Department Of Human Genetics And Molecular Medicine

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/103

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Author: search.filters.author.Singh, SandeepStart date: 2010

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Now showing 1 - 10 of 23
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    Design, Synthesis, and Anticancer Evaluation of Hemithioindigos via Inhibition of Human Topoisomerases
    (John Wiley and Sons Inc, 2023-11-06T00:00:00) Kaur, Manpreet; Suman, Prabhat; Arora, Sahil; Singh, Tashvinder; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
    Hemithioindigos were designed as topoisomerase inhibitors, synthesized, and evaluated for their anticancer properties against lung (A549) and breast (MDA-MB-468 and MCF7) cancer cell lines. Among all the synthetics, three compounds exerted potential anticancer effects on A549 (lung) and MCF7 (breast) cancer cell lines at low micromolar concentrations. The results revealed that two of these compounds blocked the cancer cells at the G1/S phase, while the third compound showed moderate G2/M inhibition, leading to necrotic cell death. Finally, the topoisomerase inhibition assays revealed their potent Topo I/II inhibitory actions as one of the primary anticancer mechanisms. Molecular docking studies further corroborated these findings. � 2023 Wiley-VCH GmbH.
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    Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes
    (Springer, 2023-07-15T00:00:00) Ludhiadch, Abhilash; Sulena; Singh, Sandeep; Chakraborty, Sudip; Sharma, Dixit; Kulharia, Mahesh; Singh, Paramdeep; Munshi, Anjana
    Platelets play a significant role in the pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and mean platelet volume (MPV) are the two significant parameters that affect the functions of platelets. In the current study, MPV and PLT count was evaluated using flow cytometry and a cell counter. SonoClot analysis was carried out to evaluate activated clot timing (ACT), clot rate (CR), and platelet function (PF). Genotyping was carried out using GSA and Sanger sequencing, and expression analysis was performed using RT-PCR. In silico analysis was carried out using the GROMACS tool and UNAFold. The interaction of significant proteins with other proteins was predicted using the STRING database. Ninety-six genes were analyzed, and a significant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated significantly with increased MPV, decreased PLT count, and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both genes. In silico analysis revealed that mutation in the THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two significant proteins interact with many other proteins, especially the ones involved in platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements, suggesting that they could be important players in the determination of MPV values. In conclusion, the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes, and higher MPV can be targeted for better therapeutic outcomes. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Genetic variations in tumor-suppressor miRNA-encoding genes and their target genes: focus on breast cancer development and possible therapeutic strategies
    (Springer Science and Business Media Deutschland GmbH, 2023-04-24T00:00:00) Chhichholiya, Yogita; Singh, Harsh Vikram; Singh, Sandeep; Munshi, Anjana
    MicroRNAs (miRNAs) negatively affect gene expression by binding to their specific mRNAs resulting in either mRNA destruction or translational repression. The aberrant expression of various miRNAs has been associated with a number of human cancer. Oncogenic or tumor-suppressor miRNAs regulate a variety of pathways involved in the development of breast cancer (BC), including cell proliferation, apoptosis, metastasis, cancer recurrence, and chemoresistance. Variations in miRNA-encoding genes and their target genes lead to dysregulated gene expression resulting in the development and progression of BC. The various therapeutic approaches to treat the disease include chemotherapy, radiation therapy, surgical removal, hormone therapy, chemotherapy, and targeted biological therapy. The purpose of the current review is to explore the genetic variations in tumor-suppressor miRNA-encoding genes and their target genes in association with the disease development and prognosis. The therapeutic interventions targeting the variants for better disease outcomes have also been discussed. � 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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    Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes
    (Springer, 2023-05-11T00:00:00) Malayil, Rhuthuparna; Chhichholiya, Yogita; Vasudeva, Kanika; Singh, Harsh Vikram; Singh, Tashvinder; Singh, Sandeep; Munshi, Anjana
    Oncogenic metabolic reprogramming impacts the abundance of key metabolites that regulate signaling and epigenetics. Metabolic vulnerability in the cancer cell is evident from the Warburg effect. The research on metabolism in the progression and survival of breast cancer (BC) is under focus. Oncogenic signal activation and loss of�tumor suppressor are important regulators of tumor cell metabolism. Several intrinsic and extrinsic factors contribute to metabolic reprogramming. The molecular mechanisms underpinning metabolic reprogramming in BC are extensive and only partially defined. Various signaling pathways involved in the metabolism play a significant role in the modulation of BC. Notably, PI3K/AKT/mTOR pathway, lactate-ERK/STAT3 signaling, loss of the tumor suppressor Ras, Myc, oxidative stress, activation of the cellular hypoxic response and acidosis contribute to different metabolic reprogramming phenotypes linked to enhanced glycolysis. The alterations in mitochondrial genes have also been elaborated upon along with their functional implications. The outcome of these active research areas might contribute to the development of novel therapeutic interventions and the remodeling of known�drugs. � 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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    Comprehensive analysis of culture conditions governing differentiation of MSCs into articular chondrocytes
    (Newlands Press Ltd, 2023-05-18T00:00:00) Singh, Harsh Vikram; Das, Lakshmana; Malayil, Rhuthuparna; Singh, Tashvinder; Singh, Sandeep; Goyal, Tarun; Munshi, Anjana
