Current Issues in Molecular Biology

16 pages, 3774 KB

Open AccessArticle

Oral and Intranasal Administration of Polydeoxyribonucleotide Isolated from Porphyra sp. Ameliorates Acute Lung Injury via Suppressing Proinflammatory Cytokine Production in Mice

by Ga-Young Lee, Won Se Lee, Jisung Han and Yung-Choon Yoo

Curr. Issues Mol. Biol. 2026, 48(2), 187; https://doi.org/10.3390/cimb48020187 - 6 Feb 2026

Abstract

Acute lung injury (ALI) is a severe inflammatory condition with high mortality rates, necessitating the development of effective therapeutic agents. Polydeoxyribonucleotide (PDRN), a DNA-derived compound known for its tissue repair and anti-inflammatory properties, has gained attention as a potential therapeutic agent. However, the [...] Read more.

Acute lung injury (ALI) is a severe inflammatory condition with high mortality rates, necessitating the development of effective therapeutic agents. Polydeoxyribonucleotide (PDRN), a DNA-derived compound known for its tissue repair and anti-inflammatory properties, has gained attention as a potential therapeutic agent. However, the efficacy of PDRN derived from marine sources, particularly Porphyra sp. (laver), remains unexplored in respiratory inflammation. In this study, we investigated the protective effects of Porphyra sp.-derived PDRN (Ps-PDRN) against LPS-induced ALI in mice through two administration routes: intranasal (IN) and oral (PO). Ps-PDRN treatment significantly attenuated fever, pulmonary edema, and histopathological changes in LPS-challenged mice. Both IN and PO administration of Ps-PDRN markedly reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokines (MCP-1, RANTES, CXCL1, and MIP-2) in bronchoalveolar lavage fluid (BALF) and serum. Comparative analysis of the two administration routes revealed distinct efficacy profiles, with oral administration demonstrating superior chemokine inhibition, while intranasal delivery showed advantages in certain cytokine suppression. Histological examination revealed that Ps-PDRN preserved alveolar architecture and reduced inflammatory cell infiltration. Furthermore, in vitro studies using RAW 264.7 macrophages demonstrated that Ps-PDRN inhibited LPS-induced production of proinflammatory cytokines, such as TNF-α and IL-6, in a dose-dependent manner. These findings suggest that Ps-PDRN exerts potent anti-inflammatory effects against ALI through both local and systemic administration routes, highlighting its potential as a novel therapeutic agent for inflammatory lung diseases. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation, 2nd Edition)

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25 pages, 4321 KB

Open AccessArticle

Genotype-Specific Rhizosphere Microbiome Assembly Mediates Biochar-Induced Salt Tolerance in Sorghum

by Yingying Xu, Lingyu Zhang, Zhichang Gao, Zhijian Shi, Peng Li, Ruitao Xu and Jianghui Cui

Curr. Issues Mol. Biol. 2026, 48(2), 186; https://doi.org/10.3390/cimb48020186 - 6 Feb 2026

Abstract

Sorghum genotypes differentially shape their rhizosphere microbiomes to cope with salt stress; however, the modulatory role of biochar in this genotype-specific plant–microbe interplay remains unclear. In this study, we investigated how salt-sensitive (Henong 16, HN16) and salt-tolerant (Jizaonuo 1, JZN) sorghum genotypes leverage [...] Read more.

Sorghum genotypes differentially shape their rhizosphere microbiomes to cope with salt stress; however, the modulatory role of biochar in this genotype-specific plant–microbe interplay remains unclear. In this study, we investigated how salt-sensitive (Henong 16, HN16) and salt-tolerant (Jizaonuo 1, JZN) sorghum genotypes leverage biochar to assemble distinct functional rhizosphere microbiomes under salt stress (5 g kg⁻¹ NaCl). Biochar application (20 g kg⁻¹) alleviated ionic stress by reducing soil electrical conductivity (EC decreased by 46% in HN16) and enhanced soil fertility through increased organic matter (SOM increased by 26% in JZN). 16S rRNA gene sequencing revealed that biochar selectively enriched genotype-specific, stress-resistant taxa. The salt-sensitive HN16 primarily recruited Sporosarcina (a genus reported to exhibit salt tolerance and nitrogen-fixing capabilities) and Intrasporangiaceae, thereby rapidly establishing a rhizosphere barrier. In contrast, the salt-tolerant JZN consistently enriched Salinimicrobium (an extreme halophile) and the family LWQ8, forming more complex and stable co-occurrence networks with a higher proportion of positive correlations (81%). Plant genotype was the primary determinant of core microbiome assembly: Bacillus and Arthrobacter dominated in HN16, whereas Sphingomonas and Streptomyces prevailed in JZN. Biochar reinforced this genotype-specific assembly by modulating soil pH and SOM, which were identified as key drivers of microbial community divergence. Importantly, these biochar-shaped microbial modules showed significant positive correlations with increased plant biomass. Our findings demonstrate that biochar enhances salt tolerance not merely by improving soil properties, but primarily by facilitating the deterministic assembly of genotype-specific, functional rhizosphere microbiomes. This mechanistic insight shifts the paradigm of biochar from a universal soil amendment to a precision tool for rhizosphere engineering, providing a genotype-aware foundation for enhancing salinity resilience in sustainable agriculture. Full article

