Editorial

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Open AccessEditorial

Advances in Molecular Medicine: Unravelling Disease Complexity and Pioneering Precision Healthcare

by Stephen A. Bustin and Kurt A. Jellinger

Int. J. Mol. Sci. 2023, 24(18), 14168; https://doi.org/10.3390/ijms241814168 - 16 Sep 2023

Cited by 1 | Viewed by 1009

The escalating impacts of the climate crisis, zoonotic spill-over, and antibiotic resistance have positioned molecular medicine at the forefront of pioneering translational research [...] Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

Review

Jump to: Editorial

21 pages, 720 KiB

Open AccessReview

Photodynamic Therapy for Colorectal Cancer: An Update and a Look to the Future

by José A. Rodrigues and José H. Correia

Int. J. Mol. Sci. 2023, 24(15), 12204; https://doi.org/10.3390/ijms241512204 - 30 Jul 2023

Cited by 5 | Viewed by 1459

Abstract

This review provides an update on the current state of photodynamic therapy (PDT) for colorectal cancer (CRC) and explores potential future directions in this field. PDT has emerged as a promising minimally invasive treatment modality that utilizes photosensitizers and specific light wavelengths to [...] Read more.

This review provides an update on the current state of photodynamic therapy (PDT) for colorectal cancer (CRC) and explores potential future directions in this field. PDT has emerged as a promising minimally invasive treatment modality that utilizes photosensitizers and specific light wavelengths to induce cell death in targeted tumor tissues. In recent years, significant progress has been made in understanding the underlying mechanisms, optimizing treatment protocols, and improving the efficacy of PDT for CRC. This article highlights key advancements in PDT techniques, including novel photosensitizers, light sources, and delivery methods. Furthermore, it discusses ongoing research efforts and potential future directions, such as combination therapies and nanotechnology-based approaches. By elucidating the current landscape and providing insights into future directions, this review aims to guide researchers and clinicians in harnessing the full potential of PDT for the effective management of CRC. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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16 pages, 781 KiB

Open AccessReview

Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape

by Shamar Young, Jack Hannallah, Dan Goldberg, Tina Sanghvi, Junaid Arshad, Aaron Scott and Gregory Woodhead

Int. J. Mol. Sci. 2023, 24(14), 11434; https://doi.org/10.3390/ijms241411434 - 14 Jul 2023

Cited by 3 | Viewed by 984

Abstract

Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard [...] Read more.

Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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24 pages, 1393 KiB

Open AccessReview

Phospholipids, the Masters in the Shadows during Healing after Acute Myocardial Infarction

by Dan-Valentin Pistritu, Anisia-Cristiana Vasiliniuc, Anda Vasiliu, Elena-Florentina Visinescu, Ioana-Elena Visoiu, Smaranda Vizdei, Paula Martínez Anghel, Antoanela Tanca, Octavian Bucur and Elisa Anamaria Liehn

Int. J. Mol. Sci. 2023, 24(9), 8360; https://doi.org/10.3390/ijms24098360 - 06 May 2023

Cited by 2 | Viewed by 3412

Abstract

Phospholipids are major components of cell membranes with complex structures, high heterogeneity and critical biological functions and have been used since ancient times to treat cardiovascular disease. Their importance and role were shadowed by the difficulty or incomplete available research methodology to study [...] Read more.

Phospholipids are major components of cell membranes with complex structures, high heterogeneity and critical biological functions and have been used since ancient times to treat cardiovascular disease. Their importance and role were shadowed by the difficulty or incomplete available research methodology to study their biological presence and functionality. This review focuses on the current knowledge about the roles of phospholipids in the pathophysiology and therapy of cardiovascular diseases, which have been increasingly recognized. Used in singular formulation or in inclusive combinations with current drugs, phospholipids proved their positive and valuable effects not only in the protection of myocardial tissue, inflammation and fibrosis but also in angiogenesis, coagulation or cardiac regeneration more frequently in animal models as well as in human pathology. Thus, while mainly neglected by the scientific community, phospholipids present negligible side effects and could represent an ideal target for future therapeutic strategies in healing myocardial infarction. Acknowledging and understanding their mechanisms of action could offer a new perspective into novel therapeutic strategies for patients suffering an acute myocardial infarction, reducing the burden and improving the general social and economic outcome. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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24 pages, 1609 KiB

