Current Issues in Molecular Biology

19 pages, 635 KiB

Open AccessReview

Relevance of Glucagon-Like Peptide 1 (GLP-1) in Inflammatory Bowel Diseases: A Narrative Review

by Antonietta Gerarda Gravina, Raffaele Pellegrino, Michele Izzo, Ilaria De Costanzo, Giuseppe Imperio, Fabio Landa, Assunta Tambaro and Alessandro Federico

Curr. Issues Mol. Biol. 2025, 47(5), 383; https://doi.org/10.3390/cimb47050383 - 21 May 2025

Viewed by 159

Abstract

Inflammatory bowel diseases (IBDs) are complex immune-mediated disorders characterised by an unpredictable direction and commonly associated metabolic comorbidities along with obesity and type 2 diabetes mellitus (T2DM). Recent evidence has highlighted the therapeutic capacity of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), already [...] Read more.

Inflammatory bowel diseases (IBDs) are complex immune-mediated disorders characterised by an unpredictable direction and commonly associated metabolic comorbidities along with obesity and type 2 diabetes mellitus (T2DM). Recent evidence has highlighted the therapeutic capacity of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), already employed in treating T2DM and obesity, in modulating systemic and intestinal inflammatory responses. This narrative review examines the general organic traits of GLP-1, with a specific awareness of its primary gastrointestinal actions and the efficacy of GLP-1 RAs in promoting weight loss and dealing with glycaemic control, mainly in sufferers with IBD. Furthermore, the effects of those agonists on the progression of IBD, their protection profile, their impact on bowel preparation for endoscopic procedures, and their therapeutic capacity, supported through preclinical and early clinical studies, are discussed. GLP-1 RAs appear to lessen the intestinal inflammatory burden by enhancing intestinal epithelial barrier features and modulating the gut microbiota. However, further clinical research will be necessary to verify whether GLP-1 RAs could play a position in IBD treatment. Full article

(This article belongs to the Special Issue Intestinal Inflammation: From Molecular Mechanisms to Therapeutic Strategies)

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22 pages, 5296 KiB

Open AccessReview

The Role of Mitochondrial Energy Metabolism in the Mechanism of Exercise Improving Depression

by Yuwei Liu, Chenghao Zhong, Yuxin Yang, Jianbo Hu, Xiaoyan Yi, Jiating Huang, Haonan Li, Xiaojie Liu, Ke Xue and Xianghe Chen

Curr. Issues Mol. Biol. 2025, 47(5), 382; https://doi.org/10.3390/cimb47050382 - 21 May 2025

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Abstract

Depression is the most disabling neuropsychiatric disorder, but its exact mechanisms remain unclear. Mitochondrial energy metabolism may play a key role in the onset and development of depression. Cytokines such as PGC-1α, NLRP3, and BDNF can influence mitochondrial energy metabolism by regulating mitochondrial [...] Read more.

Depression is the most disabling neuropsychiatric disorder, but its exact mechanisms remain unclear. Mitochondrial energy metabolism may play a key role in the onset and development of depression. Cytokines such as PGC-1α, NLRP3, and BDNF can influence mitochondrial energy metabolism by regulating mitochondrial biogenesis, immune inflammation, and neuroplasticity, thereby mediating the occurrence and progression of depression. Exercise can improve depression by regulating mitochondrial energy metabolism. The molecular mechanisms are closely related to the upregulation of exercise-induced PGC-1α, AMPK, SIRT1, and BDNF expression, as well as the downregulation of NLRP3 expression. These factors can activate key factors or pathways such as Nrf2, AMPK, and PKA/CREB, while inhibiting the excessive activation of NF-κB. Through these mechanisms, they regulate the expression of downstream target genes (such as TFAM, NRF1, CREB, and Bcl-2), thereby enhancing mitochondrial biogenesis and improving the quantity and quality of mitochondria. Additionally, they can act to inhibit the release of inflammatory factors to improve immune inflammation, enhance neuroplasticity, promote neuronal growth, and facilitate synapse formation and remodeling, thereby enhancing mitochondrial energy metabolism and improving its dysfunction, which in turn alleviates depression. Currently, there is a lack of systematic and comprehensive research on the mechanisms by which exercise improves depression through mitochondrial energy metabolism. Therefore, this article aims to review and analyze the role of mitochondrial energy metabolism in the improvement of depression through exercise, in order to provide a new theoretical basis and research ideas for the prevention and treatment of depression. Full article

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

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17 pages, 313 KiB

Open AccessReview

The Struggle Between Chimeric Antigen Receptor T-Cell Therapy and Neurological Complications in Acute Lymphoblastic Leukemia Treatment

by Norwin Kubick, Marzena Łazarczyk, Omar Awad, Michał Ławiński, Jarosław Olav Horbańczuk, Mariusz Sacharczuk, Atanas G. Atanasov, Piotr Religa and Michel Edwar Mickael

Curr. Issues Mol. Biol. 2025, 47(5), 381; https://doi.org/10.3390/cimb47050381 - 21 May 2025

Viewed by 442

Abstract

Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of childhood cancers and 20% of leukemia cases in adults, with a higher prevalence in males than females. It is characterized by symptoms such as fatigue, fever, and bone pain and poses a significant risk [...] Read more.

Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of childhood cancers and 20% of leukemia cases in adults, with a higher prevalence in males than females. It is characterized by symptoms such as fatigue, fever, and bone pain and poses a significant risk of mortality if left untreated. While chemotherapy and stem cell transplantation are standard treatments, their efficacy declines in relapsed or refractory cases, highlighting the need for innovative therapeutic approaches. CAR T-cell therapy has emerged as a transformative technology, offering the potential to overcome these challenges and deliver durable remissions. CAR T-cell therapy demonstrates significant advantages, including targeting specific antigens, overcoming high-risk genetic mutations, and achieving sustained remissions in both pediatric and adult patients. However, notable challenges remain, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In this review, we focus on neurological symptoms associated with CAR T-cell therapy in treating ALL and discuss current and future strategies aiming at reducing their risk. Full article

(This article belongs to the Special Issue Novel Immunotherapy for Neurological Diseases)

29 pages, 9570 KiB

Open AccessArticle

Neurotransmission Sex Dichotomy in the Rat Hypothalamic Paraventricular Nucleus in Healthy and Infantile Spasm Model

by Dumitru Andrei Iacobas, Jana Veliskova, Tamar Chachua, Chian-Ru Chern, Kayla Vieira, Sanda Iacobas and Libor Velíšek

Curr. Issues Mol. Biol. 2025, 47(5), 380; https://doi.org/10.3390/cimb47050380 - 21 May 2025

Viewed by 165

Abstract

We profiled the gene expressions in the hypothalamic paraventricular nuclei of 12 male and 12 female pups from a standard rat model of infantile spasms to determine the sex dichotomy of the neurotransmission genomic fabrics. Infantile spasms were triggered in rat pups prenatally [...] Read more.

We profiled the gene expressions in the hypothalamic paraventricular nuclei of 12 male and 12 female pups from a standard rat model of infantile spasms to determine the sex dichotomy of the neurotransmission genomic fabrics. Infantile spasms were triggered in rat pups prenatally primed with two doses of betamethasone followed by the postnatal repeated administration of N-methyl-D-aspartic acid to induce spasms. Publicly available microarray data were used to characterize each gene in each condition for both sexes by the independent transcriptomic features: average expression level, control of the transcript abundance, and expression correlation with every other gene. This study revealed substantial sex differences in the expression level, control, and inter-coordination of the investigated genes among the studied groups. The transcriptomic differences assist in providing a molecular explanation of the behavioral differences and development of infantile epilepsy spasm syndrome in the two sexes. Full article

(This article belongs to the Special Issue Molecules at Play in Neurological Diseases)

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18 pages, 10784 KiB

Open AccessArticle

Astragalus in Acute Pancreatitis: Insights from Network Pharmacology, Molecular Docking, and Meta-Analysis Validation

by Xingxin Cao, Suqin Duan, Aiyi Li and Zhanlong He

Curr. Issues Mol. Biol. 2025, 47(5), 379; https://doi.org/10.3390/cimb47050379 - 21 May 2025

Viewed by 95

Abstract

(1) Backgroud Astragalus, a traditional Chinese medicine, demonstrates therapeutic effectiveness in acute pancreatitis (AP). Nevertheless, its precise pharmacological mechanism remains unclear, and clinical guidelines have not been established. This study aims to systematically elucidate the active compounds and molecular mechanisms underlying Astragalus’ therapeutic [...] Read more.

