Atherosclerosis underlies aortic aneurysm (AA) and atherosclerotic stenosis (AS). Kallikrein-1 (KLK1) and angiotensin-converting enzyme (ACE) are 2 key molecules in kallikrein-kinin systems and renin-angiotensin systems, respectively, which are responsible for maintaining vascular balance and stability, playing important roles in atherosclerosis. We aimed to assess the involvement of single nucleotide polymorphism rs5516 in KLK1 as well as the insertion/deletion rs4646994 polymorphism in ACE in the development of AA and AS.

It is widely accepted that apoptosis is closely associated with cancer cell death. However, whether autophagy induces tumor cell death has not been fully elucidated. Various studies have discussed the antitumor properties of rottlerin in human malignancies. The current study aimed to investigate the effects of rottlerin, a natural product isolated from the kamala tree (Mallotus philipensis), on growth inhibition and autophagy in gastric cancer (GC) cell lines in vitro. The results of the present study demonstrated that rottlerin suppressed cell growth, induced autophagy and apoptosis, and reduced migration and invasion in the SGC‑7901 and MGC‑803 GC cell lines. Furthermore, rottlerin led to microtubule‑associated protein 1 light chain 3β‑II augmentation and the enrichment of autophagosomes. In addition, the protein expression levels of mechanistic target of rapamycin kinase and S‑phase kinase‑associated protein 2 were downregulated in GC cells following rottlerin treatment, which is associated with autophagy. The protein levels of caspase‑3, cleaved‑caspase‑3, total poly (ADP‑ribose) polymerase (PARP) and cleaved‑PARP exhibited no marked alterations in the GC cells following rottlerin treatment, indicating that caspases were likely not involved in rottlerin‑induced GC apoptosis. In summary, the results of the present study indicate that rottlerin may inhibit invasion and promote apoptosis in GC cells, which may be mediated by the activation of autophagy. Therefore, rottlerin may be of value in the treatment of GC.

Sinomenine (SIN), a pure alkaloid isolated from Sinomenium acutum, has been widely used in arthritis for its anti‑inflammatory effect, but little is known about the effect of SIN on human ulcerative colitis (UC). In the present study, the effect and mechanism of SIN was examined in a dextran sulfate sodium (DSS)‑induced murine colitis model, which mimics human UC. Oral administration of SIN significantly suppressed the elevated disease activity index and ameliorated colonic histological damage in a DSS‑induced colitis model. Tumor necrosis factor‑α, interleukin‑6 and inducible nitric oxide synthase levels were also reduced as detected by reverse transcription‑quantitative polymerase chain reaction. In addition, SIN reversed the decreased colon length and colonic superoxide dismutase activity. Furthermore, western blot analysis revealed that nuclear factor‑erythroid 2‑related factor 2 (Nrf2) and its downstream genes, heme oxygenase‑1 and NADP(H) quinone oxidoreductase 1 (NQO‑1), were markedly activated by SIN. The current results indicated that SIN alleviated DSS‑induced colitis in mice, which may be due to its antioxidant properties and was at least in part dependent on the Nrf2/NQO‑1 signaling pathway. Therefore, SIN may have potential applications as a protective drug for patients with UC.

Hepatocellular carcinoma (HCC) is a malignant cancer that threatened human life seriously. Long non-coding RNA (lncRNA) BACE1-AS has been reported as a key regulator in tumorigenesis. Yet the specific correlation between BACE1-AS and HCC still needs further investigation. The primary purpose of our study is to reveal the exact correlation between BACE1-AS and HCC.

Colorectal cancer (CRC) is one of the most mortal cancers in the world. Multiple factors and bio-processes are associated with in tumorigenesis and metastasis of CRC, including cellular senescence and immune evasion. This study aims to identify prognostic and immune-meditating effects of INHBA in CRC. Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) in senescent cells and CRC tissues from the Cancer Genome Atlas (TCGA). Key factor was settled from the alternative DEGs set. Enrichment analyses and functional networks prediction were determined from online databases. Correlation analyses were performed to reveal the association among key factor, immune infiltration, T cell biomarkers and immune checkpoints. Moreover, expressions of key factors and immune checkpoints of tissue and blood samples from CRC patients as well as human CRC cell lines were measured. Results showed that Inhibin beta A (INHBA) was sorted out as a senescence-related factor and a prognostic predictor in CRC. What's more, INHBA was found highly co-expressed with T-cell biomarkers and immune checkpoints. In conclusion, INHBA was considered as a senescence-related regulator and a prognostic predictor in CRC, which also mediating immune evasion.

