Current Issues in Molecular Biology

19 pages, 6423 KB

Open AccessArticle

Molecular Dissection of Permanent vs. Reperfused Ischemia: Multi-Omics Divergence and Precision Therapeutic Implications

by Zhiyong Shen, Yuxian Li, Tengfei Zhu, Ting Yang, Shiyu Zhou, Qian Liu, Qiong Lu, Dongyan Jing, Haiou Jiang, Jie Li and Xiao-Liang Xing

Curr. Issues Mol. Biol. 2026, 48(1), 124; https://doi.org/10.3390/cimb48010124 - 22 Jan 2026

Viewed by 317

Abstract

Objective: Cerebral ischemia–reperfusion injury (IRI) is a distinct pathological phase that differs from permanent ischemia (IR) in that it triggers secondary damage despite the restoration of blood flow. The primary objective of this study is to comprehensively characterize and compare the molecular signatures—such [...] Read more.

Objective: Cerebral ischemia–reperfusion injury (IRI) is a distinct pathological phase that differs from permanent ischemia (IR) in that it triggers secondary damage despite the restoration of blood flow. The primary objective of this study is to comprehensively characterize and compare the molecular signatures—such as differential gene expression, protein activation, and metabolic alterations—between IRI and IR. By doing so, we aim to identify key pathways and biomarkers that specifically drive IRI and IR pathology, thereby providing novel therapeutic targets to mitigate reperfusion-induced damage in stroke and related neurological conditions. Methods: We employed an integrated transcriptomic and proteomic approach to compare a permanent ischemia model (IR, 24 h ischemia) with a reperfusion model (IRI, 1 h ischemia + 24 h reperfusion), using SHAM-operated animals as controls. Results: Our results demonstrate a profound decoupling between the transcriptome and proteome in IRI. While IRI induced extensive proteomic alterations (160 changed proteins in IRI vs. IR), transcriptional changes were minimal (3 genes), indicating dominant post-transcriptional regulation. Both IR and IRI activated shared inflammatory responses (e.g., Saa3, upregulated 14.33-fold in IRI/SHAM) and metabolic shifts (Gapdh, downregulated 4.03-fold). However, IRI uniquely upregulated neuroprotective genes (Arc, Npas4), activated a specific set of reperfusion-related pathways (72 proteins), and exhibited distinct extracellular matrix remodeling (Mmp3, upregulated 11.24-fold in IR/SHAM). The overall correlation between transcriptomic and proteomic dynamics was remarkably low (r = 0.014), underscoring the importance of translation and protein decay mechanisms. Conclusions: This study redefines IRI not merely as an exacerbation of ischemic damage but as a unique adaptive molecular trajectory. We identify Pisd-ps3 and Saa3 as potential therapeutic targets and show that proteomic signatures can stratify injury phases. These findings advance the prospects of precision therapeutics aimed at neuroprotection and immunomodulation in ischemic stroke. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Graphical abstract

29 pages, 733 KB

Open AccessReview

Spermatogenesis Beyond DNA: Integrated RNA Control of the Epitranscriptome and Three-Dimensional Genome Architecture

by Aris Kaltsas, Maria-Anna Kyrgiafini, Zissis Mamuris, Michael Chrisofos and Nikolaos Sofikitis

Curr. Issues Mol. Biol. 2026, 48(1), 123; https://doi.org/10.3390/cimb48010123 - 22 Jan 2026

Viewed by 486

Abstract

Spermatogenesis is a tightly coordinated differentiation program that sustains male fertility while transmitting genetic and epigenetic information to the next generation. This review consolidates mechanistic evidence showing how RNA-centered regulation integrates with the epitranscriptome and three-dimensional (3D) genome architecture to orchestrate germ-cell fate [...] Read more.

Spermatogenesis is a tightly coordinated differentiation program that sustains male fertility while transmitting genetic and epigenetic information to the next generation. This review consolidates mechanistic evidence showing how RNA-centered regulation integrates with the epitranscriptome and three-dimensional (3D) genome architecture to orchestrate germ-cell fate transitions from spermatogonial stem cells through meiosis and spermiogenesis. Recent literature is critically surveyed and synthesized, with particular emphasis on human and primate data and on stage-resolved maps generated by single-cell and multi-omics technologies. Collectively, available studies support a layered regulatory model in which RNA-binding proteins and RNA modifications coordinate transcript processing, storage, translation, and decay; small and long noncoding RNAs shape post-transcriptional programs and transposon defense; and dynamic chromatin remodeling and 3D reconfiguration align transcriptional competence with recombination, sex-chromosome silencing, and genome packaging. Convergent nodes implicated in spermatogenic failure are highlighted, including defects in RNA metabolism, piRNA pathway integrity, epigenetic reprogramming, and nuclear architecture, and the potential of these frameworks to refine molecular phenotyping in male infertility is discussed. Finally, key gaps and priorities for causal testing in spatially informed, stage-specific experimental systems are outlined. Full article

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

► Show Figures

Figure 1

19 pages, 1393 KB

Open AccessReview

Genetic Associations with Pectus Excavatum: A Systematic Review

by Redoy Ranjan, Nafiz Imtiaz, Benjamin Waterhouse, Ian Paul, Annemarie Brunswicker and Joel Dunning

Curr. Issues Mol. Biol. 2026, 48(1), 122; https://doi.org/10.3390/cimb48010122 - 22 Jan 2026

Viewed by 334

Abstract

Background: Pectus excavatum (PE) is the most common congenital chest wall deformity, affecting approximately 1 in 400 live births. Although familial clustering supports a genetic contribution, the molecular basis of PE remains poorly defined. This systematic review synthesizes existing evidence on genetic variants [...] Read more.

Background: Pectus excavatum (PE) is the most common congenital chest wall deformity, affecting approximately 1 in 400 live births. Although familial clustering supports a genetic contribution, the molecular basis of PE remains poorly defined. This systematic review synthesizes existing evidence on genetic variants associated with PE to guide future genome-wide association studies (GWAS) and Mendelian randomization (MR) analyses. Methods: A comprehensive systematic search was conducted across all electronic databases, including Google Scholar, PubMed/MEDLINE, Web of Science, and arXiv, from inception to November 2025. Nine studies met the inclusion criteria. The search strategy utilized the terms “pectus excavatum”, “genetic variants”, “SNPs”, and “GWAS”, combined with Boolean operators. Eligible studies reported genetic associations, family-based analyses, or mechanistic investigations. The Newcastle–Ottawa Scale was used to assess study quality. Results: No population-level GWAS of isolated PE was identified. Fourteen genetic loci were reported across diverse study designs, including family-based exome sequencing (REST, SMAD4, COL5A1, COL5A2), case reports (COL1A1, COL27A1, NF1, BICD2, PTPN11), candidate gene analyses (ACAN), mouse models (GPR126, GAL3ST4), and linkage analysis implicating chromosome 18q. These genes converge on four key biological pathways: extracellular matrix and collagen metabolism, TGF-β/BMP signaling, cartilage development, and transcriptional regulation. Importantly, none of the included studies reported SNP-level effect sizes, allele frequencies, or odds ratios, precluding construction of valid MR instruments. Conclusions: Current genetic evidence for PE is largely derived from rare variants and family-based studies, with no population-level GWAS available. This critical gap limits causal inference, underscoring the urgent need for large-scale international GWAS to identify common variants and clarify the genetic architecture of PE. Full article

(This article belongs to the Special Issue Innovative Approaches in Bone and Cartilage Regeneration: From Stem Cells to Organoids)

► Show Figures

Figure 1

16 pages, 1597 KB

Open AccessReview

Natural Phytochemicals as Inhibitors of HIF-1α in Breast Cancer: Review of Preclinical Evidence and Future Prospects

by Ivan Dam, Eric Liu, Abida Ali, Chikezie O. Madu and Yi Lu

Curr. Issues Mol. Biol. 2026, 48(1), 121; https://doi.org/10.3390/cimb48010121 - 22 Jan 2026

Viewed by 291

Abstract

Breast cancer is the most prevalent form of cancer among women globally. The hypoxic microenvironment resulting from the rapid oxygen consumption of rapidly dividing cancer cells causes the accumulation of hypoxia-inducible factor-1α (HIF-1α) due to reduced catalytic activity of prolyl hydroxylase domain 2 [...] Read more.

