Quantitative evaluation of gut microbiota composition in pancreatic cancer: A pooled study.

BACKGROUND: Prior research has demonstrated a positive association between the composition of gut microbiota and the incidence of pancreatic cancer. Nevertheless, a thorough quantitative and systematic evaluation of the distinct properties of gut microbiota in individuals diagnosed with pancreatic cancer has yet to be conducted. The objective of this study is to examine alterations in the diversity of intestinal microbiota in individuals diagnosed with pancreatic cancer. METHODS: Search for relevant literature published before July 2023 in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library, without any language restrictions. RESULTS: A total of 12 studies were included, including 535 patients with pancreatic cancer and 677 healthy controls. Analysis was conducted on 6 phyla, 16 genera, and 6 species. The study found significant and distinctive changes in the α-diversity of gut microbiota, as well as in the relative abundance of multiple gut bacterial groups at the phylum, genus, and species levels in pancreatic cancer patients. CONCLUSION: Overall, there are certain characteristic changes in the gut microbiota of pancreatic cancer patients. However, further research is warranted to elucidate the specific mechanism of action and the potential for treatment.

Regional variation in NAFLD prevalence and risk factors among people living with HIV in Europe: a meta-analysis.

Background and Aim: Europe faces an elevated risk of nonalcoholic fatty liver disease (NAFLD) among people living with HIV (PLWH), contributing to the region's highest global burden of NAFLD. However, the prevalence of NAFLD across various European countries and regions remains unclear. This study aims to investigate the prevalence and risk factors associated with NAFLD among PLWH across European countries. Methods: A systematic search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane Library. Data on the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, as well as the associated risk factors, were collected among PLWH in Europe. Results: Thirty-six studies from 13 European nations were included. The prevalence of NAFLD, NASH, and fibrosis were 42% (95%CI 37-48), 35% (95%CI 21-50) and 13% (95%CI 10-15), respectively. Male gender, BMI, waist circumference, Diabetes, hypertension, metabolic syndrome, dyslipidemia, triglycerides, HDL, LDL, ALT, AST, and years on antiretroviral therapy (ART) were found to be risk factors for NAFLD. High BMI and triglycerides were associated with NASH. Patients with high BMI and triglycerides are at increased risk of significant liver fibrosis. Conclusion: The high prevalence of NAFLD, NASH, and fibrosis among PLWH in Europe highlights the need for early screening, intervention, and increased research focus on adolescents living with HIV. Furthermore, the significant variations observed between countries and regions underscore the influence of related risk factors.

Comparison of efficacy of anti-diabetics on non-diabetic NAFLD: A network meta-analysis.

Objective: This study aimed to assess the efficacy of currently used anti-diabetic medications in the treatment of non-alcoholic fatty liver disease (NAFLD) without diabetes. DESIGN: The efficacy of various anti-diabetic medicines on non-alcoholic fatty liver disease in the absence of diabetes was evaluated by searching Pubmed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCT) only. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2), and the data were analyzed using Stata software (version 15.1). RESULTS: All papers published between the time of the pooling and September 2022 were searched. There were a total of 18 randomized controlled studies with a total sample size of 1141 cases. The outcomes of interest included variations in alanine transaminase (ALT) and aspartate transaminase (AST). Rosiglitazone (SUCRA: 100%) and vildagliptin (SUCRA: 99.9%) were the best anti-diabetic medicines to improve ALT and AST, respectively, in patients with NAFLD without diabetes, according to the findings of this network meta-analysis. CONCLUSION: In accordance with the Network Ranking plot, Rosiglitazone was the best anti-diabetic medicine for improving ALT, and vildagliptin was the best for improving AST in patients with non-diabetic NAFLD.

The regulation and role of osteopontin in malignant transformation and cancer.

Osteopontin (OPN) is a predominantly secreted extracellular matrix glycophosphoprotein which binds to alpha v-containing integrins and has an important role in malignant cell attachment and invasion. High OPN expression in the primary tumor is associated with early metastasis and poor outcome in human breast and other cancers. Forced OPN overexpression in benign cells may induce neoplastic-like cell behaviour including increased attachment and invasion in vitro as well as the ability to metastasize in vivo. Conversely, OPN inhibition by antisense cDNA impedes cell growth and tumor forming capacity. OPN is not mutationally activated in cancer but its expression is regulated by Wnt/Tcf signaling, steroid receptors, growth factors, ras, Ets and AP-1 transcription factors. Presumably these factors are implicated in induction of OPN overexpression in cancer. Greater understanding of the role of OPN in neoplastic change and its transcriptional regulation may enable development of novel cancer treatment strategies.

