[Process in the role of vasoactive intestinal peptide in the treatment of ulcerative colitis by regulating the balance of T follicular helper cells/T follicular regulatory cells].

Ulcerative colitis (UC) is an autoimmune disease based on the persistent damage of colonic mucosal barrier. It has been found that the abnormal expression of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells is closely related to the occurrence and development of UC. Tfh cells can secrete pro-inflammatory factors and assist B cells to produce antibodies, which can promote the development of UC, while Tfr cells can inhibit the activity of Tfh cells and secrete anti-inflammatory factors. How to regulate the balance between them has become one of the potential therapeutic targets of UC. Vasoactive intestinal peptide (VIP) has preventive and therapeutic effect on UC, and its mechanism is closely related to the regulation of Tfh/Tfr cell balance, which can provide help for the treatment of UC.

Xiaojianzhong decoction attenuates aspirin-induced gastric mucosal injury via the PI3K/AKT/mTOR/ULK1 and AMPK/ULK1 pathways.

CONTEXT: Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear. OBJECTIVE: To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed. RESULTS: The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa. DISCUSSION AND CONCLUSIONS: XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells.

BACKGROUND: Gastric precancerous lesions (GPL) precede the development of gastric cancer (GC). They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation, bacterial infection, and injury. Abnormalities in autophagy and glycolysis affect GPL progression, and their effective regulation can aid in GPL treatment and GC prevention. Xiaojianzhong decoction (XJZ) is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL. However, its specific mechanism of action is still unclear. AIM: To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs. METHODS: Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk. The rats' body weight was monitored every 2 wk starting from the beginning of modeling. Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining. Autophagy was observed using transmission electron microscopy. The expressions of autophagy, hypoxia, and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence. The expressions of the following proteins in gastric tissues: B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3 (Bnip-3), microtubule associated protein 1 light chain 3 (LC-3), moesin-like BCL2-interacting protein 1 (Beclin-1), phosphatidylinositol 3-kimase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), p53, AMP-activated protein kinase (AMPK), and Unc-51 like kinase 1 (ULK1) were detected using western blot. The relative expressions of autophagy, hypoxia, and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction. RESULTS: Treatment with XJZ increased the rats' body weight and improved GPL-related histopathological manifestations. It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3, Beclin-1, and LC-3II expressions, resulting in inhibition of autophagy. Moreover, XJZ down-regulated glycolysis-related monocarboxylate transporter (MCT1), MCT4, and CD147 expressions. XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia, activating the PI3K/AKT/mTOR pathway, inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation. In addition, XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression. CONCLUSION: This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/ AMPK/ULK1 signaling pathways, providing a feasible strategy for the GPL treatment.

Xiaojianzhong decoction attenuates gastric mucosal injury by activating the p62/Keap1/Nrf2 signaling pathway to inhibit ferroptosis.

Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and iron dynamics in gastric mucosal epithelial cells are present throughout the occurrence and development of gastric mucosal injury. Therefore, the inhibition of oxidative stress and ferroptosis is a potential target for the treatment of the gastric mucosal injury. Xiaojianzhong decoction (XJZ), which consists of six Chinese herbal medicines and extracts, is used for the treatment of diseases related to gastrointestinal mucosal injury; however, its specific mechanism of action has yet to be clarified. In this study, we clarified the protective effect of XJZ on gastric mucosa and revealed its underlying mechanism. We established a gastric mucosal injury model using aspirin and administered XJZ. Furthermore, we systematically evaluated the mucosal injury and examined the expression of genes related to oxidative stress, ferroptosis, and inflammation. The study found that XJZ significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Our study suggests that XJZ may inhibit aspirin induced oxidative stress and ferroptosis via the p62/Keap1/Nrf2 signaling pathway, thereby attenuating gastric mucosal injury.

[Experimental study on effects of berberine combined with 6-shogaol on intestinal inflammation and flora in mice with ulcerative colitis].