(1) Backgroud Astragalus, a traditional Chinese medicine, demonstrates therapeutic effectiveness in acute pancreatitis (AP). Nevertheless, its precise pharmacological mechanism remains unclear, and clinical guidelines have not been established. This study aims to systematically elucidate the active compounds and molecular mechanisms underlying Astragalus’ therapeutic effects in AP, and provide clinical evidence supporting its efficacy. (2) Methods: TCMSP and Swiss Target Prediction identified drug targets; GeneCards, DrugBank, and OMIM provided disease targets. Venny determined the therapeutic targets, while STRING constructed a protein–protein interaction network. Cytoscape 3.10.3 validated core targets. DAVID was used to conduct GO and KEGG pathway analyses, visualized via Bioinformatic platform. Cytoscape 3.10.3 was used to build a “drug–ingredients–targets–pathways–disease” network. AutoDock Vina 1.1.2 and AutoDockTools 1.5.7 was used to performed molecular docking, with PyMOL 3.0 visualizing the results. PubMed, Embase, Cochrane, Web of Science, CNKI, Wanfang, VIP, and CBMdisc were searched. The literature was screened, extracted, and evaluated, followed by a meta-analysis, using RevMan 5.4.1 and Stata 18. (3) Results: We identified 539 targets for the active ingredients of astragalus. Among 1974 disease-related targets, 232 were found to be therapeutic targets. The GO analysis yielded 589 entries, while the KEGG pathway enrichment analysis identified 147 relevant pathways. The top five active ingredients were quercetin, kaempferol, isorhamnetin, formononetin, and calycosin. Molecular docking analysis revealed potential synergistic effects between these components and core targets. The meta-analysis, comprising six randomized controlled trials, demonstrated a significantly higher total effective rate of clinical efficacy in the astragalus group compared to the control group. (4) Conclusions: Astragalus treats AP through the synergistic action of its components, targets, and pathways. Key active compounds, such as quercetin, kaempferol, isorhamnetin, formononetin, and calycosin, engage with pivotal targets, including TP53, AKT1, TNF, IL6, EGFR, CASP3, MYC, and HIF1A, within primary pathways, such as pathways in cancer, PI3K-Akt signaling pathway, and lipid metabolism, and atherosclerosis. Astragalus effectively treats AP and alleviates clinical symptoms by reducing the time for gas or defecation passage, the disappearance time of abdominal pain or distension, and the recovery time of bowel sounds. Full article

(This article belongs to the Special Issue Molecular Biology in Drug Design and Precision Therapy)

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16 pages, 1477 KiB

Open AccessArticle

Disruption of Spore Coat Integrity in Bacillus subtilis Enhances Macrophage Immune Activation

by Bolang Liao, Yongxian Han, Zheng Wei, Xuhong Ding, Yan Lv, Xiaoqin Sun and Mingming Yang

Curr. Issues Mol. Biol. 2025, 47(5), 378; https://doi.org/10.3390/cimb47050378 - 20 May 2025

Viewed by 153

Abstract

Probiotics play a pivotal role in animal production by promoting growth, enhancing gut health, and modulating immune responses. Bacillus subtilis, a widely utilized probiotic, forms robust spores that exhibit exceptional resistance, making it ideal for feed applications. While B. subtilis spores have [...] Read more.

Probiotics play a pivotal role in animal production by promoting growth, enhancing gut health, and modulating immune responses. Bacillus subtilis, a widely utilized probiotic, forms robust spores that exhibit exceptional resistance, making it ideal for feed applications. While B. subtilis spores have been shown to stimulate innate immune signaling, the specific contributions of spore coat proteins to immune modulation remain poorly characterized. In this study, we investigated the immunostimulatory effects of spores deficient in six key coat proteins: SpoIVA, SafA, CotE, CotX, CotZ, and CgeA. These proteins are essential for the assembly and structural integrity of the spore’s multi-layered coat, and are involved in recruiting other coat components. Deletion of these genes result in defects in spore coat architecture, potentially altering spore–host interactions. Using porcine alveolar macrophages (MΦ3D4/2), we assessed cytokine responses to each mutant strain. Our findings demonstrate that the absence of specific structural proteins significantly impacts immune activation, particularly through Toll-like receptor pathways. This work provides novel insights into the immunomodulatory functions of spore coat proteins and lays the foundation for the rational design of next-generation B. subtilis-based probiotics with enhanced immunological properties for agricultural applications. Full article

(This article belongs to the Section Molecular Microbiology)

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23 pages, 2076 KiB

Open AccessArticle

Regulatory Roles of miR-155-5p, miR-21-5p, miR-93-5p, and miR-140-5p in Breast Cancer Progression

by Mai S. Degheidy, Amany A. Abou-Elalla, Mahmoud M. Kamel, Shaimaa Abdel-Ghany, Borros Arneth and Hussein Sabit

Curr. Issues Mol. Biol. 2025, 47(5), 377; https://doi.org/10.3390/cimb47050377 - 20 May 2025

Viewed by 199

Abstract

Breast cancer (BC) remains the leading cause of cancer-related morbidity and mortality worldwide, necessitating innovative approaches to improve diagnosis, prognosis, and treatment. This case-control study, aimed to evaluate the expression profiles of specific microRNAs (miRNAs)—miR-155-5p, miR-21-5p, miR-93-5p, and miR-140-5p—in 50 female BC patients [...] Read more.

Breast cancer (BC) remains the leading cause of cancer-related morbidity and mortality worldwide, necessitating innovative approaches to improve diagnosis, prognosis, and treatment. This case-control study, aimed to evaluate the expression profiles of specific microRNAs (miRNAs)—miR-155-5p, miR-21-5p, miR-93-5p, and miR-140-5p—in 50 female BC patients treated with paclitaxel (PTX) compared to 50 healthy controls. miRNA expression was analyzed using qPCR. The study revealed significant up regulation of these miRNAs in BC patients, with miR-155-5p and miR-21-5p demonstrating the highest diagnostic accuracy (AUC = 0.890 and 0.863, respectively). These miRNAs are implicated in key oncogenic processes, including tumor growth, angiogenesis, metastasis, and chemoresistance, highlighting their potential as non-invasive biomarkers for BC diagnosis and prognosis. Additionally, the study identified significant differences in demographic and biochemical parameters between BC patients and controls, such as lower hemoglobin and RBC counts in patients, indicative of cancer-related anemia, and elevated AST levels. The findings underscore the importance of miRNAs in BC biology and their potential to guide personalized therapeutic strategies. Validation in larger cohorts is recommending and exploring miRNA-based interventions to improve patient outcomes and overcome chemoresistance in BC. Full article

(This article belongs to the Special Issue The Significance of Transcription Factors, miRNAs, and lncRNAs in Anticancer Drug Development, 2nd Edition)

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14 pages, 1241 KiB

Open AccessArticle

Inhibition of TNF-α-Induced Collagen Degradation and Oxidative Damage by Centipeda minima and Brevilin A in Human Dermal Fibroblasts

by Sullim Lee, Byoung Ha Kim, Yea Jung Choi, Dong-Wook Kim, Eunsu Cho, Moonseok Kang, Doeun Kim, Jaesung Pyo and Ki Sung Kang

Curr. Issues Mol. Biol. 2025, 47(5), 376; https://doi.org/10.3390/cimb47050376 - 20 May 2025

Viewed by 139

Abstract

Skin aging and inflammatory skin lesions are exacerbated by reactive oxygen species (ROS) generated in the mitochondria of human dermal fibroblasts (HDFs). These oxidative stressors degrade the extracellular matrix (ECM), promote inflammation, and accelerate skin aging. Antioxidants that suppress reactive oxygen species (ROS) [...] Read more.