    Treatment of osteoarthritic patients requires the development of morphologically and mechanically complex hyaline cartilage at the injury site. A tissue engineering approach toward differentiating mesenchymal stem cells into articular chondrocytes has been developed to overcome the drawbacks of conventional therapeutic and surgical procedures. To imitate the native micro and macro environment of articular chondrocytes, cell culture parameters such as oxygen concentration, mechanical stress, scaffold design, and growth factor signalling cascade regulation must be addressed. This review aims to illuminate the path toward developing tissue engineering approaches, accommodating these various parameters and the role these parameters play in regulating chondrogenesis for better articular cartilage development to treat osteoarthritis effectively. � 2023 Future Medicine Ltd.
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    Natural Compound-Based Nanoparticles to Target Free Radicals in Cancer
    (Springer Singapore, 2022-09-28T00:00:00) Yadav, Umesh Prasad; Rhuthuparna, M.; Vasudeva, Kanika; Suman, Prabhat; Munshi, Anjana; Kumar, Santosh; Singh, Sandeep
    Cell proliferation and malignant transformation are enabled by genetic and epigenetic changes. During the malignancy process, malignant cells acquire distinguishing characteristics. Cancer cells have acquired the ability to generate more reactive oxygen species (ROS), resulting in high oxidative stress. ROS-mediated signaling is needed for cancer cell physiology, and high levels of ROS cause oxidative stress-induced cytotoxicity in cancer cells. To avoid ROS-mediated cytotoxicity, cancer cells modulate their redox state through various antioxidant mechanisms and keep their ROS levels below the threshold. Cancer treatment that targets oxidative stress is an appealing option. Many natural oxidative stress modulators and bioactive compounds have been used in the treatment of cancer. Conventional uptake of bioactive molecule is associated with lower bioavailability, solubility, unlikely biodistribution, and side effects. Traditional drug uptake is improved by nanoformulation, making it easier to overcome side effects, improve biodistribution, and extend drug duration time. Natural prooxidant-loaded nanoparticles efficiently carry prooxidant to the tumor site and selectively and efficiently induce oxidative stress-mediated cell death in cancer cells. � Springer Nature Singapore Pte Ltd. 2022.
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    Differential molecular mechanistic behavior of HDACs in cancer progression
    (Springer, 2022-08-16T00:00:00) Singh, Tashvinder; Kaur, Prabhsimran; Singh, Paramdeep; Singh, Sandeep; Munshi, Anjana
    Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs� role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    miRNA signatures in diabetic retinopathy and nephropathy: delineating underlying mechanisms
    (Springer Science and Business Media B.V., 2022-01-31T00:00:00) Kaur, Prabhsimran; Kotru, Sushil; Singh, Sandeep; Munshi, Anjana
    A worldwide failure to achieve glycemic targets has led to complications associated with diabetes mellitus. In addition to genetic and other risk factors, epigenetic factors like DNA methylation, histone modifications, and non-coding RNAs play a significant part in the pathogenesis of complications. Among non-coding RNAs, miRNAs have been explored extensively since they control various biological processes. Their dysregulation has been implicated in various diseases including diabetic complications. Diabetic retinopathy and nephropathy are two common microvascular diabetic complications. Diabetic retinopathy affects the retina of the eye whereas nephropathy damages kidneys on account of prolonged hyperglycemia. This review aims to evaluate the role of miRNAs in diabetic retinopathy and diabetic nephropathy with an emphasis on the dysregulation of various pathways involved. In addition, the role of significant miRNAs as biomarkers for the diagnosis and prognosis of complications has also been discussed. Further, an update on the role of important miRNAs as potential therapeutic modalities has been given. � 2021, The Author(s) under exclusive licence to University of Navarra.
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    Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4
    (BioMed Central Ltd, 2021-11-27T00:00:00) Sharma, Praveen; Sharma, Vibhuti; Ahluwalia, Tarunveer Singh; Dogra, Nilambra; Kumar, Santosh; Singh, Sandeep
    Background and objectives: MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria. Methods and results: Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells. Conclusion: These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription. � 2021, The Author(s).
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    Role of miRNAs in diabetic neuropathy: mechanisms and possible interventions
    (Springer, 2022-01-13T00:00:00) Kaur, Prabhsimran; Kotru, Sushil; Singh, Sandeep; Munshi, Anjana
    Accelerating cases of diabetes worldwide have given rise to higher incidences of diabetic complications. MiRNAs, a much-explored class of non-coding RNAs, play a significant role in the pathogenesis of diabetes mellitus by affecting insulin release, ?-cell proliferation, and dysfunction. Besides, disrupted miRNAs contribute to various complications, diabetic retinopathy, nephropathy, and neuropathy as well as severe conditions like diabetic foot. MiRNAs regulate various processes involved in diabetic complications like angiogenesis, vascularization, inflammations, and various signaling pathways like PI3K, MAPK, SMAD, and NF-KB signaling pathways. Diabetic neuropathy is the most common diabetic complication, characterized mainly by pain and numbness, especially in the legs and feet. MiRNAs implicated in diabetic neuropathy include mir-9, mir-106a, mir-146a, mir-182, miR-23a and b, miR-34a, and miR-503. The diabetic foot is the most common diabetic neuropathy, often leading to amputations. Mir-203, miR-23c, miR-145, miR-29b and c, miR-126, miR-23a and b, miR-503, and miR-34a are associated with diabetic foot. This review has been compiled to summarize miRNA involved in initiation, progression, and miRNAs affecting various signaling pathways involved in diabetic neuropathy including the diabetic foot. Besides, potential applications of miRNAs as biomarkers and therapeutic targets in this microvascular complication will also be discussed. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.