep includes short sleep duration, low quality of sleep, and sleep discrepancy. Although most studies have focused on the association between sleep duration and obesity, poor sleep is a significant risk factor for obesity. Adolescents have characteristic sleep patterns which correspond to poor sleep. Adolescents sleep late due to various biological and psychosocial factors; also, they wake up early to be on time for school. This causes them to sleep less. To make up for this sleep debt, adolescents sleep more on non-school days, which causes sleep discrepancies. Therefore, since adolescents have characteristic sleep patterns, an in-depth investigation is needed to identify whether poor sleep is a risk for obesity. This article presents an overview of the characteristic sleep patterns of adolescents, and reviews studies on the association of each sleep pattern with obesity. Full article

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18 pages, 4655 KiB

Open AccessReview

A Comprehensive Review on the Anti-Cancer Effects of Oleuropein

by Sabreen Rishmawi, Fatma Haddad, Ghadeer Dokmak and Rafik Karaman

Life 2022, 12(8), 1140; https://doi.org/10.3390/life12081140 - 28 Jul 2022

Cited by 20 | Viewed by 3064

Abstract

In Mediterranean cuisine and culture, olive oil and olive fruits play a significant role. Many people believe that those who consume olive oil and its fruit live longer and have a decreased risk of illness. Olive leaves were used to treat a range [...] Read more.

In Mediterranean cuisine and culture, olive oil and olive fruits play a significant role. Many people believe that those who consume olive oil and its fruit live longer and have a decreased risk of illness. Olive leaves were used to treat a range of diseases in ancient times, including malaria fever and lower earaches. Although it was not understood at the time what key components were responsible for these effects because they had not yet been discovered, Oleuropein is now recognized as one of the primary elements in immature olive fruits and leaves. Later research was carried out to determine the effects of this molecule, and it was determined that it functions as an antioxidant. Oleuropein consumption has aided in cancer treatment over the years, and this was assumed to be owing to its antioxidant properties. Oleuropein’s effects on cancer, however, go beyond that; it is now known that Oleuropein functions as both an anti-proliferative and an apoptotic promoter in many cancer cells. The kinetics and dosages of Oleuropein and the mechanisms behind its involvement and effects in cancer are explored in this review. Finally, the effects of Oleuropein in combination with anticancer medicines are investigated. Full article

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54 pages, 11826 KiB

Open AccessReview

The Coevolution of Biomolecules and Prebiotic Information Systems in the Origin of Life: A Visualization Model for Assembling the First Gene

by Sankar Chatterjee and Surya Yadav

Life 2022, 12(6), 834; https://doi.org/10.3390/life12060834 - 02 Jun 2022

Cited by 3 | Viewed by 4517

Abstract

Prebiotic information systems exist in three forms: analog, hybrid, and digital. The Analog Information System (AIS), manifested early in abiogenesis, was expressed in the chiral selection, nucleotide formation, self-assembly, polymerization, encapsulation of polymers, and division of protocells. It created noncoding RNAs by polymerizing [...] Read more.

Prebiotic information systems exist in three forms: analog, hybrid, and digital. The Analog Information System (AIS), manifested early in abiogenesis, was expressed in the chiral selection, nucleotide formation, self-assembly, polymerization, encapsulation of polymers, and division of protocells. It created noncoding RNAs by polymerizing nucleotides that gave rise to the Hybrid Information System (HIS). The HIS employed different species of noncoding RNAs, such as ribozymes, pre-tRNA and tRNA, ribosomes, and functional enzymes, including bridge peptides, pre-aaRS, and aaRS (aminoacyl-tRNA synthetase). Some of these hybrid components build the translation machinery step-by-step. The HIS ushered in the Digital Information System (DIS), where tRNA molecules become molecular architects for designing mRNAs step-by-step, employing their two distinct genetic codes. First, they created codons of mRNA by the base pair interaction (anticodon–codon mapping). Secondly, each charged tRNA transferred its amino acid information to the corresponding codon (codon–amino acid mapping), facilitated by an aaRS enzyme. With the advent of encoded mRNA molecules, the first genes emerged before DNA. With the genetic memory residing in the digital sequences of mRNA, a mapping mechanism was developed between each codon and its cognate amino acid. As more and more codons ‘remembered’ their respective amino acids, this mapping system developed the genetic code in their memory bank. We compared three kinds of biological information systems with similar types of human-made computer systems. Full article

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1 pages, 156 KiB

Open AccessCorrection

Correction: Hansma, H.G. Potassium at the Origins of Life: Did Biology Emerge from Biotite in Micaceous Clay? Life 2022, 12, 301

by Helen Greenwood Hansma

Life 2022, 12(5), 744; https://doi.org/10.3390/life12050744 - 17 May 2022

Cited by 3 | Viewed by 1034

Abstract

The author wishes to make the following correction to this paper [...] Full article

10 pages, 967 KiB

Open AccessReview

Point on the Aortic Bicuspid Valve

by Chloé Bernard, Marie Catherine Morgant, David Guillier, Nicolas Cheynel and Olivier Bouchot

Life 2022, 12(4), 518; https://doi.org/10.3390/life12040518 - 31 Mar 2022

Cited by 3 | Viewed by 2549

Abstract

Background—Bicuspid aortic valve (BAV) disease is the most prevalent congenital heart disease in the world. Knowledge about its subtypes origin, development, and evolution is poor despite the frequency and the potential gravity of this condition. Its prognosis mostly depends on the risk of [...] Read more.