Comparative study on the pregnancy outcomes of in vitro fertilization-embryo transfer between patients with different ovarian responses (a STROBE-compliant article).

There have been few studies on large-sample data of cleavage-stage embryo and blastocyst transfers. We compared the pregnancy outcomes of patients with different ovarian responses after the transfer of different numbers of embryos in different developmental stages.Patients were divided into 3 groups including low response group, medium response group, and high response group according to different ovarian responses. Patients in each group were further divided into 4 subgroups including group A: transfer of 1 D3 embryo, group B: transfer of 2 D3 embryos; group C: transfer of 1 D5 blastocyst; and group D: transfer of 2 D5 blastocysts.In low ovarian responders, the implantation rate, clinical pregnancy rate and live birth rate were significantly lower in the group A than in the groups B and C. In medium ovarian responders, the implantation rate was significantly higher, but the multiple pregnancy rate was significantly lower in the group C than in the group B. The multiple pregnancy rate was significantly higher in the group D than in the group C. In high ovarian responders, the implantation rate was significantly lower, but the multiple pregnancy rate was significantly higher in the group B than in group C.Based on the above results, the single blastocyst transfer is preferable for the patients with different ovarian responses.

Identification of apolipoprotein D as a novel inhibitor of osteopontin-induced neoplastic transformation.

Osteopontin that associates with metabolism of calcium is one of the important factors in the development and prognosis of human breast cancer. The aim of this study was to detect potential binding partners of osteopontin to illustrate its functional mechanism. By screening a human breast cDNA library with a bacterial two-hybrid system, apolipoprotein D was isolated as a novel interacting protein of osteopontin. This interaction was confirmed by mammalian two-hybrid assay and co-immunoprecipitation. To elucidate the influence of ApoD on cellular neoplastic specifications, adhesion, soft agar, invasion and MTT growth assays were performed with Rama37 cells. The results revealed that expression of apolipoprotein D in Rama37 cells could significantly inhibit the malignant phenotype in osteopontin-transformed Rama37 cells. These findings provide better knowledge of the osteopontin signaling pathway and suggest that apolipoprotein D could be a prospective therapeutic agent for human breast and/or other carcinomas.

Inhibition of telomerase activity by HDV ribozyme in cancers.

BACKGROUND: Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity. METHODS: A pseudo-knotted HDV ribozyme (g.RZ57) directed against the RNA component of human telomerase (hTR) was designed and synthesized. An in vitro transcription plasmid and a eukaryotic expression plasmid of ribozyme were constructed. The eukaryotic expression plasmid was induced into heptocellular carcinoma 7402 cells, colon cancer HCT116 cells and L02 hepatocytes respectively. Then we determine the cleavage activity of ribozyme against human telomerase RNA component (hTR) both in vitro and in vivo, and detect telomerase activity continuously. RESULTS: HDV ribozyme showed a specific cleavage activity against the telomerase RNA in vitro. The maximum cleavage ratio reached about 70.4%. Transfection of HDV ribozyme into 7402 cells and colon cancer cells HCT116 led to growth arrest and the spontaneous apoptosis of cells, and the telomerase activity dropped to 10% of that before. CONCLUSION: HDV ribozyme (g.RZ57) is an effective strategy for gene therapy.

CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression.

CD73, originally defined as a lymphocyte differentiation antigen, is thought to function as a cosignaling molecule on T lymphocytes and an adhesion molecule that is required for lymphocyte binding to endothelium. We show here that CD73 is widely expressed on many tumor cell lines and is upregulated in cancerous tissues. Because the ecto-5'-nucleotidase activity of CD73 catalyzes AMP breakdown to immunosuppressive adenosine, we hypothesized that CD73-generated adenosine prevents tumor destruction by inhibiting antitumor immunity. We confirmed this hypothesis by showing that combining tumor CD73 knockdown and tumor-specific T-cell transfer cured all tumor-bearing mice. In striking contrast, there was no therapeutic benefit of adoptive T-cell immunotherapy in mice bearing tumors without CD73 knockdown. Moreover, blockade of the A2A adenosine receptor with a selective antagonist also augmented the efficacy of adoptive T-cell therapy. These findings identify a potential mechanism for CD73-mediated tumor immune evasion and point to a novel cancer immunotherapy strategy by targeting the enzymatic activity of tumor CD73.