(This article belongs to the Section Molecular Plant Sciences)

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4 pages, 167 KB

Open AccessEditorial

Challenges and Advances in Bioinformatics and Computational Biology

by Tong Si and Haijun Gong

Curr. Issues Mol. Biol. 2026, 48(2), 185; https://doi.org/10.3390/cimb48020185 - 6 Feb 2026

Abstract

Modern sequencing and high-throughput profiling technologies [...] Full article

(This article belongs to the Special Issue Challenges and Advances in Bioinformatics and Computational Biology)

11 pages, 1199 KB

Open AccessArticle

Molecular Characterization of Atypical Hepatitis B Serological Profiles in HBsAg-Negative Women of Childbearing Age in Gabon

by Ismaël Pierrick Mikelet Boussoukou, Aude Sandrine Andeme Eyi, Jean Alban Ondh-Obame, Philippe Jacques Nathanaël Ondamba, Marien Juliet Magossou Mbadinga, Opheelia Makoyo Komba, Serge Thierry Omouessi, Joel Fleury Djoba Siawaya and Bénédicte Ndeboko

Curr. Issues Mol. Biol. 2026, 48(2), 184; https://doi.org/10.3390/cimb48020184 - 6 Feb 2026

Abstract

Occult hepatitis B infection (OBI) and mutated forms of the hepatitis B virus (HBV) represent diagnostic challenges, especially in individuals with atypical serological profiles. This study explores the molecular characteristics of HBV in HBsAg-negative women of childbearing age exhibiting atypical serological markers. We [...] Read more.

Occult hepatitis B infection (OBI) and mutated forms of the hepatitis B virus (HBV) represent diagnostic challenges, especially in individuals with atypical serological profiles. This study explores the molecular characteristics of HBV in HBsAg-negative women of childbearing age exhibiting atypical serological markers. We selected 100 HBsAg-negative sera from a cohort of 433 women aged 15–45 years. Additional HBV serological markers (anti-HBc, anti-HBs, HBeAg, anti-HBe) were assessed. Real-time PCR targeting the HBV S gene was performed on samples presenting atypical profiles. Socio-demographic and clinical correlates were also analyzed. Atypical serological profiles were identified in 23% of HBsAg-negative women, including combinations such as isolated anti-HBe positivity and anti-HBe with anti-HBc. Among these, none tested positive for HBV DNA by real-time PCR. Atypical profiles were more prevalent among women attending antenatal consultations and those aged under 25 years. The absence of detectable HBV DNA suggests either very low viral loads, resolved past infections, or serological artifacts due to mutated HBV strains. The high frequency of atypical serological patterns among HBsAg-negative women underscores the need to refine molecular diagnostic tools for detecting occult or mutated HBV. Further sequencing and genotypic characterization studies are warranted. Full article

(This article belongs to the Special Issue Molecular Biology of Viral Replication and Associated Disease Outcomes)

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21 pages, 3211 KB

Open AccessArticle

Comprehensive Analysis of the AP2/ERF Superfamily Identifies Key Genes Related to Various Stress Responses in Olive Tree (Olea europaea L.)

by Erli Niu, Song Gao, Mengyun Ren, Wei Wang, Qian Zhao and Ying Fu

Curr. Issues Mol. Biol. 2026, 48(2), 183; https://doi.org/10.3390/cimb48020183 - 5 Feb 2026

Abstract

The AP2/ERF superfamily is a key class of transcription factors involved in plant responses to various stresses. As an ancient species, the olive tree (Olea europaea L.) exhibits considerable stress tolerance and wide adaptability. In this study, we identified 348 AP2/ERF genes [...] Read more.

The AP2/ERF superfamily is a key class of transcription factors involved in plant responses to various stresses. As an ancient species, the olive tree (Olea europaea L.) exhibits considerable stress tolerance and wide adaptability. In this study, we identified 348 AP2/ERF genes in the cultivated olive variety ‘Arbequina’ at the whole-genome level. According to protein sequence alignments and phylogenetic analyses via the Maximum Likelihood method, these genes were classified into four major families: AP2, ERF/DREB, RAV, and Soloist. The ERF/DREB family was further divided into DREB and ERF subfamilies, each encompassing six groups (A1–A6 and B1–B6), with the ERF subfamily being the largest. Members of each group exhibited relatively consistent gene structures and domain/motif compositions of their encoded proteins; however, the distribution of cis-elements and expression patterns varied. Each AP2/ERF gene contained 12 light-responsive, three MeJA-responsive, three ABA-responsive, two anaerobic induction, and one MYB binding site on average. With the threshold of p value < 0.5, control TPM > 0, and |log₂(fold change)| > 0, 50 candidate genes were simultaneously up-regulated (30) or down-regulated (20) under four stress treatments (acid–aluminum, cold, disease, and wound), among which nine showed potential protein–protein interactions. This study provides a comprehensive genomic characterization of the AP2/ERF family in olive and identifies key candidate stress-responsive genes, establishing a foundation for future functional studies on the molecular mechanisms of stress adaptation in the olive tree. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding, 2nd Edition)

20 pages, 13338 KB

Open AccessArticle

Multi-Omic and Spatial Profiling Identifies an Epithelial DKK1 Associated with Microenvironmental Remodeling in Pancreatic Ductal Adenocarcinoma

by Jiajia Xu, Kaiqiang Qian, Yanyu Ding, Jianghao Cheng, Xu Zhang, Yong Huang and Bo Liu

Curr. Issues Mol. Biol. 2026, 48(2), 182; https://doi.org/10.3390/cimb48020182 - 5 Feb 2026

Abstract

Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic [...] Read more.

Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic datasets and subsequently validated bulk differential expression and network analyses with machine learning-based prioritization in an independent combined cohort (TCGA-PAAD plus GSE62452). Single-cell mapping was used to assess cell-type specificity, positioning candidates along inferCNV- and pseudotime-defined malignant continua. In Visium sections, a DKK1-associated program score quantified intratumoral spatial heterogeneity and informed our analyses of ligand–receptor communication. Bulk immune deconvolution linked gene levels to immune infiltration patterns, and functional assays were used to test the impact of DKK1 knockdown on migration, proliferation, clonogenic growth, and apoptosis in PDAC cells. Results: Four reproducible tumor-associated genes—DKK1, COL10A1, SULF1, and SLC24A3—were prioritized and validated externally. DKK1 was predominantly expressed by epithelial tumor cells and tracked along a malignant progression continuum. Spatially, the DKK1 program localized to epithelial-dominant regions, revealed pronounced intratumoral heterogeneity, and highlighted epithelial–endothelial and endothelial–immune signaling in high-score areas. Immune deconvolution associated higher DKK1 expression with increased myeloid infiltration and reduced cytotoxic lymphocyte signatures. Functionally, DKK1 knockdown impaired migration, proliferation, and clonogenicity while increasing apoptosis. Conclusions: We demonstrate that DKK1 is an epithelial-derived regulator linked to malignant progression and tumor–stroma–immune remodeling, supporting its potential as a biomarker and therapeutic target in PDAC treatment, including rational combinations with stroma-modulating strategies and immunotherapy. Full article

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

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2 pages, 144 KB

Open AccessCorrection

Correction: Guo et al. Bioinformatic Analysis of the Value of Mitophagy and Immune Responses in Corneal Endothelial Dysfunction. Curr. Issues Mol. Biol. 2025, 47, 670

by Ruilin Guo, Chenjia Xu, Yi Yu, Minglu Ma, Xiaojuan Dong, Jing Wu, Chen Ouyang, Jie Ling and Ting Huang

Curr. Issues Mol. Biol. 2026, 48(2), 181; https://doi.org/10.3390/cimb48020181 - 5 Feb 2026

Abstract

There was an error in the original publication [...] Full article

(This article belongs to the Section Molecular Medicine)

27 pages, 2804 KB

Open AccessReview

Phytochemical Composition and Mechanistic Pharmacology of Jerusalem Artichoke (Helianthus tuberosus L.): Implications for Functional and Therapeutic Applications

by Dong-Hwan Kim, Wonmin Lee, Yeonhee Pyo and Dong-Kug Choi

Curr. Issues Mol. Biol. 2026, 48(2), 180; https://doi.org/10.3390/cimb48020180 - 5 Feb 2026

Abstract

Jerusalem artichoke (JA) (Helianthus tuberosus), a perennial plant of the Asteraceae family, is well known for its high inulin content and diverse bioactive compounds, including flavonoids, phenolic acids, sesquiterpenes, and amino acids. Extracts derived from different parts of JA, such as [...] Read more.

Jerusalem artichoke (JA) (Helianthus tuberosus), a perennial plant of the Asteraceae family, is well known for its high inulin content and diverse bioactive compounds, including flavonoids, phenolic acids, sesquiterpenes, and amino acids. Extracts derived from different parts of JA, such as tubers, leaves, and flowers, have demonstrated a wide range of biological activities, including antioxidant, anti-inflammatory, antihyperglycemic, antihypertensive, and antifungal effects. These properties highlight JA’s potential in the prevention and management of chronic diseases such as diabetes, cardiovascular disorders, obesity, and colorectal cancer. Recent studies also suggest that JA benefits skin health through anti-aging and barrier-protective mechanisms and enhances immune function by modulating the intestinal microbiota. Owing to its multifunctional physiological activities, JA is being explored as a valuable raw material for food, nutraceutical, cosmetic, and pharmaceutical applications. However, most existing research has focused primarily on inulin, while comprehensive studies on other bioactive constituents and their clinical validation remain limited. This paper aims to provide a comprehensive overview of the bioactive compounds present in JA, elucidate their health-promoting functions, discuss their pharmacokinetics, and outline future perspectives on their potential as functional ingredients and biohealth materials. Full article

(This article belongs to the Special Issue Advances in Phytochemical Research: Molecular Pathways in Health and Disease)

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22 pages, 18391 KB

Open AccessArticle

Genetic and Epigenetic Mechanisms in Serrated Adenocarcinomas and Classical Colorectal Carcinomas: An In Silico Study

by Zeynep Sagnak Yilmaz, Sibel Demir Kececi, Ozgul Sagol and Sulen Sarioglu

Curr. Issues Mol. Biol. 2026, 48(2), 179; https://doi.org/10.3390/cimb48020179 - 4 Feb 2026

Abstract

Serrated adenocarcinoma (SAC) represents a molecularly heterogeneous subtype of colorectal carcinoma (CRC) linked to the serrated pathway. It is aimed to clarify the molecular mechanisms underlying SAC development. Digital slides from The Cancer Genome Atlas (TCGA) colorectal adenocarcinoma Firehose Legacy dataset (632 cases) [...] Read more.

