Current Issues in Molecular Biology

18 pages, 2635 KiB

Open AccessArticle

Dark Sweet Cherry (Prunus avium L.) Juice Phenolics Rich in Anthocyanins Exhibit Potential to Inhibit Drug Resistance Mechanisms in 4T1 Breast Cancer Cells via the Drug Metabolism Pathway

by Ana Nava-Ochoa, Susanne U. Mertens-Talcott, Stephen T. Talcott and Giuliana D. Noratto

Curr. Issues Mol. Biol. 2025, 47(3), 213; https://doi.org/10.3390/cimb47030213 - 20 Mar 2025

Viewed by 523

Abstract

Anthocyanins (ACNs) from dark sweet cherries (DSCs) have shown efficacy against breast cancer (BC) cells, particularly triple-negative breast cancer (TNBC) cells, without affecting normal breast cells. This study investigated the impact of ACNs on TNBC cells, focusing on drug resistance mechanisms involving drug [...] Read more.

Anthocyanins (ACNs) from dark sweet cherries (DSCs) have shown efficacy against breast cancer (BC) cells, particularly triple-negative breast cancer (TNBC) cells, without affecting normal breast cells. This study investigated the impact of ACNs on TNBC cells, focusing on drug resistance mechanisms involving drug metabolism and transport enzymes. Specifically, it was examined whether ACNs influenced Doxorubicin (DOX) metabolism by targeting drug metabolism enzymes (phase I metabolism) and drug transport enzymes (phase III metabolism) in TNBC cells. 4T1 TNBC cells were treated with ACNs, DOX, and the combination of both (ACN-DOX). Results showed a synergistic inhibition of cell viability by ACNs and DOX. In addition, the modulation of phase I drug-metabolizing enzymes was exerted by ACNs, reducing the activity of cytochrome P450 (CYP) enzymes induced by DOX. A reduction of drug efflux by ACNs was shown by decreasing P-glycoprotein (P-gp) activity, leading to a higher intracellular accumulation of DOX. These effects were confirmed using CYP and P-gp inducers and inhibitors, showing their impact on cell viability. In conclusion, the combination of ACNs with DOX has the potential to lower DOX doses, enhance its efficacy, and possibly reduce side effects, offering a promising approach for TNBC treatment. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment: 2nd Edition)

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8 pages, 3818 KiB

Open AccessBrief Report

Retinal Dystrophies Associated with Mutations in the RP1 Gene: Genotype–Phenotype Correlations

by Vito Spagnuolo, Marco Piergentili, Ilaria Passerini, Vittoria Murro, Dario Pasquale Mucciolo, Dario Giorgio, Martina Maccari, Elisabetta Pelo, Ilaria Biagini, Fabrizio Giansanti, Gianni Virgili and Andrea Sodi

Curr. Issues Mol. Biol. 2025, 47(3), 212; https://doi.org/10.3390/cimb47030212 - 20 Mar 2025

Viewed by 357

Abstract

Background: We evaluated the genetic and phenotypic features of a cohort of 10 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants. Methods: A retrospective, cross-sectional genotype–phenotype correlation study was conducted on a cohort of ten Italian patients (four males [...] Read more.

Background: We evaluated the genetic and phenotypic features of a cohort of 10 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants. Methods: A retrospective, cross-sectional genotype–phenotype correlation study was conducted on a cohort of ten Italian patients (four males and six females) seen at Careggi University Hospital between 2012 and 2024, all affected by RP carrying pathogenic variants in the RP1 gene. A comprehensive ophthalmic assessment and pedigree analysis were performed, focusing on the onset of disease symptoms, the patient’s age at first diagnosis, follow-up duration, and the presence of comorbidities. Results: Our cohort included ten Italian patients with a mean age of 59 (range of 32–79 years). The median age when symptoms first presented was 43 years (range of 2–74), with a mean follow-up period of 9.3 ± 2.6 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus examination revealed a classic RP phenotype. Fundus autofluorescence (FAF), optical coherence tomography (OCT), Electroretinogram (ERG), and visual field testing confirmed the typical features of classic retinitis pigmentosa in most cases. Conclusions: This single-center cohort of Italian patients provides insights into the clinical and genetic characteristics of RP1-associated RP. By comprehensively identifying genetic variations and their associated clinical manifestations, therapeutic interventions targeting specific genetic abnormalities can be better tailored. This approach holds promise for improving the prognosis and quality of life for individuals with RP1-associated RP. Full article

(This article belongs to the Special Issue Molecular Imaging of Cells and Tissues)

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12 pages, 6582 KiB

Open AccessArticle

USP5 Suppresses Ferroptosis in Bladder Cancer Through Stabilization of GPX4

by Caiying Liu, Yanong Deng, Liang Huang, Xinrui Nie, Yuxuan Jiang, Xia Zhang and Huihui Zhang

Curr. Issues Mol. Biol. 2025, 47(3), 211; https://doi.org/10.3390/cimb47030211 - 20 Mar 2025

Viewed by 440

Abstract

USP5 has been proven to play an important role in the proliferation of bladder cancer (BC). In this study, we focused on investigating the molecular mechanism of ferroptosis induced by USP5 in bladder cancer. The role of USP5 in bladder cancer was evaluated [...] Read more.

USP5 has been proven to play an important role in the proliferation of bladder cancer (BC). In this study, we focused on investigating the molecular mechanism of ferroptosis induced by USP5 in bladder cancer. The role of USP5 in bladder cancer was evaluated using T24 wild-type cells (WT) and USP5 knockout (USP5^−/−) by CCK8 and colony formation assays. The contents of ferrobivalent ions (Fe²⁺), reactive oxygen species (ROS), and malondialdehyde (MDA) were detected using a determination kit to observe the relationship between USP5 and ferroptosis. Furthermore, the molecular mechanism study was evaluated by employing Western blotting, co-immunoprecipitation, RT-qPCR, ubiquitination assays, etc. This study showed genetic ablation of USP5 significantly inhibited the viability and proliferation of bladder cancer cells. Genetic ablation of USP5 promoted increases in Fe²⁺ content, ROS, and MDA levels. The addition of erastin significantly increased the viability and proliferation of T24 USP5^−/− cells and significantly increased their ROS and MDA contents. We verified that USP5 deficiency led to a significant reduction in GPX4 protein levels and that the overexpression of USP5 could stabilize the GPX4 protein. Further studies showed that USP5 interacts with GPX4 and stabilizes GPX4 by inhibiting its ubiquitination These findings revealed USP5 inhibits ferroptosis in bladder cancer cells by stabilizing GPX4. The relationship between USP5 and ferroptosis could be a potential therapeutic target for bladder cancer. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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9 pages, 438 KiB

Open AccessReview

ABCB1-Mediated Colchicine Transport and Its Implications in Familial Mediterranean Fever: A Systematic Review

by Sarah Adriana Scuderi, Alessio Ardizzone, Emanuela Esposito and Anna Paola Capra

Curr. Issues Mol. Biol. 2025, 47(3), 210; https://doi.org/10.3390/cimb47030210 - 20 Mar 2025

Viewed by 407

Abstract

Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder characterized by recurrent fevers and inflammation of the serous membranes in the abdomen, lungs, and joints. Currently, the standard treatment of FMF includes colchicine, which is an alkaloid, derived from Colchicum autumnale. Colchicine’s [...] Read more.

Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder characterized by recurrent fevers and inflammation of the serous membranes in the abdomen, lungs, and joints. Currently, the standard treatment of FMF includes colchicine, which is an alkaloid, derived from Colchicum autumnale. Colchicine’s efficacy in FMF is well-established as it is used both to prevent acute attacks and reduce the risk of long-term complications. However, despite these available treatments, 5–10% of patients exhibit resistance to the drug. It has been demonstrated that polymorphisms in several genes involved in inflammation can influence treatment outcomes and the risk of FMF complications like amyloidosis. Among them, some research focused on polymorphism affecting adenosine triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1) gene encoding for P-glycoprotein. P-glycoprotein is considered a key transporter protein as it regulates the absorption, distribution, and excretion of several drugs, including colchicine. In diseases like FMF, ABCB1 polymorphisms have been shown to affect the response to colchicine, potentially leading to treatment resistance or altered toxicity. Based on this evidence, this systematic review aims to analyze available evidence on ABCB1-mediated colchicine transport and its clinical implications in FMF, showing how relevant ABCB1 variants are in response to therapy. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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13 pages, 7994 KiB

Open AccessArticle

Fisetin Mitigates Chronic Lung Injury Induced by Benzo(a)Pyrene by Regulation of Inflammation and Oxidative Stress

by Wanian M. Alwanian

Curr. Issues Mol. Biol. 2025, 47(3), 209; https://doi.org/10.3390/cimb47030209 - 19 Mar 2025

Viewed by 359

Abstract

Background: Polycyclic aromatic hydrocarbons such as Benzo(a)Pyrene, which are produced by smoking or present in air pollution, greatly contribute to lung diseases. B(a)P has been found to induce inflammation and eventually lung cancer. Fisetin, a polyphenol, abundant in many fruits and vegetables, [...] Read more.

Background: Polycyclic aromatic hydrocarbons such as Benzo(a)Pyrene, which are produced by smoking or present in air pollution, greatly contribute to lung diseases. B(a)P has been found to induce inflammation and eventually lung cancer. Fisetin, a polyphenol, abundant in many fruits and vegetables, has an appealing therapeutic potential in many disorders, including inflammation and cancer. Objectives: This study aimed to investigate the importance of fisetin in the regulation of chronic lung inflammation and oxidative stress resulting from exposure to Benzo(a)Pyrene. Methods: The effect of fisetin on rats at a concentration of 50 mg/kg was evaluated by ELISA to measure oxidative stress and inflammatory markers. The tissue architecture was also investigated using hematoxylin and eosin (H&E) staining. The expression pattern of IL-6 in lung tissues was assayed using immunohistochemistry. Fibrosis was evaluated in lung tissues using Masson Trischrome and Sirius red stains. Cell apoptosis in lung tissues was studied using a TUNEL assay. Results: After exposure to Benzo(a)Pyrene for eight weeks, the data indicated that fisetin led to a significant reduction in oxidative stress, evidenced by the reduction of SOD, MDA, NO, GPH, and GPx. Moreover, IL-6, TNF-α, and CRP levels were also decreased, indicating a reduction in inflammation. Apoptosis was reduced upon fisetin treatment. Furthermore, a significant decrease in fibrosis was also observed. Conclusions: This study reveals the importance of fisetin as a natural product in the management of chronic lung injury by protecting lung tissues from inflammation, and its use suggests better prognosis in diseases caused by exposure to B(a)P. Full article

(This article belongs to the Special Issue Natural Product Drug Activity and Biomedicine Application)

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18 pages, 3306 KiB

Open AccessArticle

Hepatic Growth Factor as a Potential Biomarker for Lung Adenocarcinoma: A Multimodal Study

by Mengxuan Sun, Yang Yu, Hanci Zhu, Yan Yao, Xintong Zhou, Xue Wang, Yubao Zhang, Xiaowei Xu, Jing Zhuang and Changgang Sun

Curr. Issues Mol. Biol. 2025, 47(3), 208; https://doi.org/10.3390/cimb47030208 - 19 Mar 2025

Viewed by 465

Abstract

(1) Background: Despite previous studies linking inflammatory cytokines to lung adenocarcinoma (LUAD), their causal mechanisms remain unclear. This study aims to explore the causal relationship between inflammatory cytokines and LUAD to fill this knowledge gap. (2) Methods: This study employs a comprehensive approach, [...] Read more.

(1) Background: Despite previous studies linking inflammatory cytokines to lung adenocarcinoma (LUAD), their causal mechanisms remain unclear. This study aims to explore the causal relationship between inflammatory cytokines and LUAD to fill this knowledge gap. (2) Methods: This study employs a comprehensive approach, integrating Mendelian randomization (MR) analysis, single-cell RNA sequencing (scRNA-seq), and transcriptomic sequencing (RNA-seq) data to investigate the relationship between inflammatory cytokines and LUAD. (3) Results: In forward MR analysis, elevated levels of hepatocyte growth factor (HGF), interleukin-1 receptor antagonist (IL-1RA), IL-5, monocyte chemoattractant protein-3, and monokine induced by interferon-γ were causally associated with an increased risk of LUAD. In reverse MR analysis, LUAD exhibited a positive causal relationship with the levels of regulated upon activation normal T cell expressed and secreted factor (RANTES) and stromal cell-derived factor-1α. The scRNA-seq data further identified specific cell populations that may influence LUAD onset and progression through the expression of particular inflammatory genes and intercellular communication. RNA-seq data analysis highlighted the role of the HGF gene in LUAD diagnosis, demonstrating its strong correlation with patient prognosis and immune cell infiltration within the tumor microenvironment. (4) Conclusions: The findings reveal a causal relationship between inflammatory cytokines and LUAD, with HGF emerging as a potential biomarker of significant clinical relevance. This study provides new insights into the molecular mechanisms underlying LUAD and lays the foundation for future therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Innovative Therapeutic Approaches in Inflammatory Diseases, Pioneering Precision Medicine Solutions)

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15 pages, 3461 KiB

Open AccessArticle

Genetic Diversity of a Wild Actinidia arguta Population in Changbai Mountain Determined by Simple Sequence Repeat Markers

by Xiaowu Sun, Guangli Shi, Songze Li, Jun Ai, Dan Sun, Zhenxing Wang, Peijin Ni, Zhendong Zhang, Shuaiming Chen, Zelong Du, Xiang Li and Fan Zhang

Curr. Issues Mol. Biol. 2025, 47(3), 207; https://doi.org/10.3390/cimb47030207 - 19 Mar 2025

Viewed by 273

Abstract

With the decrease in the number of natural populations of Actinidia arguta, there is an urgent need to collect A. arguta germplasm resources and explore their genetic diversity for better management and protection. In this study, 31 simple sequence repeat (SSR) markers [...] Read more.

With the decrease in the number of natural populations of Actinidia arguta, there is an urgent need to collect A. arguta germplasm resources and explore their genetic diversity for better management and protection. In this study, 31 simple sequence repeat (SSR) markers were used to identify 148 wild A. arguta germplasms from six natural populations in Changbai Mountain, China, and the genetic diversity of their leaf quality traits was subsequently evaluated. SSR analysis revealed rich genetic diversity among different individuals and within populations of A. arguta. Molecular variance analysis determined that the genetic diversity of wild A. arguta mainly came from within the populations (95% variance component ratio), while only a small part originated from among populations (5% variance component ratio). Abundant genetic variations were observed in the leaf quality traits of the different A. arguta resources with a high genetic diversity index (0.13–1.23). Leaf quality trait clustering and the unweighted pair group method with arithmetic average (UPGMA) clustering analysis showed similar classification results. Population structure analysis divided 148 individuals into three subgroups. Our results indicate that the populations of A. arguta in Changbai Mountain have large genetic variation and high genetic diversity. This study broadens the genetic basis of the A. arguta breeding germplasm. Full article

(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants, 2nd Edition)

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17 pages, 3001 KiB

Open AccessPerspective

A Proposal for Research Involving New Biomarkers of Hypertension, Lifestyle, and Environmental Exposure

by Angelika Edyta Charkiewicz

Curr. Issues Mol. Biol. 2025, 47(3), 206; https://doi.org/10.3390/cimb47030206 - 18 Mar 2025

Cited by 1 | Viewed by 577

Abstract

The constant monitoring of the population’s diet and assessment of occupational exposure and environmental impacts are the key to determining health risks and understanding the factors contributing to potential abnormalities in developing lifestyle diseases. Extensive long-term lifestyle monitoring studies can provide data on [...] Read more.