Breast cancer is the most prevalent form of cancer among women globally. The hypoxic microenvironment resulting from the rapid oxygen consumption of rapidly dividing cancer cells causes the accumulation of hypoxia-inducible factor-1α (HIF-1α) due to reduced catalytic activity of prolyl hydroxylase domain 2 (PHD2) and Von Hippel-Lindau (VHL). Under physiological conditions, HIF-1α regulates cell response to hypoxic environments. Activating genes are involved in glycolysis, angiogenesis, and erythropoiesis. However, the sustained hypoxic environment in breast cancer facilitates metastasis, immune evasion, and drug resistance. Consequently, HIF-1α is a key target in breast cancer treatment, and such inhibitors of HIF-1α may prove to be a viable treatment option. Increasing evidence suggests that natural chemicals, such as polyphenols, isothiocyanates, curcumin, and alkaloids, are inhibitors of HIF-1α. Preclinical studies using animal models and breast cancer cell lines indicate significant reductions in angiogenesis, despite challenges of heterogeneity, bioavailability, and dose optimization. This review intends to summarize current evidence on natural inhibitors of HIF-1α and potential future studies. Full article

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

► Show Figures

Figure 1

15 pages, 1216 KB

Open AccessArticle

Methodological and Short-Term Diurnal Variation in Surface and Cargo Proteins in Plasma Extracellular Vesicles

by Hubert Krzyslak, Weronika Maria Szejniuk, Ursula Falkmer, Bent Honoré, Malene Møller Jørgensen, Charlotte Sten, Shona Pedersen, Gunna Christiansen and Søren Risom Kristensen

Curr. Issues Mol. Biol. 2026, 48(1), 120; https://doi.org/10.3390/cimb48010120 - 22 Jan 2026

Cited by 1 | Viewed by 241

Abstract

Extracellular vesicles (EVs) are known as potential biomarkers for several diseases; nevertheless, the degree of technical and biological variability is not yet adequately characterized. Because pre-analytical factors such as blood collection time and EV subpopulation could confound biomarker studies, we performed a pilot [...] Read more.

Extracellular vesicles (EVs) are known as potential biomarkers for several diseases; nevertheless, the degree of technical and biological variability is not yet adequately characterized. Because pre-analytical factors such as blood collection time and EV subpopulation could confound biomarker studies, we performed a pilot study systematically quantifying methodological and biological variability including EV-Array (surface proteins), and proteome characterization of cargo. Plasma samples from six healthy adults were collected at two time points (morning and afternoon) and plasma was analyzed with EV-Array, and isolated EVs were analyzed using nanoparticle tracking analysis (NTA), and label-free mass spectrometry (LC-MS/MS). Methodological repeatability was high for NTA particle size (3.3% CV) and LC-MS (8.2% CV), and lower for EV-Array surface markers (22.6% CV). Variations between samples were reasonable for NTA-size, EV-Array and LC-MS/MS (5–21%) and substantially lower than between-subject variation. No evidence of systemic morning–afternoon shifts in particle size and concentration or EV cargo was observed, although small effects cannot be excluded. The same was true for most surface markers, but minor but statistically significant reductions in a few specific surface markers occurred in afternoon EV-Array samples. In this pilot we therefore do not observe any major systemic diurnal bias in healthy individuals in samples collected a.m. vs. p.m. Despite the small sample size, this study underscores the importance of accounting for individual variability and methodological standardization when designing EV-based biomarker research. Full article

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

► Show Figures

Figure 1

13 pages, 1790 KB

Open AccessArticle

Impact of Melatonin on Sepsis-Associated Acute Kidney Injury in Rat Model of Lipopolysaccharide Endotoxemia

by Milan Potić, Ivan Ignjatović, Dragoslav Bašić, Ljubomir Dinić, Aleksandar Skakić, Zoran Damnjanović, Nebojša Jovanović, Milica Mitić and Dušan Sokolović

Curr. Issues Mol. Biol. 2026, 48(1), 119; https://doi.org/10.3390/cimb48010119 - 22 Jan 2026

Viewed by 221

Abstract

Sepsis-associated acute kidney injury (S-AKI) is a frequent and life-threatening condition, characterized by rapid functional decline, which is followed by intense inflammation and tissue injury. Experimental lipopolysaccharide (LPS)-induced sepsis reproduces functional and morphological features of human S-AKI and enables investigation of melatonin which [...] Read more.

Sepsis-associated acute kidney injury (S-AKI) is a frequent and life-threatening condition, characterized by rapid functional decline, which is followed by intense inflammation and tissue injury. Experimental lipopolysaccharide (LPS)-induced sepsis reproduces functional and morphological features of human S-AKI and enables investigation of melatonin which has numerous beneficial properties, such as antioxidant properties. In this study, the effects of melatonin (50 mg/kg) on kidney dysfunction, oxidative damage, inflammation, apoptosis, and histopathological alterations in a rat model of S-AKI induced by LPS application (10 mg/kg) were studied. Acute LPS exposure caused statistically significant (p ≤ 0.05) marked renal dysfunction, increased lipid and protein oxidation, suppression of antioxidant enzymes, enhanced NO/iNOS signaling, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), activation of apoptotic pathways, and pronounced tubular and glomerular injury. Co-administration of melatonin statistically significantly (p ≤ 0.05) attenuated oxidative stress, reduced production of inflammatory cytokines, suppressed apoptosis, and ameliorated structural kidney damage, leading to partial restoration of renal function. These findings suggest that melatonin exerts renoprotective effects in S-AKI through combined antioxidant, anti-inflammatory, and anti-apoptotic actions, likely involving modulation of different signaling pathways. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Figure 1

15 pages, 3995 KB

Open AccessArticle

Long-Chain Fatty Acids Inhibit Myeloid-Derived Suppressor Cells to Delay Tumor Progression

by Xinyu Liu, Fanni Kong, Zhangyuzi Deng, Jing Yang, Ying Cao and Hongjie Chen

Curr. Issues Mol. Biol. 2026, 48(1), 118; https://doi.org/10.3390/cimb48010118 - 22 Jan 2026

Viewed by 233

Abstract

It is broadly realized that the body’s metabolism has a profound impact on tumor progression. However, pathophysiological mechanisms underlying the metabolic modulation of the tumor immune microenvironment remain incompletely understood. Here, we report that long-chain fatty acids (LCFAs) can directly modulate the function [...] Read more.

It is broadly realized that the body’s metabolism has a profound impact on tumor progression. However, pathophysiological mechanisms underlying the metabolic modulation of the tumor immune microenvironment remain incompletely understood. Here, we report that long-chain fatty acids (LCFAs) can directly modulate the function of myeloid-derived suppressor cells (MDSCs), a central component of establishing the tumor immune microenvironment. In vitro or in vivo exposure to LCFAs significantly reduces the expression levels of signature immunosuppressive genes of both monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs). As a result, mice fed with a diet of high LCFA content exhibit delayed tumor progression and prolonged survival in different cancer models. Furthermore, this LCFA-mediated inhibition of M-MDSCs and PMN-MDSCs correlates with enhanced CD8⁺ T antitumor immunity, which is abolished in tumor-bearing nude mice. These results have revealed a previously under-recognized role of LCFAs in the tumor immune microenvironment, implicating novel therapeutic strategies for cancer treatment. Full article

(This article belongs to the Special Issue Natural Products and Their Derivatives as Antitumor Agents)

► Show Figures

Figure 1

23 pages, 797 KB

Open AccessReview

Seminal Plasma and Extracellular Vesicles as Molecular Gatekeepers: Oxidative Stress, Endocrine Crosstalk, and Biomarker Discovery in Male Infertility

by Pallav Sengupta, Sulagna Dutta, Mahir Khalil Jallo, Israel Maldonado Rosas and Shubhadeep Roychoudhury

Curr. Issues Mol. Biol. 2026, 48(1), 117; https://doi.org/10.3390/cimb48010117 - 22 Jan 2026

Viewed by 265

Abstract

Conventional semen analysis fails to capture the molecular determinants underlying impaired reproductive function. Emerging evidence positions seminal plasma (SP) and extracellular vesicles (EVs) as dynamic regulators of sperm physiology, rather than passive transport components. SP, enriched with proteins, metabolites, hormones, and antioxidants, modulates [...] Read more.

