Wenyang-Tianjing-Jieyu Decoction Improves Depression Rats of Kidney Yang Deficiency Pattern by Regulating T Cell Homeostasis and Inflammation Level.

Purpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms. Materials and Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB. Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression. Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats.

Gallic acid alleviates gastric precancerous lesions through inhibition of epithelial mesenchymal transition via Wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression. AIM OF THE STUDY: To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of "inflammation-cancer transformation" and thus blocking GPL to prevent the development of gastric cancer. MATERIALS AND METHODS: In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo. RESULTS: The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/ß-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/ß-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice. CONCLUSION: Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/ß-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL.

Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis.

Background: Pancreatic injury (pancreatitis, amylase/lipase elevation) is a rare adverse event of immune checkpoint inhibitors (ICIs). With the high number of clinical studies on ICIs, the incidence and characteristics of associated pancreatic injury (PI) need to be reevaluated. Methods: A systematic review and meta-analysis was conducted to assess the incidence of PI in cancer patients who received ICIs in randomized controlled trials (RCTs). PubMed, Embase, the ASCO, ESMO, and AACR conference proceedings before 1 April 2022, were investigated for relevant research. Results: 50 RCTs involving 35,223 patients were included. The incidence of ICIs-PI was 2.22% (95% CI = 1.94%-2.53%). The incidence of PI was 3.76% (95% CI = 1.84-7.67%) when combining two ICIs, which was higher than single ICIs [2.25% (95% CI = 1.91-2.65%)]. The ICIs were ranked from high to low based on PI incidence: PD-L1 inhibitors 3.01% (95% CI = 1.86-4.87%), CTLA-4 inhibitors 2.92% (95% CI = 0.99-8.65%) and PD-1 Inhibitor 2% (95% CI = 1.67-2.39%). The ICI with the highest rate of PI was pembrolizumab 7.23.% (95% CI = 1.69-30.89%). In addition, the incidence of severe ICIs-PI was 2.08% (95% CI = 1.76-2.46%); and the incidence of severe PI was 2.32% (95% CI = 1.76-3.06%) when combining two ICIs, which was higher than single ICI [1.95% (95% CI = 1.58-2.41%)]. The ICIs were ranked from high to low according to the incidence of severe PI: PD-L1 inhibitors 3.1% (95% CI = 1.7-5.64%), CTLA-4 inhibitors 2.69% (95% CI = 0.76-9.49%), PD-1 inhibitors 1.80% (95% CI = 1.41-2.29%). Conclusion: Treatment with multiple ICIs result in a higher incidence of PI compared to single ICIs, irrespective of the grade of pancreatic injury. The incidence of PI caused by PD-L1 inhibitors is higher than that of CTLA-4 inhibitors and PD-1 Inhibitor, and Pembrolizumab has the highest rate of ICIs-PI. Although the incidence of ICIs-PI is not high, they are usually severe (≥ grade 3 events).

Ginsenoside Rg3 induces apoptosis and inhibits proliferation by down-regulating TIGAR in rats with gastric precancerous lesions.