Serrated adenocarcinoma (SAC) represents a molecularly heterogeneous subtype of colorectal carcinoma (CRC) linked to the serrated pathway. It is aimed to clarify the molecular mechanisms underlying SAC development. Digital slides from The Cancer Genome Atlas (TCGA) colorectal adenocarcinoma Firehose Legacy dataset (632 cases) were reviewed, and cases were classified as SAC, partial-SAC, or classical CRC. Genomic alterations, mRNA expression, and DNA hypermethylation were compared using cBioPortal. Enrichment analyses were performed via WebGestalt, and protein–protein interaction (PPI) networks with hub genes were identified using STRING and Cytoscape. Statistical significance was defined as p < 0.05 and q < 0.05. The results revealed that the groups showed significant differences in the expression of 327 genomic alterations, 20 mRNAs, and 21 methylated genes (p < 0.0001, q < 0.0001). Hub genes were PSMC1, FLT3LG, SNW1, H3C2, H1-2, H2BC14, H1-5, RPS16, SUPT5H, and MYOD1. The pathways associated with differently expressed genes were the following: cell structure and morphology (phagocytic vesicle, microvillus, endocytosis, and immobile cilium), protein kinase activity (particularly MAPK), and immunological mechanisms. The hub genes act as molecular bridges connecting the observed genomic and epigenetic variations, particularly driving chromatin-related regulation and MAPK signaling pathways. In particular, PSMC1, SNW1, H3C2, H1-2, and H2BC14 genes offer promising molecular targets for future therapeutic approaches in SACs. Full article

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

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25 pages, 726 KB

Open AccessReview

From Adipose Dysfunction to Multi-Organ Steatosis: Defining the Metabolic Steatotic Axis

by Almir Fajkić, Yun Wah Lam, Rijad Jahić, Ivan Ćavar, Antonio Markotić and Andrej Belančić

Curr. Issues Mol. Biol. 2026, 48(2), 178; https://doi.org/10.3390/cimb48020178 - 4 Feb 2026

Abstract

Steatosis extends beyond the liver to the pancreas, heart, and skeletal muscle, yet prevailing definitions remain narrowly organ-focused. This narrative review introduces the Metabolic Steatotic Axis (MSA) as a framework that captures the dynamic, bidirectional interactions among these organs, driving systemic metabolic dysfunction. [...] Read more.

Steatosis extends beyond the liver to the pancreas, heart, and skeletal muscle, yet prevailing definitions remain narrowly organ-focused. This narrative review introduces the Metabolic Steatotic Axis (MSA) as a framework that captures the dynamic, bidirectional interactions among these organs, driving systemic metabolic dysfunction. We synthesize evidence linking lipotoxicity, inflammatory signaling, and endocrine cross-talk into a self-amplifying network accelerating insulin resistance, β-cell failure, and cardiometabolic risk. The MSA concept provides a rationale for axis-based staging systems and composite biomarker panels to quantify cumulative disease burden better and refine risk stratification. We highlight phenotypic heterogeneity within MSA stages, the possible hierarchy of organ vulnerability, and the implications for prognosis and therapy. Viewing pharmacological and lifestyle interventions through the MSA lens reframes them as systemic modulators rather than organ-specific treatments, underscoring the need for multi-organ endpoints in clinical trials. Finally, we outline priorities for longitudinal imaging, multi-omics integration, and global harmonization to translate the MSA from a conceptual construct to a clinically actionable paradigm. By unifying fragmented observations into a systemic model, the MSA has the potential to reshape disease classification, therapeutic strategies, and precision medicine in metabolic disorders. Full article

(This article belongs to the Section Molecular Medicine)

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19 pages, 13246 KB

Open AccessArticle

Simultaneous Inhibition of MDM2 and XIAP by MX69 Induced Cell Cycle Arrest and Apoptosis in HUH7 and Hep3B Cell Lines

by Can Ali Ağca

Curr. Issues Mol. Biol. 2026, 48(2), 177; https://doi.org/10.3390/cimb48020177 - 4 Feb 2026

Abstract

Genomic instability not only drives tumor initiation and progression but also cooperates with apoptosis resistance to promote therapeutic evasion in hepatocellular carcinoma (HCC). Activation of MDM2, a negative regulator of p53, together with XIAP overexpression, represents a critical axis underlying this resistance. Simultaneous [...] Read more.