The constant monitoring of the population’s diet and assessment of occupational exposure and environmental impacts are the key to determining health risks and understanding the factors contributing to potential abnormalities in developing lifestyle diseases. Extensive long-term lifestyle monitoring studies can provide data on population health risks, including the most common cardiovascular diseases like hypertension. This paper presents research recommendations for future researchers and doctors to improve the diagnosis of hypertension and targeted, personalised treatment. The research proposal includes a lifestyle study, a diagnostic panel with new biomarkers, and an environmental exposure assessment of men working in the metallurgical industry. New developments and improved interventions are constantly being sought, including new biomarkers with high diagnostic utility for cardiovascular diseases like hypertension. This should enable early diagnosis, and consequently allow for appropriate and, most importantly, personalised therapy, and prevent an increase in CVD deaths. Only the effective diagnosis, treatment, and monitoring of hypertension can reduce the risk of developing diseases associated with hypertension. I propose that several new parameters (NO, cfDNA, MPO, PCSK9, MyBPC3, microRNA, TAS, Pb, and Cd) with prognostic and/or predictive potential should be included in screening to confirm the need for the extensive testing of middle-aged men by healthcare professionals due to the risk of hypertension. Full article

(This article belongs to the Special Issue Effects of Environmental Factors on Cardiovascular Disease: From Molecular Effects to Possible Future Clinic Application)

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18 pages, 583 KiB

Open AccessReview

Adaptations of the Genus Bradyrhizobium to Selected Elements, Heavy Metals and Pesticides Present in the Soil Environment

by Joanna Banasiewicz, Aleksandra Gumowska, Agata Hołubek and Sławomir Orzechowski

Curr. Issues Mol. Biol. 2025, 47(3), 205; https://doi.org/10.3390/cimb47030205 - 18 Mar 2025

Viewed by 394

Abstract

Rhizobial bacteria perform a number of extremely important functions in the soil environment. In addition to fixing molecular nitrogen and transforming it into a form available to plants, they participate in the circulation of elements and the decomposition of complex compounds present in [...] Read more.

Rhizobial bacteria perform a number of extremely important functions in the soil environment. In addition to fixing molecular nitrogen and transforming it into a form available to plants, they participate in the circulation of elements and the decomposition of complex compounds present in the soil, sometimes toxic to other organisms. This review article describes the molecular mechanisms occurring in the most diverse group of rhizobia, the genus Bradyrhizobium, allowing these bacteria to adapt to selected substances found in the soil. Firstly, the adaptation of bradyrhizobia to low and high concentrations of elements such as iron, phosphorus, sulfur, calcium and manganese was shown. Secondly, the processes activated in their cells in the presence of heavy metals such as lead, mercury and arsenic, as well as radionuclides, were described. Additionally, due to the potential use of Bradyrhziobium as biofertilizers, their response to pesticides commonly used in agriculture, such as glyphosate, sulfentrazone, chlorophenoxy herbicides, flumioxazine, imidazolinone, atrazine, and insecticides and fungicides, was also discussed. The paper shows the great genetic diversity of bradyrhizobia in terms of adapting to variable environmental conditions present in the soil. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2025)

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61 pages, 2110 KiB

Open AccessReview

Pinosylvin: A Multifunctional Stilbenoid with Antimicrobial, Antioxidant, and Anti-Inflammatory Potential

by Argyrios Periferakis, Aristodemos-Theodoros Periferakis, Lamprini Troumpata, Konstantinos Periferakis, Spyrangelos Georgatos-Garcia, Georgia Touriki, Christiana Diana Maria Dragosloveanu, Ana Caruntu, Ilinca Savulescu-Fiedler, Serban Dragosloveanu, Andreea-Elena Scheau, Ioana Anca Badarau, Constantin Caruntu and Cristian Scheau

Curr. Issues Mol. Biol. 2025, 47(3), 204; https://doi.org/10.3390/cimb47030204 - 18 Mar 2025

Viewed by 815

Abstract

Stilbenoids are a category of plant compounds exhibiting notable health-related benefits. After resveratrol, perhaps the most well-known stilbenoid is pinosylvin, a major phytochemical constituent of most plants characterised by the pine spines among others. Pinosylvin and its derivatives have been found to exert [...] Read more.

Stilbenoids are a category of plant compounds exhibiting notable health-related benefits. After resveratrol, perhaps the most well-known stilbenoid is pinosylvin, a major phytochemical constituent of most plants characterised by the pine spines among others. Pinosylvin and its derivatives have been found to exert potent antibacterial and antifungal effects, while their antiparasitic and antiviral properties are still a subject of ongoing research. The antioxidant properties of pinosylvin are mostly based on its scavenging of free radicals, inhibition of iNOS and protein kinase C, and promotion of HO-1 expression. Its anti-inflammatory properties are based on a variety of mechanisms, such as COX-2 inhibition, NF-κB and TRPA1 activation inhibition, and reduction in IL-6 levels. Its anticancer properties are partly associated with its antioxidant and anti-inflammatory potential, although a number of other mechanisms are described, such as apoptosis induction and matrix metalloproteinase inhibition. A couple of experiments have also suggested a neuroprotective potential. A multitude of ethnomedical and ethnobotanical effects of pinosylvin-containing plants are reported, like antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, and prokinetic actions; many of these are corroborated by recent research. The advent of novel methods of artificial pinosylvin synthesis may facilitate its mass production and adoption as a medical compound. Finally, pinosylvin may be a tool in promoting environmentally friendly pesticide and insecticide policies and be used in land remediation schemes. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products, 2nd Edition)

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10 pages, 477 KiB

Open AccessArticle

Amyloid Beta as a Candidate Blood Biomarker of Early Cognitive Decline in the Elderly—A Preliminary Study

by Oliwia McFarlane, Mariusz Kozakiewicz, Kornelia Kędziora-Kornatowska, Anita Gałęska-Śliwka and Milena Wojciechowska

Curr. Issues Mol. Biol. 2025, 47(3), 203; https://doi.org/10.3390/cimb47030203 - 18 Mar 2025

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Abstract

(1) Background/Objectives: The pathogenic process of Alzheimer’s disease (AD) is known to begin decades before its clinical onset. This period, although imperceptible to the patient, encompasses a gradual neuronal loss. The first symptoms of dementia, often classified as mild cognitive impairment (MCI), in [...] Read more.

(1) Background/Objectives: The pathogenic process of Alzheimer’s disease (AD) is known to begin decades before its clinical onset. This period, although imperceptible to the patient, encompasses a gradual neuronal loss. The first symptoms of dementia, often classified as mild cognitive impairment (MCI), in many cases converts into incipient AD, but can also remain stable or even reverse to cognitive norm. An easy and fast blood-based method of identifying patients at risk of conversion to AD would allow for the application of disease-altering therapies. This preliminary study focuses on the identification and assessment of the relationship between plasma amyloid beta (Aβ) and cognitive performance in older Polish adults with respect to its adequacy as a biomarker of an early cognitive deterioration. (2) Methods: The preliminary research sample consisted of 230 participants, 109 females and 121 males, aged 65 plus. The association between plasma Aβ concentrations with cognitive status, gender, and age were assessed. The analyses were conducted in three categories of cognitive performance: cognitive norm, mild cognitive impairment, and mild dementia, based on results of the Mini-Mental State Examination (MMSE) and functional tests. (3) Results: No significant differences in plasma Aβ levels for different cognitive statuses were identified. No significant differences were found in Aβ levels based on age or gender. (4) Conclusions: In order to thoroughly explore the power of research on plasma Aβ with respect to early cognitive deterioration, further prospective studies are required. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology Insights into Neurodegenerative Diseases: From Pathogenesis to Therapeutic Targets)

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34 pages, 1189 KiB

Open AccessReview

Genetic Variation and Sex-Based Differences: Current Considerations for Anesthetic Management

by Stephen DiMaria, Nicholas Mangano, Adam Bruzzese, Benjamin Bartula, Shruti Parikh and Ana Costa

Curr. Issues Mol. Biol. 2025, 47(3), 202; https://doi.org/10.3390/cimb47030202 - 18 Mar 2025

Cited by 1 | Viewed by 811

Abstract

Biomedical sciences have made immense progress and numerous discoveries aimed at improving the quality of life and life expectancy in modern times. Anesthesiology is typically tailored to individual patients as its clinical effects depend on multiple factors, including a patient’s physiological and pathological [...] Read more.

