Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Spontaneous spinal epidural hematoma(SSEH)is a rare clinical disease characterized by acute onset of neck,shoulder,or lumbar back pain accompanied by compression of the spinal nerve roots or spinal cord.This article reports a 71 year old female patient with SSEH who was admitted to the hospital with"neck and shoulder pain accompanied by right limb weakness for 3 hours",and was diagnosed with SSEH by cervical magnetic resonance imaging(MRI).After drug treatment,the patient achieved good clinical outcomes.The early symptoms of SSEH lack specificity and are prone to misdiagnosis or missed diagnosis.This case report discribe its diagnosis and treatment strategies in combination of relevant literature in order to improve clinical workers'understanding and diagnosis and treatment capabilities of this disease.

Objective:To evaluate the value of the skeletal muscle index (SMI) and psoas major muscle index(PMI) measured at the third lumbar vertebra(L3) level in the evaluation on nutritional status and prognosis of cirrhosis patients with ascites.Methods:The clinical data of 102 patients with cirrhosis and ascites treated in our department between September 2018 and September 2022 was analyzed retrospectively, the skeletal muscle and psoas muscle area at L3 level were measured, and L3-SMI and L3-PMI were calculated. According to L3-SMI, patients were divided into the sarcopenia group (62 cases) and the normal muscle mass group (40 cases). Differences between the two groups were compared in terms of L3-SMI, L3-PMI, body mass index (BMI), albumin, the rate of re-admissions and mortality during follow-up. The value of each index in nutritional assessment was also explored.Results:L3-SMI, L3-PMI, and albumin in the sarcopenia group were significantly lower than those in the normal muscle mass group, with statistical significance ( P<0.01).The BMI of the sarcopenia group was lower than that of the normal muscle mass group, but the difference was not significant ( P>0.05). L3-PMI showed better performance in nutritional assessment compared with albumin and BMI. The rate of re-admissions and the mortality rate in the sarcopenia group during the follow-up period were significantly higher compared with the normal muscle mass group ( P<0.05). Conclusion:L3-SMI and L3-PMI can effectively reflect the nutritional status of cirrhosis patients with ascites, and are promising indicators for prognosis prediction in cirrhosis patients with ascites.

Spontaneous spinal epidural hematoma(SSEH)is a rare clinical disease characterized by acute onset of neck,shoulder,or lumbar back pain accompanied by compression of the spinal nerve roots or spinal cord.This article reports a 71 year old female patient with SSEH who was admitted to the hospital with"neck and shoulder pain accompanied by right limb weakness for 3 hours",and was diagnosed with SSEH by cervical magnetic resonance imaging(MRI).After drug treatment,the patient achieved good clinical outcomes.The early symptoms of SSEH lack specificity and are prone to misdiagnosis or missed diagnosis.This case report discribe its diagnosis and treatment strategies in combination of relevant literature in order to improve clinical workers'understanding and diagnosis and treatment capabilities of this disease.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

Objective This study aims to investigate the effects of high-fat diet rich in perilla oil on the expression of key genes that regulate hepatic VLDL synthesis in obese rats .Methods Sixty healthy male 5-week old SD rats were randomly divided into 2 groups.The rats in the normal control group (NC, n=12) were given normal diet, and the rats in the high fat group ( HF, n=48) were given a pure high fat diet in order to induce rat models of obesity .In the intervention period, the obesity model rats were randomly divided into 4 subgroups including consistent high fat group (CHF) and three intervention groups depending on perilla oil substitution rate of lard in CHF:20%PO, 50%PO and 100%PO.The serum triglyceride (TG) of the rats was measured after 4 weeks.Real-time PCR was applied to measure microsomal triglyceride transfer protein ( Mtp) and apolipoprotein B ( Apob) mRNA, and western blot assay was used for detecting the expression of MTP and APOB in the liver .Results Compared with the NC group , the CHF rats exhibited significantly high fat deposi-tion.The serum TG was markedly higher and the MTP and APOB were decreased at gene and protein levels in the CHF group compared with the NC group .After the intervention , PO remarkably reduced the level of serum TG and decreased he-patic fat deposition as it showed by pathological examination .At the gene and protein levels , MTP and APOB were upregu-lated by PO to different degrees .Conclusions All the three PO intervention can promote VLDL synthesis and secretion , and decrease the hepatic fat deposition in the obese rats .Furthermore , PO upregulates the expression of MTP at gene and protein levels in a dose-dependent manner .

Objective This study aims to investigate the effects of high-fat diet rich in perilla oil on the insulin sensitivity-related gene expression in skeletal muscle in insulin resistant rats.Methods The insulin resistant ( IR) rat models were randomly divided into 2 groups, including high fat group ( HF) and perilla oil ( PO) intervention group fed with 20%substitution of lard energy in the HF.The insulin sensitivity of rats was measured after 4 weeks.Theα-linolenic acid ( ALA) content of PO in the rat plasma were analyzed by gas chromatograph.Real-time PCR was applied to measure glucose transporter 4 ( GLUT4 ) and insulin receptor substrate-1 ( IRS-1 ) mRNA, and Western blot assay was used for detecting the expression of GLUT4 and IRS-1 in the skeletal muscle.Results At the gene and protein levels, PO remarkably reduced the level of IRS-1 and upregulated the level of GLUT4 with increasing intake of ALA and serum ALA content in IR rats.The results of hyperinsulinemic-euglycemic clamp test showed no significant difference between the two groups.Conclusions The results of our study suggest that consumption of n-3 PUFA at levels that can typically be found in the diet fed to IR rats in the form of ALA (0.556 g/d) may not improve insulin sensitivity, even though regulating the expression of GLUT4 and IRS-1 in the skeletal muscle.