Genomic instability not only drives tumor initiation and progression but also cooperates with apoptosis resistance to promote therapeutic evasion in hepatocellular carcinoma (HCC). Activation of MDM2, a negative regulator of p53, together with XIAP overexpression, represents a critical axis underlying this resistance. Simultaneous targeting of MDM2 and XIAP by MX69, a small molecule inhibitor, may therefore offer a potent interventional strategy to suppress cell proliferation and enhance pro-apoptotic signaling in HCC in vitro models. To evaluate the effects of MX69, cell viability was assessed via CVDK-8, colony formation, and real-time cell analysis. Oxidative stress levels and DNA damage were examined using fluorescence imaging and comet assays, respectively, while mitochondrial membrane potential was monitored through JC-1 staining. Furthermore, flow cytometry was employed to quantify apoptotic cell death and cell cycle distribution, while Western blot analysis was used to characterize the expression of apoptosis-related proteins. In vitro cytotoxicity assays revealed that MX69 reduced the viability of HUH7 and Hep3B cells in a dose-dependent manner, suppressed colony formation, and exerted anti-proliferative effects in real-time proliferation assays. Cell viability and IC50 values were evaluated using CVDK-8 and RTCA assays. Furthermore, MX69 induced oxidative stress and mitochondrial dysfunction, as evidenced by elevated ROS levels and loss of mitochondrial membrane potential. This was accompanied by significant DNA damage, detected by comet assay and γ-H2AX immunofluorescence, and G0–G1 cell cycle arrest. Moreover, MX69 triggered apoptotic cell death, demonstrating potent anticancer activity. Collectively, our findings identify MDM2/XIAP dual inhibition by MX69 as a promising therapeutic approach in HCC, with potential to overcome apoptosis resistance linked to genomic instability. Full article

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

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25 pages, 2575 KB

Open AccessArticle

Network Pharmacology-Based Analysis Reveals the Mechanisms of the Tibetan Medicinal Plant Meconopsis quintuplinervia Against COPD and NAFLD: Insights from LC-MS/MS Profiling and Antioxidant/Anti-Inflammatory Activities

by Fangfang Chen, Mingjing Chen, Yiyu Chen, Chunyan Chen, Fei Li, Shudi Zhang and Yu-Pei Chen

Curr. Issues Mol. Biol. 2026, 48(2), 176; https://doi.org/10.3390/cimb48020176 - 3 Feb 2026

Abstract

Meconopsis quintuplinervia is traditionally used in Tibetan medicine for diseases of the lung and liver. This study investigated the antioxidant and anti-inflammatory activities of its extract (MQ extract), analyzed its chemical composition, and explored the potential therapeutic mechanisms against chronic obstructive pulmonary disease [...] Read more.

Meconopsis quintuplinervia is traditionally used in Tibetan medicine for diseases of the lung and liver. This study investigated the antioxidant and anti-inflammatory activities of its extract (MQ extract), analyzed its chemical composition, and explored the potential therapeutic mechanisms against chronic obstructive pulmonary disease (COPD) and non-alcoholic fatty liver disease (NAFLD) using network pharmacology. MQ extract demonstrated effective scavenging of DPPH and ABTS radicals, with activity comparable to ascorbic acid and Trolox. In cellular assays, the extract dose-dependently reduced ROS levels in H₂O₂-induced B16-F10 and RAW264.7 cells and significantly inhibited NO production in LPS-stimulated RAW264.7 macrophages. Quantitative analysis showed total phenolic content of 90.54 ± 0.91 mg/g and total flavonoid content of 44.48 ± 0.43 mg/g. LC-MS/MS analysis identified taxifolin as the predominant constituent at approximately 2.39%. Network pharmacology and molecular docking studies revealed that flavonoids including catechin, isorhamnetin, kaempferol, luteolin, naringenin, nobiletin, quercetin, and taxifolin interacted with therapeutic targets for COPD and NAFLD. These compounds likely exerted effects by inhibiting NF-κB signaling, downregulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and enhancing antioxidant enzyme activities (SOD), while also reducing hepatic lipid accumulation through SREBP-1 suppression. Our findings elucidated why Tibetan medicine traditionally uses M. quintuplinervia to treat pulmonary and hepatic disorders. Full article

(This article belongs to the Section Molecular Pharmacology)

17 pages, 2989 KB

Open AccessArticle

Sympathetic Chain Ganglia in the Female Pig During Prenatal Development: Noradrenergic and Cholinergic Neurons

by Amelia Franke-Radowiecka

Curr. Issues Mol. Biol. 2026, 48(2), 175; https://doi.org/10.3390/cimb48020175 - 3 Feb 2026

Abstract

Due to the limited data on chemical coding of sympathetic chain ganglia neurons during the prenatal period, this study, for the first time, aimed to characterise noradrenergic and cholinergic neurotransmitter expression in lumbar sympathetic chain ganglia (L SChG) of 5-, 7-, and 10-week-old [...] Read more.

