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1.
Urol Oncol ; 41(12): 486.e25-486.e32, 2023 12.
Article in English | MEDLINE | ID: mdl-37932135

ABSTRACT

INTRODUCTION: Environmental chemicals have been associated with the regulation of oxidative stress markers, which have the potential for the development of bladder cancer. However, limited studies on the function of oxidative stress parameters and nonmuscle invasive bladder cancer (NMIBC) in therapy response are available. Here we studied the oxidative stress parameters in response to BCG immunotherapy in NMIBC patients. MATERIAL AND METHODS: A total of 120 patients with NMIBC and treatment with BCG were enrolled and categorized into 2 groups on BCG response, 50 patients were BCG-responsive (BCG-R) and 70 were BCG-nonresponsive (BCG-N). BCG-R have no evidence of tumor recurrence or advancement after 1 year of BCG immunotherapy, but BCG-N has a recurrence of tumor after 3 to 6 months cycles of BCG instillation, as determined by cystoscopy. In all groups, we measured the levels of oxidative stress markers- malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT). RESULTS: The levels of oxidative stress markers viz. MDA, NO, and SOD in the BCG-N group were significantly higher (P < 0.001) than in the BCG-R group. Furthermore, the data demonstrated a significant correlation between oxidative stress marker and NMIBC T1 high grade and tumor size >2.5 cm. However, no statistically significant difference was found between studied groups with CAT. CONCLUSION: The findings suggest that the carcinogenesis of NMIBC is associated with oxidative damage of biomolecules and indicates the involvement of oxidative stress markers in the development and recurrence of NMIBC.; Therefore, it is critical to ensure the management for T1 high grade and tumor size of >2.5 cm for antioxidant protection.


Subject(s)
Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Humans , BCG Vaccine/therapeutic use , Adjuvants, Immunologic/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Immunotherapy , Oxidative Stress , Superoxide Dismutase/therapeutic use , Administration, Intravesical , Neoplasm Invasiveness
2.
Pediatr Surg Int ; 38(11): 1601-1617, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36107237

ABSTRACT

PURPOSE: Wilms' tumor is the most-frequent malignant-kidney tumor in children under 3-4 years of age and is caused by genetic alterations of oncogenes (OG) and tumor-suppressor genes (TG). Wilms' tumor has been linked to many OG-&-TG. However, only WT1 has a proven role in the development of this embryonic-tumor. METHODS: The study investigates the level of mRNA expression of 16 OGs and 20 TGs involved in key-signaling pathways, including chromatin modification; RAS; APC; Cell Cycle/Apoptosis; Transcriptional Regulation; PI3K; NOTCH-&-HH; PI3K & RAS of 24-fresh Wilms'-tumor cases by capture-and-reporter probe Code-Sets chemistry, as CNVs in these pathway genes have been reported. RESULTS: Upon extensively investigating, MEN1, MLL2, MLL3, PBRM1, PRDM1, SMARCB1, SETD2, WT1, PTPN11, KRAS, HRAS, NF1, APC, RB1, FUBP1, BCOR, U2AF1, PIK3CA, PTEN, EBXW7, SMO, ALK, CBL, EP300-and-GATA1 were found to be significantly up-regulated in 58.34, 62.5, 79.17, 91.67, 58, 66.66,54, 58.34, 66.67, 75, 62.5, 62.5, 58, 79.17, 79.17, 75, 70.84, 50, 50, 75, 66.66, 62.50, 61.66, 58.34-and-62.50% of cases respectively, whereas BRAF, NF2, CDH1, BCL2, FGFR3, ERBB2, MET, RET, EGFR-and-GATA2 were significantly down regulated in 58, 87.50, 79.16, 54.16, 79.17, 91.66, 66.66, 58.33, 91.66-and-62.50% of cases, respectively. Interestingly, the WT1 gene was five-fold down regulated in 41.66% of cases only. CONCLUSION: Hence, extensive profiling of OGs and TGs association of major-signaling pathways in Wilms' tumor cases may aid in disease diagnosis. PBRM1 (up-regulated in 91.67% of cases), ERBB2 and EGFR (down-regulated in 91.66 and 91.66% of cases, respectively) could be marker genes. However, validation of all relevant results in a larger number of samples is required.


Subject(s)
Kidney Neoplasms , Wilms Tumor , Child , Chromatin , Class I Phosphatidylinositol 3-Kinases/genetics , DNA-Binding Proteins , ErbB Receptors , Genes, Suppressor , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins p21(ras)/genetics , RNA, Messenger , RNA-Binding Proteins , Receptor Protein-Tyrosine Kinases/genetics , Signal Transduction/genetics , Splicing Factor U2AF/genetics , Wilms Tumor/genetics , Wilms Tumor/pathology
3.
Mol Biol Rep ; 49(7): 6753-6762, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35249167

ABSTRACT

INTRODUCTION: The outbreak of coronavirus disease 2019 (Covid-19) severely impacted global health and economic status. The native receptor-ligand interaction of Angiotensin-converting enzyme 2 (ACE2) and S protein induces host cell pathogenesis via immunosuppression. MATERIAL AND METHODS: The emerging evidence reports the sex disparity in Covid-19 induced mortality rate which affects abundantly men population. Although the biological interaction of Covid-19 with receptor upregulates the viral genome protein interactions and initiates the predictive multiorgan failure followed by acute kidney injury (AKI) in Covid-19 infected male population. CONCLUSION: Besides, the knowledge and lessons learned from the study depict that cellular and molecular links may explain the risk and severity of Covid-19 and AKI in the male population and lead to management of Covid-19 induced AKI. Therefore, this review explored the pathways associated with the pathogenesis of two diseased conditions with sex disparity.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , Male , SARS-CoV-2 , Sex Characteristics
4.
Soft Matter ; 18(9): 1819-1824, 2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35166748

ABSTRACT

We study the electrophoresis of metal-dielectric Janus particles with dipolar director symmetry in two nematic liquid crystals (LCs) having the same sign of conductivity anisotropy (Δσ) but opposite signs of dielectric anisotropy (Δε). The applied ac electric field is parallel and perpendicular to the director for positive and negative dielectric anisotropy LCs, respectively. We show that the Janus dipolar particles propel faster than the non-Janus dipolar particles in both LCs. The propelling speed of the Janus dipolar particles is also significantly higher compared to the quadrupolar Janus particles studied previously. We map the electroosmotic flow fields surrounding a Janus dipolar particle using microparticle image velocimetry (µ-PIV) and show that the flow on a metal hemisphere is stronger than that on a dielectric hemisphere. Altogether, Janus dipolar particles demonstrate efficient electrophoresis compared to both Janus and non-Janus quadrupolar particles. These findings may be useful for applications in active matter, microrobotic and microfluidic devices.

5.
BMC Genomics ; 22(1): 685, 2021 Sep 22.
Article in English | MEDLINE | ID: mdl-34548034

ABSTRACT

BACKGROUND: Carp fish, rohu (Labeo rohita Ham.) is important freshwater aquaculture species of South-East Asia having seasonal reproductive rhythm. There is no holistic study at transcriptome level revealing key candidate genes involved in such circannual rhythm regulated by biological clock genes (BCGs). Seasonality manifestation has two contrasting phases of reproduction, i.e., post-spawning resting and initiation of gonadal activity appropriate for revealing the associated candidate genes. It can be deciphered by RNA sequencing of tissues involved in BPGL (Brain-Pituitary-Gonad-Liver) axis controlling seasonality. How far such BCGs of this fish are evolutionarily conserved across different phyla is unknown. Such study can be of further use to enhance fish productivity as seasonality restricts seed production beyond monsoon season. RESULT: A total of ~ 150 Gb of transcriptomic data of four tissues viz., BPGL were generated using Illumina TruSeq. De-novo assembled BPGL tissues revealed 75,554 differentially expressed transcripts, 115,534 SSRs, 65,584 SNPs, 514 pathways, 5379 transcription factors, 187 mature miRNA which regulates candidate genes represented by 1576 differentially expressed transcripts are available in the form of web-genomic resources. Findings were validated by qPCR. This is the first report in carp fish having 32 BCGs, found widely conserved in fish, amphibian, reptile, birds, prototheria, marsupials and placental mammals. This is due to universal mechanism of rhythmicity in response to environment and earth rotation having adaptive and reproductive significance. CONCLUSION: This study elucidates evolutionary conserved mechanism of photo-periodism sensing, neuroendocrine secretion, metabolism and yolk synthesis in liver, gonadal maturation, muscular growth with sensory and auditory perception in this fish. Study reveals fish as a good model for research on biological clock besides its relevance in reproductive efficiency enhancement.


Subject(s)
Carps , Cyprinidae , Animals , Cyprinidae/genetics , Female , Placenta , Pregnancy , Reproduction/genetics , Sequence Analysis, RNA
6.
Transfus Apher Sci ; 60(1): 102956, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32994125

ABSTRACT

The natural history of COVID-19 infection in children is still evolving as the pandemic unfolds. Few cases of severe and often fatal COVID-19 have been reported although the infection is mild in the large majority. Children with cancers are recognised as a high risk group for all infections. Since there aren't any definite treatment guidelines established in children with severe COVID, treatment is guided by adult recommendations which too are often not evidence based. We report the case of a 4-year-old girl with severe COVID-19 associated pneumonia who presented to us as febrile neutropenia. The use of convalescent plasma along with steroids and IVIG showed dramatic results in this child and she recovered without the need for any specific treatment. This is highlighted as one of the earliest cases that is reporting the use of convalescent plasma in a child; the first ever in a child with underlying malignancy.


Subject(s)
COVID-19/therapy , Febrile Neutropenia/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , COVID-19/etiology , Child, Preschool , Febrile Neutropenia/complications , Female , Humans , Immunization, Passive , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , COVID-19 Serotherapy
7.
Cancer Manag Res ; 12: 11973-11988, 2020.
Article in English | MEDLINE | ID: mdl-33244273

ABSTRACT

INTRODUCTION: Heterogeneity of non-small cell lung carcinoma (NSCLC) among patients is currently not well studied. Pathologic markers and staging systems have not been a precise predictor of the prognosis of an individual patient. Hence, we hypothesize to develop a transcript-based signature to categorize stage IIIA-NSCLC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), plus identify markers that could indicate the prognosis of the disease. METHODS: Human Transcriptome Array 2.0 (HTA) and NanoString nCounter® platform were used for high-throughput gene-expression profiling. Initially, we profiled stage IIIA-NSCLC through HTA and validated through NanoString. Additionally, two metastatic markers SPP1 and CDH2 were validated in 47 NSCLC stage IIIA samples through real-time PCR. RESULTS: We observed distinct gene clusters in LUAD and LUSC with down-regulation of six genes and up-regulation of 57 genes through HTA. Ninety-six transcripts were randomly selected after analyzing HTA data and validated on the NanoString platform. We found 40 differentially expressed transcripts that categorized NSCLC into LUAD and LUSC. SPP1 is significantly overexpressed (4.311±1.27 fold in LUAD and 13.41±3.82 fold in LUSC compared to control), and the CDH2 transcript was significantly overexpressed (11.53 ± 4.027-fold compared to control) only in LUSC. DISCUSSION: These markers enable us to categorize stage IIIA NSCLC into LUAD and LUSC plus these markers may be helpful to understand the pathophysiology of NSCLC. However, more data required to make these findings useful in general clinical practice.

8.
Oncotarget ; 11(34): 3227-3243, 2020 Aug 25.
Article in English | MEDLINE | ID: mdl-32922662

ABSTRACT

Highly keratinized oral squamous cell carcinoma (OSCC) exhibits an improved response to treatment and prognosis compared with weakly keratinized OSCC. Therefore, we aimed to develop gene transcript signature and to identify novel full-length isoforms, fusion transcript and non-coding RNA to differentiate well-differentiated (WD) with Moderately Differentiated (MD)/Poorly Differentiated (PD)/WD-lymphadenopathy OSCC through, HTA, Isoform sequencing, and NanoString. Additionally, specific copy number gain and loss were also identify in WD keratinized OSCC through Oncoscan array and validated through Real-time PCR in histopathologically characterized FFPE-WD keratinized OSCC. Three-hundred-thirty-eight (338) differentially expressed full-length (FL) transcript isoforms (317 upregulated and 21 down-regulated in OSCC) were identified through Isoform Sequencing using the PacBio platform. Thirty-four (34) highly upregulated differentially expressed transcripts from IsoSeq data were also correlated with HTA2.0 and validated in 42 OSCC samples. We were able to identify 18 differentially expressed transcripts, 12 fusion transcripts, and two long noncoding RNAs. These transcripts were involved in increased cell proliferation, dysregulated metabolic reprogramming, oxidative stress, and immune system markers with enhanced immune rearrangements, suggesting a cancerous nature. However, an increase in proteasomal activity and hemidesmosome proteins suggested an improved prognosis and tumor cell stability in keratinized OSCC and helped to characterize WD with MD/PD/WD with lymphadenopathy OSCC. Additionally, novel isoforms of IL37, NAA10, UCHL3, SPAG7, and RAB24 were identified while in silico functionally validated SPAG7 represented the premalignant phenotype of keratinized (K4) OSCC. Most importantly we found copy number gain and overexpression of EGFR suggest that TKIs may also be used as therapeutics in WD-OSCCs.

9.
Indian J Anaesth ; 64(Suppl 2): S132-S135, 2020 May.
Article in English | MEDLINE | ID: mdl-32773852

ABSTRACT

Ever since the outbreak of novel Corona Virus 2019 pandemic, Anaesthesiologists are among the frontline leaders in not only the prevention of and control over the spread of the pandemic but also planning, organizing and coordinating the deployment and utilization of the medical and all other resources effectively and efficiently in order to minimize the losses and sufferings of human lives and recouping the global wellbeing at large. This article briefly highlights the prompt, optimal and effective contributions of the Indian Railways, Indian Railway Health Services and the Railway Association of ISA (RAISA) towards the provision of safe and scientific health services to maximum number of our fellow citizens.

10.
Biomed Res Int ; 2019: 8163591, 2019.
Article in English | MEDLINE | ID: mdl-31111067

ABSTRACT

Retrospective analysis has already shown correlation between severe Chronic Periodontitis (CP) cases with human papiloma virus (HPV). Hence, we aimed to explore deep-seated infected granulation tissue removed during periodontal flap surgery procedures for residential bacterial species between HPV+ and HVP- CP cases, which may serve as good predisposition marker for oral cancer. All CP-granulation samples showed the prominence of Firmicutes, Proteobacteria, and Bacteroidetes phyla with an abundance of gram negative anaerobes, except Streptococcus. In Beta diversity nonmetric multidimensional scaling plot, the random distribution of species was observed between HPV+ and HPV- CP granulation-samples. However, an abundance of Capnocytophaga ochracea was observed in HPV+ CP samples (p<0.05), while Porphyromonas endodontalis, Macellibacteroides fermentas, Treponema phagedenis, and Campylobacter rectus species were highly abundant in HPV- CP samples (p<0.05). The differential species richness leads altered functions related to mismatch-repair and nucleotide excision-repair and cytoskeleton-proteins. Hence, differential abundance of gram negative bacterial species between HPV+ and HPV- granulation-samples under anaerobic conditions may release virulence factors which may alter pathways favouring carcinogenesis. Hence, these species may serve as good predisposition marker for oral-cancer.


Subject(s)
Bacteria/classification , Chronic Periodontitis/microbiology , Dysbiosis , Granulation Tissue/microbiology , Microbiota , Papillomavirus Infections/complications , Adolescent , Adult , Aged , Bacteria/genetics , Biodiversity , Female , Humans , Male , Middle Aged , Papillomaviridae , Papillomavirus Infections/immunology , Periodontal Index , Periodontal Pocket , RNA, Ribosomal, 16S , Retrospective Studies , Young Adult
11.
Sci Rep ; 9(1): 81, 2019 Jan 14.
Article in English | MEDLINE | ID: mdl-30643211

ABSTRACT

Colloidal particles in nematic liquid crystals create elastic distortion and experience long-range forces. The symmetry of elastic distortion and consequently the complexity of interaction strongly depends largely on the liquid crystal anchoring, topology and shape of the particles. Here, we introduce a new nematic colloidal system made of peanut-shaped hematite particles. We report experimental studies on spontaneous orientation, mutual interaction, laser assisted self-assembly and the effect of external magnetic fields on the colloids. Majority of the colloids spontaneously orient either parallel or perpendicular to the nematic director. The colloids that are oriented perpendicularly exhibit two types of textures due to the out of plane tilting, which is corroborated by the Landau-de Gennes Q-tensor modelling. The transverse magnetic moment of the peanut-shaped colloids is estimated by using a simple analysis based on the competing effects of magnetic and elastic torques.

12.
Pediatr Surg Int ; 34(9): 991-1008, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30078147

ABSTRACT

BACKGROUND: The genetic association of hypospadias-risk studies has been conducted in Caucasians, Chinese-Han populations and few in Indian populations. However, no comprehensive approach has been followed to assess genetic involvement in the severity of the disorder. METHODS: The study evaluated to establish the correlation between genotyped single nucleotide and copy number variants (SNPs/CNVs) and severity of hypospadias by an association in a total 30 SNPs in genes related to sex hormone-biosynthesis and metabolism; embryonic-development and phospholipase-D-signalling pathways on 138 surgery-confirmed hypospadias-cases from North India (84 penile and 28 cases of penoscrotal-hypospadias as compared with 31 cases of glanular + coronal), and analyzed and identified CNVs in four familial cases (18 members) and three paired-sporadic cases (6 members) using array-based comparative-genomic-hybridization and validated in 32 hypospadias samples by TaqMan assay. RESULTS: Based on odds ratio at 95% CI, Z Statistic and Significance Levels, STS gene-rs17268974 was associated with Penile-Hypospadias and 9-SNPs [seven-SNPs (rs5934740; rs5934842; rs5934913; rs6639811; rs3923341; rs17268974; rs5934937)] of STS gene; rs7562326-SRD5A2 and rs1877031-STARD3 were associated with penoscrotal-hypospadias. On aggregate analysis with p < 0.001, we identified homozygous-loss of Ch7:q34 (PRSS3P2, PRSS2). On validation in previously CNV-characterized and new (32 hypospadias cases), we identified PRSS3P2-loss in most of the grade 3 and 4 hypospadias. Hence, Grade 1 and 2 (coronal and granular) show no-PRSS3P2-loss and no-association with SNPs in STS; SRD5A2; STARD3-gene but Grade 3 and 4 (Penile and Penoscrotal) show PRSS3P2-loss accompanied with the association of SNPs in STS; SRD5A2; STARD3. CONCLUSIONS: Hence, homozygous-loss of PRSS3P2 accompanied with the association of STS; SRD5A2; STARD3 may link to the severity of the disease.


Subject(s)
DNA Copy Number Variations , Hypospadias/genetics , Polymorphism, Single Nucleotide , Severity of Illness Index , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Carrier Proteins/genetics , Genotype , Humans , Male , Membrane Proteins/genetics , Steryl-Sulfatase/genetics , Trypsin/genetics
13.
Oncotarget ; 9(54): 30385-30418, 2018 Jul 13.
Article in English | MEDLINE | ID: mdl-30100996

ABSTRACT

Previously, it has been stated that the BCR-ABL fusion-protein is sufficient to induce Chronic Myeloid Leukemia (CML), but additional genomic-changes are required for disease progression. Hence, we profiled control and tyrosine kinase inhibitors (TKI) alone or in combination with other drug-treated CML-samples in different phases, categorized as drug-sensitive and drug-resistant on the basis of BCR-ABL transcripts, the marker of major molecular-response. Molecular-profiling was done using the molecular-inversion probe-based-array, Human Transcriptomics-Array2.0, and Axiom-Biobank genotyping-arrays. At the transcript-level, clusters of control, TKI-resistant and TKI-sensitive cases were correlated with BCR-ABL transcript-levels. Both at the gene- and exon-levels, up-regulation of MPO, TPX2, and TYMS and down-regulation of STAT6, FOS, TGFBR2, and ITK lead up-regulation of the cell-cycle, DNA-replication, DNA-repair pathways and down-regulation of the immune-system, chemokine- and interleukin-signaling, TCR, TGF beta and MAPK signaling pathways. A comparison between TKI-sensitive and TKI-resistant cases revealed up-regulation of LAPTM4B, HLTF, PIEZO2, CFH, CD109, ANGPT1 in CML-resistant cases, leading to up-regulation of autophagy-, protein-ubiquitination-, stem-cell-, complement-, TGFß- and homeostasis-pathways with specific involvement of the Tie2 and Basigin signaling-pathway. Dysregulated pathways were accompanied with low CNVs in CP-new and CP-UT-TKI-sensitive-cases with undetectable BCR-ABL-copies. High CNVs (previously reported gain of 9q34) were observed in BCR-ABL-independent and -dependent TKI, non-sensitive-CP-UT/AP-UT/B-UT and B-new samples. Further, genotyping CML-CP-UT cases with BCR-ABL 0-to-77.02%-copies, the identified, rsID239798 and rsID9475077, were associated with FAM83B, a candidate for therapeutic resistance. The presence of BCR-ABL, additional genetic-events, dysregulated-signaling-pathways and rsIDs associated with FAM83B in TKI-resistant-cases can be used to develop a signature-profile that may help in monitoring therapy.

14.
Biomed Res Int ; 2018: 4832912, 2018.
Article in English | MEDLINE | ID: mdl-30013983

ABSTRACT

Smoking has been associated with increased risk of periodontitis. The aim of the present study was to compare the periodontal disease severity among smokers and nonsmokers which may help in better understanding of predisposition to this chronic inflammation mediated diseases. We selected deep-seated infected granulation tissue removed during periodontal flap surgery procedures for identification and differential abundance of residential bacterial species among smokers and nonsmokers through long-read sequencing technology targeting full-length 16S rRNA gene. A total of 8 phyla were identified among which Firmicutes and Bacteroidetes were most dominating. Differential abundance analysis of OTUs through PICRUST showed significant (p>0.05) abundance of Phyla-Fusobacteria (Streptobacillus moniliformis); Phyla-Firmicutes (Streptococcus equi), and Phyla Proteobacteria (Enhydrobacter aerosaccus) in nonsmokers compared to smokers. The differential abundance of oral metagenomes in smokers showed significant enrichment of host genes modulating pathways involving primary immunodeficiency, citrate cycle, streptomycin biosynthesis, vitamin B6 metabolism, butanoate metabolism, glycine, serine, and threonine metabolism pathways. While thiamine metabolism, amino acid metabolism, homologous recombination, epithelial cell signaling, aminoacyl-tRNA biosynthesis, phosphonate/phosphinate metabolism, polycyclic aromatic hydrocarbon degradation, synthesis and degradation of ketone bodies, translation factors, Ascorbate and aldarate metabolism, and DNA replication pathways were significantly enriched in nonsmokers, modulation of these pathways in oral cavities due to differential enrichment of metagenomes in smokers may lead to an increased susceptibility to infections and/or higher formation of DNA adducts, which may increase the risk of carcinogenesis.


Subject(s)
Bacteria/genetics , Chronic Periodontitis/microbiology , Granulation Tissue/microbiology , RNA, Ribosomal, 16S/analysis , Adult , Aged , Bacteria/isolation & purification , Chronic Periodontitis/pathology , DNA Adducts , Humans , Middle Aged , Smokers
16.
Meta Gene ; 7: 70-5, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26862483

ABSTRACT

Here, we sequenced and functionally annotated the long reads (1-2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes--PNMT, SNN and LAMB1 show their involvement in Ependymoma.

17.
Gene ; 576(2 Pt 2): 734-42, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26456192

ABSTRACT

PURPOSE: Based on copy number alterations and transcriptional profiles, the posterior fossa tumors (medulloblastoma (MB), ependymoma and pilocytic astrocytoma) have been classified into various subgroups. The study design was aimed to identify and catalog genome-wide copy number alterations and differential gene expression in different types of North-Indian pediatric posterior fossa tumors and matched control tissue through Molecular Inversion Probe (MIP) Based and Human Transcriptome Array. EXPERIMENTAL DESIGN: MIP based OncoScan Array and Human Transcriptome Array 2.0 were used to molecularly-categorize histopathologically and immunohistochemically proven tumor samples on the basis of copy number variations and altered gene expression patterns and/or alternative splicing events. RESULTS: Based on molecular, histopathological/immunohistochemical and age-dependent factors MB was subgrouped into group-3 MB, Wnt and SHH; ependymoma into balanced, numerical and structural/anaplastic; and pilocytic astrocytoma was stratified age-dependently. Compared with the vermis tissue of MB, the vermis tissue of ependymoma showed higher levels of gain and losses compared with their counter tumor parts implicating metastasis within the confined region. Group-3 MB and anaplastic ependymoma represented highest differentially expressed genes both at gene and exon levels in the CN altered regions compared with other subgroups of MB and ependymoma respectively. CONCLUSION: This multiomics approach based molecular characterization of posterior fossa tumors together with clinical and histopathological factors may help us in the area of personalized medicine.


Subject(s)
Brain Neoplasms/genetics , DNA Copy Number Variations/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genome, Human , Genomics/methods , Adolescent , Child , Child, Preschool , Cluster Analysis , Humans , India , Infant , Mutation/genetics
18.
PLoS One ; 10(7): e0132450, 2015.
Article in English | MEDLINE | ID: mdl-26148098

ABSTRACT

Rohu is a leading candidate species for freshwater aquaculture in South-East Asia. Unlike common carp the monsoon breeding habit of rohu restricts its seed production beyond season indicating strong genetic control over spawning. Genetic information is limited in this regard. The problem is exacerbated by the lack of genomic-resources. We identified 182 reproduction-related genes previously by Sanger-sequencing which were less to address the issue of seasonal spawning behaviour of this important carp. Therefore, the present work was taken up to generate transcriptome profile by mRNAseq. 16 GB, 72 bp paired end (PE) data was generated from the pooled-RNA of twelve-tissues from pre-spawning rohu using IlluminaGA-II-platform. There were 64.97 million high-quality reads producing 62,283 contigs and 88,612 numbers of transcripts using velvet and oases programs, respectively. Gene ontology annotation identified 940 reproduction-related genes consisting of 184 mainly associated with reproduction, 223 related to hormone-activity and receptor-binding, 178 receptor-activity and 355 embryonic-development related-proteins. The important reproduction-relevant pathways found in KEGG analysis were GnRH-signaling, oocyte-meiosis, steroid-biosynthesis, steroid-hormone biosynthesis, progesterone-mediated oocyte-maturation, retinol-metabolism, neuroactive-ligand-receptor interaction, neurotrophin-signaling and photo-transduction. Twenty nine simple sequence repeat containing sequences were also found out of which 12 repeat loci were polymorphic with mean expected-&-observed heterozygosity of 0.471 and 0.983 respectively. Quantitative RT-PCR analyses of 13-known and 6-unknown transcripts revealed differences in expression level between preparatory and post-spawning phase. These transcriptomic sequences have significantly increased the genetic-&-genomic resources for reproduction-research in Labeo rohita.


Subject(s)
Cyprinidae/physiology , Fish Proteins/biosynthesis , Gene Expression Regulation/physiology , Reproduction/physiology , Transcriptome/physiology , Animals , Female , Male
19.
Article in English | MEDLINE | ID: mdl-24741325

ABSTRACT

In this article, we have reviewed current literature regarding the regulation of hepatocellular carcinoma (HCC) by the interaction of malignant hepatocytes and their tissue environment through cytokine signaling, here represented by transforming growth factor-beta (TGF-ß) signaling. We have discussed responses of TGF-ß signaling in transition of hepatic stellate cells to myofibroblasts (MFBs), recruitment of tumor-associated macrophages (TAMs), and enrichment of tumor-associated endothelial cells (TECs). The malignant hepatocytes also secrete various factors such as platelet-derived growth factors (PDGFs), vascular endothelial growth factor (VEGF), and TGF-ß. TGF-ß, a super-family of cytokines, creates tumor microenvironment by interacting through other growth factors (epidermal growth factor receptor (EGFR), PDGF, fibroblast growth factor (FGF), hepatocyte growth factor (HGF), VEGF), cytokines and chemokines, and extracellular matrix (ECM) remodeling. Hence, the HCC tumor microenvironment may now be recognized as an important participant of tumor progression to act as potential target to systemic therapies compared to targeted therapies.

20.
Indian J Anaesth ; 56(3): 287-90, 2012 May.
Article in English | MEDLINE | ID: mdl-22923830

ABSTRACT

We report a case of "dry tap" during spinal anaesthesia in a patient posted for incision and drainage of lower limb with cellulitis. When the patient was being given sub-arachnoid block (SAB) for regional anaesthesia, it turned out to be a case of pyogenic ilio-psoas abscess extended up to the paravertebral and epidural spaces. The causative organism was Staphylococcus aureus. This is probably the first case reported when epidural abscess is diagnosed during SAB.

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