Open AccessReview

Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

by Evanthia Tourkochristou, Athanasia Mouzaki and Christos Triantos

Int. J. Mol. Sci. 2023, 24(9), 8288; https://doi.org/10.3390/ijms24098288 - 05 May 2023

Cited by 9 | Viewed by 3102

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca²⁺ channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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20 pages, 1628 KiB

Open AccessReview

The Contribution of the Nrf2/ARE System to Mechanotransduction in Musculoskeletal and Periodontal Tissues

by Athanassios Fragoulis, Mersedeh Tohidnezhad, Yusuke Kubo, Christoph Jan Wruck, Rogerio Bastos Craveiro, Anna Bock, Michael Wolf, Thomas Pufe, Holger Jahr and Frank Suhr

Int. J. Mol. Sci. 2023, 24(9), 7722; https://doi.org/10.3390/ijms24097722 - 23 Apr 2023

Cited by 2 | Viewed by 1813

Abstract

Mechanosensing plays an essential role in maintaining tissue functions. Across the human body, several tissues (i.e., striated muscles, bones, tendons, ligaments, as well as cartilage) require mechanical loading to exert their physiological functions. Contrary, mechanical unloading triggers pathological remodeling of these tissues and, [...] Read more.

Mechanosensing plays an essential role in maintaining tissue functions. Across the human body, several tissues (i.e., striated muscles, bones, tendons, ligaments, as well as cartilage) require mechanical loading to exert their physiological functions. Contrary, mechanical unloading triggers pathological remodeling of these tissues and, consequently, human body dysfunctions. At the cellular level, both mechanical loading and unloading regulate a wide spectrum of cellular pathways. Among those, pathways regulated by oxidants such as reactive oxygen species (ROS) represent an essential node critically controlling tissue organization and function. Hence, a sensitive balance between the generation and elimination of oxidants keeps them within a physiological range. Here, the Nuclear Factor-E2-related factor 2/Antioxidant response element (Nrf2/ARE) system plays an essential role as it constitutes the major cellular regulation against exogenous and endogenous oxidative stresses. Dysregulations of this system advance, i.a., liver, neurodegenerative, and cancer diseases. Herein, we extend our comprehension of the Nrf2 system to the aforementioned mechanically sensitive tissues to explore its role in their physiology and pathology. We demonstrate the relevance of it for the tissues’ functionality and highlight the imperative to further explore the Nrf2 system to understand the physiology and pathology of mechanically sensitive tissues in the context of redox biology. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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19 pages, 1141 KiB

Open AccessReview

Severe Asthmatic Responses: The Impact of TSLP

by Efthymia Theofani, Aikaterini Tsitsopoulou, Ioannis Morianos and Maria Semitekolou

Int. J. Mol. Sci. 2023, 24(8), 7581; https://doi.org/10.3390/ijms24087581 - 20 Apr 2023

Cited by 6 | Viewed by 3230

Abstract

Asthma is a chronic inflammatory disease that affects the lower respiratory system and includes several categories of patients with varying features or phenotypes. Patients with severe asthma (SA) represent a group of asthmatics that are poorly responsive to medium-to-high doses of inhaled corticosteroids [...] Read more.

Asthma is a chronic inflammatory disease that affects the lower respiratory system and includes several categories of patients with varying features or phenotypes. Patients with severe asthma (SA) represent a group of asthmatics that are poorly responsive to medium-to-high doses of inhaled corticosteroids and additional controllers, thus leading in some cases to life-threatening disease exacerbations. To elaborate on SA heterogeneity, the concept of asthma endotypes has been developed, with the latter being characterized as T2-high or low, depending on the type of inflammation implicated in disease pathogenesis. As SA patients exhibit curtailed responses to standard-of-care treatment, biologic therapies are prescribed as adjunctive treatments. To date, several biologics that target specific downstream effector molecules involved in disease pathophysiology have displayed superior efficacy only in patients with T2-high, eosinophilic inflammation, suggesting that upstream mediators of the inflammatory cascade could constitute an attractive therapeutic approach for difficult-to-treat asthma. One such appealing therapeutic target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine with critical functions in allergic diseases, including asthma. Numerous studies in both humans and mice have provided major insights pertinent to the role of TSLP in the initiation and propagation of asthmatic responses. Undoubtedly, the magnitude of TSLP in asthma pathogenesis is highlighted by the fact that the FDA recently approved tezepelumab (Tezspire), a human monoclonal antibody that targets TSLP, for SA treatment. Nevertheless, further research focusing on the biology and mode of function of TSLP in SA will considerably advance disease management. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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22 pages, 1529 KiB

Open AccessReview

Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness

by Rosanna Squitti, Giuseppe Reale, Vincenzo Tondolo, Daniela Crescenti, Sonia Bellini, Marco Moci, Pietro Caliandro, Luca Padua and Mauro Rongioletti

Int. J. Mol. Sci. 2023, 24(7), 6867; https://doi.org/10.3390/ijms24076867 - 06 Apr 2023

Cited by 4 | Viewed by 2123

Abstract

Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the [...] Read more.

Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions. We aimed to summarize the role of these essential metals in TBI and its possible link with consciousness alterations. We found that TBI alters many neuronal molecular mechanisms involving essential metals, causing neurodegeneration, neural apoptosis, synaptic dysfunction, oxidative stress, and inflammation. This final pattern resembles that described for Alzheimer’s disease (AD) and other neurological and psychiatric diseases. Furthermore, we found that amantadine, zolpidem, and transcranial direct current stimulation (tDCS)—the most used treatments for DoC recovery—seem to have an effect on essential metals-related pathways and that Zn might be a promising new therapeutic approach. This review summarizes the neurophysiology of essential metals in the brain structures of consciousness and focuses on the mechanisms underlying their imbalance following TBI, suggesting their possible role in DoC. The scenario supports further studies aimed at getting a deeper insight into metals’ role in DoC, in order to evaluate metal-based drugs, such as metal complexes and metal chelating agents, as potential therapeutic options. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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15 pages, 2161 KiB

Open AccessReview

Role of the Gut–Liver Axis in the Pathobiology of Cholangiopathies: Basic and Clinical Evidence

by Maria Consiglia Bragazzi, Rosanna Venere, Anthony Vignone, Domenico Alvaro and Vincenzo Cardinale

Int. J. Mol. Sci. 2023, 24(7), 6660; https://doi.org/10.3390/ijms24076660 - 03 Apr 2023

Cited by 4 | Viewed by 1579

Abstract

The “Gut–Liver Axis” refers to the physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of a change in [...] Read more.

The “Gut–Liver Axis” refers to the physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of a change in gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions cause cholangiocytes to be exposed to an increasing amount of microorganisms that can reactivate inflammatory responses, thus inducing the onset of liver fibrosis. The present review focuses on the role of the gut–liver axis in the pathogenesis of cholangiopathies. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

29 pages, 1746 KiB

Open AccessReview

Uncovering the Underworld of Axial Spondyloarthritis

by Sergio Del Vescovo, Vincenzo Venerito, Claudia Iannone and Giuseppe Lopalco

Int. J. Mol. Sci. 2023, 24(7), 6463; https://doi.org/10.3390/ijms24076463 - 30 Mar 2023

Cited by 6 | Viewed by 3598

Abstract

Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, [...] Read more.

Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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22 pages, 802 KiB

Open AccessReview

The Applications and Potentials of Extracellular Vesicles from Different Cell Sources in Periodontal Regeneration

by Xin Huang, Huiyi Wang, Chuan Wang and Zhengguo Cao

Int. J. Mol. Sci. 2023, 24(6), 5790; https://doi.org/10.3390/ijms24065790 - 17 Mar 2023

Cited by 1 | Viewed by 1697

Abstract

Periodontitis is a chronic infectious disease worldwide that can cause damage to periodontal supporting tissues including gingiva, bone, cementum and periodontal ligament (PDL). The principle for the treatment of periodontitis is to control the inflammatory process. Achieving structural and functional regeneration of periodontal [...] Read more.

Periodontitis is a chronic infectious disease worldwide that can cause damage to periodontal supporting tissues including gingiva, bone, cementum and periodontal ligament (PDL). The principle for the treatment of periodontitis is to control the inflammatory process. Achieving structural and functional regeneration of periodontal tissues is also essential and remains a major challenge. Though many technologies, products, and ingredients were applied in periodontal regeneration, most of the strategies have limited outcomes. Extracellular vesicles (EVs) are membranous particles with a lipid structure secreted by cells, containing a large number of biomolecules for the communication between cells. Numerous studies have demonstrated the beneficial effects of stem cell-derived EVs (SCEVs) and immune cell-derived EVs (ICEVs) on periodontal regeneration, which may be an alternative strategy for cell-based periodontal regeneration. The production of EVs is highly conserved among humans, bacteria and plants. In addition to eukaryocyte-derived EVs (CEVs), a growing body of literature suggests that bacterial/plant-derived EVs (BEVs/PEVs) also play an important role in periodontal homeostasis and regeneration. The purpose of this review is to introduce and summarize the potential therapeutic values of BEVs, CEVs and PEVs in periodontal regeneration, and discuss the current challenges and prospects for EV-based periodontal regeneration. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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15 pages, 1812 KiB