Due to the limited data on chemical coding of sympathetic chain ganglia neurons during the prenatal period, this study, for the first time, aimed to characterise noradrenergic and cholinergic neurotransmitter expression in lumbar sympathetic chain ganglia (L SChG) of 5-, 7-, and 10-week-old porcine foetuses as a model increasingly recognised in biomedical research. Double immunohistochemical staining was performed using antibodies against PGP 9.5 (marker of neuronal structures), β-hydroxylase tyrosine (DβH), and vesicular acetylcholine transporter (VAChT). The current findings demonstrated that, in 5-week-old foetuses, approximately 79.83 ± 4.37% of nerve cell bodies were DβH-positive, 25.90 ± 5.60% contained VAChT, and some neurons were DβH/VAChT-positive (12.45 ± 4.36%). In 7-week-old foetuses, the proportion of DβH-positive neurons increased to 82.0 ± 9.7%, while VAChT-positive neurons decreased to 6.5 ± 1.0%, and 9.1 ± 0.7% DβH-positive L SChG perikarya contained VAChT. In 10-week-old foetuses, DβH-positive neurons accounted for 88.5 ± 2.1%, VAChT-positive for 1.98 ± 0.64%, and DβH/VAChT-positive perikarya decreased to 5.4 ± 0.4%. These findings provide new insight into the differentiation of the autonomic nervous system and the timing of neurotransmitter phenotype specification. Understanding the ontogeny of noradrenergic and cholinergic neurons may contribute to a better understanding of developmental disorders affecting the autonomic nervous system and may have implications for regenerative medicine, neurodevelopmental diagnostics, and therapeutic strategies targeting sympathetic dysfunction. Full article

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

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11 pages, 2614 KB

Open AccessArticle

Plasma-Derived Extracellular Vesicles Inhibit Lipopolysaccharide-Induced Apoptosis and Oxidative Stress in Human AC16 Cardiomyocytes

by Yuli Yang, Tingting Yang, Zhihong Li and Youshuang Zhu

Curr. Issues Mol. Biol. 2026, 48(2), 174; https://doi.org/10.3390/cimb48020174 - 3 Feb 2026

Abstract

Sepsis is frequently accompanied by myocardial dysfunction, which significantly worsens clinical outcomes. Lipopolysaccharide (LPS), a key component of Gram-negative bacteria, induces excessive oxidative stress and apoptosis in cardiomyocytes, contributing to sepsis-associated cardiac injury. Plasma-derived extracellular vesicles (EVs) have emerged as important mediators of [...] Read more.

Sepsis is frequently accompanied by myocardial dysfunction, which significantly worsens clinical outcomes. Lipopolysaccharide (LPS), a key component of Gram-negative bacteria, induces excessive oxidative stress and apoptosis in cardiomyocytes, contributing to sepsis-associated cardiac injury. Plasma-derived extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and cardiovascular protection; however, their role in LPS-induced cardiomyocyte injury remains unclear. In this study, human AC16 cardiomyocytes were exposed to LPS in the presence or absence of plasma-derived EVs. Intracellular reactive oxygen species (ROS) production and apoptosis were assessed by flow cytometry, while apoptosis-related proteins and NF-κB signaling components were analyzed by Western blotting. The involvement of NF-κB signaling was further examined using pharmacological rescue experiments. Our results demonstrate that EV treatment markedly attenuated LPS-induced ROS accumulation and cardiomyocyte apoptosis. These protective effects were associated with reduced phosphorylation of NF-κB p65 and IκBα, as well as inhibition of p65 nuclear translocation. Notably, activation of NF-κB signaling abolished the anti-apoptotic and antioxidative effects of EVs under LPS challenge. Collectively, these findings suggest that plasma-derived EVs mitigate LPS-induced oxidative stress and apoptosis in human cardiomyocytes, potentially through modulation of NF-κB signaling. This study provides molecular insights into the cardioprotective actions of EVs and supports their potential as therapeutic candidates for sepsis-associated cardiovascular dysfunction. Full article

(This article belongs to the Section Molecular Medicine)

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16 pages, 2091 KB

Open AccessArticle

Genetic Variation in the Main Cultivar Collection of Castanea henryi Revealed by Genome Resequencing

by Yifan Wang, Xueting Yuan, Jinhui Yang, Xibing Jiang, Shipin Chen, Hui Chen and Yu Li

Curr. Issues Mol. Biol. 2026, 48(2), 173; https://doi.org/10.3390/cimb48020173 - 3 Feb 2026

Abstract

Castanea henryi is an important economic tree species in China. Its nutrient-rich nuts play a key role in raising farmers’ income in mountainous areas, promoting forestry industry development, and maintaining ecological balance, thereby providing significant economic and ecological value. To systematically elucidate the [...] Read more.

