Diabetic nephropathy(DN), a progressive chronic kidney disease(CKD) induced by diabetes mellitus, is the main cause of end-stage renal disease. Renal interstitial fibrosis(RIF) is an irreversible factor in the progression and deterioration of the renal function in DN. Chronic inflammation has become a key link in the pathogenesis of DN-RIF. The NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome is an important inflammatory regulator regulated by a variety of signals. It promotes the production of pro-inflammatory cytokines and induces renal inflammatory cell infiltration to participate in the process of renal fibrosis, demonstrating a complex mechanism of action. In view of the important role of NLRP3 inflammasomes in the prevention and treatment of DN-RIF, a large number of experimental studies have demonstrated that traditional Chinese medicine(TCM) can reduce the inflammation by regulating the pathways involving NLRP3 inflammasome, thereby slowing down the progression of DN-RIF and improving the renal function. This paper reviews the relationship between NLRP3 inflammasomes and DN-RIF, and the research progress in the mechanism of TCM intervention in NLRP3 inflammasomes to alleviate DN-RIF, aiming to provide new ideas for the targeted treatment of DN-RIF.

Alzheimer\'s disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid β-protein(Aβ) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aβ deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.

The uterine cervix is one of the key factors involved in ensuring a proper track of gestation and labor. At the end of the gestational period, the cervix undergoes extensive changes, which can be summarized as a transformation from a non-favorable cervix to one that is soft and prone to dilation. During a process called cervical ripening, fundamental remodeling of the cervical extracellular matrix (ECM) occurs. The cervical ripening process is a derivative of many interlocking and mutually driving biochemical and molecular pathways under the strict control of mediators such as inflammatory cytokines, nitric oxide, prostaglandins, and reactive oxygen species. A thorough understanding of all these pathways and learning about possible triggering factors will allow us to develop new, better treatment algorithms and therapeutic goals that could protect women from both dysfunctional childbirth and premature birth. This review aims to present the possible role of the NLRP3 inflammasome in the cervical ripening process, emphasizing possible mechanisms of action and regulatory factors.

Pyroptosis is a novel pro-inflammatory mode of programmed cell death that differs from ferroptosis, necrosis, and apoptosis in terms of its onset and regulatory mechanisms. Pyroptosis is dependent on cysteine aspartate protein hydrolase (caspase)-mediated activation of GSDMD, NLRP3, and the release of pro-inflammatory cytokines, interleukin-1 (IL-1β), and interleukin-18 (IL-18), ultimately leading to cell death. Non-coding RNA (ncRNA) is a type of RNA that does not encode proteins in gene transcription but plays an important regulatory role in other post-transcriptional links. NcRNA mediates pyroptosis by regulating various related pyroptosis factors, which we termed the pyroptosis signaling pathway. Previous researches have manifested that pyroptosis is closely related to the development of liver diseases, and is essential for liver injury, alcoholic fatty liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. In this review, we attempt to address the role of the ncRNA-mediated pyroptosis pathway in the above liver diseases and their pathogenesis in recent years, and briefly outline that TCM (Traditional Chinese Medicine) intervene in liver diseases by modulating ncRNA-mediated pyroptosis, which will provide a strategy to find new therapeutic targets for the prevention and treatment of liver diseases in the future.

Atherosclerosis is a chronic, progressive cardiovascular disease characterized by cholesterol deposition within blood vessel walls. Recent literature has suggested that the NLRP3 [NOD (nucleotide oligomerization domain)-, LRR (leucine-rich repeat)-, and PYD (pyrin domain)-containing protein 3] inflammasome is a key mediator in the development, progression, and destabilization of atherosclerotic plaques. This review aims to evaluate the current literature on the role of NLRP3 in human atherosclerosis. This systematic review was registered on the PROSPERO database (ID = CRD42022340039) and involved the search of a total of 8 databases. Records were screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies were included and quality assessed using the NIH: NHLBI tool. Six were eligible for meta-analysis using RevMan 5.4.1. We identified 20 relevant articles representing 3388 participants. NLRP3 mRNA levels and downstream cytokines, interleukin (IL)-1β and IL-18 were found to be associated with atherosclerotic disease. Fold changes in NLRP3 mRNA levels were most strongly associated with high risk atherosclerotic disease, compared to controls [0.84 (95 % CI: 0.41-1.28)]. IL-1β mRNA fold change was more robustly associated with high-risk atherosclerotic disease [0.61 (95 % CI: 0.10-1.13)] than IL-18 [0.47 (95 % CI: 0.02-0.91)]. NLRP3, IL-1β, and IL-18 are associated with high-risk atherosclerotic disease. However, given the scope of this review, the role of this inflammasome and its cytokine counterparts in acting as prognosticators of coronary artery disease severity is unclear. Several upstream activators such as cholesterol crystals are involved in the canonical or non-canonical activation of the NLRP3 inflammasome and its downstream cytokines. These findings highlight the necessity for further research to delineate the exact mechanisms of NLRP3 inflammasome activation and potential drug targets.

