Jun-Fei Zhang

Diquat (1,1′-ethylene-2,2′-bipyridyl, DQ) is a herbicide widely used for weed control in both agricultural and non-cultivated areas. Although its acute toxicity is lower than that of paraquat, its high-water solubility and stability in acidic and neutral environments contribute to its prolonged environmental persistence. As DQ gradually replaces paraquat in agricultural practice, the incidence of DQ poisoning has increased significantly. DQ poisoning typically results from accidental ingestion, suicidal intake, or improper agricultural handling. To date, no specific antidote is available, and the high mortality associated with DQ poisoning presents a critical challenge for clinical management. Accumulating evidence indicates that the toxicity of DQ is primarily attributed to its capacity to generate reactive oxygen species (ROS), leading to oxidative stress and subsequent oxidative damage to lipids, proteins, and DNA, ultimately resulting in multi-organ dysfunction, with the kidneys and intestines being the primary target organs. The pathogenesis of DQ poisoning involves multiple factors, including oxidative stress imbalance, regulated cell death, mitochondrial dysfunction, and disturbances in energy metabolism. This review systematically examines the physicochemical properties, metabolic characteristics, biodistribution, and target organ toxicity of DQ, with a particular focus on the interplay between excessive ROS production and mitochondrial dysfunction in the context of oxidative stress. Furthermore, we provide an in-depth discussion on the roles of regulated cell death—including pyroptosis, ferroptosis, and mitophagy—and metabolic dysregulation in DQ-induced toxicity. In addition, this review summarizes the classical signaling pathways involved in organ dysfunction, current therapeutic strategies, and potential intervention targets, thereby offering a theoretical framework and future research directions for the management of DQ poisoning.

Sepsis, a severe systemic infection triggered by the invasion of bacterial, viral, fungal, and other pathogens into human tissues, frequently results in substantial damage to the heart, which is one of the primary organs affected. This myocardial injury is strongly linked to poor patient outcomes in sepsis. Recent research has identified key factors such as mitochondrial dysfunction, metabolic disturbances, cell death, and dysregulated inflammatory responses as critical contributors to the pathogenesis of sepsis-induced myocardial injury (SIMI). These mechanisms not only enhance our understanding of SIMI but also offer potential therapeutic targets. The review aims to investigate the pathophysiological mechanisms driving myocardial injury in sepsis, particularly from the perspective of mitochondrial dysfunction. It will examine the complex interactions between inflammatory dysregulation, calcium homeostasis disruption, metabolic reprogramming, and mitochondrial dysfunction in the onset and progression of SIMI. By exploring therapeutic approaches focused on restoring mitochondrial function, this research aims to establish a theoretical framework for interventions targeting SIMI, thereby providing a robust foundation for the development of targeted therapies for SIMI.

18β-Glycyrrhetinic acid (18β-GA) has a therapeutic effect on gastric cancer (GC), but its mechanism of action is still unclear. We analyzed the effects of 18β-GA on the proliferation, migration and invasion of GC cells using CCK technology, colony formation assay, wound healing assay and Transwell assay. BALB/c nude mice were used to establish subcutaneous transplantation models, orthotopic transplantation models and tail vein Liver metastasis models, and GC proliferation and metastasis models were constructed using zebrafish. After continuous treatment with 18β-GA, the inhibitory effect of drug on tumor was observed in vivo. Finally, western blot, immunohistochemistry (IHC) and immunofluorescence (IF) were used to detect the expression of key proteins in the TCTP/AKT/P53 signaling pathway and the key proteins in the cell apoptosis, cell cycle and EMT signaling pathways. Our in vitro and in vivo functional experiments showed that 18β-GA treatment could inhibit GC proliferation and metastasis, and the effect of 18β-GA alone was similar to that of TCTP knockdown, while the inhibition effect of 18β-GA combined with TCTP knockdown was the best. In GC, the expression of TCTP, p-AKT and Ki67 protein was significantly decreased after treatment with 18β-GA, while the expression of P53 protein was increased. In addition, 18β-GA treatment significantly increased the protein expression levels of Bax, P27, P21 and E-Cadherin, and decreased the protein expression levels of Bcl-2, Cyclin D1, N-Cadherin and Vimentin. Therefore, 18β-GA can promote cell apoptosis by inhibiting the TCTP/AKT/P53 signaling pathway, arrest the cell cycle and inhibit the proliferation and metastasis of GC.

Sepsis represents a severe condition characterized by organ dysfunction resulting from a dysregulated host response to infection. Among the organs affected, the kidneys are particularly vulnerable, with significant functional impairment that markedly elevates mortality rates. Previous researches have highlighted that both inflammatory response dysregulation and metabolic reprogramming are crucial in the onset and progression of sepsis associated acute kidney injury (SA-AKI), making these processes potential targets for innovative therapies. This study aims to elucidate the pathophysiological mechanisms of renal injury in sepsis by perspective of inflammatory response dysregulation, with particular emphasis on pyroptosis, necroptosis, autophagy, and ferroptosis. Furthermore, it will incorporate insights into metabolic reprogramming to provide a detailed analysis of the mechanisms driving SA-AKI and explore potential targeted therapeutic strategies, providing solid theoretical framework for the development of targeted therapies for SA-AKI.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is characterized by high morbidity and mortality and one of the major diseases that seriously hang over global human health. Autophagy is a crucial regulator in the complicated pathophysiological processes of sepsis. The activation of autophagy is known to be of great significance for protecting sepsis induced organ dysfunction. Recent research has demonstrated that N6-methyladenosine (m6A) methylation is a well-known post-transcriptional RNA modification that controls epigenetic and gene expression as well as a number of biological processes in sepsis. In addition, m6A affects the stability, export, splicing and translation of transcripts involved in the autophagic process. Although it has been suggested that m6A methylation regulates the biological metabolic processes of autophagy and is more frequently seen in the progression of sepsis pathogenesis, the underlying molecular mechanisms of m6A-modified autophagy in sepsis have not been thoroughly elucidated. The present article fills this gap by providing an epigenetic review of the processes of m6A-modified autophagy in sepsis and its potential role in the development of novel therapeutics.

Objective: Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ's cardio-protection during sepsis and the mechanisms. Methods: In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue. Results: The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1β, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group (p<0.05). TUNEL staining's results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl (p <0.05). Conclusions: In here, we observed that XBJ's cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.