Conventional semen analysis fails to capture the molecular determinants underlying impaired reproductive function. Emerging evidence positions seminal plasma (SP) and extracellular vesicles (EVs) as dynamic regulators of sperm physiology, rather than passive transport components. SP, enriched with proteins, metabolites, hormones, and antioxidants, modulates sperm motility, capacitation, acrosome reaction, and immune tolerance. Complementarily, EVs, including prostasomes, epididymosomes, and testicular vesicles, deliver proteins, lipids, and small RNAs that remodel sperm membranes, protect against oxidative insults, and influence fertilization success. A critical dimension of the SP-EV axis is its role in balancing oxidative stress (OS) and endocrine signaling. Hormones and metabolic regulators within SP, together with EV-mediated transfer of receptors and regulatory RNAs, further integrate systemic metabolic health with local reproductive outcomes. Dysregulation of these networks, particularly in conditions such as varicocele, obesity, diabetes, and idiopathic infertility, compromises sperm function and reduces assisted reproductive technology (ART) success. This evidence-based review synthesizes current evidence on SP and EVs as ‘molecular gatekeepers’ in male infertility, emphasizing OS regulation, endocrine crosstalk, and their potential as biomarker reservoirs. By integrating proteomic, metabolomic, and transcriptomic insights, the translational opportunities for biomarker-informed diagnostics, prognostication, and therapeutic interventions are highlighted. Full article

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

► Show Figures

Figure 1

15 pages, 6066 KB

Open AccessArticle

Aryl Hydrocarbon Receptor (AhR) and Vascular Endothelial Growth Factor (VEGF) Crosstalk in Doxorubicin Nephrotoxicity: Mechanisms and Therapeutic Perspectives

by Noha A. Alshuwayer, Qamraa H. Alqahtani, Marwa H. Hussein, Raeesa Mohammed and Iman H. Hasan

Curr. Issues Mol. Biol. 2026, 48(1), 116; https://doi.org/10.3390/cimb48010116 - 22 Jan 2026

Viewed by 204

Abstract

Doxorubicin (DOX), a widely used chemotherapeutic, is constrained by its nephrotoxicity, characterized by endothelial injury, inflammation, and oxidative stress. Vascular endothelial growth factor (VEGF) signaling in the kidney serves a dual function. Under normal conditions, it supports the survival of glomerular endothelial cells [...] Read more.

Doxorubicin (DOX), a widely used chemotherapeutic, is constrained by its nephrotoxicity, characterized by endothelial injury, inflammation, and oxidative stress. Vascular endothelial growth factor (VEGF) signaling in the kidney serves a dual function. Under normal conditions, it supports the survival of glomerular endothelial cells and maintains vascular stability, but when excessively activated, it disrupts angiogenesis and contributes to kidney injury. In this context, we hypothesize that Nanocurcumin (CUR-NP), a nano-formulated curcumin derivative with enhanced bioavailability, can modulate the VEGF pathway and restore regular renal activity. Thus, this study aims to explore the potential protective effect of CUR-NP on DOX-induced renal injury in male rats. Thirty-two Wistar albino rats were used and distributed into four groups. CUR-NP (80 mg/kg dissolved in 1% CMC) was administered by oral gavage for two weeks. A single dose of DOX (15 mg/kg) (i.p.) was injected on day seven of the study. Results showed that DOX increased the circulating creatinine, urea, and urea-nitrogen levels, while pretreatment with CUR-NP markedly alleviated kidney function. In addition, CUR-NP treatment significantly normalized oxidative stress markers in renal tissues, such as NO, GSH, and SOD, and improved renal pro-inflammatory mediators, TNF-α, IL-6, and NF-κB-p65. DOX caused degeneration of glomeruli and tubules with degenerated epithelial lining and casts in their lumens. Conversely, CUR-NP maintained standard tubular and glomerular structure. Immunohistochemistry showed that DOX strongly upregulated VEGF and AhR, while CUR-NP markedly reduced their expression, countering VEGF/AhR pathway disruption and helping restore physiological signaling. Full article

(This article belongs to the Special Issue Natural Phytochemicals as Modulators of Cellular Pathways and Therapeutic Targets in Disease Models)

► Show Figures

Figure 1

20 pages, 1101 KB

Open AccessReview

Mediterranean Diet and Oxidative Balance During Pregnancy: Molecular Insights into Mitigating the Impact of Environmental Pollution

by Eirini Kontopidou, Areti Kourti, Apostolos Athanasiadis and Aikaterini Itziou

Curr. Issues Mol. Biol. 2026, 48(1), 115; https://doi.org/10.3390/cimb48010115 - 21 Jan 2026

Viewed by 233

Abstract

Pregnancy represents a period of heightened oxidative demand in which maternal metabolic adaptations are tightly regulated by redox-sensitive molecular pathways. Imbalances in these systems have been associated with gestational complications, impaired placental function, and long-term effects on offspring health. This review examines the [...] Read more.

Pregnancy represents a period of heightened oxidative demand in which maternal metabolic adaptations are tightly regulated by redox-sensitive molecular pathways. Imbalances in these systems have been associated with gestational complications, impaired placental function, and long-term effects on offspring health. This review examines the molecular mechanisms through which adherence to the Mediterranean diet (MD) influences oxidative balance during pregnancy. We summarize evidence on how MD-derived bioactives regulate oxidative stress pathways and affect oxidative stress biomarkers, as well as the expression of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. At the same time, certain MD foods containing environmental contaminants may potentially attenuate its protective effects. In addition, the review explores molecular insights into how the MD may counteract oxidative stress induced by environmental pollutants through modulation of redox signaling and detoxification pathways. By integrating biochemical, molecular, and environmental perspectives, this review highlights the MD as a potential nutrigenomic intervention to optimize oxidative balance, support healthy pregnancy outcomes linked to environmental pollution. Full article

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

► Show Figures

Figure 1

16 pages, 8077 KB

Open AccessArticle

The Senescence-SASP Landscape in Colon Adenocarcinoma: Prognostic and Therapeutic Implications

by Tianyu Ren, Suyouwei Gao, Yangrong Feng, Yangyang Xu, Xinyi Mi, Jite Shi and Man Chu

Curr. Issues Mol. Biol. 2026, 48(1), 114; https://doi.org/10.3390/cimb48010114 - 21 Jan 2026

Viewed by 227

Abstract

Cellular senescence, characterized by permanent cell cycle arrest, significantly influences cancer development, immune regulation, and progression. However, the precise mechanisms by which senescence contributes to colorectal cancer prognosis remain to be fully elucidated. By integrating expression profiles of senescence-related and prognostic genes in [...] Read more.

Cellular senescence, characterized by permanent cell cycle arrest, significantly influences cancer development, immune regulation, and progression. However, the precise mechanisms by which senescence contributes to colorectal cancer prognosis remain to be fully elucidated. By integrating expression profiles of senescence-related and prognostic genes in colon adenocarcinoma (COAD) patients, we formulated and confirmed a nine-gene cellular senescence-related signature (CSRS) that integrates senescence-associated and prognosis-predictive genes using data from the CellAge, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A cell senescence-related prognostic formula was developed as follows: CSRS = (CASP2 × 0.2098) + (CDKN2A × 0.1196) + (FOXD1 × 0.1472) + (ING5 × 0.3723) + (OXTR × 0.0786) + (PHGDH × 0.1408) + (SERPINE1 × 0.1127) + (SNAI1 × 0.1034) + (LIMK1 × 0.0747). In a multivariate Cox proportional hazards model, the CSRS score, age and TNM stage were all identified as significant independent indicators for overall survival, affirming their prognostic value in colorectal cancer. The CSRS-high group exhibited significantly up-regulated senescence-associated secretory phenotype (SASP) and immune cell infiltration, whereas the CSRS-low group showed an apparent better response to immune-checkpoint inhibitor therapy. Our findings suggest CSRS score and its constituent genes represent potential biomarkers for prognosis and immunotherapeutic benefit in COAD patients. Extending this nine-gene set into a broader senescence-associated panel should be a next step toward delivering truly individualized treatment plans. Full article

(This article belongs to the Special Issue Molecular and Immunological Research on Colorectal Cancer: Pathogenesis, Microenvironment, and Future Therapies)

► Show Figures

Figure 1

14 pages, 1121 KB

Open AccessArticle

Diagnostic Value of Serum sST2 and MicroRNA-29a in Ovarian Cancer: A Dual-Biomarker Pilot Study

by Fatma Tuba Akdeniz, Zerrin Barut, Orcun Avsar, Selvi Duman Bakırezer, Rukset Attar and Turgay Isbir

Curr. Issues Mol. Biol. 2026, 48(1), 113; https://doi.org/10.3390/cimb48010113 - 21 Jan 2026

Viewed by 208

Abstract

Ovarian cancer is frequently diagnosed at an advanced stage due to non-specific symptoms, contributing to high mortality. The limited diagnostic performance of current serum assays in early disease underscores the need for complementary circulating biomarkers. Circulating microRNAs and inflammation-related markers are promising candidates. [...] Read more.

