Sublethal toxicity of carbofuran in cattle egret (Bubulcus ibis coromandus): hematological, biochemical, and histopathological alterations

This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.

Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1α and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.

Evaluation of anti-inflammatory and antioxidant for chrysanthemum stem and leaf in zebrafish inflammatory bowel disease model and identification of the bioactive compositions by UPLC-TQ/MS

Background Modern studies have shown that chrysanthemum has anti-inflammatory, regulating intestinal function and other effects, chrysanthemum stem and leaf as a nonmedicinal part of chrysanthemum, has similar chemical components with chrysanthemum, so it is speculated that chrysanthemum stem and leaf also has the effect of regulating intestinal inflammation. The purpose of this study was to evaluate the antiinflammatory and antioxidant effect of chrysanthemum stem and leaf extract through zebrafish inflammatory bowel disease model, and to detect flavonoids, phenolic acids and polysaccharides in chrysanthemum stem and leaf extract. Methods DSS induced inflammatory bowel disease model of zebrafish was used. Aliciin blue staining was used to observe the secretion of intestinal acid mucin, and H&E staining was used to detect the inflammatory cell infiltration. Superoxide dismutase activity was determined by kit, and the expression levels of key inflammatory cytokines IL-1 β , IL8 and MMP9 were detected by quantitative polymerase chain reaction. Furthermore, UPLC-TQ /MS method was used to detect the contents of flavonoids and phenolic acids in chrysanthemum stem and leaf extracts. Neutral and acidic polysaccharides were determined by the phenol-sulfuric acid method and the carbazol-sulfuric acid method. Results H&E staining showed that extracts from chrysanthemum stem and leaf inhibited inflammatory cell infiltration to varying degrees. The expressions of inflammatory cytokines IL-1 β , IL8 and MMP9 were significantly increased in DSS induced zebrafish. The extracts inhibited the expression of IL-1 β , IL8 and MMP9 in DSS induced zebrafish. The water extract 0.2mg/ mL and alcohol extract 0.04mg/ mL had the most significant inhibition. Superoxide dismutase activity in extract treatment group was also up-regulated compared with model group. The results showed that the contents of total flavonoids and phenolic acids in the alcohol extract of chrysanthemum stem and leaf were significantly higher than those in the water extract of chrysanthemum stem and leaf, but the water-soluble polysaccharides were significantly more in the water extract of chrysanthemum stem and leaf. Conclusions In conclusion, this study suggests that chrysanthemum stem and leaf extract can improve inflammatory bowel disease of zebrafish through antiinflammatory and antioxidant activities.

SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients’ lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1β/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

Nephropathic Cystinosis: Pathogenic Roles of Inflammation and Potential for New Therapies

The activation of several inflammatory pathways has recently been documented in patients and different cellular and animal models of nephropathic cystinosis. Upregulated inflammatory signals interact with many pathogenic aspects of the disease, such as enhanced oxidative stress, abnormal autophagy, inflammatory cell recruitment, enhanced cell death, and tissue fibrosis. Cysteamine, the only approved specific therapy for cystinosis, ameliorates many but not all pathogenic aspects of the disease. In the current review, we summarize the inflammatory mechanisms involved in cystinosis and their potential impact on the disease pathogenesis and progression. We further elaborate on the crosstalk between inflammation, autophagy, and apoptosis, and discuss the potential of experimental drugs for suppressing the inflammatory signals in cystinosis.

Acute localized exanthematous pustulosis: A novel side effect of piroxicam

Acute generalized exanthematous pustulosis (AGEP) is a rare yet well-known cutaneous reaction pattern, mostly caused by drugs. Acute localized exanthematous pustulosis (ALEP) is a localized variant of AGEP. A 42-year-old female presented with multiple erythematous pustules on the face, which appeared three days after the intramuscular injection of piroxicam. Histopathology revealed subcorneal pustules, epidermal spongiosis, and mixed inflammatory cell infiltration in the dermis. The pustules resolved within several days once the patient had discontinued the drug. Herein, we report the first case, as far as we know, of a female with a cutaneous drug reaction consistent with ALEP caused by piroxicam.