As the most common chronic liver disease around the world, nonalcoholic fatty liver disease (NAFLD) has a close connection with obesity, diabetes, and metabolic syndrome. Bariatric surgery (BS) is considered to be the most effective treatment for NAFLD. However, the regulatory mechanism of hepatic lipid metabolism after BS remains poorly elucidated. By analyzing two transcriptome datasets regarding liver tissues after BS, namely, GSE83452 and GSE106737, we acquired 110 differentially expressed genes (DEGs). By further analysis of DEGs in terms of the weighted gene coexpression network analysis (WGCNA) and support vector machine-recursive feature elimination (SVM-RFE) algorithms, we identified four crucial genes participating in the regulation of hepatic lipid metabolism: SRGN, THEMIS2, SGK1, and FPR3. In addition, the results of gene set enrichment analysis (GSEA) showed that BS can activate immune-related regulatory pathways and change immune cell infiltration levels. Finally, through cellular level studies, we found that the silencing of SRGN affects the expression of SREBP-1, SIRT1, and FAS during adipogenesis in the liver and the formation of lipid droplets in the liver. In summary, the immune system in the liver is activated after BS, and SRGN participates in the regulation of hepatic lipid metabolism.

Nonalcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases worldwide and no effective drugs or treatments have been approved for disease management. Recently, bariatric surgery (BS) is considered to be a novel disease-modifying therapy for NASH and liver metabolic diseases, according to clinical follow-up studies. Despite the revealment of physiopathological alterations, underlying mechanisms and key factors remain indeterminate. This study included multiple bulk RNA-sequencing datasets to investigate transcriptome variation in one-year follow-up BS and diet management (Diet) NASH patients' liver biopsies. Liver functions, fibrosis, and carcinogenesis were predicted in liver samples via hallmark-based function enrichment analysis. Key factors generated from multi-dataset comparison were further assessed with hepatocellular carcinoma (HCC) progression and prognosis. BS leads to active gene expression alterations in NASH liver in comparison to diet management (Diet). Both approaches reduce cell stress and immune response, whereas BS contributes to higher metabolic levels and lower apoptosis levels. The macrophage infiltration, adipose accumulation, and fibroblast activation were revealed to be lower in post-BS NASH livers, further demonstrating positive correlations mutually. Seven key genes (MNDA, ALOX5AP, PECAM1, SPP1, CD86, FGF21, CSTA) were screened out as potential macrophage-associated and carcinogenetic factors suppressed by BS. SPP1 was identified as a crucial factor participating in BS intervened NASH-HCC progression. This study determined that BS exerts potentially superior protective functions in NASH livers compared to diet management. SPP1 may serve as a novel factor to study the functionalities of BS on NASH patients.

Sleeve gastrectomy (SG) is the most currently popular operation for obesity and related metabolic disorders. The aim of this study was to compare the effect of antrum preservation SG (AP-SG) and antrum resection SG (AR-SG) on the body composition, glycemic control and bone mineral density (BMD) in mice.

Long non-coding RNA (lncRNA) PCED1B-AS1 was shown to play essential roles in human cancers, while its function in colorectal adenocarcinoma remains unclear. This study was carried out to investigate the function of PCED1B-AS1 in regulating the microRNA(miR)-633/HOXA9 axis in colorectal adenocarcinoma. The expression of PCED1B-AS1, miR-633 and HOXA9 was measured by quantitative real-time PCR (qRT-PCR) or Western blot analysis. Cell behaviors of colorectal adenocarcinoma cell lines were assessed by CCK-8, EdU, Transwell and flow cytometry assays. The interaction among PCED1B-AS1, miR-633 and HOXA9 was determined by luciferase reporter and RIP assays. Rescue experiments were performed to determine the regulatory axis in colorectal adenocarcinoma. Moreover, an animal model was established to verify the role of PCED1B-AS1. We found that PCED1B-AS1 was upregulated and miR-633 was downregulated in colorectal adenocarcinoma tissues and corresponding cell lines. Knockdown of PCED1B-AS1 inhibited cell proliferation and promoted apoptosis, while miR-633 inhibitor elevated proliferation and reduced apoptosis of cancer cell lines. In addition, overexpression of HOXA9 obviously attenuated the protective role of knockdown of PCED1B-AS1 or miR-633 mimics in colorectal adenocarcinoma progression. PCED1B-AS1 could negatively regulate the expression of HOXA9 by sponging miR-633. The in vivo experiments confirmed the role of PCED1B-AS1 and miR-633 in colorectal adenocarcinoma, as well as the regulatory relationship of this axis. Our results demonstrated that knockdown of PCED1B-AS1 inhibited the progression of colorectal adenocarcinoma by regulating the miR-633/HOXA9 axis.