Background—Bicuspid aortic valve (BAV) disease is the most prevalent congenital heart disease in the world. Knowledge about its subtypes origin, development, and evolution is poor despite the frequency and the potential gravity of this condition. Its prognosis mostly depends on the risk of aortic aneurysm development with an increased risk of aortic dissection. Aims—This review aims to describe this complex pathology in way to improve the bicuspid patients’ management. Study design—We reviewed the literature with MEDLINE and EMBASE databases using MeSH terms such as “bicuspid aortic valve”, “ascending aorta”, and “bicuspid classification”. Results—There are various classifications. They depend on the criteria chosen by the authors to differentiate subtypes. Those criteria can be the number and position of the raphes, the cusps, the commissures, or their arrangements regarding coronary ostia. Sievers’ classification is the reference. The phenotypic description of embryology revealed that all subtypes of BAV are the results of different embryological pathogenesis, and therefore, should be considered as distinct conditions. Their common development towards aortic dilatation is explained by the aortic media’s pathological histology with cystic medial necrosis. At the opposite, BAV seems to display a profound genetic heterogeneity with both sporadic and familial forms. BAV can be even isolated or combined with other congenital malformations. Conclusions—All those characteristics make this pathology a highly complex condition that needs further genetic, embryological, and hemodynamic explorations to complete its well described anatomy. Full article

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15 pages, 3746 KiB

Open AccessReview

Shining Light on Protein Kinase Biomarkers with Fluorescent Peptide Biosensors

by May C. Morris

Life 2022, 12(4), 516; https://doi.org/10.3390/life12040516 - 31 Mar 2022

Cited by 1 | Viewed by 2234

Abstract

Protein kinases (PKs) are established gameplayers in biological signalling pathways, and a large body of evidence points to their dysregulation in diseases, in particular cancer, where rewiring of PK networks occurs frequently. Fluorescent biosensors constitute attractive tools for probing biomolecules and monitoring dynamic [...] Read more.

Protein kinases (PKs) are established gameplayers in biological signalling pathways, and a large body of evidence points to their dysregulation in diseases, in particular cancer, where rewiring of PK networks occurs frequently. Fluorescent biosensors constitute attractive tools for probing biomolecules and monitoring dynamic processes in complex samples. A wide variety of genetically encoded and synthetic biosensors have been tailored to report on PK activities over the last decade, enabling interrogation of their function and insight into their behaviour in physiopathological settings. These optical tools can further be used to highlight enzymatic alterations associated with the disease, thereby providing precious functional information which cannot be obtained through conventional genetic, transcriptomic or proteomic approaches. This review focuses on fluorescent peptide biosensors, recent developments and strategies that make them attractive tools to profile PK activities for biomedical and diagnostic purposes, as well as insights into the challenges and opportunities brought by this unique toolbox of chemical probes. Full article

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24 pages, 6644 KiB

Open AccessReview

Next-Generation Molecular Discovery: From Bottom-Up In Vivo and In Vitro Approaches to In Silico Top-Down Approaches for Therapeutics Neogenesis

by Sophie E. Kenny, Fiach Antaw, Warwick J. Locke, Christopher B. Howard, Darren Korbie and Matt Trau

Life 2022, 12(3), 363; https://doi.org/10.3390/life12030363 - 02 Mar 2022

Cited by 1 | Viewed by 2935

Abstract

Protein and drug engineering comprises a major part of the medical and research industries, and yet approaches to discovering and understanding therapeutic molecular interactions in biological systems rely on trial and error. The general approach to molecular discovery involves screening large libraries of [...] Read more.

Protein and drug engineering comprises a major part of the medical and research industries, and yet approaches to discovering and understanding therapeutic molecular interactions in biological systems rely on trial and error. The general approach to molecular discovery involves screening large libraries of compounds, proteins, or antibodies, or in vivo antibody generation, which could be considered “bottom-up” approaches to therapeutic discovery. In these bottom-up approaches, a minimal amount is known about the therapeutics at the start of the process, but through meticulous and exhaustive laboratory work, the molecule is characterised in detail. In contrast, the advent of “big data” and access to extensive online databases and machine learning technologies offers promising new avenues to understanding molecular interactions. Artificial intelligence (AI) now has the potential to predict protein structure at an unprecedented accuracy using only the genetic sequence. This predictive approach to characterising molecular structure—when accompanied by high-quality experimental data for model training—has the capacity to invert the process of molecular discovery and characterisation. The process has potential to be transformed into a top-down approach, where new molecules can be designed directly based on the structure of a target and the desired function, rather than performing screening of large libraries of molecular variants. This paper will provide a brief evaluation of bottom-up approaches to discovering and characterising biological molecules and will discuss recent advances towards developing top-down approaches and the prospects of this. Full article

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18 pages, 3384 KiB

Open AccessHypothesis

Potassium at the Origins of Life: Did Biology Emerge from Biotite in Micaceous Clay?

by Helen Greenwood Hansma

Life 2022, 12(2), 301; https://doi.org/10.3390/life12020301 - 17 Feb 2022

Cited by 10 | Viewed by 3605 | Correction

Abstract

Intracellular potassium concentrations, [K⁺], are high in all types of living cells, but the origins of this K⁺ are unknown. The simplest hypothesis is that life emerged in an environment that was high in K⁺. One such environment [...] Read more.