Skin aging and inflammatory skin lesions are exacerbated by reactive oxygen species (ROS) generated in the mitochondria of human dermal fibroblasts (HDFs). These oxidative stressors degrade the extracellular matrix (ECM), promote inflammation, and accelerate skin aging. Antioxidants that suppress reactive oxygen species (ROS) production play a crucial role in mitigating these effects. This study investigated the protective effects of Centipeda minima (CMX) and its active constituent, brevilin A, against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and ECM degradation in normal human dermal fibroblasts (NHDFs). Both CMX and brevilin A significantly inhibited TNF-α-induced elevations in ROS, nitric oxide (NO), and prostaglandin E₂ (PGE₂) levels, thereby reducing oxidative stress and inflammatory responses. Additionally, they effectively suppressed matrix metalloproteinase-1 (MMP-1) expression and restored the procollagen I α1 (COLIA1) levels, indicating their potential to preserve ECM integrity. Mechanistically, brevilin A selectively inhibited ERK phosphorylation in the mitogen-activated protein kinase (MAPK) pathway, suggesting its role in regulating collagen degradation and inflammation. These findings highlight that CMX and brevilin A are promising natural agents for protection against skin aging and inflammation. However, further in vivo studies are necessary to validate their efficacy and explore their potential applications in dermatological formulations. Full article

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

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10 pages, 1300 KiB

Open AccessPerspective

The Molecular Pathology of Pre-Eclamptic Hypertension

by Robin W. Carrell, Randy J. Read and Aiwu Zhou

Curr. Issues Mol. Biol. 2025, 47(5), 375; https://doi.org/10.3390/cimb47050375 - 20 May 2025

Viewed by 136

Abstract

The central role of angiotensinogen in the control of blood pressure is revealed by a series of crystallographic structures, including complexes with renin. Specifically, the structures provide an understanding of the sequential molecular events that lead to the pre-eclamptic hypertensive crises of pregnancy. [...] Read more.

The central role of angiotensinogen in the control of blood pressure is revealed by a series of crystallographic structures, including complexes with renin. Specifically, the structures provide an understanding of the sequential molecular events that lead to the pre-eclamptic hypertensive crises of pregnancy. The release of the precursor vasopressor peptide from the amino-terminal tail of angiotensinogen appears to be modulated by a redox-sensitive disulphide bridge. Our findings indicate that the activation of the thiol-switch in the circulating maternal angiotensinogen occurs at the placental level in response to oxidative stress, exacerbated by placental insufficiency. We propose here that a contributory factor is the inherent redox stress accompanying the placental exchange of oxygenation between the haemoglobin of the mother (oxy-HbA) and the deoxygenated haemoglobin of the foetus (deoxy-HbF). Full article

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

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38 pages, 916 KiB

Open AccessReview

The Impact and Molecular Mechanisms of Exercise in Cancer Therapy

by Yingjie Sun, Yixiao Ma, Lei Shi, Tong Liu, Yahong Dong and Qiguan Jin

Curr. Issues Mol. Biol. 2025, 47(5), 374; https://doi.org/10.3390/cimb47050374 - 20 May 2025

Viewed by 243

Abstract

Cancer is a major global health issue, and exercise has become a key supportive treatment. It contributes to reducing cancer risk, enhancing prognosis, and aiding recovery, especially for survivors. However, the exact mechanisms, such as how exercise reduces cancer risk or enhances treatment, [...] Read more.

Cancer is a major global health issue, and exercise has become a key supportive treatment. It contributes to reducing cancer risk, enhancing prognosis, and aiding recovery, especially for survivors. However, the exact mechanisms, such as how exercise reduces cancer risk or enhances treatment, are still unclear. Current research often focuses on specific cancer types, ignoring the diverse needs of patients. This limits the development of personalized exercise plans. Additionally, there is insufficient comparison of exercise types—like aerobic, resistance, and high-intensity interval training—regarding their adverse effects and long-term benefits. The best combination of exercises and personalized strategies remains unknown. This review underscores the contribution of physical exercise to cancer prevention and treatment, emphasizing its positive effects on reducing fatigue, improving physical strength, and enhancing mental health. It also explores the molecular mechanisms of regulating tumor immunity and energy metabolism. Additionally, the article covers criteria for selecting exercise types and intensities, and the development of personalized exercise plans. Finally, it provides guidelines for exercise prescriptions and suggests future research directions to improve interventions for cancer patients. Full article

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

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14 pages, 1914 KiB

Open AccessArticle

Light-Regulated Gene Expression Patterns During Conidial Formation in Aspergillus oryzae

by Shangfei Lin, Jiali Yang, Aixia Wang, Qiqi Fu, Shijie Huang and Muqing Liu

Curr. Issues Mol. Biol. 2025, 47(5), 373; https://doi.org/10.3390/cimb47050373 - 20 May 2025

Viewed by 154

Abstract

With the effect of light on the conidial formation of Aspergillus oryzae now being known, the molecular mechanism of its light response has become a research hotspot. However, the light-regulated genes investigated in earlier studies do not clearly explain the light response patterns [...] Read more.

With the effect of light on the conidial formation of Aspergillus oryzae now being known, the molecular mechanism of its light response has become a research hotspot. However, the light-regulated genes investigated in earlier studies do not clearly explain the light response patterns of related genes at the transcriptional level. This study employed RNA sequencing technology to preliminarily identify the light-regulated genes among the genes related to conidia production and photoreception in A. oryzae GDMCC 3.31. Subsequently, the effects of light dose on the light-regulated genes were analyzed by qRT-PCR. We identified a total of six genes (tcsA, catA, gld1, Aowc-1, abaA, and AofphA) as light-regulated genes. The expression pattern of abaA was dependent on the light spectrum and light dose. When the light dose was maintained at a high level, the abaA gene served as a red–green light-regulated gene. Otherwise, the abaA gene showed no response to light. The phytochrome-like gene AofphA was regulated by red and blue light with a biphasic response under varying light doses, suggesting the existence of a light dose threshold. These findings provide new targets for the photoresponse molecular mechanisms in A. oryzae. Full article

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

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17 pages, 3590 KiB

Open AccessArticle

Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi Targeting Cyp2e1 In Vivo

by Wenwen Liu, Liwen Huan, Cai Zhang, Runting Yin, Zhen Ouyang and Yuan Wei

Curr. Issues Mol. Biol. 2025, 47(5), 372; https://doi.org/10.3390/cimb47050372 - 19 May 2025

Viewed by 265

Abstract

The overdose of acetaminophen (APAP) has become the leading cause of acute liver failure in the United States and some Western countries. As a principal member of the cytochrome P450 enzymes (CYPs), CYP2E1 is a vital enzyme in regard to the production of [...] Read more.

