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Volume 12
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Life, Volume 12, Issue 1 (January 2022) – 133 articles

Cover Story (view full-size image): It has been proposed that viroids are direct descendants of primordial RNA replicons that are present in the hypothetical RNA world. We argue, however, that a much later origin of viroids, possibly from recently discovered mobile genetic elements known as retrozymes, is a far more plausible evolutionary scenario. Nevertheless, viroids and viroid-like circular RNAs are minimal replicators that are likely to be close to the theoretical lower limit of replicator size and arguably comprise the paradigm for replicator emergence. Thus, although viroid-like replicators are unlikely to be direct descendants of primordial RNA replicators, the study of the diversity and evolution of these ultimate genetic parasites can yield insights into the earliest stages of evolution. View this paper.
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18 pages, 630 KiB  
Article
Taurine Stabilizing Effect on Lysozyme
by Leonardo Mastrella, Paolo Moretti, Silvia Pieraccini, Simona Magi, Silvia Piccirillo and Maria Grazia Ortore
Life 2022, 12(1), 133; https://doi.org/10.3390/life12010133 - 17 Jan 2022
Cited by 5 | Viewed by 2875
Abstract
Taurine is an important organic osmolyte in mammalian cells, and it weakens inflammation and oxidative stress mediated injuries in some diseases. Recently, taurine has been demonstrated to play a therapeutic role against neurodegenerative disorders, although its parallel involvement in several biochemical mechanisms makes [...] Read more.
Taurine is an important organic osmolyte in mammalian cells, and it weakens inflammation and oxidative stress mediated injuries in some diseases. Recently, taurine has been demonstrated to play a therapeutic role against neurodegenerative disorders, although its parallel involvement in several biochemical mechanisms makes not clear taurine specific role in these diseases. Furthermore, the stabilizing effect of this molecule in terms of protein stability is known, but not deeply investigated. In this work we explore by Circular Dichroism the stabilizing impact of taurine in lysozyme thermal denaturation and its influence in lysozyme aggregation into amyloid fibrils. Taurine even at low concentration modifies protein-protein interactions in lysozyme native state, as revealed by Small Angle X-ray Scattering experiments, and alters the amyloid aggregation pattern without completely inhibiting it, as confirmed by UV/Vis spectroscopy with Congo Red and by Atomic Force Microscopy. Evaluation of the cytotoxicities of the amyloid fibrils grown in presence or in absence of taurine is investigated on SH-SY5Y neuroblastoma cells. Full article
(This article belongs to the Special Issue How Cosolvents and Cosolutes Affect Biomolecules Stability and Activity)
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14 pages, 2745 KiB  
Article
Epidermal Barrier Function and Skin Homeostasis in Atopic Dermatitis: The Impact of Age
by Trinidad Montero-Vilchez, Carlos Cuenca-Barrales, Juan-Angel Rodriguez-Pozo, Pablo Diaz-Calvillo, Jesús Tercedor-Sanchez, Antonio Martinez-Lopez, Alejandro Molina-Leyva and Salvador Arias-Santiago
Life 2022, 12(1), 132; https://doi.org/10.3390/life12010132 - 17 Jan 2022
Cited by 21 | Viewed by 2796
Abstract
Skin is damaged in atopic dermatitis (AD) patients. Age is also believed to have a negative effect on epidermal barrier function. The aim of this study was to investigate skin barrier function changes with age in AD patients. A cross-sectional study was conducted [...] Read more.
Skin is damaged in atopic dermatitis (AD) patients. Age is also believed to have a negative effect on epidermal barrier function. The aim of this study was to investigate skin barrier function changes with age in AD patients. A cross-sectional study was conducted including 162 participants, 81 AD patients and 81 healthy volunteers. Skin barrier function parameters, such as transepidermal water loss (TEWL), erythema, temperature, stratum corneum hydration (SCH), pH, and elasticity, were evaluated. Healthy volunteers were evaluated on the volar forearm. AD patients were measured on two regions: on an eczematous lesion on the volar forearm and on a non-involved area 5 cm from the affected area. TEWL was lower on healthy skin than uninvolved AD skin (9.98 vs. 25.51 g·m−2·h−1, p < 0.001) and AD eczematous lesions (9.98 vs. 28.38 g·m−2·h−1, p < 0.001). SCH was lower on AD eczematous lesions than uninvolved AD skin (24.23 vs. 39.36 AU, p < 0.001) and healthy skin (24.23 vs. 44.36 AU, p < 0.001). Elasticity was lower on AD eczematous lesions than uninvolved AD skin (0.69 vs. 0.74, p = 0.038) and healthy skin (0.69 vs. 0.77, p = 0.014). A negative correlation was found between age and elasticity in all the population (r = −0.383, p < 0.001). This correlation was stronger in AD patients (r = −0.494, p < 0.001) than in controls (r = −0.266, p = 0.092). After conducting a linear regression model in AD patients adjusted by age, sex, and SCORing Atopic Dermatitis (SCORAD), it was found that elasticity was impaired by an increasing age (β = −0.004, p < 0.001) and a higher SCORAD (β = −0.003, p < 0.001). The skin barrier function is impaired by age and AD, reflected mainly in poor elasticity values in older AD patients. Full article
(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)
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12 pages, 2041 KiB  
Article
Gradual Expansion of a Stent to Prevent Periprocedural Complications after Carotid Artery Stenting for Vulnerable Severe Stenotic Lesions with Intraplaque Hemorrhages: A Retrospective Observational Study
by Takahisa Mori, Kazuhiro Yoshioka, Yuhei Tanno and Shigen Kasakura
Life 2022, 12(1), 131; https://doi.org/10.3390/life12010131 - 17 Jan 2022
Viewed by 1642
Abstract
Vulnerable lesions with intraplaque hemorrhages are associated with a high incidence of complications following carotid artery stenting (CAS). CAS for vulnerable lesions has not been established; therefore, we gradually expand stents in such patients. This study aimed to compare the incidences of complications [...] Read more.
Vulnerable lesions with intraplaque hemorrhages are associated with a high incidence of complications following carotid artery stenting (CAS). CAS for vulnerable lesions has not been established; therefore, we gradually expand stents in such patients. This study aimed to compare the incidences of complications between gradual-expansion CAS for vulnerable lesions and standard CAS for non-vulnerable lesions. For gradual-expansion CAS, we used 3.0 or 4.0 mm balloons for minimal luminal diameters (MLDs) <2.0 or ≥2.0 mm, respectively, for pre-stenting angioplasty (SA) and did not overinflate them. By contrast, for standard CAS, we used a 4.0 mm balloon and overinflated it to 4.23 mm. A closed-cell stent was deployed, and post-SA was not performed in both groups. We evaluated the MLD before and minimal stent diameter (MSD) immediately after CAS, as well as periprocedural complications of combined stroke, death, and myocardial infarction within 30 days after CAS. In the vulnerable and non-vulnerable groups, 30 and 38 patients were analyzed, the MLDs were 0.76 and 0.96 mm before CAS, the MSDs were 2.97 mm and 3.58 mm after CAS, and the numbers of complications were 0 and 1, respectively. Gradual-expansion CAS for vulnerable lesions was as safe as standard CAS for non-vulnerable lesions. Full article
(This article belongs to the Special Issue Challenges in Stroke Care)
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28 pages, 3081 KiB  
Review
A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease
by Yuefeng Wu and Hai Song
Life 2022, 12(1), 130; https://doi.org/10.3390/life12010130 - 17 Jan 2022
Cited by 1 | Viewed by 2838
Abstract
Antibodies are a type of protein produced by active B cells in response to antigen stimulation. A series of monoclonal antibodies and neutralizing antibodies have been invented and put into clinical use because of their high therapeutic effect and bright developing insight. Patients [...] Read more.
