Current Issues in Molecular Biology

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Molecular Distinctions, Diagnosis, and Mechanism-Based Therapies in Lipedema and Obesity

by Yiğit Ege Güney, Sıla Çağla Demiralay and İlke Keser

Curr. Issues Mol. Biol. 2026, 48(9), 892; https://doi.org/10.3390/cimb48090892 - 1 Sep 2026

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Lipedema and obesity are often misdiagnosed or clinically confused yet arise via distinct mechanisms, complicating diagnosis and treatment. This review synthesizes evidence differentiating these conditions across genetic, hormonal, inflammatory and mechanical pathways to identify therapeutic targets. Lipedema may involve genetic predisposition (forkhead box [...] Read more.

Lipedema and obesity are often misdiagnosed or clinically confused yet arise via distinct mechanisms, complicating diagnosis and treatment. This review synthesizes evidence differentiating these conditions across genetic, hormonal, inflammatory and mechanical pathways to identify therapeutic targets. Lipedema may involve genetic predisposition (forkhead box C2 [FOXC2], prospero homeobox 1 [PROX1]), hormonal dysregulation with aberrant aromatase activity, and altered adipogenesis (peroxisome proliferator-activated receptor gamma [PPARγ], CCAAT/enhancer-binding protein [C/EBP]). A proinflammatory microenvironment with macrophage M1/M2 imbalance, elevated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and extracellular matrix remodeling is hypothesized to drive fibrosis. Emerging evidence implicates gut-derived endotoxemia (lipopolysaccharide [LPS]-toll-like receptor 4 [TLR4]-nuclear factor kappa-B [NF-κB]) and mechanotransduction (Yes-associated protein [YAP]/transcriptional coactivator with PDZ-binding motif [TAZ]) in adipocyte hypertrophy and treatment resistance. Obesity involves systemic metabolic dysfunction with visceral adiposity and cardiometabolic comorbidities. Lipedema patients maintain metabolic health, exhibit gluteofemoral fat distribution and experience neuropathic pain via nociceptor sensitization (transient receptor potential vanilloid 1 [TRPV1] and ankyrin 1 [TRPA1]) with central amplification. Weight-loss interventions are ineffective, necessitating targeted strategies. Promising targets include TLR4 antagonism, vascular endothelial growth factor C/vascular endothelial growth factor receptor-3 (VEGF-C/VEGFR3) modulation for lymphatic enhancement, YAP/TAZ inhibition and neuromodulators for pain. Physical therapy functions as a biological modifier targeting inflammation, lymphatic drainage and mechanotransduction. This review highlights promising but largely hypothesis-generating molecular insights and calls for validated biomarkers, rigorous clinical trials, and mechanism-based therapies. Many of the pathways discussed require further confirmation in human studies. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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21 pages, 928 KB

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Molecular Mechanisms in Responses to Combined Stresses in Strawberry

by Xiang Zhang, Xuemei Xia, Shuang Wang, Qi Sun, Lingxue Kong, Jiajie Yu and Xiaohong Li

Curr. Issues Mol. Biol. 2026, 48(8), 793; https://doi.org/10.3390/cimb48080793 - 5 Aug 2026

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Abstract

Strawberry is a globally important yet stress-sensitive crop, increasingly threatened by combined abiotic and biotic stresses. Unlike single stresses, combined stresses elicit unique, non-additive responses through complex signaling and gene regulatory networks. This review synthesizes current knowledge on the molecular mechanisms underlying strawberry [...] Read more.