Biomedical sciences have made immense progress and numerous discoveries aimed at improving the quality of life and life expectancy in modern times. Anesthesiology is typically tailored to individual patients as its clinical effects depend on multiple factors, including a patient’s physiological and pathological states, age, environmental exposures, and genetic variations. Sex differences are also paramount for a complete understanding of the effects of specific anesthetic medications on men and women. However, women-specific research and the inclusion of women in clinical trials, specifically during child-bearing years, remain disproportionately low compared to the general population at large. This review describes and summarizes genetic variations, including sex differences, that affect responses to common anesthetic medications such as volatile anesthetics, induction agents, neuromuscular blocking drugs, opioids, and local anesthetics. It also discusses the influence of genetic variations on anesthesia outcomes, such as postoperative nausea and vomiting, allergic reactions, pain, depth of anesthesia, awareness under anesthesia and recall, and postoperative delirium. Full article

(This article belongs to the Special Issue Innovative Strategies and Applications for Drug Discovery)

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Graphical abstract

23 pages, 8865 KiB

Open AccessArticle

A Novel Ferroptosis-Related Gene Prognosis Signature and Identifying Atorvastatin as a Potential Therapeutic Agent for Hepatocellular Carcinoma

by Ling Wang, Xiaoqin He, Yang Shen, Jiayu Chen, Yukai Chen, Zhuolin Zhou and Ximing Xu

Curr. Issues Mol. Biol. 2025, 47(3), 201; https://doi.org/10.3390/cimb47030201 - 18 Mar 2025

Cited by 2 | Viewed by 515

Abstract

Among the most common malignant tumors, hepatocellular carcinoma (HCC) is a primary liver cancer type that has a high mortality rate. HCC often presents insidiously, is prone to recurrence, and has limited treatment efficacy. Ferroptosis regulates tumorigenesis, progression, and metastasis, which is a [...] Read more.

Among the most common malignant tumors, hepatocellular carcinoma (HCC) is a primary liver cancer type that has a high mortality rate. HCC often presents insidiously, is prone to recurrence, and has limited treatment efficacy. Ferroptosis regulates tumorigenesis, progression, and metastasis, which is a novel form of iron-dependent cell death. Numerous studies suggest that HCC is sensitive to ferroptosis, indicating that targeted therapies aimed at inducing ferroptosis may represent a promising new approach to cancer treatment. This study aims to find genes associated with HCC and ferroptosis, as well as to screen for potential agents that may cause ferroptosis in HCC. Transcriptome and clinical sample data were obtained from the TCGA database to identify differentially expressed genes related to ferroptosis. Using various regression and survival analysis techniques, we developed a prognostic model based on four core genes and evaluated its predictive potential. Subsequently, we screened for potential therapeutic agents in the Connective Map (CMap) database, designated as compound Atorvastatin, based on differential genes from two risk groups and related to ferroptosis. Through experiments conducted in vivo and in vitro, we demonstrated that Atorvastatin can induce ferroptosis in HCC cells while inhibiting their growth and migration. In conclusion, this research targets ferroptosis therapy and provides new insights for improving the prediction and prevention of HCC. Full article

(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era, 2nd Edition)

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16 pages, 16392 KiB

Open AccessArticle

Gene Co-Expression Analysis Reveals Functional Differences Between Early- and Late-Onset Alzheimer’s Disease

by Abel Isaías Gutiérrez Cruz, Guillermo de Anda-Jáuregui and Enrique Hernández-Lemus

Curr. Issues Mol. Biol. 2025, 47(3), 200; https://doi.org/10.3390/cimb47030200 - 18 Mar 2025

Viewed by 425

Abstract

The rising prevalence of Alzheimer’s disease (AD), particularly among older adults, has driven increased research into its underlying mechanisms and risk factors. Aging, genetic susceptibility, and cardiovascular health are recognized contributors to AD, but how the age of onset affects disease progression remains [...] Read more.

The rising prevalence of Alzheimer’s disease (AD), particularly among older adults, has driven increased research into its underlying mechanisms and risk factors. Aging, genetic susceptibility, and cardiovascular health are recognized contributors to AD, but how the age of onset affects disease progression remains underexplored. This study investigates the role of early- versus late-onset Alzheimer’s disease (EOAD and LOAD, respectively) in shaping the trajectory of cognitive decline. Leveraging data from the Religious Orders Study and Memory and Aging Project (ROSMAP), two cohorts were established: individuals with early-onset AD and those with late-onset AD. Comprehensive analyses, including differential gene expression profiling, pathway enrichment, and gene co-expression network construction, were conducted to identify distinct molecular signatures associated with each cohort. Network modularity learning algorithms were used to discern the inner structure of co-expression networks and their related functional features. Computed network descriptors provided deeper insights into the influence of age at onset on the biological progression of AD. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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15 pages, 956 KiB

Open AccessReview

Genetic Variations in Vascular Endothelial Growth Factor and Their Impact on Preeclampsia: Insights into Risk, Severity, and Pregnancy Outcomes

by Ioanna Zouganeli, Efthalia Moustakli, Anastasios Potiris, Chrysi Christodoulaki, Ioannis Arkoulis, Nikolaos Kathopoulis, Charalampos Theofanakis, Ekaterini Domali, Periklis Panagopoulos, Peter Drakakis and Sofoklis Stavros

Curr. Issues Mol. Biol. 2025, 47(3), 199; https://doi.org/10.3390/cimb47030199 - 17 Mar 2025

Viewed by 397

Abstract

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and placental development, which are vital for a healthy pregnancy. Preeclampsia (PE), a hypertension condition that can cause major difficulties for both the mother and the fetus, has been linked to VEGF [...] Read more.

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and placental development, which are vital for a healthy pregnancy. Preeclampsia (PE), a hypertension condition that can cause major difficulties for both the mother and the fetus, has been linked to VEGF gene polymorphisms in several studies. PE susceptibility has been associated with several VEGF polymorphisms, including VEGF −2578C/A, −634G/C, +936C/T, and +405G/C, with differing outcomes in various ethnicities. Some polymorphisms, like VEGF −2578C/A, are linked to the disease’s progression, whereas others, like VEGF +405G/C, may protect severe PE. The findings are still uncertain, though, with some studies reporting noteworthy outcomes and others finding no correlation. Further complicating our knowledge of VEGF’s role in PE is the possibility that the interaction between maternal and fetal VEGF polymorphisms may affect PE risk. Studies on environmental variables and placental and fetal VEGF gene polymorphisms point to a complicated interaction in influencing the severity and susceptibility of PE. The precise genetic processes behind PE are still unknown, despite the mounting evidence, necessitating additional research to confirm possible biomarkers and treatment targets. In at-risk pregnancies, a better understanding of the connection between VEGF polymorphisms and PE may help with risk assessment and management techniques. Full article

(This article belongs to the Special Issue Advanced Molecular Research on Hypertensive Disorders of Pregnancy (HDPs))

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23 pages, 12079 KiB

Open AccessArticle

Structure-Based Identification of SARS-CoV-2 nsp10-16 Methyltransferase Inhibitors Using Molecular Dynamics Insights

by Ahmad M. Alharbi

Curr. Issues Mol. Biol. 2025, 47(3), 198; https://doi.org/10.3390/cimb47030198 - 17 Mar 2025

Viewed by 375

Abstract

SARS-CoV-2 evades immune detection via nsp10-16 methyltransferase-mediated 2′-O-methylation of viral mRNA, making it a key antiviral target. Our study employed structure-based drug discovery—including virtual screening, molecular docking, and molecular dynamics (MD) simulations—to identify potent inhibitors of nsp10-16. We identified seven promising inhibitors (Z1–Z7) [...] Read more.