Antibodies are a type of protein produced by active B cells in response to antigen stimulation. A series of monoclonal antibodies and neutralizing antibodies have been invented and put into clinical use because of their high therapeutic effect and bright developing insight. Patients with cancer, infectious diseases, and autoimmune diseases can all benefit from antibody therapy. However, the targeting aspects and potential mechanisms for treating these diseases differ. In the treatment of patients with infectious diseases such as COVID-19, neutralizing antibodies have been proposed as reliable vaccines against COVID-19, which target the ACE2 protein by preventing virus entry into somatic cells. Monoclonal antibodies can target immune checkpoints (e.g., PD-L1 and CTLA-4), tyrosine kinase and subsequent signaling pathways (e.g., VEGF), and cytokines in cancer patients (e.g. IL-6 and IL-1β). It is debatable whether there is any connection between the use of antibodies in these diseases. It would be fantastic to discover the related points and explain the burden for the limitation of cross-use of these techniques. In this review, we provided a comprehensive overview of the use of antibodies in the treatment of infectious disease and cancer patients. There are also discussions of their mechanisms and history. In addition, we discussed our future outlook on the use of antibodies. Full article
(This article belongs to the Section Medical Research)
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11 pages, 8766 KiB  
Article
Ex Vivo Effect of Novel Lipophosphonoxins on Root Canal Biofilm Produced by Enterococcus faecalis: Pilot Study
by Yuliya Morozova, Iva Voborná, Radovan Žižka, Kateřina Bogdanová, Renata Večeřová, Dominik Rejman, Milan Kolář, Duy Dinh Do Pham, Pavel Holík, Roman Moštěk, Matej Rosa and Lenka Pospíšilová
Life 2022, 12(1), 129; https://doi.org/10.3390/life12010129 - 17 Jan 2022
Cited by 5 | Viewed by 2160
Abstract
(1) Background: The root canal system has complex anatomical and histological features that make it impossible to completely remove all bacteria by mechanical means only; they must be supplemented with disinfectant irrigation. Current disinfectants are unable to eliminate certain microorganisms that persist in [...] Read more.
(1) Background: The root canal system has complex anatomical and histological features that make it impossible to completely remove all bacteria by mechanical means only; they must be supplemented with disinfectant irrigation. Current disinfectants are unable to eliminate certain microorganisms that persist in the root canal, resulting in treatment failure. At the Institute of Organic Chemistry and Biochemistry, Prague, novel substances with the bactericidal effect, termed lipophosphonoxins (LPPOs), have been discovered. The aim of this pilot study was to investigate the ex vivo effects of second- and third-generation LPPOs on Enterococcus faecalis and compare them with 5% sodium hypochlorite (NaOCl), 0.12% chlorhexidine digluconate, and 17% ethylenediaminetetraacetic acid (EDTA). (2) Methods: The root canal’s dentin was used as a carrier for biofilm formation in the extracted human mature mandibular premolars. The samples were filled with cultivation broth and 0.25% glucose with tested solutions. In control samples, only fresh cultivation broth (negative control) and cultivation broth with bacterial suspension (growth control) were used. Each sample was inoculated with E. faecalis CCM4224 except for the negative control, and cultivation was performed. To determine the number of planktonic cells, the sample content was inoculated on blood agar. To evaluate biofilm formation inhibition, samples were placed in tubes with BHI. (3) Results: LPPOs exhibited a reduction in biofilm growth and bacteria comparable to NaOCl, and they were superior to other tested disinfectants. (4) Conclusions: The study results suggest the effect of lipophosphonoxins on E. faecalis CCM 4224 reduces planktonic bacterial cells and inhibits formation of biofilm in root canal samples. Full article
(This article belongs to the Collection Bacterial Infections, Treatment and Antibiotic Resistance)
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14 pages, 1929 KiB  
Article
Assessment of 2-Pentadecyl-2-oxazoline Role on Lipopolysaccharide-Induced Inflammation on Early Stage Development of Zebrafish (Danio rerio)
by Davide Di Paola, Sabrina Natale, Enrico Gugliandolo, Marika Cordaro, Rosalia Crupi, Rosalba Siracusa, Ramona D’Amico, Roberta Fusco, Daniela Impellizzeri, Salvatore Cuzzocrea, Nunziacarla Spanò, Fabio Marino and Alessio Filippo Peritore
Life 2022, 12(1), 128; https://doi.org/10.3390/life12010128 - 17 Jan 2022
Cited by 20 | Viewed by 2418
Abstract
Lipopolysaccharide (LPS), or bacterial endotoxin, is an important virulence factor in several human and animal pathologies. Oxazoline of Palmitoylethanolamide (PEAOXA) has shown strong anti-inflammatory activity in several animal models. LPS was applied for 24 h to zebrafish embryos to induce inflammation, and then [...] Read more.
Lipopolysaccharide (LPS), or bacterial endotoxin, is an important virulence factor in several human and animal pathologies. Oxazoline of Palmitoylethanolamide (PEAOXA) has shown strong anti-inflammatory activity in several animal models. LPS was applied for 24 h to zebrafish embryos to induce inflammation, and then the anti-inflammatory action of PEAOXA was evaluated for the first time in the zebrafish model (Danio rerio). Different concentrations of PEAOXA were tested for toxicity on zebrafish embryonic development; only the highest concentration of 30 mg/L showed toxic effects. Quantitative RT-PCR was applied to detect Tumor necrosis factor-α, Interleukin 1β, 6, and 8, and members of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Exposure to LPS induced an increase in pro-inflammatory cytokines (tumor necrosis factor and interleukin 1, 6, and 8) in both gene and protein expression, as well as an increase of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the nuclear factor kappa light polypeptide enhancer in B-cells inhibitor (IκBα) gene expression. Furthermore, acute LPS exposure also induced an increase in tryptase release, related to mast cell activity, and in the production of apoptosis-related proteins (caspase 3, bax, and bcl-2). Treatment with PEAOXA 10 mg/L significantly counteracts LPS-induced inflammation in terms of cytokine expression and decreases tryptase release and the apoptosis pathway. Full article
(This article belongs to the Section Pharmaceutical Science)
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15 pages, 4054 KiB  
Article
Pharmacological Effect of GABA Analogues on GABA-ϱ2 Receptors and Their Subtype Selectivity
by Moawiah M. Naffaa, David E. Hibbs, Mary Chebib and Jane R. Hanrahan
Life 2022, 12(1), 127; https://doi.org/10.3390/life12010127 - 17 Jan 2022
Cited by 2 | Viewed by 1756
Abstract
GABAϱ receptors are distinctive GABAergic receptors from other ionotropic GABAA and metabotropic GABAB receptors in their pharmacological, biochemical, and electrophysiological properties. Although GABA-ϱ1 receptors are the most studied in this subfamily, GABA-ϱ2 receptors are widely distributed [...] Read more.
