Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Liver/pathology , Inflammation/metabolism , Fibrosis , Macrophages/metabolism
RATIONALE: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal background mucosa, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time. Here, we present a case of neoplastic transformation of GHP in a context of autoimmune gastritis (AIG). PATIENT CONCERNS: In 2020, a 67-year-old woman was admitted for endoscopic review 6 years after gastric polyp resection, the histological diagnosis of gastric polyp was neoplastic transformation of GHP as before. The patient had undergone multiple polypectomies at the same part. Then histological examination revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. DIAGNOSES AND INTERVENTIONS: We further found that the background diagnosis was AIG. These results supported the diagnosis of neoplastic transformation of GHP in a context of AIG. With the doubt of missed diagnose, we retrospectively analyzed the medical history in 2014, 2015 and 2016, confirmed the presence of AIG. Unfortunately, serological tests and special treatment were not performed. OUTCOMES: The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. LESSONS: The purpose of this case report is to increase clinical awareness of neoplastic transformation of GHP in a context of AIG, and hope promise for early diagnosis and treatment.
Cell Transformation, Neoplastic , Aged , Humans , Retrospective Studies
Yinchen Linggui Zhugan decoction (YLZD) is an effective and classical traditional herbal prescription for treating the nonalcoholic fatty liver disease (NAFLD) and has been proven to be effective in the regulation of lipid metabolism disorder and attenuate inflammation for a NAFLD rat model. However, the exact underlying mechanism has not been elucidated. In the current study, a NAFLD rat model was established using a high-fat diet (HFD) for 10 weeks, followed by YLZD treatment with 1.92 g/kg/day for 4 weeks to explore the mechanisms of YLZD. Our results showed that YLZD decreased the hepatic lipid deposition, restored the liver tissue pathological lesions, inhibited the expression of oxidative stress, and decreased the inflammatory cytokines levels. Meanwhile, the genes and proteins expressions of SIRT1/Nrf2 signaling pathway together with downstream factors including HO-1 and NQO1 were elevated in the YLZD treated NAFLD rats. For further elaborating the upstream mechanism, short-chain fatty acids (SCFAs) in serum and feces were measured by liquid chromatograph mass spectrometer and gas chromatograph mass spectrometer, and the differences in gut microbiota of rats in each group were analyzed through high-throughput sequencing of 16S rRNA. The results demonstrated that the contents of butyric acid (BA) and total SCFAs in YLZD-treated NAFLD rats were significantly increased in serum and feces. 16S rRNA sequencing analysis illustrated that YLZD intervention led to a modification of the gut microbiota composition, with a decrease of Oribacterium, Lactobacillus and the ratio of Firmicutes/Bacteroides, as well as the increase in SCFAs-producing bacteria such as Christensenellaceae, Clostridia, Muribaculaceae, and Prevotellaceae. Spearman rank correlation analysis indicated that BA and total SCFAs were negatively co-related with oxidative stress-related factors and inflammatory cytokines, while they were positively co-related with SIRT1/Nrf2 pathway related genes and proteins. Furthermore, in vitro study confirmed that BA effectively reduced oxidative stress by activating SIRT1/Nrf2 signaling pathway in L02 cells. Together, the present data revealed YLZD could ameliorate HFD-induced NAFLD in rats by the modulation of SIRT1/Nrf2 signaling pathway and gut microbiota.
Objectives: Conventional approaches for patients with nonerosive gastroesophageal reflux disease (NERD) were not satisfactory. This study aimed to evaluate the effectiveness and mechanisms of Chinese herbal medicine Hewei Jiangni Decoction (HWJND) as a novel and promising regimen for NERD. Methods: A total of 128 patients with NERD were randomly assigned to the Treatment group and Control group. The patients from the Treatment group were administered HWJND (81 g) plus dummy omeprazole (20 mg) daily for 8 weeks, and the others were given dummy HWJND granules (81 g) plus omeprazole (20 mg). The clinical efficacy was assessed using the gastroesophageal reflux disease questionnaire (GERD-Q) scale, patient reported outcomes (PRO) scale, and short form health survey 36 (SF-36) scale at week 4. Moreover, its pharmacological and molecular mechanisms were elucidated based on network pharmacology and molecular docking. Results: Due to case shedding and other reasons, 109 patients, including 56 in the Treatment group and 53 in the Control group completed this study. Our results showed that HWJND significantly improved heartburn, regurgitation, epigastric pain, nausea, and sleep disturbance, which led to a significant reduction of GERD-Q scores in NERD patients. In addition, PRO scores of NERD patients with HWJND administration were improved, and sufficient relief of physical role, body pain, general health, social function, and mental health on the SF-36 scale was also observed in patients after HWJND treatment. We further showed that the curative effect of HWJND was close to that of omeprazole, except for the better improvement of general health and social function. What's more, the main active ingredients of HWJND included quercetin, beta-sitosterol, naringenin, baicalein, and kaempferol were retrieved, and the protective effects of HWJND against NERD may be closely related to targets such as TNF, IL6, IL1B, MMP9, CXCL8, and EGFR, which were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. Conclusion: Our findings demonstrate that HWJND is noninferior to oral omeprazole for the treatment of patients with NERD, plays a therapeutic role through multiple targets and diverse pathways, and holds promise for complementary and alternative therapy for the treatment of NERD. This trial is registered with http://www.chictr.org.cn, Chinese Clinical Trials Registry [ChiCTR2200055960].
