Pyroptosis is a novel regulated cell death (RCD) mode associated with inflammation and innate immunity. Gasdermin E (GSDME), a crucial component of the gasdermin (GSDM) family proteins, has the ability to convert caspase-3-mediated apoptosis to pyroptosis of cancer cells and activate anti-tumor immunity. Accumulating evidence indicates that GSDME methylation holds tremendous potential as a biomarker for early detection, diagnosis, prognosis, and treatment of tumors. In fact, GSDME-mediated pyroptosis performs a dual role in anti-tumor therapy. On the one side, pyroptotic cell death in tumors caused by GSDME contributes to inflammatory cytokines release, which transform the tumor immune microenvironment (TIME) from a ‘cold’ to a ‘hot’ state and significantly improve anti-tumor immunotherapy. However, due to GSDME is expressed in nearly all body tissues and immune cells, it can exacerbate chemotherapy toxicity and partially block immune response. How to achieve a balance between the two sides is a crucial research topic. Meanwhile, the potential functions of GSDME-mediated pyroptosis in anti-programmed cell death protein 1 (PD-1) therapy, antibody-drug conjugates (ADCs) therapy, and chimeric antigen receptor T cells (CAR-T cells) therapy have not yet been fully understood, and how to improve clinical outcomes persists obscure. In this review, we systematically summarize the latest research regarding the molecular mechanisms of pyroptosis and discuss the role of GSDME-mediated pyroptosis in anti-tumor immunity and its potential applications in cancer treatment.

Pyroptosis is a novel inflammatory form of regulated cell death (RCD), characterized by cell swelling, membrane rupture, and pro-inflammatory effects. It is recognized as a potent inflammatory response required for maintaining organismal homeostasis. However, excessive and persistent pyroptosis contributes to severe inflammatory responses and accelerates the progression of numerous inflammation-related disorders. In pyroptosis, activated inflammasomes cleave gasdermins (GSDMs) and generate membrane holes, releasing interleukin (IL)-1β/18, ultimately causing pyroptotic cell death. Mechanistically, pyroptosis is categorized into caspase-1-mediated classical pyroptotic pathway and caspase-4/5/11-mediated non-classical pyroptotic pathway. Renal fibrosis is a kidney disease characterized by the loss of structural and functional units, the proliferation of fibroblasts and myofibroblasts, and extracellular matrix (ECM) accumulation, which leads to interstitial fibrosis of the kidney tubules. Histologically, renal fibrosis is the terminal stage of chronic inflammatory kidney disease. Although there is a multitude of newly discovered information regarding pyroptosis, the regulatory roles of pyroptosis involved in renal fibrosis still need to be fully comprehended, and how to improve clinical outcomes remains obscure. Hence, this review systematically summarizes the novel findings regarding the role of pyroptosis in the pathogenesis of renal fibrosis and discusses potential biomarkers and drugs for anti-fibrotic therapeutic strategies.

Pulmonary fibrosis (PF) is a chronic interstitial lung disorder characterized by abnormal myofibroblast activation, accumulation of extracellular matrix (ECM), and thickening of fibrotic alveolar walls, resulting in deteriorated lung function. PF is initiated by dysregulated wound healing processes triggered by factors such as excessive inflammation, oxidative stress, and coronavirus disease (COVID-19). Despite advancements in understanding the disease’s pathogenesis, effective preventive and therapeutic interventions are currently lacking. Ferroptosis, an iron-dependent regulated cell death (RCD) mechanism involving lipid peroxidation and glutathione (GSH) depletion, exhibits unique features distinct from other RCD forms (e.g., apoptosis, necrosis, and pyroptosis). Imbalance between reactive oxygen species (ROS) production and detoxification leads to ferroptosis, causing cellular dysfunction through lipid peroxidation, protein modifications, and DNA damage. Emerging evidence points to the crucial role of ferroptosis in PF progression, driving macrophage polarization, fibroblast proliferation, and ECM deposition, ultimately contributing to alveolar cell death and lung tissue scarring. This review provides a comprehensive overview of the latest findings on the involvement and signaling mechanisms of ferroptosis in PF pathogenesis, emphasizing potential novel anti-fibrotic therapeutic approaches targeting ferroptosis for PF management.

