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  1. Article ; Online: Unravelling the role of cathepsins in cardiovascular diseases.

    Maheshwari, Sonali / Patel, Bhoomika M

    Molecular biology reports

    2024  Volume 51, Issue 1, Page(s) 579

    Abstract: Lysosomal cathepsins as a regulatory medium have been assessed as potential therapeutic targets for the treatment of various cardiac diseases such as abdominal aortic aneurysm, hypertension, cardiomyopathy, coronary heart disease, atherosclerosis, etc. ... ...

    Abstract Lysosomal cathepsins as a regulatory medium have been assessed as potential therapeutic targets for the treatment of various cardiac diseases such as abdominal aortic aneurysm, hypertension, cardiomyopathy, coronary heart disease, atherosclerosis, etc. They are ubiquitous lysosomal proteases with papain-like folded protein structures that are involved in a variety of physiological processes, such as the digestion of proteins, activation of pro-inflammatory molecules, degradation of extracellular matrix components, and maturation of peptide hormones. Cathepsins are classified into three major groups: cysteine cathepsins, aspartic cathepsins, and serine-threonine cathepsins. Each of these groups is further divided into subgroups based on their substrate specificity, structural characteristics, and biochemical properties. Several studies suggest that cathepsins control the degradation of ECM components such as collagen and elastin fibres. These enzymes are highly expressed in macrophages and inflammatory cells, and their upregulation has been demonstrated to be critical in the progression of atherosclerotic lesions. Additionally, increased cathepsin activity has been linked to increased vascular inflammation and oxidative stress, both of which are associated with CVDs. Specifically, the inhibition of cathepsins may reduce the release of pro-apoptotic mediators such as caspase-3 and PARP-1, which are thought to contribute to plaque instability. The potential of cathepsins as biomarkers and therapeutic targets has also been supported by the identification of potential cathepsin inhibitors, which could be used to modulate the activities of cathepsins in a range of diseases. This review shall familiarise the readers with the role of cysteinyl cathepsins and their inhibitors in the pathogenesis of cardiovascular diseases.
    MeSH term(s) Humans ; Cathepsins/metabolism ; Cardiovascular Diseases/metabolism ; Animals ; Oxidative Stress ; Atherosclerosis/metabolism ; Biomarkers/metabolism ; Lysosomes/metabolism ; Extracellular Matrix/metabolism
    Chemical Substances Cathepsins (EC 3.4.-) ; Biomarkers
    Language English
    Publishing date 2024-04-26
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-024-09518-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Corrigendum to "Investigation into the role of anti-diabetic agents in cachexia associated with metastatic cancer" [Life Sci. 274 (2021) 119329].

    Bora, Vivek / Patel, Bhoomika M

    Life sciences

    2023  Volume 328, Page(s) 121905

    Language English
    Publishing date 2023-07-01
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2023.121905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Long-acting opioids and cardiovascular diseases: Help or hindrance!

    Mehta, Ankita / Patel, Bhoomika M

    Vascular pharmacology

    2023  Volume 149, Page(s) 107144

    Abstract: Opioids are widely being used for chronic pain management, cough and diarrhea suppressants, anesthetic agents, and opioid de-addiction therapy. Opioid receptors, present in the central nervous system and peripheral tissues, are documented to regulate ... ...

    Abstract Opioids are widely being used for chronic pain management, cough and diarrhea suppressants, anesthetic agents, and opioid de-addiction therapy. Opioid receptors, present in the central nervous system and peripheral tissues, are documented to regulate several cardiac functions through different signaling pathways. Long-acting opioids (LAO) have been successfully evaluated for their beneficial effects in various cardiovascular diseases viz. myocardial infarction, ischemic reperfusion injuries, atherosclerosis etc. However, on the other hand, several research studies pointed towards the harmful effects of LAOs which are mainly associated with QTc prolongation, torsade de pointes, ventricular arrhythmias, and cardiac arrest. This review shall familiarize readers with the benefits as well as the harmful effects of long-acting opioids in cardiovascular diseases. We have also provided an overview of cardiac opioid receptors, endogenous cardiac opioid peptides, and regulation of cardiovascular functions by central and cardiac opioid receptors.
    MeSH term(s) Humans ; Analgesics, Opioid/adverse effects ; Methadone ; Cardiovascular Diseases/drug therapy ; Torsades de Pointes ; Receptors, Opioid/metabolism
    Chemical Substances Analgesics, Opioid ; Methadone (UC6VBE7V1Z) ; Receptors, Opioid
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2082846-9
    ISSN 1879-3649 ; 1537-1891 ; 1879-3649
    ISSN (online) 1879-3649 ; 1537-1891
    ISSN 1879-3649
    DOI 10.1016/j.vph.2023.107144
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Unveiling the Role of the Proton Gateway, Uncoupling Proteins (UCPs), in Cancer Cachexia.