The overdose of acetaminophen (APAP) has become the leading cause of acute liver failure in the United States and some Western countries. As a principal member of the cytochrome P450 enzymes (CYPs), CYP2E1 is a vital enzyme in regard to the production of toxic APAP metabolites and in the development of APAP-induced liver injury (AILI). In this study, we investigated the therapeutic effects and mechanisms of lipid nanoparticle (LNP)-based delivery of small interfering RNA targeting Cyp2e1 (si-Cyp2e1 LNPs) on AILI in mice. C57BL/6J male mice were injected with 300 mg/kg APAP to establish an AILI model, and si-Cyp2e1 LNPs were administered via the tail vein. The results showed that the levels of serum alanine aminotransferase and aspartate aminotransferase were lower than those in APAP mice after treatment with si-Cyp2e1 LNPs immediately. Moreover, si-Cyp2e1 LNPs significantly inhibited liver necrosis and oxidative stress in APAP mice. RNA sequencing revealed that si-Cyp2e1 LNPs exerted regulatory effects on pathways and genes related to peroxisome proliferator-activated receptor (PPAR). Consistent with this finding, we also proved that si-Cyp2e1 LNPs markedly regulated the expressions of genes involved in the PPAR signaling pathway (CYP4A, PPARα, FABP 1, and CD36) in APAP mice, as well as inflammatory factors (Il-6, Il-1β, and Tnf-α). These findings suggested that si-Cyp2e1 LNPs may alleviate APAP-induced oxidative stress and inflammation by regulating lipid metabolism via PPAR-related pathways. Full article

(This article belongs to the Special Issue Advances in Molecular Biology Methods in Hepatology Research)

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11 pages, 2192 KiB

Open AccessArticle

Effects of Aerobic Exercise on Irisin and Skeletal Muscle Autophagy in ApoE^−/− Mice

by Wenxin Wang, Fengting Zheng, Jiawei Zhou, Yangfan Cao, Liang Zhang, Yao Lu, Qingbo Li, Ting Li, Mallikarjuna Korivi, Lifeng Wang and Wei Li

Curr. Issues Mol. Biol. 2025, 47(5), 371; https://doi.org/10.3390/cimb47050371 - 19 May 2025

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Abstract

As a chronic inflammatory disease, atherosclerosis can affect the occurrence of skeletal muscle autophagy through a variety of mechanisms. Previous studies have demonstrated that exercise enhances autophagic activity through irisin-mediated pathways. Building upon this evidence, this study investigated the effects of a 12-week [...] Read more.

As a chronic inflammatory disease, atherosclerosis can affect the occurrence of skeletal muscle autophagy through a variety of mechanisms. Previous studies have demonstrated that exercise enhances autophagic activity through irisin-mediated pathways. Building upon this evidence, this study investigated the effects of a 12-week aerobic exercise training on irisin levels and skeletal muscle autophagy-related proteins in atherosclerotic mice. Male C57BL/6J and ApoE^−/− mice were randomly assigned to four groups: Control Group (C), Aerobic Exercise Group (CE), ApoE^−/− Control Group (AC), and ApoE^−/− Aerobic Exercise Group (AE). Serum and muscle irisin levels were measured by ELISA; the expression levels of FNDC5, AMPK/mTOR pathway proteins and autophagy markers were detected by immunoblots, and muscle morphology was examined using H&E staining. Compared with the C group, the serum levels of TAG, TC, and LDL-C were higher than the AC group. Aerobic exercise increased irisin levels in skeletal muscle, upregulated the expression of LKB1 and p-AMPK, and presented an elevated LC3-II/I ratio, accompanied by reduced mTORC1 expression in CE mice. Aerobic exercise increased FNDC5 expression and irisin levels in serum and skeletal muscle, but also upregulated mTORC1 expression and reduced the LC3-II/I ratio in the AE group. Aerobic exercise enhances irisin synthesis and improves dyslipidemia in ApoE^−/− mice. However, the increased expression of the mTORC1 protein contributed to decreasing the expression of autophagy-related proteins following exercise. Full article

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

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13 pages, 4323 KiB

Open AccessArticle

D-Limonene Exhibits Antiproliferative Activity Against Human Colorectal Adenocarcinoma (Caco-2) Cells via Regulation of Inflammatory and Apoptotic Pathways

by Abdullah A. A. Alghamdi

Curr. Issues Mol. Biol. 2025, 47(5), 370; https://doi.org/10.3390/cimb47050370 - 18 May 2025

Viewed by 234

Abstract

Current therapies for colorectal cancer (CRC) are associated with significant side effects and limitations, driving the search for novel therapeutic approaches. This study investigated the antiproliferative potential of D-limonene, a natural compound, on human colorectal adenocarcinoma (Caco-2) cells and analyzed its underlying mechanisms. [...] Read more.

Current therapies for colorectal cancer (CRC) are associated with significant side effects and limitations, driving the search for novel therapeutic approaches. This study investigated the antiproliferative potential of D-limonene, a natural compound, on human colorectal adenocarcinoma (Caco-2) cells and analyzed its underlying mechanisms. Caco-2 cells were treated with D-limonene or doxorubicin (DOX) for 24 h. Cell viability was assessed using the MTT assay, with D-limonene and DOX showing IC50 values of 18.6 and 6.4 µM, respectively. In comparison to controls, D-limonene treatment dramatically enhanced the formation of reactive oxygen species (ROS) and decreased cellular antioxidant capacity, as seen by concentration-dependent lower glutathione (GSH) levels. The substance also increased the levels of pro-apoptotic proteins (caspase-3, Bax), tumor suppressor p53, lactate dehydrogenase (LDH), and inflammatory indicators [tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)]. Furthermore, in a concentration-dependent way, D-limonene therapy decreased the levels of matrix metalloproteinases (MMP2, MMP9), proliferation marker Ki67, and the anti-apoptotic protein Bcl-2. These results imply that the induction of oxidative stress, inflammation, and apoptotic pathways mediates D-limonene’s antiproliferative actions in colon cancer cells. Our findings show that D-limonene has therapeutic promise as a natural substitute for the treatment of colorectal cancer. Full article

(This article belongs to the Special Issue Natural Compounds: An Adjuvant Strategy in Cancer Management)

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14 pages, 3990 KiB

Open AccessArticle

TNF Signaling Pathway Is the Key Pathway Regulated by Disitamab Vedotin in Bladder Cancer Cells

by Xingxing Tang, Jia Liu, Qiang Zhao, Yudong Cao, Xiao Yang, Peng Du and Yong Yang

Curr. Issues Mol. Biol. 2025, 47(5), 369; https://doi.org/10.3390/cimb47050369 - 18 May 2025

Viewed by 201

Abstract

Disitamab Vedotin has shown good therapeutic efficacy against bladder cancer. Although its mechanism is clear, the regulation of gene expression in bladder cancer cells by Disitamab Vedotin is not fully understood. We searched the GEO database and identified the GSE237789 dataset, in which [...] Read more.

Disitamab Vedotin has shown good therapeutic efficacy against bladder cancer. Although its mechanism is clear, the regulation of gene expression in bladder cancer cells by Disitamab Vedotin is not fully understood. We searched the GEO database and identified the GSE237789 dataset, in which researchers treated the bladder cancer cell line SW780 with Disitamab Vedotin and performed high-throughput transcriptome sequencing. Compared with the control SW780 cells, the expression levels of the vast majority of genes (16,223/16,390, 98.98%) in Disitamab Vedotin-treated SW780 cells remained unchanged. Only one hundred fifty-nine genes (0.97%) were upregulated, and eight genes (0.05%) were downregulated. Enrichment analysis results showed that the related differentially expressed genes (DEGs) were mainly enriched in the TNF signaling pathway, NF-κB signaling pathway, and other pathways. Protein–protein interaction analysis revealed that 10 genes, TNF, IL1B, IL1A, CXCL8, CXCL1, CCL2, MMP9, ICAM1, CXCL10, and CCL20, had the highest connectivity, and all of these genes belong to the TNF signaling pathway. These results suggest that the TNF signaling pathway is the key pathway regulated by Disitamab Vedotin in bladder cancer cells, which may represent a stress response of bladder cancer cells to Disitamab Vedotin. Full article

(This article belongs to the Section Molecular Medicine)

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14 pages, 445 KiB

Open AccessArticle

Assessment of TNF-α, IL-12/23, and IL-17 in Psoriasis: Only TNF-α Reflects Clinical Response After 12 Weeks of Biologic Treatment

by Alessandra-Mădălina Matei-Man, Ștefan Cristian Vesa, Alexandra Dana Pușcaș, Meda Sandra Orăsan, Bianca Homorozeanu, Elisabeta Candrea and Teodora Mocan

Curr. Issues Mol. Biol. 2025, 47(5), 368; https://doi.org/10.3390/cimb47050368 - 16 May 2025

Viewed by 500

Abstract

Background: Tumor necrosis factor-alpha (TNF-α), IL-12/23, IL-17A, and IL-17F are key proinflammatory cytokines involved in the pathogenesis of psoriasis. Biologic therapies targeting these interleukins have demonstrated clinical efficacy. However, the exact relationship between their serum levels and clinical response remains unclear. The aims [...] Read more.

