Chronic kidney disease (CKD) is a global health concern and public health priority. The condition often involves inflammation due to the accumulation of toxins and the reduced clearance of inflammatory cytokines, leading to gradual loss of kidney function. Because of the tremendous burden of CKD, finding effective treatment strategies against inflammation is crucial. Substantial evidence suggests an association between kidney disease and the inflammasome. As a well-known multiprotein signaling complex, the NLR family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in inducing renal inflammation and fibrosis. Small molecule inhibitors targeting the NLRP3 inflammasome are potential agents for the treatment of CKD.The NLRP3 inflammasome activation amplifies the inflammation response, promoting pyroptotic cell death. Thus, it may contribute to the onset and progression of CKD, but the mechanism behind inflammasome activation in CKD remains obscure.In this review, we summarized recent findings on the role of the NLRP3 inflammasome in CKD and new strategies targeting the NLRP3 inflammasome.

UNASSIGNED: Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1-34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1-34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1-34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms.
UNASSIGNED: In vivo study, eight-week-old male mice including wild-type (WT) (n ​= ​54) and OPG-/- (n ​= ​54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n ​= ​18), the DMM group (WT-DMM; n ​= ​18), and the PTH (1-34)-treated group (WT-DMM ​+ ​PTH (1-34); n ​= ​18). Similarly, the OPG-/- mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1-34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1-34) in vitro.
UNASSIGNED: Compared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1-34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1-34) treatment. Among the OPG-/- mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn\'t show any response to the PTH (1-34) treatment. Compared with the WT-DMM mice, the OPG-/--DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG-/--DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1-34). In vitro study, PTH (1-34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6).
UNASSIGNED: Both wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG-/- mice. PTH (1-34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA.
UNASSIGNED: Systemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.

UNASSIGNED: Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce.
UNASSIGNED: In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics.
UNASSIGNED: Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid).
UNASSIGNED: Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future.
UNASSIGNED: This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

UNASSIGNED: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice.
UNASSIGNED: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and pole-climbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i.
UNASSIGNED: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells.
UNASSIGNED: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

UNASSIGNED: Lipopolysaccharides (LPS) stimulate production of inflammatory cytokines. Chrysin is flavonoid beneficial for treatment of inflammatory conditions. Bone marrow mesenchymal stem cell (BM-MSC) exosomes have regenerative ability in different tissues.
UNASSIGNED: To assess potential role of chrysin and BM-MSC exosomes on ultra-structure, viability and function of human dermal fibroblasts-adult (HDFa) stimulated by LPS.
UNASSIGNED: HDFa cells were divided into: Group I: Cells received no treatment. Group II: Cells were stimulated with LPS. Group III: LPS stimulated cells were treated with chrysin. Group IV: LPS stimulated cells were treated with exosomes.
UNASSIGNED: After 48 h, ultrastructural examination of HDFa cells in Group I revealed intact plasma membrane and numerous cytoplasmic organelles. Group II displayed destructed plasma membrane and apoptotic bodies. Group III showed intact plasma membrane with loss of its integrity at some areas. Group IV demonstrated intact plasma membrane that showed fusion with exosomes at some areas. Statistical analysis of MTT represented highest mean value of cell viability% in Group IV followed by Groups III, I and II respectively. Statistical analysis of enzyme-linked immunosorbent assay (ELISA) showed the highest mean value of interleukin-1β (IL-1β) was in Group II followed by Groups III, IV and I, while highest mean values of interleukin-10 (IL-10), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins were in Group I, followed by Groups IV, III and II respectively.
UNASSIGNED: LPS have harmful consequences on ultra-structure, viability and function of HDFa cells. BM-MSC exosomes have better regenerative action on inflamed fibroblasts in comparison to chrysin.

UNASSIGNED: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.
UNASSIGNED: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.
UNASSIGNED: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.
UNASSIGNED: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose-effect relationship.

This study aimed to evaluate the efficacy of chitosan-silver nanocomposites in the treatment of experimentally infested pigeons with Pseudolynchia canariensis (P. canariensis) with evaluation of different immunological parameters before and after treatment. Therefore, fourteen birds were divided into 2 groups; group1(infested group including 12 birds) which subdivided into 6 sub-groups experimentally infested pigeons 2 pigeons each, and five group of them were treated with chitosan-silver nanocomposites and sub-group number 6 was treated with deltamethrin while, group 2 including two pigeons were kept as control negative ones. P. canariensis flies distributed under the wing and /or under the tail in infested group and these pigeons showed significantly lower RBCs and higher WBCs than that in non-infested pigeons. The cell mediated immune response against experimentally infested pigeons with P. canariensis was studied. P. canariensis infestation in pigeons have a negative impact on pigeon\'s blood parameters, increase TNF-α and IL-1β cytokines levels. This study cleared out the role of P. canariensis in the induction of a case of oxidative stress indicated by high level of nitric oxide and malondialdehyde (MDA) with low antioxidant capacity in shape of reduced zinc concentration in the sera of experimentally infested pigeon. Chitosan-silver nanocomposite has a promising effect in the elimination of P. canariensis infestation in pigeons.

Acoustic trauma induces an inflammatory response in the cochlea, resulting in debilitating hearing function. Clinically, amelioration of inflammation substantially prevents noise-induced hearing loss. The Limulus factor C, Cochlin, and Lgl1 (LCCL) peptide plays an important role in innate immunity during bacteria-induced inflammation in the cochlea. We aimed to investigate the LCCL-induced innate immune response to noise exposure and its impact on hearing function.
METHODS: We used Coch (encodes cochlin harboring LCCL peptide) knock-out and p.G88E knock-in mice to compare the immune responses before and after noise exposure. We explored their hearing function and hair cell degeneration. Moreover, we investigated distinct characteristics of immune responses upon noise exposure using flow cytometry and RNA sequencing.
RESULTS: One day after noise exposure, the LCCL peptide cleaved from cochlin increased over time in the perilymph space. Both Coch-/- and CochG88E/G88E mutant mice revealed more preserved hearing following acoustic trauma compared to wild-type mice. The outer hair cells were more preserved in Coch-/- than in wild-type mice upon noise exposure. The RNA sequencing data demonstrated significantly upregulated cell migration gene ontology in wild-type mice than in Coch-/- mice following noise exposure, indicating that the infiltration of immune cells was dependent on cochlin. Notably, infiltrated monocytes from blood (C11b+/Ly6G-/Ly6C+) were remarkably higher in wild-type mice than in Coch-/- mice at 1 day after noise exposure.
CONCLUSIONS: Noise-induced hearing loss was attributed to over-stimulated cochlin, and led to the cleavage and secretion of LCCL peptide in the cochlea. The LCCL peptide recruited more monocytes from the blood vessels upon noise stimulation, thus highlighting a novel therapeutic target for noise-induced hearing loss.