GABAϱ receptors are distinctive GABAergic receptors from other ionotropic GABAA and metabotropic GABAB receptors in their pharmacological, biochemical, and electrophysiological properties. Although GABA-ϱ1 receptors are the most studied in this subfamily, GABA-ϱ2 receptors are widely distributed in the brain and are considered a potential target for treating neurological disorders such as stroke. The structure of GABA-ϱ2 receptors and their pharmacological features are poorly studied. We generated the first homology model of GABA-ϱ2 channel, which predicts similar major interactions of GABA with the binding-site residues in GABA-ϱ1 and GABA-ϱ2 channels. We also investigated the pharmacological properties of several GABA analogues on the activity of GABA-ϱ2 receptors. In comparison to their pharmacological effect on GABA-ϱ1 receptors, the activation effect of these ligands and their potentiation/inhibition impact on GABA response have interestingly shown inter-selectivity between the two GABA-ϱ receptors. Our results suggest that several GABA analogues can be used as research tools to study the distinctive physiology of GABA-ϱ1 and GABA-ϱ2 receptors. Furthermore, their partial agonist effect may hold promise for the future discovery of selective modulatory agents on GABAA receptors. Full article
(This article belongs to the Special Issue New Trends in Pharmaceutical Science)
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11 pages, 3882 KiB  
Communication
A Severe Acute Pancreatitis Mouse Model Transited from Mild Symptoms Induced by a “Two-Hit” Strategy with L-Arginine
by Jing Yang, Xujiao Tang, Qingqing Wu, Panpan Ren and Yishu Yan
Life 2022, 12(1), 126; https://doi.org/10.3390/life12010126 - 16 Jan 2022
Cited by 6 | Viewed by 2191
Abstract
To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and [...] Read more.
To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease. Full article
(This article belongs to the Topic Inflammation and Fibrosis in Digestive Diseases)
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11 pages, 1620 KiB  
Article
Intestinal Disorder in Zebrafish Larvae (Danio rerio): The Protective Action of N-Palmitoylethanolamide-oxazoline
by Davide Di Paola, Sabrina Natale, Carmelo Iaria, Marika Cordaro, Rosalia Crupi, Rosalba Siracusa, Ramona D’Amico, Roberta Fusco, Daniela Impellizzeri, Salvatore Cuzzocrea, Nunziacarla Spanò, Enrico Gugliandolo and Alessio Filippo Peritore
Life 2022, 12(1), 125; https://doi.org/10.3390/life12010125 - 16 Jan 2022
Cited by 18 | Viewed by 2940
Abstract
IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to [...] Read more.
IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to induce enterocolitis and study the protective action of PEAOXA. After repetitive exposure with 0.25% DSS, larvae presented gut alteration with an increase in mucus production. Furthermore, DSS exposure induced an increase in the inflammatory pathway in the intestine, related to an increase in the Endoplasmic-reticulum (ER) stress genes. PEAOXA exposure at a concentration of 10 mg/L decreased the DSS-induced gut damage and mucus production, as well as being able to reduce the inflammatory and ER stress-related genes expression. In conclusion, our results demonstrate that the alterations induced by repeated exposure to DSS were counteracted by PEAOXA action that was able to inhibit the increase in inflammation and ER stress involved in the progression of enterocolitis. Full article
(This article belongs to the Special Issue Pharmaceutical Biotechnology)
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8 pages, 3439 KiB  
Case Report
Multiple Inflammatory Pseudotumors of the Liver Demonstrating Spontaneous Regression: A Case Report
by Noriko Ishii-Kitano, Hirayuki Enomoto, Takashi Nishimura, Nobuhiro Aizawa, Yoko Shibata, Akiko Higashiura, Tomoyuki Takashima, Naoto Ikeda, Yukihisa Yuri, Aoi Fujiwara, Kohei Yoshihara, Ryota Yoshioka, Shoki Kawata, Shogo Ota, Ryota Nakano, Hideyuki Shiomi, Seiichi Hirota, Tsutomu Kumabe, Osamu Nakashima and Hiroko Iijima
Life 2022, 12(1), 124; https://doi.org/10.3390/life12010124 - 16 Jan 2022
Viewed by 6737
Abstract
Inflammatory pseudotumor (IPT) of the liver is a rare benign disease. IPTs generally develop as solitary nodules, and cases with multiple lesions are uncommon. We herein report a case of multiple IPTs of the liver that spontaneously regressed. A 70-year-old woman with a [...] Read more.
Inflammatory pseudotumor (IPT) of the liver is a rare benign disease. IPTs generally develop as solitary nodules, and cases with multiple lesions are uncommon. We herein report a case of multiple IPTs of the liver that spontaneously regressed. A 70-year-old woman with a 10-year history of primary biliary cholangitis and rheumatoid arthritis visited our hospital to receive a periodic medical examination. Abdominal ultrasonography revealed multiple hypoechoic lesions, with a maximum size of 33 mm, in the liver. Contrast-enhanced computed tomography revealed low-attenuation areas in the liver with mild peripheral enhancement at the arterial and portal phases. We first suspected metastatic liver tumors, but fluorodeoxyglucose positron emission tomography, magnetic resonance imaging and contrast-enhanced ultrasonography suggested the tumors to be inconsistent with malignant nodules. A percutaneous biopsy showed shedding of liver cells and abundant fibrosis with infiltration of inflammatory cells. Given these findings, we diagnosed the multiple tumors as IPTs. After careful observation for two months, the tumors almost vanished spontaneously. Physicians should avoid a hasty diagnosis of multiple tumors based solely on a few clinical findings, and a careful assessment with various imaging modalities should be conducted. Full article
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25 pages, 2467 KiB  
Article
SAXS Reveals the Stabilization Effects of Modified Sugars on Model Proteins
by Astra Piccinini, Eva C. Lourenço, Osvaldo S. Ascenso, Maria Rita Ventura, Heinz Amenitsch, Paolo Moretti, Paolo Mariani, Maria Grazia Ortore and Francesco Spinozzi
Life 2022, 12(1), 123; https://doi.org/10.3390/life12010123 - 15 Jan 2022
Cited by 3 | Viewed by 2218
Abstract
Many proteins are usually not stable under different stresses, such as temperature and pH variations, mechanical stresses, high concentrations, and high saline contents, and their transport is always difficult, because they need to be maintained in a cold regime, which is costly and [...] Read more.