SARS-CoV-2 evades immune detection via nsp10-16 methyltransferase-mediated 2′-O-methylation of viral mRNA, making it a key antiviral target. Our study employed structure-based drug discovery—including virtual screening, molecular docking, and molecular dynamics (MD) simulations—to identify potent inhibitors of nsp10-16. We identified seven promising inhibitors (Z1–Z7) targeting the binding site of the SARS-CoV-2 nsp10-16 methyltransferase, with Z2, Z3, Z4, and Z7 exhibiting strong binding affinities. Further, molecular dynamics simulations confirmed that Z2, Z3, and Z7 effectively stabilized the enzyme by reducing conformational fluctuations and maintaining structural compactness, comparable to the native ligand-bound complex. The conformational deviation revealed that Z2, Z6, and Z7 restricted large-scale conformational transitions, reinforcing their stabilizing effect on the enzyme. The binding free energy calculations ranked Z4 (−37.26 kcal/mol), Z7 (−35.37 kcal/mol), and Z6 (−35.22 kcal/mol) as the strongest binders, surpassing the native tubercidin complex (−23.70 kcal/mol). The interactions analysis identified Asp99, Tyr132, and Cys115 as key stabilizing residues, with Z2, Z6, and Z7 forming high-lifetime hydrogen bonds. The drug-likeness analysis highlighted the selected compounds as promising candidates, exhibiting high gastrointestinal absorption, optimal solubility, and minimal CYP450 inhibition. Further experimental validation and lead optimization are needed to develop potent methyltransferase inhibitors with improved pharmacokinetics and antiviral efficacy. Full article

(This article belongs to the Special Issue New Insight: Enzymes as Targets for Drug Development, 2nd Edition)

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24 pages, 8232 KiB

Open AccessArticle

Bioinformatics Approach to Investigating the Immuno-Inflammatory Mechanisms of Periodontitis in the Progression of Atherosclerosis

by Wenling Yang, Jianhua Xie, Xing Zhao, Xuelian Li, Qingyi Liu, Jinpeng Sun, Ruiyu Zhang, Yumiao Wei and Boyuan Wang

Curr. Issues Mol. Biol. 2025, 47(3), 197; https://doi.org/10.3390/cimb47030197 - 17 Mar 2025

Viewed by 538

Abstract

Unstable atherosclerotic plaques are a major cause of acute cardiovascular events and ischemic stroke. Clinical studies have suggested a link between periodontitis and atherosclerotic plaque progression, but the underlying mechanisms remain unclear. To investigate this, transcriptomic datasets related to periodontitis and atherosclerosis were [...] Read more.

Unstable atherosclerotic plaques are a major cause of acute cardiovascular events and ischemic stroke. Clinical studies have suggested a link between periodontitis and atherosclerotic plaque progression, but the underlying mechanisms remain unclear. To investigate this, transcriptomic datasets related to periodontitis and atherosclerosis were downloaded from Gene Expression Omnibus. A weighted gene co-expression network analysis was used to identify gene modules associated with periodontitis, and the Limma R package identified differentially expressed genes (DEGs) between unstable and stable plaques. Overlapping genes were defined as periodontitis-related DEGs, followed by functional enrichment analysis and protein–protein interaction network construction. Machine learning methods were used to identify biomarkers for unstable plaques related to periodontitis, which were validated using external datasets. Immune infiltration and single-cell analyses were performed to explore the relationship between biomarkers and immune cells. A total of 161 periodontitis-related DEGs were identified, with the pathway analysis showing associations with immune regulation and collagen matrix degradation. HCK, NCKAP1L, and WAS were identified as biomarkers for unstable plaques, demonstrating a high diagnostic value (AUC: 0.9884, 95% CI: 0.9641–1). Immune infiltration analysis revealed an increase in macrophages within unstable plaques. Single-cell analysis showed HCK expression in macrophages and dendritic cells, while NCKAP1L and WAS were expressed in macrophages, dendritic cells, NK cells, and T cells. Consensus clustering identified three expression patterns within unstable plaques. Our findings were validated in atherosclerotic mouse models with periodontitis. This study provides insights into how periodontitis contributes to plaque instability, supporting diagnosis and intervention in patients with periodontitis. Full article

(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)

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14 pages, 1938 KiB

Open AccessArticle

Urinary Kim-1 Correlates with Interstitial Nephritis Activity in Patients with Microscopic Polyangiitis

by Chisato Ashida, Yuji Nozaki, Jinhai Li, Hiroki Akazawa, Kazuya Kishimoto, Koji Kinoshita and Itaru Matsumura

Curr. Issues Mol. Biol. 2025, 47(3), 196; https://doi.org/10.3390/cimb47030196 - 16 Mar 2025

Viewed by 404

Abstract

Background: Microscopic polyangiitis (MPA) is a type of necrotizing vasculitis that primarily affects small vessels and belongs to the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). While previous studies have identified potential prognostic biomarkers, further research is needed to validate a reliable [...] Read more.

Background: Microscopic polyangiitis (MPA) is a type of necrotizing vasculitis that primarily affects small vessels and belongs to the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). While previous studies have identified potential prognostic biomarkers, further research is needed to validate a reliable marker for risk stratification in clinical practice. Kidney injury molecule-1 (Kim-1), a transmembrane protein expressed on proximal tubular epithelial cells, has been implicated in tubular damage. This study investigated the potential of Kim-1 as a biomarker in MPA. Methods: Kidney biopsy tissues, along with urine and blood samples, were retrospectively analyzed from 52 MPA patients and compared to urine samples from 7 healthy controls. Global disease activity was assessed using the Birmingham vasculitis activity score (BVAS) and vasculitis damage index, while renal disease activity was evaluated using renal BVAS (BVAS-R). Results: Urinary Kim-1 levels were significantly elevated in MPA patients compared to healthy controls. Urinary Kim-1 was positively correlated with the Mayo Clinic Chronicity Score (MCCS) but not with the ANCA Kidney Risk Score (AKRiS), whereas tubular Kim-1 was associated with AKRiS but not with MCCS, indicating their distinct pathological significance. Higher tubular Kim-1 expression was observed in patients with elevated BVAS-R. Urinary Kim-1 levels correlated with proteinuria and were associated with the Mayo Clinic Chronicity Score (MCCS) and ANCA Kidney Risk Score (AKRiS) but not with glomerular lesion severity. Unlike C-reactive protein (CRP), neither urinary nor tubular Kim-1 predicted MPA recurrence. Conclusions: Urinary Kim-1 reflects histopathologic findings and renal impairment but does not predict systemic disease activity or recurrence in MPA, demonstrating its potential clinical utility as a biomarker for assessing chronic renal damage. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Innovative Therapeutic Approaches in Inflammatory Diseases, Pioneering Precision Medicine Solutions)

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14 pages, 8900 KiB

Open AccessArticle

Genome-Wide Identification of β-Ketoacyl CoA Synthase Gene Family in Melon (Cucumis melo L.) and Its Expression Analysis in Autotoxicity, Saline-Alkali, and Microplastic Exposure Environments

by Lizhen Zhang, Mingcheng Wang, Xianhuan Tang, Xinyue Yang, Zhizhong Zhang and Jinghua Wu

Curr. Issues Mol. Biol. 2025, 47(3), 195; https://doi.org/10.3390/cimb47030195 - 16 Mar 2025

Viewed by 426

Abstract

β-ketoacyl CoA synthase (KCS) is a key enzyme in the synthesis of long-chain fatty acids. It affects plant stress resistance by regulating the chain length of fatty acid elongation products, the wax deposition in plant epidermis, and the formation of suberization layers. Through [...] Read more.