Tumor endothelial marker 7 (TEM7) is included in the endothelial cells of tumors as a greatly expressed protein. In previous studies, it has been confirmed that TEM7 is highly expressed in gastric cancer (GC) cells and related to tumor invasion and migration. However, the relationship between TEM7 gene expressions, prognostic and tumor-infiltrating lymphocyte in GC is still unclear.

The roles of circRNA and N6-methyladenosine (m6 A) methylation in Crohn's disease (CD) have drawn much attention. Therefore, this investigation aimed to discover how the m6 A modification of circRNAs contributes to CD progression.

Caffeine is one of the most widely consumed substances found in beverages, and has demonstrated anticancer effects in several types of cancer. The present study aimed to examine the anticancer effects of caffeine on gastric cancer (GC) cells (MGC‑803 and SGC‑7901) in vitro, and to determine whether the apoptosis‑related caspase‑9/-3 pathway is associated with these effects. The sustained antiproliferative effects of caffeine on gastric cancer were also investigated. GC cell viability and proliferation were evaluated using cell counting and colony forming assays, following treatment with various concentrations of caffeine. Flow cytometry was performed to assess cell cycle dynamics and apoptosis. Western blot analysis was conducted to detect the activity of the caspase‑9/-3 pathway. The results indicated that caffeine treatment significantly suppressed GC cell growth and viability and induced apoptosis by activating the caspase‑9/-3 pathway. Furthermore, the anticancer effects of caffeine appeared to be sustained, as the caspase‑9/-3 pathway remained active following caffeine withdrawal. In conclusion, caffeine may function as a sustained anticancer agent by activating the caspase‑9/-3 pathway, which indicates that it may be useful as a therapeutic candidate in gastric cancer.

LncRNA NR2F2-AS1 has been characterized as an oncogenic lncRNA in non-small cell lung cancer. This study aims to explore the role of NR2F2-AS1 in colorectal cancer (CRC).

Collagen type X alpha 1 (COL10A1) is a member of the collagen family and the main matrix component. However, COL10A1 expression and prognosis relationship remains unclear in gastric cancer (GC). Through the analysis of database of Oncomine, the Cancer Genome Atlas (TCGA) as well as the Gene Expression Omnibus (GEO), in contrast to the tissue of normal gastric, COL10A1 in gastric cancer, had been upregulated. The high expression of COL10A1 was obviously related to T stage (P = 0.025) and lymph node metastasis (P = 0.025). It has been illustrated by the analysis of logistic regression that COL10A1's heightened expression in gastric cancer had been essentially linked with pathological stage, tumor differentiation, and T classification. The Kaplan-Meier curve in the Kaplan-Meier plotter database (P = 0.0371) and GSE84437 (P = 0.002) indicate that patients with high COL10A1 expression possess poor prognosis, specifically GC patients with lymph node metastasis have it. TCGA's Multivariate analysis (P = 0.025) and GSE84437 dataset (P = 0.034) show that high expression COL10A1 is a key independent predictor of poor overall survival. Searching KEGG pathway enrichment by GSEA, the results suggested that 29 pathways were enriched. qRT-PCR technique was used for verification of the COL10A1's high expression in gastric cancer in contrast to the normal gastric tissues. In conclusion, COL10A1 is of great importance in predicting the survival rate of GC patients.

During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.

Fluorochloridone (FLC) is a widely used herbicide, and its target organs are testes and epididymides. The Globally Harmonized System of Classification and Labelling of Chemicals classified FLC as Level 2-possibly cause fertility or fetal damage (no relevant data support). The maximum residue levels of FLC in processed crops have been reviewed in the latest European Food Safety Authority (EFSA) report in 2018. However, the toxic effect of FLC on fertility and early embryonic development is limited, and the health risk assessment of FLC needs further consideration. This study investigated the potential effects of FLC on fertility and early embryonic development in rats.

