Journal of cellular biochemistry最新文献

Mesenchymal stem cells (MSCs) are adult stem cells with the capacity to differentiate into several cell types, including hepatocyte-like cells, neural-like cells, islet-like clusters and so on. However, the differentiation into ovarian-related cells such as ovarian granulosa cells (OGCs) has not been well studied. Here, we established an efficient culture system to differentiate human umbilical cord mesenchymal stem cells (HUCMSCs) into pre-granulosa cells, which can further mature into granulosa-like cells. HUCMSCs were cocultured with hormones (E2, FSH) and cytokines (TGF-β), a simple differentiation method was used to induce morphological changes and positive expression of forkhead transcription factor (FOXL2). In the process of further mature, the cells differentiated into mature granulosa-like cells, expressed mature granulosa cell markers (FSHR, AMHR2, CYP19A1) and likely possesses some granulosa cell hormone secretion capacity. In conclusion, we successfully established an efficient protocol to generate pre-granulosa cells from HUCMSCs that can further differentiate into mature granulosa-like cells, opening a new avenue for the further study of therapies for female reproductive health.

Heptamethine cyanine dyes and anticancer agents based conjugates are being developed for enhanced targeting and killing of cancer cells. DZ-1 dye conjugated agents induced cytotoxicity and mechanism of action have been shown in previous studies. In this study, a conjugated form of DZ-1 and artesunate (DZ-1-ART) was used to evaluate its cytotoxicity and elucidate the mechanism of actions in various cancer cell lines. Cells survival assays indicated dose-dependent cytotoxic activities of DZ-1-ART in HCT116, BxPC-3, and OVCAR-3 cell lines. Immunoblotting and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay confirmed involvement of apoptosis in DZ-1-ART-induced cytotoxicity. To elucidate the anticancer mechanism of the action of DZ-1-ART, MitoTracker and JC-1 assay were used. The results showed that translocation of DZ-1-ART in the mitochondria was followed by disruption of mitochondrial outer membrane potential. Dichlorofluorescin diacetate assay confirmed the generation of reactive oxygen species (ROS) in DZ-1-ART treated cancer cells. An antioxidant, N-acetyl cysteine treatment with DZ-1-ART showed reduction in cell death as well as suppression of ROS generation. When compared to HCT116 wild-type cells, Bak and Bax-deficient HCT116 cells also showed similar levels of cytotoxicity of DZ-1-ART. Taken together, this study's results reported that DZ-1-ART could induce mitochondria-mediated, ROS-generated, and Bak and Bax-independent apoptosis in cancer cells.

Survivors of COVID-19 are facing a new vulnerability of encountering post-COVID complications, including cardiovascular diseases (CVDs). Despite the increasing prevalence of CVDs, post-COVID-induced cardiac abnormalities significantly escalate mortality and morbidity. However, some recent studies have begun to elucidate complex pathological signaling pathways in these conditions, further investigation is required to distinguish key genetic and proteomic regulators in post-COVID states precisely. Gene Expression Omnibus (GEO) databases were used to investigate gene expression profiles in post-COVID-19 patients. The selected data set underwent normalization and PCA using prcomp and limma to visualize the correlation and patterns. Differentially expressed genes (DEGs) were identified to evaluate their role in molecular functions, and biological processes by Gene Ontology and KEGG analysis. Moreover, transcriptional regulators of selected DEGs were identified using the TRUST database. The comprehensive consequences from post-COVID patients revealed unique DEGs (five downregulated and two upregulated). Transcriptional factors (TFs) like ATRX, GATA1, and KLF4 have been identified as key regulators of HBA2 gene expression, which could encode crucial components of adult hemoglobin and cardiac functionality in post-COVID conditions. Moreover, immunoregulators NF-κB1 and SLA2 affect inflammatory cascades through the downregulation of the CD69 gene, which may be considered a promising pathway highlighting target sites for ameliorating CVDs in the post-COVID states. The present investigation revealed the promising TFs and DEGs, based on their persuasive biological function, that need to be validated for developing competent health interventions to mitigate the associated cardiac complications at the primary stage in post-COVID incidents.