Many proteins are usually not stable under different stresses, such as temperature and pH variations, mechanical stresses, high concentrations, and high saline contents, and their transport is always difficult, because they need to be maintained in a cold regime, which is costly and very challenging to achieve in remote areas of the world. For this reason, it is extremely important to find stabilizing agents that are able to preserve and protect proteins against denaturation. In the present work, we investigate, by extensively using synchrotron small-angle X-ray scattering experiments, the stabilization effect of five different sugar-derived compounds developed at ExtremoChem on two model proteins: myoglobin and insulin. The data analysis, based on a novel method that combines structural and thermodynamic features, has provided details about the physical-chemical processes that regulate the stability of these proteins in the presence of stabilizing compounds. The results clearly show that some modified sugars exert a greater stabilizing effect than others, being able to maintain the active forms of proteins at temperatures higher than those in which proteins, in the absence of stabilizers, reach denatured states. Full article
(This article belongs to the Special Issue How Cosolvents and Cosolutes Affect Biomolecules Stability and Activity)
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7 pages, 229 KiB  
Communication
Telemedicine as a Means to an End, Not an End in Itself
by Michele Vitacca and Simonetta Scalvini
Life 2022, 12(1), 122; https://doi.org/10.3390/life12010122 - 15 Jan 2022
Cited by 2 | Viewed by 1974
Abstract
Telemedicine (TM)—the management of disease at a distance—has potential usefulness for patients with advanced respiratory disease. Underscoring this potential is the dramatic expansion of its applications in clinical medicine. However, since clinical studies testing this intervention often provide heterogeneous results, its role in [...] Read more.
Telemedicine (TM)—the management of disease at a distance—has potential usefulness for patients with advanced respiratory disease. Underscoring this potential is the dramatic expansion of its applications in clinical medicine. However, since clinical studies testing this intervention often provide heterogeneous results, its role in the medical management of respiratory disorders remains inconclusive. A major problem in establishing TM’s effectiveness is that it is not a single intervention; rather, it includes a number of divergent diagnostic and therapeutic modalities—and each must be tested separately. Reflecting the discord between the need for further documentation of its approaches and effectiveness and its rapid utilization without this needed information, a major challenge is the lack of international guidelines for its integration, regulation, operational plans, and guidance for professionals. Tailored TM, with increased flexibility to address differing healthcare contexts, has the potential to improve access to and quality of services while reducing costs and direct input by health professionals. We should view TM as a tool to aid healthcare professionals in managing their patients with respiratory diseases rather than as a stand-alone substitute to traditional medical care. As such, TM is a means rather than an end. Full article
(This article belongs to the Special Issue Utilizing Telemedicine as a Tool to Enhance Outcomes in Individuals with Chronic Respiratory Diseases)
10 pages, 278 KiB  
Article
High-Throughput Sequencing Haplotype Analysis Indicates in LRRK2 Gene a Potential Risk Factor for Endemic Parkinsonism in Southeastern Moravia, Czech Republic
by Kristyna Kolarikova, Radek Vodicka, Radek Vrtel, Julia Stellmachova, Martin Prochazka, Katerina Mensikova, Tereza Bartonikova, Tomas Furst, Petr Kanovsky and Jan Geryk
Life 2022, 12(1), 121; https://doi.org/10.3390/life12010121 - 14 Jan 2022
Cited by 1 | Viewed by 1746
Abstract
Parkinson’s disease and parkinsonism are relatively common neurodegenerative disorders. This study aimed to assess potential genetic risk factors of haplotypes in genes associated with parkinsonism in a population in which endemic parkinsonism and atypical parkinsonism have recently been found. The genes ADH1C, EIF4G1, [...] Read more.
Parkinson’s disease and parkinsonism are relatively common neurodegenerative disorders. This study aimed to assess potential genetic risk factors of haplotypes in genes associated with parkinsonism in a population in which endemic parkinsonism and atypical parkinsonism have recently been found. The genes ADH1C, EIF4G1, FBXO7, GBA, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1 PLA2G6, SNCA, UCHL1, and VPS35 were analyzed in 62 patients (P) and 69 age-matched controls from the researched area (C1). Variants were acquired by high-throughput sequencing using Ion Torrent workflow. As another set of controls, the whole genome sequencing data from 100 healthy non-related individuals from the Czech population were used (C2); the results were also compared with the Genome Project data (C3). We observed shared findings of four intron (rs11564187, rs36220738, rs200829235, and rs3789329) and one exon variant (rs33995883) in the LRRK2 gene in six patients. A comparison of the C1–C3 groups revealed significant differences in haplotype frequencies between ratio of 2.09 for C1, 1.65 for C2, and 6.3 for C3, and odds ratios of 13.15 for C1, 2.58 for C2, and 7.6 for C3 were estimated. The co-occurrence of five variants in the LRRK2 gene (very probably in haplotype) could be an important potential risk factor for the development of parkinsonism, even outside the recently described pedigrees in the researched area where endemic parkinsonism is present. Full article
(This article belongs to the Special Issue Identification of Novel Disease Mechanisms and Biomarkers Using High-Throughput Sequencing Techniques)
11 pages, 15444 KiB  
Article
Lactic Acid Permeability of Aquaporin-9 Enables Cytoplasmic Lactate Accumulation via an Ion Trap
by Katharina Geistlinger, Jana D. R. Schmidt and Eric Beitz
Life 2022, 12(1), 120; https://doi.org/10.3390/life12010120 - 14 Jan 2022
Cited by 5 | Viewed by 2079
Abstract
(1) Background: Human aquaporin-9 (AQP9) conducts several small uncharged metabolites, such as glycerol, urea, and lactic acid. Certain brain tumors were shown to upregulate AQP9 expression, and the putative increase in lactic acid permeability was assigned to severity. (2) Methods: We expressed AQP9 [...] Read more.
