Zhaogallegos2244
In conclusion, this is the first report on the gut microbiota of PCOS with high LDLC, suggesting that in the drug development or treatment of PCOS patients, the difference of gut microbiota in PCOS patients with different LDLC levels should be fully considered.The metabolite-rich environment that is the intestinal lumen contains metabolic by-products deriving from microbial fermentation and host cell metabolism, with resident macrophages being constantly exposed to this metabolic flux. Succinate, lactate and itaconate are three metabolites secreted by primed macrophages due to a fragmented tri-carboxylic acid (TCA) cycle. Additionally, succinate and lactate are known by-products of microbial fermentation. How these metabolites impact biological functioning of resident macrophages particularly in response to bacterial infection remains poorly understood. We have investigated the potential influence of these metabolites on macrophage phagocytosis and clearance of Escherichia coli (E. coli) infection. Treatment of murine bone-marrow-derived macrophages (BMDMs) with succinate reduced numbers of intracellular E. coli early during infection, while lactate-treated BMDMs displayed no difference throughout the course of infection. Treatment of BMDMs with itaconate lead to h response to infection, whereby succinate and itaconate regulate phagocytosis and bactericidal mechanisms, limiting the intracellular bacterial niche and impeding the pathogenesis of infection.Multimorbidity, the presence of 1+ chronic condition in an individual, remains one of the greatest challenges to health on a global scale. Although the prevalence of multimorbidity has been well-established, its incidence is not fully understood. This systematic review determined the incidence of multimorbidity across the lifespan; the order in which chronic conditions accumulate to result in multimorbidity; and cataloged methods used to determine and report accumulation of chronic conditions resulting in multimorbidity. Studies were identified by searching MEDLINE, Embase, CINAHL, and Cochrane electronic databases. Two independent reviewers evaluated studies for inclusion and performed quality assessments. Of 36 included studies, there was high heterogeneity in study design and operational definitions of multimorbidity. Studies reporting incidence (n = 32) reported a median incidence rate of 30.7 per 1,000 person-years (IQR 39.5 per 1,000 person-years) and a median cumulative incidence of 2.8% (IQR 28.7%). Incidence was notably higher for persons with older age and 1+ chronic conditions at baseline. Studies reporting patterns in accumulation of chronic conditions (n = 5) reported hypertensive and heart diseases, and diabetes, as among the common starting conditions resulting in later multimorbidity. Methods used to discern patterns were highly heterogenous, ranging from the use of latent growth trajectories to divisive cluster analyses, and presentation using alluvial plots to cluster trajectories. Studies reporting the incidence of multimorbidity and patterns in accumulation of chronic conditions vary greatly in study designs and definitions used. To allow for more accurate estimations and comparison, studies must be transparent and consistent in operational definitions of multimorbidity applied.[This retracts the article DOI 10.3389/fonc.2020.589241.].
Exercise is vital to health and well-being after a cancer diagnosis yet is poorly integrated in cancer care. Knowledge mobilization (KM) is essential to enhance exercise opportunities. We aimed to (1) develop and refine a list of highly important exercise oncology research and KM themes and (2) establish the relative importance of the themes for supporting the implementation of exercise as a standard of care for people living with and beyond cancer.
Informed by the Co-Produced Pathway to Impact KM framework, a modified Delphi study approach was used to develop, rate, and rank exercise oncology research and KM themes through an international stakeholder workshop and a three-round iterative online survey. Open-ended stakeholder feedback from cancer survivors, healthcare practitioners (HCPs), qualified exercise professionals (QEPs), policy makers, and researchers was used to update themes between survey rounds. Themes were ranked from highest to lowest importance and agreement was examined across all stakehokers that warrants further study.
These findings can be used to guide initiatives and align stakeholders on priorities to support exercise implementation as a standard of cancer care. Additional research is needed to better understand the differences in the proposed research and KM priorities across stakeholders.
These findings can be used to guide initiatives and align stakeholders on priorities to support exercise implementation as a standard of cancer care. Additional research is needed to better understand the differences in the proposed research and KM priorities across stakeholders.Adjuvant chemotherapy with temozolomide (TMZ) is an intrinsic part of glioblastoma multiforme (GBM) therapy targeted to eliminate residual GBM cells. Despite the intensive treatment, a GBM relapse develops in the majority of cases resulting in poor outcome of the disease. Here, we investigated off-target negative effects of the systemic chemotherapy on glycosylated components of the brain extracellular matrix (ECM) and their functional significance. check details Using an elaborated GBM relapse animal model, we demonstrated that healthy brain tissue resists GBM cell proliferation and invasion, thereby restricting tumor development. TMZ-induced [especially in combination with dexamethasone (DXM)] changes in composition and content of brain ECM proteoglycans (PGs) resulted in the accelerated adhesion, proliferation, and invasion of GBM cells into brain organotypic slices ex vivo and more active growth and invasion of experimental xenograft GBM tumors in SCID mouse brain in vivo. These changes occurred both at core proteins and polysaccharide chain levels, and degradation of chondroitin sulfate (CS) was identified as a key event responsible for the observed functional effects. Collectively, our findings demonstrate that chemotherapy-induced changes in glycosylated components of brain ECM can impact the fate of residual GBM cells and GBM relapse development. ECM-targeted supportive therapy might be a useful strategy to mitigate the negative off-target effects of the adjuvant GBM treatment and increase the relapse-free survival of GBM patients.