Cold-heat combination is a common method in the treatment of ulcerative colitis, which is represented by classic drug pair, Coptidis Rhizoma and Zingiberis Rhizoma.The present study explored the synergetic effects of berberine and 6-shogaol, the primary components of Coptidis Rhizoma and Zingiberis Rhizoma, respectively, on intestinal inflammation and intestinal flora in mice with ulcerative colitis to reveal the effect and mechanism of cold-heat combination in the treatment of ulcerative colitis.The ulcerative colitis model was induced by dextran sulfate sodium(DSS) in mice.The model mice were administered with berberine(100 mg·kg~(-1)), 6-shogaol(100 mg·kg~(-1)), and berberine(50 mg·kg~(-1)) combined 6-shogaol(50 mg·kg~(-1)) by gavage, once per day.After 20 days of drug administration, mouse serum, colon tissues, and feces were sampled.Hematoxylin-eosin(HE) staining was used to observe histopathological changes in colon tissues.Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to observe the changes in the mucus layer of colon tissues.Enzyme-linked immunosorbent assay(ELISA) was employed to detect the serum content of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6).Immunohistochemical method was adopted to detect the protein expression of macrophage surface markers F4/80, mucin-2, claudin-1, and zonula occludens-1(ZO-1) in colon tissues.High-throughput Meta-amplicon library sequencing was used to detect changes in the intestinal flora of mice.The results indicated that the 6-shogaol group, the berberine group, and the combination group showed significantly relieved intestinal injury, reduced number of F4/80-labeled positive macrophages in colon tissues, increased protein expression of mucin-2, claudin-1, and ZO-1, and decreased serum le-vels of TNF-α, IL-1ß, and IL-6.Shannon, Simpson, Chao, and Ace indexes of the intestinal flora of mice in the 6-shogaol group and the combination group significantly increased, and Chao and Ace indexes in the berberine group significantly increased.As revealed by the bioinformatics analysis of intestinal flora sequencing, the relative abundance of Verrucomicrobia at the phylum, class, and order levels decreased significantly in all treatment groups after drug administration, while that of Bacillibacteria gradually increased.In the 6-shogaol group and the combination group, Akkermansia muciniphila completely disappeared, but acid-producing bacillus still existed in large quantities.As concluded, both 6-shogaol and berberine can inhibit intestinal inflammation, reduce the infiltration and activation of macrophages, relieve intestinal damage, reduce intestinal permeability, improve the structure of flora, and promote intestinal microecological balance.The combined application of berberine and 6-shogaol has a significant synergistic effect.

CagA and VacA inhibit gastric mucosal epithelial cell autophagy and promote the progression of gastric precancerous lesions. / CagA和VacAæŠ‘åˆ¶èƒƒé»è†œä¸Šçš®ç»†èƒžçš„è‡ªå™¬å¹¶ä¿ƒè¿›èƒƒç™Œå‰ç— å˜çš„æ¶åŒ–.

Cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) are the keys to the pathogenic role of Helicobacter pylori and the high-risk factors for the progression of gastric precancerous lesions. Autophagy can stabilize the intracellular environment, resist Helicobacter pylori infection, prevent the accumulation of damaged DNA, and inhibit the proliferation of gastric precancerous variant cells. However, CagA and VacA can inhibit the activation of upstream signals of autophagy and the maturation of autophagy-lysosomes in various ways, thus inhibiting the autophagy of gastric mucosal cells in precancerous lesions of gastric cancer. This change can cause Helicobacter pylori to be unable to be effectively cleared by autophagy, so CagA and VacA can persist and promote the inflammation, oxidative stress, apoptosis of gastric mucosal tissue cells, and the glycolytic activity and proliferation of variant cells in gastric precancerous lesions and a series of malignant biological processes. In recent years, the research on drugs specifically inhibiting the activities of CagA and VacA has become a new direction for the prevention and treatment of Helicobacter pylori-related severe gastric diseases, and a variety of drugs or components that can precisely and effectively regulate the factors for the treatment of gastric precancerous lesions are emerged, which opens a new strategy for the treatment of gastric precancerous lesions in the future.