(1) Background: Human aquaporin-9 (AQP9) conducts several small uncharged metabolites, such as glycerol, urea, and lactic acid. Certain brain tumors were shown to upregulate AQP9 expression, and the putative increase in lactic acid permeability was assigned to severity. (2) Methods: We expressed AQP9 and human monocarboxylate transporter 1 (MCT1) in yeast to determine the uptake rates and accumulation of radiolabeled l-lactate/l-lactic acid in different external pH conditions. (3) Results: The AQP9-mediated uptake of l-lactic acid was slow compared to MCT1 at neutral and slightly acidic pH, due to low concentrations of the neutral substrate species. At a pH corresponding to the pKa of l-lactic acid, uptake via AQP9 was faster than via MCT1. Substrate accumulation was fundamentally different between AQP9 and MCT1. With MCT1, an equilibrium was reached, at which the intracellular and extracellular l-lactate/H+ concentrations were balanced. Uptake via AQP9 was linear, theoretically yielding orders of magnitude of higher substrate accumulation than MCT1. (4) Conclusions: The selectivity of AQP9 for neutral l-lactic acid establishes an ion trap for l-lactate after dissociation. This may be physiologically relevant if the transmembrane proton gradient is steep, and AQP9 acts as the sole uptake path on at least one side of a polarized cell. Full article
(This article belongs to the Special Issue Aquaporins and Human Health)
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12 pages, 1500 KiB  
Article
Sleep Apnea Detection Based on Multi-Scale Residual Network
by Hengyang Fang, Changhua Lu, Feng Hong, Weiwei Jiang and Tao Wang
Life 2022, 12(1), 119; https://doi.org/10.3390/life12010119 - 14 Jan 2022
Cited by 4 | Viewed by 1599
Abstract
Aiming at the fact that traditional convolutional neural networks cannot effectively extract signal features in complex application scenarios, a sleep apnea (SA) detection method based on multi-scale residual networks is proposed. First, we analyze the physiological mechanism of SA, which uses the RR [...] Read more.
Aiming at the fact that traditional convolutional neural networks cannot effectively extract signal features in complex application scenarios, a sleep apnea (SA) detection method based on multi-scale residual networks is proposed. First, we analyze the physiological mechanism of SA, which uses the RR interval signals and R peak signals derived from the ECG signals as input. Then, a multi-scale residual network is used to extract the characteristics of the original signals in order to obtain sensitive characteristics from various angles. Because the residual structure is used in the model, the problem of model degradation can be avoided. Finally, a fully connected layer is introduced for SA detection. In order to overcome the impact of class imbalance, a focal loss function is introduced to replace the traditional cross-entropy loss function, which makes the model pay more attention to learning difficult samples in the training phase. Experimental results from the Apnea-ECG dataset show that the accuracy, sensitivity and specificity of the proposed multi-scale residual network are 86.0%, 84.1% and 87.1%, respectively. These results indicate that the proposed method not only achieves greater recognition accuracy than other methods, but it also effectively resolves the problem of low sensitivity caused by class imbalance. Full article
(This article belongs to the Special Issue Artificial Intelligence with Applications in Life Sciences)
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18 pages, 776 KiB  
Review
Neurological Complications of Biological Treatment of Psoriasis
by Mateusz Kamil Ożóg, Beniamin Oskar Grabarek, Magdalena Wierzbik-Strońska and Magdalena Świder
Life 2022, 12(1), 118; https://doi.org/10.3390/life12010118 - 14 Jan 2022
Cited by 6 | Viewed by 4566
Abstract
In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well [...] Read more.
In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well as to analyze the mechanisms that lead to neurological complications during anticytokine therapies in psoriasis. However, this connection requires further analysis. The use of biological drugs in psoriasis, although it yields positive therapeutic results, is not without numerous side effects. Serious neurological side effects of the therapy are most often visible with the use of anti-TNF-alpha, which is why patients should be monitored for their potential occurrence. Early detection of complications and rapid discontinuation of treatment with the drug may potentially increase the patient’s chances of a full recovery or improvement of his/her neurological condition. It also seems reasonable that, in the case of complications occurring during anti-TNF-alpha therapy, some of the drugs from other groups should be included in the therapy. Full article
(This article belongs to the Section Pharmaceutical Science)
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13 pages, 1723 KiB  
Review
Tissue Engineering and Regeneration of the Human Hair Follicle in Androgenetic Alopecia: Literature Review
by José María Llamas-Molina, Alejandro Carrero-Castaño, Ricardo Ruiz-Villaverde and Antonio Campos
Life 2022, 12(1), 117; https://doi.org/10.3390/life12010117 - 14 Jan 2022
Cited by 11 | Viewed by 4397
Abstract
Androgenetic alopecia (AGA) is an androgen-dependent process and represents the most frequent non-scarring alopecia. Treatments for AGA do not always achieve a satisfactory result for the patient, and sometimes cause side effects that lead to discontinuation of treatment. AGA therapeutics currently includes topical [...] Read more.
Androgenetic alopecia (AGA) is an androgen-dependent process and represents the most frequent non-scarring alopecia. Treatments for AGA do not always achieve a satisfactory result for the patient, and sometimes cause side effects that lead to discontinuation of treatment. AGA therapeutics currently includes topical and oral drugs, as well as follicular unit micro-transplantation techniques. Tissue engineering (TE) is postulated as one of the possible future solutions to the problem and aims to develop fully functional hair follicles that maintain their cyclic rhythm in a physiological manner. However, despite its great potential, reconstitution of fully functional hair follicles is still a challenge to overcome and the knowledge gained of the key processes in hair follicle morphogenesis and biology has not yet been translated into effective replacement therapies in clinical practice. To achieve this, it is necessary to research and develop new approaches, techniques and biomaterials. In this review, present and emerging hair follicle bioengineering strategies are evaluated. The current problems of these bioengineering techniques are discussed, as well as the advantages and disadvantages, and the future prospects for the field of TE and successful hair follicle regeneration. Full article
(This article belongs to the Section Cell Biology and Tissue Engineering)
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25 pages, 19211 KiB  
Article
Ritonavir and xk263 Binding-Unbinding with HIV-1 Protease: Pathways, Energy and Comparison
by Jianan Sun, Mark Anthony V. Raymundo and Chia-En A. Chang
Life 2022, 12(1), 116; https://doi.org/10.3390/life12010116 - 13 Jan 2022
Cited by 4 | Viewed by 1781
Abstract
Understanding non-covalent biomolecular recognition, which includes drug–protein bound states and their binding/unbinding processes, is of fundamental importance in chemistry, biology, and medicine. Fully revealing the factors that govern the binding/unbinding processes can further assist in designing drugs with desired binding kinetics. HIV protease [...] Read more.