Increased expression of the progesterone receptor membrane component 1, a heme and progesterone binding protein, is frequently found in triple negative breast cancer tissue. The basis for the expression of PGRMC1 and its regulation on cellular signaling mechanisms remain largely unknown. Therefore, we aim to study microRNAs that target selective genes and mechanisms that are regulated by PGRMC1 in TNBCs.
To identify altered miRNAs, whole human miRNome profiling was performed following AG-205 treatment and PGRMC1 silencing. Network analysis identified miRNA target genes while KEGG, REACTOME and Gene ontology were used to explore altered signaling pathways, biological processes, and molecular functions.
KEGG term pathway analysis revealed that upregulated miRNAs target specific genes that are involved in signaling pathways that play a major role in carcinogenesis. While multiple downregulated miRNAs are known oncogenes and have been previously demonstrated to be overexpressed in a variety of cancers. Overlapping miRNA target genes associated with KEGG term pathways were identified and overexpression/amplification of these genes was observed in invasive breast carcinoma tissue from TCGA. Further, the top two genes (
and
) which are highly genetically altered are also associated with poorer overall survival.
Thus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
Thus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
We aimed compare the oncologic outcomes of radical prostatectomy (RP) with those of external beam radiotherapy (EBRT), brachytherapy (BT), or EBRT + BT (EBBT) in elderly patients with localised prostate cancer (PCa).
Localised PCa patients aged ≥70 years who underwent RP, EBRT, BT, or EBBT between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable competing risks survival analyses were used to estimate prostate cancer-specific mortality (CSM) and other-cause mortality (OCM). Subgroup analyses according to risk categories were also conducted.
Overall, 14057, 37712, 8383, and 5244 patients aged ≥70 years and treated with RP, EBRT, BT, and EBBT, respectively, were identified. In low- to intermediate-risk patients, there was no significant difference in CSM risk between RP and the other three radiotherapy modalities (all P > 0.05). The corresponding 10-year CSM rates for these patients were 1.2%, 2.3%, 2.0%, and 1.8%, respectively. In high-risk patially favourable to those of RP, but RP is more beneficial than EBRT. More high-quality trials are warranted to confirm and expand the present findings.
To investigate the differential expression of lncRNA in glioma cells, as well as the effect of lncRNA NKX3-1 on glioma cells.
Glioma-related data were first downloaded from the TCGA database and analyzed using bioinformatics, after which the lncRNA NKX3-1 was chosen for further experiments. The expression of the lncRNA NKX3-1 in glioma tumor samples was detected using qRT-PCR. The subcellular localization of lncRNA NKX3-1 was determined using fluorescence
hybridization (FISH). CCK-8, flow cytometry, cell scratch, and transwell assays were used to detect cell proliferation, apoptosis, and invasion. The downstream pathway of lncRNA NKX3-1 was investigated using luciferase assays and detected using western blot, transwell, and cell scratch assays.
The differential expression profile of lncRNA in glioma was obtained. NKX3-1 lncRNA was found to be significantly increased in glioma tumor tissues. LncRNA NKX3-1 was found in the nucleus. Proliferation, invasion, and migration of glioma cells were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group, while apoptosis ability was significantly decreased (P <0.05). Tumor volume and weight were significantly increased in the lncRNA NKX3-1 overexpression group in nude mice (P <0.05). LncRNA NKX3-1 significantly increased the luciferase activity of Fem1b 3'-UTR-WT reporter genes (P <0.05) as well as the levels of SPDEF protein (P <0.05). The protein level of FEM1B was significantly reduced. Cell invasion and migration were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group plus SPDEF group.
We investigated the differential expression profile of lncRNAs in glioma and discovered that the lncRNA NKX3-1 plays an important role in cancer promotion
the Fem1b/SPDEF pathway.
We investigated the differential expression profile of lncRNAs in glioma and discovered that the lncRNA NKX3-1 plays an important role in cancer promotion via the Fem1b/SPDEF pathway.
