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1.
Sci Rep ; 14(1): 19510, 2024 08 22.
Article in English | MEDLINE | ID: mdl-39174586

ABSTRACT

Unpredictable fatal outcome of COVID-19 is attributed to dysregulated inflammation. Impaired early adaptive immune response leads to late-stage inflammatory outcome. The purpose of this study was to develop biomarkers for early detection of host immune impairment at first diagnosis from leftover RNA samples, which may in turn identify high risk patients. Leftover RNA samples of COVID-19 patients at first diagnosis were stored. Following prospective follow-up, the samples were shorted and categorized into outcome groups. Impaired adaptive T cell response (severity score) and Impaired IL-10 response (undetectable IL-10 in the presence of high expression of a representative interferon response gene) were determined by RT-PCR based assay. We demonstrate that a T cell response based 'severity score' comprising rational combination of Ct values of a target genes' signature can predict high risk noncomorbid potentially critical COVID-19 patients with a sensitivity of 91% (95% CI 58.7-99.8) and specificity of 92.6% (95% CI 75.7-99) (AUC:0.88). Although inclusion of comorbid patients reduced sensitivity to 77% (95% CI 54.6-92.2), the specificity was still 94% (95% CI 79.8-99.3) (AUC:0.82). The same for 'impaired IL-10 response' were little lower to predict high risk noncomorbid patients 64.2% (95% CI 35.1-87.2) and 82% (95% CI 65.5-93.2) respectively. Inclusion of comorbid patients drastically reduce sensitivity and specificity51.6% (95% CI 33.1-69.8) and 80.5% (95% CI 64.0-91.8) respectively. As best of our knowledge this is the first demonstration of a metric-based approach showing the 'severity score' as an indicator of early adoptive immune response, could be used as predictor of severe COVID-19 outcome at the time of first diagnosis using the same leftover swab RNA. The work flow could reduce expenditure and reporting time of the prognostic test for an earliest clinical decision ensuring possibility of early rational management.


Subject(s)
COVID-19 , Interleukin-10 , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/diagnosis , COVID-19/virology , Male , Female , Interleukin-10/genetics , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , RNA, Viral/genetics , Aged , Nasopharynx/virology , Nasopharynx/immunology , Adult , Biomarkers , Prospective Studies , Oropharynx/virology , Oropharynx/immunology , Prognosis , Adaptive Immunity , T-Lymphocytes/immunology
2.
Mol Oncol ; 16(8): 1650-1660, 2022 04.
Article in English | MEDLINE | ID: mdl-34725903

ABSTRACT

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Female , Humans , Leukocytes, Mononuclear/metabolism , Leukoplakia, Oral/diagnosis , Leukoplakia, Oral/genetics , Leukoplakia, Oral/metabolism , Male , Mouth Neoplasms/genetics , Telomere/metabolism , Telomere/pathology
3.
Iran J Microbiol ; 5(3): 309-14, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24475341

ABSTRACT

BACKGROUND AND OBJECTIVES: In the last few decades, losses of our cultural heritage due to biodeteriorationare beinghighly recognized. From museum objects to rock monuments, the microbial biodeterioration agents are found to be the most destructive. Possibilities for proper preservative measure(s) are always more when it is only a monument, statue, museum article, or pre-historic art in any small subterranean cave. Nevertheless, preservation/protection of the footprints occupying a big area, lying scattered in a very negligible manner requires safeguard against several deterioration factors; right from various physical, chemical and biological agents which are indeed interrelated to each other. MATERIALS AND METHODS: In the present study, some microbial communities possibly responsible for deteriorating the rocks of Kabra-pahad, where the most famous pre-historic rock paints of India prevail have been identified. The diversity of fungi and bacteria present in the stone crust of the infected areas has been studied by employing standard laboratory methods. RESULTS: The cultivated cultures confirmed total fifteen fungal species, among which Aspergillus group were the most dominant. Among bacteria, total 80 numbers of colonies were observed that dominated by two major groups; Micrococcus.spp and Staphylococcus spp. CONCLUSION: The pre-historic footprint in the form of rock paints in Kabra-pahad of district Raigarh, Chhattisgarh, India is lying in a very deteriorated manner. In the present study, we have tried to identify few major deteriorating factors that are responsible for such degradation of our existing pre-historic footprints.

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