Understanding non-covalent biomolecular recognition, which includes drug–protein bound states and their binding/unbinding processes, is of fundamental importance in chemistry, biology, and medicine. Fully revealing the factors that govern the binding/unbinding processes can further assist in designing drugs with desired binding kinetics. HIV protease (HIVp) plays an integral role in the HIV life cycle, so it is a prime target for drug therapy. HIVp has flexible flaps, and the binding pocket can be accessible by a ligand via various pathways. Comparing ligand association and dissociation pathways can help elucidate the ligand–protein interactions such as key residues directly involved in the interaction or specific protein conformations that determine the binding of a ligand under certain pathway(s). Here, we investigated the ligand unbinding process for a slow binder, ritonavir, and a fast binder, xk263, by using unbiased all-atom accelerated molecular dynamics (aMD) simulation with a re-seeding approach and an explicit solvent model. Using ritonavir-HIVp and xk263-HIVp ligand–protein systems as cases, we sampled multiple unbinding pathways for each ligand and observed that the two ligands preferred the same unbinding route. However, ritonavir required a greater HIVp motion to dissociate as compared with xk263, which can leave the binding pocket with little conformational change of HIVp. We also observed that ritonavir unbinding pathways involved residues which are associated with drug resistance and are distal from catalytic site. Analyzing HIVp conformations sampled during both ligand–protein binding and unbinding processes revealed significantly more overlapping HIVp conformations for ritonavir-HIVp rather than xk263-HIVp. However, many HIVp conformations are unique in xk263-HIVp unbinding processes. The findings are consistent with previous findings that xk263 prefers an induced-fit model for binding and unbinding, whereas ritonavir favors a conformation selection model. This study deepens our understanding of the dynamic process of ligand unbinding and provides insights into ligand–protein recognition mechanisms and drug discovery. Full article
(This article belongs to the Special Issue Computational Modeling of Kinetics in Biological Systems)
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21 pages, 5357 KiB  
Article
Metabolomic Profiles of the Creeping Wood Sorrel Oxalis corniculata in Radioactively Contaminated Fields in Fukushima: Dose-Dependent Changes in Key Metabolites
by Ko Sakauchi, Wataru Taira and Joji M. Otaki
Life 2022, 12(1), 115; https://doi.org/10.3390/life12010115 - 13 Jan 2022
Cited by 6 | Viewed by 2709
Abstract
The biological impacts of the Fukushima nuclear accident, in 2011, on wildlife have been studied in many organisms, including the pale grass blue butterfly and its host plant, the creeping wood sorrel Oxalis corniculata. Here, we performed an LC–MS-based metabolomic analysis on [...] Read more.
The biological impacts of the Fukushima nuclear accident, in 2011, on wildlife have been studied in many organisms, including the pale grass blue butterfly and its host plant, the creeping wood sorrel Oxalis corniculata. Here, we performed an LC–MS-based metabolomic analysis on leaves of this plant collected in 2018 from radioactively contaminated and control localities in Fukushima, Miyagi, and Niigata prefectures, Japan. Using 7967 peaks detected by LC–MS analysis, clustering analyses showed that nine Fukushima samples and one Miyagi sample were clustered together, irrespective of radiation dose, while two Fukushima (Iitate) and two Niigata samples were not in this cluster. However, 93 peaks were significantly different (FDR < 0.05) among the three dose-dependent groups based on background, low, and high radiation dose rates. Among them, seven upregulated and 15 downregulated peaks had single annotations, and their peak intensity values were positively and negatively correlated with ground radiation dose rates, respectively. Upregulated peaks were annotated as kudinoside D (saponin), andrachcinidine (alkaloid), pyridoxal phosphate (stress-related activated vitamin B6), and four microbe-related bioactive compounds, including antibiotics. Additionally, two peaks were singularly annotated and significantly upregulated (K1R1H1; peptide) or downregulated (DHAP(10:0); decanoyl dihydroxyacetone phosphate) most at the low dose rates. Therefore, this plant likely responded to radioactive pollution in Fukushima by upregulating and downregulating key metabolites. Furthermore, plant-associated endophytic microbes may also have responded to pollution, suggesting their contributions to the stress response of the plant. Full article
(This article belongs to the Special Issue Radioactive Pollution and Biological Effects of Radioactivity)
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16 pages, 5109 KiB  
Article
Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells
by Ahmed Al Saqr, El-Sayed Khafagy, Mohammed F. Aldawsari, Khaled Almansour and Amr S. Abu Lila
Life 2022, 12(1), 114; https://doi.org/10.3390/life12010114 - 13 Jan 2022
Cited by 9 | Viewed by 1861
Abstract
Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae, has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer [...] Read more.
Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae, has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner. In addition, treatment with FDN potentially triggered apoptosis in A549 cells via not only disrupting the nuclear morphology, but by activating capsase-9 and caspase-3 with concomitant modulation of the pro- and antiapoptotic gene expression as well. Furthermore, FDN revealed its competence in inducing cell cycle arrest at G0/G1 phase in A549 cells, which was associated with decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4), along with increased expression of CDK inhibitor p21Cip1. Intriguingly, FDN treatment efficiently downregulated the Wnt signaling pathway, which was correlated with increased apoptosis, as well as cell cycle arrest, in A549 cells. Collectively, FDN might represent a promising adjuvant therapy for the management of lung cancer. Full article
(This article belongs to the Special Issue Molecular Signaling of Natural Compounds in Oncology)
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10 pages, 1274 KiB  
Review
Histocompatibility and Reproduction: Lessons from the Anglerfish
by Noah Isakov
Life 2022, 12(1), 113; https://doi.org/10.3390/life12010113 - 13 Jan 2022
Cited by 4 | Viewed by 4623
Abstract
Reproduction in certain deep-sea anglerfishes involves the permanent attachment of dwarf males to much larger females and fusion of their tissues leading to the establishment of a shared circulatory system. This unusual phenomenon of sexual parasitism enables anglerfishes to maximize reproductive success in [...] Read more.
Reproduction in certain deep-sea anglerfishes involves the permanent attachment of dwarf males to much larger females and fusion of their tissues leading to the establishment of a shared circulatory system. This unusual phenomenon of sexual parasitism enables anglerfishes to maximize reproductive success in the vast and deep oceans, where females and males otherwise rarely meet. An even more surprising phenomenon relates to the observation that joining of genetically disparate male and female anglerfishes does not evoke a strong anti-graft immune rejection response, which occurs in vertebrates following allogeneic parabiosis. Recent studies demonstrated that the evolutionary processes that led to the unique mating strategy of anglerfishes coevolved with genetic changes that resulted in loss of functional genes encoding critical components of the adaptive immune system. These genetic alterations enabled anglerfishes to tolerate the histoincompatible tissue antigens of their mate and prevent the occurrence of reciprocal graft rejection responses. While the exact mechanisms by which anglerfishes defend themselves against pathogens have not yet been deciphered, it is speculated that during evolution, anglerfishes adopted new immune strategies that compensate for the loss of B and T lymphocyte functions and enable them to resist infection by pathogens. Full article
(This article belongs to the Section Evolutionary Biology)
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13 pages, 2829 KiB  
Article
Modeling Sexual Differences of Body Size Variation in Ground Beetles in Geographical Gradients: A Case Study of Pterostichus melanarius (Illiger, 1798) (Coleoptera, Carabidae)
by Sergey Luzyanin, Anatoly Saveliev, Nadezhda Ukhova, Iraida Vorobyova, Igor Solodovnikov, Anatoliy Anciferov, Rifgat Shagidullin, Teodora Teofilova, Sargylana Nogovitsyna, Viktor Brygadyrenko, Viktor Alexanov and Raisa Sukhodolskaya
Life 2022, 12(1), 112; https://doi.org/10.3390/life12010112 - 13 Jan 2022
Cited by 5 | Viewed by 2310
Abstract
The aim of this study was to test the steepness of body size variation in males and females in the widespread ground beetle Pterostichus melanarius in geographical gradients. Beetles were sampled in 15 regions of Europe and Asia, and sampling territories differed 17° [...] Read more.