β-ketoacyl CoA synthase (KCS) is a key enzyme in the synthesis of long-chain fatty acids. It affects plant stress resistance by regulating the chain length of fatty acid elongation products, the wax deposition in plant epidermis, and the formation of suberization layers. Through a comprehensive, genome-wide analysis, we identified members of the melon KCS (CmKCS) family and characterized their sequence features, phylogenetic relationships, and expression profiles under three abiotic stress conditions, employing bioinformatics tools and methods. Fifteen CmKCSs were identified in the melon genome and found to be unevenly distributed across eight chromosomes. The subcellular localization of most members is located on the cytoplasmic membrane and chloroplasts. The CmKCS family amplifies its members in a tandem repeat manner, which is more closely related to the cucumber KCS and has similar gene functions. Subfamilies I, IV, and VI exhibit variations in conserved domain sequences, which may indicate specific functional differentiation. The promoter region harbors various cis-acting elements related to plant hormones and abiotic stress responses. Among these, the most abundant are elements responsive to abscisic acid, methyl jasmonate, salicylic acid, and anaerobic induction. CmKCS5, CmKCS6, CmKCS10, and CmKCS12 showed high expression in autotoxicity, saline-alkali stress, and microplastic exposure environments. These four CmKCSs may play important roles in melon development and stress response. In conclusion, this study provides a comprehensive analysis of the CmKCS gene family, revealing its potential roles in melon’s response to abiotic stresses and laying a foundation for further functional characterization of these genes in stress tolerance mechanisms. Full article

(This article belongs to the Section Molecular Plant Sciences)

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16 pages, 1951 KiB

Open AccessArticle

Synergistic Effect of Serratia fonticola and Pseudomonas koreensis on Mitigating Salt Stress in Cucumis sativus L.

by Sajid Ali, Murtaza Khan and Yong-Sun Moon

Curr. Issues Mol. Biol. 2025, 47(3), 194; https://doi.org/10.3390/cimb47030194 - 15 Mar 2025

Viewed by 627

Abstract

Beneficial microbes enhance plant growth and development, even under stressful conditions. Serratia fonticola (S1T1) and Pseudomonas koreensis (S4T10) are two multi-trait plant growth-promoting rhizobacteria (PGPRs) that are resistant to saline conditions. This study evaluated the synergistic effect of these PGPRs on mitigating salinity [...] Read more.

Beneficial microbes enhance plant growth and development, even under stressful conditions. Serratia fonticola (S1T1) and Pseudomonas koreensis (S4T10) are two multi-trait plant growth-promoting rhizobacteria (PGPRs) that are resistant to saline conditions. This study evaluated the synergistic effect of these PGPRs on mitigating salinity stress (200 mM) in Cucumis sativus. Presently, the synergistic effect of both strains enhances the plant growth-promoting attributes of cucumber, and the growth parameters were significantly higher than those of uninoculated plants. The PGPR-treated plants revealed a significantly higher biomass and improved chlorophyll content. The inoculation of S1T1 and S4T10 and the synergistic effect of both promoted 23, 24, and 28% increases, respectively, in the fresh biomass and 16, 19.8, and 24% increases, respectively, in the dry biomass. Similarly, S1T1 and S4T10 and their synergistic effects led to 16.5, 28.4, and 38% increases, respectively, in the water potential and 18, 22, and 28% decreases, respectively, in abscisic acid (ABA). A reduction in the electrolytic leakage (EL) was additional proof of successful PGPR activities. Similarly, a decrease in the antioxidant levels, including those of malondialdehyde (21–30%), hydrogen peroxide (19–38%), and superoxide anions (24–34%), was observed, alongside an increase in antioxidant enzymes such as catalase (22–29%) and superoxide dismutase (17–27%). Additionally, the synergistic inoculation of the PGPRs enhanced the NaCl stress tolerance by upregulating the expression of the ion transporter genes HKT1 (1–2-fold), NHX (1–3-fold), and SOS1 (2–4-fold). Conclusively, the synergistic effect of the multi-trait PGPRs significantly enhances C. sativus L. growth under salt stress. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Plant Stress Tolerance)

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20 pages, 2975 KiB

Open AccessArticle

Molecular Docking and Pharmacological In Silico Evaluation of Camptothecin and Related Ligands as Promising HER2-Targeted Therapies for Breast Cancer

by Elmer Joel Millan-Casarrubias, Yunia Verónica García-Tejeda, Claudia Haydée González-De la Rosa, Lucero Ruiz-Mazón, Yazmín Mariela Hernández-Rodríguez and Oscar Eduardo Cigarroa-Mayorga

Curr. Issues Mol. Biol. 2025, 47(3), 193; https://doi.org/10.3390/cimb47030193 - 15 Mar 2025

Viewed by 888

Abstract

Breast cancer is one of the leading causes of cancer-related mortality in women worldwide, highlighting the importance of effective therapies. This study evaluates the interaction between camptothecin, a potent anticancer agent, and two key receptors implicated in breast cancer progression: HER2 (human epidermal [...] Read more.

Breast cancer is one of the leading causes of cancer-related mortality in women worldwide, highlighting the importance of effective therapies. This study evaluates the interaction between camptothecin, a potent anticancer agent, and two key receptors implicated in breast cancer progression: HER2 (human epidermal growth factor receptor 2) and EGFR (epidermal growth factor receptor), using molecular docking. The results reveal a stronger binding affinity between camptothecin and HER2 than EGFR, in contrast to neratinib, which demonstrated affinity exclusively for HER2. Camptothecin exhibits significant hydrophobic and pi-alkyl interactions with HER2, whereas its interactions with EGFR are primarily mediated by hydrogen bonds. Molecular dynamics (MD) simulations of the camptothecin-HER2 complex indicate stable binding, with minimal fluctuations observed over 100 nanoseconds, confirming the stability of the ligand–receptor interaction. Pharmacokinetic evaluations, based on Lipinski’s rule of five, demonstrate that camptothecin adheres to essential drug-likeness parameters, suggesting favorable bioavailability. Furthermore, the analysis comparing the pharmacological properties of camptothecin with other well-known anticancer compounds, such as neratinib, shows that camptothecin exhibited superior compliance with drug-likeness rules. Despite its low solubility, the binding stability and pharmacokinetic profile suggest its potential as an effective therapeutic agent for breast cancer, particularly when combined with drug delivery systems that enhance solubility. This work underscores the importance of receptor-specific ligand interactions in drug design and highlights the need for further studies into camptothecin’s clinical applications, especially in HER2-positive breast cancer treatment. Full article

(This article belongs to the Special Issue Drugs: Mechanisms of Action, Molecular Targets and Biological Activities, 2nd Edition)

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14 pages, 316 KiB

Open AccessReview

The Role of the Arcuate Nucleus in Regulating Hunger and Satiety in Prader-Willi Syndrome

by Charlotte Höybye and Maria Petersson

Curr. Issues Mol. Biol. 2025, 47(3), 192; https://doi.org/10.3390/cimb47030192 - 14 Mar 2025

Viewed by 866

Abstract

Prader-Willi syndrome (PWS) is a rare genetic disorder. The main characteristics are muscular hypotonia, failure to thrive and feeding problems in infancy, which switch to hyperphagia in early childhood and continue into adulthood. Due to hyperphagia, the risk of developing morbid obesity is [...] Read more.