Intracellular potassium concentrations, [K⁺], are high in all types of living cells, but the origins of this K⁺ are unknown. The simplest hypothesis is that life emerged in an environment that was high in K⁺. One such environment is the spaces between the sheets of the clay mineral mica. The best mica for life’s origins is the black mica, biotite, because it has a high content of Mg⁺⁺ and because it has iron in various oxidation states. Life also has many of the characteristics of the environment between mica sheets, giving further support for the possibility that mica was the substrate on and within which life emerged. Here, a scenario for life’s origins is presented, in which the necessary processes and components for life arise in niches between mica sheets; vesicle membranes encapsulate these processes and components; the resulting vesicles fuse, forming protocells; and eventually, all of the necessary components and processes are encapsulated within individual cells, some of which survive to seed the early Earth with life. This paper presents three new foci for the hypothesis of life’s origins between mica sheets: (1) that potassium is essential for life’s origins on Earth; (2) that biotite mica has advantages over muscovite mica; and (3) that micaceous clay is a better environment than isolated mica for life’s origins. Full article

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16 pages, 795 KiB

Open AccessReview

Of Cockroaches and Symbionts: Recent Advances in the Characterization of the Relationship between Blattella germanica and Its Dual Symbiotic System

by Amparo Latorre, Rebeca Domínguez-Santos, Carlos García-Ferris and Rosario Gil

Life 2022, 12(2), 290; https://doi.org/10.3390/life12020290 - 15 Feb 2022

Cited by 5 | Viewed by 3852

Abstract

Mutualistic stable symbioses are widespread in all groups of eukaryotes, especially in insects, where symbionts have played an essential role in their evolution. Many insects live in obligate relationship with different ecto- and endosymbiotic bacteria, which are needed to maintain their hosts’ fitness [...] Read more.

Mutualistic stable symbioses are widespread in all groups of eukaryotes, especially in insects, where symbionts have played an essential role in their evolution. Many insects live in obligate relationship with different ecto- and endosymbiotic bacteria, which are needed to maintain their hosts’ fitness in their natural environment, to the point of even relying on them for survival. The case of cockroaches (Blattodea) is paradigmatic, as both symbiotic systems coexist in the same organism in two separated compartments: an intracellular endosymbiont (Blattabacterium) inside bacteriocytes located in the fat body, and a rich and complex microbiota in the hindgut. The German cockroach Blattella germanica is a good model for the study of symbiotic interactions, as it can be maintained in the laboratory in controlled populations, allowing the perturbations of the two symbiotic systems in order to study the communication and integration of the tripartite organization of the host–endosymbiont–microbiota, and to evaluate the role of symbiotic antimicrobial peptides (AMPs) in host control over their symbionts. The importance of cockroaches as reservoirs and transmission vectors of antibiotic resistance sequences, and their putative interest to search for AMPs to deal with the problem, is also discussed. Full article

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16 pages, 82661 KiB

Open AccessReview

Were the First Trace Fossils Really Burrows or Could They Have Been Made by Sediment-Displacive Chemosymbiotic Organisms?

by Duncan McIlroy

Life 2022, 12(2), 136; https://doi.org/10.3390/life12020136 - 18 Jan 2022

Cited by 2 | Viewed by 3111

Abstract

This review asks some hard questions about what the enigmatic graphoglyptid trace fossils are, documents some of their early fossil record from the Ediacaran–Cambrian transition and explores the idea that they may not have been fossils at all. Most researchers have considered the [...] Read more.

This review asks some hard questions about what the enigmatic graphoglyptid trace fossils are, documents some of their early fossil record from the Ediacaran–Cambrian transition and explores the idea that they may not have been fossils at all. Most researchers have considered the Graphoglyptida to have had a microbial-farming mode of life similar to that proposed for the fractal Ediacaran Rangeomorpha. This begs the question “What are the Graphoglyptida if not the Rangeomorpha persevering” and if so then “What if…?”. This provocative idea has at its roots some fundamental questions about how to distinguish burrows sensu-stricto from the external molds of endobenthic sediment displacive organisms. Full article

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2021

Jump to: 2024, 2023, 2022

34 pages, 1112 KiB

Open AccessReview

Endothelial Dysfunction in Childhood Cancer Survivors: A Narrative Review

by Marco Crocco, Giuseppe d’Annunzio, Alberto La Valle, Gianluca Piccolo, Decimo Silvio Chiarenza, Carolina Bigatti, Marta Molteni, Claudia Milanaccio, Maria Luisa Garrè, Natascia Di Iorgi and Mohamad Maghnie

Life 2022, 12(1), 45; https://doi.org/10.3390/life12010045 - 29 Dec 2021

Cited by 4 | Viewed by 2598

Abstract

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological [...] Read more.

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological interventions, it is essential to monitor endothelial function, even if the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, as well as invasive and non-invasive tools with and without pharmacological stimuli have been studied. Human clinical studies that have examined lifestyle or cancer treatment protocols have yielded evidence showing the involvement of lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress markers on the state of endothelial health and its role as an early indicator of cardiometabolic risk. However, with regards to pharmacological interventions, cautious interpretation of the result attained whilst monitoring the endothelial function is warranted due to methodological limitations and substantial heterogeneity of the results reported in the published studies. In this narrative review, an overview of evidence from human clinical trials examining the effects of cancer therapies on endothelial disease is provided together with a discussion of endothelial function assessment using the different non-invasive techniques available for researchers and clinicians, in recent years. Full article

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19 pages, 1427 KiB

Open AccessEditor’s ChoiceReview

From Life in the Sea to the Clinic: The Marine Drugs Approved and under Clinical Trial

by Emiliano Cappello and Paola Nieri

Life 2021, 11(12), 1390; https://doi.org/10.3390/life11121390 - 11 Dec 2021

Cited by 22 | Viewed by 4862

Abstract

In the last decades Blue Growth policy in european and non-european countries produced a great impulse in applied marine sciences, comprehending the research of new bioactive molecules in marine organisms. These organisms are a great source of natural compounds with unique features resulting [...] Read more.