Background: Tumor necrosis factor-alpha (TNF-α), IL-12/23, IL-17A, and IL-17F are key proinflammatory cytokines involved in the pathogenesis of psoriasis. Biologic therapies targeting these interleukins have demonstrated clinical efficacy. However, the exact relationship between their serum levels and clinical response remains unclear. The aims of this study are to assess changes in cytokine levels (TNF-α, IL-12/23, IL-17A, IL-17F) after 12 weeks of biologic treatment in psoriasis to test if there is any correlation between their serum level and PASI (Psoriasis Area Severity Index) and DLQI (Dermatology Life Quality Index) scores before or after treatment and to check the influence of clinical and lifestyle factors on these levels. Methods: In this prospective study, 36 patients with moderate-to-severe plaque psoriasis receiving anti-TNF-α, anti-IL-17, or anti-IL-23 therapy were assessed at baseline and after 12 weeks. The serum levels of these cytokines were measured using the ELISA technique. Clinical response was evaluated using PASI and DLQI scores. Spearman correlation analysis was used to assess the relationship between interleukins’ serum levels and these scores. Results: A significant decrease in TNF-α levels and DLQI and PASI scores was observed after 12 weeks across all treatments. A moderate positive correlation (r = 0.391, p = 0.018) was found between serum TNF-α levels and PASI scores at week 12. Conclusions: The serum levels of TNF-α are significantly correlated with PASI scores following 12 weeks of biologic therapy, supporting their potential role as a biomarker for monitoring treatment efficacy in psoriasis. 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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29 pages, 1950 KiB

Open AccessReview

Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions

by Antonios Mouzakis, Vasileios Petrakis, Eleni Tryfonopoulou, Maria Panopoulou, Periklis Panagopoulos and Katerina Chlichlia

Curr. Issues Mol. Biol. 2025, 47(5), 367; https://doi.org/10.3390/cimb47050367 - 16 May 2025

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Abstract

This review explores the mechanisms by which Human Immunodeficiency Virus type 1 (HIV-1) regulatory proteins manipulate host cellular pathways to promote viral replication and immune evasion. Key viral proteins, such as Nef, Vpu, Vif, Vpr, and Env, disrupt immune defenses by downregulating surface [...] Read more.

This review explores the mechanisms by which Human Immunodeficiency Virus type 1 (HIV-1) regulatory proteins manipulate host cellular pathways to promote viral replication and immune evasion. Key viral proteins, such as Nef, Vpu, Vif, Vpr, and Env, disrupt immune defenses by downregulating surface molecules such as CD4 (Cluster of Differentiation 4) and Major Histocompatibility Complex (MHC) class I, degrading antiviral enzymes like APOBEC3G (Apolipoprotein B mRNA editing catalytic polypeptide-3G) and SAMHD1 (Sterile Alpha Motif and Histidine Aspartate domain-containing protein 1), and counteracting restriction factors including BST-2 (Bone Marrow Stromal Antigen 2)/Tetherin and SERINC5 (Serin Incorporator 5). These interactions support viral persistence and contribute to the establishment of chronic infection. Emerging therapeutic strategies aim to disrupt these HIV-host interactions to restore innate antiviral responses and enhance immune clearance. Approaches such as stabilizing host restriction factors or blocking viral antagonists offer a promising alternative to conventional antiretroviral therapy. By targeting host-dependent pathways, these interventions may reduce drug resistance, tackle latent reservoirs, and provide a pathway toward sustained viral remission or functional cure. Full article

(This article belongs to the Special Issue Infectious Diseases and Molecular Epidemiology: A Focus on Pathogenic Microorganisms)

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23 pages, 7956 KiB

Open AccessArticle

PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights

by Jinhui Liu, Qi-An Chen, Yannan Yang, Lin Zhang, Weihao Lin, Yuheng Hong and Yibo Gao

Curr. Issues Mol. Biol. 2025, 47(5), 366; https://doi.org/10.3390/cimb47050366 - 16 May 2025

Viewed by 153

Abstract

Background: Lung adenocarcinoma is the most common NSCLC and is associated with metabolic dysregulation. Purine biosynthesis, regulated by PAICS, plays a key role in tumor progression and therapy resistance. Methods: We focused on LUAD using pan-cancer and KEGG enrichment analyses. TCGA-LUAD and three [...] Read more.

Background: Lung adenocarcinoma is the most common NSCLC and is associated with metabolic dysregulation. Purine biosynthesis, regulated by PAICS, plays a key role in tumor progression and therapy resistance. Methods: We focused on LUAD using pan-cancer and KEGG enrichment analyses. TCGA-LUAD and three GEO datasets were analyzed to confirm the prognostic relevance of purine biosynthesis. A prognostic model, the Purine Biosynthesis-Related Score (PBRS), was developed using LASSO regression and validated in independent cohorts. Gene set variation analysis, immune profiling, tumor mutational burden analysis, and drug sensitivity analysis were conducted. PAICS expression was validated in LUAD tissues, and its role was assessed via proliferation and migration assays. Results: PBRS classified LUAD patients into high-risk (PBRS-high) and low-risk (PBRS-low) subgroups, with distinct prognostic outcomes. PBRS-high patients showed enrichment in cell cycle regulation and DNA repair pathways and had higher TMB, suggesting potential sensitivity to immunotherapy, although immune escape mechanisms may limit the efficacy of immune checkpoint inhibitors. PBRS-low patients were more responsive to metabolic inhibitors. PAICS overexpression correlated with poor prognosis, while its knockdown suppressed LUAD progression. Conclusion: PBRS is a prognostic tool in LUAD, identifying PBRS-high patients who may benefit from immunotherapy or DDR-targeted therapies. PBRS-low patients exhibit sensitivity to metabolic inhibitors. PAICS is a potential therapeutic target. Full article

(This article belongs to the Section Molecular Medicine)

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11 pages, 756 KiB

Open AccessArticle

Investigating LATS1 and NF-κB as Predictors of Radiotherapy Response in Cervical Cancer

by Andi Darma Putra, Andrijono, Hariyono Winarto, Ani Retno Prijanti, Lisnawati, Trevino Aristarkus Pakasi, Supriadi Gandamihardja, Jourdan Wirasugianto, Amelia and Lasmini Syariatin

Curr. Issues Mol. Biol. 2025, 47(5), 365; https://doi.org/10.3390/cimb47050365 - 16 May 2025

Viewed by 142

Abstract

Cervical cancer is the fourth most prevalent cancer among women globally. Protein concentrations of Large Tumor Suppressor Kinase-1 (LATS1) and Nuclear Factor Kappa-B (NF-κB) have been identified as prospective biomarkers of radioresistance in cervical cancer. This preliminary study aimed to investigate the effectiveness [...] Read more.

