Correlations between serum trypsinogen-2 and pancreatic cancer.

BACKGROUND/AIMS: To investigate associations be- tween serum trypsinogen-2, pancreatitis and pancreatic cancer (PC) and determine cutoff values for PC diagnosis. METHODOLOGY: We recruited 88 patients from Internal Medicine/Surgical Departments of General Military Hospital of Beijing PLA between 12/2009 and 6/2010. Serum samples were collected preoperatively from 23 PC patients, 30 pancreatitis patients and 35 healthy controls. Enzyme-linked immunosorbent assay was used to detect trypsinogen-2 semiquantitatively. RESULTS: Serum trypsinogen-2 levels of PC and pancreatitis patients were significantly higher than those of controls (51.2 ± 80.3, 107.7 ± 98.1 vs. 1.0 ± 0.5, p = 0.03, p < 0.001) and significantly higher in pancreatitis vs. PC patients (107.7 ± 98.1 vs. 51.2 ± 80.3, p = 0.01). Higher Balthazar CT grades correlated with higher trypsinogen-2 in pancreatitis group. ROC curves for trypsinogen-2 revealed optimal cutoff value 1.8 as lower PC detection limit with 95.7% sensitivity and 91.4% specificity, and optimal cutoff value 19.9 for upper PC detection limit with 87.0% sensitivity and 97.1% specificity. Trypsinogen-2 levels correlated with pancreatic injury level. An AUC of 0.73 (95% Cl: 0.59-0.84, p = 0.002) distinguished PC from pancreatitis. CONCLUSION: Serum trypsinogen-2 is associated with PC and pancreatitis. Levels between 1.8 µg/L and 19.9 µg/L strongly suggest PC. Detection of serum trypsinogen-2 may provide simple, sensitive, specific non-invasive initial screening for early PC diagnosis.

Integrating Bioinformatics and Drug Sensitivity Analyses to Identify Molecular Characteristics Associated with Targeting Necroptosis in Breast Cancer and their Clinical Prognostic Significance.

BACKGROUND: Breast cancer accounts for over 1.8 million new cases worldwide annually, and prompt diagnosis and treatment are imperative to prevent mortality. Necroptosis, a form of programmed cell death, is thought to be a critical pathway for cancer cell apoptosis, yet, its relationship with breast cancer progression and molecular mechanisms remains largely unexplored. OBJECTIVES: Our study aims to investigate the molecular characteristics and clinical prognostic value of necroptosis-related genes in breast cancer using a comprehensive approach that involves integrated bioinformatics analysis along with drug sensitivity assessment. METHODS: Transcriptional, clinical, and tumor mutation burden (TMB) data related to breast cancer from the TCGA and GEO databases were integrated, and the necroptosis gene set was downloaded from the GSEA website for analysis. The screening conditions were set as adjusted P<0.05 and |log2FC(fold change)|>0.585 to screen for differential expression genes related to breast cancer necroptosis. Survival prognosis analysis was conducted on breast cancer necroptosis genes. Further analysis was conducted on prognosis-related necroptosis genes, including immune infiltration analysis and GO/KEGG enrichment analysis, to explore the potential biological functions and signaling pathway mechanisms of breast cancer necroptosis genes. Drug sensitivity screening was conducted on the prognosis-related necroptosis to identify potential drugs that target the promotion of necroptosis gene expression, and ultimately, single-gene analysis was performed on the core target genes obtained. RESULTS: Through integrated bioinformatics analysis, 29 differentially expressed mRNAs related to BRCA-Necroptosis were identified, including 18 upregulated mRNAs and 11 downregulated mRNAs. In addition, single-factor analysis of differential genes showed that the expression of HSPA4, PLK1, TNFRSF1B, FLT3, and LEF1 was closely related to BRCA survival prognosis. Based on the expression of these genes, a breast cancer prognosis model was constructed, and it was found that the area under the curve (AUC) of the curve of the risk genes for necroptosis was the largest, indicating that these genes have a certain clinical predictive significance for the occurrence and prognosis of BRCA. Additionally, there were significant differences in clinical characteristics of BRCA patients with different necroptosis gene expressions. Furthermore, GSVA and immune infiltration analysis revealed that Necroptosis-DEGs mainly affect the occurrence and progression of BRCA by participating in immune functions such as APC co-inhibition, APC co-stimulation, CCR, checkpoint, as well as infiltrating immune cells such as B cells naive, plasma cells, and T cells CD8. Moreover, the necroptosis gene group column chart indicated a 1-year survival rate of 0.979, a 3-year survival rate of 0.883, and a 5-year survival rate of 0.774. The necroptosis gene group and column chart are important indicators for evaluating BRCA prognosis. Finally, drug sensitivity screening of BRCA-Necroptosis genes showed that compounds such as A-770041, AC220, AP-24534, Bexarotene, and BMS-509744 have certain effects as potential targeted drugs for the treatment of BRCA necroptosis genes. CONCLUSION: Necroptosis genes are implicated in the pathogenesis and progression of breast cancer and are thought to impact the prognosis and response to drug treatments in individuals with BRCA. Consequently, understanding the role of these genes in breast cancer may aid in identifying more precise and efficacious therapeutic targets.