In the last decades Blue Growth policy in european and non-european countries produced a great impulse in applied marine sciences, comprehending the research of new bioactive molecules in marine organisms. These organisms are a great source of natural compounds with unique features resulting from the huge variability of marine habitats and species living in them. Most of the marine compounds in use and in clinical trials are drugs for cancer therapy and many of them are conjugated to antibody to form antibody-drug conjugates (ADCs). Severe pain, viral infections, hypertriglyceridemia, obesity, Alzheimer’s and other CNS diseases are further target conditions for these pharmaceuticals. This review summarizes the state-of-the-art marine drugs focusing on the most successful results in the fast expanding field of marine pharmacology. Full article

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17 pages, 1094 KiB

Open AccessEditor’s ChoiceReview

Potential Reasons for Unresponsiveness to Anti-PD1 Immunotherapy in Young Patients with Advanced Melanoma

by Devayani Machiraju, Sarah Schäfer and Jessica C. Hassel

Life 2021, 11(12), 1318; https://doi.org/10.3390/life11121318 - 30 Nov 2021

Cited by 9 | Viewed by 4073

Abstract

The impact of age on the clinical benefit of anti-PD1 immunotherapy in advanced melanoma patients has been evolving recently. Due to a reduced immune function in elderly patients, young patients with a robust immune system are theoretically expected to benefit more from the [...] Read more.

The impact of age on the clinical benefit of anti-PD1 immunotherapy in advanced melanoma patients has been evolving recently. Due to a reduced immune function in elderly patients, young patients with a robust immune system are theoretically expected to benefit more from the treatment approach. However, in contrast to this hypothesis, recent studies in patients with metastatic melanoma have demonstrated that immunotherapy, especially with anti-PD1 treatment, is less effective in patients below 65 years, on average, with significantly lower responses and reduced overall survival compared to patients above 65 years of age. Besides, data on young patients are even more sparse. Hence, in this review, we will focus on age-dependent differences in the previously described resistance mechanisms to the treatment and discuss the development of potential combination treatment strategies for enhancing the anti-tumor efficacy of anti-PD1 or PDL1 treatment in young melanoma patients. Full article

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19 pages, 31908 KiB

Open AccessReview

Automated Exploration of Prebiotic Chemical Reaction Space: Progress and Perspectives

by Siddhant Sharma, Aayush Arya, Romulo Cruz and Henderson James Cleaves II

Life 2021, 11(11), 1140; https://doi.org/10.3390/life11111140 - 26 Oct 2021

Cited by 6 | Viewed by 6488

Abstract

Prebiotic chemistry often involves the study of complex systems of chemical reactions that form large networks with a large number of diverse species. Such complex systems may have given rise to emergent phenomena that ultimately led to the origin of life on Earth. [...] Read more.

Prebiotic chemistry often involves the study of complex systems of chemical reactions that form large networks with a large number of diverse species. Such complex systems may have given rise to emergent phenomena that ultimately led to the origin of life on Earth. The environmental conditions and processes involved in this emergence may not be fully recapitulable, making it difficult for experimentalists to study prebiotic systems in laboratory simulations. Computational chemistry offers efficient ways to study such chemical systems and identify the ones most likely to display complex properties associated with life. Here, we review tools and techniques for modelling prebiotic chemical reaction networks and outline possible ways to identify self-replicating features that are central to many origin-of-life models. Full article

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13 pages, 576 KiB

Open AccessReview

Uncovering the Roles of MicroRNAs in Major Depressive Disorder: From Candidate Diagnostic Biomarkers to Treatment Response Indicators

by Claudia Homorogan, Diana Nitusca, Edward Seclaman, Virgil Enatescu and Catalin Marian

Life 2021, 11(10), 1073; https://doi.org/10.3390/life11101073 - 11 Oct 2021

Cited by 9 | Viewed by 2030

Abstract

Major depressive disorder (MDD) is a recurrent debilitating illness that represents a major health burden due to its increasing worldwide prevalence, unclear pathological mechanism, nonresponsive treatment, and lack of reliable and specific diagnostic biomarkers. Recently, microRNA species (miRs) have gained particular interest because [...] Read more.