Treatment of ulcerative colitis with Wu-Mei-Wan by inhibiting intestinal inflammatory response and repairing damaged intestinal mucosa.

BACKGROUND: Wu-Mei-Wan (WMW), a traditional Chinese medicine, has been applied in the treatment of gastrointestinal diseases with long-term diarrhea and mucopurulent bloody stool as the main symptoms since ancient times. Studies have shown that WMW inhibits intestinal inflammation, repairs damaged intestinal mucosa, resists colon necrosis, and resists intestinal fibrosis. However, the specific mechanism of action is not yet clear. OBJECTIVE: Ulcerative colitis (UC), an intestinal disease with intestinal inflammation and injury as the main pathological manifestations, is one of the high-risk factors for colon cancer. Inhibiting the inflammatory response and promoting colonic epithelial repair are critical to the treatment of UC. However, there is still a lack of remedies with satisfactory curative effects. In this study, the role of WMW in dextran sulfate sodium (DSS)-induced colitis in mice and its related mechanisms are discussed from two aspects: intestinal inflammation and tissue repair. METHODS: DSS was used to induce colitis in mice and the therapeutic effect of WMW was analyzed by disease activity score, histopathological score, colon length measurement, serum cytokine detection, and flow cytometry. Macrophage activation and colonic stem cell proliferation were observed by immunohistochemistry. The expression of critical molecules in macrophage activation and colonic stem cell proliferation signaling pathways in colon tissue was detected with immunohistochemistry, immunofluorescence staining, RT-qPCR, and Western blot. RESULTS: WMW could significantly alleviate DSS-induced colitis. We showed that WMW could reduce disease activity, reduce pathological scores, limit weight loss, inhibit colon shortening, inhibit inflammatory factor secretion, attenuate inflammatory response, and promote the repair of damaged colonic epithelium. WMW inhibited the activation of colonic macrophages, and its mechanism might be inhibiting the Notch/NF-κB/NLRP3 pathway; WMW promoted the proliferation of colonic stem cells, and its mechanism was associated with the regulation of the Hippo/YAP signaling pathway. CONCLUSION: The results of this study suggested that WMW could treat UC via a mechanism that inhibited the intestinal inflammatory response and repaired damaged intestinal mucosa.

Wu-Mei-Wan Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization.

An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-α, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg-1, and TGF-ß1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-κB signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-κB and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis.

CircTP53 promotes colorectal cancer by acting as a miR-876-3p sponge to increase cyclin-dependent kinase-like 3 expression.

According to ceRNA theory, circular RNAs could regulate certain protein expression through targeting corresponding microRNAs to affect the progression of multiple diseases, including colorectal cancer. CircTP53 (hsa_circ_0107702), highly expressed in thyroid cancer tissues, could promote the proliferation of thyroid cancer. However, the function of circTP53 in colorectal cancer is still unclear. In our study, we found circTP53 was significantly up-regulated in colorectal cancer tissues from patients and in colorectal cell lines. Next, using colorectal cell lines, we confirmed that circTP53 promoted the proliferation, migration and invasion, and reduced the apoptotic rate. Furthermore, through bioinformatics analysis and experimental confirmation, we found circTP53 functioned as the sponge of miR-876-3p, and miR-876-3p reversed the phenotype of circTP53 on the facilitation of colorectal cancer. Additionally, we found circTP53 promoted the progression of colorectal cancer by elevating the expression of CDKL3. At last, we suggested that circTP53 knockdown could inhibit colorectal cancer progression in vivo. In conclusion, circTP53 was highly expressed in colorectal cancer tissues, and promoted colorectal cancer progression via modulating miR-876-3p/CDKL3 axis.

CircFAT1 promotes hepatocellular carcinoma progression via miR-30a-5p/REEP3 pathway.