Ovarian cancer is frequently diagnosed at an advanced stage due to non-specific symptoms, contributing to high mortality. The limited diagnostic performance of current serum assays in early disease underscores the need for complementary circulating biomarkers. Circulating microRNAs and inflammation-related markers are promising candidates. Although miRNAs are implicated in cancer diagnostics, the role of miRNA-29a in ovarian cancer remains underexplored. Given that sST2 is elevated in several malignancies and is a direct target of miRNA-29a, concurrent evaluation may be informative. This pilot study compared serum miRNA-29a and sST2 levels in 23 ovarian cancer patients and 22 healthy female controls. miRNA-29a expression was quantified by real-time PCR (2^−ΔΔCt), and sST2 was measured by ELISA; diagnostic performance was assessed using ROC analysis. miRNA-29a levels were significantly reduced (p < 0.05), whereas sST2 concentrations were significantly increased (p < 0.001) in patients versus controls. ROC analysis showed modest discrimination for miRNA-29a (AUC 0.678) and higher performance for sST2 (AUC 0.825). No significant correlation was observed between the two markers. These findings suggest that circulating miRNA-29a and sST2 may have biomarker potential in ovarian cancer; larger, well-designed studies are required to confirm clinical utility. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Figure 1

20 pages, 2026 KB

Open AccessArticle

Temporal Urinary Metabolomic Profiling in ICU Patients with Critical COVID-19: A Pilot Study Providing Insights into Prognostic Biomarkers via ¹H-NMR Spectroscopy

by Emir Matpan, Ahmet Tarik Baykal, Lütfi Telci, Türker Kundak and Mustafa Serteser

Curr. Issues Mol. Biol. 2026, 48(1), 112; https://doi.org/10.3390/cimb48010112 - 21 Jan 2026

Viewed by 261

Abstract

Although the impact of COVID-19, caused by SARS-CoV-2, may appear to have diminished in recent years, the emergence of new variants still continues to cause significant global health and economic challenges. While numerous metabolomic studies have explored serum-based alterations linked to the infection, [...] Read more.

Although the impact of COVID-19, caused by SARS-CoV-2, may appear to have diminished in recent years, the emergence of new variants still continues to cause significant global health and economic challenges. While numerous metabolomic studies have explored serum-based alterations linked to the infection, investigations utilizing urine as a biological matrix remain notably limited. This gap is especially significant given the potential advantages of urine, a non-invasive and easily obtainable biofluid, in clinical settings. In the context of patients in intensive care units (ICUs), temporal monitoring through such non-invasive samples may offer a practical and effective approach for tracking disease progression and tailoring therapeutic interventions. This study retrospectively explored the longitudinal metabolomic alterations in COVID-19 patients admitted to the ICU, stratified into three prognostic outcome groups: healthy discharged (HD), polyneuropathic syndrome (PS), and Exitus. A total of 32 urine samples, collected at four distinct time points per patient during April 2020 and preserved at −80 °C, were analyzed by proton nuclear magnetic resonance (¹H-NMR) spectroscopy for comprehensive metabolic profiling. Statistical evaluation using two-way ANOVA and ANOVA–Simultaneous Component Analysis (ASCA) identified significant prognostic variations (p < 0.05) in the levels of taurine, 3-hydroxyvaleric acid and formic acid. Complementary supervised classification via random forest modeling yielded moderate predictive performance with out-of-bag error rate of 40.6% based on prognostic categories. Particularly, taurine, 3-hydroxyvaleric acid and formic acid levels were highest in the PS group. However, no significant temporal changes were observed for any metabolite in analyses. Additionally, metabolic pathway analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the “taurine and hypotaurine metabolism” pathway as the most significantly affected (p < 0.05) across prognostic classifications. Harnessing urinary metabolomics, as indicated in our preliminary study, could offer valuable insights into the dynamic metabolic responses of ICU patients, thereby facilitating more personalized and responsive critical care strategies in COVID-19 patients. Full article

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

► Show Figures

Figure 1

16 pages, 6156 KB

Open AccessArticle

Integrated Analysis of Proteomics and Metabolomics Uncovered the Anti-Inflammatory Mechanisms of Baicalin in CIA Rat FLS

by Li Wang, Si Yao, Jing Wang, Yuxin Yang, Tiansong Wang, Maiyan Hai, Wei Zhang, Na Wang and Qiaofeng Wan

Curr. Issues Mol. Biol. 2026, 48(1), 111; https://doi.org/10.3390/cimb48010111 - 20 Jan 2026

Viewed by 257

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, in which fibroblast-like synoviocytes (FLSs) serve as the primary effector cells that drive the destruction of joints. Baicalin has previously demonstrated efficacy in significantly ameliorating joint symptoms in rats with CIA. [...] Read more.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, in which fibroblast-like synoviocytes (FLSs) serve as the primary effector cells that drive the destruction of joints. Baicalin has previously demonstrated efficacy in significantly ameliorating joint symptoms in rats with CIA. As such, this study aims to investigate its underlying molecular mechanisms and impact on the FLSs of rats with CIA through an integrated proteomics and transcriptomics analysis. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted based on two datasets; it revealed that the retrograde endocannabinoid signaling pathway—associated with susceptibility to RA—is the only one involved in both the signaling and metabolic processes modulated by baicalin. Nineteen differentially expressed proteins (DEPs) downregulated by baicalin comprise seventeen subunits of NADH dehydrogenase and two receptors, glutamate receptor 2 (GRIA2) and γ-aminobutyric acid receptor subunit alpha-5 (GABRA5). Three differential metabolites (DMs) were also affected by baicalin: γ-aminobutyric acid (GABA) and phosphatidylcholine (PC) were upregulated and phosphatidylethanolamine (PE) was downregulated. Our findings suggest that the baicalin-mediated alleviation of joint synovitis is closely related to the upregulation of GABA and PC; downregulation of GRIA2, GABRA5, and PE; and preservation of mitochondrial homeostasis within the retrograde endocannabinoid signaling pathway in FLSs. Full article

(This article belongs to the Special Issue Molecular Research in Osteoarthritis and Osteoarticular Diseases, 2nd Edition)

► Show Figures

Figure 1

13 pages, 525 KB

Open AccessArticle

The Effect of Soy Protein–Phycocyanin Concentrate Complex Treatment on Biomarkers of HDL Functional Properties in Male Wistar Rats

by Ilya Vorozhko, Yuliya Sidorova, Nadezhda Biryulina, Sergey Zorin, Nikita Petrov, Tatyana Korotkova and Alla Kochetkova

Curr. Issues Mol. Biol. 2026, 48(1), 110; https://doi.org/10.3390/cimb48010110 - 20 Jan 2026

Viewed by 202

Abstract

Due to improper nutrition, high-density lipoproteins (HDLs) can be subjected to structural changes, acquiring a dysfunctional phenotype. Therefore, research efforts are currently focused on improving HDL functionality despite its blood level. The aim of this study was to evaluate the effect of phycocyanin [...] Read more.

Due to improper nutrition, high-density lipoproteins (HDLs) can be subjected to structural changes, acquiring a dysfunctional phenotype. Therefore, research efforts are currently focused on improving HDL functionality despite its blood level. The aim of this study was to evaluate the effect of phycocyanin concentrate (as part of a food matrix) on the functional properties of HDL. Male Wistar rats were fed a high-fat diet containing 2% cholesterol for 113 days. Experimental animals were treated with 30 and 300 mg/kg b.w. of phycocyanin concentrate mixed with soy protein isolate. Serum and hepatic cholesterol and triglyceride levels, and the content of protein, triglycerides, choline-containing phospholipids, malondialdehyde, sphingosine-1-phosphate, and paraoxonase-1 in HDL fractions were assessed. The decrease in protein in HDL particles is characteristic for dysfunctional phenotype of these particles. Phycocyanin concentrate diet prevented the depletion of protein in HDL particles, regardless of the dosage. The functionality of HDL is associated with paraoxonase-1 activity, which inhibits lipid peroxidation in lipoproteins. Our results have shown a significant increase in the level of paraoxonase-1 in HDL particles in groups treated with phycocyanin. HDL particles become more enriched with triglycerides with the development of hyperlipidemia. Triglycerides in HDL particles and in serum decreased by two times in animals receiving 30 mg/kg b.w. of phycocyanin. The MDA content in HDL particles decreased in all animals receiving a high-fat diet with the addition of 2% cholesterol. The introduction of 300 mg/kg of phycocyanin returned this indicator to the values of the Control group. Thus, biomarkers of dysfunctional changes in HDL in rodent hyperlipidemia models may be a useful tool for assessing lipid metabolism disorders. Also, the results confirm the potential ability to use phycocyanin concentrate as part of lipid-lowering products. Full article

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

► Show Figures

Figure 1

17 pages, 2601 KB

Open AccessArticle

Protective Effects of Magnolia kobus DC. Extract on Inflammatory Response and Alveolar Bone Loss in Ligature-Induced Periodontitis Rats

by Da-Eun Min, Sung-Kwon Lee, Eunji Kim, Seong-Hyeon Park, Deok-Geun Kim and Bong-Keun Choi

Curr. Issues Mol. Biol. 2026, 48(1), 109; https://doi.org/10.3390/cimb48010109 - 20 Jan 2026

Viewed by 190

Abstract

Periodontitis is a chronic inflammatory condition characterized by dysregulated immune responses that promote alveolar bone destruction. Targeting inflammatory signaling pathways has therefore become an important area of investigation. This study investigated the anti-inflammatory and bone-protective effects of Magnolia kobus DC. extract (MKE) in [...] Read more.