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BACKGROUND: Immune-mediated conjunctivitis is a prevalent ocular ailment characterized by inflammation and immune reactions in the conjunctiva. However, the precise causes and therapeutic approaches for this condition remain the main focus for numerous ophthalmological specialists. Recently, accumulating evidence from human and mouse experiments has demonstrated the critical involvement of the NLRP3 inflammasome, IL-1β, and IL-18 in the development of allergic diseases. Targeting specific NLRP3 inflammasome and its related inhibitors may hold potential as therapeutic agents for immunologic conjunctivitis. Despite this, there has been no systematic review specifically addressing the treatment of immunologic conjunctivitis related to NLRP3. Therefore, this study aims to conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCTs) on NLRP3-related treatments for immunologic conjunctivitis patients, with the goal of evaluating their efficacy and safety.
METHODS: We will conduct a comprehensive search for relevant studies on NLRP3 inflammasome inhibitors or NLRP3-related treatments for immunologic conjunctivitis in various databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang. The search will encompass studies from their respective inception dates to July 2023. A meta-analysis will be performed using data extracted from eligible randomized controlled trials (RCTs), focusing on the clinical manifestations of immunologic conjunctivitis, levels of NLRP3-related factors in serum or tear samples, quality of life outcomes, and adverse events. Review Manager 5.4.1 software will be employed for the meta-analysis, and the results will be analyzed using either random-effects or fixed-effects models, depending on the presence of heterogeneity. The reliability and quality of evidence will be evaluated using the Grading of Recommendations, Development, and Evaluation (GRADE) system.
RESULTS: The findings of this study will yield robust and high-quality evidence regarding the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. This evidence will contribute significantly to our understanding of the potential benefits and risks associated with such treatments and will assist healthcare professionals in making informed decisions regarding the management of immunologic conjunctivitis.
CONCLUSIONS: This study represents the first comprehensive meta-analysis aiming to evaluate the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. The findings from this study will provide valuable evidence to guide clinical management strategies for this disease. The results are anticipated to significantly contribute to the understanding of the therapeutic potential and safety profile of NLRP3-related treatments, offering valuable insights for healthcare professionals involved in the care of patients with immunologic conjunctivitis.
BACKGROUND: Systematic review registration: PROSPERO with registration number CRD42023437076.

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL‑1β and IL‑18, as well as gasdermin‑D‑mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3‑mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

Diabetic cardiomyopathy (DCM), one of the common complications of diabetes, presents as a specific cardiomyopathy with anomalies in the structure and function of the heart. With the increasing prevalence of diabetes, DCM has a high morbidity and mortality worldwide. Recent studies have found that pyroptosis, as a programmed cell death accompanied by an inflammatory response, exacerbates the growth and genesis of DCM. These studies provide a theoretical basis for exploring the potential treatment of DCM. Therefore, this review aims to summarise the possible mechanisms by which pyroptosis promotes the development of DCM as well as the relevant studies targeting pyroptosis for the possible treatment of DCM, focusing on the molecular mechanisms of NLRP3 inflammasome-mediated pyroptosis, different cellular pyroptosis pathways associated with DCM, the effects of pyroptosis occurring in different cells on DCM, and the relevant drugs targeting NLRP3 inflammasome/pyroptosis for the treatment of DCM. This review might provide a fresh perspective and foundation for the development of therapeutic agents for DCM.