Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol.

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.

Severe acute pancreatitis (SAP) is a life-threatening acute abdominal disease with two peaks of death: the first in the early stage, characterized by systemic inflammatory response-associated organ failure; and the second in the late stage, characterized by infectious complications. Neutrophils are the main immune cells participating in the whole process of SAP. In addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens, neutrophil extracellular traps (NETs) also play an important roles in inflammatory reactions. We reviewed the role of NETs in the occurrence and development of SAP and its fatal complications, including multiple organs injury, infected pancreatic necrosis, and thrombosis. This review provides novel insights into the involvement of NETs throughout the entire process of SAP, showing that targeting NETs might be a promising strategy in SAP treatment. However, precision therapeutic options targeting NETs in different situations require further investigation.

Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact

Some traditional Chinese medicine technologies,with strong safety, quick and significant effect, standerdized manipulation, simple operation and good prospect for promotion and application are selected in the research project for application and demonstration of rural health appropriate technology. Through the application of the project, we have new experience in medical teaching.

Objective To investigate the expression of pancreatic thioredoxin-1 (TRX-1) in rats with acute necrotizing pancreatitis (ANP) and the effect of pretreatment of melatonin on its expression. Methods Male Spraque-Dawley rats (n = 12) were randomly divided to ANP group, melatonin group, control group with 24 rats in each group. The rats in ANP group received three intraperitoneal injections of 25 ml/kg body weight 6% L-arginine at an interval of 1 h to induce ANP. The rats in melatonin group received intraperitoneal injections of 25 ml/kg body weight 6% melatonin 30 min before ANP induction; rats in ANP group and control group received intraperitoneal injections of same amount of saline. Rats were sacrificed at 6 h, 12 h and 24 h after ANP induction. The serum level of amylase was measured and the pathological evaluation of pancreatic tissues was performed. The concentrations of malondialdehyde (MDA) and myeloperoxidase (MPO) in pancreatic tissues were measured. The expressions of TRX-1 protein were detected by immunohistochemistry and the expressions of TRX-1 mRNA in pancreatic tissues were determined by RT-PCR.Results In ANP group, serum level of amylase, MDA, MPO, TRX-1 mRNA and TRX-1 protein in pancreatic tissues were (3 012 ±1 425) U/L, (4.13 ± 1. 85)nmol/mg prot,(7.45 ± 1.26)nmol/mg prot, 0.68 ±0. 18, 66.8 ±8. 1, while they were (1 835±499)U/L, (3.03 ±2.12) nmol/mg prot, (5. 32 ± 1.06) nmol/mg prot, 0.50±0.09, 80. 29 ±8. 14, respectively in melatonin group, the values in melatonin group were significantly lower thanthose in ANP group (P < 0.05). The peak value of TRX-1 mRNA and TRX-1 protwein expressions shifted from 12 h after ANP induction in ANP group to 6 h after ANP induction in melatonin group. Conclusions The expression of pancreatic TRX-1 protein and TRX-1 mRNA in rats with ANP was significantly increased. Melatonin pretreatment could promote pancreatic tissues to express TRX-1 protein and TRX-1 mRNA, and may be protective for pancreatic tissues damages.

To explore the effects of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine, on pancreatic acinar cell apoptosis in a rat model of experimental acute pancreatitis.

Objective: To explore the effects of ranitidine on pharmacokinetics of rhein in rats after oral administration of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine. Methods: Twelve male Sprague-Dawley rats were divided into DCQD group and DCQD plus ranitidine group, and were orally administered with DCQD at a dose of 10 g/kg or DCQD (10 g/kg) combined with ranitidine (150 mg/kg), respectively. Blood samples were gathered after a series of time intervals. Metabolism of rhein was determined with a reversed-phase high-performance liquid chromatography with internal standard of 1, 8-dihydroxyanthraquinone and the data were analyzed with DAS 2.1 program. The pharmacokinetic parameters were compared between the two groups. Results: The pharmacokinetic parameters of rhein in the DCQD group, including peak concentration (C(max)), area under the plasma concentration-time curve (AUC), distribution phase half-life (t(1/2alpha)), elimination rate constant (K(10)) and central to peripheral transfer rate constant (K(12)), were significantly different to those in the DCQD plus ranitidine group (P<0.05, P<0.01). There were no significant differences in the other parameters between the two groups. Conclusion: Ranitidine can influence the pharmacokinetics of rhein in rats after oral administration of DCQD.

To simultaneously determine the contents and explore the pharmacokinetics of ferulic acid and paeoniflorin by high performance liquid chromatography (HPLC) after oral administration of Modified Xiao-yao Decoction (MXYD), a compound of traditional Chinese herbal medicine.

OBJECTIVE: To evaluate the safety and efficacy of Yiqi Pingchuan Granule in treating acute attack of asthma due to qi deficiency and cold syndrome. METHODS: A randomized controlled trial was conducted. A total of 80 patients with an acute attack of asthma were included. They were allocated into two groups randomly in a ratio of three to one. Sixty patients in the treatment group received Yiqi Pingchuan Granule and 20 patients in the control group received Ruyi Dingchuan Pill. Patients in both groups were treated for 7 days. RESULTS: There were no significant differences in traditional Chinese medicine syndrome, clinical symptoms and lung function between the two groups (P>0.05). After treatment, the forced expiratory volume in 1 second was increased in the treatment group (P<0.05), and the peak expiratory flow was accelerated in the control group (P<0.05). No significant side effects were noted in both groups. CONCLUSION: Yiqi Pingchuan Granule is safe and effective in treating acute attack of asthma due to qi deficiency and cold syndrome.