Castanea henryi is an important economic tree species in China. Its nutrient-rich nuts play a key role in raising farmers’ income in mountainous areas, promoting forestry industry development, and maintaining ecological balance, thereby providing significant economic and ecological value. To systematically elucidate the genetic characteristics of major C. henryi cultivars in China, this study conducted phenotypic trait measurements on 42 cultivars collected from Taining and Jian’ou in Fujian Province. Combined with whole-genome resequencing technology and using the C. henryi genome as a reference, systematic analyses were carried out. The results indicated that the Jian’ou group (HJO) generally exhibited superior performance in key fruit phenotypic traits compared to the Taining group (HTNC), with greater phenotypic diversity observed within the HJO group. Clustering analysis of phenotypic traits further revealed a cross-geographic convergent clustering pattern among the 42 C. henryi cultivars. Further analysis revealed that the overall genetic diversity of the 42 C. henryi cultivars was relatively low (observed heterozygosity: HJO = 0.0275, HTNC = 0.0194). Notably, parameters such as heterozygosity, minor allele frequency, nucleotide polymorphism, and polymorphic information content were slightly higher in the Jian’ou group compared to the Taining group. Divergent selection signal analysis (Fst top 5%) identified 3129 genomic regions under divergent selection. Genes within these regions showed homology to 1205 Arabidopsis thaliana genes, reflecting adaptive divergence driven by differential historical selection pressures between the two groups. Population genetic structure analysis indicated that the two regional groups exhibit high genetic similarity and low differentiation. This study reveals low genetic diversity and high genetic background homogeneity among C. henryi cultivars, findings that could inform the design of future breeding strategies. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding, 2nd Edition)

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35 pages, 1803 KB

Open AccessReview

Plant-Derived Secondary Metabolites Modulating Inflammation-Driven Pathways in Hepatocellular Carcinoma: Preclinical Insights

by Sergio Arael Mendoza-Calderón, Holanda Isabel Cruz Luis, Laura Pérez-Campos Mayoral, Itzel Patricia Vásquez-Martínez, Eduardo Pérez-Campos, Irma Leticia Bazán Salinas, Juan de Dios Ruiz-Rosado, Nahui Samanta Nájera-Segura, Efrén Emmanuel Jarquín González, Jeanet Elizabeth Aragón Ayala, Christopher Torres Flores, Serafina Pérez Rodríguez, María Teresa Hernández-Huerta and Hector A. Cabrera-Fuentes

Curr. Issues Mol. Biol. 2026, 48(2), 172; https://doi.org/10.3390/cimb48020172 - 2 Feb 2026

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily driven by chronic inflammation from viral hepatitis, metabolic dysfunction, alcohol-induced liver disease, and cirrhosis. Conventional therapies often fail in advanced stages, highlighting the need for mechanism-based, precision-guided interventions. Plant-derived secondary metabolites [...] Read more.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily driven by chronic inflammation from viral hepatitis, metabolic dysfunction, alcohol-induced liver disease, and cirrhosis. Conventional therapies often fail in advanced stages, highlighting the need for mechanism-based, precision-guided interventions. Plant-derived secondary metabolites represent a promising class of bioactive compounds with structural diversity, multitarget activity, anti-inflammatory effects, and favorable toxicity profiles. This review follows a semi-systematic narrative that synthesizes preclinical and experimental evidence on the anti-inflammatory and anticancer properties of key phytochemicals, including epigallocatechin-3-gallate, galangin, resveratrol, quercetin, curcumin, berberine, genistein, and thymoquinone. These compounds consistently modulate critical inflammation-driven signaling pathways, PI3K/AKT/mTOR, NF-κB, JAK/STAT, Wnt/β-catenin, and MAPK, resulting in apoptosis induction, cell cycle arrest, inhibition of angiogenesis, and reduced invasion and metastasis in multiple HCC models. Despite strong preclinical evidence, clinical translation remains limited by variable bioavailability, incomplete safety data, and insufficient human studies. A staged development strategy is recommended: standardized formulations, Good Laboratory Practice-compliant pharmacokinetic/toxicology studies, validation in patient-derived models, and early-phase, biomarker-guided clinical trials with combination therapy arms. Addressing regulatory, manufacturing, and quality control considerations will be essential for advancing these compounds as adjuvant or complementary agents in precision HCC therapy. Full article

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

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18 pages, 1681 KB

Open AccessArticle

Investigating Potential 5′ UTR G-Quadruplexes Within NRF2 mRNA

by Hatice Esenkaya and Joe Bryant

Curr. Issues Mol. Biol. 2026, 48(2), 171; https://doi.org/10.3390/cimb48020171 - 2 Feb 2026

Abstract

Post-transcriptional regulation of gene expression is influenced by RNA-binding proteins (RBPs) and small non-coding RNAs that bind to conserved mRNA sequences to modulate mRNA processing. These regulatory molecules affect the structural conformation of mRNAs, creating formations like G-quadruplexes (G4s), which alter translation initiation [...] Read more.

Post-transcriptional regulation of gene expression is influenced by RNA-binding proteins (RBPs) and small non-coding RNAs that bind to conserved mRNA sequences to modulate mRNA processing. These regulatory molecules affect the structural conformation of mRNAs, creating formations like G-quadruplexes (G4s), which alter translation initiation and regulatory-factor site accessibility. Recent studies have highlighted Nuclear factor erythroid 2–related factor 2 (NRF2) as a key regulator of cellular redox homeostasis and cellular response to oxidative stress. An intriguing feature of NRF2 is the structural formation of its 5′ untranslated region (UTR), which may promote or inhibit translation initiation depending on the cellular context. In this study with minigenes, we provide in vitro evidence of RNA G4s in the NRF2 mRNA’s 5′ UTR under basal (no stress) conditions. Achieved via electrophoretic mobility shift assay and fluorescence spectra in the presence of Pyridostatin. Understanding how structural motifs within NRF2 5′ UTRs influence mRNA function provides insights into a common molecular mechanism underlying diseases where NRF2 is dysregulated, like cancers, cardiovascular disease, and neurodegeneration, and highlights potential therapeutic avenues through regulation of NRF2. Full article