U-shaped association between online information exchange and app usage frequency: a large-scale survey of China 's online young and middle-aged people with pre diabetes and diabetes.

Background: China has the world's largest diabetic population, and the cost of caring for all these people every day is substantial. Online information exchange and app usage frequency have been demonstrated to play a significant influence in the management of blood glucose and enhancement of diabetes-related quality of life. However, the association between online information exchange and app usage frequency among actual online populations remains unclear and deserves additional study. Therefore, we evaluated the factors affecting the frequency of app usage in the online glucose management population, with a particular emphasis on the connection between online information exchange and app use frequency, contributing to the expansion of the research of diabetes management models. Method: This cross-sectional study was conducted by disseminating questionnaires in blood glucose management-related forums and WeChat groups and included 1586 online users concerned about blood glucose management. Information exchange and app usage frequency were considered as independent and dependent variables, respectively. We performed stratified and single factor analysis, multiple equation regression analysis, smooth curve fitting, and threshold effect and saturation effect analysis. R (version 4.1.3, http://www.Rproject.org) and EmpowerStats were used for data analysis. Result: After adjusting for other covariates, information exchange was independently and positively associated with app use frequency (ß = 8.6, 95% CI: 6.5 to 11.2, p < 0.001). Through interaction analysis, the most significant interaction factors influencing the relationship between information exchange and app usage frequency were identified as health insurance status, whether living with parents, glycated hemoglobin status in the previous month, and self-monitoring of blood glucose (SMBG). The association between information exchange and app usage frequency is U-shaped, with information exchange inflection points of 3.0 and 4.2. Information exchange and app usage frequency are negatively correlated when the average information exchange score is less than 3.0, and for every point increase in the average information exchange score, the likelihood of the app high usage frequency group compared to the app low usage frequency group decreases by 70%. The relationship between information exchange and app usage frequency is strongest when it is greater than or equal to 3.0 and less than or equal to 4.2. The probability of the app high usage frequency group occurring compared to the app low usage frequency group rises 17.3 times for every 1 point increase in the average information exchange score. The probability of the app high usage frequency group occurring in comparison to the app low usage frequency group increased by 1.8 times for every 1 point rise in information exchange when the average information exchange score was higher than 4.2. Conclusion: Age, body mass index, married, living with parents, hemoglobin level, SMBG, and information exchange were positively connected with app usage frequency in our study of online blood glucose management population. The link between information exchange and app use frequency was significantly U-shaped. The app usage frequency changed the most with the rise in information exchange when the information exchange score was greater than or equal to 3.0 and less than or equal to 4.2. Therefore, we ought to offer effort to concentrate on and increase the health-related behaviors and activities of those in this score interval.

Shugan Huoxue Huayu Fang attenuates carbon tetrachloride-induced hepatic fibrosis in rats by inhibiting transforming growth factor-ß1/Smad signaling.