Cervical cancer is the fourth most prevalent cancer among women globally. Protein concentrations of Large Tumor Suppressor Kinase-1 (LATS1) and Nuclear Factor Kappa-B (NF-κB) have been identified as prospective biomarkers of radioresistance in cervical cancer. This preliminary study aimed to investigate the effectiveness of LATS1 and NF-κB levels as a biomarker for radioresistance and evaluate their response to radiation in cervical cancer patients. A comprehensive cross-sectional study was conducted involving 114 subjects diagnosed with advanced stages cervical cancer (stage IIIB and IVA) who underwent definitive radiotherapy. The concentrations of LATS1 and NF-κB were measured using ELISA from biopsy samples taken prior to the initiation of radiotherapy. This study’s finding included 114 subjects, with a median age of 53 years. A total of 85 (74.5%) subjects had stage IIIB, while 29 (25.4%) subjects had stage IVA. The cut-offs for LATS1 and NF-κB were 0.02765 ng/mg and 192.42 pg/mg, respectively. Subjects with a higher expression of LATS1 were found to be unresponsive to radiation therapy (p ≤ 0.001; AUC = 32.7%), and subjects with a lower expression of NF-κB were found to be unresponsive to radiation therapy (p = 0.009; AUC = 61%). This study suggests that elevated LATS1 expression may inversely predict radioresistance, while NF-κB expression shows a weak correlation with resistance to radiation therapy. Full article

(This article belongs to the Special Issue Molecular Insights into Radiation Oncology)

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16 pages, 3374 KiB

Open AccessArticle

Kiperin Double-Hydrolyzed Collagen as a Potential Anti-Tumor Agent: Effects on HCT116 Colon Carcinoma Cells and Oxidative Stress Modulation

by Lutfiye Karcioglu Batur, Cuneyd Yavas and Nezih Hekim

Curr. Issues Mol. Biol. 2025, 47(5), 364; https://doi.org/10.3390/cimb47050364 - 15 May 2025

Viewed by 326

Abstract

Double-hydrolyzed collagen, a key structural protein, has gained increasing attention for its role in cancer progression and its potential therapeutic applications. This study aims to investigate the effects of double-hydrolyzed collagen (Type I and III peptides) on HCT116 colon carcinoma cells and CCD-18Co [...] Read more.

Double-hydrolyzed collagen, a key structural protein, has gained increasing attention for its role in cancer progression and its potential therapeutic applications. This study aims to investigate the effects of double-hydrolyzed collagen (Type I and III peptides) on HCT116 colon carcinoma cells and CCD-18Co fibroblasts as a normal control. Cells were treated with 0.5 µg/mL, 1 µg/mL, and 1.5 µg/mL of collagen peptide solution. HCT116 and CCD-18Co cells were cultured under standard conditions and treated with 1 µg/mL collagen. Cell viability (MTT assay), migration (scratch assay), oxidative stress (TAS/TOS kits), TNF-α expression (qRT-PCR), and tumor marker levels (CA19-9, CEA, CA72-4, and CYFRA 21-1; CLIA) were evaluated. Cell viability, proliferation, migration, oxidative stress, and tumor marker levels were assessed. Statistical analyses were performed to determine significance. Double-hydrolyzed collagen treatment significantly increased CCD-18Co fibroblast proliferation (p = 0.0143), while HCT116 cancer cell numbers significantly decreased (p = 0.0045). Migration of HCT116 cells was markedly reduced (p < 0.0001), whereas no significant effect was observed in CCD-18Co fibroblasts (p = 0.559). Oxidative stress analysis showed decreased total oxidative status (TOS) and increased total antioxidant status (TAS) in HCT116 cells (p = 0.0075 and p = 0.0095, respectively), with no significant changes in normal fibroblasts. Among tumor markers, CA19-9 levels were significantly reduced in HCT116 cells (p = 0.013), while CEA, CA72-4, and CYFRA 21-1 remained unchanged. TNF-α gene expression analysis confirmed the absence of inflammatory or adverse effects in normal fibroblasts. These findings suggest that double-hydrolyzed collagen selectively inhibits colon cancer cell proliferation and migration, modulates oxidative stress, and reduces CA19-9 levels while promoting fibroblast growth. The differential effects between cancerous and normal cells highlight collagen’s potential as a complementary therapeutic approach for colorectal cancer. Further research is needed to elucidate the underlying mechanisms and assess its clinical applicability. Double-hydrolyzed collagen appears to be a safe and beneficial dietary component with promising biological effects and therapeutic potential. Full article

(This article belongs to the Section Molecular Medicine)

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2 pages, 148 KiB

Open AccessEditorial

Editorial for Special Issue “Current Advances in Oxytocin Research”

by Claudia Camerino

Curr. Issues Mol. Biol. 2025, 47(5), 363; https://doi.org/10.3390/cimb47050363 - 15 May 2025

Viewed by 191

Abstract

Very few hormones and neurotransmitters are as fascinating as oxytocin [...] Full article

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

18 pages, 804 KiB

Open AccessReview

Herbal Medicine in Breast Cancer Therapy: Mechanisms, Evidence, and Future Perspectives

by Hsien-Chang Wu, Chung-Che Tsai, Po-Chih Hsu and Chan-Yen Kuo

Curr. Issues Mol. Biol. 2025, 47(5), 362; https://doi.org/10.3390/cimb47050362 - 15 May 2025

Viewed by 317

Abstract

Breast cancer remains a leading global cause of cancer-related mortality among women, requiring the development of safer and more effective therapeutic strategies. Herbal medicines have gained increasing attention as complementary approaches due to their multi-targeted actions, more limited toxicities, and the potential ability [...] Read more.

Breast cancer remains a leading global cause of cancer-related mortality among women, requiring the development of safer and more effective therapeutic strategies. Herbal medicines have gained increasing attention as complementary approaches due to their multi-targeted actions, more limited toxicities, and the potential ability to overcome resistance associated with conventional treatments. This review highlights the antitumor properties and underlying mechanisms of several well-studied herbal compounds, including curcumin, resveratrol, epigallocatechin gallate, withaferin A, thymoquinone, baicalin, berberine, Oldenlandia diffusa, and Salvia miltiorrhiza. These phytochemicals exert antitumor effects by inducing apoptosis, inhibiting cell proliferation and metastasis, modulating immune responses, and sensitizing tumor cells to chemotherapy and radiotherapy. Furthermore, many of these agents regulate key signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells, phosphatidylinositol 3-kinase/AKT, p53, signal transducer and activator of transcription 3, and extracellular signal-regulated kinases 1/2, and the tumor microenvironment. Despite promising preclinical and early clinical evidence, challenges remain regarding the bioavailability, standardization, and large-scale clinical validation of these phytochemicals. This review underscores the therapeutic potential of herbal medicines in breast cancer treatment and advocates for further research to facilitate their integration into evidence-based oncology practice. Full article

(This article belongs to the Special Issue Natural Compounds: An Adjuvant Strategy in Cancer Management)

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21 pages, 10277 KiB

Open AccessArticle

Impact of SARS-CoV-2 Variant NSP6 on Pathogenicity: Genetic Analysis and Cell Biology

by Yangye Gao, Peng Ni, Yanqiao Hua, Shuaiyin Chen and Rongguang Zhang

Curr. Issues Mol. Biol. 2025, 47(5), 361; https://doi.org/10.3390/cimb47050361 - 14 May 2025

Viewed by 251

Abstract

SARS-CoV-2 nonstructural protein (NSP) 6 is one of the factors affecting viral pathogenicity. Mutations in NSP6 continuously emerge during viral transmission and are closely associated with alterations in viral pathogenicity. This study investigated the structural and functional impacts of NSP6 mutations by analyzing [...] Read more.