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

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27 pages, 1025 KB

Open AccessReview

Botanical Adjuvants in Oncology: A Review on Natural Compounds in Synergy with Conventional Therapies as Next-Generation Enhancers of Breast Cancer Treatment

by Hidaya Mansouri, Ahmed Irchad, Clarence Rubaka, Lydia Kisula, Abdou Azali Hamza and Elingarami Sauli

Curr. Issues Mol. Biol. 2026, 48(2), 170; https://doi.org/10.3390/cimb48020170 - 2 Feb 2026

Abstract

Breast cancer remains a major global health challenge despite advances in chemotherapy, endocrine therapy, targeted therapy, and radiotherapy, which are frequently constrained by therapeutic resistance, cumulative toxicity, and high costs. Accumulating preclinical and translational evidence demonstrates that plant-derived natural compounds can synergistically enhance [...] Read more.

Breast cancer remains a major global health challenge despite advances in chemotherapy, endocrine therapy, targeted therapy, and radiotherapy, which are frequently constrained by therapeutic resistance, cumulative toxicity, and high costs. Accumulating preclinical and translational evidence demonstrates that plant-derived natural compounds can synergistically enhance the efficacy of conventional treatments, improve tumor response, and potentially reduce adverse effects. This review critically synthesizes in vitro, in vivo, and emerging clinical studies from 2015 to 2025, focusing on key phytochemicals, including curcumin, epigallocatechin-3-gallate, resveratrol, kaempferol, genistein, and other bioactive molecules as stand alone agents and as mechanistically validated adjuvants to chemotherapy, hormonal therapy, and radiotherapy. These compounds exert complementary actions, including the inhibition of PI3K/Akt/mTOR and NF-κB signaling, induction of apoptosis and cell-cycle arrest, suppression of epithelial–mesenchymal transition, and modulation of drug resistance pathways. Preclinical studies consistently show that combination strategies enhance tumor inhibition and may permit cytotoxic dose reduction, mitigating systemic and cardiotoxic effects. Nanocarrier-based delivery systems further optimize solubility, bioavailability, and tumor targeting. Despite robust preclinical evidence, clinical translation is limited by variability in raw materials, lack of standardization, regulatory barriers, and scarce large-scale trials. This review emphasizes both the therapeutic promise and translational challenges of integrating natural compounds as synergistic adjuvants in evidence-based breast cancer therapy. Full article

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

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17 pages, 1718 KB

Open AccessArticle

Integrated Transcriptomic and Metabolomic Analysis Reveals Molecular Signatures Associated with Natural Degeneration of Puccinia striiformis f. sp. tritici

by Congying Yuan, Tianyu Long, Jiani Dong, Bingyu Yan, Tingxuan Chen, Yubin Zhang, Yuanhan Yan, Mengyu Cheng and Sitong Xue

Curr. Issues Mol. Biol. 2026, 48(2), 169; https://doi.org/10.3390/cimb48020169 - 2 Feb 2026

Abstract

Stripe rust of wheat, caused by the obligate biotrophic fungus Puccinia striiformis f. sp. tritici (Pst), is a devastating disease. The natural degeneration and viability loss of Pst urediniospores directly impact its dispersal and epidemic potential, yet the underlying molecular mechanisms remain unclear. [...] Read more.

Stripe rust of wheat, caused by the obligate biotrophic fungus Puccinia striiformis f. sp. tritici (Pst), is a devastating disease. The natural degeneration and viability loss of Pst urediniospores directly impact its dispersal and epidemic potential, yet the underlying molecular mechanisms remain unclear. This study aimed to systematically decipher the key molecular changes during the natural degeneration of Pst urediniospores using a multi-omics approach. We performed integrated transcriptomic (RNA-seq) and metabolomic (LC-MS) analyses on relatively purified fresh urediniospores (CC group) and those undergoing room-temperature-induced degeneration (CM group) of the prevalent Pst race CYR34. A total of 1622 differentially expressed genes (DEGs) and 382 differentially accumulated metabolites (DAMs) were identified. Transcriptomic analysis revealed significant downregulation of core energy and biosynthetic pathways, including ribosome biogenesis and oxidative phosphorylation. Metabolomic profiling showed that lipids and lipid-like molecules, along with organic acids and derivatives, constituted the major classes of altered metabolites. DAMs were primarily enriched in pathways such as “Metabolic pathways” and “ABC transporters.” Integrated analysis indicated a prevalent negative correlation pattern between gene expression levels and metabolite abundance. This study provides a systematic molecular landscape associated with Pst urediniospore degeneration, revealing characteristics concomitant with the suppression of energy metabolism and translation functions, thereby offering novel insights and a data foundation for understanding the mechanisms of viability maintenance and loss. Full article

(This article belongs to the Section Molecular Microbiology)

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