OBJECTIVE: To investigate the potential mechanism by which Shugan Huoxue Huayu Fang (SGHXHYF) ameliorates liver fibrosis. METHODS: Liver fibrosis was induced in rats by intraperitoneal injection of carbon tetrachloride (CCl4) in peanut oil solution (40%, 3 mL/kg body weight) twice a week for 8 weeks. A normal control group received the same volume of peanut oil alone. During weeks 5-8, the CCl4-injected rat groups were administered saline (vehicle control), colchicine (0.1 mg/mL, 1 mg/kg, positive control), or SGHXHYF (0.1 mg/mL; 0.3, 0.6 and 1.2 mg/kg) once daily by oral gavage. Rats were sacrificed 24 h after the last treatment. Blood samples were collected for measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), collagen Ⅰ and collagen Ⅲ levels. Liver samples were analyzed by histopathological staining, Masson's staining of extracellular matrix proteins, and immune-ohistochemical staining of αsmooth muscle actin (α-SMA). TGF-ß1/Smad protein and mRNA levels were analyzed by Western blot and quantitative reverse transcription-polymerase chain reaction analysis, respectively. In vitro experiments were also performed using rat hepatic stellate cells (HSCs). RESULTS: Compared with the control animals, CCl4-exposed rats exhibited elevated serum levels of ALT, AST, ALP, collagen I, and collagen III; reduced serum levels of ALB; and increased collagen deposition and αSMA expression in liver sections, reflecting liver fibrosis. CCl4 also increased expression of TGF-ß1 and the activated (phosphorylated) forms of Smad2 and Smad3 but reduced expression of the negative regulator Smad7 in the liver. Notably, concomitant administration of SGHXHYF to CCl4-exposed rats was found to significantly reverse or abolish the pro-fibrotic effects of CCl4 in the liver and reduced serum transferase levels. Analysis of HSCs in vitro confirmed that, mechanistically, SGHXHYF inhibited activation of the TGF-ß1/Smad signaling pathway by downregulating phosphorylated Smad2 and Smad3 and upregulating Smad7 levels. CONCLUSION: SGHXHYF ameliorated CCl4-induced liver fibrosis by inhibiting the TGF-ß1/Smad signaling pathway. These findings suggest that SGHXHYF may have clinical utility for the treatment or prevention of liver fibrosis.

Ganodermanontriol inhibits expression of special AT rich sequence binding protein 1 gene in human hepatocellular carcinoma.

CONTEXT: The metastasis of liver cancer is a major cause of clinical treatment failure, restrain, and control the cancer metastasis is the major strategy of the treatment and prevention of the disease. Special AT-rich sequence-binding protein 1 (SATB1) gene was overexpressed in many malignant tumors and considered as a potential target of anticancer drug. This study investigated the mechanism how ganodermanontriol effect the expression of SATB1 and thus inhibits the growth and metastasis in hepatocellular carcinoma (HCC). AIMS: This study explored mainly on the mechanism how ganodermanontriol affects the expression of SATB1 and inhibits proliferation of tumor on human hepatoma cell line HepG2. SETTINGS AND DESIGN: The cancer cells were treated with ganodermanontriol. The status of the cells was detected by different methods. The mechanism was checked by various methods. MATERIALS AND METHODS: In HepG2 cancer cells treated with various concentrations of ganodermanontriol, the cell proliferation of was detected by MTT assay, cell apoptosis was analyzed by flow cytometry; the mRNA of SATB1, Bcl-2, Bax were detected by reverse transcription-polymerase chain reaction (RT-PCR) and the protein level of SATB1, Bcl-2, Bax, and caspase 3 were analyzed by Western blot. STATISTICAL ANALYSIS USED: Data are presented as the mean ± standard deviation. The data were analyzed using SPSS 18.0 software (SPSS, Inc., Chicago, IL, USA) and GraphPad Prism software (GraphPad Software, Inc., La Jolla, CA, USA). A one-way analysis of variance test was used to compare the differences among groups. RESULTS: This study showed that ganodermanontriol could significantly reduce the expression level of SATB1. CONCLUSION: Therefore, downregulate the cascade effect caused by the expression level of Bcl-2 in HCC HepG2 cells.

Rho/ROCK signal cascade mediates asymmetric dimethylarginine-induced vascular smooth muscle cells migration and phenotype change.

Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cells (VSMCs) migration. VSMC phenotype change is a prerequisite of migration. RhoA and Rho-kinase (ROCK) mediate migration of VSMCs. We hypothesize that ADMA induces VSMC migration via the activation of Rho/ROCK signal pathway and due to VSMCs phenotype change. ADMA activates Rho/ROCK signal pathway that interpreted by the elevation of RhoA activity and phosphorylation level of a ROCK substrate. Pretreatment with ROCK inhibitor, Y27632 completely reverses the induction of ADMA on ROCK and in turn inhibits ADMA-induced VSMCs migration. When the Rho/ROCK signal pathway has been blocked by pretreatment with Y27632, the induction of ERK signal pathway by ADMA is completely abrogated. Elimination of ADMA via overexpression of dimethylarginine dimethylaminohydrolase 2 (DDAH2) and L-arginine both blocks the effects of ADMA on the activation of Rho/ROCK and extra cellular signal-regulated kinase (ERK) in VSMCs. The expression of differentiated phenotype relative proteins was reduced and the actin cytoskeleton was disassembled by ADMA, which were blocked by Y27632, further interpreting that ADMA inducing VSMCs migration via Rho/ROCK signal pathway is due to its effect on the VSMCs phenotype change. Our present study may help to provide novel insights into the therapy and prevention of atherosclerosis.