HIV-1 protease is a key therapeutic target for antiretroviral drug development. In this study, a structure-based high-throughput virtual screening (HTVS) approach was employed to identify novel quinazoline-based inhibitors targeting the protease's catalytic site. A library of 5000 compounds from the PubChem database was screened, and CID-2135609 emerged as the top hit with the strongest binding affinity (–12.39 kcal/mol). In addition to its superior docking score, CID-2135609 exhibited favorable drug-like properties, including optimal molecular weight, high Caco-2 permeability, balanced lipophilicity, and acceptable blood-brain barrier penetration. Molecular docking revealed that CID-2135609 engages key catalytic residues (Asp25, Ile50, Gly49) through van der Waals and π-interactions, with additional contributions from Arg8, Asp30, and Ile47. Thermodynamic profiling indicated that binding is exothermic and entropically favorable, driven by hydrophobic contacts and water displacement, with a negative ΔG confirming spontaneous association. All-atom molecular dynamics simulations over 200 ns demonstrated that CID-2135609 maintains stable binding within the active site, preserving critical contacts while adapting its orientation to enhance fit. The protease structure remained conformationally stable, with minimal deviation in secondary structure or global compactness. Time-resolved interaction profiling revealed sustained and expanded interactions with residues including Pro81, Ile84, and Thr80. Comparative analysis with the apo form showed reduced solvent exposure and conformational flexibility upon ligand binding, as supported by SASA and PCA analyses. Free energy decomposition further validated complex stability. Overall, CID-2135609 is a promising candidate for HIV-1 protease inhibition and merits further experimental validation.

Osteoporosis (OP) is a major health problem among the elderly. It involves a loss of bone mass and deterioration of the structure of bone. Age, genetic factors, and hormonal changes are all contributing causes that increase the tendency to skeletal imbalance between osteoblast and osteoclast activity. Prolonged use and side effects are the problems with current medication therapies. As a result, nonpharmacological interventions especially those using natural products are attracting more attention due to their distinct structures, less toxicity, and side effects. Autophagy plays a role in maintaining cellular balance and is engaged in both normal and abnormal physiological processes. The development of OP is also characterized by the disruption of autophagy in osteoblasts and osteoclasts. This comprehensive review examines natural products that regulate autophagy and their consequent impacts on bone cells. These compounds may prove useful in strengthening osteoblastic differentiation, stimulating bone formation and inhibiting osteoclastic resorption. Uncovering the complex relationship between autophagy and OP may open up new avenues of treatment. Also, it can teach us how to design personalized medical interventions for those patients at greatest risk. The autophagy pathway is a recently discovered target for natural products in the prevention and treatment of OP. However, more research is needed to explore the action mechanisms, good clinical effects and possible adverse reactions of these compounds so as to find novel and safer treatment for the common bone disease OP.

Mitophagy, a selective autophagic process, is critical for maintaining mitochondrial quality and cellular homeostasis. It plays a dual role, facilitating cell survival by removing damaged mitochondria or contributing to programmed cell death in certain conditions. Dysregulation of mitophagy is implicated in various diseases, including neurodegenerative disorders, metabolic syndromes, cardiovascular diseases, and cancers. This review examines the key regulatory mechanisms of mitophagy, focusing on pathways such as the PINK1-Parkin, BNIP3/NIX, and FUNDC1 pathways, alongside emerging modulators. Notably, mitophagy is frequently associated with various cell death pathways, such as apoptosis, necroptosis, ferroptosis, and pyroptosis. Primarily, mitophagy functions as a protective mechanism rather than a direct trigger of cell death. It may be connected to cell death when its capacity is overwhelmed rather than actively promoting the process. For instance, impaired mitophagy exacerbates neurodegeneration in Parkinson's and Alzheimer's diseases, while its activation protects against ischemic injury in cardiovascular diseases. In cancer, mitophagy is paradoxical, as it either inhibits tumor growth or promotes survival under stress. Therapeutic interventions targeting mitophagy, including small-molecule modulators, show promise in preclinical studies; however, they require further clinical validation. Advancements in imaging techniques, single-cell omics, and high-throughput screenings are anticipated to deepen our understanding of mitophagy dynamics and therapeutic potential. This review highlights mitophagy as a pivotal target for treating diseases associated with mitochondrial dysfunction, providing insights into innovative therapeutic strategies.