Strawberry is a globally important yet stress-sensitive crop, increasingly threatened by combined abiotic and biotic stresses. Unlike single stresses, combined stresses elicit unique, non-additive responses through complex signaling and gene regulatory networks. This review synthesizes current knowledge on the molecular mechanisms underlying strawberry responses to combined stresses, focusing on signal perception and transduction as well as gene regulation. We examine how combined stresses are perceived by membrane-localized sensors and calcium channels, and how these signals are transduced through MAPK (mitogen-activated protein kinase) cascades, CDPKs (calcium-dependent protein kinases), and hormonal crosstalk involving ABA (abscisic acid), JA (jasmonic acid), and ethylene. At the gene regulation level, we discuss the roles of key transcription factors (WRKY, NAC (NAM, ATAF1, ATAF2 and CUC2), GRAS (GAI-RGA-and-SCR), DREB (Dehydration-Responsive Element-Binding protein), bZIP (basic leucine zipper transcription factor), CAMTA (calmodulin-binding transcription activator), ARF (auxin response factor), and LAV (Leafy Cotyledon2–Abscisic Acid Insensitive3–Val)), transcriptional cascades, epigenetic regulation via DNA methylation, and post-transcriptional (miRNAs such as Fan-miR73) and post-translational (ubiquitination and phosphorylation) control mechanisms. The review also evaluates emerging mitigation strategies informed by these molecular insights, including genomic selection, and explores future directions such as CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing and multi-omics integration. We conclude that understanding the integrated signaling and gene regulatory networks is essential for developing climate-resilient strawberry cultivars capable of withstanding increasingly complex stress combinations. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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13 pages, 3343 KB

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Bacterial Sentience Is Determined by the Stochastic, Chaotic, and Deterministic Behavior of Cytoplasmic Particles

by Leon M. T. Dicks, Carolina Pohl and Alfred Botha

Curr. Issues Mol. Biol. 2026, 48(8), 777; https://doi.org/10.3390/cimb48080777 - 30 Jul 2026

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Abstract

Bacteria are constantly exposed to stress, which intensifies as cells age, nutrients are depleted, and metabolite levels change. As metabolic activity increases, the cytoplasm transitions from a glass-like to a more fluid state, supporting the stochastic (spontaneous) and chaotic (nonlinear and unpredictable) movement [...] Read more.

Bacteria are constantly exposed to stress, which intensifies as cells age, nutrients are depleted, and metabolite levels change. As metabolic activity increases, the cytoplasm transitions from a glass-like to a more fluid state, supporting the stochastic (spontaneous) and chaotic (nonlinear and unpredictable) movement of particles. The rate at which suspended particles or those in vacuole-like “cages” move depends on the cytoplasm’s energized and fluidic state. Cells respond to stochastic and chaotic behavior by regulating gene transcription, translation, and post-translational modifications. These stochastic and chaotic reactions generate a liquid–liquid phase separation (LLPS), causing particles to separate. This produces a dynamic force that drives cytoplasmic “turnover”. Internal and external physicochemical changes are monitored by chemoreceptors on the cell surface and embedded in the cell membrane, which activate transcriptional regulators to control gene expression, modulate enzymatic fluctuations, and regulate post-translational modifications. Sentience may also arise from the quantum-like behavior of ions, electrons, neutrons, and protons (tunneling and entanglement) and from hyperstructures that drive complex enzymatic reactions. This is, however, a highly debated topic. We argue that bacteria are conscious and do not rely solely on phosphorylation states, as in two-component systems (TCSs), but also on other cytoplasmic dynamics. We provide several examples to support the argument. It is, however, important to note that bacterial consciousness cannot be compared to that of higher life forms with a central nervous system. We refer to bacteria’s awareness of their environment as sentience and define bacterial sentience as the ability to respond to external stimuli and to reactions within a dynamic cytoplasm, thereby transferring signals either directly or via signal transduction pathways to turn gene expression on or off. We also point out that stochastic/chaotic randomness keeps the cytoplasm in a permanently dynamic, flexible, and stochastic state, safeguarding the cell against sudden, unpredictable environmental changes. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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21 pages, 5371 KB

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Rhizosphere Reactive Oxygen Species: Detection Methods, Distribution Characteristics, Production Mechanisms, and Environmental Effects

by Xiaoling Xu, Chuanxiang Li, Jian He, Jian Wang and Jinbo Liu

Curr. Issues Mol. Biol. 2026, 48(8), 758; https://doi.org/10.3390/cimb48080758 - 26 Jul 2026

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Abstract

The rhizosphere, the zone around the roots of plants, including the root, the soil on the root itself, and the surrounding area soil, is the hotspot for the production of reactive oxygen species (ROS). Functioning as redox signaling mediators, rhizosphere ROS regulate a [...] Read more.

