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Menon, J.

Publications and source records attributed to Menon, J..

2 recordsLinked to original sources

Gender-specific MetS prediction using pathophysiological determinants: Beyond diagnostic constraints

Metabolic syndrome (MetS), constituted by obesity, hyperglycemia, hypertension, and dyslipidemia, is a growing public health concern due to its associated risk with cardiovascular and other metabolic disorders. Early-stage detection and prevention of MetS are key factors in an effective management strategy. Thus, the current study aimed to develop a risk score for MetS progression based on features pertaining to its pathophysiology, that can facilitate early detection and treatment strategies. A multivariate logistic regression model was developed using a representative feature from MetS pathophysiological pathways of inflammation, endothelial dysfunction, and hepatic dysregulation. The model was built on NHANES dataset and validated in Chinese and Indian datasets. The model performance evaluated using ROC resulted in an AUC of 0.81 in training and 0.87 and 0.79 for Chinese and Indian validation datasets, respectively. In conclusion, a MetS predictive model built on three MetS pathophysiological determinants was developed and validated in distinct datasets. HighlightsO_LIA MetS prediction model, trained on NHANES data, is validated with two datasets of varied ethnicity. C_LIO_LIThe three parameter model, independent of MetS diagnostic criteria, is reflective of inflammation, endothelial dysfunction, and hepatic dysregulation. C_LIO_LIThe model achieved an AUC of 0.81 in NHANES data; 0.87 and 0.79 for Chinese and Indian validation datasets respectively. C_LI

bioinformatics↗

PBRM1 is a vulnerability in ARID1A deficient multicellular tumor spheroids

ARID1A, a subunit of SWI/SNF, has been shown to play a major role in recruitment of the chromatin remodeler to enhancers for transcriptional regulation. Mutations inARID1A have been found in various cancers, many of which form solid tumors. Recent studies have revealed vulnerabilities in cells lacking ARID1A, specifically ARID1B, an ortholog and mutually exclusive subunit, in 2D cell culture. However, identification of vulnerabilities within SWI/SNF for loss of ARID1A in a multicellular tumor spheroid, that mimic in vivo condition within tumors, has not been explored. Here we show in the absence of ARID1A in a MTS model, ARID1B continues to be a vulnerability but we have identified PBRM1 as a new vulnerability within SWI/SNF. Levels of ARID1B and PBRM1 are elevated on loss of ARID1A. Further, reduction of ARID1B and PBRM1 protein levels, decreases cell survival and reduces induction of several hypoxia regulated genes in ARID1A deficient MTSs. Our studies have identified PBRM1 as a new vulnerability in ARID1a deficient cancers and which provides a new target for therapeutic strategies.

biochemistry↗