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The application of co-design within building exercising treatments regarding seniors: a new scoping review protocol.
hile mutant PKC-ζ reversed this effect. Furthermore, the gene expression levels of enzymes involved in serine biosynthesis, phosphoserine phosphatase (PSPH), phosphoserine aminotransferase (PSAT1), and phosphoglycerate dehydrogenase (PHGDH) showed upregulation following glucose deprivation with PKC-ζ deficiency. The PHGDH upregulation was inhibited by ectopically expressing wild type but not mutated PKC-ζ in glucose-deprived conditions.

Our results support the upregulation of serine biosynthesis pathway genes and downregulation of PKC-ζ as potential metabolic alterations for bone metastatic breast cancer cells.
Our results support the upregulation of serine biosynthesis pathway genes and downregulation of PKC-ζ as potential metabolic alterations for bone metastatic breast cancer cells.Gallbladder cancer (GBC) with poor prognosis has been a major cause of cancer-related deaths worldwide. In this study, we aimed to screen and identify crucial genes in GBC through integrative analysis of multiple datasets and further experimental validation. A candidate crucial gene, up-regulated haptoglobin (HP), was firstly screened, and then further analysis and validation mainly focused on whether higher enrichment level of HP was responsible for pathophysiological process of GBC. HP was found with diverse expression patterns in various cancer types, and the dynamic expression patterns indicated its spatiotemporal characteristics in different tissues and disease stages, implicating its role in multiple biological processes. Further experimental validation showed that HP could promote the GBC-SD cell proliferation, migration and invasion, implying its role in pathophysiological process of GBC. HP may have a crucial role in occurrence and development of GBC, and it provides possibility as a potential biomarker or target in cancer prognosis and treatment.Epstein-Barr virus nuclear antigens 2 (EBNA2) mediated super-enhancers, defined by in silico data, localize near genes associated with B cell transcription factors including RUNX3. However, the biological function of super-enhancer for RUNX3 gene (seR3) remains unclear. Here, we show that two seR3s, tandemly-located at 59- and 70-kb upstream of RUNX3 transcription start site, named seR3 -59h and seR3 -70h, are required for RUNX3 expression and cell proliferation in Epstein-Barr virus (EBV)-positive malignant B cells. A BET bromodomain inhibitor, JQ1, potently suppressed EBV-positive B cell growth through the reduction of RUNX3 and MYC expression. Excision of either or both seR3s by employing CRISPR/Cas9 system resulted in the decrease in RUNX3 expression and the subsequent suppression of cell proliferation and colony forming capability. The expression of MYC was also reduced when seR3s were deleted, probably due to the loss of trans effect of seR3s on the super-enhancers for MYC. These findings suggest that seR3s play a pivotal role in expression and biological function of both RUNX3 and MYC. seR3s would serve as a potential therapeutic target in EBV-related widespread tumors.
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic that often progresses to liver cirrhosis and hepatocellular carcinoma. In contrast to most world populations where NAFLD is mostly prevalent among obese, NAFLD among Indians and generally among South and South-East Asians is unique and highly prevalent among individuals who are lean. Genetics of NAFLD in Indian populations is understudied. In this study, we have used an exome-wide approach to identify genetic determinants of hepatic fat content (HFC) in India.

HFC was measured in 244 participants using Proton magnetic resonance spectroscopy (H1-MRS). Quantitative trait loci (QTL) mapping was done exome-wide, to identify SNPs associated with HFC. The effects of the interaction between adiposity and QTLs on HFC were studied using a regression model. Association of the significant loci with disease severity was studied in 146 NAFLD patients among 244 participants, who underwent liver biopsy.

Our study identified 4 significantly associated SNPs (rs738409 and rs2281135 (PNPLA3), rs3761472 (SAMM50), rs17513722 (FAM161A) and rs4788084), with HFC after adjusting for the effects of covariates (p-value < 0.0005). rs738409, rs2281135 (PNPLA3), and rs3761472 (SAMM50) were associated with hepatocyte ballooning, lobular and portal inflammation and non-alcoholic steatohepatitis (NASH) (p-value < 0.05). rs4788048 is an eQTL for IL27 and SULT1A2 genes, both of which are highly expressed in healthy livers and are likely to be involved in NAFLD pathogenesis.

Our study identified the novel association of rs4788084 with HFC, which regulates the expression of IL-27, an immune regulatory gene. We further showed that adiposity affected the HFC, irrespective of the genetic predisposition.
Our study identified the novel association of rs4788084 with HFC, which regulates the expression of IL-27, an immune regulatory gene. We further showed that adiposity affected the HFC, irrespective of the genetic predisposition.Forkhead Box Protein3 Transcription Factor (FOXP3) gene is an essential role player in the function and differentiation of regulatory T cells. Polymorphisms/mutations in FOXP3 gene cause Treg cell dysfunction, promote autoimmunity and inflammation. Based on this presumption, we screened 600 subjects from south India (equal number of diabetic (T2DM), diabetic nephropathy (T2DN) and healthy controls) for promoter and intronic (rs3761548C/A and rs2294021C/T) polymorphisms of FOXP3 gene. PCR-RFLP method used for genotyping, revealed an association of promoter SNP for both T2DM (OR = 2.41, 95% C.I = 1.67-3.49; p less then 0.0001) and T2DN (OR = 2.16, 95% C.I = 1.45-3.24; p less then 0.005). While intronic polymorphism with T2DN (OR = 1.91, 95% C.I = 1.28-2.84; p less then 0.05). Further, in females rs3761548C/A showed 2.6 and 5.5-fold; rs2294021C/T showed 2.2- and 2.5-fold predisposition towards T2DM and T2DN respectively. Males exhibited a twofold risk (OR = 2.01, 95% C.I = 1.22-3.30; p less then 0.05) towards T2DM with promoter and no association with intronic polymorphism. The combined genotypes in females with AA-CC; AA-TT predisposed and CA-CC; CA-CT protected heading towards T2DM and T2DN respectively, suggesting irrespective of type of allele at intronic locus AA and CA at promoter locus promote or protect the individual for diabetes and diabetic nephropathy, further confirmed by MLR. To our knowledge, the current study is the first of its kind that revealed an association of these polymorphisms of FOXP3 gene and gender influence on T2DM and T2DN among South Indians. Functional and cell-based studies on Treg cells are warranted to confirm our results that help to develop FOXP3/Treg based therapeutic interventions. Lack of data on Treg cells is the limitation of this study.Nucleic acid aptamers for biosensing are developed from a complex ssDNA library through Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process. Monitoring of SELEX process is crucial for generating high-affinity aptamers. Extant methods for monitoring aptamer selection are either arduous or give false-positive signals, which adversely impact the outcome of selection. We describe a colorimetric, simple and cost-effective, novel method to monitor the progress of in vitro selections. The power of rolling circle amplification (RCA) and inherent Horse Radish Peroxidase (HRP)-mimicking activity of G-quadruplex/hemin DNAzyme were employed to produce a colorimetric signal. A unique extension of DNA population at 3'-OH end by PCR generated concatenated repeats by rolling circle amplification (RCA) reaction. Oxidation of substrate ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) in presence of H2O2 and hemin cofactor produced colorimetric signal. Analysis of the signal generated by the DNA pool bound to their target provided a quantitative measurement of SELEX. AMI-1 We demonstrate the reproducibility and accuracy of the method by evaluating the progress of two discrete selections.The transcriptomic response of Senegalese sole (Solea senegalensis) triggered by two betanodaviruses with different virulence to that fish species has been assessed using an OpenArray® platform based on TaqMan™ quantitative PCR. The transcription of 112 genes per sample has been evaluated at two sampling times in two organs (head kidney and eye/brain-pooled samples). Those genes were involved in several roles or pathways, such as viral recognition, regulation of type I (IFN-1)-dependent immune responses, JAK-STAT cascade, interferon stimulated genes, protein ubiquitination, virus responsive genes, complement system, inflammatory response, other immune system effectors, regulation of T-cell proliferation, and proteolysis and apoptosis. The highly virulent isolate, wSs160.3, a wild type reassortant containing a RGNNV-type RNA1 and a SJNNV-type RNA2 segments, induced the expression of a higher number of genes in both tested organs than the moderately virulent strain, a recombinant harbouring mutations in the protruding domain of the capsid protein. The number of differentially expressed genes was higher 2 days after the infection with the wild type isolate than at 3 days post-inoculation. The wild type isolate also elicited an exacerbated interferon 1 response, which, instead of protecting sole against the infection, increases the disease severity by the induction of apoptosis and inflammation-derived immunopathology, although inflammation seems to be modulated by the complement system. Furthermore, results derived from this study suggest a potential important role for some genes with high expression after infection with the highly virulent virus, such as rtp3, sacs and isg15. On the other hand, the infection with the mutant does not induce immune response, probably due to an altered recognition by the host, which is supported by a different viral recognition pathway, involving myd88 and tbkbp1.Melissa officinalis (lemon balm) is a well-known pharmaceutical plant in traditional medicine around the world because of the high-value secondary metabolites. Nowadays, advances in computational biology and bioinformatics have opened new avenues to plant-based natural product drug discovery. Despite the pharmacological importance, there is low information about the genes encoding the important biosynthetic pathways related to the secondary metabolite in M. officinalis. In this study, the main genes related to the rosmarinic acid (RA) and terpenoid biosynthesis pathways were detected using transcriptome analysis. Furthermore, we isolated and characterized a novel M. officinalis Hydroxyphenylpyruvate reductase (HPPR) gene involved in RA biosynthesis pathway. An effective pipeline was used to generate 37,055 unigenes by evaluating 42,837,601 Illumina paired-end reads. Functional annotation of the unigenes revealed that 27,363 (73.84%) and 35,822 (96.67%) unigenes had significant similarity to identified proteins in the SwissProt and NR databases, respectively. Also, 10,062 (36.83%) out of 37,055 unigenes were assigned to 399 KEGG pathways. Since terpenes and RA are two prominent metabolites in this plant, the attention of this study has been on the pathways related to them. A total of 149 unigenes were found that are related to the terpenoids biosynthesis, including 75 unigenes involved in the methyl-erythritol phosphate and mevalonate pathway, terpenoid backbone biosynthesis genes, and 74 unigenes related to the terpene synthase. We also identified 144 and 30 unigenes that were associated with the biosynthesis of phenylpropanoid and the rosmarinic acid pathway. Consequently, this investigation can be a comprehensive and accurate transcriptome basis for further investigation in the metabolic engineering and detection of new genes and pathways in M. officinalis.
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