As newly found non-coding RNAs, circular RNAs (circRNAs) are involved in multiple biological processes. Emerging evidence has illustrated the pivotal roles of circRNAs in various human cancers. However, the function of circFAT1 in hepatocellular carcinoma (HCC) remains largely unclear. In the present study, we found that circFAT1 expression is up-regulated in HCC tissues and cells. In addition, circFAT1 level is positively correlated with TNM stage and tumour size. To further explore the function of circFAT1 in HCC, in vitro and in vivo experiments were performed. The results show that circFAT1 inhibition reduces the proliferation and invasion of HCC cells and tumorigenesis in vivo, whereas REEP3 overexpression reverses these processes. In conclusion, circFAT1 sponges miR-30a-5p to regulate the expression of REEP3, thus promoting hepatocarcinogenesis. New HCC diagnosis or treatment strategies may be developed from circFAT1 as a target.

Glutamine relieves oxidative stress through PI3K/Akt signaling pathway in DSS-induced ulcerative colitis mice.

OBJECTIVES: Ulcerative colitis (UC) is a kind of complex immune disease, and a major cause of destruction of intestinal barrier and oxidative stress in this field. In this paper, glutamine (Gln) was believed to offer protection against oxidative stress injury in colitis mice. MATERIALS AND METHODS: Thirty mice were randomly assigned into control, model, LY294002 (PI3K/Akt inhibitor), Gln, Gln+LY294002 and 5-Aminosalicylic acid (5-ASA) groups. The mice in the experimental group drank 4% dextran sulfate sodium salt (DSS) for 7 consecutive days. The protective effect of Gln on oxidative stress was quantified by keeping colitis mice, involving Phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt)/mammalian target of Rapamycin (mTOR) signaling pathway, with different medications or distilled water through intragastric administration for 10 consecutive days. RESULTS: In vivo administration of Gln, LY294002 or 5-ASA was found to ameliorate the symptoms of colitis in mice, such as reduced growth, loose stools and stool bleeding; protected DSS-induced colitis mice from goblet cell loss, lymphocytosis, mucosal erosion, loss of crypts, and neutrophil infiltration; improved the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-XP); decreased the content of malondialdehyde (MDA); and inhibited the activation of PI3K/Akt signaling pathway. CONCLUSION: Administration of Gln to the DSS-induced colitis mice led to a clearly reduction in oxidative stress-induced injury. The Gln is confirmed as inhibiting the PI3K/Akt signaling pathway activity.

Curcumin Inhibits Hepatocellular Carcinoma via Regulating miR-21/TIMP3 Axis.

BACKGROUND/AIM: Curcumin exhibits anticancer effects against various types of cancer including hepatocellular carcinoma (HCC). miR-21 has been reported to be involved in the malignant biological properties of HCC. However, whether miR-21 plays a role in curcumin-mediated treatment of HCC is unknown. The purpose of this study was to identify the potential functions and mechanisms of miR-21 in curcumin-mediated treatment of HCC. METHODS: The anticancer effects of curcumin were assessed in vivo and in vitro. The underlying mechanism of miR-21 in curcumin-mediated treatment of HCC was assessed by quantitative real-time PCR (RT-qPCR), western blot, and Dual-Luciferase Reporter assays. RESULTS: The present study revealed that curcumin suppressed HCC growth in vivo and inhibited HCC cell proliferation and induced cell apoptosis in a dose-dependent manner in vitro. Meanwhile, the curcumin treatment can downregulate miR-21 expression, upregulate TIMP3 expression, and inhibit the TGF-ß1/smad3 signaling pathway. miR-21 inhibition enhanced the effect of curcumin on cell proliferation inhibition, apoptosis, and TGF-ß1/smad3 signaling pathway inhibition in HepG2 and HCCLM3 cells. It demonstrated that TIMP3 was a direct target gene of miR-21. Interestingly, the effect of miR-21 inhibition on cell proliferation, apoptosis, and TGF-ß1/smad3 signaling pathway in HepG2 and HCCLM3 cells exposed to curcumin was attenuated by TIMP3 silencing. CONCLUSION: Taken together, the present study suggests that miR-21 is involved in the anticancer activities of curcumin through targeting TIMP3, and the mechanism possibly refers to the inhibition of TGF-ß1/smad3 signaling pathway.

[Effects of 6-Shogaol on Notch signaling pathway in colonic epithelial cells of ulcerative colitis mice].

OBJECTIVE: To observe the regulatory effect of 6-Shogaol on Notch signal pathway in colonic epithelial cells of mice with ulcerative colitis. METHODS: Forty Kunming mice were randomly divided into normal group (n=10) and model group (n=30). The model of ulcerative colitis was induced by free drinking of 2% dextran sulfate sodium salt(DSS). After 15 days, the mice were divided into model group, 6-gingerenol group and positive control group with 10 mice in each group. Normal group and model group were treated with normal saline, 6-gingerenol group was treated with 6-Shogaol 100 mg/(kg·d), positive control group was treated with sulfasalazine 100 mg/(kg·d), for 20 days. The histopathological changes of colon were observed, and the expressions of Hes-1 and Math-1protein in colonic epithelial cells were detected by immunofluorescence double labeling method. The expressions of Notch-1, Hes-1 and Math-1 mRNA in colonic epithelial tissue were detected by RT-PCR. The expressions of Notch-1, Hes-1 and Math-1 protein in colonic epithelial tissue was detected by Western blot. RESULTS: Compared with the normal group, the expression of Notch-1 and Hes-1 protein and the relative expression of mRNA in colonic epithelium of model group were significantly increased (P＜0.01), while the relative expressions of Math-1 mRNA and protein were decreased significantly (P＜0.01). Compared with the model group, the expressions of Notch-1 and Hes-1 protein and the relative expression of mRNA in colonic epithelium of 6-Shogaol group and sulfasalazine group were decreased significantly(P＜0.01), while the relative expressions of Math-1 mRNA and protein were increased significantly(P＜0.01). CONCLUSION: 6-Shogaol can inhibit the over activation of Notch pathway and regulate the balance of differentiation between colonic epithelialabsorptive cell line and secretory cell line and repair damaged mucosal tissue.

[Predictive Value of Pancreatic Steatosis for Severity of Coronary Atherosclerosis in Patients with Type 2 Diabetes Mellitus].

Objective To investigate the association of pancreatic steatosis with coronary atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods Patients with T2DM who underwent coronary computed tomography angiography(CCTA)in our center due to chest pain were enrolled from January 2016 to February 2019. According to the CCTA findings,patients were divided into normal group,mild-to-moderate coronary atherosclerosis group and severe coronary atherosclerosis group. CT attenuation of pancreas and spleen was measured on abdominal non-enhanced CT,and the CT attenuation indexes including the difference between pancreatic and splenic attenuation (P-S) and the ratio of pancreas-to-spleen attenuation (P/S) were calculated. Analysis of variance or Kruskal-Wallis rank test were used to assess differences among each group. Logistic regression analysis was used to analyze the risk factors of severe coronary stenosis. The accuracy of P/S in predicting severe coronary artery stenosis was assessed by receiver operator characteristic (ROC) curve analysis. Results A total of 173 consecutive T2DM patients were enrolled. These patients included 27 patients with normal coronary artery (15.6%),124 patients with mild to moderate stenosis (71.7%),and 22 patients with severe stenosis (12.7%). There were significant differences in CT attenuation of pancreas (Z=11.543,P=0.003),P-S (Z=11.152,P=0.004) and P/S (Z=11.327,P=0.004) among normal coronary artery group,mild and moderate stenosis group,and severe stenosis group. The CT attenuation of pancreatic head,body,and tail significantly differed in patients with coronary artery stenosis (Z=14.737,P=0.001). After adjusting for confounding factors,multiple Logistic regression showed that P/S (OR=0.062,95%CI=0.008-0.487,P=0.008) was still significantly associated with the severe coronary artery stenosis. The area under the ROC curve of P/S for the diagnosis of severe coronary artery stenosis was 0.701,and the optimal cutoff point was 0.660. Conclusion CT attenuation of pancreas and CT attenuation indexes are associated with the severity of coronary stenosis in T2DM patients,suggesting that pancreatic steatosis may be used as one of the indicators for predicting severe coronary artery stenosis.

Circ_0001178 regulates miR-382/VEGFA axis to facilitate hepatocellular carcinoma progression.

Circular RNAs (circRNAs) have been reported to regulate the gene expression through sponging corresponding microRNAs in multiple malignant tumors, including hepatocellular carcinoma (HCC). Up to now, the effects of circ_0001178 in HCC are barely known. In our current work, we tested circ_0001178 expression in HCC tissues and HCC cells and found it was greatly elevated. Then, we evaluated the function of circ_0001178 on HCC cell proliferation. We found HepG2 and Huh-7 cell proliferation was repressed after circ_0001178 shRNA was infected into the cells. Moreover, flow cytometry evidenced that HepG2 and Huh-7 cell apoptosis was markedly triggered and cell cycle was arrested. Meanwhile, it was shown that HCC cell migration and invasion capacity were markedly inhibited by loss of circ_0001178. Knockdown of circ_0001178 restrained HCC tumor growth in vivo. Then, miR-382 was predicted and confirmed as the target of circ_0001178. Circ_0001178 was demonstrated to modulate miR-382 expression negatively. The effect of circ_0001178 on HCC tumor was rescued by miR-382 overexpression. Furthermore, vascular epithelial growth factor A (VEGFA) is identified in various cancers. Currently, VEGFA was proved to be the downstream target of miR-382. To conclude, this research revealed that circ_0001178 induced HCC progression via modulating miR-382 and VEGFA axis.

Long Non-coding RNA SNHG17 Upregulates RFX1 by Sponging miR-3180-3p and Promotes Cellular Function in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancer that is associated with poor quality of life in patients and a global health burden. The mechanisms involved in the development and progression of HCC remain poorly understood. METHODS: Hepatocellular carcinoma human samples and cell lines were subjected to qRT-PCR for expression assessment. CCK-8 assay, Transwell migration and invasion assay, were applied for cell function detection. Animal experiment was used to measure the function of SNHG17 on cell growth in vivo. Western blot was conducted to evaluate the level of EMT in cells. RIP, RNA pull-down and luciferase reporter assays were performed to assess the correlation between SNHG17, miR-3180-3p and RFX1. RESULTS: Our study demonstrated that SNHG17 was upregulated in HCC human samples and involved cell proliferation, migration, invasion progress. SNHG17 promoted HCC cell growth and metastasis in vivo. Furthermore, we investigated the downstream factor of SNHG17, SNHG17 acted as a molecular sponge for miR-3180-3p, and SNHG17 regulated RFX1 expression via miR-3180-3p. SNHG17 promotes tumor-like behavior in HCC cells via miR-3180-3p/RFX1. CONCLUSION: We determined RFX1 as the target of miR-3810-3p; SNHG17 enhanced the progression of HCC via the miR-3180-3p/RFX1 axis. Taken together, our findings may provide insight into the molecular mechanism involved in the progression of HCC and develop SNHG17 as a novel therapeutic target against HCC.

[Roumudan formulation attenuated liver fibrosis by inhibiting TGF-ß1/Smad4 pathway in mice].

Objective: To investigate underlying mechanism involving Roumudan(RMD) formulation (Z20160012) suppressed liver fibrosis induced by CCl4 injection in mice by inhibiting TGF-ß1/Smad4 pathway. Methods: Male BALB/c mice were randomly divided into control group, liver fibrosis model group and RMD-treated group(n=11). Mice in liver fibrosis model and RMD-treaded groups were injected intraperitoneally with CCl4 (20% in olive oil) at the dose of 2.5 mL/kg two times for one week and 5 mL/kg two times for 4 weeks. Mice in control group were treated intraperitoneally with the same volume of olive oil at the same time intervals. From sixth week, Mice in liver fibrosis model group were administrated with CCl4 (20% in olive oil, 1.5 ml/kg once per week) intraperitoneally and given distilled water by intragastric gavage. Mice in the RMD-treated group were administrated with CCl4 (20% in olive oil, 1.5 ml/kg/mouse once per week) intraperitoneally and given RMD(6.2 g/kg everyday) by intragastric gavage. Mice in the control group were administrated with olive oil (1.5 ml/kg/mouse once per week) intraperitoneally and given distilled water by intragastric gavage. The serum AST and ALT levels were estimated for assessment of liver function. The pathologic changes of mice' livers were examined by the HE, Masson, immunohistochemical staining, Western Blot, Q-PCR and so on. Results: After intraperitoneally injected with CCl4 in mice, the pathological characteristics of liver fibrosis were observed compared with the control group at the sixth week. Compared with the liver fibrosis model group, RMD improved the liver function significantly through reducing liver index(P＜0.01) and the levels of ALT(P＜0.01), AST(P＜0.01) and HYP(P＜0.05). The expression of TGF-ß1(P＜0.05), α-SMA(P＜0.05), COL1A1(P＜0.01) and COL3A1(P＜0.01) were decreased by RMD. The positive expression area of Smad4 mRNA in RMD treated group was lower than that in liver fibrosis model group. Conclusion: The RMD formulation could attenuate liver fibrosis by inhibiting TGF-ß1/Smad4 pathway and extracellular matrix (ECM) production in mice.

[Progress in the study of macrophage activation and ulcerative colitis from the Notch/NF-κB/NLRP3 signaling pathway].

Ulcerative colitis is an intestinal inflammatory disease characterized by diarrhea, abdominal pain and purulent stool. Uncontrolled inflammation caused by macrophage hyper-activation is an important cause of ulcerative colitis. Therefore, inhibiting macrophage hyper-activation is an effective way to treat ulcerative colitis. Notch signaling pathway is involved in regulating the immune response of macrophages and promoting inflammation. NF-κB signaling pathway is the "star pathway" involved in inflammation. NLRP3 inflammatory body is involved in the activation of macrophages. Notch, NF-κB and NLRP3 inflammatory bodies constitute the upstream and downstream signal pathways in the existing immune inflammatory diseases. Notch signal pathway can regulate the activation of macrophage via NF-κB/NLRP3 inflammatory body signaling pathway.

[An analysis of clinical factors for coronary artery calcification score].

OBJECTIVE: To evaluate the correlating clinical factors of coronary artery calcification score (CACS). METHODS: 141 patients suspected of coronary artery disease were included. They underwent multi-slice row computed tomography, pulse wave velocity (PWV), UCG and blood biochemistry within a period of 3 months. The subjects were divided into three groups according to CAC score: A (CACS = 0 - 10), B (CACS = 11 - 400), C (CACS > 400). RESULTS: CACS was significantly associated with age, history of hypertension and diabetes mellitus. It was also associated with the presence of mitral annular calcification and aortic valve calcification, low ankle brachial pressure index (ABI) and high mean artery pressure (MAP) as well as high values of brachial ankle PWV (baPWV) and Upstroke time (UT). Multifactorial logistic regression analysis showed that the presence of aortic valve calcification and mitral annular calcification, the history of diabetes mellitus and high value of UT were independently correlated with severe coronary artery calcification. CONCLUSIONS: Aortic valve calcification, mitral annular calcification, history of diabetes mellitus, high value of UT were independently correlated with severe coronary artery calcification. Measurement of PWV and UCG should be performed before multi-slicerow computed tomography, because the assessment of coronary artery lumen narrowing with multi-slice row computed tomography can not be carried out accurately in the presence of severe coronary artery calcification.