A systemic approach to explore the mechanisms of drug resistance and altered signaling cascades in extensively drug-resistant tuberculosis

Kumar, Sanjit; Saleem, Aisha; Kumar, Dhirendra; Preethi, V. Anu; Younes, Salma; Zayed, Hatem; Tayubi, Iftikhar Aslam; C, George Priya Doss

doi:10.1016/bs.apcsb.2021.02.002

Cited by 30 publications

(13 citation statements)

References 41 publications

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“…IGHM is involved in oxidative stress and in skin regeneration [ 62 ], suggesting that it may be involved in cell proliferation. We tried to find relevant IGHM-regulated cascade response signals, similar to other studies [ 63–67 ]. Transcription factor binding to IGHM enhancer 3 (TFE3) is related to renal cell carcinoma [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Gao

2021

Annals of Medicine

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Aim Endometriosis is one of the most common reproductive system diseases, but the mechanisms of disease progression are still unclear. Due to its high recurrence rate, searching for potential therapeutic biomarkers involved in the pathogenesis of endometriosis is an urgent issue. Methods Due to the similarities between endometriosis and ovarian cancer, four endometriosis datasets and one ovarian cancer dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein–protein interaction (PPI) analyses. Then, we validated gene expression and performed survival analysis with ovarian serous cystadenocarcinoma (OV) datasets in TCGA/GTEx database, and searched for potential drugs in the Drug-Gene Interaction Database. Finally, we explored the miRNAs of key genes to find biomarkers associated with the recurrence of endometriosis. Results In total, 104 DEGs were identified in the endometriosis datasets, and the main enriched GO functions included cell adhesion, extracellular exosome and actin binding. Fifty DEGs were identified between endometriosis and ovarian cancer datasets including 11 consistently regulated genes, and nine DEGs with significant expression in TCGA/GTEx. Only IGHM had both significant expression and an association with survival, three module DEGs and two significantly expressed DEGs had drug associations, and 10 DEGs had druggability. Conclusions ITGA7 , ITGBL1 and SORBS1 may help us understand the invasive nature of endometriosis, and IGHM might be related to recurrence; moreover, these genes all may be potential therapeutic targets. KEY MESSAGE This manuscript used a bioinformatics approach to find target genes for the treatment of endometriosis. This manuscript used a new approach to find target genes by drawing on common characteristics between ovarian cancer and endometriosis. We screened relevant therapeutic agents for target genes in the drug database, and performed histological validation of target genes with both expression and survival analysis difference in cancer databases.

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Section: Discussionmentioning

confidence: 99%

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Gao

2021

Annals of Medicine

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“…Related to pathway-associated biomarkers, some research tried to identify and map potential novel genes, [ 66 , 67 ] probe the relationship between the DEGs and altered or dysregulated pathways, [ 68 , 69 ] and to predict and prioritize pathway-associated biomarkers. [ 70 ] Based on NOS-cGMP-PDE5 pathway, the critical biomarkers identified in this study may provide some help on ED treatment from above points.…”

Section: Discussionmentioning

confidence: 99%

Comparison of critical biomarkers in 2 erectile dysfunction models based on GEO and NOS-cGMP-PDE5 pathway

et al. 2021

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“…Rifampicin’s known mechanism of bacterial growth inhibition occurs through the suppression of RNA synthesis by binding of the drug to the β subunit of RNA polymerase, RpoB. 31 Mtb gains rifampicin resistance primarily through rpoB mutations, and more than 95% of these mutations are present within an 81 bp rifampicin resistance-determining region (RRDR, corresponding to codons 426–452 in Mtb and codons 507–533 in E. coli ). 32 Mutations in codons 450, 445 and 435 are common among clinical rifampicin-resistant isolates; of these mutations, S450L occurs most frequently.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that rpoB expression is upregulated in XDR-TB strains that are exposed to rifampicin. 31 RNA expression needs to be further tested to explore the reason.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Factors Influencing Multidrug-Resistant Tuberculosis and Validation of Whole-Genome Sequencing in Children with Drug-Resistant Tuberculosis

Zhang¹,

Zhao²,

Zhang³

et al. 2021

IDR

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Objective Pediatric tuberculosis (TB) is one of the top ten causes of death in children. Our study was to analyze influencing factors of multidrug-resistant tuberculosis (MDR-TB) and validation of whole-genome sequencing (WGS) used in children with drug-resistant TB (DR-TB). Methods All Mycobacterium tuberculosis (Mtb) strains were isolated from patients aged below 18 years old of Children’s Hospital of Chongqing Medical University, China. A total of 208 Mtb isolates were tested for eight anti-TB drugs with phenotypic drug susceptibility test (DST) and for genetic prediction of the susceptible profile with WGS. The patients corresponding to each strain were grouped according to drug resistance and genotype. Influencing factors of MDR-TB and DR-TB were analyzed. Results According to the phenotypic DST and WGS, 82.2% of Mtb strains were susceptible to all eight drugs, and 6.3% were MDR-TB. Using the phenotypic DSTs as the gold standard, the kappa value of WGS to predict isoniazid, rifampin, ethambutol, rifapentine, prothionamide, levofloxacin, moxifloxacin and amikacin was 0.84, 0.89, 0.59, 0.86, 0.89, 0.82, 0.88 and 1.00, respectively. There was significant difference in the distribution of severe TB, diagnosis, treatment and outcome between MDR and drug-susceptible group (P<0.05). The distribution of severe TB and treatment between DR and drug-susceptible group was statistically different (P<0.05). The results of binary logistic regression showed that Calmette–Guérin bacillus (BCG) vaccine is the protective factor for MDR-TB (OR=0.19), and MDR-TB is the risk factor for PTB and EPTB (OR=17.98). Conclusion The BCG vaccine is a protective factor for MDR-TB, and MDR-TB might not be confined to pulmonary infection, spreading to extrapulmonary organs in children. MDR-TB had more severe cases and a lower recovery rate than drug-susceptible TB. WGS could provide an accurate prediction of drug susceptibility test results for anti-TB drugs, which are needed for the diagnosis and precise treatment of TB in children.

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A systemic approach to explore the mechanisms of drug resistance and altered signaling cascades in extensively drug-resistant tuberculosis

Cited by 30 publications

References 41 publications

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Comparison of critical biomarkers in 2 erectile dysfunction models based on GEO and NOS-cGMP-PDE5 pathway

Analysis of Factors Influencing Multidrug-Resistant Tuberculosis and Validation of Whole-Genome Sequencing in Children with Drug-Resistant Tuberculosis

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