Browsing by Author "Kaur, Prabhsimran"

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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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    Epigenetic Instability Caused by Oxidative Stress Triggers Tumorigenesis
    (Springer Nature, 2022-01-31T00:00:00) Preet Kaur, Raman; Kaur, Prabhsimran; Munshi, Anjana
    Cancer is a multifactorial disease that is caused by various modifiable as well as non-modifiable factors. Among non-modifiable factors, genetic and epigenetic factors have been reported to play a critical role in the progression of cancer. Epigenetics refers to the change in gene expression without any change in the genome. The major epigenome targets include modification of histones by either methylation or acetylation and methylation of DNA at CpG islands. Change in acetylation and methylation pattern leads to not only inhibition of tumor suppressor genes but also the activation of oncogenes. Oxidative stress is a significant phenomenon observed in human body as a result of various intracellular as well as extracellular factors. This stress interferes with the function of histone methyltransferases and histone deacetylases, resulting in modifications of the epigenome. Further, these oxidative stress-induced epigenetic modifications may occur at various regions, including the promoters of tumor suppressor genes. These result in silencing of genes, leading to increased cell proliferation. In addition, reactive oxygen species have also been found to be involved in regulating the various steps of tumor development, including transformation, survival, proliferation, invasion, metastasis, and angiogenesis. Therefore, oxidative stress can be used as a target for developing cancer-related treatment modalities that reduce oxidative stress levels and thereby help in the resumption of the normal activity of epigenetic enzymes preserving epigenetic integrity. � Springer Nature Singapore Pte Ltd. 2022.
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    High-throughput sequencing technologies in metagenomics
    (Elsevier, 2022-09-30T00:00:00) Vasudeva, Kanika; Kaur, Prabhsimran; Munshi, Anjana
    Microbes are a distinct and dynamic group of organisms that require a diverse set of nutritional requirements and environmental conditions to thrive. To culture the desired microorganism a chemically defined media can be prepared based on the nutritional requirements of the specific species. However, all microbes cannot be cultured under similar laboratory conditions since specific microorganisms require unique growing conditions and therefore, the existence of the significant members (nearly 99.99%) of microbiota remains undiscovered. This cultivation constraint has limited our understanding of microbial diversity and restricted our appreciation for the microbial world and thereby suggests the need for a detailed metagenomic analysis. Metagenomics is the study of the genome sequences of a community of organisms sharing a common environment. In contrast, genomics involves the complete decoding of the genetic material of an organism by high-throughput sequencing. Metagenomics has the potential to highlight the community structure and functional potential of a microbial community in an unprejudiced manner. Any species can be subjected to metagenomic analysis bearing either DNA or RNA as the genetic material. Metagenomic techniques have been used to define a wide range of niches, from coastal environments to hazardous soils to vectors causing arthropod diseases as well as microbiome of humans. These methods are also being used to detect infections in the anthropological remains and uncover new pathogenic viruses and characterize the human microbiome in disease and health conditions as well as for forensic purposes. Metagenomic studies have been revolutionized since 2005 when the NGS technologies were developed. The introduction of next-generation sequencing (NGS) technologies in 2005 sparked the metagenomics revolution. A variety of novel sequencing technologies and platforms like Roche 454 sequencing, sanger sequencing, Illumina sequencing, and ion torrent Personal Genome Machine (PGM) have emerged in recent years, increasing the practicality of metagenomic research. The current chapter aims to explore the potential high throughput sequencing technologies for metagenomic analysis of species from diverse environmental backgrounds. In addition, the challenges faced and future perspectives will also be discussed. � 2023 Elsevier Inc. All rights reserved.
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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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    Pharmacogenomics of GLP-1 receptor agonists: Focus on pharmacological profile
    (Elsevier B.V., 2022-10-28T00:00:00) Jakhar, Kalpna; Vaishnavi, Swetha; Kaur, Prabhsimran; Singh, Paramdeep; Munshi, Anjana
    Type 2 Diabetes mellitus (T2DM) is a multifactorial metabolic disorder also known as a silent killer disease. Macrovascular and microvascular complications associated with diabetes worsen the condition leading to higher comorbidity and mortality rate. Currently, available treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4 (dipeptidyl-peptidase-4) inhibitors, SGLT-2 inhibitors, and Glucagon Like Peptide-1 receptor agonists (GLP-1RAs). Synthetic agonists of GLP-1 hormone, GLP-1RAs are an emerging class of anti-diabetic drugs which target the pathophysiology of diabetes through various mechanisms and at multiple sites. They promote insulin secretion from beta cells, and the proliferation of beta cells inhibits glucagon secretion, delays gastric emptying and induces satiety. However, treatment is reported to be associated with inter-individual variations and adverse drug reactions, which are also influenced by genetic variations. There have been a few pharmacogenetic studies have been carried out on this drug class. This review discusses all the available GLP-1RAs, their pharmacokinetics, pharmacodynamics and genetic variation affecting the inter-individual variation. � 2022 Elsevier B.V.