The rhizosphere, the zone around the roots of plants, including the root, the soil on the root itself, and the surrounding area soil, is the hotspot for the production of reactive oxygen species (ROS). Functioning as redox signaling mediators, rhizosphere ROS regulate a series of key processes in the rhizosphere microenvironment. These biological and geochemical events cover root morphogenesis, the formation of beneficial plant–microbe symbioses, and element biogeochemical transformations. Nevertheless, the pronounced spatial heterogeneity, drastic redox fluctuations, and intricate interfacial interactions within the rhizosphere impede accurate in situ detection of ROS. Beyond technical barriers, the coupled regulatory effects exerted by biotic and abiotic factors on ROS dynamics, together with the associated ecological outcomes induced by rhizosphere ROS, remain difficult to fully disentangle. This review first discusses updated strategies and optimized methodologies for in situ rhizosphere ROS monitoring. We then characterize the spatial distribution patterns and microscale hotspots of rhizosphere ROS. Importantly, this review dissects the complex coupled regulatory network formed by biotic, abiotic, and environmental factors and molecular regulatory pathways that control ROS production. Furthermore, this study systematically illustrates diverse environmental effects triggered by rhizosphere ROS. Finally, the present work identifies prevailing research gaps and unresolved limitations in current studies. On this basis, we further propose targeted research directions for future studies in this field, providing comprehensive theoretical evidence to deepen the understanding of rhizosphere ROS formation and their mediated biogeochemical processes. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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56 pages, 3148 KB

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Plant Bioactive Constituents and Their Potential Benefits in HPV-Positive Oropharyngeal Squamous Cell Carcinoma—A Narrative Review

by Violeta Popovici, Emma Adriana Ozon, Manuela Apetrei, Rodica Boca and Cerasela Elena Gîrd

Curr. Issues Mol. Biol. 2026, 48(6), 626; https://doi.org/10.3390/cimb48060626 - 16 Jun 2026

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Abstract

Human papillomavirus (HPV) has become a leading cause of oropharyngeal cancers, alongside well-known risk factors such as tobacco and alcohol use. Currently, HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) has increased significantly in developed countries, with HPV-16 being the most common high-risk subtype. [...] Read more.

Human papillomavirus (HPV) has become a leading cause of oropharyngeal cancers, alongside well-known risk factors such as tobacco and alcohol use. Currently, HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) has increased significantly in developed countries, with HPV-16 being the most common high-risk subtype. Clinically, HPV+ OPSCC shows clear differences in prognosis compared to HPV-negative tumors, particularly regarding survival rates and treatment responses. Patients with HPV+ OPSCC tend to have notably better survival outcomes and a more favorable outlook. Strong evidence indicates that HPV-related oropharyngeal cancers represent a distinct epidemiological, clinical, and molecular group, setting them apart from non-HPV-related cancers. As a result, treatment strategies for these subtypes should follow specific clinical protocols to optimize outcomes. Additionally, the viral oncoproteins E6 and E7, which systematically disrupt host tumor-suppressor networks, provide strong reasons for targeted phytotherapeutic interventions. Therefore, there is increasing interest in exploring plant bioactive compounds with promising anti-HPV and anticancer effects that target key oncogenic pathways. This review aims to compile the latest data on bioactive phytochemicals with mechanistic evidence in HPV+ OPSCC, highlight their molecular interactions across oncogenic signaling pathways, and discuss evidence-based findings focusing on research published from 2000 to 2025. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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17 pages, 11952 KB

Open AccessEditor’s ChoiceReview

Microbial α-L-Rhamnosidases: Regioselective Biocatalysts for Flavonoid Biotransformation and Nutraceutical Applications

by Massimo Iorizzo

Curr. Issues Mol. Biol. 2026, 48(6), 625; https://doi.org/10.3390/cimb48060625 - 16 Jun 2026

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Abstract

Microbial α-L-rhamnosidases are increasingly recognised as selective biocatalysts in food biotechnology, nutraceutical production, and health-related applications. These glycoside hydrolases catalyse the hydrolysis of terminal alpha-L-rhamnose residues from flavonoids, terpenoids, saponins, and other glycosylated natural products, thereby modulating sensory properties, solubility, intestinal absorption, and [...] Read more.

