BACKGROUND:It has been elucidated that downregulation of nuclear enriched abundant transcript 1(NEAT1)inhibits the progression of keloid fibroblasts,but the exact mechanism is not fully understood. OBJECTIVE:To investigate the influences of long non-coding RNA nuclear enriched abundant transcript 1(lncRNA NEAT1)on the proliferation,apoptosis and migration of keloid fibroblasts by regulating the miR-136-5p/ubiquitin-specific protease 4(USP4)axis. METHODS:Keloid fibroblasts were divided into five groups:si-NC group,control check group,si-NEAT1 group,si-NEAT1+miR-136-5p inhibitor group,and si-NEAT1+inhibitor-NC group.qRT-PCR was performed to measure the expressions of NEAT1 and miR-136-5p;cell counting kit-8 assay and EDU staining were performed to measure cell proliferation;flow cytometry was performed to measure apoptosis;scratch-healing experiment was performed to measure cell migration;western blot assay was performed to measure the protein expressions of USP4,p27,Bax,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain;dual-luciferase assay was performed to examine the relationship of NEAT1 with miR-136-5p as well as the relationship of miR-136-5p with USP4. RESULTS AND CONCLUSION:Compared with the si-NC group,the NEAT1 expression,absorbance value at 450 nm,percentage of EDU positive cells,scratch-healing rate,the protein expressions of USP4,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain decreased in the si-NEAT1 group(P<0.05),while the expression of miR-136-5p,apoptosis rate,and the protein expressions of p27 and Bax increased(P<0.05).miR-136-5p inhibitor reversed the effect of silencing NEAT1 on the biological behavior of keloid fibroblasts.There was a targeted regulatory relationship between NEAT1 and miR-136-5p as well as between miR-136-5p and USP4.To conclude,silencing NEAT1 may inhibit the proliferation and migration of keloid fibroblasts and induce apoptosis by regulating the miR-136-5p/USP4 axis..

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway. METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression. The successfully modeled rats were randomly divided into model group， positive control group （0.18 g/kg metformin and 1.8 mg/kg fluoxetine， gavage）， curcumin low-dose and high-dose groups （30， 60 mg/kg， gavage） and curcumin high-dose+CREB inhibitor group [60 mg/kg curcumin （gavage）+5 mg/kg CREB inhibitor 666-15 （intraperitoneal injection）]， with 12 rats in each group. Another 12 healthy rats were selected as the normal group. Each group was given a corresponding intervention for 4 weeks， the fasting blood glucose level of rats was detected， and the depression of rats was assessed. The levels of corticosterone （CORT） and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin- 1β （IL-1β）， IL-6] in serum， and the levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT） in hippocampal tissue were determined. The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group； the expression levels of CREB， BDNF mRNA and protein in hippocampal tissue were detected. RESULTS Compared with the normal group， the hippocampal tissue of rats in the model group was severely damaged， and neurons were scattered， while the fasting blood glucose， the forced swimming immobility time， the tail suspension immobility time， serum levels of CORT， TNF-α， IL-1β and IL-6， and neuron apoptosis indexes were all increased or prolonged significantly （P＜0.05）. The levels of NE and 5-HT， the number of surviving neurons， and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly （P＜0.05）. Compared with the 的model group， the damage to hippocampal tissue was relieved in the positive control group and curcumin groups， while the above indexes were improved significantly （P＜0.05）. The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group （P＜0.05）. CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats （P＜0.05）. CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression， and relieve neuronal damage and inflammatory response， the mechanism of which may be associated with activating CREB/BDNF signaling pathway.

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Helicobacter pylori (Hp) is a unipolar, microaerobic, multiflagellar, spiral-shaped Gram-negative bacterium that survives and colonizes human gastric mucosa. As a classⅠcarcinogen associated with gastric cancer, long-term stimulation of gastric mucosa by Hp can cause atrophic gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It has been reported that Hp can cause epithelial-mesenchymal transition (EMT) in gastric epithelial cells, thereby inducing gastric cancer. We review the mechanism of Hp-induced EMT in gastric epithelial cells, in order to provide new insights for early diagnosis and targeted therapy of gastric cancer.

  Objective  To establish a model that can predict the occurrence of acute kidney disease (AKD) in liver cirrhotic patients and evaluate its performance.  Methods  Liver cirrhotic patients who hospitalized in the department of gastroenterology of the First Hospital of Lanzhou University from January 2017 to January 2022 were retrospectively included. They were divided into AKD and non-AKD groups according to whether they were combined with AKD during hospitalization, and were randomized into training and validation sets in a 7∶3 ratio. The clinical data of patients in the two groups were collected, and LASSO regression and multifactorial Logistic regression were used to screen the influencing factors for the occurrence of AKD in patients with liver cirrhosis and to establish a prediction model. The model was then evaluated by using the receiver operating characteristic curve, the calibration curve and the clinical decision curve.  Results  A total of 796 cases of liver cirrhotic patients who met the inclusion and exclusion criteria were enrolled. Among them, 103 cases were in the AKD group and 693 cases were in the non-AKD group; 561 cases were in the training set and 235 cases were in the validation set. The results of LASSO regression and multifactorial Logistic regression showed that a history of diabetes (OR=2.922, 95% CI: 1.290-6.564, P=0.009), hepatic encephalopathy (OR=6.210, 95% CI: 2.278-17.479, P < 0.001), gastrointestinal bleeding (OR=2.501, 95% CI: 1.236-5.073, P=0.011), ascites (OR=3.219, 95% CI: 1.664-6.539, P < 0.001), male (OR=0.477, 95% CI: 0.254-0.879, P=0.019), hemoglobin (OR=0.987, 95% CI: 0.975-0.999, P=0.044), albumin (OR=0.952, 95% CI: 0.911-0.991, P=0.023), and prothrombin time (OR=0.865, 95% CI: 0.779-0.920, P < 0.001) were the independent influences on the occurrence of AKD in liver cirrhotic patients, and were used to construct a prediction model. The area under the curve of the model in the training set and validation set for predicting the occurrence of AKD in liver cirrhotic patients was 0.895 (95% CI: 0.865-0.925) and 0.869 (95% CI: 0.807-0.930), respectively. The calibration curves showed that the model had good fit and consistency and the clinical decision curves showed that the use of the model for predicting the risk of AKD could benefit liver cirrhotic patients overall.  Conclusions  A prediction model for the occurrence of AKD in liver cirrhotic patients was established based on eight influencing factors, including gender, history of diabetes, and hepatic encephalopathy. It was validated to have good discrimination, calibration, and clinical utility, and is expected to assist in the clinical early screening and identification of liver cirrhosis-associated AKD.

Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.