Thursday, November 26, 2020

Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer

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Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase, is a signal transduction molecule shared by the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) family and the TNFR superfamily. TRAF6 has a unique TRAF domain and RING finger domain that mediate intracellular signaling events. In the immune system, TRAF6-mediated signaling has been shown to be critical for the development, homeostasis, and activation of a variety of immune cells, including B cells, T cells, dendritic cells, and macrophages. Although the pathogenesis and etiology of autoimmune diseases and cancer are not fully understood, it is worth noting that existing studies have shown that TRAF6 is involved in the pathogenesis and development of a variety of these diseases. Herein, we reviewed the role of TRAF6 in certain immune cells, as well as the function and potential effect of TRAF6 in autoimmune diseases and cancer. Our review indicates that TRAF6 may be a novel target for autoimmune diseases and cancer.
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Ischemic Colitis after Colonoscopy with Bisacodyl Bowel Preparation: A Report of Two Cases

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Background. Colonoscopy is widely used for the diagnosis and management of colorectal disease and requires adequate bowel preparation. Ischemic colitis is a form of intestinal ischemia that presents with abdominal pain, diarrhea, and hematochezia. Risk factors include advanced age, cardiovascular disease, and diabetes. Both colonoscopy and bisacodyl bowel preparation have been described as rare causes of ischemic colitis with less than 35 cases collectively in the literature. Our review found that of these cases, there exists significant heterogeneity within individual patient characteristics. The majority of the cases are managed conservatively without complications or sequela. Due to the risk of ischemic colitis, the FDA has withdrawn bisacodyl bowel preparations from use in the USA. Bisacodyl bowel p reparations are still used in Canada. Cases. Here, we present two cases of ischemic colitis in previously healthy women aged 57 and 69 who underwent screening colonoscopy using bisacodyl bowel preparation. Both were treated conservatively without complications. Conclusion. Thus far, there has been one documented case of ischemic colitis following colonoscopy with bisacodyl bowel preparation; here, we present two additional cases with one case occurring without the presence of known risk factors for ischemic colitis. Our literature review finds that there is limited evidence surrounding bisacodyl as a causative agent of ischemic colitis. Cases often contain confounding variables such as the presence of known risk factors for ischemic colitis. Our report aims to highlight the need for a more comprehensive analysis evaluating the safety of bowel preparations as well as increasing the clinical awareness surrounding the rare risk of colonoscopy-induced ischemic colitis.
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Prevalence and Antifungal Susceptibility Profile of Clinically Relevant Candida Species in Postmenopausal Women with Diabetes

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The incidence of diabetes mellitus has increased in Saudi Arabia, which has raised the risk of vulvovaginal candidiasis (VVC). This study highlights the prevalence and antifungal susceptibility of Candida species among postmenopausal women with diabetes with symptoms of VVC in Taif, a city in Saudi Arabia. Several diagnostic tools were used to differentiate the yeast isolates, including microscopic examination, culture morphology on CHROM agar, further confirmation with the VITEK 2 system, and ITS1 and ITS4 region sequencing. Antifungal susceptibility of the selected Candida species was determined using the VITEK 2 system (bioMérieux Inc., USA). Out of the 550 high vaginal swabs investigated, 86 specimens were Candida species positive (15.6%) with a significant difference according to age; the positivity in the 45–50 years' age group (12%) was higher than that in the 51–55 years' age group (3.6%). Candida albicans was the most common causative agent in 51 samples (59.3%), followed by C. glabrata in 21 samples (24.41%) and C. krusei in 14 samples (16.27%), with no significant differences between the age groups. Three isolates, including two C. albicans and one C. krusei, exhibited resistance against all the tested antifungal agents. CHROM agar and VITEK 2 were accurate phenotypic tools to identify Candida species with 100% sensitivity and specificity and were consistent with the phylogenetic characterization. The data emphasized the importance of identifying Candida species and their antifungal susceptibility among postmenopausal women with diabetes, highlighting the potential risk posed by diabetes in this age group.
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Prosthetic Valve Candida Endocarditis: A Case Report with 18F-FDG-PET/CT as Part of the Diagnostic Workup

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Diagnosis of Candida spp. infective endocarditis (IE) is challenging, and diagnostic delays are common. We describe two patients with Candida spp. prosthetic valve endocarditis (PVE) and 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a part of diagnostic workup. We also refer to 5 other cases we found from the published literature. These cases highlight that 18F-FDG-PET/CT can improve diagnostic accuracy in prosthetic valve Candida endocarditis.
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Comparison of Macular Choroidal Thickness and Volume between Pseudoexfoliative Glaucoma and Pseudoexfoliative Syndrome