Periodontitis is a chronic inflammatory condition characterized by dysregulated immune responses that promote alveolar bone destruction. Targeting inflammatory signaling pathways has therefore become an important area of investigation. This study investigated the anti-inflammatory and bone-protective effects of Magnolia kobus DC. extract (MKE) in a ligature-induced periodontitis rat model. Rats were assigned to five groups (n = 5 per group): non-ligature control, ligature control, doxycycline (20 mg/kg), MKE 100 mg/kg, and MKE 400 mg/kg, and treated orally for eight weeks. Periodontal damage and alveolar bone loss were assessed by micro-computed tomography (micro-CT), gingival index, and tooth mobility. Micro-CT analysis demonstrated a dose-dependent reduction in alveolar bone loss, as evidenced by a significant decrease in the cementoenamel junction–alveolar bone crest (CEJ–ABC) distance and reduced furcation involvement in MKE-treated groups compared with the ligature control group, while tooth mobility scores were significantly improved. Serum levels of receptor activator of nuclear factor kappa-B ligand, interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2 were significantly decreased, while nuclear factor kappa-B signaling was suppressed in gingival tissue. The extract also significantly reduced matrix metalloproteinases 3, 8, 9, and 13, and increased collagen type I and II expression. In summary, MKE exerted anti-inflammatory and bone-protective properties, effectively reducing alveolar bone loss and maintaining periodontal structure. These findings support MKE’s potential application as a natural anti-inflammatory and bone-protective agent and as a functional food ingredient for periodontitis prevention and treatment, meriting further clinical evaluation. Full article

(This article belongs to the Section Molecular Pharmacology)

► Show Figures

Figure 1

16 pages, 21309 KB

Open AccessArticle

Comprehensive Transcriptomic Analysis and Biomarker Prioritization of Hydroxyprogesterone in Breast Cancer

by Abdallah Rafi, Şükrü Tüzmen, Osman Uğur Sezerman and Fikret Dirilenoğlu

Curr. Issues Mol. Biol. 2026, 48(1), 108; https://doi.org/10.3390/cimb48010108 - 20 Jan 2026

Viewed by 291

Abstract

Hydroxyprogesterone (HP) is a synthetic progestogen widely used in obstetric care, and its potential influence on breast cancer biology has become an emerging area of interest. Despite its clinical use, the molecular mechanisms by which HP affects tumor tissue remain insufficiently explored. In [...] Read more.

Hydroxyprogesterone (HP) is a synthetic progestogen widely used in obstetric care, and its potential influence on breast cancer biology has become an emerging area of interest. Despite its clinical use, the molecular mechanisms by which HP affects tumor tissue remain insufficiently explored. In this study, transcriptomic profiling was performed to investigate gene expression changes associated with HP in operable breast cancer. Pre-operative 17α-HP caproate (17-OHPC) exposure was associated, in normal adjacent tissue (NAT), with activation of steroid-hormone and lipid/xenobiotic-metabolism programs and crosstalk to phosphoinositide 3-kinase (PI3K)–Akt and nuclear factor kappa B (NF-κB). In NAT, these pathways showed the largest absolute log₂ fold-change (|log₂FC|); significance is reported as false discovery rate (FDR) throughout (e.g., FKBP5↑ with HP). In tumor tissue, the dominant signal reflected tight-junction/apical-junction and extracellular matrix (ECM)-receptor remodeling (e.g., CLDN4↑). We prioritized FKBP5 (HP pharmacodynamics) and CLDN4 (tumor baseline) as the main candidates; TSPO and SGK1 are reported as exploratory. This discovery-level, hypothesis-generating analysis nominates candidate biomarkers and pathway signals for prioritization and evaluation in independent datasets and future studies. These findings provide mechanistic insight into HP’s molecular effects in breast cancer and suggest potential applications in biomarker perioperative management. Full article

(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era, 3rd Edition)

► Show Figures

Figure 1

14 pages, 412 KB

Open AccessArticle

Host Immunogenetic Profile Modulates Susceptibility to Apical Periodontitis in a Colombian Population

by Ingrid Giraldo-Quiceno, Natalia Andrea Torres-Calvo, Andrés Felipe Ayala-Jaramillo, Christina Garcés, Sandra Catalina Garzón-Castaño, Beatriz Giraldo-Ospina, Nora Elena Valencia-Marroquín, Carlos Manuel Beltrán-Díaz, Iván Alberto Lopera-Castrillón and Carlos Andrés Naranjo-Galvis

Curr. Issues Mol. Biol. 2026, 48(1), 107; https://doi.org/10.3390/cimb48010107 - 20 Jan 2026

Viewed by 259

Abstract

Apical periodontitis (AP) is a chronic immunoinflammatory disease influenced by complex interactions between microbial factors and host immune response. Although genetic susceptibility has been implicated in AP, evidence is limited, particularly in admixed populations. This exploratory study aimed to assess whether functional polymorphisms [...] Read more.

Apical periodontitis (AP) is a chronic immunoinflammatory disease influenced by complex interactions between microbial factors and host immune response. Although genetic susceptibility has been implicated in AP, evidence is limited, particularly in admixed populations. This exploratory study aimed to assess whether functional polymorphisms in MMP1 (rs1799750), IL10 (rs1800872), and IL17A (rs7747909) are associated with susceptibility to radiographically defined AP in a Colombian population. A case–control design was employed, including individuals with radiographic evidence of AP and controls without periapical lesions. Genotyping was performed using TaqMan^® assay. The association between single-nucleotide polymorphisms and AP was evaluated using a dominant inheritance model. Effect sizes were estimated as odds ratios (ORs) with 95% confidence intervals (CIs), and p-values were adjusted using the Benjamini–Hochberg false discovery rate (FDR) procedure. The MMP1 rs1799750 polymorphism was associated with increased susceptibility to AP (OR = 3.47, 95% CI = 1.40–8.58; FDR = 0.013). Similarly, the IL10 rs1800872 variant was significantly associated with AP risk (OR = 3.00, 95% CI = 1.52–5.91; FDR = 0.007). The strongest association was observed for IL17A rs7747909 (OR = 8.95, 95% CI = 3.61–22.15; FDR < 0.001). This exploratory candidate-gene study provides preliminary evidence suggesting that genetic variations in MMP1, IL10, and IL17A may contribute to susceptibility to AP in the Colombian population. Given the exploratory design, modest sample size, and absence of ancestry adjustment or functional validation, these findings should be interpreted cautiously and confirmed in larger ancestry-informed cohorts integrating host genetic and microbial data. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Innovative Therapeutic Approaches in Inflammatory Diseases, Pioneering Precision Medicine Solutions, 2nd Edition)

► Show Figures

Figure 1

14 pages, 667 KB

Open AccessReview

Regulatory B Cells in Tumor Microenvironment

by Zhuoyan Cai and Lin Xie

Curr. Issues Mol. Biol. 2026, 48(1), 106; https://doi.org/10.3390/cimb48010106 - 20 Jan 2026

Viewed by 314

Abstract

Regulatory B cells (Bregs) are integral to the tumor microenvironment (TME) and influence immune responses through the secretion of immunosuppressive cytokines such as IL-10, IL-35, and TGF-β. This review highlights recent findings on the phenotype and mechanisms of Bregs, emphasizing their dual role [...] Read more.

Regulatory B cells (Bregs) are integral to the tumor microenvironment (TME) and influence immune responses through the secretion of immunosuppressive cytokines such as IL-10, IL-35, and TGF-β. This review highlights recent findings on the phenotype and mechanisms of Bregs, emphasizing their dual role in regulating immune responses within the TME. Importantly, we further explored the latest advances in Breg regulatory mechanisms from the novel perspectives of epigenetics and metabolic remodeling, including the effects of DNA methylation, histone acetylation, glycolysis, and oxidative phosphorylation on Bregs. We also investigate the therapeutic targeting of Bregs, with a focus on STAT3 inhibitors such as lipoxin A4, cucurbitacins, and resveratrol, which show promising potential in mitigating the suppressive function of Bregs. Furthermore, this review provides a detailed analysis of the impact of Bregs on tumorigenesis and metastasis, emphasizing the importance of inhibiting specific immune pathways to prevent tumor escape. Finally, this review offers a prospective outlook on immunotherapy strategies based on Bregs, foreseeing a more nuanced understanding of their TME function and the evolution of targeted treatments with enhanced therapeutic efficacy. Full article

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

► Show Figures

Graphical abstract

20 pages, 349 KB

Open AccessReview

Prokaryotic Molecular Defense Mechanisms and Their Potential Applications in Cancer Biology: A Special Consideration for Cyanobacterial Systems

by Nermin Adel Hussein El Semary, Ahmed Fadiel, Kenneth D. Eichenbaum and Sultan A. Alhusayni

Curr. Issues Mol. Biol. 2026, 48(1), 105; https://doi.org/10.3390/cimb48010105 - 19 Jan 2026

Viewed by 339

Abstract

Cyanobacteria harbor sophisticated molecular defense systems that have evolved over billions of years to protect against viral invasion and foreign genetic elements. These ancient photosynthetic organisms possess a diverse array of restriction-modification (R-M) systems and CRISPR-Cas arrays that present challenges for genetic engineering, [...] Read more.