Prader-Willi syndrome (PWS) is a rare genetic disorder. The main characteristics are muscular hypotonia, failure to thrive and feeding problems in infancy, which switch to hyperphagia in early childhood and continue into adulthood. Due to hyperphagia, the risk of developing morbid obesity is high without treatment. PWS is considered a hypothalamic disease, and within the hypothalamus the arcuate nucleus (AC) is of central importance for controlling metabolism, hunger, and satiety. The AC has been studied in several animal models as well as in humans, including PWS. The function of AC is regulated by several neuropeptides and proteins produced within the central nervous system such as oxytocin, orexin, tachykinins as well as the hypothalamic hormones, regulating the adeno-hypophyseal hormones, also acting as neurotransmitters. Additionally, there are many peripheral hormones among which insulin, leptin, adiponectin, ghrelin, and glucagon-like peptide (GLP-1) are the most important. High levels of adiponectin and ghrelin have consistently been reported in PWS, but dysregulation and deviating levels of many other factors and hormones have also been demonstrated in both individuals with PWS and in animal models. In this review, we focus on the role of AC and peptides and proteins produced within the central nervous system in the regulation of hunger and satiety in PWS. Full article

(This article belongs to the Special Issue Current Advances in Oxytocin Research)

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22 pages, 1080 KiB

Open AccessReview

Emerging Therapeutic Innovations for Vitiligo Treatment

by Weiran Li, Penghao Dong, Guiyuan Zhang, Junjie Hu and Sen Yang

Curr. Issues Mol. Biol. 2025, 47(3), 191; https://doi.org/10.3390/cimb47030191 - 14 Mar 2025

Viewed by 3110

Abstract

Vitiligo is a chronic autoimmune disorder with a multifactorial etiology, typically manifesting as localized or generalized hypopigmentation or depigmentation of the skin and mucous membranes. The pathogenesis of vitiligo is complex and significantly impacts patients’ quality of life. Although traditional treatments such as [...] Read more.

Vitiligo is a chronic autoimmune disorder with a multifactorial etiology, typically manifesting as localized or generalized hypopigmentation or depigmentation of the skin and mucous membranes. The pathogenesis of vitiligo is complex and significantly impacts patients’ quality of life. Although traditional treatments such as hormone therapy, topical medications, and laser therapy can help control the disease to some extent, their outcomes remain unsatisfactory. Therefore, ongoing research is crucial to explore and develop novel treatment strategies while assessing their efficacy and safety. This review aims to classify and summarize various new candidate drugs for vitiligo currently undergoing clinical trials, providing a reference for clinical practice. Recent advancements in the understanding of the pathogenesis of vitiligo have facilitated the development of potential treatment strategies, such as Janus kinase inhibitors, cytokine blockers, and agents targeting tissue-resident memory or regulatory T cells. These emerging therapies offer hope to patients with vitiligo, though further investigation is needed to confirm their safety, efficacy, and optimal treatment regimens. Full article

(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses, 2nd Edition)

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17 pages, 796 KiB

Open AccessReview

Exploring Oxylipins in Host–Microbe Interactions and Their Impact on Infection and Immunity

by Robert J. Neff and Christopher D. Radka

Curr. Issues Mol. Biol. 2025, 47(3), 190; https://doi.org/10.3390/cimb47030190 - 14 Mar 2025

Viewed by 616

Abstract

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While [...] Read more.

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting inflammation and PUFAs mitigating it. Oxylipins, bioactive molecules derived from the oxidation of PUFAs, play crucial roles in immune regulation across various organisms, including plants, fungi, and bacteria. These molecules, such as prostaglandins, leukotrienes, and resolvins, regulate immune responses during infection and inflammation. The production of oxylipins extends beyond mammals, with fungi and bacteria synthesizing these molecules to modulate immune responses, promoting both defense and pathogenesis. This review delves into the multifaceted effects of oxylipins, exploring their impact on host and microbial interactions, with a focus on their potential for therapeutic applications in modulating infection and immune response. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation)

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26 pages, 12261 KiB

Open AccessArticle

Unravelling Convergent Signaling Mechanisms Underlying the Aging-Disease Nexus Using Computational Language Analysis

by Marina Junyent, Haki Noori, Robin De Schepper, Shanna Frajdenberg, Razan Khalid Abdullah Hussen Elsaigh, Patricia H. McDonald, Derek Duckett and Stuart Maudsley

Curr. Issues Mol. Biol. 2025, 47(3), 189; https://doi.org/10.3390/cimb47030189 - 14 Mar 2025

Viewed by 622

Abstract

Multiple lines of evidence suggest that multiple pathological conditions and diseases that account for the majority of human mortality are driven by the molecular aging process. At the cellular level, aging can largely be conceptualized to comprise the progressive accumulation of molecular damage, [...] Read more.

Multiple lines of evidence suggest that multiple pathological conditions and diseases that account for the majority of human mortality are driven by the molecular aging process. At the cellular level, aging can largely be conceptualized to comprise the progressive accumulation of molecular damage, leading to resultant cellular dysfunction. As many diseases, e.g., cancer, coronary heart disease, Chronic obstructive pulmonary disease, Type II diabetes mellitus, or chronic kidney disease, potentially share a common molecular etiology, then the identification of such mechanisms may represent an ideal locus to develop targeted prophylactic agents that can mitigate this disease-driving mechanism. Here, using the input of artificial intelligence systems to generate unbiased disease and aging mechanism profiles, we have aimed to identify key signaling mechanisms that may represent new disease-preventing signaling pathways that are ideal for the creation of disease-preventing chemical interventions. Using a combinatorial informatics approach, we have identified a potential critical mechanism involving the recently identified kinase, Dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3) and the epidermal growth factor receptor (EGFR) that may function as a regulator of the pathological transition of health into disease via the control of cellular fate in response to stressful insults. Full article

(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)

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18 pages, 2683 KiB

Open AccessArticle

Evaluation of the Antiaging Potential of the Dendropanax morbiferus-Derived Compound Dendropanoxide in TNF-α-Stimulated Human Dermal Fibroblasts

by Si-Young Ahn, Sanghyun Lee, Daeyoung Kim and Sullim Lee

Curr. Issues Mol. Biol. 2025, 47(3), 188; https://doi.org/10.3390/cimb47030188 - 14 Mar 2025

Viewed by 744

Abstract

In this study, we investigated the antiaging potential of dendropanoxide (DP), an active compound derived from Dendropanax morbiferus, in human dermal fibroblasts (NHDFs) induced by Tumor Necrosis Factor-alpha (TNF-α) and in human epidermal keratinocytes (NHEKs) induced by TNF-α and interferon gamma (IFN-γ). [...] Read more.

In this study, we investigated the antiaging potential of dendropanoxide (DP), an active compound derived from Dendropanax morbiferus, in human dermal fibroblasts (NHDFs) induced by Tumor Necrosis Factor-alpha (TNF-α) and in human epidermal keratinocytes (NHEKs) induced by TNF-α and interferon gamma (IFN-γ). We induced oxidative stress related to ultraviolet (UV) radiation with TNF-α and IFN-γ and then treated the cells with various concentrations of DP to evaluate its effects on reactive oxygen species (ROS) production, matrix metalloproteinase-1 (MMP-1) expression, collagen synthesis, inflammatory cytokine expression, and skin barrier protection. The results showed that DP significantly reduced ROS production, indicating its potential to alleviate oxidative stress in the skin. Additionally, DP effectively inhibited MMP-1 production, suggesting that it could prevent collagen degradation in the dermis, significantly increase the secretion of pro-collagen I, promote collagen synthesis, and protect the dermal extracellular matrix (ECM). Moreover, DP significantly reduced the expression of inflammatory cytokines IL-1β and IL-6, thereby inhibiting excessive inflammatory responses in the skin. DP also enhanced the gene expression of key factors involved in skin barrier maintenance, including Kazal-type 5 (SPINK5), loricrin (LOR), aquaporin-3 (AQP3), filaggrin (FLG), and keratin 1 (KRT1), suggesting its potential to maintain and protect the skin barrier. Western blot analysis revealed that DP inhibited TNF-α-induced phosphorylation of JNK and p38, implying that DP exerts antiaging effects through the regulation of the JNK and p38 signaling pathways. Collectively, these findings suggest that DP has significant potential as an antiaging agent. Full article

(This article belongs to the Special Issue Exploring Molecular Pathways in Skin Health and Diseases)

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17 pages, 4874 KiB

Open AccessArticle

Detection of Helicobacter pylori and the Genotypes of Resistance to Clarithromycin, Fluoroquinolones, and Metronidazole in Gastric Biopsies: An In Silico Analysis to Help Understand Antibiotic Resistance

by Pedro Valada, Ana Mata, Rui M. M. Brito, Teresa Gonçalves, José A. Medeiros and Célia Nogueira

Curr. Issues Mol. Biol. 2025, 47(3), 187; https://doi.org/10.3390/cimb47030187 - 13 Mar 2025

Cited by 1 | Viewed by 746

Abstract

Antibiotic resistance in Helicobacter pylori is increasing rapidly and emerging as a major factor in treatment failure. We aimed to identify genetic mutations associated with resistance to clarithromycin (23S rRNA peptidyl transferase), fluoroquinolones (gyrA), and metronidazole (rdxA), and to [...] Read more.