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, characterized by excessive accumulation of hepatocyte fat. However, there is no exact and effective pharmacotherapy for NAFLD. Yinchen linggui zhugan decoction (YLZD) has been widely used to treat NAFLD. Nevertheless, its pharmacological and molecular mechanisms have not been clearly elucidated. This study was carried out to investigate the active components of YLZD and explore its potential mechanisms for treating NAFLD by network pharmacology and experimental verification. The results showed that a total of 120 active components of YLZD and 365 targets were retrieved through databases, and the main active ingredients of YLZD consisted of chlorogenic acid, emodin, aloe-emodin, rhein, and geniposide. KEGG enrichment analysis revealed fundamental roles of TNF, PI3K/AKT, HIF-1α, and insulin resistance signaling pathways in the treatment of NAFLD by YLZD. Moreover, our experimental verification results showed that YLZD improved the liver pathological and cholesterol level, and reduced the expressions of TNF-α, IL-1ß, IL-6, NF-κB, CCL2, and CXCL10 in NAFLD rats, which all belonged to TNF signaling pathway. The molecular docking confirmed the correlation between the four core components (chlorogenic acid, emodin, rhein, and geniposide) and key factors (TNF-α, IL-6, and NF-κB) in TNF signaling pathway. In conclusion, the present study systematically clarified the protective mechanisms of YLZD against NAFLD through targeting the TNF signaling pathway, and provided new ideas for the drug research of this disease.
Yinchen Linggui Zhugan Decoction (YCLGZGD) is the combination of Linggui Zhugan (LGZGD) and Yinchenhao (YCHD) decoctions, two famous traditional Chinese medicine prescriptions. In previous studies, we found that Yinchen Linggui Zhugan Decoction (YCLGZGD) could regulate lipid metabolism disorder and attenuate inflammation in pathological process of nonalcoholic fatty liver disease (NAFLD). However, the exact underlying mechanism remains unknown. The aim of this study was to explore the effect of Yinchen Linggui Zhugan Decoction on experimental NAFLD and its mechanism in rats with high-fat diet (HFD) which was established by 8-week administration of HFD. YCLGZGD, LGZGD, and YCHD were administered daily for 4 weeks, after which the rats were euthanized. The level of blood lipid, liver enzymes, H&E, and Oil Red O staining were determined to evaluate NAFLD severity. Western blotting and real-time polymerase chain reaction were, respectively, used to determine hepatic protein and gene expression of Keap1, Nrf2, NQO1, and HO-1. Oral YCLGZGD ameliorated HFD-induced NAFLD. Furthermore, YCLGZGD increased the protein and gene expression of Nrf2, NQO1, and HO-1 without changing Keap1. Overall, these results suggest that YCLGZGD ameliorates HFD-induced NAFLD in rats by upregulating the Nrf2/ARE signaling pathway.
OBJECTIVE: To observe the efficacy of Jinghuaweikang gelatin pearls plus proton pump inhibitor (PPI)-based triple regimen in the treatment of chronic atrophic gastritis (CAG) patients with Helicobacter pylori (H.pylori) infection. METHODS: For this multicenter, randomized, controlled clinical study, 90 patients of endoscopically confirmed CAG with positive H.pylori ((13)C or (14)C-urea breath test (UBT) or rapid urease test) were enrolled. There were 46 males and 44 females with an age range of (54 ± 10) years. None of them had H.pylori eradication background. They were randomly divided into 2 groups, Group LACJ (n = 45) received lansoprazole 30 mg+amoxicillin 1000 mg+clarithromycin 500 mg + jinghuaweikang gelatin pearls 240 mg, twice daily, for 10 days (d1-10) plus another 14 days (d11-24) only with jinghuaweikang gelatin pearls 240 mg, twice daily. Group LACB (n = 45) had standard quadruple regimen treatment: lansoprazole 30 mg+amoxicillin 1000 mg+clarithromycin 500 mg+bismuth potassium citrate 220 mg, twice daily for 10 days (d1-10). The status of H.pylori was detected by (13)C-UBT at least 28 days after therapy. RESULTS: The eradication rates in Groups LACJ and LACB were as follows: per-protocol (PP): 70.5% (31/44) and 83.3% (35/42), intention-to-treat (ITT): 68.9% (31/45) and 77.8% (35/45) (both P > 0.05). The symptomatic improvements of bloating in upper abdomen, belching and epigastric pain after treatment in both groups. And those in Group LACJ was higher than those of Group LACB, but no statistical difference existed between two groups (all P > 0.05). CONCLUSIONS: The efficacy of LACJ for the treatment of CAG patients with H.pylori infection is similar to LACB. And the symptomatic improvement of patients is better than LACB.
Drugs, Chinese Herbal/therapeutic use , Gastritis, Atrophic/drug therapy , Helicobacter Infections/drug therapy , Proton Pump Inhibitors/therapeutic use , Adult , Aged , Drug Therapy, Combination , Drugs, Chinese Herbal/administration & dosage , Female , Gastritis, Atrophic/microbiology , Helicobacter pylori , Humans , Male , Middle Aged , Prospective Studies , Proton Pump Inhibitors/administration & dosage