The aim of this study was to test the steepness of body size variation in males and females in the widespread ground beetle Pterostichus melanarius in geographical gradients. Beetles were sampled in 15 regions of Europe and Asia, and sampling territories differed 17° in latitude and 121° in longitude. We measured six linear traits in every captured beetle and formed a data set that included 2154 individuals. Body size variation in all traits in general was sawtooth, both in latitude and in longitude gradients. Regression analysis showed slight trends: in the latitude gradient, elytra parameters increased, pronotum length did not change but the width increased, and head parameters decreased. In the longitude gradient, the changes were as follows: elytra length increased, but its width did not change; pronotum length did not change, but its width increased; the head parameters decreased. Thus, we observed the elytra length increase and the head parameters decrease northwards and eastwards. We compared female and male regression curves (trait size on latitude/longitude): p-levels were significant only in four cases out of 12. Thus, we conclude that, in general, there is no evidence for the steepness in trait variation in males compared with females. Full article
(This article belongs to the Special Issue Functional and Morphological Adaptations in Insects)
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15 pages, 7357 KiB  
Article
Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis
by Dóra Romhányi, Kornélia Szabó, Lajos Kemény, Endre Sebestyén and Gergely Groma
Life 2022, 12(1), 111; https://doi.org/10.3390/life12010111 - 13 Jan 2022
Cited by 4 | Viewed by 2504
Abstract
An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset [...] Read more.
An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related process. Our in silico analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T-cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators. Full article
(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)
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5 pages, 529 KiB  
Case Report
Botulinum Toxin Injection for Painful Adductor Pollicis Contracture after Thumb Carpometacarpal Resection Arthroplasty
by Matthias Holzbauer, Gerhard Großbötzl and Stefan Mathias Froschauer
Life 2022, 12(1), 110; https://doi.org/10.3390/life12010110 - 13 Jan 2022
Cited by 1 | Viewed by 2787
Abstract
Pollux adductus deformity is an accompanying symptom of thumb carpometacarpal osteoarthritis. We describe a case of a patient who presented with increased muscle tone of the adductor pollicis muscle and chronic pain in the thenar musculature, i.e., recurrence of an adduction deformity. The [...] Read more.
Pollux adductus deformity is an accompanying symptom of thumb carpometacarpal osteoarthritis. We describe a case of a patient who presented with increased muscle tone of the adductor pollicis muscle and chronic pain in the thenar musculature, i.e., recurrence of an adduction deformity. The patient reported a symptom-free period of 5.5 years after having received resection-suspension-arthroplasty for stage IV thumb carpometacarpal osteoarthritis until spasmodic pain appeared. Due to the functional impairment of this condition, we administered therapy including 100 units of Botox® (onabotulinumtoxinA, Allergan, Dublin, Ireland) injected with a fanning technique into the adductor pollicis muscle. Thus, we observed a substantial improvement in the patient-reported outcome measures as well as pain levels compared with initial values. The current case shows the pivotal role of the adductor pollicis muscle when patients report pain at the base of the thumb, which can cause considerable impairments despite the complication-free surgical treatment of thumb CMC OA. Full article
(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)
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15 pages, 1711 KiB  
Review
The Role of Nucleophosmin 1 (NPM1) Mutation in the Diagnosis and Management of Myeloid Neoplasms
by Katalin Kelemen
Life 2022, 12(1), 109; https://doi.org/10.3390/life12010109 - 13 Jan 2022
Cited by 6 | Viewed by 3572
Abstract
Nucleophosmin (NPM1) is a multifunctional protein with both proliferative and growth-suppressive roles in the cell. In humans, NPM1 is involved in tumorigenesis via chromosomal translocations, deletions, or mutation. Acute myeloid leukemia (AML) with mutated NPM1, a distinct diagnostic entity by the current [...] Read more.
Nucleophosmin (NPM1) is a multifunctional protein with both proliferative and growth-suppressive roles in the cell. In humans, NPM1 is involved in tumorigenesis via chromosomal translocations, deletions, or mutation. Acute myeloid leukemia (AML) with mutated NPM1, a distinct diagnostic entity by the current WHO Classification of myeloid neoplasm, represents the most common diagnostic subtype in AML and is associated with a favorable prognosis. The persistence of NPM1 mutation in AML at relapse makes this mutation an ideal target for minimal measurable disease (MRD) detection. The clinical implication of this is far-reaching because NPM1-mutated AML is currently classified as being of standard risk, with the best treatment strategy (transplantation versus chemotherapy) yet undefined. Myeloid neoplasms with NPM1 mutations and <20% blasts are characterized by an aggressive clinical course and a rapid progression to AML. The pathological classification of these cases remains controversial. Future studies will determine whether NPM1 gene mutation may be sufficient for diagnosing NPM1-mutated AML independent of the blast count. This review aims to summarize the role of NPM1 in normal cells and in human cancer and discusses its current role in clinical management of AML and related myeloid neoplasms. Full article
(This article belongs to the Special Issue Molecular Pathways in Hematologic Neoplasm)
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13 pages, 1119 KiB  
Review
Transcription–Replication Coordination
by Marco Saponaro
Life 2022, 12(1), 108; https://doi.org/10.3390/life12010108 - 13 Jan 2022
Cited by 5 | Viewed by 3436
Abstract
Transcription and replication are the two most essential processes that a cell does with its DNA: they allow cells to express the genomic content that is required for their functions and to create a perfect copy of this genomic information to pass on [...] Read more.
Transcription and replication are the two most essential processes that a cell does with its DNA: they allow cells to express the genomic content that is required for their functions and to create a perfect copy of this genomic information to pass on to the daughter cells. Nevertheless, these two processes are in a constant ambivalent relationship. When transcription and replication occupy the same regions, there is the possibility of conflicts between transcription and replication as transcription can impair DNA replication progression leading to increased DNA damage. Nevertheless, DNA replication origins are preferentially located in open chromatin next to actively transcribed regions, meaning that the possibility of conflicts is potentially an accepted incident for cells. Data in the literature point both towards the existence or not of coordination between these two processes to avoid the danger of collisions. Several reviews have been published on transcription–replication conflicts, but we focus here on the most recent findings that relate to how these two processes are coordinated in eukaryotes, considering advantages and disadvantages from coordination, how likely conflicts are at any given time, and which are their potential hotspots in the genome. Full article
(This article belongs to the Special Issue Transcription-Associated Genetic Instability)
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17 pages, 7770 KiB  
Review
Post-Intensive Care Syndrome in Survivors from Critical Illness including COVID-19 Patients: A Narrative Review
by Charikleia S. Vrettou, Vassiliki Mantziou, Alice G. Vassiliou, Stylianos E. Orfanos, Anastasia Kotanidou and Ioanna Dimopoulou
Life 2022, 12(1), 107; https://doi.org/10.3390/life12010107 - 12 Jan 2022
Cited by 31 | Viewed by 7577
Abstract
Current achievements in medical science and technological advancements in intensive care medicine have allowed better support of critically ill patients in intensive care units (ICUs) and have increased survival probability. Post-intensive care syndrome (PICS) is a relatively new term introduced almost 10 years [...] Read more.