Open AccessReview

Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

by Qiwei Yang and Ayman Al-Hendy

Int. J. Mol. Sci. 2023, 24(6), 5778; https://doi.org/10.3390/ijms24065778 - 17 Mar 2023

Cited by 6 | Viewed by 3284

Abstract

Uterine fibroids (UFs), also known as leiomyomas, are benign tumors of the myometrium affecting over 70% of women worldwide, particularly women of color. Although benign, UFs are associated with significant morbidity; they are the primary indication for hysterectomy and a major source of [...] Read more.

Uterine fibroids (UFs), also known as leiomyomas, are benign tumors of the myometrium affecting over 70% of women worldwide, particularly women of color. Although benign, UFs are associated with significant morbidity; they are the primary indication for hysterectomy and a major source of gynecologic and reproductive dysfunction, ranging from menorrhagia and pelvic pain to infertility, recurrent miscarriage, and preterm labor. So far, the molecular mechanisms underlying the pathogenesis of UFs are still quite limited. A knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve UF patient outcomes. Excessive ECM accumulation and aberrant remodeling are crucial for fibrotic diseases and excessive ECM deposition is the central characteristics of UFs. This review summarizes the recent progress of ascertaining the biological functions and regulatory mechanisms in UFs, from the perspective of factors regulating ECM production, ECM-mediated signaling, and pharmacological drugs targeting ECM accumulation. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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23 pages, 2763 KiB

Open AccessReview

Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets

by Shahinda S. R. Alsayed and Hendra Gunosewoyo

Int. J. Mol. Sci. 2023, 24(6), 5202; https://doi.org/10.3390/ijms24065202 - 08 Mar 2023

Cited by 21 | Viewed by 15222

Abstract

Mycobacterium tuberculosis (M. tb), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form [...] Read more.

Mycobacterium tuberculosis (M. tb), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host’s immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) M. tb strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB—the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years—reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the M. tb pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in M. tb. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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21 pages, 9200 KiB

Open AccessReview

Extracellular Vesicles: The Future of Diagnosis in Solid Organ Transplantation?

by Nekane Romero-García, Javier Huete-Acevedo, Cristina Mas-Bargues, Jorge Sanz-Ros, Mar Dromant, Rafael Badenes and Consuelo Borrás

Int. J. Mol. Sci. 2023, 24(6), 5102; https://doi.org/10.3390/ijms24065102 - 07 Mar 2023

Cited by 4 | Viewed by 1858

Abstract

Solid organ transplantation (SOT) is a life-saving treatment for end-stage organ failure, but it comes with several challenges, the most important of which is the existing gap between the need for transplants and organ availability. One of the main concerns in this regard [...] Read more.

Solid organ transplantation (SOT) is a life-saving treatment for end-stage organ failure, but it comes with several challenges, the most important of which is the existing gap between the need for transplants and organ availability. One of the main concerns in this regard is the lack of accurate non-invasive biomarkers to monitor the status of a transplanted organ. Extracellular vesicles (EVs) have recently emerged as a promising source of biomarkers for various diseases. In the context of SOT, EVs have been shown to be involved in the communication between donor and recipient cells and may carry valuable information about the function of an allograft. This has led to an increasing interest in exploring the use of EVs for the preoperative assessment of organs, early postoperative monitoring of graft function, or the diagnosis of rejection, infection, ischemia-reperfusion injury, or drug toxicity. In this review, we summarize recent evidence on the use of EVs as biomarkers for these conditions and discuss their applicability in the clinical setting. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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23 pages, 2274 KiB

Open AccessReview

Only Small Effects of Mindfulness-Based Interventions on Biomarker Levels of Inflammation and Stress: A Preregistered Systematic Review and Two Three-Level Meta-Analyses

by Jakob Grasmann, Frederick Almenräder, Martin Voracek and Ulrich S. Tran

Int. J. Mol. Sci. 2023, 24(5), 4445; https://doi.org/10.3390/ijms24054445 - 23 Feb 2023

Cited by 2 | Viewed by 1924

Abstract

Mindfulness-based interventions (MBIs) have a positive effect on biomarkers of inflammation and stress in patients with psychiatric disorders and physical illnesses. Regarding subclinical populations, results are less clear. The present meta-analysis addressed the effects of MBIs on biomarkers in psychiatric populations and among [...] Read more.

