Xuanpan Ding’s research while affiliated with Northeast Agricultural University and other places

Aloe vera is an important raw material for medicine and food, and aloe-emodin (AE) is one of the main extracts of Aloe vera. The aim of this study was to investigate the inhibitory effect of AE on multidrug-resistant Escherichia coli (MDR-E. coli) and the anti-inflammatory mechanism of this pathogenic bacterial infection. The minimum inhibitory concentration of AE against MDR-E. coli was determined in vitro. The potential therapeutic targets and signaling pathways of AE on inflammation were predicted by network pharmacology, and a mouse infection model was constructed by intraperitoneal injection of pathogenic bacteria and treated with AE. The results showed that AE had a better bacteriostatic effect and modulated the inflammatory response by affecting the expression of multiple inflammatory factors, and AE treatment significantly reduced symptoms such as inflammation, organ swelling, and bacterial load in the mouse model. The results suggest that AE may be an important active ingredient for Aloe vera to exert therapeutic health effects.

Background Sepsis-associated acute kidney injury (AKI) is a serious complication of systemic infection with high morbidity and mortality in patients. However, no effective drugs are available for AKI treatment. Dexmedetomidine (DEX) is an alpha 2 adrenal receptor agonist with antioxidant and anti-apoptotic effects. This study aimed to investigate the therapeutic effects of DEX on sepsis-associated AKI and to elucidate the role of mitochondrial dynamics during this process. Methods A lipopolysaccharide (LPS)-induced AKI rat model and an NRK-52E cell model were used in the study. This study investigated the effects of DEX on sepsis-associated AKI and the molecular mechanisms using histologic assessment, biochemical analyses, ultrastructural observation, western blotting, immunofluorescence, immunohistochemistry, qRT-PCR, flow cytometry, and si-mRNA transfection. Results In rats, the results showed that administration of DEX protected kidney structure and function from LPS-induced septic AKI. In addition, we found that DEX upregulated the α2-AR/SIRT1/PGC-1α pathway, protected mitochondrial structure and function, and decreased oxidative stress and apoptosis compared to the LPS group. In NRK-52E cells, DEX regulated the mitochondrial dynamic balance by preventing intracellular Ca²⁺ overloading and activating CaMKII. Conclusions DEX ameliorated septic AKI by reducing oxidative stress and apoptosis in addition to modulating mitochondrial dynamics via upregulation of the α2-AR/SIRT1/PGC-1α pathway. This is a confirmatory study about DEX pre-treatment to ameliorate septic AKI. Our research reveals a novel mechanistic molecular pathway by which DEX provides nephroprotection. Supplementary Information The online version contains supplementary material available at 10.1186/s10020-024-00964-y.

Simple Summary Bovine endometritis is characterized by reduced milk production and high infertility rates, resulting in substantial economic losses for the dairy farming sector. Melatonin, an amine hormone produced in the mammalian pineal gland, has been widely studied for its anti-inflammatory effects. In this work, we aimed to investigate whether melatonin inhibits Lipopolysaccharide (LPS)-induced endometritis and explore its anti-inflammatory mechanism. In LPS-induced bovine endometrial epithelial cell lines (BEND cells), melatonin promotes autophagy to inhibit the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and thus exerts anti-inflammatory effects. In a mouse model of LPS-induced endometritis, melatonin inhibited the expression of inflammatory factors and alleviated pathological changes. These findings demonstrate that melatonin inhibition of LPS-induced inflammation in vivo and in vitro may be a novel treatment for endometritis. Abstract Bovine endometritis is characterized by reduced milk production and high rates of infertility. Prior research has indicated that melatonin may possess anti-inflammatory and antioxidant properties that can counteract the progression of inflammatory diseases. In this research, we attempted to elucidate the protective effects of melatonin on LPS-induced endometritis. The results obtained from enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) revealed that melatonin effectively reduced the production and release of pro-inflammatory cytokines in an LPS-induced bovine endometrial epithelial cell line (BEND cells). Furthermore, western blotting demonstrated that melatonin treatment reduced the expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-related proteins, including NLRP3, activated caspase-1, and cleaved IL-1β. Importantly, we further demonstrated that the anti-inflammatory effect of melatonin on BEND cells was related to autophagy by western blotting. Moreover, we used western blotting to detect autophagy-related proteins, MitoSOX to detect mitochondrial reactive oxygen species production (mtROS), and mitochondrial membrane potential (MMP) assay to detect mitochondrial membrane potential. The administration of melatonin demonstrated a significant enhancement in autophagy within BEND cells, leading to the effective elimination of impaired mitochondria. This process resulted in a reduction in the generation of reactive oxygen species within the mitochondria, restoration of mitochondrial membrane potential, and inhibition of the NLRP3 inflammasome activation. Moreover, in a mouse model of LPS-induced endometritis, melatonin treatment repressed the expression of pro-inflammatory cytokines by ELISA and qRT-PCR, alleviated pathological changes by hematoxylin–eosin staining (H&E), and inhibited myeloperoxidase (MPO) activity. In conclusion, our study showed that melatonin inhibited the activation of the NLRP3 inflammasome in BEND cells through autophagy, which may provide a novel therapeutic strategy for bovine endometritis.

Pathogenic bacteria were isolated from the uterine lavage fluid of a mare with endometritis. After identification and purification, the pathogenic bacteria were injected into the uterus of rabbits to induce endometritis. Then, anatomical, blood routine, chemical examination, and histopathological examinations were performed on the rabbits. Rabbit uterus was collected, and quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression of inflammatory factors including IL-1β, IL-6, and TNF-α in the rabbit uterus. In addition, enzyme-linked immunosorbent assay (ELISA) was used to detect the uterine concentrations of the inflammatory factors IL-1β, IL-6, and TNF-α. Western Blot was used to detect the protein expressions of NF-kB, IkBα, and TNF-α in the NF-kB pathway. An antibiotic treatment group was also set up to verify the accuracy of the results. The clinical examination results showed that there was a significant increase of leukocytes in the blood of the rabbits in the model group (P < 0.01). The uterus was congested, enlarged, and purulent. The integrity of the uterine lining was destroyed, and there was a significant increase of lymphocytes in the uterus (P < 0.01). The qPCR and ELISA results showed that the expressions of the inflammatory factors IL-1β, IL-6, and TNF-α in the uterus of rabbits were significantly increased (P < 0.01). Western blot results showed that the inflammatory factors IL-1β, IL-6, and TNF-α play a role in promoting inflammation through the NF-kB pathway. The results of the test provide a simple, economical, and reliable means of studying the occurrence, development, prevention, and treatment of equine endometritis.