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    �The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics�
    (Elsevier B.V., 2021-05-11T00:00:00) Kaur, Prabhsimran; Behera, Bidwan Sekhar; Singh, Sandeep; Munshi, Anjana
    Diabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dipeptidyl peptidase-4) and GLP-1 (glucagon-like peptide) analogs. However, many side effects contributing to the devastation of the disease are associated with them. Sodium glucose co-transporter-2 (SGLT2) inhibition has been reported to be new insulin-independent approach to diabetes therapy. It blocks glucose uptake in the kidneys by inhibiting SGLT2 transporters, thereby promoting glycosuria. Dapagliflozin, empagliflozin and canagliflozin are the most widely used SGLT2 inhibitors. They are effective in controlling blood glucose and HbA1c levels with few side effects including hypoglycemia or weight gain which makes them preferable to other anti-diabetic drugs. However, treatment is found to be associated with inter-individual drug response to SGLT2 inhibitors and adverse drug reactions which are also affected by genetic variations. There have been very few pharmacogenetics trials of these drugs. This review discusses the various SGLT2 inhibitors, their pharmacokinetics, pharmacodynamics and genetic variation influencing the inter-individual drug response. � 2021 Elsevier B.V.
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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.
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    Trehalose and its Diverse Biological Potential
    (Bentham Science Publishers, 2023-06-07T00:00:00) Sharma, Eva; Shruti, P.S.; Singh, Shagun; Singh, Tashvinder; Kaur, Prabhsimran; Jodha, Bhavana; Srivastava, Yashi; Munshi, Anjana; Singh, Sandeep
    Trehalose, a disaccharide molecule of natural origin, is known for its diverse biological ap-plications, like in drug development, research application, natural scaffold, stem cell preservation, food, and various other industries. This review has discussed one such diverse molecule �trehalose aka mycose�, and its diverse biological applications with respect to therapeutics. Due to its inertness and higher stability at variable temperatures, it has been developed as a preservative to store stem cells, and later, it has been found to have anticancer properties. Trehalose has recently been associated with modulating cancer cell metabolism, diverse molecular processes, neuroprotective effect, and so on. This article describes the development of trehalose as a cryoprotectant and protein stabilizer as well as a dietary component and therapeutic agent against various diseases. The article discusses its role in diseases via modulation of autophagy, various anticancer pathways, metabolism, inflammation, aging and oxidative stress, cancer metastasis and apoptosis, thus highlighting its diverse biological potential. � 2023 Bentham Science Publishers.
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    Trehalose and its Diverse Biological Potential
    (Bentham Science Publishers, 2023-06-07T00:00:00) Sharma, Eva; Shruti, P.S.; Singh, Shagun; Singh, Tashvinder; Kaur, Prabhsimran; Jodha, Bhavana; Srivastava, Yashi; Munshi, Anjana; Singh, Sandeep
    Trehalose, a disaccharide molecule of natural origin, is known for its diverse biological ap-plications, like in drug development, research application, natural scaffold, stem cell preservation, food, and various other industries. This review has discussed one such diverse molecule �trehalose aka mycose�, and its diverse biological applications with respect to therapeutics. Due to its inertness and higher stability at variable temperatures, it has been developed as a preservative to store stem cells, and later, it has been found to have anticancer properties. Trehalose has recently been associated with modulating cancer cell metabolism, diverse molecular processes, neuroprotective effect, and so on. This article describes the development of trehalose as a cryoprotectant and protein stabilizer as well as a dietary component and therapeutic agent against various diseases. The article discusses its role in diseases via modulation of autophagy, various anticancer pathways, metabolism, inflammation, aging and oxidative stress, cancer metastasis and apoptosis, thus highlighting its diverse biological potential. � 2023 Bentham Science Publishers.