scholarly journals Gut microbiome dysbiosis and correlation with blood biomarkers in active-tuberculosis in endemic setting

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245534
Author(s):  
Aasia Khaliq ◽  
Resmi Ravindran ◽  
Samia Afzal ◽  
Prasant Kumar Jena ◽  
Muhammad Waheed Akhtar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Disease ◽  
Gut Microbiome ◽  
Gene Copy Number ◽  
Chronic Inflammatory Disease ◽  
Gene Copy ◽  
Gut Health ◽  
Plasma Antibody ◽  
Immune Impairment

Tuberculosis (TB) is the largest infectious disease with 10 million new active-TB patients and1.7 million deaths per year. Active-TB is an inflammatory disease and is increasingly viewed as an imbalance of immune responses to M. tb. infection. The mechanisms of a switch from latent infection to active disease is not well worked out but a shift in the immune responses is thought to be responsible. Increasingly, the role of gut microbiota has been described as a major influencer of the immune system. And because the gut is the largest immune organ, we aimed to analyze the gut microbiome in active-TB patients in a TB-endemic country, Pakistan. The study revealed that Ruminococcacea, Enetrobactericeae, Erysipelotrichaceae, Bifidobacterium, etc. were the major genera associated with active-TB, also associated with chronic inflammatory disease. Plasma antibody profiles against several M. tb. antigens, as specific biomarkers for active-TB, correlated closely with the patient gut microbial profiles. Besides, bcoA gene copy number, indicative of the level of butyrate production by the gut microbiome was five-fold lower in TB patients compared to healthy individuals. These findings suggest that gut health in TB patients is compromised, with implications for disease morbidity (e.g., severe weight loss) as well as immune impairment.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Experimental Verification ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Tyrosine Phosphatase ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Potential Therapeutic Target ◽  
Single Cell Rna Sequencing

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

scholarly journals The role of the gut microbiome in systemic inflammatory disease

BMJ ◽  
2018 ◽  
pp. j5145 ◽  
Author(s):  
Jose C Clemente ◽  
Julia Manasson ◽  
Jose U Scher
Keyword(s):  
Inflammatory Disease ◽  
Gut Microbiome ◽  
Systemic Inflammatory Disease

The Role of Cell Growth-Related Gene Copy Number Variation in Autoimmune Thyroid Disease

2019 ◽  
Vol 195 (2) ◽  
pp. 409-416 ◽  
Author(s):  
Yunfeng Guan ◽  
Lixiang Liu ◽  
Qingzhen Jia ◽  
Xing Jin ◽  
Yi Pang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Copy Number ◽  
Autoimmune Thyroid Disease ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Related Gene ◽  
Autoimmune Thyroid ◽  
Gene Copy Number Variation ◽  
Number Variation

Frequent LOH of CYP2D6 in ER+ breast cancer determined by next-generation sequencing (NGS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 534-534
Author(s):  
Mark J. Ratain ◽  
James Sun ◽  
Yusuke Nakamura ◽  
Nancy J Cox ◽  
Tarek Sahmoud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sequence Data ◽  
Biological Significance ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Full Cohort ◽  
Next Generation Sequencing Ngs ◽  
Apparent Association

534 Background: The role of CYP2D6 genetic variation in predicting response to tamoxifen in ER+ breast cancer is a subject of ongoing debate. There has been great variability in approaches to both genotyping and phenotyping, and in particular many investigators have extracted DNA from breast cancer samples rather than peripheral blood. We hypothesized that CYP2D6 gene copy number alterations are common in ER+ breast cancer, affecting genotype results, and used NGS to characterize CYP2D6 in patients with ER+ disease. Methods: CYP2D6 sequencing was performed as part of a comprehensive NGS profile of cancer-related genes for 261 predominantly relapsed and metastatic ER+ breast cancer FFPE specimens. Sequence data were resolved into genotypes according to the * allele nomenclature. Tumor LOH was determined at CYP2D6, and its error impact on genotyping methods was estimated. To assess biological significance, the prevalence of CYP2D6 alleles and LOH in ER+ disease was compared against a control set of 99 ER- tumors. Results: CYP2D6 allele frequencies in our full cohort (ER+, 261; ER-, 99) were consistent with prior studies; 64.4%, 16.8%, 9.0% vs. 63.1%, 17.2%, 7.0% for *1/*2, *4, and *41 respectively, and 1%-2% for the rarer alleles *9, *10, and *5. The rate of CYP2D6 LOH was higher in ER+ disease (41% vs. 26%, p<0.01), with all excess arising from copy-loss (as opposed to copy-neutral) changes (22% vs. 7%, p<0.002). The estimated impact of LOH on germline genotype assessment from tumor was considerable; an assay sensitive at >20% minor allele frequency (e.g., Sanger sequencing) can misclassify >10% of heterozygotes, leading to significant Hardy-Weinberg disequilibrium (e.g., p=8.3x10-8 for *4). Interestingly, an enrichment of reduced or non-functional CYP2D6 alleles in ER+ samples was observed (61% vs. 47%, p<0.03). Conclusions: Our results demonstrate the distorting effect of extensive LOH on genotype assessment of CYP2D6 in breast cancer. Therefore, tumor DNA should not be routinely used for determination of germline 2D6 genotype, although it appears possible to use NGS. The apparent association between reduced function CYP2D6 alleles and ER+ breast cancer in our dataset requires further investigation.

Prognostic role of plasma HER2 gene copy number in patients with HER2 positive metastatic breast cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13018-e13018 ◽  
Author(s):  
Ran Ran ◽  
Wenfa Huang ◽  
Shao Lin ◽  
Yunyun Niu ◽  
Hope S. Rugo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Metastatic Breast ◽  
Gene Copy ◽  
Prognostic Role ◽  
Her2 Gene ◽  
Her2 Positive

scholarly journals Pyrite oxidization accelerates bacterial carbon sequestration in copper mine tailings Type of contribution

2018 ◽  
Author(s):  
Yang Li ◽  
Zhaojun Wu ◽  
Xingchen Dong ◽  
Zifu Xu ◽  
Zhongjun Jia ◽  
...  
Keyword(s):  
Carbon Sequestration ◽  
Mine Tailings ◽  
Copy Number ◽  
Isotope Labeling ◽  
Gene Copy Number ◽  
Stable Isotope Probing ◽  
Gene Copy ◽  
Cbbl Gene ◽  
Heavy Fractions

Abstract. Polymetallic mine tailings have great potential as carbon sequestration tools to stabilize atmospheric CO2 concentrations. However, previous studies focused on carbonate mineral precipitation, while the role of autotrophs in carbon sequestration by mine tailings has been neglected. In this study, carbon sequestration in two mine tailings treated with FeS2 and 13C-labeled CO2 was analyzed using 13C isotope labeling, pyrosequencing and DNA-based stable isotope probing (SIP) to identify carbon fixers. Mine tailings treated with FeS2 exhibited a higher percentage of 13C atoms (1.76 ± 0.06 in Yangshanchong and 1.36 ± 0.01 in Shuimuchong) than the control groups over a 14-day incubation, as well an increase in the total organic carbon (TOC) content (0.20 ± 0.11 mg/g in Yangshanchong and 0.28 ± 0.14 mg/g in Shuimuchong). These data demonstrated the role of autotrophs in carbon sequestration with pyrite addition. Pyrite treatment led to changes in the composition of bacterial communities, and the genera Sulfobacillus (8.04 %) and Novosphingobium (8.60 %) were found to be dominant in these communities. In addition, the DNA-SIP results indicated that the cbbL gene copy number was 8.20–16.50 times greater than the cbbL gene copy number in 13C-labeled heavy fractions. Furthermore, a Sulfobacillus-like cbbL gene sequence (cbbL-OTU1) accounted for 30.11–34.74 % of all cbbL gene sequences in the 13C-labeled heavy fractions of mine tailings treated with FeS2. These findings highlight the importance of the RubisCO form I-encoding gene, cbbL, in bacterial carbon sequestration and demonstrate the ability of chemoautotrophs to sequester carbon during sulfide mineral oxidation in mine tailings. This study is the first to investigate carbon sequestration by autotrophic groups in mine tailings through the use of isotope tracers and DNA-SIP.

scholarly journals TERT aberrancies: a screening tool for malignancy in follicular thyroid tumours

2018 ◽  
Vol 25 (7) ◽  
pp. 723-733 ◽  
Author(s):  
Johan O Paulsson ◽  
Ninni Mu ◽  
Ivan Shabo ◽  
Na Wang ◽  
Jan Zedenius ◽  
...  
Keyword(s):  
Screening Tool ◽  
Gene Copy Number ◽  
Promoter Hypermethylation ◽  
Malignant Potential ◽  
Gene Copy ◽  
Clinical Parameters ◽  
Uncertain Malignant Potential ◽  
Increased Risk ◽  
Promoter Mutations

Telomerase reverse transcriptase (TERT) promoter mutations have been linked to adverse clinical parameters in thyroid cancer, butTERT-expressing tumours are not always mutated. Little is known regarding otherTERT-related genetic aberrations. To delineate the role ofTERTgene aberrancies in follicular thyroid tumours, 95 follicular carcinomas (FTCs), 43 follicular adenomas (FTAs) and 33 follicular tumours of uncertain malignant potential (FT-UMPs) were collected. The tumours were assayed forTERTexpression,TERTpromoter mutations,TERTpromoter hypermethylation andTERTgene copy number (CN) alterations and the results were compared to clinical parameters. Cases with mutation, detectable mRNA expression, CN gain or hypermethylation were classified asTERTaberrant, and these aberrancies were regularly found in FTC and FT-UMP but uncommonly found in FTA. In total, 59% FTCs and 63% FT-UMPs exhibited one or more of theseTERTgene aberrancies. Moreover, 24 out of 28 FTCs (86%) withTERTexpression displayed an evidentTERTgene aberration, and statistics showed an increased risk for relapse in FTCs withTERTexpression, CN gain or hypermethylation. We conclude thatTERTexpression in follicular thyroid tumours is coupled to promoter mutations, CN gain and increased promoter methylation. The molecular similarities regardingTERTaberrations between the FTC and FT-UMP groups indicate that a significant subset of FT-UMP cases may display future recurrences.TERTaberrancies are thus promising as future additional markers for determining malignant potential of follicular thyroid tumours.

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