Biology subjects

Mondal, S. K.

Publications and source records attributed to Mondal, S. K..

4 recordsLinked to original sources

bioRxiv2026

Structural insights into the inhibition of sickle hemoglobin polymerization by asymmetric hemoglobin tetramer HbFS (α2γβS)

Sickle cell disease (SCD) is caused by a single amino acid substitution in the {beta}S globin chain at 6th position (6E[->]V). This results in polymerization of deoxy state of sickle hemoglobin (HbS), followed by its precipitation and subsequent sickling of erythrocytes. These deformed cells can block small capillaries (vaso-occlusion), causing cardiovascular complications, ultimately leading to ischemia-reperfusion injury, severe oxygen deficiency, and progressive systemic damage. Occasionally, patients with SCD have been observed to produce exorbitantly high levels of fetal hemoglobin (HbF), which has been linked with the inhibition of HbS polymerization. One of the effects of hydroxyurea, the most commonly used therapeutic for SCD, is to elevate HbF levels. However, the mechanism of inhibitory role of HbF on HbS polymerization is largely unknown. This study attempts to gain insights into the mechanisms involved in this process by means of native mass spectrometry, ion mobility mass spectrometry, and hydrogen deuterium exchange-based mass spectrometry (H/DX-MS). The conformational flexibility of asymmetric hemoglobin, HbFS (2{gamma}{beta}S), for the observed regions in the tetrameric molecule appears to be more in the deoxy state as compared to the oxy state, eventually leading to reduced polymerization of sickle hemoglobin in patients with SCD that express elevated HbF levels.

biochemistry↗

bioRxiv2025

Spatial differentiation of proteome in cervical cancer tissues using Imaging Mass Spectrometry

Cervical cancer, which is the fourth most common gynaecological cancer across the globe, has a poorly understood molecular pathogenesis and etiology. Current methods of diagnosis are based on cytology, histology and presence of Human Papillomavirus (HPV). Shortcomings of these methods lie with poor quality of smears which is very common in Papanicolaou (pap) smears, limited sensitivity in terms of early detection, dependence on presence of HPV, etc. Due to its high sensitivity and non-targeted approach, Matrix Assisted Laser Desorption Ionization based Imaging Mass Spectrometry (MALDI-IMS) might be advantageous to understand the pathogenesis, molecular mechanism, precise identification of surgical margins and identification of novel biomarkers. Since it can also identify proteins in the extracellular matrix, it is especially beneficial for the tissue types with sparse cells and excessive extracellular matrix. Although tissue proteome profiling for cervical cancer were reported, the heterogeneous distribution of proteins across cervical cancer tissues havent been explored. In this study, we employed a non-targeted MALDI-IMS based approach to profile the spatial distribution of proteins within cervical cancer tissues. We observed overexpression of Keratin 5 and Prelamin A/C in the region of cervical cancer tissues which were categorically labelled with cancerous morphology using histopathological examination. Both these proteins have been earlier associated with progression and aggressiveness of other cancers like breast and prostate cancers. However, no such reports are available for cervical cancer. Further studies are required on a large dataset to validate and quantitate these proteins as biomarkers for early diagnosis and prognosis of cervical cancer.

cancer biology↗

bioRxiv2024

Effect of p-benzoquinone, a cigarette smoke-derived component, on the architecture and function of human RBC

p-benzoquinone (pBQ), a cigarette smoke-derived component, stands as one of the lethal oxidants of cigarette smoke. Health hazards caused by cigarette smoking are a profound global health concern. It has been reported to contribute significantly to several health disorders, such as lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, etc. These adverse health effects might be attributed to the complex mixture of approximately 4,000 chemicals present in cigarette smoke, such as nicotine, tar, nitric oxide, and p-benzosemiquinone (pBSQ). pBSQ, ranging from 100-200 {micro}g per cigarette, gets oxidized to pBQ in the lungs of smokers and subsequently enters into the bloodstream. In the present study, we investigated the detrimental effect of pBQ on the architecture of human RBCs. Previously, we showed that the covalent modification of human hemoglobin with pBQ results in an alteration in its structure and function. In addition, we explored the potential neutralizing role of N-acetyl cysteine (NAC) in the reactivity of pBQ. Our results demonstrated that pBQ exposure to human red blood cells (RBCs), ex vivo, significantly decreases the reduced glutathione (GSH) content of RBCs, leading to the elevation of reactive oxygen species (ROS) and consequently causing oxidative damage to cellular components. pBQ exposure resulted in increased RBC sedimentation, altered membrane fluidity, enhanced lipid peroxidation, and significant morphological changes, such as bulging and distortion on the surface of RBCs, which eventually compromise membrane integrity. In addition, the coexistence of NAC with pBQ was found to be effective in neutralizing pBQ, thereby restoring GSH levels and RBC membrane architecture. These findings highlight the potential of NAC in mitigating the harmful effects of cigarette smoke on RBCs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/619387v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@8c3d58org.highwire.dtl.DTLVardef@10f7655org.highwire.dtl.DTLVardef@21d140org.highwire.dtl.DTLVardef@30d65c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

TGFb-ANGPT2-Tie2 axis in cancer-associated fibroblasts reprograms oral cancer cells to embryonic-like cell state with predictive significance of poor prognosis

Myofibroblastic cancer-associated fibroblasts (CAFs) in tumor stroma is identified as poor-prognostic indicator in oral cancer; however, biological mechanisms are largely unexplored. Here, we discovered the role of autocrine or exogenous transforming growth factor beta (TGF{beta}) in inducing Tunica Interna Endothelial cell kinase 2 (Tie2) -signaling through histone deacetylase-mediated downregulation of Tie2-antagonist, Angiopoietin-2 in CAFs, responsible for induction and maintenance of myofibroblastic differentiation. To understand the influence of CAF-specific Tie2-signaling on cancer cell properties, we performed CAF-Cancer cell co-culture and its single-cell RNA sequencing (scRNA-Seq). Distinct clustering of CAFs suggested their transcriptional heterogeneity, driven by TGF{beta}-Tie2 activation. Interestingly, CAF-specific Tie2-signaling was responsible to reprogram cancer cells, producing embryonic-like cell state with increased stemness and EMT signatures. Importantly, both the Tie2-specific gene expression signature as well as reprogrammed cancer cell specific gene expression modules were validated respectively in fibroblasts clusters and malignant cell clusters in two independent earlier reported scRNAseq studies of HNSCC tumors. Highlighting the translatability of our study, the gene expression signature derived from reprogrammed cancer cells showed significant association with poor prognosis in HNSCC patient of TCGA cohort. Pharmacological inhibition of Tie2-signaling in CAFs, significantly abrogated the tumor initiating ability of co-cultured oral cancer cell lines. Overall, combining our molecular and computational analysis, we may propose Tie2 as a novel factor responsible for CAF mediated cancer cell plasticity, associated with aggressive nature of oral cancer. TeaserTie2-signaling is activated in myofibroblasts which impacts the behaviour of malignant cells by inducing cancer cell plasticity to acquire stemness.

cancer biology↗