Effects of RIPK1 inhibitor necrostatin-1s on cardiovascular responses and inflammatory damage in a bilateral hind limb I/R injury model in rats

β-Hydroxybutyrate induces microglial M2 polarization by inhibiting the NF-κB/NLRP3 pathway to ameliorate cerebral ischemia–reperfusion injury

Elevated endogenous BHB under obese conditions exerts neuroprotective effects against CIRI, and exogenous BHB can mimic this effect.

Thymosin β4 Mitigates Acute Cerebral Infarction Via Inhibition of the TLR4/NF-κB Pathway and Suppression of Neuronal Pyroptosis.

Involvement of COX-2 in the Neurovascular Unit Damage Through Up-Regulating Calpain/PARP/NF-κB Inflammatory Signaling During Ischemic Stroke

TRPM7 exacerbates testicular ischemia-reperfusion injury by activating the NLRP3 inflammasome to drive pyroptosis.

BACKGROUND Testicular ischemia-reperfusion injury (IRI) represents a critical determinant of fertility outcomes following torsion. Pyroptosis, an inflammatory form of cell death, involved in IRI within other organs, but its role and regulation in testicular damage remain unclear. The cation channel-kinase TRPM7 is a known stress sensor, yet its role in testicular IRI is unknown. METHODS Both a murine testicular I/R model and an in vitro OGD/R model using GC-1 cells were constructed. The extent of pyroptosis was determined by detecting cleaved caspase-1 (CASP1), GSDMD-N, and IL-1β/18. TRPM7 expression was estimated by qRT-PCR, western blot (WB), and immunohistochemistry. Gain- and loss-of-function investigations were conducted using overexpression plasmids, siRNA, and the inhibitor NS8593. The involvement of the NLRP3 inflammasome was tested using its inhibitor MCC950. RESULTS Testicular I/R and OGD/R robustly activated pyroptosis. TRPM7 expression was significantly upregulated in both models. Functionally, TRPM7 overexpression exacerbated OGD/R-induced cell death and pyroptosis, while its knockdown or inhibition attenuated these effects. Mechanistically, TRPM7 triggered the expression and stimulation of the NLRP3 inflammasome. Critically, the NLRP3 inhibitor MCC950 completely reversed the enhanced pyroptosis driven by TRPM7 overexpression. CONCLUSION This study identifies a novel TRPM7/NLRP3/pyroptosis axis as a key pathogenic mechanism in testicular IRI. TRPM7 acts as an upstream regulator, transducing ischemic stress into NLRP3 inflammasome stimulation and inflammatory cell death, positioning it as a prospective therapeutic target.

Imeglimin confers protection against intestinal ischemia/reperfusion injury in rats through AMPK-dependent inhibition of NF-κB/NLRP3 inflammasome signaling and mitigation of oxidative stress and apoptosis

IMEG exerts a protective effect against intestinal I/R injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Cuminaldehyde alleviates inflammation in isoproterenol-induced acute myocardial infarction through Nrf-2/HO-1 and NF-κB signaling pathways.

Myocardial infarction (MI) is a leading cause of death, and the limited efficacy of current treatments pushes the exploration of novel drug candidates.The purpose of this study was to assess the anti-inflammatory effects of cuminaldehyde, a monocyclic terpenoid, in an in vivo model of isoproterenol-induced acute myocardial infarcted rats.Rats were induced to undergo MI by isoproterenol(100 mg/kg body weight).Then, rats were treated with cuminaldehyde (20 mg/kg body weight) daily for three weeks.Cardiac oxidative stress and inflammation were investigated. Moreover, nuclear factor (erythroid-derived-2)-like 2(Nrf-2)/heme oxygenase-1(HO-1) and nuclear factor kappa B (NF-κB)/tumor necrosis factor-alpha(TNF-α)/interleukin-6(IL-6)/interleukin-8(IL-8)/inducible nitric oxide synthase (iNOS)/cyclooxygenase-2(COX-2)-mediated signaling pathways were evaluated to unravel the molecular mechanisms of cuminaldehyde.The serum cardiac diagnostic markers and heart thiobarbituric acid reactive substances were increased, and heart glutathione peroxidase and reduced glutathione were reduced in isoproterenol-induced myocardial infarcted rats.RT-PCR analysis revealed a reduction in myocardial expression of the Nrf-2 and HO-1 genes.Isoproterenol also elevated plasma total homocysteine and serum high-sensitivity C-reactive protein.Furthermore,ELISA and RT-PCR results revealed elevated serum and myocardial expression of NF-κB, TNF-α, IL-6, IL-8, iNOS, and COX-2 in MI rats.The 2,3,5-triphenyltetrazolium chloride (TTC) staining of the heart revealed an increased myocardial infarct area in MI rats.Moreover, histopathology revealed inflammatory infiltration in the hearts of myocardial infarcted rats.Nevertheless,cuminaldehyde attenuated all the aforementioned biochemical,RT-PCR, TTC, and histopathological parameters investigated, inhibited oxidative stress, and thereby reduced isoproterenol-induced inflammation by modulating Nrf-2/HO-1 and NF-κB/TNF-α/IL-6/IL-8/iNOS/COX-2 signaling pathways through its antioxidant and anti-inflammatory effects.Additionally,it reduced myocardial infarct size by anti-myocardial infarct size effects.Thus, cuminaldehyde alleviated inflammation in isoproterenol-induced acute MI.