Journal of Biochemical and Molecular Toxicology最新文献

Postoperative cognitive dysfunction (POCD) is a common neurological complication after surgery and general anesthesia, and the incidence increases with age. Will have a negative impact on patients, family and society. At present, neuroinflammation and oxidative stress are the main recognized mechanisms. Glutathione (GSH) is a powerful reducing agent and may be related to POCD. Data Collection: Using medical search engines such as PubMed, Web of Science, we analyzed articles on topics such as: POCD, GSH, microglia, astrocyte, oligodendrocyte, ferroptosis, BDNF, Neuroinflammation, oxidative stress. The above topics are searched in databases using Boolean operations. We included original articles, reviews and other article types such as medical books. Results: According to the reviewed literature, GSH may be a treatment for POCD. Conclusions: Specific and targeted therapies for POCD still sparse, therefore, the implementation of preventive strategies appears to remain the optimal attitude. Further research is needed for a better understanding of GSH and POCD.

Recently, many studies focused on the billions of native bacteria found inside and all over the human body, commonly known as the microbiota, and its interactions with the eukaryotic host. One of the niches for such microbiota is the gastrointestinal tract (GIT), which harbors hundreds to thousands of bacterial species commonly known as enteric bacteria. Changes in the enteric bacterial populations were linked to various pathologies such as irritable bowel syndrome and obesity. The gut microbiome could affect the health status of individuals. MicroRNAs (miRNAs) are one of the extensively studied small-sized noncoding RNAs (ncRNAs) over the past decade to explore their multiple roles in health and disease. It was proven that miRNAs circulate in almost all body fluids and tissues, showing signature patterns of dysregulation associated with pathologies. Both cellular and circulating miRNAs participate in the posttranscriptional regulation of genes and are considered the potential key regulators of genes and participate in cellular communication. This manuscript explores the unique interplay between miRNAs and enteric bacteria in the gastrointestinal tract, emphasizing their dual role in shaping host-microbiota dynamics. It delves into the molecular mechanisms by which miRNAs influence bacterial colonization and host immune responses, linking these findings to gut-related diseases. The review highlights innovative therapeutic and diagnostic opportunities, offering insights for targeted treatments of dysbiosis-associated pathologies.

Lung ischemia reperfusion injury (LIRI) represents an evitable but significant pathologic complication post pulmonary transplantation. Dexmedetomidine (Dex) that is extensively applied as an anesthetic adjuvant in the intensive care setting has increasingly presented outstandingly protective effect on LIRI. This article concerns the elaborate role of Dex in ferroptosis after LIRI and the correlative downstream mechanism. Upon hypoxia/reoxygenation (H/R) in human (A549) and mouse (MLE-12) alveolar epithelial cells, reverse transcription-quantitative PCR and western blot analysis tested nuclear receptor coactivator 4 (NCOA4) expression. CCK-8 kit determined cell viability. Western blot analysis and immunofluorescence assay estimated ferritinophagy. C11-BODIPY 581/591 staining, western blot analysis, assay kits and ferro-orange staining appraised ferroptosis. Molecular docking technology investigated the binding affinity between Dex and nuclear factor erythroid 2-related factor 2 (NRF2). Cell viability was eliminated and ferritinophagy was aggravated in A549 and MLE-12 cells in response to H/R. Disturbance of NCOA4 or treatment with Dex suppressed the ferroptosis in H/R-stimulated cells. Also, Dex docked with NRF2 and upregulated NRF2 to concentration-dependently obstruct NCOA4-mediated ferritinophagy and ferroptosis in H/R-challenged cells. Collectively, Dex might protect against NCOA4-mediated ferritinophagy through targeting NRF2, thereby alleviating ferroptosis during LIRI.

Cancer ranks as the second leading cause of death in the United States and poses a significant health challenge globally. Numerous therapeutic options exist for treating cancer, with chemotherapy being one of the most prominent. Chemotherapy involves the use of antineoplastic drugs, either alone or in combination with other medications, to target and kill cancer cells. However, these drugs can also adversely affect healthy cells, leading to various side effects. Among the most commonly used chemotherapy agents are anthracyclines, which include doxorubicin, daunorubicin, and epirubicin. Doxorubicin is particularly notable for its effectiveness but is also associated with significant cardiotoxicity, a common concern for patients undergoing chemotherapy. Unfortunately, there is currently no definitive treatment to prevent or reverse this cardiotoxicity. The cardiac effects of doxorubicin can manifest in several ways, including changes in electrocardiograms, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, heart failure, and congestive heart failure. These complications may arise during treatment, shortly after it concludes, or even weeks later. Various mechanisms have been proposed to explain doxorubicin-induced cardiotoxicity. Key factors include the inhibition of topoisomerase IIβ, mitochondrial damage, reactive oxygen species (ROS) production due to iron metabolism, increased oxidative stress, heightened inflammatory responses, and elevated rates of apoptosis and necrosis within cardiac tissue. This review article will provide a comprehensive overview of the current state of knowledge regarding doxorubicin-induced cardiomyopathy. We will explore the underlying molecular mechanisms contributing to this condition and discuss emerging therapeutic strategies aimed at mitigating its impact on cancer survivors.

Circular RNA (CircRNA)s, a newly discovered type of noncoding RNAs, have been found to play a role in controlling the development and aggressiveness of tumors. Abnormal control of circRNA has been observed in various types of human cancers, including bladder cancer, hepatocellular carcinoma (HCC), breast cancer, and gastric cancer (GC). CircRNAs possess binding sites for microRNAs (miRNAs) and function as miRNA sponges in posttranscriptional regulation. This mechanism has been documented to influence the course of cancer. Significantly, among these putative circRNAs, circular RNA protein tyrosine kinase 2 (circPTK2) exhibited increased expression and displayed a substantial association with adverse clinical characteristics and a negative prognosis. The production of these transcripts occurs via a back-splicing mechanism. The enclosed conformation of circRNAs shields them from destruction and enhances their potential as biomarkers. Gaining insight into the molecular mechanisms involved in these processes would aid in the development of treatment approaches and the discovery of new tumor markers. This article provides a comprehensive assessment of the latest research on the biosynthesis and features of circRNAs. It examines the role of circPTK2 in the diagnosis, treatment, and prognosis evaluation of cancer.

Crystalline nephropathy (CN) is characterized by deposition of microcrystals within the kidney tubular microstructure, specifically in the renal tubular cells. Nephropathic conditions have been observed in kidney stone patients as nephrocalcinosis, resulting from the deposition of calcium phosphate (CaP) microcrystals mainly within the renal tubule. CaP microcrystals trigger nephrotoxicity and cell death leading to acute and chronic kidney disease and in some cases end stage renal disease. Although supersaturation of calcium (Ca²⁺)- and phosphate (PO₄³⁻) ions in the urine was described as a main factor the precise mechanism of cell death by distinguishing the impact of supersaturated solution vs the crystalline substances is unclear. Here we show the differential effect of CaP solution vs preformed crystal (as crystalline CaP) on the nephrotoxicity and the degree and type of cell death using a murine kidney tubular cell line, LLCPK1. We examined the cellular [cell viability, lactate dehydrogenase (LDH) and H₂O₂ releases and Annexin+ propidium iodide (PI) staining] and molecular events [gene expressions, oxidative and endoplasmic reticular (ER) stress] towards understanding the mechanism of CN. The results of the study demonstrated that CaP in solution exerts injury effect on LLCPK1 cells. The addition of CaP solution showed stronger necrosis than the preformed crystals as shown by PI staining and the releases of LDH and H₂O₂. Overall, the results in the study revealed a novel mechanism differentiating the kidney cell injury between the insult mediated by supersaturated CaP solution and preformed CaP crystals.

Monoclonal antibodies (mAbs) are a key class of biotherapeutic medicines used to treat a wide range of diseases, such as cancer, infectious diseases, autoimmune disorders, cardiovascular diseases, and hemophilia. They can be engineered for greater effectiveness and specific applications while maintaining their structural elements for immune targeting. Traditional immunoglobulin treatments have limited therapeutic uses and various adverse effects. That makes mAbs show rapid growth in the pharmaceutical market, with over 250 mAbs in clinical studies. Although mAbs offer higher specificity, they are less effective against complex antigens. They have become essential in treating diseases with limited medical options, providing innovative solutions that improve patients' quality of life through increasing survival rates, shortening the length of stay in hospitals with an improved treatment outcome, and reducing side effects. This review outlines the mechanisms, applications, and advancements of mAbs, highlighting their transformative role in modern medicine and their potential to shape future therapeutic interventions.

The prevalence of chronic kidney disease (CKD) is on the rise globally, posing a significant public health concern. Numerous studies have indicated that the consumption of a high-fat diet (HFD) can lead to renal injury, a condition closely linked to CKD. Additionally, research has shown that exposure to ambient PM2.5 is associated with an increased risk of CKD, suggesting that PM2.5 may serve as an environmental risk factor for CKD. However, the synergistic impact of PM2.5 and HFD on renal injury remains poorly understood. Therefore, the objective of our study was to investigate the combined effect of PM2.5 and HFD on renal injury. Male C57BL/6J mice were subjected to a 12-week feeding regimen of either a normal diet or a HFD, while also being exposed to either saline or ambient PM2.5 through intratracheal instillation twice a week. Evaluation of renal function demonstrated that the HFD significantly elevated levels of serum blood urea nitrogen and serum creatinine. Furthermore, the combination of PM2.5 and HFD exhibited a synergistic effect, exacerbating the aforementioned indicators of kidney injury. Masson's trichrome staining revealed that both the HFD and/or PM2.5 induced renal fibrosis, with PM2.5 exacerbating the HFD-induced renal fibrosis in the mice. In this study, Western blot analysis was conducted to examine the protein expressions of TGF-β1 and p-Smad2 in kidney tissues, which were found to be significantly increased in response to a HFD and/or exposure to PM2.5. Additionally, the impact of PM2.5 combined with HFD on renal ferroptosis was investigated. The results revealed that both HFD and PM2.5 led to an elevation in 4-HNE concentration, a reduction in GSH content, a decrease in GPX4 protein expression, and an increase in ACSL4 protein expression in kidney tissues. Moreover, the combined exposure to PM2.5 and HFD exhibited a synergistic effect on GPX4 alterations in the kidney. Collectively, our findings suggest that the presence of PM2.5 exacerbates the renal injury, oxidative stress, and renal fibrosis induced by a HFD. This detrimental effect may be attributed to the activation of the ferroptosis-mediated TGF-β1/Smad2 signaling pathway.