Cryptococcal Prostatitis Forming Caseous and Suppurative Granulomas Diagnosed by Needle Biopsy: A Case Report

Cryptococcal granulomatous prostatitis is extremely rare, and there have been few reports of its diagnosis by prostate needle biopsy. The patient, an 81–year–old man, was receiving immunosuppressive treatment for rheumatoid arthritis. He had an oropharyngeal ulcer, and it was diagnosed alongside a methotrexate-related diffuse large B-cell lymphoma. A systemic imaging examination revealed a prostatic tumor-like mass clinically suspected to be prostatic cancer, and a needle biopsy was performed. The biopsy specimen showed various types of inflammatory cell infiltration, and suppurative granuloma and caseous granuloma were observed. Both granulomas showed multiple round and oval organisms that were revealed with Grocott methenamine silver staining. Acid–fast bacilli were not detected by Ziehl–Neelsen staining. We histologically diagnosed granulomatous prostatitis caused by Cryptococcus infection. Caseous granulomas often develop in the prostate after bacillus Calmette–Guerin immunotherapy for bladder cancer, although the possibility of cryptococcal granulomatous prostatitis should also be considered.

GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage

Acute lung injury (ALI) has been known to be a devastating form of respiratory infection and an important contributor to mortality in intensive care, due to its lacking of effective treatment. Inflammation, oxidative stress, and pyroptosis are associated with multiple kinds of inflammatory diseases such as ALI. It is commonly accepted that Gly-Pro-Ala (GPA) peptide regulates oxidative stress and pyroptosis in different kinds of inflammatory diseases. Our study is aimed at exploring the regulatory function and protective effects of GPA peptides on ALI. In the current study, the cecal ligation and puncture (CLP) technique was used to evoke sepsis in mice, and GPA peptide was administered intraperitoneally with different concentrations (50, 100, and 150 mg/kg) after CLP. Histopathological changes and the ratio of wet-to-dry in lung were recorded and analyzed. We also investigated the level of oxidative stress, inflammation, and pyroptosis. Results showed that GPA peptide significantly ameliorated CLP-stimulated lung tissue injury, impeded proinflammatory cytokine release, and reduced inflammatory cell infiltration. Additionally, GPA peptide suppressed oxidative stress and caspase-1-dependent pyroptosis in alveolar macrophages. Furthermore, our study showed that the GPA peptide prevents alveolar macrophage from undergoing pyroptosis by attenuating ROS. In conclusion, results demonstrated that GPA peptide has protective effects in CLP-stimulated ALI by inhibiting oxidative stress as well as pyroptosis of alveolar macrophage.

Substance P/NK1R antagonistic effect of 17-Trifluoromethyl phenyl trinor prostaglandin F2α in Breast cancer

17-Trifluoromethyl phenyl trinor prostaglandin F2α (17-TPGF2α) is extracted from Zinc data base, but its value for inhibiting breast cancer through SP/NK1R system remains unknown. This study was designed to investigate the potential antagonist effect of 17-TPGF2α through NK1Receptor. The effect of 17-TPGF2α on the proliferation and apoptosis of breast cancer cell lines were determined through invitro cell lines. Based on invitro results we planned to investigate anticancer activity in Female Balb/c and used SC injection of DMBA for cancer induction. Oral administration of 17-TPGF2α significantly suppress the tumor volume as compared with an untreated group. The serum parameters like ALP, AST and ALT and haematological parameters were normalized in test treated group. Histological examination revealed normal histoarchitecture of mammary gland and focal areas showed minimal inflammatory cell infiltration. There is no necrosis is seen both test treated and standard treated group when compared with Disease group. All these findings concluded that 17-TPGF2α may have potential as a novel antitumor candidate for breast cancer.