Cyanobacteria harbor sophisticated molecular defense systems that have evolved over billions of years to protect against viral invasion and foreign genetic elements. These ancient photosynthetic organisms possess a diverse array of restriction-modification (R-M) systems and CRISPR-Cas arrays that present challenges for genetic engineering, but also offer unique opportunities for cancer-targeted biotechnological applications. These systems exist in prokaryotes mainly as defense mechanisms but they are currently used in molecular applications as gene editing tools. Moreover, latest developments in nucleases such as zinc finger nucleases (ZFNs), TALENs (transcription-activator-like effector nucleases) are discussed. A comprehensive genomic analysis of 126 cyanobacterial species found 89% encode multiple R-M systems, averaging 3.2 systems per genome, creating formidable barriers to transformation but also providing molecular machinery that could be harnessed for precise recognition and targeting of cancer cells. This review critically examines the dual nature of these defense systems, their ecological functions, and the emerging strategies to translate their molecular precision into advanced anticancer therapeutics. Hence, the review main objectives are to explore the recent understanding of these mechanisms and to exploit the knowledge gained in opening new avenues for cancer-focused targeted interventions, while acknowledging the significant challenges to translate these systems from laboratory curiosities to practical applications. Full article

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

19 pages, 1159 KB

Open AccessReview

The Genetic Landscape and Precision Medicine in Neonatal Diabetes Mellitus: From Molecular Mechanisms to Clinical Management

by Yuanyuan Meng, Lina Zhu, Guanping Dong and Chao Tang

Curr. Issues Mol. Biol. 2026, 48(1), 104; https://doi.org/10.3390/cimb48010104 - 19 Jan 2026

Viewed by 323

Abstract

Neonatal Diabetes Mellitus (NDM) is a rare, heterogeneous monogenic disorder typically presenting within the first six months of life. Unlike type 1 or type 2 diabetes, NDM is caused by single-gene mutations that disrupt pancreatic β-cell function or development. With the advent of [...] Read more.

Neonatal Diabetes Mellitus (NDM) is a rare, heterogeneous monogenic disorder typically presenting within the first six months of life. Unlike type 1 or type 2 diabetes, NDM is caused by single-gene mutations that disrupt pancreatic β-cell function or development. With the advent of next-generation sequencing, the genetic spectrum of NDM has expanded significantly, necessitating a shift from symptomatic management to precision medicine. This narrative review summarizes the genetic basis and pathogenic mechanisms of NDM, categorizing them into three major pathways: (1) ATP-sensitive potassium (K_ATP) channelopathies (e.g., ABCC8, KCNJ11), where gain-of-function mutations inhibit insulin secretion; (2) Transcription factor defects (e.g., GLIS3, PAX6, GATA6), which impair pancreatic development and often present with syndromic features; and (3) Endoplasmic reticulum (ER) stress-mediated β-cell apoptosis, exemplified by WFS1 mutations. Furthermore, we highlight the clinical complexity of these mutations, including the “biphasic phenotype” observed in ABCC8 and HNF1A variants. Understanding these molecular mechanisms is critical for clinical decision-making. We discuss the transformative impact of genetic diagnosis in treatment, particularly the successful transition from insulin to oral sulfonylureas in patients with K_ATP channel mutations, and emphasize the importance of early genetic testing to optimize glycemic control and prevent complications. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Figure 1

25 pages, 3649 KB

Open AccessArticle

Identification of Tumor- and Immunosuppression-Driven Glioblastoma Subtypes Characterized by Clinical Prognosis and Therapeutic Targets

by Pei Zhang, Dan Liu, Xiaoyu Liu, Shuai Fan, Yuxin Chen, Tonghui Yu and Lei Dong

Curr. Issues Mol. Biol. 2026, 48(1), 103; https://doi.org/10.3390/cimb48010103 - 19 Jan 2026

Viewed by 293

Abstract

Glioblastoma multiforme (GBM) is the most aggressive primary brain cancer (with a median survival time of 14.5 months), characterized by heterogeneity. Identifying prognostic molecular subtypes could provide a deeper exposition of GBM biology with potential therapeutic implications. In this study, we classified GBM [...] Read more.

Glioblastoma multiforme (GBM) is the most aggressive primary brain cancer (with a median survival time of 14.5 months), characterized by heterogeneity. Identifying prognostic molecular subtypes could provide a deeper exposition of GBM biology with potential therapeutic implications. In this study, we classified GBM into two prognostic subtypes, C1-GBM (n = 57; OS: 313 days) and C2-GBM (n = 109; OS: 452 days), using pathway-based signatures derived from RNA-seq data. Unsupervised consensus clustering revealed that only binary classification (cluster number, CN = 2; mean cluster consensus score = 0.84) demonstrated statistically prognostic differences. We characterized C1 and C2 based on oncogenic pathway and immune signatures. Specifically, C1-GBM was categorized as an immune-infiltrated “hot” tumor, with high infiltration of immune cells, particularly macrophages and CD4⁺ T cells, while C2-GBM as an “inherent driving” subtype, showing elevated activity in G2/M checkpoint genes. To predict the C1 or C2 classification and explore therapeutic interventions, we developed a neural network model. By using Weighted Correlation Network Analysis (WGCNA), we obtained the gene co-expression module based on both gene expression pattern and distribution among patients in TCGA dataset (n = 166) and identified nine hub genes as potentially prognostic biomarkers for the neural network. The model showed strong accuracy in predicting C1/C2 classification and prognosis, validated by the external CGGA-GBM dataset (n = 85). Based on the classification of the BP neural network model, we constructed a Cox nomogram prognostic prediction model for the TCGA-GBM dataset. We predicted potential therapeutic small molecular drugs by targeting subtype-specific oncogenic pathways and validated drug sensitivity (C1-GBM: Methotrexate and Cisplatin; C2-GBM: Cytarabine) by assessing IC₅₀ values against GBM cell lines (divided into C1/C2 subtypes based on the nine hub genes) from the Genomics of Drug Sensitivity in Cancer database. This study introduces a pathway-based prognostic molecular classification of GBM with “hot” (C1-GBM) and “inherent driving” (C2-GBM) tumor subtypes, providing a prediction model based on hub biomarkers and potential therapeutic targets for treatments. Full article

(This article belongs to the Special Issue Advanced Research in Glioblastoma and Neuroblastoma)

► Show Figures

Graphical abstract

18 pages, 685 KB

Open AccessReview

Fibroblast Growth Factor-7 and Hair Biology: Bridging Basic Science and Therapeutic Applications

by Huey-Chun Huang, Wang-Ju Hsieh, Ivona Percec and Tsong-Min Chang

Curr. Issues Mol. Biol. 2026, 48(1), 102; https://doi.org/10.3390/cimb48010102 - 19 Jan 2026

Viewed by 508

Abstract

Alopecia profoundly impacts psychological well-being and quality of life, yet current therapeutic options such as minoxidil and finasteride exhibit limited efficacy. Fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor (KGF), is a paracrine growth factor secreted by dermal papilla cells [...] Read more.

