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1.
J Environ Manage ; 301: 113854, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34607141

RESUMO

Insights into thermal degradation behaviour, kinetics, reaction mechanism, possible synergism, and thermodynamic analysis of co-pyrolysis of carbonaceous materials are crucial for efficient design of co-pyrolysis reactor systems. Present study deals with comprehensive kinetics and thermodynamic investigation of co-pyrolysis of petroleum coke (PC) and banana leaves biomass (BLB) for realizing the co-pyrolysis potential. Thermogravimetric non-isothermal studies have been performed at 10, 20, and 30 °C/min heating rates. Synergistic effect between PC and BLB was determined by Devolatilization index (Di) and mass loss method. Kinetic parameters were estimated using seven model-free methods. Standard activation energy for PC + BLB blend from FWO, KAS, Starink, and Vyazovkin methods was ≈165 kJ/mol and that from Friedman and Vyazovkin advanced isoconversional methods was ≈171 kJ/mol. The frequency factor calculated for the blend from Kissinger method was found to be in the range of 106-1016s-1. Devolatilization index (Di) showed synergistic effect of blending. The data pertaining to co-pyrolysis was found to fit well with R2 (second order) and D3 (three dimensional) from Z(α) master plot. Thermodynamic parameters, viz. ΔH ≈ 163 kJ/mol and ΔG ≈ 151 kJ/mol were calculated to determine the feasibility and reactivity of the co-pyrolysis process. The results are expected to be useful in the design of petcoke and banana leaves biomass co-pyrolysis systems.


Assuntos
Coque , Musa , Petróleo , Biomassa , Cinética , Folhas de Planta , Pirólise , Termodinâmica , Termogravimetria
2.
Cell Biol Toxicol ; 37(5): 731-749, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33566221

RESUMO

Cervical cancer (CC) is a leading cause of cancer-related death among women in developing countries. However, the underlying mechanisms and molecular targets for therapy remain to be fully understood. We investigated the epigenetic regulation, biological functions, and clinical utility of zinc-finger protein 471 (ZNF471) in CC. Analysis of cervical tissues and five independent public datasets of CC showed significant hypermethylation of the ZNF471 gene promoter. In CC cell lines, promoter DNA methylation was inversely correlated with ZNF471 expression. The sensitivity and specificity of the ZNF471 hypermethylation for squamous intraepithelial lesion (SIL) vs tumor and normal vs tumor was above 85% with AUC of 0.937. High methylation and low ZNF471 expression predicted poor overall and recurrence-free survival. We identified -686 to +114 bp as ZNF471 promoter, regulated by methylation using transient transfection and luciferase assays. The promoter CpG site methylation of ZNF471 was significantly different among cancer types and tumor grades. Gal4-based heterologous luciferase reporter gene assays revealed that ZNF471 acts as a transcriptional repressor. The retroviral mediated overexpression of ZNF471 in SiHa and CaSki cells inhibited growth, proliferation, cell migration, invasion; delayed cell cycle progression in vitro by increasing cell doubling time; and reduced tumor growth in vivo in nude mice. ZNF471 overexpression inhibited key members of epithelial-mesenchymal transition (EMT), Wnt, and PI3K-AKT signaling pathways. ZNF471 inhibited EMT by directly targeting vimentin as analyzed by bioinformatic analysis, ChIP-PCR, and western blotting. Thus, ZNF471 CpG specific promoter methylation may determine the prognosis of CC and could function as a potential tumor suppressor by targeting EMT signaling.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias do Colo do Útero , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA , Epigênese Genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases , Prognóstico , Neoplasias do Colo do Útero/genética
3.
Gynecol Oncol ; 155(1): 135-143, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31434614

RESUMO

OBJECTIVE: The altered miRNAs expression in cervical cancer tissue can be a critical player during tumorigenesis, may contribute to tumor cell heterogeneity and may determine distinct phenotypes within the tumor. Recent studies have highlighted the role of circulating miRNAs as a minimally-invasive biomarker and its potential as biosignature to complement routine tissue-based procedures. METHODS: In order to determine whether miRNAs in serum can indicate changes in cervical tissue specimens, we performed small RNA sequencing and selected miRNAs were validated using qRT-PCR in serum and tissue specimens (n = 115). Further, luciferase assay were performed to investigate the interactions between hsa-miR-409-3p and hsa-miR-454-3p binding sites on 3'UTR region of MTF2 and ST18 respectively. RESULTS: We have identified a total of 14 differentially expressed miRNAs common in serum and tissue specimens. Among them, hsa-miR-17-5p, hsa-miR-32-5p and hsa-miR-454-3p were upregulated while, hsa-miR-409-3p was downregulated in serum and tissue of cervical cancer subjects. Our in-silico small RNA sequencing data analysis identified isomiRs and classified miRNA into clusters and subtypes (exonic, intronic and intergenic) with respect to the expression status in serum and tissue specimens. Expression level of hsa-miR-409-3p and hsa-miR-454-3p were inversely correlated with their target genes MTF2 and ST18 levels respectively in human cervical cancer specimens. Luciferase assay demonstrated that hsa-miR-409-3p and hsa-miR-454-3p functionally interacts with 3'-UTR of MTF2 and ST18 respectively to decrease their activity. CONCLUSION: Our results support the significant role of circulating miRNAs in disease dissemination and their potential utility as biosignatures of clinical relevance.


Assuntos
MicroRNAs/biossíntese , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , MicroRNAs/sangue , MicroRNAs/genética , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologia
4.
Infect Dis Obstet Gynecol ; 2019: 4376902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019362

RESUMO

Introduction: Young women (20-35 years) are at high risk of HPV infection, although the majority of the infections are asymptomatic and are cleared spontaneously by the host immune system. These are also the group of women who are sexually active and are in the population of pregnant women. During pregnancy, the changes in the hormonal milieu and immune response may favor persistence of HPV infection and may aid in transgenerational transmission thereby furthering the cancer risk. In the present study, we determined the prevalence of vaginal HPV infection in early pregnancy and attempted to relate with pregnancy outcome. Material and Methods: Vaginal cytology samples were collected from the condoms used to cover the vaginal sonography probe during a routine first trimester visit to the hospital. All women were followed up throughout pregnancy and childbirth. Maternal and neonatal outcomes were recorded. Results: We found a prevalence of HPV infection around 39.4% in our population. Interestingly all HPV positive women were infected with one or more high risk HPV viruses with an overlap of intermediate and low risk in 43% and 7.3%, respectively. Women with preterm prelabor rupture of membranes (PPROM) showed a statistically higher incidence in HPV positive (7.3%) group as compared to the HPV negative (3.2%) group. Conclusion: The prevalence of genital HPV infection is high during pregnancy (around 40%) and was associated with higher incidence of PPROM.


Assuntos
Infecções por Papillomavirus/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Estudos de Coortes , Feminino , Ruptura Prematura de Membranas Fetais/etiologia , Humanos , Infecções por Papillomavirus/complicações , Gravidez , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Prevalência , Estudos Prospectivos , Adulto Jovem
5.
Mol Carcinog ; 57(3): 370-382, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29077234

RESUMO

Regulation of miRNA gene expression by DNA promoter methylation may represent a key mechanism to drive cervical cancer progression. In order to understand the impact of DNA promoter methylation on miRNAs at various stages of cervical carcinogenesis, we performed DNA methylation microarray on Normal Cervical Epithelium (NCE), Cervical Intraepithelial Neoplasia (CIN I-III) and Squamous Cell Carcinoma (SCC) tissues to identify differentially methylated miRNAs followed by validation by bisulfite sequencing. Further, expression of miRNAs was analyzed by qRT-PCR in clinical tissues and cervical cancer cell lines. Transcriptional activity was determined by luciferase assay. We identified a total of 69 hypermethylated and hypomethylated miRNA promoters encompassing 78 CpG islands in all except Y chromosome, among the three groups. The candidate DNA promoters of miR-424 were significantly hypermethylated and miR-200b and miR-34c were significantly hypomethylated in SCC compared to NCE (P < 0.05). Expression of miR-424, miR-200b, and miR-34c were inversely correlated with promoter DNA methylation in tissue samples. Treatment of cell lines with 5-aza-2'-deoxycytidine showed differential expression in all three miRNAs. We observed a decrease in miRNA promoter activity following in vitro SssI methylase treatment of miR-424, miR-200b, and miR-34c. Luciferase assay demonstrated that miR-200b and miR-424 functionally interacts with 3'-UTR of HIPK3 and RBBP6 respectively and decreased their activity in presence of miR-200b and miR-424 mimics transfected in SiHa cells. Taken together, we have identified deregulation of miRNAs by aberrant DNA promoter methylation, leading to its transcriptional silencing during cervical carcinogenesis, which can be potential targets for diagnosis and therapy.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Epigênese Genética , Feminino , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/patologia
6.
Tumour Biol ; 39(3): 1010428317694573, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28351298

RESUMO

Multicomponent molecular modifications such as DNA methylation may offer sensitive and specific cervical intraepithelial neoplasia and cervical cancer biomarkers. In this study, we tested cervical tissues at various stages of tumor progression for 5-methylcytosine and 5-hydroxymethylcytosine levels and also DNA promoter methylation profile of a panel of genes for its diagnostic potential. In total, 5-methylcytosine, 5-hydroxymethylcytosine, and promoter methylation of 33 genes were evaluated by reversed-phase high-performance liquid chromatography, enzyme-linked immunosorbent assay based technique, and bisulfate-based next generation sequencing. The 5-methylcytosine and 5-hydroxymethylcytosine contents were significantly reduced in squamous cell carcinoma and receiver operating characteristic curve analysis showed a significant difference in (1) 5-methylcytosine between normal and squamous cell carcinoma tissues (area under the curve = 0.946) and (2) 5-hydroxymethylcytosine levels among normal, squamous intraepithelial lesions and squamous cell carcinoma. Analyses of our next generation sequencing results and data from five independent published studies consisting of 191 normal, 10 low-grade squamous intraepithelial lesions, 21 high-grade squamous intraepithelial lesions, and 335 malignant tissues identified a panel of nine genes ( ARHGAP6, DAPK1, HAND2, NKX2-2, NNAT, PCDH10, PROX1, PITX2, and RAB6C) which could effectively discriminate among the various groups with sensitivity and specificity of 80%-100% (p < 0.05). Furthermore, 12 gene promoters (ARHGAP6, HAND2, LHX9, HEY2, NKX2-2, PCDH10, PITX2, PROX1, TBX3, IKBKG, RAB6C, and DAPK1) were also methylated in one or more of the cervical cancer cell lines tested. The global and gene-specific methylation of the panel of genes identified in our study may serve as useful biomarkers for the early detection and clinical management of cervical cancer.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA/genética , Neoplasias do Colo do Útero/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas Nucleares , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Regiões Promotoras Genéticas , Fatores de Transcrição , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
7.
Int J Gynecol Cancer ; 26(4): 705-10, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26937755

RESUMO

OBJECTIVE: This study aimed to evaluate a specific glomerular pattern for prognostication of endometrial cancer (EC). MATERIALS AND METHODS: The office hysteroscopy's picture and video of 4197 women were reviewed, 48 women who were suspected of type I EC were analyzed: 26 have glomerular pattern (group 1) and 22 without it (group 2). RESULTS: The histopathological grading after hysterectomy with glomerular pattern had grade 2 or grade 3 disease on final histology (n = 25; 96%). The sensitivity and specificity of this test were 84.6% and 81.8%, respectively, with a likelihood ratio of 4:6 in predicting and prognosticating those women who have high-grade tumor or invasive disease. CONCLUSIONS: This hysteroscopic picture might be used as a novel marker for risk stratification of EC.


Assuntos
Adenocarcinoma/patologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Histerectomia , Histeroscopia/métodos , Neoplasias Uterinas/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Hiperplasia Endometrial/cirurgia , Neoplasias do Endométrio/cirurgia , Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Reconhecimento Automatizado de Padrão , Prognóstico , Estudos Retrospectivos , Neoplasias Uterinas/cirurgia
8.
J Biol Chem ; 289(15): 10637-10649, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24570007

RESUMO

Double C2-like domain ß (DOC2B) gene encodes for a calcium-binding protein, which is involved in neurotransmitter release, sorting, and exocytosis. We have identified the promoter region of the DOC2B gene as hypermethylated in pre-malignant, malignant cervical tissues, and cervical cancer cell lines by methylation-sensitive dimethyl sulfoxide-polymerase chain reaction and bisulfite genome sequencing; whereas, it was unmethylated in normal cervical tissues (p < 0.05). The promoter hypermethylation was inversely associated with mRNA expression in SiHa, CaSki, and HeLa cells and treatment with demethylating agent 5-aza-2-deoxycytidine restored DOC2B expression. The region -630 to +25 bp of the DOC2B gene showed robust promoter activity by a luciferase reporter assay and was inhibited by in vitro artificial methylation with Sss1 methylase prior to transient transfections. Overexpression of the DOC2B gene in SiHa cells when compared with controls showed significantly reduced colony formation, cell proliferation, induced cell cycle arrest, and repressed cell migration and invasion (p < 0.05). Ectopic expression of DOC2B resulted in anoikis-mediated cell death and repressed tumor growth in a nude mice xenograft model (p < 0.05). DOC2B expressing cells showed a significant increase in intracellular calcium level (p < 0.05), impaired AKT1 and ERK1/2 signaling, and induced actin cytoskeleton remodeling. Our results show that promoter hypermethylation and silencing of the DOC2B gene is an early and frequent event during cervical carcinogenesis and whose reduced expression due to DNA promoter methylation may lead to selective cervical tumor growth.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/metabolismo , Actinas/metabolismo , Animais , Apoptose , Cálcio/química , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ilhas de CpG , Feminino , Genótipo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Proteínas do Tecido Nervoso/metabolismo , Papillomaviridae/metabolismo , Estrutura Terciária de Proteína , Transdução de Sinais , Sulfitos/química
9.
J Pathol ; 231(1): 53-62, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23674368

RESUMO

Transformation of epithelial cells by high-risk human papillomavirus (hrHPV) types can lead to anogenital carcinomas, particularly cervical cancer, and oropharyngeal cancers. This process is associated with DNA methylation alterations, often affecting tumour suppressor gene expression. This study aimed to comprehensively unravel genome-wide DNA methylation events linked to a transforming hrHPV-infection, which is driven by deregulated expression of the viral oncogenes E6 and E7 in dividing cells. Primary human keratinocytes transduced with HPV16E6E7 and their untransduced counterparts were subjected to methylation-specific digital karyotyping (MSDK) to screen for genome-wide DNA-methylation changes at different stages of HPV-induced transformation. Integration of the obtained methylation profiles with genome-wide gene expression patterns of cervical carcinomas identified 34 genes with increased methylation in HPV-transformed cells and reduced expression in cervical carcinomas. For 12 genes (CLIC3, CREB3L1, FAM19A4, LFNG, LHX1, MRC2, NKX2-8, NPTX-1, PHACTR3, PRDM14, SOST and TNFSF13) specific methylation in HPV-containing cell lines was confirmed by semi-quantitative methylation-specific PCR. Subsequent analysis of FAM19A4, LHX1, NKX2-8, NPTX-1, PHACTR3 and PRDM14 in cervical tissue specimens showed increasing methylation levels for all genes with disease progression. All six genes were frequently methylated in cervical carcinomas, with highest frequencies (up to 100%) seen for FAM19A4, PHACTR3 and PRDM14. Analysis of hrHPV-positive cervical scrapes revealed significantly increased methylation levels of the latter three genes in women with high-grade cervical disease compared to controls. In conclusion, MSDK analysis of HPV16-transduced keratinocytes at different stages of HPV-induced transformation resulted in the identification of novel DNA methylation events, involving FAM19A4, LHX1, NKX2-8, PHACTR3 and PRDM14 genes in cervical carcinogenesis. These genes may provide promising triage markers to assess the presence of (pre)cancerous cervical lesions in hrHPV-positive women.


Assuntos
Metilação de DNA , Queratinócitos/metabolismo , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/genética , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Linhagem Celular , Transformação Celular Neoplásica/genética , Transformação Celular Viral , Epigênese Genética , Feminino , Regulação Viral da Expressão Gênica/fisiologia , Papillomavirus Humano 16/fisiologia , Humanos , Cariotipagem/métodos , Queratinócitos/virologia , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas , Reação em Cadeia da Polimerase em Tempo Real , Transdução Genética , Transfecção , Neoplasias do Colo do Útero/virologia
10.
BMJ Case Rep ; 17(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38442970

RESUMO

An early adolescent girl was referred to us with cryptomenorrhoea, and pelvic pain consistent with obstructed menstruation. Originally presumed to be a case of imperforate hymen, she was referred to our centre after two failed surgical misadventures at correcting the obstruction. MRI revealed a haematometrocolpos, high transverse complete vaginal septum and an occluded vagina. She underwent a laparoscopic drainage of the collection, septal resection and a vaginoplasty with an absorbable Interceed graft. Postoperative recovery was smooth and she was sent with instructions to use a vaginal mould daily. Successful surgical treatment requires precise preoperative planning with MRI. A vaginal-assisted laparoscopic approach turned out to be advantageous in resecting the septum to a large extent due to the associated cicatrised vagina. The use of Interceed, a novel mould and harnessing system, ensured a favourable postoperative outcome by bolstering patient motivation due to its less challenging technique of use.


Assuntos
Laparoscopia , Vagina , Adolescente , Feminino , Humanos , Vagina/cirurgia , Drenagem , Cicatriz , Dor Pélvica
11.
Mol Oncol ; 18(6): 1608-1630, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38400534

RESUMO

Cervical cancer (CC) is a key contributor to cancer-related mortality in several countries. The identification of molecular markers and the underlying mechanism may help improve CC management. We studied the regulation and biological function of the chromosome 14 microRNA cluster (C14MC; miR-379/miR-656) in CC. Most C14MC members exhibited considerably lower expression in CC tissues and cell lines in The Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma patient cohorts. Bisulfite Sanger sequencing revealed hypermethylation of the C14MC promoter in CC tissues and cell lines. 5-aza-2 deoxy cytidine treatment reactivated expression of the C14MC members. We demonstrated that C14MC is a methylation-regulated miRNA cluster via artificial methylation and luciferase reporter assays. C14MC downregulation correlated with poor overall survival and may promote metastasis. C14MC activation via the lentiviral-based CRISPRa approach inhibited growth, proliferation, migration, and invasion; enhanced G2/M arrest; and induced senescence. Post-transcriptional regulatory network analysis of C14MC transcriptomic data revealed enrichment of key cancer-related pathways, such as metabolism, the cell cycle, and phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Reduced cell proliferation, growth, migration, invasion, and senescence correlated with the downregulation of active AKT, MYC, and cyclin E1 (CCNE1) and the overexpression of p16, p21, and p27. We showed that C14MC miRNA activation increases reactive oxygen species (ROS) levels, intracellular Ca2+ levels, and lipid peroxidation rates, and inhibits epithelial-mesenchymal transition (EMT). C14MC targets pyruvate dehydrogenase kinase-3 (PDK3) according to the luciferase reporter assay. PDK3 is overexpressed in CC and is inversely correlated with C14MC. Both miR-494-mimic transfection and C14MC activation inhibited PDK3 expression. Reduced glucose uptake and lactate production, and upregulation of PDK3 upon C14MC activation suggest the potential role of these proteins in metabolic reprogramming. Finally, we showed that C14MC activation may inhibit EMT signaling. Thus, C14MC is a tumor-suppressive and methylation-regulated miRNA cluster in CC. Reactivation of C14MC can be useful in the management of CC.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias do Colo do Útero , Feminino , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA/genética , Genes Supressores de Tumor , MicroRNAs/genética , MicroRNAs/metabolismo , Família Multigênica , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo
12.
BioTechnologia (Pozn) ; 104(2): 105-119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427031

RESUMO

Candida auris is a major public health concern due to its high transmission and mortality rates, as well as the emergence of pan-resistant strains. This study aimed to identify an antifungal compound from Sarcochlamys pulcherrima , an ethnomedicinal plant, that can inhibit the growth of C. auris. Methanol and ethyl acetate extracts of the plant were obtained, and high-performance thin-layer chromatography (HPTLC) analysis was conducted to identify the major compounds in the extracts. The major compound detected by HPTLC was subjected to in vitro antifungal activity testing, and its antifungal mechanism was determined. The plant extracts inhibited the growth of both C. auris and Candida albicans. HPTLC analysis revealed the presence of gallic acid in the leaf extract. Furthermore, the in vitro antifungal assay showed that gallic acid inhibited the growth of different C. auris strains. In silico studies indicated that gallic acid can bind to the active sites of carbonic anhydrase (CA) proteins in both C. auris and C. albicans, affecting their catalytic activities. Compounds that target virulent proteins such as CA can aid in the reduction of drug-resistant fungi and the development of novel antifungal compounds with unique modes of action. However, additional in vivo and clinical studies are required to conclusively determine gallic acid's antifungal properties. Gallic acid derivatives may be developed in the future to possess more potent antifungal properties and target various pathogenic fungi.

13.
J Chin Med Assoc ; 86(5): 506-514, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36658688

RESUMO

BACKGROUND: The appropriateness of hysterectomy has gained an interest in scrutiny and debate. Periodic audits of the prevailing clinical practices are imperative for insight, and to formulate recommendations and guidelines. We report the temporal trends of hysterectomies, over the last 10 years in a teaching hospital. METHODS: Present study involved all patients who underwent hysterectomy at a teaching hospital, from January 1, 2012 to December 31, 2021. Patients were identified by medical record tracking using International Classification of Diseases-9 codes. Case records were reviewed for demography, indication for surgery, approach, complications, hospital stay, and histopathological correlation. RESULTS: Over the years the absolute number of hysterectomies in our hospital has ranged from 414 to 597 (mean 476), barring the coronavirus 19 pandemic year. The proportion of hysterectomy among all gynaecological admissions has ranged from 6% to 9%, except in 2020 where this proportion dropped down to 4%. The indications, age distribution, surgical approach, and complications have remained almost same. CONCLUSION: We report a static trend in hysterectomy over the past 10 years. This audit provides an insight for the need of shifting the abdominal to vaginal route, in carefully chosen patients. This will be beneficial for the patients, and for the trainees, where they can learn under supervision. Availability and patient education about the nonsurgical management options for benign gynecological conditions, as well as awareness about sequelae of hysterectomy, will bring down the rate in countries such as India.


Assuntos
Doenças dos Genitais Femininos , Laparoscopia , Feminino , Humanos , Histerectomia , Hospitais de Ensino , Abdome , Estudos Retrospectivos
14.
Biol Methods Protoc ; 7(1): bpac031, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479434

RESUMO

Antibiotic resistance has escalated as a significant problem of broad public health significance. Regular surveillance of antibiotic resistance genes (ARGs) in microbes and metagenomes from human, animal and environmental sources is vital to understanding ARGs' epidemiology and foreseeing the emergence of new antibiotic resistance determinants. Whole-genome sequencing (WGS)-based identification of the microbial ARGs using antibiotic resistance databases and in silico prediction tools can significantly expedite the monitoring and characterization of ARGs in various niches. The major hindrance to the annotation of ARGs from WGS data is that most genome databases contain fragmented genes/genomes (due to incomplete assembly). Herein, we describe an insilicoBacterial Antibiotic Resistance scan (BacARscan) (http://proteininformatics.org/mkumar/bacarscan/) that can detect, predict and characterize ARGs in -omics datasets, including short sequencing, reads, and fragmented contigs. Benchmarking on an independent non-redundant dataset revealed that the performance of BacARscan was better than other existing methods, with nearly 92% Precision and 95% F-measure on a combined dataset of ARG and non-ARG proteins. One of the most notable improvements of BacARscan over other ARG annotation methods is its ability to work on genomes and short-reads sequence libraries with equal efficiency and without any requirement for assembly of short reads. Thus, BacARscan can help monitor the prevalence and diversity of ARGs in microbial populations and metagenomic samples from animal, human, and environmental settings. The authors intend to constantly update the current version of BacARscan as and when new ARGs are discovered. Executable versions, source codes, sequences used for development and usage instructions are available at (http://www.proteininformatics.org/mkumar/bacarscan/downloads.html) and GitHub repository (https://github.com/mkubiophysics/BacARscan).

15.
Eur J Obstet Gynecol Reprod Biol ; 278: 57-65, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36115261

RESUMO

INTRODUCTION: Natural history of urinary incontinence (UI) in women is a less understood domain. Stratifying severity of stress urinary incontinence (SUI) can be an important tool to understand the natural history, prognosticate the disease and plan optimal management. Present study was aimed to test a novel score (Stress Incontinence Combined score: SICS) with the currently popular tools International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and Incontinence Symptom Index (ISI) scores. MATERIAL AND METHODS: This was a prospective study conducted at a university teaching hospital, over a period of 2 years. After screening women for SUI, SICS was administered. The novel SICS score was then compared with ICIQ-UI SF and ISI. RESULTS: A total of 1750 women, attending various OPDs in a tertiary care hospital, were screened for urinary incontinence. The prevalence of UI and SUI was 26.6% and 12.8% respectively. The agreement between ISI and SICS was 81.7%, while the ICIQ- UI SF agreed with the SICS in 80.8% of the cases. AUROC analysis done showed that a score of 10 or more on the SICS (total score 16) could diagnose high-grade SUI with a sensitivity of 97%, specificity of 96% (Reference: ISI), and a sensitivity of 100%, and specificity of 93% (Reference: ICIQ- UI SF) CONCLUSION: SICS is the first of its kind tool, developed to specifically grade the severity of SUI, while incorporating both subjective and objective measures, with excellent reliability and reproducibility.


Assuntos
Incontinência Urinária por Estresse , Incontinência Urinária , Feminino , Humanos , Incontinência Urinária por Estresse/diagnóstico , Reprodutibilidade dos Testes , Estudos Prospectivos , Incontinência Urinária/diagnóstico , Inquéritos e Questionários , Qualidade de Vida
16.
Front Microbiol ; 13: 1039687, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713195

RESUMO

ß-Lactams are a broad class of antimicrobial agents with a high safety profile, making them the most widely used class in clinical, agricultural, and veterinary setups. The widespread use of ß-lactams has induced the extensive spread of ß-lactamase hydrolyzing enzymes known as ß-lactamases (BLs). To neutralize the effect of ß-lactamases, newer generations of ß-lactams have been developed, which ultimately led to the evolution of a highly diverse family of BLs. Based on sequence homology, BLs are categorized into four classes: A-D in Ambler's classification system. Further, each class is subdivided into families. Class B is first divided into subclasses B1-B3, and then each subclass is divided into families. The class to which a BL belongs gives a lot of insight into its hydrolytic profile. Traditional methods of determining the hydrolytic profile of BLs and their classification are time-consuming and require resources. Hence we developed a machine-learning-based in silico method, named as ß-LacFamPred, for the prediction and annotation of Ambler's class, subclass, and 96 families of BLs. During leave-one-out cross-validation, except one all ß-LacFamPred model HMMs showed 100% accuracy. Benchmarking with other BL family prediction methods showed ß-LacFamPred to be the most accurate. Out of 60 penicillin-binding proteins (PBPs) and 57 glyoxalase II proteins, ß-LacFamPred correctly predicted 56 PBPs and none of the glyoxalase II sequences as non-BLs. Proteome-wide annotation of BLs by ß-LacFamPred showed a very less number of false-positive predictions in comparison to the recently developed BL class prediction tool DeepBL. ß-LacFamPred is available both as a web-server and standalone tool at http://proteininformatics.org/mkumar/blacfampred and GitHub repository https://github.com/mkubiophysics/B-LacFamPred respectively.

17.
Antibiotics (Basel) ; 10(12)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34943751

RESUMO

ESKAPE pathogens are the leading cause of nosocomial infections. The Global Priority List of WHO has categorized ESKAPE as priority 1 and 2 pathogens. Even though several mechanisms contribute to antimicrobial resistance, OXA ß-lactamase has emerged as a new threat in combating nosocomial infections. In the present study we have investigated the presence of OXA and their variants, copy number, distribution on chromosomes/plasmids, subfamilies, phylogenetic relationships, amino acid identities and variabilities in ESKAPE pathogens. Our results revealed that a total of 929 OXA were present in 2258 completely assembled genomes, which could be further subdivided into 16 sub-families. Among all the ESKAPE pathogens, OXA were highly prevalent in A. baumannii, followed by P. aeruginosa and K. pneumoniae but completely absent in E. faecium and S. aureus while, only a few copies were found in Enterobacter spp. Most of the OXA variants belonged to the OXA-51-like subfamily (200 proteins), followed by OXA-50-like subfamily (189 proteins), OXA-23-like subfamily (156 proteins) and OXA-1-like subfamily (154 proteins). OXA-51-like, OXA-213-like, OXA-134-like, OXA-58-like, OXA-24-like and OXA-20-like subfamilies were present exclusively in A. baumannii. Phylogenetic tree of the subfamilies revealed that OXA-1-like and OXA-33-like, OXA-51-like and OXA-213-like and, OXA-5-like and OXA-10-like belonged to the same branches with amino acid identities as 100%, 97.10% and 80.90% respectively. This indicates that the members of these subfamily-pairs might have evolved from the same ancestor or have recently diverged. Thus, a judicious use of carbapenems is warranted to curtail the rise of new OXA enzymes and preserve them. This is the first detailed report about the OXA of ESKAPE pathogens.

18.
Eur J Obstet Gynecol Reprod Biol ; 260: 78-84, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33744504

RESUMO

INTRODUCTION: Mid-urethral sling (MUS) surgeries have revolutionized the management of stress urinary incontinence (SUI). However, MUS is a delicate balance of tension on the mid urethral segment with a 12 % risk of failure to achieve complete continence; and up-to 20 % chance of post-operative voiding dysfunction. We propose a simple technical modification in which the long ends of the tape at suprapubic or groin area are not cut immediately and are covered with a sterile dressing. After 48-72 h post-surgery the patient is checked for continence and voiding difficulties. Following this an ultrasonographic assessment of post-void residual urine is performed. Keeping in mind these 3 criteria the tape is adjusted. After complete subjective as well as objective satisfaction the long ends of tape are cut. MATERIAL AND METHODS: This is a retrospective analysis of women who underwent MUS surgery for the management of SUI, with our simple technical modification of tape adjustment in the postoperative period. A total of 17 patients operated by single surgeon in one year were included. RESULTS: Our results show that 58.8 % of our patients who underwent MUS procedures required post-operative tape adjustment. The number was significantly higher in the MUS - Retropubic group (85.7 %) as compared to the MUS - Obturator group (40 %). Three patients in the MUS - Retropubic group required a second time tape adjustment. Following tape adjustment all patients had complete continence (subjective and objective), with no voiding dysfunction. CONCLUSION: The incidence of postoperative voiding dysfunction is significant following MUS surgery for SUI. A simple technical modification of delaying the cutting of the tape for two to three days gives the opportunity for perfect tension adjustment.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Feminino , Humanos , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Slings Suburetrais/efeitos adversos , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos
19.
Bioresour Technol ; 339: 125631, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34332178

RESUMO

Critical analysis of thermogravimetric data, characterization of the biomass, and kinetic and thermodynamic analyses are crucial in the design of efficient biomass pyrolysis systems. In this study, characterization, kinetic and thermodynamic analysis was performed for pyrolysis of mustard oil residue (MOR). Thermogravimetric analysis (TGA) with differential thermal analysis (DTA) was applied to study thermal decomposition behaviour of MOR at 10, 20, and 30 °C/min. FTIR and XRD analyses were used to characterize MOR. Average activation energy estimated from employed isoconversional methods was ≈155 kJ/mol. Variation in activation energy was found to be statistically insignificant as suggested by p-value of 0.992 by one-way ANOVA method. The pyrolytic temperature for MOR ranged from 234 to 417 °C. Reaction mechanism predicted as R3 (third order) and D3 (three dimensional). Thermodynamic parameters (ΔHα, ΔGα, and ΔSα) showed that endothermicity increased from 0.2 to 0.8 conversion and product had highest energy at 0.8 conversion.


Assuntos
Pirólise , Biomassa , Cinética , Mostardeira , Óleos de Plantas , Termodinâmica , Termogravimetria
20.
Crit Rev Oncol Hematol ; 157: 103178, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33279812

RESUMO

Cervical cancer (CC) is a major gynecological problem in developing and underdeveloped countries. Despite the significant advancement in early detection and treatment modalities, several patients recur. Moreover, the molecular mechanisms responsible for CC recurrence remains obscure. The patients with CC recurrence often show poor prognosis and significantly high mortality rates. The clinical management of recurrent CC depends on treatment history, site, and extent of the recurrence. Owing to poor prognosis and limited treatment options, recurrent CC often presents a challenge to the clinicians. Several in vitro, in vivo, and patient studies have led to the identification of the critical molecular changes responsible for CC recurrence. Both aberrant genetic and epigenetic modifications leading to altered cell signaling pathways have been reported to impact CC recurrence. Researchers are currently trying to dissect the molecular pathways in CC and translate these findings for better management of disease. This article attempts to review the existing knowledge of disease relapse, accompanying challenges, and associated molecular players in CC.


Assuntos
Neoplasias do Colo do Útero , Doença Crônica , Epigênese Genética , Feminino , Humanos , Recidiva Local de Neoplasia/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia
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