Microbial α-L-rhamnosidases are increasingly recognised as selective biocatalysts in food biotechnology, nutraceutical production, and health-related applications. These glycoside hydrolases catalyse the hydrolysis of terminal alpha-L-rhamnose residues from flavonoids, terpenoids, saponins, and other glycosylated natural products, thereby modulating sensory properties, solubility, intestinal absorption, and biological activity. While their traditional uses include debittering citrus juice and enhancing wine aroma, recent evidence demonstrates their wider value in selective flavonoid biotransformation, production of rare mono-glycosylated derivatives, probiotic fermentations, and microbiome-associated metabolism. This review summarises microbial sources, catalytic mechanisms, CAZy classification, substrate specificity, structure–function relationships, analytical methods, industrial process engineering, and emerging applications in functional foods and targeted nutraceutical applications. Particular attention is given to the distinction between alpha-(1→2)- and alpha-(1→6)-linked substrates, the production of isoquercitrin and prunin, recombinant enzyme platforms, immobilised biocatalysts, and potential future opportunities arising from metagenomics, synthetic biology, and AI-assisted protein engineering. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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52 pages, 4432 KB

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Molecular-Genetic Basis of Pulmonary Arterial Hypertension (PAH)

by Mark Okot, Aneesa Ahmed, Colin W. Wright and Md Talat Nasim

Curr. Issues Mol. Biol. 2026, 48(6), 572; https://doi.org/10.3390/cimb48060572 - 29 May 2026

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Abstract

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, [...] Read more.

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20–30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional “second hits”, including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53–86% of heritable PAH and 14–35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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22 pages, 1554 KB

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DPP-4 Inhibitors in Female Cancers: Opportunities for Drug Repurposing

by Hiba F. Muddather, Zsuzsanna Schelz and István Zupkó

Curr. Issues Mol. Biol. 2026, 48(5), 445; https://doi.org/10.3390/cimb48050445 - 24 Apr 2026

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Abstract

Female malignancies, including breast, cervical, ovarian, and endometrial cancers, remain a significant health challenge. Meanwhile, treatment options for advanced-stage remain limited. Drug repurposing has emerged as a promising approach to accelerate the development of effective cancer therapies using existing medications. Growing evidence indicates [...] Read more.

Female malignancies, including breast, cervical, ovarian, and endometrial cancers, remain a significant health challenge. Meanwhile, treatment options for advanced-stage remain limited. Drug repurposing has emerged as a promising approach to accelerate the development of effective cancer therapies using existing medications. Growing evidence indicates that metabolic disorders such as type 2 diabetes mellitus are linked with an elevated risk of tumors, highlighting antidiabetic drugs as potential anticancer agents. Among these, inhibitors of dipeptidyl peptidase 4 (DPP4) have attracted attention as potential therapeutic candidates, due to their diverse biological functions in glucose metabolism, inflammation, immune regulation, and tumor biology. This review summarizes current epidemiological, preclinical, and clinical evidence regarding the role of DPP4 in female cancers and the therapeutic potential of DPP4 inhibitors. Studies demonstrate that DPP4 influences key oncogenic processes, including proliferation, invasion, metastasis, immune modulation, and metabolic reprogramming. However, available data on DPP4 inhibition and its influence in cancer therapy are controversial and scarce. Further mechanistic studies and well-designed clinical investigations are required to clarify their safety and clinical applicability in the management of female malignancies. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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26 pages, 1342 KB

Open AccessEditor’s ChoiceReview

Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels

by Rebecca Jung, Emily Kao, Victor H. Guaiquil, Ali R. Djalilian and Mark I. Rosenblatt

Curr. Issues Mol. Biol. 2026, 48(3), 332; https://doi.org/10.3390/cimb48030332 - 21 Mar 2026

Cited by 1 | Viewed by 2289

Abstract

Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component [...] Read more.

Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component of ocular pain experienced by a growing subset of patients. Recent developments in sensory neuroscience have highlighted the pivotal role of ion channels in mediating ocular surface homeostasis, pain signaling, and inflammation. This review examines the role of the following major ion channel families in the pathophysiology of DED and neuropathic ocular pain: transient receptor potential (TRP) channels, voltage-gated sodium (Nav) channels, and purinergic P2X receptors. The review details their anatomical distribution, molecular function, and responses to environmental stimuli such as heat, cold, osmolarity, and injury. Current treatments, such as artificial tears, anti-inflammatory drops, and systemic neuromodulators, are also reviewed in relation to their effects on ion channel modulation. Additionally, emerging therapies that directly target sensory transduction pathways are introduced. This review highlights the therapeutic potential of ion channel modulation in personalizing treatment for patients with ocular surface pain, particularly those with neuropathic features unresponsive to standard care. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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24 pages, 401 KB

Open AccessReview

Blood and Saliva Composition in Cancer: Similarities or Differences?

by Elena I. Dyachenko and Lyudmila V. Bel’skaya

Curr. Issues Mol. Biol. 2026, 48(3), 308; https://doi.org/10.3390/cimb48030308 - 12 Mar 2026

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Abstract

Saliva is of great interest for diagnosing and monitoring various diseases, including cancer. Saliva contains a wide range of proteins, some of which are found in blood plasma, while others are unique. Despite the obvious advantages of using saliva for diagnostics and patient [...] Read more.

Saliva is of great interest for diagnosing and monitoring various diseases, including cancer. Saliva contains a wide range of proteins, some of which are found in blood plasma, while others are unique. Despite the obvious advantages of using saliva for diagnostics and patient monitoring, difficulties in interpreting salivary values remain. Furthermore, the extent to which salivary results correlate with blood test results remains unclear. In this review, we have collected and analyzed all currently available parallel studies of saliva and blood on the nature of changes in biochemical parameters, cytokines, growth factors, hormones, and tumor markers in cancer patients. The most contradictory and divergent changes in saliva and blood were observed when measuring biochemical parameters. Cytokines, growth factors, hormones, and tumor markers in both saliva and blood have a higher reproducibility between independent studies. It is important to consider that the causes and mechanisms behind a particular indicator in saliva may differ from those underlying the same indicators in the blood. Furthermore, these indicators may not always be directly related to cancer. We suggest that comparing identical parameters in blood and saliva is useful in the context of “pathological process routing.” The paper also provides interpretations and hypotheses regarding the causes and nature of changes in saliva and blood composition in cancer. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

20 pages, 1680 KB

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From Metabolism to Longevity: Molecular Mechanisms Underlying Metformin’s Anticancer and Anti-Aging Effects

by Slavica Vujovic, Svetlana Perovic, Milorad Vlaovic, Andjelka Scepanovic and Stasa Scepanovic

Curr. Issues Mol. Biol. 2026, 48(3), 286; https://doi.org/10.3390/cimb48030286 - 7 Mar 2026

Cited by 3 | Viewed by 2263

Abstract

Metformin has stood as the primary clinical tool for type 2 diabetes for decades, yet its potential reach into oncology and gerontology is only now being critically dissected. This review evaluates how metformin might actually pull the levers of cancer progression and biological [...] Read more.

Metformin has stood as the primary clinical tool for type 2 diabetes for decades, yet its potential reach into oncology and gerontology is only now being critically dissected. This review evaluates how metformin might actually pull the levers of cancer progression and biological aging. Evidence from across various models suggests that the drug works by recalibrating cellular energy homeostasis—specifically by triggering AMPK and dampening the mTOR pathway. This signaling shift ripples through downstream processes like autophagy and oxidative stress regulation, theoretically slowing tumor growth and pushing back against cellular senescence. However, our look at the literature from PubMed, Scopus, and Web of Science shows a messy reality where preclinical success often stalls during clinical translation. Even though observational data point toward lower cancer rates in diabetic cohorts, these “wins” are frequently skewed by clinical confounders and inconsistent data. This makes the leap from metabolic control to a broad-spectrum anti-aging or anticancer therapy a point of serious contention. We argue that only large-scale, randomized trials can truly verify if metformin is safe and effective for non-diabetic populations. In the end, untangling these molecular routes is the only way to see if metformin belongs in future oncological or healthy aging strategies. That being said, at least mechanistically, metformin definitely offers potential that warrants such large-scale research. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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27 pages, 1356 KB