Antibiotic resistance in Helicobacter pylori is increasing rapidly and emerging as a major factor in treatment failure. We aimed to identify genetic mutations associated with resistance to clarithromycin (23S rRNA peptidyl transferase), fluoroquinolones (gyrA), and metronidazole (rdxA), and to explore their mechanisms of action through molecular modeling. H. pylori detection and the molecular characterization of genes were conducted directly on gastric biopsies by real-time PCR followed by nucleotide sequencing. A 3D model was used to evaluate molecular interactions between the antibiotics and respective target proteins. H. pylori was identified in 66.7% of 33 patients. An analysis of 23SrRNA revealed novel mutations that, by in silico analysis, do not appear to contribute to clarithromycin resistance. In gyrA, mutations in amino acid residues 87 and 91 had an incidence of 27%, and the in silico analysis revealed that these positions are relevant in the binding and resistance to fluoroquinolones. It is also reported for other mutations, some of which are never described. All rdxA mutations were missense, with R16H, M56V, H97T, G98S, A118T, V123T, and R131K predicted by in silico analysis to impact metronidazole resistance. Monitoring H. pylori gene mutations is crucial for tailoring effective antibiotic therapies. Our study advances personalized medicine by introducing novel methods to detect resistance-related mutations and uncovering the molecular mechanisms driving this resistance. Full article

(This article belongs to the Special Issue Bioinformatics Research in Bacterial Genomics, Metagenomics and Metatranscriptomics)

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13 pages, 1944 KiB

Open AccessArticle

Antioxidant Mechanisms of the Protective Action of Selenase in Experimental Chronic Generalized Periodontitis

by Valeriy Salnykov, Igor Belenichev, Lyudmyla Makyeyeva, Dmytro Skoryna, Valentyn Oksenych and Oleksandr Kamyshnyi

Curr. Issues Mol. Biol. 2025, 47(3), 186; https://doi.org/10.3390/cimb47030186 - 12 Mar 2025

Viewed by 602

Abstract

Inflammatory periodontal diseases, despite all the efforts of modern dentistry, remain an important predictor of tooth loss worldwide. Oxidative stress plays a crucial role in the pathogenesis of periodontitis, making the use of antioxidants an attractive option for its treatment. Our attention was [...] Read more.

Inflammatory periodontal diseases, despite all the efforts of modern dentistry, remain an important predictor of tooth loss worldwide. Oxidative stress plays a crucial role in the pathogenesis of periodontitis, making the use of antioxidants an attractive option for its treatment. Our attention was drawn to the selenium compound Selenase as an antioxidant therapeutic agent. In this study, we modeled a calcium-deficient prooxidant chronic generalized periodontitis (CGP) model in white non-linear rats. Then, after 14 days, Selenase (50 μg/kg) and Mexidol (250 mg/kg) were administered intragastrically. Blood samples from the animals were analyzed using ELISA and biochemical methods to determine Cu-Zn SOD, nitrotyrosine, GPX-4, iNOS, NO_x, GSH, and GSSG levels. The CGP model led to the typical clinical signs of periodontitis, including hyperemia, edema, gingival pocket formation, bleeding, tooth mobility, as well as an increase in molecular–biochemical markers of nitrosative stress and a reduction of endogenous antioxidants in the blood. Selenase resulted in a decrease in the clinical manifestations of CGP, reduced iNOS, nitrotyrosine, and NO_x levels, and an increase in Cu-Zn SOD and GPX-4 compared to the control group (p < 0.05). Mexidol had a less pronounced effect on these markers compared to Selenase (p < 0.05). Full article

(This article belongs to the Special Issue Molecular Research on Free Radicals and Oxidative Stress)

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19 pages, 2966 KiB

Open AccessArticle

Anti-Infective Screening of Selected Nine Cannabinoids Against Clostridium perfringens and Influenza A (H5N1) Neuraminidases, and SARS-CoV-2 Main Protease and Spike Protein Interactions

by Thanet Pitakbut and Oliver Kayser

Curr. Issues Mol. Biol. 2025, 47(3), 185; https://doi.org/10.3390/cimb47030185 - 12 Mar 2025

Viewed by 768

Abstract

Recently, cannabinoids have gained scientific interest as a promising anti-infective natural product class, as reported in several studies. However, the existing knowledge is mainly limited to common cannabinoids like THC and CBD. Therefore, this study aims to fill the knowledge gap by investigating [...] Read more.

Recently, cannabinoids have gained scientific interest as a promising anti-infective natural product class, as reported in several studies. However, the existing knowledge is mainly limited to common cannabinoids like THC and CBD. Therefore, this study aims to fill the knowledge gap by investigating the anti-infective potential of nine selected cannabinoids (both common and rare cannabinoids): THC, CBD, CBC, CBE, CBF, CBG, CBL, CBN, and CBT against Clostridium perfringens and Influenza A (H5N1) neuraminidases and SARS-CoV-2 main protease and spike protein–human ACE2 interaction using a standard in vitro biochemical enzyme-binding assay. As a result, to the authors’ knowledge, this study is the first to demonstrate the most promising effect of CBG over others in its class against C. perfringens and influenza A (H5N1) neuraminidases and SARS-CoV-2 main protease and spike protein–human ACE2 interaction. In comparison to CBG, CBD and THC were the second and third most promising candidates. Meanwhile, the other derivatives, such as CBC, CBE, CBF, CBL, CBN, and CBT, showed at least one anti-infective effect. Our findings during the early drug discovery process indicate a promising anti-infective potential of cannabinoids, which can be considered for further investigation in a biological setup. Full article

(This article belongs to the Special Issue Natural Product Drug Activity and Biomedicine Application)

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14 pages, 274 KiB

Open AccessArticle

A Comparison of the Treatment Effects of a Risperidone Solution, an Equal Ratio of DHA/ARA, and a Larger Ratio of Omega-6 PUFA Added to Omega-3 PUFA: An Open-Label Clinical Trial

by Kunio Yui and George Imataka

Curr. Issues Mol. Biol. 2025, 47(3), 184; https://doi.org/10.3390/cimb47030184 - 12 Mar 2025

Viewed by 537

Abstract

We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each [...] Read more.

We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each n = 13): RIS-OS; equal doses of 240 mg of omega-3 PUFA docosahexaenoic acid and omega-6 PUFA arachidonic acid (1:1) (aravita); and omega-6 precursor linoleic acid (480 mg) and omega-3 precursor alpha-linolenic acid (120 mg) (4:1) (awake). The primary outcome was the Autism Diagnostic Interview—Revised score. The secondary outcomes were the Social Responsiveness Scale (SRS) and Aberrant Behavior Check scores. The results of the linear mixed-effects model revealed that the RIS-OS group exhibited significant improvement in the SRS subscale scores of social motivation at weeks 8, 12, and 16 compared with the aravita and awake groups, as well as in the SRS subscale score of social mannerisms at weeks 12 and 16 compared with the aravita group. Moreover, the RIS-OS group showed a trend towards significantly lower plasma ceruloplasmin (Cp) levels. Their plasma insulin-like growth factor (IGF) levels were significantly higher at week 8 than in the subsequent weeks. The high Cp and IGF levels may be attributed to reduced neuroinflammation. These findings demonstrate, firstly, that reduced inflammation through increased anti-inflammatory proteins such as Cp and IGF has clinical effects on the motivation–reward system and mannerisms in patients with ASD through the amelioration of dopamine D2, 5-HT2a, and 5-HT2b dysfunction. Full article

(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)

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Curr. Issues Mol. Biol., Volume 47, Issue 3 (March 2025) – 79 articles

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