Major depressive disorder (MDD) is a recurrent debilitating illness that represents a major health burden due to its increasing worldwide prevalence, unclear pathological mechanism, nonresponsive treatment, and lack of reliable and specific diagnostic biomarkers. Recently, microRNA species (miRs) have gained particular interest because they have the ability to post-transcriptionally regulate gene expression by modulating mRNA stability and translation in a cohesive fashion. By regulating entire genetic circuitries, miRs have been shown to have dysregulated expression levels in blood samples from MDD patients, when compared to healthy subjects. In addition, antidepressant treatment (AD) also appears to alter the expression pattern of several miRs. Therefore, we critically and systematically reviewed herein the studies assessing the potential biomarker role of several candidate miRs for MDD, as well as treatment response monitoring indicators, in order to enrich the current knowledge and facilitate possible diagnostic biomarker development for MDD, which could aid in reducing both patients’ burden and open novel avenues toward a better understanding of MDD neurobiology. Full article

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13 pages, 790 KiB

Open AccessReview

Understanding Vernal Keratoconjunctivitis: Beyond Allergic Mechanisms

by Marta Sacchetti, Rocco Plateroti, Alice Bruscolini, Rosalia Giustolisi and Marco Marenco

Life 2021, 11(10), 1012; https://doi.org/10.3390/life11101012 - 26 Sep 2021

Cited by 12 | Viewed by 3926

Abstract

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease of the cornea and conjunctiva mostly affecting boys in prepubertal age. VKC recurrence is characterized by intense symptoms of itching, redness, and photophobia associated with corneal damage, impairment of visual function, and quality of [...] Read more.

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease of the cornea and conjunctiva mostly affecting boys in prepubertal age. VKC recurrence is characterized by intense symptoms of itching, redness, and photophobia associated with corneal damage, impairment of visual function, and quality of life. The pathogenesis of VKC has not yet been completely understood, and it is still controversial. In fact, VKC is considered an ocular allergic disease due to the involvement of immunoglobulin E, eosinophils, and mast cells, and of a lymphocyte T-helper type 2 reaction. However, approximately half of VKC patients have negative allergological history and testing, suggesting that other pathogenic mechanisms participate in VKC development and severity. Specifically, evidence suggests that genetic, endocrine, neuronal factors and an imbalance of innate immunity are involved in the pathogenesis of VKC. The purpose of this review is to summarize evidence on the pathogenic role of innate immunity, neuroimmune reaction, and hormonal changes in VKC. Increasing understanding of the pathogenic mechanisms behind VKC may lead to the identification of novel biomarkers for diagnosis and/or potential therapeutic targets in order to improve the management of this challenging condition. Full article

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20 pages, 2931 KiB

Open AccessReview

The Epidemiology and Global Burden of Atopic Dermatitis: A Narrative Review

by Hazrina Ab Hadi, Aine Inani Tarmizi, Kamarul Ariffin Khalid, Márió Gajdács, Adeel Aslam and Shazia Jamshed

Life 2021, 11(9), 936; https://doi.org/10.3390/life11090936 - 09 Sep 2021

Cited by 68 | Viewed by 12117

Abstract

The global epidemiology of atopic dermatitis (AD) in the current decade (2009–2019) has not been extensively reported. Epidemiological studies play an important role in presenting the risk factors of AD, as detailed prevalence and incidence data could demonstrate the burden of disease in [...] Read more.

The global epidemiology of atopic dermatitis (AD) in the current decade (2009–2019) has not been extensively reported. Epidemiological studies play an important role in presenting the risk factors of AD, as detailed prevalence and incidence data could demonstrate the burden of disease in the population of adults, adolescents, and children in different geographical regions. Thus, the primary objective of this review was to assess and summarize the epidemiological studies of the prevalence and incidence of AD in different age groups, focusing on data from studies published for 2009 to 2019. After a thorough literature search, six countries were identified from African, Asian, and European regions respectively, who published studies on AD. In contrast, only two studies were identified from Australia and New Zealand, three countries from North America and two from South America published AD studies, respectively. The highest prevalence of AD from included studies was noted among Swedish children with 34%, while the lowest prevalence was in Tunisian children with 0.65%; studies reporting incidence data were far less numerous. A common trend in the prevalence of AD was that children would have a higher prevalence as compared to adolescents and adults. The severity and morbidity of the disease showed variance with age, sex, socioeconomic characteristics, geographical location, and ethnicity. Environmental factors played an important role as causative agents in AD. The risk factors that were proven to cause and induce AD were skin barrier impairments due to FLG mutation, changes in the environment, and diet. FLG mutation may impair the skin barrier function by disruption of pH and hydration maintenance of the skin. Lastly, there were only a few studies on the incidence of AD in the 21st century. Therefore, epidemiological studies on childhood and adulthood AD in different continents are still needed, especially on the incidence of AD during adulthood. Full article

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12 pages, 1188 KiB

Open AccessEditor’s ChoiceReview

Horizontal Gene Transfers in Plants

by Emilie Aubin, Moaine El Baidouri and Olivier Panaud

Life 2021, 11(8), 857; https://doi.org/10.3390/life11080857 - 21 Aug 2021

Cited by 14 | Viewed by 5363

Abstract

In plants, as in all eukaryotes, the vertical transmission of genetic information through reproduction ensures the maintenance of the integrity of species. However, many reports over the past few years have clearly shown that horizontal gene transfers, referred to as HGTs (the interspecific [...] Read more.

In plants, as in all eukaryotes, the vertical transmission of genetic information through reproduction ensures the maintenance of the integrity of species. However, many reports over the past few years have clearly shown that horizontal gene transfers, referred to as HGTs (the interspecific transmission of genetic information across reproductive barriers) are very common in nature and concern all living organisms including plants. The advent of next-generation sequencing technologies (NGS) has opened new perspectives for the study of HGTs through comparative genomic approaches. In this review, we provide an up-to-date view of our current knowledge of HGTs in plants. Full article

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16 pages, 1333 KiB

Open AccessReview

Roles of AMPK and Its Downstream Signals in Pain Regulation

by Shenglan Wang and Yi Dai

Life 2021, 11(8), 836; https://doi.org/10.3390/life11080836 - 16 Aug 2021

Cited by 8 | Viewed by 3316

Abstract

Pain is an unpleasant sensory and emotional state that decreases quality of life. A metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK), which is ubiquitously expressed in mammalian cells, has recently attracted interest as a new target of pain research. Abnormal AMPK expression and [...] Read more.

