School Of Health Sciences
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Item Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer�s disease(Springer Science and Business Media Deutschland GmbH, 2021-11-23T00:00:00) Dhapola, Rishika; Hota, Subhendu Shekhar; Sarma, Phulen; Bhattacharyya, Anusuya; Medhi, Bikash; Reddy, Dibbanti HariKrishnaAlzheimer�s disease (AD) is a major contributor of dementia leading to the degeneration of neurons in the brain with major symptoms like loss of memory and learning. Many evidences suggest the involvement of neuroinflammation in the pathology of AD. Cytokines including TNF-? and IL-6 are also found increasing the BACE1 activity and expression of NF?B resulting in generation of A? in AD brain. Following the interaction of A? with microglia and astrocytes, other inflammatory molecules also get translocated to the site of inflammation by chemotaxis and exaggerate neuroinflammation. Various pathways like NF?B, p38 MAPK, Akt/mTOR, caspase, nitric oxide and COX trigger microglia to release inflammatory cytokines. PPAR? agonists like pioglitazone increases the phagocytosis of A? and reduces inflammatory cytokine IL-1?. Celecoxib and roficoxib like selective COX-2 inhibitors also ameliorate neuroinflammation. Non-selective COX inhibitor indomethacin is also potent inhibitor of inflammatory mediators released from microglia. Mitophagy process is considered quite helpful in reducing inflammation due to microglia as it promotes the phagocytosis of over activated microglial cells and other inflammatory cells. Mitophagy induction is also beneficial in the removal of damaged mitochondria and reduction of infiltration of inflammatory molecules at the site of accumulation of the damaged mitochondria. Targeting these pathways and eventually ameliorating the activation of microglia can mitigate neuroinflammation and come out as a better therapeutic option for the treatment of Alzheimer�s disease. � 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.Item Diagnostic and therapeutic approaches for endometriosis: a patent landscape(Springer Science and Business Media Deutschland GmbH, 2023-08-25T00:00:00) Singh, Maninder; Jassal, Reena; Khetarpal, PreetiObjective: The aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field. Methodology: Patent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords �Endometriosis OR Adenomyosis� AND �Diagnostic OR Therapeutics� were used along with wildcard search queries in the �Title�, �Abstract� and �Descriptions� fields. Results: A patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories. Conclusion: Efforts are being made to improve current diagnostic instruments.�Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item Components of IGF-axis in growth disorders: a systematic review and patent landscape report(Springer, 2022-05-06T00:00:00) Singh, Amit; Pajni, Ketan; Panigrahi, Inusha; Dhoat, Navdeep; Senapati, Sabyasachi; Khetarpal, PreetiPurpose: In this review, epi/genetic mutations of IGF-axis components associated with growth disorders have been summarized alongwith assessment of relevant diagnostic and therapeutic technology through patent literature. Methodology: PROSPERO protocol registration CRD42021279468. For scientific literature search Literature databases (PubMed, EMBASE, ScienceDirect, and Google Scholar) were queried using the appropriate syntax. Various filters were applied based on inclusion and exclusion criteria. Search results were further refined by two authors for finalizing studies to be included in this synthesis. For patent documents search Patent databases (Patentscope and Espacenet) were queried using keywords: IGF or IGFBP. Filters were applied according to International Patent Classification (IPC) and Cooperative Patent Classification (CPC). Search results were reviewed by two authors for inclusion in the patent landscape report. Results: For scientific literature analysis, out of 545 search results, 196 were selected for review based on the inclusion criteria. For Patent literature search, out of 485 results, 37 were selected for this synthesis. Conclusion: Dysregulation of IGF-axis components leads to various abnormalities and their key role in growth and development suggests epi/mutations or structural defects among IGF-axis genes can be associated with growth disorders and may explain some of the idiopathic short stature cases. Trend of patent filings indicate advent of recombinant technology for therapeutics. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Biomedical applications of L-alanine produced by Pediococcus acidilactici BD16 (alaD +)(Springer Science and Business Media Deutschland GmbH, 2022-01-28T00:00:00) Sharma, Anshula; Mehta, Vikrant; Rani, Suman; Noda, Masafumi; Sugiyama, Masanori; Chander, Harish; Kaur, BaljinderAbstract: L-alanine possesses extensive physiological functionality and tremendous pharmacological significance, therefore could be considered as potential ingredient for food, pharmaceutical, and personal care products. However, therapeutic properties of L-alanine still need to be addressed in detail to further strengthen its utilization as a viable ingredient for developing natural therapeutics with minimum side effects. Thus, the present study was aimed to explore the anticipated therapeutic potential of L-alanine, produced microbially using a lactic acid bacterial strain Pediococcus acidilactici BD16 (alaD+) expressing L-alanine dehydrogenase enzyme. The anticipated therapeutic potential of L-alanine was assessed in terms of anti-proliferative, anti-bacterial, and anti-urolithiatic properties. Anti-bacterial assays revealed that L-alanine successfully inhibited growth and in vitro proliferation of important human pathogens including Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, and Vibrio cholerae in a concentration-dependent manner. Current investigation has also revealed its significant anti-proliferative potential against human lung adenocarcinoma (A549; IC50 7.32�?M) and mammary gland adenocarcinoma (MCF-7; IC50 8.81�?M) cells. The anti-urolithiatic potential of L-alanine was augmented over three different phases, viz., nucleation inhibition, aggregation inhibition, and oxalate depletion. Further, an in vitro cell culture�based kidney stone dissolution model using HEK293-T cells was also established to further strengthen its anti-urolithiatic potential. This is probably the first in vitro cell culture�based model which experimentally validates the immense therapeutic efficacy of L-alanine in treating urolithiasis disease. Key points: � Assessment of therapeutic potential of L-alanine produced by LAB. � L-alanine exhibited significant anti-proliferative and anti-bacterial activities. � L-alanine as potential anti-urolithiatic agent. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item Role of p53 gene in breast cancer: Focus on mutation spectrum and therapeutic strategies(Bentham Science Publishers B.V., 2018) Kaur, Raman Preet; Vasudeva, Kanika; Kumar, Roshan; Munshi, AnjanaTP53 is a tumor suppressor gene which is commonly mutated in various cancers including breast cancer. Alterations in the gene lead to an altered expression of various genes that are directly or indirectly under the transcriptional control of p53. This results in malfunctioning of DNA damage repair pathways, cell-cycle arrest, chromatin remodeling and apoptosis. Different mutations in TP53 gene have been reported in different ethnic groups and exon 4 and intron 3 are reported to be frequently mutated in breast cancer patients especially triple-negative breast cancer. Increased global burden of TP53 mutated breast tumors has paved the path for various therapies targeting p53/TP53. Numerous molecules including nutilins, MI series, RO5693, PRIMA-1, RITA, etc. have been developed. Majority of these restore p53/TP53 function by targeting negative regulators of p53/TP53, wtp53/TP53 (wild-type) and mtp53/TP53 (mutant). Most of these molecules are in the preclinical phase except for two APR-246 and COTI-2 that have progressed to clinical trials. The current review has been compiled with an aim to give an overview of mutations in p53 across various ethnic groups, the effect of these alterations on TP53 function and the therapeutic strategies developed till date targeting p53/TP53 especially in breast cancer.