Journal of cellular biochemistry最新文献

The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.

Bronchopulmonary dysplasia (BPD) affects patients' quality of life. Circular RNAs participated in BPD. However, circ-ECH1's role in BPD has not been reported yet. This study aimed to explore the role and mechanism of circ-ECH1 in BPD. Hyperoxia-treated type II alveolar epithelial cells (L2 cells) were used as the in vitro BPD model. CCK-8, flow cytometry, and reactive oxygen species (ROS) were used to evaluate cell viability. Fluorescence in situ hybridization confirmed the subcellular localization. Circ-ECH1 overexpression (or inhibited) and miR-708-5p mimics were used to investigate the roles of circ-ECH1 and miR-708-5p in BPD. Quantitative reverse-transcription polymerase reaction (qRT-PCR) detected the expressions of circ-ECH1, miR-708-5p, and neurotrophic receptor tyrosine kinase 2 (Ntrk2). Ntrk2 expression was evaluated by Western blot analysis. Changes in lung tissues were evaluated by hematoxylin and eosin staining. Pulmonary fibrosis was examined by Mason staining. TUNEL staining was performed to evaluate cell apoptosis in lung tissues. RNA sequencing was performed in the lung tissues of BPD rats. The binding between circ-ECH1 and miR-708-5p was confirmed through dual luciferase activity. Hyperoxia reduced cell viability and increased cell apoptosis and ROS accumulation. In addition, hyperoxia decreased the expression levels of circ-ECH1, which is mainly located in the cytoplasm. Circ-ECH1 overexpression increased cell viability but reduced cell apoptosis and ROS accumulation. On the contrary, interference with circ-ECH1 further promoted cell apoptosis and reduced cell activity. Furthermore, circ-ECH1 overexpression reduced the incidence of pulmonary fibrosis and lung cell apoptosis. RNA sequencing, followed by qRT-PCR, confirmed that the expressions of Ntrk2 and miR-708-5p were affected by circ-ECH1. miR-708-5p mimics reversed the role of circ-ECH1 in the BPD. Mechanistically, circ-ECH1 may bind with miR-708-5p to regulate Ntrk2 expression. Circ-ECH1 may compet with miR-708-5p to regulate Ntrk2 expression in BPD. The findings provided a new target for BPD treatment.

The expression of claudins (CLDNs), major components of tight junctions (TJs), is abnormal in various solid tumors. CLDN14 is highly expressed in human colorectal cancer (CRC) tissues and confers chemoresistance. CLDN14 may become a novel therapeutic target for CRC, but CLDN14-targeting drugs have not been developed. Here, we searched for a CLDN14-targeting peptide, which can suppress CLDN14 expression and chemoresistance using human CRC-derived DLD-1 and LoVo cells. Among some short peptides which mimic the second extracellular loop structure of CLDN14, PSGMK most strongly suppressed the protein expression of CLDN14. The mRNA expression of other endogenous TJ components was unchanged by PSGMK. The PSGMK-induced reduction of CLDN14 protein was inhibited by chloroquine, a lysosome inhibitor, and monodansylcadaverine, a clathrin-dependent endocytosis inhibitor, indicating that PSGMK may enhance endocytosis and lysosomal degradation of CLDN14. In a three-dimensional culture model, the oxidative stress was significantly reduced by PSGMK, whereas hypoxia stress was not. Furthermore, the expression levels of nuclear factor erythroid 2-related factor 2, an oxidative stress response factor, and its target genes were decreased by PSGMK. These results suggest that PSGMK relieves stress conditions in spheroids. The cell viability of spheroids was decreased by anticancer drugs such as doxorubicin and oxaliplatin, which was exaggerated by the cotreatment with PSGMK. Our data indicate that CLDN14-targeting peptide, PSGMK has an anti-chemoresistance effect in CRC cells.

Multidrug-resistant (MDR) cancer cells maintain redox homeostasis to eliminate oxidative stress-mediated cell death. This study explores the effects of solasodine on regulating P-glycoprotein (P-gp) expression through the Nrf2/Keap1 signaling pathway and oxidative stress-induced sensitization of drug-resistant cancer cells to chemotherapeutics. Initially, the oxidative stress indicators such as intracellular ROS generation, the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and gamma-H2AX (γ-H2AX) in the KBChR-8-5 drug-resistant cells were measured. Additionally, the protein expression levels of Nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap1), and ATP Binding Cassette Subfamily B Member 1 (ABCB1)/P-gp were measured at various concentrations of solasodine (1, 5, & 10 µM) through immunofluorescence and western blot analysis. The antioxidant activities in the KBChR-8-5 cells were assessed using established protocols. In this investigation, the treatment with solasodine and doxorubicin combination showed a notable increase in intracellular ROS generation in KBChR-8-5 cells. Furthermore, this combination treatment led to enhanced nuclear condensation, elevated levels of 8-OHdG, and increased γ-H2AX foci formation in the KBChR-8-5 cells. Solasodine treatment effectively inhibited the nuclear translocation of Nrf2 and activation of the ABCB1 gene, consequently preventing overexpression of P-gp in KBChR-8-5 cells. Additionally, the combination therapy increased the lipid peroxidation levels while simultaneously reducing the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of glutathione (GSH). These results demonstrated that solasodine disrupts redox balance, and overcomes drug resistance by downregulating P-gp via regulating Nrf2/Keap1 signaling pathway in MDR cancer cells.

Streptococcus pneumonia is a Gram-positive and facultative anaerobic bacterium that causes a number of diseases, including otitis media, community-acquired pneumonia, sepsis, and meningitis. With the emergence of antibiotic-resistant strains, there is an urgent need to develop antibiotics with a novel mechanism. The toxin–antitoxin (TA) system, which is primarily found in prokaryotes, consists of a toxin and its equivalent antitoxin genes. The YefM–YoeB module is a Type II TA system, where the YoeB toxin functions as a putative mRNA interferase upon activation, while the YefM antitoxin acts as a transcription repressor by binding to its promoter region along with YoeB. In this study, we determined the crystal structure of the YefM–YoeB complex from S. pneumoniae TIGR4 to comprehend the binding mechanism of the TA system. Furthermore, an in vitro ribonuclease activity assay was conducted to identify the ribonuclease activity of the YoeB toxin. Additionally, furthermore, the oligomeric state of the YefM–YoeB complex in solution was investigated, and a DNA-binding mode was proposed. These structural and functional insights into the YefM–YoeB complex could provide valuable information for the development of novel antibiotics targeting S. pneumonia-associated diseases.

Chrysosplenetin (CHR), an O-methylated flavonol from Chamomilla recutita and Laggera pterodonta, has previously demonstrated efficacy in enhancing osteoblast differentiation for treating postmenopausal osteoporosis. This study aims to evaluate CHR's potential to inhibit osteoclastogenesis and prevent bone deterioration in both in vitro and in vivo models. Using tartaric acid-resistant acid phosphatase staining and hydroxyapatite resorption assays, we examined the impact of CHR on RANKL-induced osteoclasts derived from mouse bone marrow monocytes. Additionally, Western blot analysis and qRT-PCR were utilized to assess the protein and gene expressions within the MAPK and NF-κB signaling pathways, as well as the NFATc1 pathway. In vivo, CHR's effects were validated using micro-CT and histomorphometry in an ovariectomized mouse model, showing significant reduction in osteoclast activity and bone loss. The study confirms CHR's inhibition of osteoclastogenesis through interference with RANKL-mediated signaling pathways, suggesting its potential as a novel therapeutic agent for osteolytic conditions related to osteoclast-osteoblast dysregulation.