Alopecia profoundly impacts psychological well-being and quality of life, yet current therapeutic options such as minoxidil and finasteride exhibit limited efficacy. Fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor (KGF), is a paracrine growth factor secreted by dermal papilla cells that specifically activates the epithelial receptor FGFR2b. Receptor engagement triggers multiple downstream signaling cascades, including the MAPK/ERK, PI3K/Akt, and Wnt/β-catenin pathways, promoting keratinocyte proliferation, stem cell activation, and the transition of hair follicles into the anagen phase. Both in vitro and in vivo animal studies consistently demonstrate that FGF-7 accelerates telogen-to-anagen transition and enhances follicular regeneration. FGF-7 acts synergistically with insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) to sustain nutrient delivery and cell proliferation. Human scalp studies further reveal a strong association between the FGF-7/FGFR2b signaling and follicular activity; however, clinical trials remain scarce. Topical application of FGF-7 has demonstrated an excellent safety profile, whereas systemic administration necessitates careful monitoring. Future directions include the development of engineering to extend the systemic half-life, advanced delivery systems, and gene or mRNA-based therapeutic approaches. Thus, the FGF-7/FGFR2b axis is a highly compelling molecular target for next-generation hair regeneration therapies. Full article

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

► Show Figures

Figure 1

16 pages, 2949 KB

Open AccessArticle

Genome-Wide Insights into Intermittent Milking Behavior of Pandharpuri Buffalo

by Akshata Patil, Parth Gaur, Pritam Pal, Rani Alex, Supriya Chhotaray, Ravi Kumar Gandham and Vikas Vohra

Curr. Issues Mol. Biol. 2026, 48(1), 101; https://doi.org/10.3390/cimb48010101 - 19 Jan 2026

Viewed by 287

Abstract

Buffaloes (Bubalus bubalis) are central to the dairy and agricultural economy, contributing high-quality milk, meat, draft power, and manure. Rich milk composition, the ability to utilize low-quality roughage, and strong disease resistance make buffaloes indispensable across diverse production systems. Among India’s [...] Read more.

Buffaloes (Bubalus bubalis) are central to the dairy and agricultural economy, contributing high-quality milk, meat, draft power, and manure. Rich milk composition, the ability to utilize low-quality roughage, and strong disease resistance make buffaloes indispensable across diverse production systems. Among India’s major dairy breeds—Murrah, Nili-Ravi, Jaffarabadi, Surti, Bhadawari, Mehsana, and Nagpuri, none exhibit the distinctive trait of intermittent milking, which is uniquely observed in the Pandharpuri buffalo, a registered indigenous breed of Maharashtra. Despite coexisting with dominant dairy breeds such as Murrah, Pandharpuri buffalo is considered to possess primitive riverine ancestry and may represent one of the ancestral lineages from which several Indian breeds evolved. Its evolutionary relevance and unique intermittent milking capacity underscore the need to understand its genomic architecture. To address this, we applied whole-genome resequencing and the De-Correlated Composite of Multiple Signals (DCMS) approach to identify within-breed selection signatures. Our analyses identified 1337 candidate genes, including several linked to milk production, particularly those relevant to the physiological capacity for intermittent milking. Notable genes included ERBB4, ESR1, SYK, INSR, PTPN11, VAV3, MAPK3, and PRKG1. These signatures provide insights into genomic regions and biological pathways that may be involved in lactation-related processes relevant to intermittent milking. The identified genomic regions offer promising targets for functional validation and future genome-informed breeding strategies aimed at conserving this unique indigenous germplasm while improving lactation efficiency and resilience. Full article

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

► Show Figures

Figure 1

19 pages, 6151 KB

Open AccessArticle

SGPP2 Ameliorates Chronic Heart Failure by Attenuating ERS via the SIRT1/AMPK Pathway

by Yang Kang, Yang Wang, Lili Wang and Lu Fu

Curr. Issues Mol. Biol. 2026, 48(1), 100; https://doi.org/10.3390/cimb48010100 - 19 Jan 2026

Viewed by 315

Abstract

Objective: To investigate the mechanism by which sphingosine-1-phosphatase 2 (SGPP2) modulates endoplasmic reticulum stress (ERS) through the SIRT1/AMPK pathway to improve ischemic cardiomyopathy-induced chronic heart failure (IHF). Methods: Key genes of IHF and ERS were identified through bioinformatics analysis, and significantly associated pathways [...] Read more.

Objective: To investigate the mechanism by which sphingosine-1-phosphatase 2 (SGPP2) modulates endoplasmic reticulum stress (ERS) through the SIRT1/AMPK pathway to improve ischemic cardiomyopathy-induced chronic heart failure (IHF). Methods: Key genes of IHF and ERS were identified through bioinformatics analysis, and significantly associated pathways of the key genes were obtained via single-gene enrichment analysis. In vivo, IHF was induced in Sprague–Dawley (male) rats via ligation of the left anterior descending coronary artery, with cardiac function examined through echocardiography. Myocardial tissue injury and fibrosis were evaluated utilizing hematoxylin-eosin, Masson, and TUNEL staining. Serum levels of NT-proBNP and cTnT were measured via ELISA. SGPP2 protein expression was assessed via immunohistochemistry and Western blotting (WB). In vitro, neonatal rat cardiomyocytes (NRCMs) were isolated and underwent oxygen-glucose deprivation (OGD) to establish an IHF model. SGPP2-overexpressing NRCMs were constructed and treated with the ERS inducer tunicamycin (Tu) or the SIRT1 inhibitor EX527. Cell injury was evaluated using Cell Counting Kit-8 and lactate dehydrogenase release assays, as well as flow cytometry. Endoplasmic reticulum structure was examined by transmission electron microscopy. The endoplasmic reticulum was labeled with the ER-Tracker Red molecular probe. WB was utilized to detect the expression of apoptosis- and ERS-linked proteins, and the activity of the SIRT1/AMPK signaling pathway. Results: Six key genes (CTSK, FURIN, SLC2A1, RSAD2, SGPP2, and STAT3) were identified through bioinformatics analysis, with SGPP2 showing the most significant differential expression. Additionally, SGPP2 was found to be downregulated in IHF. Single-gene enrichment analysis showed that SGPP2 exhibited a significant association with the AMPK signaling pathway. Animal experiments demonstrated that rats with IHF exhibited significantly impaired cardiac function, marked myocardial tissue injury and fibrosis, ERS in myocardial tissue, lowered SGPP2 expression, and decreased SIRT1/AMPK signaling pathway activity. In vitro experiments confirmed that SGPP2 overexpression alleviated OGD-induced cardiomyocyte injury by inhibiting ERS and simultaneously activating the SIRT1/AMPK signaling pathway. Rescue experiments further demonstrated that both Tu and EX527 significantly promoted ERS and cellular injury, thereby counteracting the protective effects of SGPP2. Conclusions: SGPP2 alleviates IHF by inhibiting ERS modulated by the SIRT1/AMPK pathway. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Figure 1

12 pages, 781 KB

Open AccessArticle

Two Cultivars of Peanut (Arachis hypogaea) Show Different Responses to Iron Deficiency

by Lei Chen, Zifei Liu, Lei Zhou and Hong Wang

Curr. Issues Mol. Biol. 2026, 48(1), 99; https://doi.org/10.3390/cimb48010099 - 18 Jan 2026

Viewed by 218

Abstract

Background: Peanut is susceptible to iron (Fe) deficiency, particularly in calcareous soils. However, comparative studies on the adaptive mechanisms of different peanut cultivars to Fe deficiency remain limited. This study aimed to investigate the physiological and molecular responses of two distinct peanut [...] Read more.

Background: Peanut is susceptible to iron (Fe) deficiency, particularly in calcareous soils. However, comparative studies on the adaptive mechanisms of different peanut cultivars to Fe deficiency remain limited. This study aimed to investigate the physiological and molecular responses of two distinct peanut cultivars to Fe deprivation and to identify the key traits contributing to differential Fe efficiency. Methods: Two peanut cultivars, LH11 and YZ9102, were cultivated under Fe-sufficient and Fe-deficient conditions, using both hydroponic and pot-based soil culture systems. Multiple parameters were assessed, including visual symptomology, biomass, tissue Fe concentration, active Fe in leaves, chlorophyll (Chl) content (SPAD value), net photosynthetic rate (Pn), Chl fluorescence (Fv/Fm), rhizosphere pH, root ferric chelate reductase (FCR) activity, and the relative expression of two Fe-acquisition-related genes (AhIRT1 and AhFRO1) via qRT-PCR. Results: Cultivar YZ9102 exhibited more severe Fe deficiency chlorosis symptoms, which also appeared earlier than in LH11, under both cultivation systems. Under Fe deficiency, YZ9102 showed significantly lower Chl content, Pn, and Fv/Fm compared to LH11. In contrast, LH11 demonstrated a greater capacity for rhizosphere acidification and maintained significantly higher root FCR activity under Fe-limited conditions. Gene expression analysis revealed that Fe deficiency induced the up-regulation of AhIRT1 and AhFRO1 in the roots of LH11, while their transcript levels were suppressed or unchanged in YZ9102. Conclusions: The peanut cultivar LH11 possesses superior tolerance to Fe deficiency compared to YZ9102. This enhanced tolerance is attributed to a synergistic combination of traits: the maintenance of photosynthetic performance, efficient rhizosphere acidification, heightened root Fe³⁺ reduction capacity, and the positive transcriptional regulation of key Fe uptake genes. These findings provide crucial insights for the selection and breeding of Fe-efficient peanut varieties for cultivation in Fe-deficient environments. Full article

(This article belongs to the Section Molecular Plant Sciences)

► Show Figures

Figure 1

30 pages, 5371 KB

Open AccessReview

Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer

by Xin Hu, Rui Chen, Famin Ke, Dandan Wang, Xiaowei Gao, Can Song, Aimin Fu, Zuojin Ao, Hanyu Yang, Xiaoyan Liu, Xiurong Guo and Qiuyu Liu

Curr. Issues Mol. Biol. 2026, 48(1), 98; https://doi.org/10.3390/cimb48010098 - 18 Jan 2026

Viewed by 274

Abstract

The hypoxic microenvironment within breast cancer tumors leads to the sustained activation of hypoxia-inducible factors (HIFs), notably HIF-1α, which, in turn, triggers adaptive responses such as angiogenesis and metabolic reprogramming. These processes contribute to tumor invasion, progression, metastasis, and therapy resistance. Although a [...] Read more.