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Purpose. To evaluate the difference in macular choroidal thickness and volume between patients with pseudoexfoliative glaucoma (PXG), patients with pseudoexfoliative syndrome (PEX), and normal controls. Methods. This case-control study included 49 PXG patients (group A), 33 PEX patients (group B), and 42 sex-, age-, and axial length-matched healthy volunteer eyes (group C). The macular choroidal thickness and volume of all subjects studied were measured by enhanced depth imaging optical coherence tomography. Results. The average macular (AM) choroidal thickness was 170.79 ± 50.18 μm, 184.65 ± 57.54 μm, and 206.46 ± 48.90 μm, and the average volume was 0.52 ± 0.15 μm3, 0.56 ± 0.17 μm3, and 0.63 ± 0.15 μm3 in groups A, B, and C, respectively. The macular choroi dal thickness, the volumes of various macular regions, and the average choroidal thickness and volume in group A were lower than those in group C (all ). There were no significant differences in the macular choroidal thickness, volumes of various macular regions, or average choroidal thickness or volume between group A and B (all ). The macular choroidal thickness and volume of the TIM and SOM in group B were lower than those in group C (). There was no association between the macular choroidal thickness of various macular regions and visual field mean defect (MD) in group A (all ).Conclusion. The macular choroidal thickness in patients with PXG or PEX (TIM and SOM) is thinner than that in normal subjects. The macular choroidal thickness in patients with PXG is not significantly different from that in patients with PEX. The role of macular choroidal thickness changes in the glaucomatous damage of patients with PXG is still unclear.
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Antiproliferative Activity, Proapoptotic Effect, and Cell Cycle Arrest in Human Cancer Cells of Some Marine Natural Product Extract

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Bioactive constituents of numerous marine organisms have been investigated recently for their preclinical and clinical anticancer activity. Three marine organisms: black-spotted sea cucumber: Pearsonothuria graeffei (Pg), lollyfish: Holothuria atra (Ha), and sea hare: Aplysia dactylomela (Ad), were collected during winter 2019 from Gulf of Aqaba, Red Sea, Egypt, and macerated with ethanol into three different extracts: PgE, HaE, and AdE, where each was in vitro assessed for its antiproliferative and proapoptotic properties on HepG2, HCT-116, and MCF-7 cancer cells. PgE dose-dependently inhibited the growth of HepG2, HCT-116, and MCF-7 cells within IC50 values 16.22, 13.34, and 18.09 μg/mL, respectively, while the IC50 values for the antiproliferative activity of HaE were 12.48, 10.45, and 10.36 μg/mL , respectively, and the IC50 values of AdE were 6.51, 5.33, and 6.87 μg/mL, respectively. All extracts were found to induce G0/G1 cell cycle arrest for HepG2 cells side by side with their inhibition of CDK2 on all three cell lines while all extracts were also showed to induce apoptosis in HepG2 cell line at pre-G1 phase supplemented by their anticancer activity via proapoptotic protein Bax, caspase-3, and cleavage PARP increase, and antiapoptotic protein Bcl-2 downturn. Moreover, necrosis has been relatively noticed in HepG2 cell line as an additional anticancer activity for each extract. Our data introduced three ethanolic marine extracts as natural chemotherapeutic agents to be further developed for cancer control.
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Social Risk Early Warning of Environmental Damage of Large-Scale Construction Projects in China Based on Network Governance and LSTM Model

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With the improvement of citizens' risk perception ability and environmental protection awareness, social conflicts caused by environmental problems in large-scale construction projects are becoming more and more frequent. Traditional social risk prevention management has some defects in obtaining risk data, such as limited coverage, poor availability, and insufficient timeliness, which makes it impossible to realize effective early warning of social risks in the era of big data. This paper focuses on the three environments of diversification of stakeholders, risk media, and big data era. The evolution characteristics of the social risk of environmental damage of large-scale construction projects are analyzed from the four stages of incubation, outbreak, mitigation, and regression in ess ence. On this basis, a social risk early warning model is constructed, and the multicenter network governance mode of social risk of environmental damage in large-scale construction projects and practical social risk prevention strategies in different stages are put forward. Experiments show that the long short-term memory neural network model is effective and feasible for predicting the social risk trend of environmental damage of large-scale construction projects. Compared with other classical models, the long short-term memory model has the advantages of strong processing capability and high early warning accuracy for time-sensitive data and will have broad application prospects in the field of risk control research. By using the network governance framework and long short-term memory model, this paper studies the environmental mass events of large-scale construction projects on the risk early warning method, providing reference for the government to effectively prevent and con trol social risk of environmental damage of large-scale construction project in China.
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Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