Pain is an unpleasant sensory and emotional state that decreases quality of life. A metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK), which is ubiquitously expressed in mammalian cells, has recently attracted interest as a new target of pain research. Abnormal AMPK expression and function in the peripheral and central nervous systems are associated with various types of pain. AMPK and its downstream kinases participate in the regulation of neuron excitability, neuroinflammation and axonal and myelin regeneration. Numerous AMPK activators have reduced pain behavior in animal models. The current understanding of pain has been deepened by AMPK research, but certain issues, such as the interactions of AMPK at each step of pain regulation, await further investigation. This review examines the roles of AMPK and its downstream kinases in neurons and non-neuronal cells, as well as their contribution to pain regulation. Full article

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11 pages, 992 KiB

Open AccessEditor’s ChoiceHypothesis

Evaluating the Microbial Habitability of Rogue Planets and Proposing Speculative Scenarios on How They Might Act as Vectors for Panspermia

by Dirk Schulze-Makuch and Alberto G. Fairén

Life 2021, 11(8), 833; https://doi.org/10.3390/life11080833 - 14 Aug 2021

Cited by 3 | Viewed by 3887

Abstract

There are two types of rogue planets, sub-brown dwarfs and “rocky” rogue planets. Sub-brown dwarfs are unlikely to be habitable or even host life, but rocky rogue planets may have a liquid ocean under a thick atmosphere or an ice layer. If they [...] Read more.

There are two types of rogue planets, sub-brown dwarfs and “rocky” rogue planets. Sub-brown dwarfs are unlikely to be habitable or even host life, but rocky rogue planets may have a liquid ocean under a thick atmosphere or an ice layer. If they are overlain by an insulating ice layer, they are also referred to as Steppenwolf planets. However, given the poor detectability of rocky rogue planets, there is still no direct evidence of the presence of water or ice on them. Here we discuss the possibility that these types of rogue planets could harbor unicellular organisms, conceivably based on a variety of different energy sources, including chemical, osmotic, thermal, and luminous energy. Further, given the theoretically predicted high number of rogue planets in the galaxy, we speculate that rogue planets could serve as a source for galactic panspermia, transferring life to other planetary systems. Full article

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26 pages, 1599 KiB

Open AccessReview

Experimental Approaches for Testing the Hypothesis of the Emergence of Life at Submarine Alkaline Vents

by Thiago Altair, Luiz G. F. Borges, Douglas Galante and Hamilton Varela

Life 2021, 11(8), 777; https://doi.org/10.3390/life11080777 - 31 Jul 2021

Cited by 9 | Viewed by 3744

Abstract

Since the pioneering experimental work performed by Urey and Miller around 70 years ago, several experimental works have been developed for approaching the question of the origin of life based on very few well-constructed hypotheses. In recent years, attention has been drawn to [...] Read more.

Since the pioneering experimental work performed by Urey and Miller around 70 years ago, several experimental works have been developed for approaching the question of the origin of life based on very few well-constructed hypotheses. In recent years, attention has been drawn to the so-called alkaline hydrothermal vents model (AHV model) for the emergence of life. Since the first works, perspectives from complexity sciences, bioenergetics and thermodynamics have been incorporated into the model. Consequently, a high number of experimental works from the model using several tools have been developed. In this review, we present the key concepts that provide a background for the AHV model and then analyze the experimental approaches that were motivated by it. Experimental tools based on hydrothermal reactors, microfluidics and chemical gardens were used for simulating the environments of early AHVs on the Hadean Earth (~4.0 Ga). In addition, it is noteworthy that several works used techniques from electrochemistry to investigate phenomena in the vent–ocean interface for early AHVs. Their results provided important parameters and details that are used for the evaluation of the plausibility of the AHV model, and for the enhancement of it. Full article

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13 pages, 544 KiB

Open AccessEditor’s ChoiceReview

Role of Matrix Gla Protein in the Complex Network of Coronary Artery Disease: A Comprehensive Review

by Marko Kumric, Josip A. Borovac, Tina Ticinovic Kurir, Dinko Martinovic, Ivan Frka Separovic, Ljupka Baric and Josko Bozic

Life 2021, 11(8), 737; https://doi.org/10.3390/life11080737 - 24 Jul 2021

Cited by 4 | Viewed by 2558

Abstract

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather [...] Read more.

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability. Full article

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16 pages, 633 KiB

Open AccessEditor’s ChoiceReview

Non-Coding RNAs and Splicing Activity in Testicular Germ Cell Tumors

by Marco Barchi, Pamela Bielli, Susanna Dolci, Pellegrino Rossi and Paola Grimaldi

Life 2021, 11(8), 736; https://doi.org/10.3390/life11080736 - 24 Jul 2021

Cited by 8 | Viewed by 2889

Abstract

Testicular germ cell tumors (TGCTs) are the most common tumors in adolescent and young men. Recently, genome-wide studies have made it possible to progress in understanding the molecular mechanisms underlying the development of tumors. It is becoming increasingly clear that aberrant regulation of [...] Read more.

