Journal of cellular biochemistry最新文献

Supervillin (SVIL), the biggest member of the villin/gelsolin superfamily, has recently been reported to promote the metastasis of hepatocellular carcinoma by stimulating epithelial-mesenchymal transition (EMT). However, little is known about the roles of SVIL in the migration of colorectal cancer cells. Here, we investigated the effects of SVIL on the migration of cisplatin-resistant colorectal cancer cells. The model of cisplatin-resistant HCT116 cells (HCT116/DDP) was established. Migration was assessed after SVIL knockdown. Tumor metastasis was assessed using a mouse model with tail vein injection of colorectal cancer cells. The results showed that the expression of SVIL was upregulated in HCT116/DDP cells compared to that in their parental cells. Also, the HCT116/DDP cells showed increased cell migration and lung metastasis. Furthermore, we revealed that the expression of SVIL was associated with the migration of HCT116/DDP cells. Reduced SVIL expression inhibited migration and lung metastasis in HCT116/DDP cells. Further work showed that SVIL knockdown blocked cell migration by targeting zona occludens-1 (ZO-1) mediated tight-junction remodeling. The expression of ZO-1, but not occludin and cludin5, was downregulated after SVIL knockdown. Immunofluorescence indicated that the linear ZO-1 was interrupted while the SVIL knockdown reversed the interruption. This study displayed the relationship between SVIL and ZO-1 in cisplatin-resistant colon cancer cells, providing a new insight into the mechanism of colorectal cancer migration.

Cellular prion protein (PRNP) has been implicated in various physiological processes in different cell types, for decades. Little has been known how PRNP functions in multiple, yet related processes within a particular system. In our current study, with the aid of high-throughput RNA-sequencing technique, we have presented an overall transcriptome profile of rat vascular smooth muscle cells (VSMCs) with Prnp knockdown. Fifty-one genes were found to be differentially regulated, of which, genes involved in cell proliferation and endoplasmic reticulum (ER) stress pathway, show significant upregulation. That PRNP negatively regulates VSMC proliferation, has been demonstrated using immunoblot assays, BrdU incorporation assay and Ki-67 immunofluorescence staining. As revealed from our RNA-Seq data, ATF4, a downstream effector of the PERK arm of ER stress pathway is upregulated upon RNA interference of Prnp in VSMCs. As a result, the expression of the functional phosphorylated isoform of translation initiation factor eIF2α (p-eIF2α) is elevated. Additionally, we also showed that downregulation of Prnp leads to excess intracellular ROS accumulation, subsequently leading to splicing of Xbp1 mRNA and triggering unfolded protein response (UPR) within the cell. Therefore, our findings highlight that PRNP directly or indirectly modulates an array of biological processes and plays a pivotal role in preserving the equilibrium between excess proliferation and optimal endoplasmic reticulum function, in VSMCs.

MicroRNAs (miRNAs) have emerged as intricate players in rheumatoid arthritis (RA), holding promise as discerning biomarkers for diagnostic and prognostic purposes. The lack of sensitivity and specificity in current diagnostic techniques, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), causes diagnosis delays in RA. The miR-146a and miR-155 act in inflammatory cascades and reduce joint deterioration, and miR-223 is paradoxical, acting differently in different illness scenarios. The microenvironment of RA is shaped by the complex modulation of gene expression and cytokine dynamics by miR-126 and miR-24. miRNAs serve as a promising candidate for precision medicine in the management of RA. There are obstacles encountered in validation, delivery optimization, and off-target effect mitigation before miRNA-based biomarkers may be applied in clinical settings. Machine learning (ML) and artificial intelligence (AI) have been used to integrate miRNA expression patterns with clinical data to greatly advance the treatment of RA. Because of the disease's inherent complexity and variability, these state-of-the-art models provide accurate predictions regarding the onset, development, and response to treatment of RA. By using clinical information and miRNA expression data, ML algorithms are revolutionizing the treatment of RA by predicting the onset and course of the disease with remarkably high accuracy. The development of therapeutic modalities and miRNA profiling has great potential to transform the diagnosis, prognosis, and treatment of RA, providing fresh hope for better patient outcomes.

Breast cancer ranks among the most prevalent cancers. Enhancing the effectiveness of chemotherapy and patient survival is the objective of many studies. In the literature, no study has investigated the combined effect of vitamin c and curcumin with chemotherapy drugs on cell viability in the MCF-7 cell line, nor the mechanism of inflammation induced by cancer drugs, both in vitro and in silico. Thus, the purpose of this study was to assess the synergistic effect of curcumin and vitamin c in combination with the chemotherapy drugs 5-fluorouracil and doxorubicin. The cytokine hub genes of the Toll-like receptor pathway for the administered drugs were identified using the Cytoscape program, and docking studies were conducted via the Cb Dock2 website. In silico analyses indicated that doxorubicin and curcumin displayed comparable characteristics, achieving the highest interaction scores (-10) with marker proteins, whereas 5-fluorouracil and vitamin c showed lower interaction scores. Cell viability was evaluated through MTT analysis and AO/PI staining, while the expression of inflammation-related markers IL-6, IL-10, and TNF-α proteins determined using the ELISA method. After 24 h, the cell viability of the chemotherapeutic drugs administered in combination with curcumin decreased by up to 28%. Subsequently, applications at 48 and 72 h were performed. These results indicate that the effect of curcumin on cell viability is significant when combined with chemotherapy drugs. In the ELISA test, a 52% expression of IL-6 was noted in MCF-7 cells treated with curcumin, whereas the IL-6 level decreased to 15% in the other experimental groups. An increase was observed in the TNF-α expression with 5-fluorouracil and doxorubicin compared to the control, while a notable decrease was recorded in the applications with vitamin c and curcumin (p < 0.05). This study demonstrates that vitamin c and curcumin exhibit a synergistic effect with chemotherapeutic agents in the inflammatory system.

Acute pancreatitis (AP) is a common emergency in the digestive system, and in severe cases, it can progress to severe acute pancreatitis (SAP), with a mortality rate of up to 30%, representing a dire situation. SAP in mice was induced by l-arginine (l-Arg). HE, IHC, WB and ELISA were used to study the role and regulation of HIF1A in SAP. At the same time, QPCR, WB, CHIP-QPCR and luciferase report were used to explore the specific mechanism of HIF1A regulation of SAP in vitro. The research results indicate that following SAP induction, the pancreatic tissue of mice exhibited significant glycolytic abnormalities, accompanied by a marked upregulation of HIF1A expression. This led to apparent damage in the pancreatic tissue, lungs, and kidneys. However, in sh-HIF1A mice, the degree of these injuries was significantly alleviated, along with a reduction in the production of inflammatory factors, oxidative products, and lipid peroxidation markers. This suggests that HIF1A plays a crucial role in the inflammatory and oxidative stress processes during SAP. Further exploration revealed that the absence or overexpression of HIF1A affects SAP by inducing ferroptosis through the ACSL4/LPCAT3/ALOX15 pathway. Notably, the elevated lactate level resulting from glycolytic abnormalities further enhances the histone lactylation in the HIF1A promoter region, thereby aggravating the expression of HIF1A. Lactate-dependent HIF1A transcriptional activation exacerbates severe acute pancreatitis through the ACSL4/LPCAT3/ALOX15 pathway induced ferroptosis.