As an alternative mesenchymal stem cell- (MSC-) based therapy, MSC-derived extracellular vesicles (EVs) have shown promise in the field of regenerative medicine. We previously found that human umbilical cord mesenchymal stem cell-derived EVs (hUCMSC-EVs) improved functional recovery and nerve regeneration in a rat model of sciatic nerve transection. However, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that hUCMSC-EVs promoted the proliferation of Schwann cells by activating the PI3K/AKT signaling pathway. Furthermore, we showed that hUCMSC-EVs mediated Schwann cell proliferation via transfer of miR-21. Our findings highlight a novel mechanism of hUCMSC-EVs in treating peripheral nerve injury and suggest that hUCMSC-EVs may be an attractive option for clinical application in the treatment of peripheral nerve injury.

Adipogenesis and fat accumulation are closely associated with the development of obesity. Sleeve gastrectomy (SG) is an effective treatment for obesity and associated metabolic disorders. Leptin is downregulated after SG and Src homology phosphatase 2 (Shp2) has an important role in leptin signaling. The role of Shp2 in SG and the mechanisms of fat reduction following SG were further investigated in the current study. Sham and SG operations were performed on obese type-2 diabetes model Sprague-Dawley rats. Primary pre-adipocytes were isolated from the inguinal white adipose tissue (ingWAT) of the rats. Shp2 expression in ingWAT pre-adipocytes was silenced using small interfering RNA transfection. Shp2 function was inhibited using the specific inhibitor, SHP099. In addition, Shp2 was overexpressed using lentivirus. Gene and protein expression analysis was performed after adipocyte differentiation. Furthermore, Shp2-overexpressing ingWAT pre-adipocytes treated with the β-catenin inhibitor, PNU-74654, were also used for gene and protein expression analysis. Adipogenic markers, including triglycerides, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (Cebpα), adiponectin, fatty acid-binding protein 4 and leptin, were examined. Compared with the sham, triglyceride, leptin, PPARγ and Cebpα levels were significantly reduced in the ingWAT from the SG group. Shp2 expression levels were reduced following leptin treatment. Moreover, genetic analysis demonstrated depot-specific adipogenesis following Shp2 silencing or inhibition in ingWAT pre-adipocytes. Conversely, Shp2 overexpression decreased the expression of adipogenic markers by enhancing β-catenin expression. PNU-74654 treatment abolished the downregulation of adipogenic markers caused by Shp2 overexpression. SG decreased leptin levels in ingWAT, which in turn upregulated Shp2, and Shp2 suppressed fat accumulation and adipogenic differentiation by activating the Wnt/β-catenin signaling pathway. Overall, this may represent a potential mechanism of fat reduction in SG, and Shp2 may serve as a potential therapeutic target for the treatment of obesity and type-2 diabetes.

This study aimed to at explore exploring the biological functions of dysregulated circRNA in Crohn's disease (CD) pathogenesis, with the overarching goal of and providing potential novel therapeutic targets. CircRNA microarray and quantitative real time-polymerase chain reaction (qRT-PCR) analyses were performed to investigate and verify the candidate dysregulated circRNA. The Next, clinical, in vivo, and in vitro studies were performed to investigate explore the biological function and mechanisms of the candidate circRNA in CD. The therapeutic effect of poly (lactic-co-glycolic acid)-microspheres (PLGA MSs)-carried oe-circGMCL1 in experimental colitis models of IL-10 knock-out mice was assessed. CircGMCL1 was identified as the candidate circRNA by microarray and qRT-PCR analyses. Results showed that circGMCL1 expression was negatively correlated with CD-associated inflammatory indices, suggesting that it is a CD-associated circRNA. Microarray and bioinformatics analyses identified miR-124-3p and Annexin 7 (ANXA7) as its downstream mechanisms. The in vitro studies revealed that circGMCL1 mediates its effects on autophagy and NLRP3 inflammasome-mediated pyroptosis in epithelial cells through the ceRNA network. Moreover, the in vivo studies identified the therapeutic effect of PLGA MSs-carried oe-circGMCL1 in experimental colitis models. This study suggests that circGMCL1 protects intestinal barrier function against Crohn's colitis through alleviating NLRP3 inflammasome-mediated epithelial pyroptosis by promoting autophagy through regulating ANXA7 via sponging miR-124-3p. Therefore, circGMCL1 can serve as a potential biological therapeutic target for Crohn's colitis.