Testicular germ cell tumors (TGCTs) are the most common tumors in adolescent and young men. Recently, genome-wide studies have made it possible to progress in understanding the molecular mechanisms underlying the development of tumors. It is becoming increasingly clear that aberrant regulation of RNA metabolism can drive tumorigenesis and influence chemotherapeutic response. Notably, the expression of non-coding RNAs as well as specific splice variants is deeply deregulated in human cancers. Since these cancer-related RNA species are considered promising diagnostic, prognostic and therapeutic targets, understanding their function in cancer development is becoming a major challenge. Here, we summarize how the different expression of RNA species repertoire, including non-coding RNAs and protein-coding splicing variants, impacts on TGCTs’ onset and progression and sustains therapeutic resistance. Finally, the role of transcription-associated R-loop misregulation in the maintenance of genomic stability in TGCTs is also discussed. Full article

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12 pages, 2845 KiB

Open AccessReview

Transforaminal Lumbar Interbody Fusion (TLIF) versus Oblique Lumbar Interbody Fusion (OLIF) in Interbody Fusion Technique for Degenerative Spondylolisthesis: A Systematic Review and Meta-Analysis

by Min Cheol Chang, Gang-Un Kim, Yoo Jin Choo and Gun Woo Lee

Life 2021, 11(7), 696; https://doi.org/10.3390/life11070696 - 15 Jul 2021

Cited by 23 | Viewed by 5751

Abstract

Preoperative pathology requiring fusion surgery has a great impact on postoperative outcomes. However, the previous clinical and meta-analysis studies did not control for the pathology. In this systematic review, the authors aimed to compare oblique lumbar interbody fusion (OLIF) with transforaminal interbody fusion [...] Read more.

Preoperative pathology requiring fusion surgery has a great impact on postoperative outcomes. However, the previous clinical and meta-analysis studies did not control for the pathology. In this systematic review, the authors aimed to compare oblique lumbar interbody fusion (OLIF) with transforaminal interbody fusion (TLIF) as an interbody fusion technique in lumbar fusion surgery for patients with degenerative spondylolisthesis (DS). We systematically searched for relevant articles in the available databases. Among the 3022 articles, three studies were identified and met the inclusion criteria. In terms of radiological outcome, the amount of disc height restoration was greater in the OLIF group than in the TLIF group, but there was no significant difference between the two surgical techniques (p = 0.18). In the clinical outcomes, the pain improvement was not significantly different between the two surgical techniques. In terms of surgical outcomes, OLIF resulted in a shorter length of hospital stay and less blood loss than TLIF (p < 0.0001 and p = 0.02, respectively). The present meta-analysis indicated no significant difference in clinical, radiological outcomes, and surgical time between TLIF and OLIF for DS, but the lengths of hospital stay and blood loss were better in OLIF than TLIF. Though encouraging, these findings were based on low-quality evidence from a small number of retrospective studies that are prone to bias. Full article

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26 pages, 2065 KiB

Open AccessEditor’s ChoiceReview

‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life

by Clifford F. Brunk and Charles R. Marshall

Life 2021, 11(7), 690; https://doi.org/10.3390/life11070690 - 14 Jul 2021

Cited by 13 | Viewed by 5149

Abstract

While most advances in the study of the origin of life on Earth (OoLoE) are piecemeal, tested against the laws of chemistry and physics, ultimately the goal is to develop an overall scenario for life’s origin(s). However, the dimensionality of non-equilibrium chemical systems, [...] Read more.

While most advances in the study of the origin of life on Earth (OoLoE) are piecemeal, tested against the laws of chemistry and physics, ultimately the goal is to develop an overall scenario for life’s origin(s). However, the dimensionality of non-equilibrium chemical systems, from the range of possible boundary conditions and chemical interactions, renders the application of chemical and physical laws difficult. Here we outline a set of simple criteria for evaluating OoLoE scenarios. These include the need for containment, steady energy and material flows, and structured spatial heterogeneity from the outset. The Principle of Continuity, the fact that all life today was derived from first life, suggests favoring scenarios with fewer non-analog (not seen in life today) to analog (seen in life today) transitions in the inferred first biochemical pathways. Top-down data also indicate that a complex metabolism predated ribozymes and enzymes, and that full cellular autonomy and motility occurred post-LUCA. Using these criteria, we find the alkaline hydrothermal vent microchamber complex scenario with a late evolving exploitation of the natural occurring pH (or Na⁺ gradient) by ATP synthase the most compelling. However, there are as yet so many unknowns, we also advocate for the continued development of as many plausible scenarios as possible. Full article

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16 pages, 1073 KiB

Open AccessEditor’s ChoiceReview

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

by Antonina Giammanco, Davide Noto, Carlo Maria Barbagallo, Emilio Nardi, Rosalia Caldarella, Marcello Ciaccio, Maurizio Rocco Averna and Angelo Baldassare Cefalù

Life 2021, 11(6), 581; https://doi.org/10.3390/life11060581 - 18 Jun 2021

Cited by 9 | Viewed by 3889

Abstract

Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce [...] Read more.

Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options. Full article

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17 pages, 888 KiB

Open AccessReview

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

by Arianna Giorgetti, Jennifer P. Pascali, Paolo Fais, Guido Pelletti, Andrea Gabbin, Giorgia Franchetti, Giovanni Cecchetto and Guido Viel

Life 2021, 11(5), 440; https://doi.org/10.3390/life11050440 - 14 May 2021

Cited by 15 | Viewed by 3738

Abstract

Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the [...] Read more.

Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions. Full article

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28 pages, 3121 KiB

Open AccessEditor’s ChoiceReview

The “Water Problem”(sic), the Illusory Pond and Life’s Submarine Emergence—A Review

by Michael J. Russell

Life 2021, 11(5), 429; https://doi.org/10.3390/life11050429 - 10 May 2021

Cited by 19 | Viewed by 6286

Abstract

The assumption that there was a “water problem” at the emergence of life—that the Hadean Ocean was simply too wet and salty for life to have emerged in it—is here subjected to geological and experimental reality checks. The “warm little pond” that would [...] Read more.

The assumption that there was a “water problem” at the emergence of life—that the Hadean Ocean was simply too wet and salty for life to have emerged in it—is here subjected to geological and experimental reality checks. The “warm little pond” that would take the place of the submarine alkaline vent theory (AVT), as recently extolled in the journal Nature, flies in the face of decades of geological, microbiological and evolutionary research and reasoning. To the present author, the evidence refuting the warm little pond scheme is overwhelming given the facts that (i) the early Earth was a water world, (ii) its all-enveloping ocean was never less than 4 km deep, (iii) there were no figurative “Icelands” or “Hawaiis”, nor even an “Ontong Java” then because (iv) the solidifying magma ocean beneath was still too mushy to support such salient loadings on the oceanic crust. In place of the supposed warm little pond, we offer a well-protected mineral mound precipitated at a submarine alkaline vent as life’s womb: in place of lipid membranes, we suggest peptides; we replace poisonous cyanide with ammonium and hydrazine; instead of deleterious radiation we have the appropriate life-giving redox and pH disequilibria; and in place of messy chemistry we offer the potential for life’s emergence from the simplest of geochemically available molecules and ions focused at a submarine alkaline vent in the Hadean—specifically within the nano-confined flexible and redox active interlayer walls of the mixed-valent double layer oxyhydroxide mineral, fougerite/green rust comprising much of that mound. Full article

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15 pages, 1087 KiB

Open AccessEditor’s ChoiceReview

Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

by Giuseppe Bellastella, Maria Ida Maiorino, Lorenzo Scappaticcio, Annamaria De Bellis, Silvia Mercadante, Katherine Esposito and Antonio Bellastella

Life 2021, 11(5), 426; https://doi.org/10.3390/life11050426 - 10 May 2021

Cited by 8 | Viewed by 3042

Abstract

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the [...] Read more.

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the control of a central clock, and the hormones of the pituitary–thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer. Full article

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9 pages, 234 KiB

Open AccessReview

Different Chronic Disorders That Fall within the Term Juvenile Idiopathic Arthritis

by Lucia M. Sur, Remus Gaga, Emanuela Duca, Genel Sur, Iulia Lupan, Daniel Sur, Gabriel Samasca, Cecilia Lazea and Calin Lazar

Life 2021, 11(5), 398; https://doi.org/10.3390/life11050398 - 27 Apr 2021

Cited by 5 | Viewed by 2067

Abstract

Juvenile idiopathic arthritis (JIA) represents a significant challenge for pediatricians who intend to diagnose and treat this pathology. The classification criteria for JIA subtypes are rigid and often do not fully satisfy the possibilities of classification in the subtype. The objective of this [...] Read more.

Juvenile idiopathic arthritis (JIA) represents a significant challenge for pediatricians who intend to diagnose and treat this pathology. The classification criteria for JIA subtypes are rigid and often do not fully satisfy the possibilities of classification in the subtype. The objective of this study was to identify clearer criteria for classifying JIA subtypes. The 2019 expert committee meeting (PRINTO) shows the difficulties of this classification and proposes new research directions for the identification of disease subtypes. Four different chronic disorders are used to define JIA in a concise and easy to follow classification system. However, dates from the literature suggest that at least 10% of cases are still difficult to classify. Possibly in the future, different classifications of JIA based on pathophysiological and genetic criteria would be necessary. Full article

20 pages, 7513 KiB

Open AccessEditor’s ChoiceReview

The “Genomic Code”: DNA Pervasively Moulds Chromatin Structures Leaving no Room for “Junk”

by Giorgio Bernardi

Life 2021, 11(4), 342; https://doi.org/10.3390/life11040342 - 13 Apr 2021

Cited by 6 | Viewed by 3158

Abstract

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin [...] Read more.

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin located peripherally. This bimodality was later confirmed and extended by the discoveries (1) of LADs, the Lamina-Associated Domains, and InterLADs; (2) of two “spatial compartments”, A and B, identified on the basis of chromatin interactions; and (3) of “forests and prairies” characterized by high and low CpG islands densities. Chromatin compartments were shown to be associated with the compositionally different, flat and single- or multi-peak DNA structures of the two, GC-poor and GC-rich, “super-families” of isochores. At the second, sub-compartment, level, chromatin corresponds to flat isochores and to isochore loops (due to compositional DNA gradients) that are susceptible to extrusion. Finally, at the short-sequence level, two sets of sequences, GC-poor and GC-rich, define two different nucleosome spacings, a short one and a long one. In conclusion, chromatin structures are moulded according to a “genomic code” by DNA sequences that pervade the genome and leave no room for “junk”. Full article

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