Current Issues in Molecular Biology最新文献

While there have been reports indicating the potential anticancer benefits of blue light irradiation and its enhanced effectiveness when combined with anticancer drugs, no studies have explored its combined use with radiation therapy. In this study, the anticancer effects of blue light irradiation alone and in combination with radiation therapy were investigated in vitro. Blue light was applied using a transilluminator (470 nm). For combination experiments, cells were exposed to X-rays 24 h after blue light irradiation. Cell viability was assessed using the trypan blue exclusion method, and protein expression was analyzed by Western blotting. Blue light irradiation suppressed the proliferation of human head and neck squamous cell carcinoma (HNSCC) cells. Furthermore, combined blue light and X-ray irradiation more effectively inhibited the proliferation of human HNSCC cells compared to either irradiation alone. Mechanistically, the irradiation of HNSCC cell line SAS with blue light suppressed the activity of extracellular signal-regulated kinase (ERK1/2), which is an important kinase that is involved in cell proliferation. Collectively, these findings suggest that blue light suppresses the proliferation of HNSCC cells, at least in part through ERK1/2 inactivation observed in SAS cells, and that its combination with radiation may represent a promising therapeutic approach.

Molecular pharmacology sits at the nexus of fundamental molecular science and therapeutic innovation [...].

Dynamic environmental changes significantly affect trace element balance and exposure to toxic metals, influencing vascular homeostasis. The endothelium, as a key regulator of vascular tone and inflammation, is highly sensitive to fluctuations in micronutrient and heavy metal concentrations. This review summarizes current evidence on the molecular mechanisms by which essential trace elements, such as zinc, selenium, copper, and magnesium, support endothelial function through antioxidant defense, nitric oxide regulation, and anti-inflammatory signaling. Conversely, exposure to heavy metals including cadmium, lead, mercury, and arsenic induces oxidative stress, disrupts nitric oxide bioavailability, and promotes endothelial dysfunction, accelerating the pathogenesis of many diseases. The paper examines how these alterations contribute to the development of major cardiovascular diseases and outlines preventive measures to reduce associated risks. Understanding these interactions is crucial for society's health amid growing environmental challenges.

The excessively concentrated ripening period of mulberries causes seasonal surplus. Fruit mulberry (Morus spp.) exhibits the unique trait of "simultaneous flowering and leaf flushing", rendering budburst timing closely correlated with fruit ripening time. Thus, deciphering the molecular mechanism underlying winter bud dormancy maintenance in fruit mulberry is urgently needed. Herein, an F₁ hybrid population comprising 337 individuals, derived from Morus wittiorum (♀) and '322' (♂), was utilized as research material. Through Bulked Segregant Analysis Sequencing (BSA-Seq), we successfully mapped a dormancy-associated QTL interval designated as LB (Late Burst), spanning 9,990,001-11,990,000 bp on Chromosome 13. Integrating Weighted Gene Co-expression Network Analysis (WGCNA) results, MaSVP was identified as a candidate gene within this interval. Virus-induced gene silencing (VIGS) of MaSVP in winter buds of Morus wittiorum significantly accelerated budburst compared to the control, demonstrating that MaSVP represses winter bud dormancy release and plays a crucial role in regulating dormancy maintenance in fruit mulberry. Dynamic expression profiling of dormancy-related genes revealed that the transcript levels of MaSVP, MaSAPK3, MaCASL2, and MaPYR8 were significantly downregulated (Tukey's test, p < 0.05) as budburst approached, whereas those of MaFT and MaGA20ox1-D were significantly upregulated (Tukey's test, p < 0.05). These results indicate that winter bud dormancy maintenance in Morus wittiorum is associated with abscisic acid (ABA) and gibberellin (GA) metabolism. Collectively, this study provides critical insights into the biological basis of winter bud dormancy maintenance in fruit mulberry and offers valuable genetic resources for breeding late-maturing cultivars.

Mucopolysaccharidosis (MPS IVA) is caused by pathogenic variations in the GALNS gene, leading to the accumulation of glycosaminoglycans in tissues and causing progressive skeletal lesions. While conventional lentiviral vectors (LVs) provide long-term stable expression, they do not deliver therapeutic levels to bone and cartilage. We hypothesized that engineering the LV envelope with a collagen type II-targeting peptide (WYRGRL) increases the binding affinity of the LVs for bone and cartilage. These modified vectors carrying the CBh and COL2A1 promoters delivered the GALNS gene to MPS IVA newborn mice via intravenous (IV) or intraarticular (IA) administration. The peptide-modified LVs exhibited markedly increased uptake in the liver when administered IV, but lower enzyme activity than that of the conventional vector. The modified WYRGRL-LV-COL2A1 vector elevated GALNS activity in other tissues, suggesting systemic benefits. When administered IA, the modified vectors showed potential for local treatment due to the WYRGRL peptide-mediated uptake. Additionally, there was a reduction in keratan sulfate glycosaminoglycan levels in plasma and tissues, indicating that this peptide can be a suitable candidate for disease modification. These findings pave the way for further preclinical and clinical studies, offering new possibilities for the development of targeted therapies for skeletal diseases.

The past three years (2023-2025) have witnessed substantial progress in molecular plant science, driven by technological innovations and deepened mechanistic insights [...].