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Epigenetic, Genetic, and Functional Germline Alterations of PAX Genes in Human Pathology: A Comprehensive Update

by Valentina Lopez Gomez, Samantha Wegner, Stephanie Ocejo, Dezaray Perez, Diana Jabbour, Virginia Fernandez, Amr Abulaban, Marwan Bahmad, Tarec K. Elajami, Wassim Abou-Kheir and Hisham F. Bahmad

Curr. Issues Mol. Biol. 2026, 48(2), 236; https://doi.org/10.3390/cimb48020236 - 23 Feb 2026

Cited by 1 | Viewed by 1832

Abstract

Paired box (PAX) genes encode a family of nine transcription factors that function as master regulators of embryogenesis, organogenesis, and lineage specification. Their tightly regulated spatial and temporal expression is essential for the development of multiple organ systems, including the central [...] Read more.

Paired box (PAX) genes encode a family of nine transcription factors that function as master regulators of embryogenesis, organogenesis, and lineage specification. Their tightly regulated spatial and temporal expression is essential for the development of multiple organ systems, including the central nervous system, eyes, kidneys, immune system, musculoskeletal system, and endocrine organs. Germline mutations of PAX genes result in a broad and often pleiotropic spectrum of human disease, reflecting the developmental programs governed by each family member. Pathogenic variants in PAX genes underlie diverse congenital disorders such as aniridia (PAX6), renal coloboma syndrome (PAX2), otofaciocervical syndrome with immunodeficiency (PAX1), Waardenburg syndrome (PAX3), maturity-onset diabetes of the young (PAX4), and tooth agenesis (PAX9). These conditions frequently demonstrate variable expressivity, incomplete penetrance, and overlapping phenotypes, which make it challenging to be clinically recognized. Beyond embryogenesis and embryologic development, emerging evidence indicates that several PAX proteins remain active in postnatal tissue maintenance, adult stem cell regulation, immune function, and regenerative responses (particularly PAX7 in skeletal muscle satellite cells and PAX5 in B-cell homeostasis), further expanding their clinical relevance. This review provides a synopsis of the major, clinically relevant, germline PAX gene mutations, emphasizing genotype–phenotype correlations, developmental mechanisms, and disease classification across the organ systems. By integrating molecular genetics with human pathology, we highlight the diagnostic implications of PAX genes as central determinants of congenital disease and provide a framework for understanding how alterations in the developmental transcriptional networks translate into human pathology. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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17 pages, 766 KB

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Contact Unmodified Antisense DNA Biotechnology (CUADb)-Based Oligonucleotide Insecticides and RNA Biocontrols: Molecular Bases and Potential in Plant Protection

by Vol Oberemok, Kate Laikova, Jamin Ali, Ilyas Chachoua and Nikita Gal’chinsky

Curr. Issues Mol. Biol. 2026, 48(2), 235; https://doi.org/10.3390/cimb48020235 - 23 Feb 2026

Cited by 1 | Viewed by 1354

Abstract

Recent advances in molecular genetics, nucleic acid synthesis, and bioinformatics have provided novel opportunities for plants’ protection against insect pests. Currently, both DNA and RNA serve as active insecticidal ingredients, transcending their traditional role as carriers of genetic information. This novel activity is [...] Read more.

Recent advances in molecular genetics, nucleic acid synthesis, and bioinformatics have provided novel opportunities for plants’ protection against insect pests. Currently, both DNA and RNA serve as active insecticidal ingredients, transcending their traditional role as carriers of genetic information. This novel activity is achieved through two fundamentally distinct mechanisms. The first one is DNA containment (DNAc), employing oligonucleotide insecticides based on contact unmodified antisense DNA biotechnology (CUADb), also known as ’genetic zipper’ technology. The second one is RNA interference (RNAi), employing RNA biocontrols based on double-stranded RNA (dsRNA) technology. The investigation of the molecular mechanism underlying the antisense activity of nucleic acids emerged in the early 1960s. While the antisense effects of RNA in gene silencing through interference (RNAi) was documented in the late 1990s as antiviral immune responses in nematodes, the CUADb antisense approach initially emerged as a powerful strategy for pest control against lepidopterans in 2008. The CUADb approach relies on disrupting rRNA biogenesis and ribosome production, while RNAi shows the best results in mRNA degradation and no efficient result is known for rRNA. The efficacy of these approaches appears to be species dependent. For example, CUADb demonstrates optimal activity against Sternorrhyncha (e.g., aphids, mealybugs, psyllids, and scale insects), thrips, and mites. In turn, the RNAi strategy shows a strong insecticidal potential against beetles from the Tenebrionidae and Chrysomelidae families. Here, we will review the differences between the two technologies, their mechanisms of action and the current challenges facing their adoption. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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14 pages, 451 KB