The hypoxic microenvironment within breast cancer tumors leads to the sustained activation of hypoxia-inducible factors (HIFs), notably HIF-1α, which, in turn, triggers adaptive responses such as angiogenesis and metabolic reprogramming. These processes contribute to tumor invasion, progression, metastasis, and therapy resistance. Although a substantial portion of the human genome is transcribed into non-coding RNAs (ncRNAs), which have been shown to play key regulatory roles in the development and progression of breast cancer, the interplay between HIFs and ncRNAs—and how such crosstalk influences breast cancer pathogenesis—remains poorly understood. This review aims to systematically outline the mechanisms of hypoxia-related signaling and ncRNA function in breast cancer, with a focus on their molecular interactions in disease progression and their potential clinical implications. Full article

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

► Show Figures

Figure 1

37 pages, 1229 KB

Open AccessReview

Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms

by Cristian-Mihai Ilie, Teodora-Cristiana Grădinaru, Cătălina Anamaria Boromiz and Marilena Gilca

Curr. Issues Mol. Biol. 2026, 48(1), 97; https://doi.org/10.3390/cimb48010097 - 18 Jan 2026

Viewed by 406

Abstract

Systemic sclerosis (SSc) is a rare multisystemic autoimmune disease associated with progressive fibrosis, vasculopathy, and immune dysregulation. Despite advances in its management, the disease remains associated with substantial morbidity and mortality, with limited therapeutic options. This systematic review aimed to identify phytocompounds and [...] Read more.

Systemic sclerosis (SSc) is a rare multisystemic autoimmune disease associated with progressive fibrosis, vasculopathy, and immune dysregulation. Despite advances in its management, the disease remains associated with substantial morbidity and mortality, with limited therapeutic options. This systematic review aimed to identify phytocompounds and medicinal plants that had demonstrated efficacy in SSc. A comprehensive literature search was performed in PubMed and ScienceDirect, yielding 7797 records, of which 32 studies met the inclusion criteria. A second search was performed using the SwissTargetPrediction tool to identify new putative molecular targets for these phytocompounds, whose relevance for SSc pathogenesis was verified by a third search in PubMed and ScienceDirect databases. Our search found 24 phytocompouds (e.g., halofunginone, crocetin, and tanshinone IIA) and 5 plant extracts (e.g., caper bush and ciplukan) reported to modulate key pathogenic processes in SSc. These phytochemicals were mainly associated with effects on endothelial to mesenchymal transition, oxidative stress, inflammation, and profibrotic signaling pathways, particularly TGF-β/Smad. The SwissTargetPrediction tool indicated 93 new potential molecular targets of the selected phytochemicals, among which only 41 showed relevance to SSc pathogenesis. In conclusion, available evidence is scarce but promising. Further studies, especially human investigations, are required to clarify clinical efficacy, safety, and potential interactions with drugs used in SSc. Full article

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

► Show Figures

Graphical abstract

15 pages, 8399 KB

Open AccessArticle

Magnolol Ameliorates Cisplatin-Induced Acute Kidney Injury with Activation of Nrf2-Associated Antioxidant Responses

by Mi-Gyeong Gwon, Min Hui Park and Jaechan Leem

Curr. Issues Mol. Biol. 2026, 48(1), 96; https://doi.org/10.3390/cimb48010096 - 17 Jan 2026

Viewed by 253

Abstract

Cisplatin (CDDP) is a cornerstone chemotherapeutic drug, yet its efficacy is frequently compromised by renal toxicity, primarily manifesting as acute kidney injury (AKI). Magnolol (MG) is a polyphenol from Magnolia officinalis and has been widely documented for its pronounced antioxidant and anti-inflammatory properties. [...] Read more.

Cisplatin (CDDP) is a cornerstone chemotherapeutic drug, yet its efficacy is frequently compromised by renal toxicity, primarily manifesting as acute kidney injury (AKI). Magnolol (MG) is a polyphenol from Magnolia officinalis and has been widely documented for its pronounced antioxidant and anti-inflammatory properties. This study evaluated the renoprotective effects of MG in a murine model of CDDP-induced AKI. Male C57BL/6 mice received MG (20 mg/kg) via daily intraperitoneal injection for four consecutive days, starting one day before a single CDDP injection. MG significantly reduced the serum concentrations of blood urea nitrogen and creatinine. Histopathological assessment revealed attenuated tubular damage and reduced expression of tubular injury markers. MG inhibited pro-inflammatory cytokines at both systemic and renal levels, alleviated endoplasmic reticulum stress, and suppressed activation of mitogen-activated protein kinase signaling pathways. Apoptotic damage was mitigated, as shown by the fewer TUNEL-positive cells and lowered expression of pro-apoptotic markers. In parallel, ferroptotic processes were alleviated through downregulation of pro-ferroptotic proteins and preservation of key antioxidant regulators. Importantly, MG restored nuclear factor erythroid 2-related factor 2 activity and upregulated downstream antioxidant effectors. These findings highlight the multi-targeted renoprotective actions of MG and support its possible utility as a therapeutic agent to prevent CDDP-induced renal injury. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Kidney Diseases)

► Show Figures

Figure 1

22 pages, 1866 KB

Open AccessReview

Correlation of MLASA2 Clinical Phenotype and Survival with Mt-TyrRS Protein Damage: Linking Systematic Review, Meta-Analysis and 3D Hotspot Mapping

by José Rafael Villafan-Bernal, Angélica Martínez-Hernández, Humberto García-Ortiz, Cecilia Contreras-Cubas, Israel Guerrero-Contreras, José Luis Frías-Cabrera, Federico Centeno-Cruz, Monserrat Ivonne Morales Rivera, Jhonatan Rosas Hernández, Alessandra Carnevale, Francisco Barajas-Olmos and Lorena Orozco

Curr. Issues Mol. Biol. 2026, 48(1), 95; https://doi.org/10.3390/cimb48010095 - 16 Jan 2026

Viewed by 307

Abstract

Myopathy, Lactic Acidosis, and Sideroblastic Anemia type 2 (MLASA2) is a rare mitochondrial disorder caused by pathogenic variants (PVs) in the YARS2 gene (which encodes the Mt-TyrRS protein. We performed a comprehensive clinical–molecular synthesis by integrating a systematic review and meta-analysis of all [...] Read more.

Myopathy, Lactic Acidosis, and Sideroblastic Anemia type 2 (MLASA2) is a rare mitochondrial disorder caused by pathogenic variants (PVs) in the YARS2 gene (which encodes the Mt-TyrRS protein. We performed a comprehensive clinical–molecular synthesis by integrating a systematic review and meta-analysis of all published MLASA2 cases with survival modeling and three-dimensional structural mapping. Across the aggregated cohort, anemia (88.6%), sideroblastic phenotype (85.7%), and lactic acidosis (82.9%) were the most prevalent phenotypes. Fifteen PVs were identified, dominated by p.(Phe52Leu) (29.4%). Survival estimates were 94.1% at 10 years, 70.7% at 30 years, and 42.4% at 50 years; cardiomyopathy and diagnosis before age 10 were associated with decreased survival. We generated the first 3D structural map of all reported Mt-TyrRS PVs, identifying nine spatial hotspots across catalytic, anticodon-binding, and tRNA-binding domains. An integrated framework combining structural density, clinical severity, in silico predictions, and ΔΔG destabilization classified three clusters as High-risk, three as Medium-risk, and three as Low-risk. Among them, cluster 3, a large catalytic hotspot encompassing 44 residues and including nearly half of all MLASA2 cases, showed the strongest pathogenic convergence. This clinical–structural integration provides new insights for a better comprehension of MLASA2, enhancing variant interpretation and improving diagnostic and prognostic precision. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Curr. Issues Mol. Biol., Volume 48, Issue 1 (January 2026) – 124 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI