NLRP

Anthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective and anti-sarcopenic strategies are needed. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death. This study highlighted the potential cardioprotective and anti-sarcopenic properties of vericiguat during anthracycline therapy. Human cardiomyocytes and primary skeletal muscle cells were exposed to doxorubicin (DOXO) with or without a pre-treatment with vericiguat...

Accumulating evidence indicates that the adverse neuroimmune activation of microglia, brain immunocytes that support neurons, contributes to a range of neuroinflammatory disorders, including Alzheimer's disease. Correcting the abnormal functions of microglia is a potential therapeutic strategy for these diseases. Nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor (NLRP) 3 inflammasomes are implicated in adverse microglial activation and their inhibitors, such as the natural compounds oridonin and shikonin, reduce microglial immune responses...

This study aimed to investigate the changes in oxidative stress, adenosine monophosphate-activated protein kinase (AMPK), connexin43 (Cx43), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression, and extracellular matrix (ECM) in the gastric smooth muscle tissues of rats with diabetic gastroparesis (DGP) and high glucose-cultured gastric smooth muscle cells, determine the existence of oxidative stress-AMPK-Cx43-NLRP3 pathway under high glucose condition, and the involvement of this pathway in ECM remodeling in DGP rats...

NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, despite their protective role, aberrant NLPR inflammasome activation and gain-of-function mutations in NLRP sensor proteins are involved in occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases...

Nod-like receptor protein 3 (NLRP-3), is an intracellular sensor that is involved in inflammasome activation, and the aberrant expression of NLRP3 is responsible for diabetes mellitus, its complications, and many other inflammatory diseases. NLRP3 is considered a promising drug target for novel drug design. Here, a pharmacophore model was generated from the most potent inhibitor, and its validation was performed by the Gunner-Henry scoring method. The validated pharmacophore was used to screen selected compounds databases...

BACKGROUND: Programmed death ligand-1(PD-L1) has been postulated to play a crucial role in the regulation of barrier functions of the vascular endothelium, yet how this novel molecule mediates dysfunction in endothelial cells (ECs) during acute lung injury(ALI) remains largely unknown. METHODS: PD-L1 siRNA and plasmids were synthesized and applied respectively to down- or up-regulate PD-L1 expression in human lung microvascular endothelial cells(HMVECs). RNA sequencing was used to explore the differentially expressed genes following PD-L1 overexpression...

BACKGROUND: Inflammation in adipose tissue, resulting from imbalanced caloric intake and energy expenditure, contributes to the metabolic dysregulation observed in obesity. The production of inflammatory cytokines, such as IL-1β and IL-18, plays a key role in this process. While IL-1β promotes insulin resistance and diabetes, IL-18 regulates energy expenditure and food intake. Previous studies have suggested that caspase-1, activated by the Nlrp3 inflammasome in response to lipid excess, mediates IL-1β production, whereas activated by the Nlrp1b inflammasome in response to energy excess, mediates IL-18 production...

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated...

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is a severe lung inflammatory condition that has the capacity to impair gas exchange and lead to hypoxemia. This condition is found to have been one of the most prevalent in patients of COVID-19 with a more serious condition. Green tea ( Camellia sinensis L. ) contains polyphenols that possess many health benefits. The purpose of this study was to assess the anti-inflammatory activities of green tea extract in Lipopolysaccharide (LPS)-induced lung cells as ARDS cells model...

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse...

Sunitinib (SUN) is a chemotherapeutic agent clinically approved for treatment of metastatic renal carcinoma. Despite its remarkable benefits, various renal toxicities have been reported that limit its clinical uses. Oleuropein (OLE) is the main polyphenolic constituent of olive tree and mediates the majority of its valuable pharmacological activities. The current study examined the probable renoprotective effects of OLE against SUN-induced nephrotoxicity. Adult male albino rats were co-treated by SUN (25mg/kg, 3 times/week, PO) with either a drug vehicle or OLE (60mg/kg/day, daily, PO) for four weeks...

BACKGROUND: Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 1 (NLRP1) participates in neuroinflammation. This study aimed to identify serum NLRP as a potential prognostic biomarker of acute intracerebral hemorrhage (ICH). METHODS: This prospective cohort study enrolled 145 patients with supratentorial ICH and 51 healthy controls. Serum NLRP1 levels were quantified on admission of all 145 patients, on days 1, 3, 5, 7, and 10 after stroke in 51 of 145 patients and at entry into the study of controls...

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE)...

BACKGROUND: Repetitive mild traumatic brain injury (rmTBI) can lead to somatic, emotional, and cognitive symptoms that persist for years after the initial injury. Although the ability of various treatments to promote recovery after rmTBI has been explored, the optimal time window for early intervention after rmTBI is unclear. Previous research has shown that hydrogen-rich water (HRW) can diffuse through the blood-brain - barrier, attenuate local oxidative stress, and reduce neuronal apoptosis in patients with severe traumatic brain injury...

Glycinin (11S) and β-conglycinin (7S) from soybean (glycine max) cause diarrhea and intestinal barrier damage in young animals. Understanding the mechanisms underlying the damage caused by 7S and 11S, it is vital to develop strategies to eliminate allergenicity. Consequently, we investigated 7S/11S-mediated apoptosis in porcine intestinal epithelial (IPEC-J2) cells. IPEC-J2 cells suffered endoplasmic reticulum stress (ERS) in response to 7S and 11S, activating protein kinase RNA-like ER kinase, activating transcription factor 6, C/EBP homologous protein, and inositol-requiring enzyme 1 alpha...

Acute kidney injury (AKI) is a disease characterised by acute onset, high mortality, and poor prognosis, and is mainly caused by ischemia-reperfusion (I/R). Human urine-derived stem cells (USCs) exhibit antioxidant, anti-inflammatory, and anti-apoptotic cytoprotective effects. Previously, we found that exosomes from USCs had the ability to inhibit apoptosis and protect kidneys from I/R injury. This study aimed to investigate the role of USC-derived exosomes (USC-Exos) in reducing pyroptosis and alleviating I/R-AKI...

Recent studies by Ball et al (Ball et al., 2022) and Zhang et al (Zhang et al., 2023) have provided evidence for the direct binding of thioredoxin1 (TRX1) to a component of inflammasome complex NLRP-1. This interaction suggests a potential role for TRX1 in the regulation of the NLR family pyrin domain containing 1 (NLRP-1) inflammasome. Furthermore, the NLRP-3 inflammasome is known to bind TRX1 and its inhibitor, thioredoxin-binding protein-2/thioredoxin-interacting protein/vitamin D3 upregulated protein-1 (TBP2/TXNP1/VDUP-1)...

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1β, the maturation of which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies the inflammatory response but also triggers osteoclastogenesis, thereby accelerating the progression of periodontitis. Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on the effectiveness of Dioscin for the management of periodontitis remains scarce...

OBJECTIVE: NOD-like receptor pyrin domain-containing 3 (NLRP3 ) is a cytosolic multi-protein complex that induces inflammation and is negatively regulated by progesterone. Previous researches have reported abnormal induction of reactive oxygen species (ROS) and progesterone resistance in endometriosis (EM). Since progesterone regulates ROS level and, consequently, inflammation, our objective is to investigate whether dienogest (DNG) regulates NLRP3 and whether the regulation of NLRP3 inflammasome by DNG in the blood plasma of patients with EM can affect oxidant and antioxidant markers...

BACKGROUND: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer...