Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) is steadily increasing in China, becoming the second leading cause of AP. Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies. HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components. However, the impact of metabolic syndrome components on HTG-AP clinical outcomes remains unclear. AIM: To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP. METHODS: In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University, we collected data on patient demographics, clinical scores, complications, and clinical outcomes. Subsequently, we analyzed the influence of the presence and number of individual metabolic syndrome components, including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), on the aforementioned parameters in HTG-AP patients. RESULTS: This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP, with low HDL-C being the most significant risk factor for clinical outcomes. The risk of complications increased with the number of metabolic syndrome components. Adjusted for age and sex, patients with high-component metabolic syndrome had significantly higher risks of renal failure [odds ratio (OR) = 3.02, 95%CI: 1.12-8.11)], SAP (OR = 5.05, 95%CI: 2.04-12.49), and intensive care unit admission (OR = 6.41, 95%CI: 2.42-16.97) compared to those without metabolic syndrome. CONCLUSION: The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTG-AP, making it crucial to monitor these components for effective disease management.

The food preservative sodium propionate induces hyperglycaemic state and neurological disorder in zebrafish.

Propionate is an effective mould inhibitor widely used as a food preservative. In this study, we used zebrafish to explore the adverse effects of long-term exposure to low concentrations of sodium propionate and the underlying molecular mechanisms (from larvae to adult). When exposed for 3 months, we found that blood glucose, total cholesterol, and triglyceride levels increased, and zebrafish developed a hyperglycaemic state. New tank test results showed depression in zebrafish reduced 5-hydroxytryptamine levels in the brain and damaged the dopamine system. At the same time, the results of the color preference test showed that zebrafish had cognitive impairments. In addition, Hypothalamic-Pituitary-Adrenal axis analysis revealed abnormal gene expression, increased cortisol levels, and reduced glucocorticoid receptor mRNA levels, which were consistent with depressive behavior. We also observed abnormal transcription of inflammatory and apoptotic factors. Overall, we found that chronic exposure to sodium propionate induces depressive symptoms. This may be related to the activation of the HPA axis by the hyperglycaemic state, thereby inducing inflammation and disrupting the dopaminergic system. In summary, this study provides theoretical and technical support for the overlap of the emotional pathogenesis associated with diabetes.

SphK1-driven autophagy potentiates focal adhesion paxillin-mediated metastasis in colorectal cancer.

Invasion and metastasis are the main causes of colorectal cancer (CRC)-related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1-driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p-paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p-paxillin, MMP-2, and vimentin was enhanced in SphK1-overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E-cadherin was suppressed in SphK1-overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1-overexpressed CRC cells, indicated that SphK1-driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1-driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation.

Sphingosine kinase 1 promotes the metastasis of colorectal cancer by inducing the epithelial­mesenchymal transition mediated by the FAK/AKT/MMPs axis.

It was demonstrated that Sphingosine kinase 1 (SphK1) promotes tumor progression and confers the malignancy phenotype of colorectal cancer by activating the focal adhesion kinase (FAK) pathway. However, further clarification is required to determine if SphK1 promotes the metastasis of colorectal cancer by inducing epithelial­mesenchymal transition (EMT), and its mechanisms have not been fully elucidated. Immunohistochemistry staining was used to detect protein expression in normal colonic mucosa tissues and colorectal cancer tissues. Cells were transfected to overexpress SphK1, downregulate SphK1 or downregulate FAK. An MTT assay was used to detect the drug toxicity to cells. Transwell and wound healing assays were used to detect cell migration ability. Reverse transcription­polymerase chain reaction and western blot analysis were used to detect the expression of mRNA and protein, respectively. Scanning electron microscopy was used to observe the microvilli and pseudopodia of the cells. The analysis of protein expression in 114 human colorectal cancer tissues demonstrated that the expressions of SphK1, FAK, phosphorylated (p)­FAK, E­cadherin and vimentin were associated with the metastasis of colorectal cancer. Furthermore, the patients with colorectal cancer with SphK1­positive cancer demonstrated poorer prognosis compared with SphK1­negative cancer. FAK knockdown and SphK1 knockdown of human colon cancer RKO cells inhibited the EMT and migrational potency, along with the expression of p­FAK, p­protein kinase B (AKT) and matrix metalloproteinase (MMP)2/9. In contrast, SphK1 overexpression promoted EMT, migrational potency, and the expression of p­FAK, p­AKT and MMP2/9 in HT29 cells. Additionally, the EMT and migrational potency of SphK1­overexpressing HT29 cells was suppressed by a FAK inhibitor, and the expression of p­FAK, p­AKT and MMP2/9 was suppressed by blocking the FAK pathway. In conclusion, SphK1 promoted the migration and metastasis of colon cancer by inducing EMT mediated by the FAK/AKT/MMPs axis.

NIK­ and IKKß­binding protein contributes to gastric cancer chemoresistance by promoting epithelial­mesenchymal transition through the NF­κB signaling pathway.

Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK­ and IKKß­binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex 9) is a regulator of the cytokine­induced NF­κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies. Nevertheless, it is still ambiguous whether NIBP is involved in the chemoresistance of gastric cancer. The aim of the present study was to investigate the effect of NIBP on chemotherapy resistance of gastric cancer (GC) and to research the mechanisms of Ginkgo biloba extract 761 (EGb 761®) on reversing chemoresistence which has been confirmed in our previous study. In the present study, the results of immumohistochemisty revealed that the positive staining rates of NIBP, NF­κB p65 and NF­κB p­p65 in gastric cancer tissues were obviously higher than those in normal tissues. Furthermore, a close correlation was found to exist between the expression of NIBP and NF­κB p65 (p­p65) in gastric cancer tissues. Moreover, the overexpression of NIBP was closely related to tumor differentiation, depth of invasion, clinical stage and lymphatic metastasis in gastric cancer. Western blot analysis, real­time PCR, MTT assay and flow cytometric analysis were performed and the results demonstrated that compared with the gastric cancer SGC­7901 cells, the expression of NIBP, NF­κB p65, NF­κB p­p65 and mesenchymal marker vimentin were significantly increased in gastric cancer multidrug­resistant SGC­7901/CDDP cells, and the epithelial cell marker ZO­1 was significantly decreased. Meanwhile, it was found that SGC­7901/CDDP cells were accompanied by spindle­like mesenchymal appearance and upregulation of stem cell marker CD133 which has been verified to be an upstream regulatory gene of epithelial­mesenchymal transition (EMT). Further research confirmed that downregulation of NIBP by Ginkgo biloba extract (EGb) 761 EGb 761 suppressed the cis­diamminedichloroplatinum(II) (CDDP)­induced NF­κB signaling pathway, EMT and the expression of CD133 in SGC­7901 and SGC­7901/CDDP cells. Altogether, these data indicate that the NIBP­regulated NF­κB signaling pathway plays a pivotal role in the chemoresistance of gastric cancer by promoting CD133­induced EMT.

[Establishment of a SD rat model of vulvar lichen simplex chronicus and detection of the expression of protease activated receptor 2].

OBJECTIVE: To establish a SD rat model of vulvar lichen simplex chronicus (LSC) and investigate the expression of protease activated receptor 2 (PAR2) in the genital skin. METHODS: Seventy female SD rats were randomly divided into group A (blank control group, n=10), group B (with application of acetone solution 3 times per week for 10 weeks, n=10), group C (with chronic mechanical irritation 3 times per week for 10 weeks, n=10), and group D (with topical treatment with 0.5= 7,12-Dimethylbenzanthracene [DMBA] in acetone solution and chronic mechanical irritation 3 times per week for 10 weeks, n=40). The changes of the genital skin changes were observed regularly and the expression of PAR2 in groups A and D was detected with immunohistochemistry, Western blotting and qRT-PCR. RESULTS: In group D, LSC occurred in 23 rats (57.5=) at 8 weeks and in 38 rats (95=) at 10 weeks; 8 rats (20=) showed papilloma at 12 weeks. Acetone treatment or chronic mechanical irritation did not cause LSC in the rats. Immunohistochemistry, Western blotting and qRT-PCR showed significantly increased expressions of PAR2 in group D at both the protein and mRNA levels as compared with those in group A (P<0.05). CONCLUSION: 0.5= DMBA in acetone solution along with chronic mechanical irritation can induce LSC in female SD rats, and PAR2 is closely related with the occurrence and progression of LSC.