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Parkinson's disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from i mmunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.
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Prognostic Value of Long Noncoding RNA SNHG12 in Various Carcinomas: A Meta-Analysis

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Background. Numerous recent studies suggested that overexpression of the long noncoding RNA small nucleolar RNA host gene 12 (SNHG12) exhibited prooncogenic activity in multiple cancers. However, results regarding the prognostic value of SNHG12 in cancers still remained controversial. Therefore, we conducted a meta-analysis complemented with bioinformatics analysis to elucidate the clinical significance of SNHG12 in cancer patients. Methods. PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases were searched for eligible studies until July 2020. Additionally, bioinformatics analysis was applied to verify the results of meta-analysis. Results. Twenty-three related studies consisting of 1389 cancer patients were enrolled in the current meta-analysis. Elevat ed SNHG12 expression was found to be significantly associated with poor overall survival (OS) (; 95% CI: 1.53-2.13; ) and disease-free survival (DFS) (; 95% CI: 1.12-1.76; ) in multiple cancers, which were also verified by the results of bioinformatics analysis. Moreover, overexpression of SNHG12 was also related to clinicopathological characteristics including LNM, distant metastasis, high clinical stage, large tumor size, and poor tumor differentiation in diverse types of cancers. Conclusion. The present findings indicated that SNHG12 might act as a novel biomarker for diagnosis or prognosis in human cancers.
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A Validated Method for the Simultaneous Determination of Methamphetamine and 3,4-Methylenedioxy-N-methamphetamine in Blood-Based Liquid Chromatography-Tandem Mass Spectrometry

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A liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been validated for the simultaneous determination of methamphetamine (MA) and 3,4-methylenedioxy-N-methamphetamine (MDMA) in the blood sample. Under the optimal experimental conditions, the concentration of MA can be determined in the range from 1 µg/L to 5000 µg/L with the method detection limit (MDL) of 0.31 µg/L. The range from 0.5 to 500 µg/L is observed for the determination of MDMA with the MDL down to 0.25 µg/L. The practical applicability of the method is performed with the recovery ranging from 85.3% to 94% for MA and from 86.9% to 95.5% for MDMA. At the different concentrations of drugs, the relative standard deviations (RSD) for both MA and MDMA are lower than 5.7%. The method was applied to analyse 1995 bloo d samples that had been collected from the Forensic Medicine Centre of Ho Chi Minh City. The results showed 1.75% positive with MA and 0.25% positive with MDMA. These two drugs take 10% of the total drugs positive samples. By using deuterium-labelled methamphetamine-d5 and 3,4-methylenedioxy-N-methamphetamine-d5 as the internal standards in the determination and the use of MS/MS in multiple reaction monitoring mode signal readout, the method exhibits robustness specificity and can be applied in simultaneous determination of MA and MDMA in blood with high selectivity and sensitivity.
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Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer

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Purpose. Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. Materials and Methods. Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape soft ware. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. Results. One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B ( NF-κB) signaling pathways. Conclusion. The study elucidated the "multiingredient, multitarget, and multipathway" mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.
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Removal of Fluorescein Dye from Aqueous Solutions Using Natural and Chemically Treated Pine Sawdust

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The various factors affecting the removal of fluorescein dye using sawdust from aqueous solutions such as time, initial concentration, pH, and temperature were studied. The optimal conditions for removing the FD are 1 g of sawdust at pH 3 and 120 min time of contact. Dye removal dropped from 93.42% to 80.04% with natural pine sawdust (NPS) and from 96.83% to 81.51% with synthetic pine sawdust (SPS) by increasing their concentration from 2 to 10 mg/L. Isotherm, kinetic, and thermodynamic models were applied for determining their constants. The results indicated that the FD removal equilibrium was effectively defined by the Langmuir, Freundlich, and Temkin models. Kinetic studies showed that the pseudo-second order was well suited for dye removal, and the internal diffusion process was by two steps. Th e thermodynamic parameter values suggested that FD removal were physical adsorption, exothermic, lower randomness, and spontaneous.
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