Mindfulness-based interventions (MBIs) have a positive effect on biomarkers of inflammation and stress in patients with psychiatric disorders and physical illnesses. Regarding subclinical populations, results are less clear. The present meta-analysis addressed the effects of MBIs on biomarkers in psychiatric populations and among healthy, stressed, and at-risk populations. All available biomarker data were investigated with a comprehensive approach, using two three-level meta-analyses. Pre–post changes in biomarker levels within treatment groups (k = 40 studies, total N = 1441) and treatment effects compared to control group effects, using only RCT data (k = 32, total N = 2880), were of similar magnitude, Hedges g = −0.15 (95% CI = [−0.23, −0.06], p < 0.001) and g = −0.11 (95% CI = [−0.23, 0.001], p = 0.053). Effects increased in magnitude when including available follow-up data but did not differ between type of sample, MBI, biomarker, and control group or duration of the MBI. This suggests that MBIs may ameliorate biomarker levels in both psychiatric and subclinical populations to a small extent. However, low study quality and evidence of publication bias may have impacted on the results. More large and preregistered studies are still needed in this field of research. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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14 pages, 593 KiB

Open AccessReview

Natural Inhibitors of P-glycoprotein in Acute Myeloid Leukemia

by Manuela Labbozzetta, Paola Poma and Monica Notarbartolo

Int. J. Mol. Sci. 2023, 24(4), 4140; https://doi.org/10.3390/ijms24044140 - 18 Feb 2023

Cited by 5 | Viewed by 2245

Abstract

Acute myeloid leukemia (AML) remains an insidious neoplasm due to the percentage of patients who develop resistance to both classic chemotherapy and emerging drugs. Multidrug resistance (MDR) is a complex process determined by multiple mechanisms, and it is often caused by the overexpression [...] Read more.

Acute myeloid leukemia (AML) remains an insidious neoplasm due to the percentage of patients who develop resistance to both classic chemotherapy and emerging drugs. Multidrug resistance (MDR) is a complex process determined by multiple mechanisms, and it is often caused by the overexpression of efflux pumps, the most important of which is P-glycoprotein (P-gp). This mini-review aims to examine the advantages of using natural substances as P-gp inhibitors, focusing on four molecules: phytol, curcumin, lupeol, and heptacosane, and their mechanism of action in AML. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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12 pages, 1427 KiB

Open AccessReview

Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient

by Calogero Caruso, Gabriella Marcon, Giulia Accardi, Anna Aiello, Anna Calabrò, Mattia Emanuela Ligotti, Mauro Tettamanti, Claudio Franceschi and Giuseppina Candore

Int. J. Mol. Sci. 2023, 24(3), 2638; https://doi.org/10.3390/ijms24032638 - 30 Jan 2023

Cited by 10 | Viewed by 3191

Abstract

In the present paper, we have analysed the role of age and sex in the fatal outcome of COVID-19, as there are conflicting results in the literature. As such, we have answered three controversial questions regarding this aspect of the COVID-19 pandemic: (1) [...] Read more.

In the present paper, we have analysed the role of age and sex in the fatal outcome of COVID-19, as there are conflicting results in the literature. As such, we have answered three controversial questions regarding this aspect of the COVID-19 pandemic: (1) Have women been more resilient than men? (2) Did centenarians die less than the remaining older people? (3) Were older centenarians more resistant to SARS-CoV-2 than younger centenarians? The literature review demonstrated that: (1) it is women who are more resilient, in agreement with data showing that women live longer than men even during severe famines and epidemics; however, there are conflicting data regarding centenarian men; (2) centenarians overall did not die less than remaining older people, likely linked to their frailty; (3) in the first pandemic wave of 2020, centenarians > 101 years old (i.e., born before 1919), but not “younger centenarians”, have been more resilient to COVID-19 and this may be related to the 1918 Spanish flu epidemic, although it is unclear what the mechanisms might be involved. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics 2023)

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