BACKGROUND: Ginsenoside Rg3 (GRg3) is one of the main active ingredients in Chinese ginseng extract and has various biological effects, such as immune-enhancing, antitumour, antiangiogenic, immunomodulatory and anti-inflammatory effects. This study aimed to investigate the therapeutic effect of GRg3 on gastric precancerous lesion (GPL) induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and the potential mechanism of action. METHODS: The MNNG-ammonia composite modelling method was used to establish a rat model of GPL. Histopathological changes in the rat gastric mucosa were observed by pathological analysis using haematoxylin-eosin staining to assess the success rate of the composite modelling method. Alcian blue-periodic acid Schiff staining was used to observe intestinal metaplasia in the rat gastric mucosa. Apoptosis was detected in rat gastric mucosal cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling staining. The production level of reactive oxygen species (ROS) was determined by the dihydroethidium fluorescent probe method, and that of TP53-induced glycolysis and apoptosis regulator (TIGAR) protein was determined by immunohistochemical staining and western blotting. The production levels of nicotinamide adenine dinucleotide phosphate (NADP) and glucose-6-phosphate dehydrogenase (G6PDH) were determined by an enzyme-linked immunosorbent assay, and that of glutathione (GSH) was determined by microanalysis. RESULTS: GRg3 significantly alleviated the structural disorganization and cellular heteromorphism in the form of epithelial glands in the gastric mucosa of rats with GPL and retarded the progression of the disease. Overexpression of TIGAR and overproduction of NADP, GSH and G6PDH occurred in the gastric mucosal epithelium of rats with GPL, which in turn led to an increase in the ROS concentration. After treatment with GRg3, the expression of TIGAR and production of NADP, GSH G6PDH decreased, causing a further increase in the concentration of ROS in the gastric mucosal epithelium, which in turn induced apoptosis and played a role in inhibiting the abnormal proliferation and differentiation of gastric mucosal epithelial cells. CONCLUSION: Grg3 can induce apoptosis and inhibit cell proliferation in MNNG-induced GPL rats. The mechanism may be related to down-regulating the expression levels of TIGAR and production levels of GSH, NADP and G6PD, and up-regulating the concentration of ROS.

A Role of IL-17 in Rheumatoid Arthritis Patients Complicated With Atherosclerosis.

Rheumatoid arthritis (RA) is mainly caused by joint inflammation. RA significantly increases the probability of cardiovascular disease. Although the progress of RA has been well controlled recently, the mortality of patients with RA complicated with cardiovascular disease is 1.5-3 times higher than that of patients with RA alone. The number of people with atherosclerosis in patients with RA is much higher than that in the general population, and atherosclerotic lesions develop more rapidly in patients with RA, which has become one of the primary factors resulting in the death of patients with RA. The rapid development of atherosclerosis in RA is induced by inflammation-related factors. Recent studies have reported that the expression of IL-17 is significantly upregulated in patients with RA and atherosclerosis. Simultaneously, there is evidence that IL-17 can regulate the proliferation, migration, and apoptosis of vascular endothelial cells and vascular smooth muscle cells through various ways and promote the secretion of several cytokines leading to the occurrence and development of atherosclerosis. Presently, there is no clear prevention or treatment plan for atherosclerosis in patients with RA. Therefore, this paper explores the mechanism of IL-17 in RA complicated with atherosclerosis and shows the reasons for the high incidence of atherosclerosis in patients with RA. It is hoped that the occurrence and development of atherosclerosis in patients with RA can be diagnosed or prevented in time in the early stage of lesions, and the prevention and treatment of cardiovascular complications in patients with RA can be enhanced to reduce mortality.

Factors Affecting Social Media Users' Emotions Regarding Food Safety Issues: Content Analysis of a Debate among Chinese Weibo Users on Genetically Modified Food Security.

Social media is gradually building an online information environment regarding health. This environment is filled with many types of users' emotions regarding food safety, especially negative emotions that can easily cause panic or anger among the population. However, the mechanisms of how it affects users' emotions have not been fully studied. Therefore, from the perspective of communication and social psychology, this study uses the content analysis method to analyze factors affecting social media users' emotions regarding food safety issues. In total, 371 tweet samples of genetically modified food security in Sina Weibo (similar to Twitter) were encoded, measured, and analyzed. The major findings are as follows: (1) Tweet account type, tweet topic, and emotion object were all significantly related to emotion type. Tweet depth and objectivity were both positively affected by emotion type, and objectivity had a greater impact. (2) Account type, tweet topic, and emotion object were all significantly related to emotion intensity. When the depths were the same, emotion intensity became stronger with the decrease in objectivity. (3) Account type, tweet topic, emotion object, and emotion type were all significantly related to a user's emotion communication capacity. Tweet depth, objectivity, and user's emotion intensity were positively correlated with emotion communication capacity. Positive emotions had stronger communication capacities than negative ones, which is not consistent with previous studies. These findings help us to understand both theoretically and practically the changes and dissemination of user's emotions in a food safety and health information environment.