SARS-CoV-2 nonstructural protein (NSP) 6 is one of the factors affecting viral pathogenicity. Mutations in NSP6 continuously emerge during viral transmission and are closely associated with alterations in viral pathogenicity. This study investigated the structural and functional impacts of NSP6 mutations by analyzing NSP6 proteins from the Wuhan-Hu-1/B (WT) strain and predominant variants Alpha, XBB.1.16, BA.2.86, and JN.1 using bioinformatics, transcriptomics, and cellular experiments. The results demonstrate that the V3593F mutation decreased the β-sheet proportion and modified hydrogen bonding patterns, while the L3829F mutation enhanced structural stability by promoting random coils. The R3821K substitution exposed lysine residues, potentially enhancing molecular interactions. Combined transcriptomic profiling and functional assays revealed that WT-NSP6 significantly inhibited poly (I: C)-induced immune factor transcription and reduced the phosphorylation levels of p-IRF3 and p-STAT1, effects absent in the XBB.1.16 variant. Furthermore, WT-NSP6 markedly activated p-AKT and p-mTOR expression, with JN.1-NSP6 maintaining limited capacity to upregulate p-mTOR. However, p53 inhibitor treatment reversed Alpha-NSP6- and BA.2.86-NSP6-upregulated p-mTOR protein expression in cells. This study demonstrates that a high frequency of NSP6 mutations alters NSP6’s structure, impairing the type I interferon signaling pathway and affecting host antiviral responses through the p53-AKT-mTOR signaling pathway. These findings contribute to the understanding of evolution, immune evasion, and viral pathogenesis mechanisms, with potential implications for the development of antiviral therapies and preventive strategies for this viral infection. Full article

(This article belongs to the Section Molecular Microbiology)

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15 pages, 4213 KiB

Open AccessArticle

Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing

by Nihal Almuraikhi, Latifa Alkhamees, Sumaiya Tareen, Hessah Alshammari and Manikandan Muthurangan

Curr. Issues Mol. Biol. 2025, 47(5), 360; https://doi.org/10.3390/cimb47050360 - 14 May 2025

Viewed by 209

Abstract

TGF-β is a multifunctional pathway that controls significant cellular and physiological processes and several pathological activities. TGF-β-induced signaling can be triggered upon binding to specific receptors to initiate the transcriptional activation of several genes and cellular processes. However, the detailed role of TGF-β [...] Read more.

TGF-β is a multifunctional pathway that controls significant cellular and physiological processes and several pathological activities. TGF-β-induced signaling can be triggered upon binding to specific receptors to initiate the transcriptional activation of several genes and cellular processes. However, the detailed role of TGF-β signaling in osteoblast differentiation remains to be explicated. SB525334, a selective TGF-βRI inhibitor, was investigated for its effect on the osteoblastic differentiation of human bone marrow MSCs at different concentrations. Alkaline phosphatase (ALP) activity was used to assess osteoblast differentiation marker, while Alizarin red staining was used as a marker for mineralization. Expressions of osteoblast-specific genes were evaluated using real-time PCR. A migration assay was performed to assess the effect of TGF-β on wound healing. Moreover, immunofluorescent staining for SMAD2/3 and SMAD4 was employed to confirm the activation of the TGF-β pathway. The inhibition of TGF-β1 signaling using a high concentration of SB525334 (3 µM) significantly reduced ALP activity and mineralization and downregulated osteoblast-specific genes. However, the opposite effect was reported using a lower concentration (0.03 µM), where osteoblast-associated genes were significantly upregulated, and ALP activity and mineralization were higher. Significant scratch/wound healing was achieved at a lower concentration of SB525334, while a higher concentration of SB525334 resulted in lower healing. Moreover, a low concentration of SB525334 demonstrated nuclear translocation of SMAD 2/3 and 4. Our study confirms that the effect of TGF-β signaling in bone formation and wound healing is dose-dependent, and the use of TGF-β is recommended as a valuable therapeutic approach. Full article

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

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19 pages, 2190 KiB

Open AccessArticle

Evaluation of the Expression of IDO and PTEN in Human Kidney Cancer

by Gábor Kónya, Zsuzsanna Szabó, Nikoletta Dobos, József Király, Krisztián Szegedi, Anna Vass, Ákos Steli, Csaba Szász, Balázs Dezső, Barbara Zsebik and Gábor Halmos

Curr. Issues Mol. Biol. 2025, 47(5), 359; https://doi.org/10.3390/cimb47050359 - 13 May 2025

Viewed by 285

Abstract

Immunotherapy has become one of the primary forms of cancer treatment. The inhibition of immune checkpoint molecules, including indoleamine 2,3-dioxygenase (IDO), is a promising approach for immunotherapy. Phosphatase and tensin homolog (PTEN) is well known as a tumor suppressor that antagonizes oncogenic signaling [...] Read more.

Immunotherapy has become one of the primary forms of cancer treatment. The inhibition of immune checkpoint molecules, including indoleamine 2,3-dioxygenase (IDO), is a promising approach for immunotherapy. Phosphatase and tensin homolog (PTEN) is well known as a tumor suppressor that antagonizes oncogenic signaling molecules/pathways and plays a key role in the prognosis and (immuno)therapy of the disease. In this study, twenty healthy and tumorous renal tissue pairs were investigated, and the mRNA (RT-qPCR) and protein (Western blot) expression of IDO and PTEN were analyzed. In two cancer cell lines (CAKI-2; A-498), the protein of IDO and PTEN was measured followed by IDO induction with interferon alpha-2 (IFN-α2). According to our results, a significantly higher mRNA expression of IDO and PTEN was found in tumorous tissues compared to the adjacent healthy kidney specimens. The mRNA expression of IDO and PTEN showed a positive correlation in 80% of the sample pairs. Western blot results confirmed the protein expression of both IDO and PTEN. In the cell lines, immunocytochemistry showed that IDO is inducible with IFN-α2. In summary, our results suggest that IDO expression may play a role in the development of renal cancer, and IDO as well as PTEN might be potential biomarkers for patients with RCC. Full article

(This article belongs to the Special Issue The Significance of Transcription Factors, miRNAs, and lncRNAs in Anticancer Drug Development, 2nd Edition)

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21 pages, 6696 KiB

Open AccessArticle

Ethanol Extract of Adlay Hulls Suppresses Acute Myeloid Leukemia Cell Proliferation via PI3K/Akt Pathway Inhibition

by Guangjie Li, Wenyuan Yang, Jiahui Xu, Ziqian Liu, Zhijian Li, Xiaoqiu Wu, Tongtong Li, Ruoxian Wang, Yamin Zhu and Ning Liu

Curr. Issues Mol. Biol. 2025, 47(5), 358; https://doi.org/10.3390/cimb47050358 - 13 May 2025

Viewed by 220

Abstract

Acute myeloid leukemia (AML) is a common hematologic malignancy in the elderly with frequent relapse and poor prognosis. Limited treatments highlight the need for novel natural anticancer compounds. Adlay, valued for its medicinal and dietary properties, exhibits anti-inflammatory and anticancer effects. However, research [...] Read more.

Acute myeloid leukemia (AML) is a common hematologic malignancy in the elderly with frequent relapse and poor prognosis. Limited treatments highlight the need for novel natural anticancer compounds. Adlay, valued for its medicinal and dietary properties, exhibits anti-inflammatory and anticancer effects. However, research on adlay hulls, particularly their anti-AML bioactive molecules, remains insufficient. This study evaluated the effects of adlay hull ethanol extract (AHE) on AML cell proliferation and apoptosis. AHE was extracted with ethanol and fractionated using n-hexane, ethyl acetate, and n-butanol, followed by silica gel chromatography. Cytotoxicity was assessed via the CCK-8 assay, and mechanisms were analyzed by flow cytometry and Western blotting. The bioactive components were characterized by UPLC-IMS-QTOF-MS. AHE-EA-C (ethyl acetate fraction C) inhibited AML cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis. It suppressed the PI3K/Akt pathway by reducing PI3K and Akt phosphorylation. Using UPLC-IMS-QTOF-MS analysis, a total of 52 compounds with potential anti-AML activity were identified in AHE-EA-C, among which neohesperidin and cycloartanol have been previously reported to exhibit anti-AML activity and thus hold promise as candidates for further development as AML inhibitors. This study is the first to identify adlay hull bioactive components and their anti-AML mechanisms via PI3K/Akt pathway inhibition, providing a foundation for developing natural anti-AML therapies. Full article

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

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15 pages, 542 KiB

Open AccessReview

The Mechanisms of Chronic Inflammation in Obesity and Potential Therapeutic Strategies: A Narrative Review

by Elvira Meni Maria Gkrinia and Andrej Belančić

Curr. Issues Mol. Biol. 2025, 47(5), 357; https://doi.org/10.3390/cimb47050357 - 13 May 2025

Viewed by 445

Abstract

Obesity, a global health concern of increasing significance, is characterized by chronic low-grade inflammation (LGCI) that significantly contributes to metabolic dysfunction. This narrative review explores the intricate pathophysiological mechanisms driving LGCI in obesity, emphasizing the role of adipose tissue, immune cell activation, and [...] Read more.