Dandelion (Taraxacum genus), a perennial herb belonging to the Asteraceae family is widely distributed in hillside grasslands, roadsides, fields, and river beaches in middle and low-altitude areas. It has a long history of traditional Chinese medicine usage as a heat-clearing and detoxifying agent, often consumed as tea or vegetable. Multiple pharmacological studies have demonstrated the antiviral, antibacterial, anti-inflammatory, immune-regulating, antioxidant, anti-tumor, and other effects of the Taraxacum genus. Bioactive compounds associated with these effects include triterpenes and their saponins, phenolic acids, sterols and their glycosides, flavonoids, organic acids, volatile oils, and saccharides.

Background and Objective: Buyanghuanwu Decoction (BYHWD) is a clinically proven prescription effective in treating pulmonary fibrosis (PF), but the molecular mechanism underlying its action remains unclear. The network pharmacology analysis was performed to elucidate the acting substances and related pathways of BYHWD in treating bleomycin (BLM) induced PF mouse. Methods: First, the pharmacologically active components and corresponding targets in BYHWD were identified through the TCMSP database and literature review. Second, PF-related targets were identified through the DisGeNet database. Then, the components-targets network of BYHWD in PF treatment was constructed using Cytoscape. The DAVID database was used for the enrichment analysis of GO terms and KEGG pathways. At last, the therapeutic effect of BYHWD on BLMinduced PF mice were verified, and the mRNA and protein expression of related targets was determined through RT-PCR and western blotting, respectively. Results: The core component-target network contained 58 active components and 147 targets. Thirty-nine core targets were mainly involved in the regulation of biological functions and KEGG pathways, such as the positive regulation of nitric oxide biosynthesis and the TNF signaling pathway. These core targets were obtained through enrichment analysis. Moreover, animal studies revealed that BYHWD down-regulated the mRNA expression levels of TNF, IL-6, IL-1β, and NOS2 and inhibited NF-κB and p38 phosphorylation. Conclusion: The effects of BYHWD on PF mice are therapeutic, and its anti-PF mechanism mainly involves the effects on inflammatory factors and the NF-κB/p38 pathway.

Background: Previous studies have shown that polycystic ovary syndrome is a predictor of gestational diabetes mellitus, but we do not know exactly how many polycystic ovary syndrome patients may develop gestational diabetes mellitus. Currently, the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome varies greatly across studies, ranged from 4.12% to 59.50%. Besides, many factors have been found to be related to the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, but the results among different studies are not consistent. The possible causes of inconsistencies between the current estimates were unclear. This review aimed at exploring the pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, summarizing possible causes of the inconsistencies in the current estimates, try to provide a reference for prevention of gestational diabetes mellitus and polycystic ovary syndrome in the future. Methods: Systematic searches of different databases (including EMBASE, Web of Science, MEDLINE, The Cochrane Library, CNKI and PubMed) were conducted for studies published until 31 May 2021. Statistical analyses were performed using R software, the pooled incidence of gestational diabetes mellitus among polycystic ovary syndrome patients was combined using random effects model. Cochrane’s “Tool to Assess Risk of Bias in Cohort Studies” was used for quality assessment. Results: Twenty-two longitudinal studies were included. A total of 24,574 women with polycystic ovary syndrome were identified in the 22 articles, of which 4478 were reported with gestational diabetes mellitus. The pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome was 20.64%, with a 95% CI of 14.64% to 28.30%. In the meta-regression model, several variables including age, area, quality score and sample size were suggested as significant sources of heterogeneity, accounted for 77.57% of the heterogeneity across studies. Conclusions: Evidence in this review suggests that gestational diabetes mellitus were common among women with polycystic ovary syndrome. More research is needed to found effective interventions for preventing gestational diabetes mellitus among women with polycystic ovary syndrome.