Anthracycline's clinical application is often hampered by severe life-threatening cardiotoxicity, which could result in death in approximately one-third of patients. Previous studies have found that during the anthracycline-induced cardiotoxicity (AIC), uric acid (UA) levels increase abnormally. However, the role of UA in AIC remains elusive. Here, we conducted a correlation analysis between UA and cardiac damage markers (NT-pro-BNP, hs-cTnT, LDH, CRP and hs-CRP) by using the National Health and Nutrition Examination Survey database (NHANES); the results revealed that the elevated UA levels showed significant positive associations with the levels of several cardiac damage markers. Secondly, molecular docking experiments suggested potential binding interactions between UA and BNP, cTnT, CRP, and LDH. Finally, animal experiments were performed to validate this correlation we explored and further validated the effect of UA on AIC by adding or lowering UA in animal models. We observed that under high uric acid (HUA) conditions, AIC not only manifested earlier but also progressed more severely. In contrast, AIC was alleviated under UA clearance conditions. Collectively, these results suggested that HUA might be an important contributing factor in the development and progression of AIC, supporting the further investigation of UA-lowering strategies for potential prevention. This work might offer new prevention and treatment strategies for AIC.

Acne vulgaris is a prevalent chronic inflammatory skin disorder affecting over 85% of adolescents. Emerging evidence indicates that Cutibacterium acnes phylotype IA₁ contributes to acne initiation and progression, yet its precise mechanisms in epidermal keratinocytes remain unclear. This study investigated C. acnes IA1's effects on keratinocyte behavior using an in vitro HaCaT cell model. Cells were co-cultured with live C. acnes IA₁ (CICC 10864) for 24 h. Transcriptomic profiling identified 769 differentially expressed genes (DEGs; adjusted p < 0.05, |log2FC| > 1), including 392 upregulated and 377 downregulated. The protein-protein interaction network analysis via Cytoscape revealed key hub genes (HNRNPA2B1, HNRNPM, RBM39). Enrichment analyses (GO, KEGG, Reactome, DO) highlighted significant involvement of the C-type lectin receptor (CLR) signaling pathway. Validation experiments showed cellular morphological changes, altered structure, and markedly elevated interleukin-6 (IL-6; p < 0.01), underscoring its role in inflammation. These findings suggest C. acnes IA₁ drives acne pathogenesis by regulating hub genes that influence sebaceous gland inflammation, immune activity, and keratinocyte proliferation, positioning them as potential biomarkers for microbiome-targeted therapies. Limitations include the in vitro model's lack of in vivo skin microenvironment complexity and use of only one representative IA₁ strain.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with a poor prognosis. Sestrin2 (Sesn2), a stress-inducible protein, has been implicated in various cancers, but its precise role and mechanism in OSCC remain unclear. This study investigated the molecular mechanisms of Sesn2 in OSCC. Sesn2 expression was analyzed using data from TCGA and immunohistochemical results from the HPA. Functional assays, including CCK-8, flow cytometry for cell cycle, wound healing, and Transwell assays, were performed following Sesn2 knockdown with siRNA in OSCC cell lines (CAL-27 and SAS). Underlying mechanisms were investigated by Western blotting and ELISA for MMP-2 and MMP-9 levels. Sesn2 was significantly upregulated in OSCC tissues compared to normal controls. Its knockdown markedly suppressed cell proliferation, induced G1 phase cell cycle arrest, and impaired migratory and invasive capabilities. This reduction in invasion was further confirmed by decreased levels of MMP-2 and MMP-9 upon Sesn2 knockdown. Furthermore, Sesn2 silencing induced apoptosis via Caspase-3 activation with divergent BAX/BCL-2 modulation; SAS cells exhibited elevated BAX and reduced BCL-2, whereas these proteins remained unchanged in CAL-27 cells. Mechanistically, we found that Sesn2 depletion downregulated the PI3K/AKT/mTOR pathway and reduced the phosphorylation of AKT and p38 MAPK. Our findings demonstrate that Sesn2 functions as an oncogene in OSCC, promoting tumor progression by modulating the PI3K/AKT/mTOR and MAPK signaling pathways, suggesting its potential as a therapeutic target for OSCC.

Nobiletin, a citrus-derived polymethoxylated flavone, has been reported to exert anti-obesity effects, but its molecular mechanisms remain poorly understood. This study aimed to investigate whether nobiletin suppresses adipogenesis and promotes browning in 3T3-L1 adipocytes by modulating exosomal microRNAs (miRNAs) and AMPK signaling. To this end, we treated 3T3-L1 adipocytes with various concentrations of nobiletin and evaluated gene and protein expression by RT-qPCR and Western blotting. Nobiletin significantly reduced intracellular lipid accumulation at 50 μM (p < 0.001) and downregulated key adipogenic transcription factors, PPARγ, C/EBPα, and SREBP-1c, and suppressed the lipogenic enzyme FAS, while activating the AMPK/ACC signaling pathway. Concomitantly, it enhanced the expression of thermogenic markers UCP-1, PRDM16, and PGC-1α, indicating a metabolic shift toward energy expenditure. Exosomal RNA-seq revealed 10 differentially expressed miRNAs, of which miR-181d-5p (3.1-fold) and miR-221-3p (2.4-fold) were upregulated, whereas miR-205-5p (-2.9-fold), miR-331-3p (-3.2-fold), miR-130b-3p (-2.6-fold), miR-143-5p (-2.9-fold), miR-183-3p (-2.8-fold), miR-196b-5p (-2.4-fold), miR-26b-3p (-2.2-fold), and miR-378d (-2.7-fold) were verified by RT-qPCR after nobiletin treatment (50 μM). These miRNAs are functionally associated with adipogenic and thermogenic pathways, supporting a regulatory role of the exosomal miRNA network in nobiletin's action. Collectively, our results identify a novel exosome-miRNA-AMPK axis underlying the anti-adipogenic and browning-inducing activities of nobiletin, highlighting its potential as a therapeutic phytochemical for obesity prevention.