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Comparative Analysis of Methodological Aspects of the Study of Extracellular Vesicles and Extracellular Mitochondria: From Isolation to Internalization

by Natalia Yunusova, Dmitry Svarovsky, Evgenya Kaigorodova, Alexey Dobrodeev, Virab Sisakian and Svetlana Tamkovich

Curr. Issues Mol. Biol. 2026, 48(2), 217; https://doi.org/10.3390/cimb48020217 - 16 Feb 2026

Cited by 2 | Viewed by 1730

Abstract

Mitochondrial transfer in mammals has been proven to occur both under physiological conditions and during pathological conditions. It has been shown that neighboring cells can exchange mitochondria via nanotunnel tubes. However, there is evidence that free mitochondria, as well as whole mitochondria and [...] Read more.

Mitochondrial transfer in mammals has been proven to occur both under physiological conditions and during pathological conditions. It has been shown that neighboring cells can exchange mitochondria via nanotunnel tubes. However, there is evidence that free mitochondria, as well as whole mitochondria and individual mitochondrial fragments, can be transported between cells within extracellular vesicles (EVs). This review discusses the methodological aspects of isolation and a minimal set of methods for characterizing mitochondria-rich EVs (mitoEVs), as well as methodological approaches for studying the nucleic acid, protein, and lipid composition. It has been shown that mitoEVs, as well as extracellular mitochondria, contain a characteristic set of nucleic acids of mitochondrial origin. First and foremost, the dominant fraction of mitochondrial nucleic acids is mitochondrial DNA (mtDNA), a circular double-stranded molecule approximately 16.6 thousand base pairs in length. The mechanisms involved in EV internalization include clathrin-dependent endocytosis, caveolin-dependent endocytosis, raft-mediated endocytosis, and macropinocytosis. Mitochondrial-enriched autologous and xenogeneic EVs are thought to be internalized by similar mechanisms. The review also presents the main sources (stem cells, platelet concentrate, peripheral blood mononuclear cells) for obtaining mitochondria-rich EVs for therapeutic purposes. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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21 pages, 1381 KB

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Diverse Bacterial Anti-Phage Strategies: From the Laboratory to the Clinic

by Yong Shao, Zhu Gao, Ying Zhang and Jianqiong Zhang

Curr. Issues Mol. Biol. 2026, 48(2), 191; https://doi.org/10.3390/cimb48020191 - 8 Feb 2026

Cited by 1 | Viewed by 1706

Abstract

Refractory infections caused by multidrug-resistant bacteria have emerged as a substantial threat to public health, prompting renewed interest in phage therapy. Bacteria and phages are ubiquitous in diverse environments, engaging in continuous interaction and co-evolution. In response to phage infection, bacteria have developed [...] Read more.

Refractory infections caused by multidrug-resistant bacteria have emerged as a substantial threat to public health, prompting renewed interest in phage therapy. Bacteria and phages are ubiquitous in diverse environments, engaging in continuous interaction and co-evolution. In response to phage infection, bacteria have developed an array of defense mechanisms. Current studies on bacteria–phage interactions predominantly focus on laboratory settings using artificial media, whereas the final goal of phage therapy—to combat antibiotic-resistant bacteria—lies in its clinical application. This review describes bacterial defense strategies against phage infection in the context of laboratory-based artificial media, animal experiments and clinical cases, aiming to deepen the understanding of bacteria–phage interactions and promote the advancement of effective phage therapy for clinical applications. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)

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