Browsing by Author "Sarkar, Subendu"

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    Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status–Dependent Manner
    (American Diabetes Association, 2019-11) Singh, Kanhaiya; Sinha, Mithun; Pal, Durba; Tabasum, Saba; Gnyawali, Surya C.; Khona, Dolly; Sarkar, Subendu; Mohanty, Sujit K.; Soto-Gonzalez, Fidel; Khanna, Savita; Roy, Sashwati; Sen, Chandan K.; Surgery, School of Medicine
    Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical interrelated processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis. The role of ZEB1 in cutaneous wounds was assessed using Zeb1+/− mice, as Zeb1−/− mice are not viable. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics was used to elucidate the effect of elevated ZEB1, as noted during hyperglycemia. Under different glycemic conditions, ZEB1 binding to E-cadherin promoter was investigated using chromatin immunoprecipitation. Cutaneous wounding resulted in loss of epithelial marker E-cadherin with concomitant gain of ZEB1. The dominant proteins downregulated after ZEB1 overexpression functionally represented adherens junction pathway. Zeb1+/− mice exhibited compromised wound closure complicated by defective EMT and poor wound angiogenesis. Under hyperglycemic conditions, ZEB1 lost its ability to bind E-cadherin promoter. Keratinocyte E-cadherin, thus upregulated, resisted EMT required for wound healing. Diabetic wound healing was improved in ZEB+/− as well as in db/db mice subjected to ZEB1 knockdown. This work recognizes ZEB1 as a key regulator of cutaneous wound healing that is of particular relevance to diabetic wound complication.
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    Exploring the role of Azadirachta indica (neem) and its active compounds in the regulation of biological pathways: an update on molecular approach
    (Springer, 2021) Sarkar, Subendu; Singh, Rajender Pal; Bhattacharya, Gorachand; Surgery, School of Medicine
    In ethnomedicine, plant parts and compounds are used traditionally to treat different diseases. Neem (Azadirachta indica A. Juss) is the most versatile and useful medicinal plant ever found. Its every part is rich in bioactive compounds, which have traditionally been used to treat different ailments including infectious diseases. Bioactive compounds such as nimbolide, azarirachtin, and gedunin of neem are reported to have a tremendous ability to regulate numerous biological processes in vitro and in vivo. The present review article aims to explore the importance of neem extracts and bioactive compounds in the regulation of different biological pathways. We have reviewed research articles up to March 2020 on the role of neem in antioxidant, anti-inflammatory, antiangiogenic, immunomodulatory, and apoptotic activities. Studies on the concerned fields demonstrate that the bioactive compounds and extracts of neem have a regulatory effect on several biological mechanisms. It has been unveiled that extensive research is carried out on limonoids such as nimbolide and azarirachtin. It is evidenced by different studies that neem extracts are the potential to scavenge free radicals and reduce ROS-mediated damage to cells. Neem can be used to normalize lipid peroxidation and minimize ROS-mediated cell death. Besides, neem extracts can significantly reduce the release of proinflammatory cytokines and elevate the count of CD4 + and CD8 + T-cells. This review indicates the pivotal roles of A. indica in the regulation of different biological pathways. However, future investigations on other bioactive compounds of neem may reveal different therapeutic potentials.
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    Novel Bacterial Diversity and Fragmented eDNA Identified in Hyperbiofilm-Forming Pseudomonas aeruginosa Rugose Small Colony Variant
    (Elsevier, 2020-02-21) Deng, Binbin; Ghatak, Subhadip; Sarkar, Subendu; Singh, Kanhaiya; Ghatak, Piya Das; Mathew-Steiner, Shomita S.; Roy, Sashwati; Khanna, Savita; Wozniak, Daniel J.; McComb, David W.; Sen, Chandan K.; Surgery, School of Medicine
    Pseudomonas aeruginosa biofilms represent a major threat to health care. Rugose small colony variants (RSCV) of P. aeruginosa, isolated from chronic infections, display hyperbiofilm phenotype. RSCV biofilms are highly resistant to antibiotics and host defenses. This work shows that RSCV biofilm aggregates consist of two distinct bacterial subpopulations that are uniquely organized displaying contrasting physiological characteristics. Compared with that of PAO1, the extracellular polymeric substance of RSCV PAO1ΔwspF biofilms presented unique ultrastructural characteristics. Unlike PAO1, PAO1ΔwspF released fragmented extracellular DNA (eDNA) from live cells. Fragmented eDNA, thus released, was responsible for resistance of PAO1ΔwspF biofilm to disruption by DNaseI. When added to PAO1, such fragmented eDNA enhanced biofilm formation. Disruption of PAO1ΔwspF biofilm was achieved by aurine tricarboxylic acid, an inhibitor of DNA-protein interaction. This work provides critical novel insights into the contrasting structural and functional characteristics of a hyperbiofilm-forming clinical bacterial variant relative to its own wild-type strain.