Current achievements in medical science and technological advancements in intensive care medicine have allowed better support of critically ill patients in intensive care units (ICUs) and have increased survival probability. Post-intensive care syndrome (PICS) is a relatively new term introduced almost 10 years ago, defined as “new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond acute care hospitalization”. A significant percentage of critically ill patients suffer from PICS for a prolonged period of time, with physical problems being the most common. The exact prevalence of PICS is unknown, and many risk factors have been described well. Coronavirus disease 2019 (COVID-19) survivors seem to be at especially high risk for developing PICS. The families of ICU survivors can also be affected as a response to the stress suffered during the critical illness of their kin. This separate entity is described as PICS family (PICS-F). A multidisciplinary approach is warranted for the treatment of PICS, involving healthcare professionals, clinicians, and scientists from different areas. Improving outcomes is both challenging and imperative for the critical care community. The review of the relevant literature and the study of the physical, cognitive, and mental sequelae could lead to the prevention and timely management of PICS and the subsequent improvement of the quality of life for ICU survivors. Full article
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15 pages, 35171 KiB  
Article
Structural and Functional Characterization of Camelus dromedarius Glutathione Transferase M1-1
by Fereniki Perperopoulou, Nirmal Poudel, Anastassios C. Papageorgiou, Farid S. Ataya and Nikolaos E. Labrou
Life 2022, 12(1), 106; https://doi.org/10.3390/life12010106 - 12 Jan 2022
Viewed by 1352
Abstract
Glutathione transferases (GSTs; EC. 2.5.1.18) are a large family of multifunctional enzymes that play crucial roles in the metabolism and inactivation of a broad range of xenobiotic compounds. In the present work, we report the kinetic and structural characterization of the isoenzyme GSTM1-1 [...] Read more.
Glutathione transferases (GSTs; EC. 2.5.1.18) are a large family of multifunctional enzymes that play crucial roles in the metabolism and inactivation of a broad range of xenobiotic compounds. In the present work, we report the kinetic and structural characterization of the isoenzyme GSTM1-1 from Camelus dromedarius (CdGSTM1-1). The CdGSΤM1-1 was expressed in E. coli BL21 (DE3) and was purified by affinity chromatography. Kinetics analysis showed that the enzyme displays a relative narrow substrate specificity and restricted ability to bind xenobiotic compounds. The crystal structures of CdGSΤM1-1 were determined by X-ray crystallography in complex with the substrate (GSH) or the reaction product (S-p-nitrobenzyl-GSH), providing snapshots of the induced-fit catalytic mechanism. The thermodynamic stability of CdGSTM1-1 was investigated using differential scanning fluorimetry (DSF) in the absence and in presence of GSH and S-p-nitrobenzyl-GSH and revealed that the enzyme’s structure is significantly stabilized by its ligands. The results of the present study advance the understanding of camelid GST detoxification mechanisms and their contribution to abiotic stress adaptation in harsh desert conditions. Full article
(This article belongs to the Section Proteins and Proteomics)
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8 pages, 247 KiB  
Article
Weight Loss in Advanced Cancer: Sex Differences in Health-Related Quality of Life and Body Image
by Charlotte Goodrose-Flores, Helén Eke, Stephanie E. Bonn, Linda Björkhem-Bergman and Ylva Trolle Lagerros
Life 2022, 12(1), 105; https://doi.org/10.3390/life12010105 - 12 Jan 2022
Cited by 2 | Viewed by 1364
Abstract
Weight maintenance is a priority in cancer care, but weight loss is common and a serious concern. This study explores if there are sex differences in the perception of weight loss and its association to health-related quality of life (HRQoL) and body image. [...] Read more.
Weight maintenance is a priority in cancer care, but weight loss is common and a serious concern. This study explores if there are sex differences in the perception of weight loss and its association to health-related quality of life (HRQoL) and body image. Cancer patients admitted to Advanced Medical Home Care were recruited to answer a questionnaire, including characteristics, the HRQoL-questionnaire RAND-36, and a short form of the Body Image Scale. Linear regression analyses stratified by sex and adjusted for age were performed to examine associations between percent weight loss and separate domains of HRQoL and body image score in men and women separately. In total, 99 participants were enrolled, of which 80 had lost weight since diagnosis. In men, an inverse association between weight loss and the HRQoL-domain physical functioning, β = −1.34 (95%CI: −2.44, −0.24), and a positive association with body image distress, β = 0.22 (95%CI: 0.07, 0.37), were found. In women, weight loss was associated with improvement in the HRQoL-domain role limitations due to physical health, β = 2.02 (95%CI: 0.63, 3.41). Following a cancer diagnosis, men appear to experience weight loss more negatively than women do. Recognizing different perceptions of weight loss may be of importance in clinical practice. Full article
(This article belongs to the Section Medical Research)
22 pages, 5437 KiB  
Article
Alterations in Energy Metabolism, Mitochondrial Function and Redox Homeostasis in GK Diabetic Rat Tissues Treated with Aspirin
by Annie John, Layla Amiri, Jasmin Shafarin, Saeed Tariq, Ernest Adeghate, Frank Christopher Howarth and Haider Raza
Life 2022, 12(1), 104; https://doi.org/10.3390/life12010104 - 12 Jan 2022
Cited by 4 | Viewed by 2195
Abstract
Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated [...] Read more.
Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated the mechanism of action of aspirin in maintaining mitochondrial bioenergetics and redox metabolism in the liver and kidneys of GK rats. Aspirin reduced the production of reactive oxygen species (ROS) and oxidative stress-induced changes in GSH metabolism. Aspirin treatment also improved mitochondrial respiratory function and energy metabolism, in addition to regulating the expression of cell signaling proteins that were altered in diabetic animals. Ultrastructural electron microscopy studies revealed decreased accumulation of glycogen in the liver of aspirin-treated diabetic rats. Hypertrophic podocytes with irregular fusion of foot processes in the renal glomerulus and detached microvilli, condensed nuclei and degenerated mitochondria observed in the proximal convoluted tubules of GK rats were partially restored by aspirin. These results provide additional evidence to support our previous observation of moderation of diabetic complications by aspirin treatment in GK rats and may have implications for cautious use of aspirin in the therapeutic management of diabetes. Full article
(This article belongs to the Special Issue Mitochondrial Mechanisms of Oxidative Stress and Endothelial Dysfunction)
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