Obesity, a global health concern of increasing significance, is characterized by chronic low-grade inflammation (LGCI) that significantly contributes to metabolic dysfunction. This narrative review explores the intricate pathophysiological mechanisms driving LGCI in obesity, emphasizing the role of adipose tissue, immune cell activation, and inflammatory signaling pathways. Hypertrophic adipocytes and infiltrating immune cells, particularly macrophages, release a cascade of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, creating a self-perpetuating cycle of inflammation. These mediators disrupt insulin signaling through JNK and NF-κB pathway activation, leading to systemic insulin resistance, cardiovascular complications, gut dysbiosis and other metabolic disorders. The review further discusses therapeutic strategies to mitigate obesity-related LGCI, focusing on lifestyle interventions, nutritional approaches, and pharmacological agents. Physical activity, specific nutrients, and dietary patterns can modulate inflammatory responses, while anti-obesogenic medicines and bariatric procedures offer additional avenues for intervention. By understanding and addressing the root causes of inflammation in obesity, healthcare professionals can develop targeted strategies to improve metabolic health and overall well-being of individuals with obesity and, ultimately, prevent and manage the wide-ranging complications associated with this condition. Full article

(This article belongs to the Special Issue Molecular Insights into Multifactorial Causes of Insulin Resistance in Obesity)

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13 pages, 3171 KiB

Open AccessArticle

K-Homology Splicing Regulatory Protein (KSRP) Augments Survival and Proliferation of Human Melanoma Cells

by Harunur Rashid, Mohammad Asif Sherwani, Jung Vin Seo, Azeem Ahmad, Sumaiya Tasnim, Quamarul Hassan and Nabiha Yusuf

Curr. Issues Mol. Biol. 2025, 47(5), 356; https://doi.org/10.3390/cimb47050356 - 13 May 2025

Viewed by 190

Abstract

Melanoma is one of the most aggressive and fatal cancers; however, effective and long-lasting treatment options for melanoma continue to be sought after due to the development of resistance mechanisms to the currently available therapies. Background: The K-homology-type splicing regulatory protein (KSRP) is [...] Read more.

Melanoma is one of the most aggressive and fatal cancers; however, effective and long-lasting treatment options for melanoma continue to be sought after due to the development of resistance mechanisms to the currently available therapies. Background: The K-homology-type splicing regulatory protein (KSRP) is an RNA-binding regulatory protein that binds to the AU-rich elements at the 3′-UTR of target mRNAs. Prior studies have demonstrated that KSRP plays a crucial role in the post-transcriptional regulation of gene expression in human melanoma. Subsequently, in this study, we further examined the role of KSRP in cell migration, colony formation, apoptosis, and tumorigenicity of human melanoma. Methods: KSRP was knocked down in two different human melanoma cell lines: A375 and SK-MEL-28, using lenti-shRNA techniques. By doing so, we studied the effects of KSRP inhibition on cell migration, colony formation, proliferation, apoptosis, and tumorigenicity in these melanoma cell lines. Results: We observed a significant decrease in cell migration, colony formation, proliferation, and tumorigenicity, while also observing a substantial increase in apoptosis in the KSRP knock down melanoma cell lines. Conclusions: Our data establishes that KSRP plays a vital role in cell migration, colony formation, proliferation, apoptosis, and tumorigenicity in both the A375 and SK-MEL-28 human melanoma cell lines. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy, 3rd Edition)

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7 pages, 861 KiB

Open AccessCommunication

Construction and Evaluation of a HCoV-OC43 S2 Subunit Vaccine Fused with Nasal Immuno-Inducible Sequence Against Coronavirus Infection

by Hiraku Sasaki, Hiroki Ishikawa, Ayako Shigenaga, Yoshio Suzuki and Masayuki Iyoda

Curr. Issues Mol. Biol. 2025, 47(5), 355; https://doi.org/10.3390/cimb47050355 - 13 May 2025

Viewed by 174

Abstract

A partial sequence of an human coronavirus (HCoV)-OC43 S2 subunit that cross-reacts with the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was fused with a nasal immuno-inducible sequence (NAIS), and the resulting complex was used for intranasal immunization of rabbits. [...] Read more.

A partial sequence of an human coronavirus (HCoV)-OC43 S2 subunit that cross-reacts with the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was fused with a nasal immuno-inducible sequence (NAIS), and the resulting complex was used for intranasal immunization of rabbits. Crude serum from rabbits immunized with three doses showed an IgG titer > 1000 against the S2 subunits of HCoV-OC43 and SARS-CoV-2 and inhibited OC43 viral replication as a neutralizing antibody in vitro. Full article

(This article belongs to the Special Issue Recombinant Proteins for Molecular Biology Research: Technologies and Applications)

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22 pages, 5867 KiB

Open AccessArticle

Effect of 14-Week Supplementation of Highly Purified Policosanol (Raydel^®) and a Sugar Cane Extract Powder (SCEP) on Dyslipidemia and Oxidative Variables in Hyperlipidemic Zebrafish: Insight into Liver, Kidney, and Brain Health

by Kyung-Hyun Cho, Ashutosh Bahuguna, Sang Hyuk Lee, Ji-Eun Kim, Yunki Lee and Cheolmin Jeon

Curr. Issues Mol. Biol. 2025, 47(5), 354; https://doi.org/10.3390/cimb47050354 - 13 May 2025

Viewed by 295

Abstract

The efficacy of Cuban sugarcane-extracted policosanol (Raydel^®), a purified blend of eight long-chain aliphatic alcohols, was compared to copycat sugarcane-extract powder (SCEP) to assess their effects on dyslipidemia, oxidative stress, and vital organs of zebrafish under the influence of a high-cholesterol [...] Read more.

The efficacy of Cuban sugarcane-extracted policosanol (Raydel^®), a purified blend of eight long-chain aliphatic alcohols, was compared to copycat sugarcane-extract powder (SCEP) to assess their effects on dyslipidemia, oxidative stress, and vital organs of zebrafish under the influence of a high-cholesterol diet (HCD). Zebrafish were fed with HCD (final 4%, w/w) or HCD infused with policosanol (PCO, final 1%, w/w) or SCEP (final 1%, w/w). Post 14-week consumption, blood and organs were harvested and processed for various biochemical, histological, and immunohistochemical (IHC) examinations, and fluorescent staining. Following 14-week consumption, the PCO-supplemented group exhibited higher zebrafish survival probability than the SCEP-supplemented group. Both PCO and SCEP substantially impacted the HCD-disrupted plasma lipid profile; however, PCO supplementation exhibited a significantly better effect than SCEP. Similarly, PCO supplementation significantly improved the blood glucose level, hepatic function biomarkers, and oxidative-antioxidant balance disturbed by HCD. PCO supplementation displayed a substantial inhibitory effect against HCD-induced fatty liver changes, nephromegaly, and cellular senescence. Likewise, PCO effectively protected the brain against HCD-induced apoptosis and accumulation of 4-hydroxynonenal (4-HNE); in contrast, SCEP supplementation showed almost no effect in reducing such adverse changes. The comparative findings between PCO and SCEP highlight the protective effects of PCO against HCD-induced oxidative stress and dyslipidemia via the enhancement of antioxidant markers, leading to protection of the liver, kidney, and brain, while SCEP failed to achieve similar outcomes. Full article

(This article belongs to the Section Molecular Pharmacology)

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