    Joshi, Mit / Patel, Bhoomika M

    Cancers

    2023  Volume 15, Issue 5

    Abstract: Uncoupling proteins (UCPs) are identified as carriers of proton ions between the mitochondrial inner membrane and the mitochondrial matrix. ATP is mainly generated through oxidative phosphorylation in mitochondria. The proton gradient is generated across ...

    Abstract Uncoupling proteins (UCPs) are identified as carriers of proton ions between the mitochondrial inner membrane and the mitochondrial matrix. ATP is mainly generated through oxidative phosphorylation in mitochondria. The proton gradient is generated across the inner mitochondrial membrane and the mitochondrial matrix, which facilitates a smooth transfer of electrons across ETC complexes. Until now, it was thought that the role of UCPs was to break the electron transport chain and thereby inhibit the synthesis of ATP. UCPs allow protons to pass from the inner mitochondrial membrane to the mitochondrial matrix and decrease the proton gradient across the membrane, which results in decreased ATP synthesis and increased production of heat by mitochondria. In recent years, the role of UCPs in other physiological processes has been deciphered. In this review, we first highlighted the different types of UCPs and their precise location across the body. Second, we summarized the role of UCPs in different diseases, mainly metabolic disorders such as obesity and diabetes, cardiovascular complications, cancer, wasting syndrome, neurodegenerative diseases, and kidney complications. Based on our findings, we conclude that UCPs play a major role in maintaining energy homeostasis, mitochondrial functions, ROS production, and apoptosis. Finally, our findings reveal that mitochondrial uncoupling by UCPs may treat many diseases, and extensive clinical studies are required to meet the unmet need of certain diseases.
    Language English
    Publishing date 2023-02-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15051407
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Deliberation on debilitating condition of cancer cachexia: Skeletal muscle wasting.

    Dave, Srusti / Patel, Bhoomika M

    Fundamental & clinical pharmacology

    2023  Volume 37, Issue 6, Page(s) 1079–1091

    Abstract: Background: Cancer cachexia is a debilitating syndrome associated with marked body loss because of muscular atrophy and fat loss. There are several mechanisms contributing to the pathogenesis of cachexia. The presence of the tumor releases cytokines ... ...

    Abstract Background: Cancer cachexia is a debilitating syndrome associated with marked body loss because of muscular atrophy and fat loss. There are several mechanisms contributing to the pathogenesis of cachexia. The presence of the tumor releases cytokines from inflammatory and immune cells, which play a significant role in activating and deactivating certain pathways associated with protein, carbohydrate, and lipid metabolism. This review focuses on various cascades involving an imbalance between protein synthesis and degradation in the skeletal muscles.
    Objectives: This study aimed to elucidate the mechanisms involved in skeletal muscle wasting phenomenon over the last few years.
    Methods: This article briefly overviews different pathways responsible for muscle atrophy in cancer cachexia. Studies published up to April 2023 were included. Important findings and study contributions were chosen and compiled using several databases including PubMed, Google Scholar, Science Direct, and ClinicalTrials.gov using relevant keywords.
    Results: Cancer cachexia is a complex disease involving multiple factors resulting in atrophy of skeletal muscles. Systemic inflammation, altered energy balance and carbohydrate metabolism, altered lipid and protein metabolism, and adipose tissue browning are some of the major culprits in cancer cachexia. Increased protein degradation and decreased protein synthesis lead to muscle atrophy. Changes in signaling pathway like ubiquitin-proteasome, autophagy, mTOR, AMPK, and IGF-1 also lead to muscle wasting. Physical exercise, nutritional supplementation, steroids, myostatin inhibitors, and interventions targeting on inflammation have been investigated to treat cancer cachexia. Some therapy showed positive results in preclinical and clinical settings, although more research on the efficacy and safety of the treatment should be done.
    Conclusion: Muscle atrophy in cancer cachexia is the result of multiple complex mechanisms; as a result, a lot more research has been done to describe the pathophysiology of the disease. Targeted therapy and multimodal interventions can improve clinical outcomes for patients.
    MeSH term(s) Humans ; Cachexia/etiology ; Cachexia/therapy ; Cachexia/metabolism ; Neoplasms/complications ; Neoplasms/pathology ; Muscular Atrophy/etiology ; Muscular Atrophy/therapy ; Muscular Atrophy/metabolism ; Muscle, Skeletal/metabolism ; Inflammation/metabolism
    Language English
    Publishing date 2023-07-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 639134-5
    ISSN 1472-8206 ; 0767-3981
    ISSN (online) 1472-8206
    ISSN 0767-3981
    DOI 10.1111/fcp.12931
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Corrigendum to "Cardioprotective effects of magnesium valproate in type 2 diabetes mellitus" [Eur. J. Pharmacol. 728 (5 April 2014) 128-134].

    Patel, Bhoomika M / Raghunathan, Suchi / Porwal, Urvashi

    European journal of pharmacology

    2023  Volume 954, Page(s) 175900

    Language English
    Publishing date 2023-07-12
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2023.175900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The burning furnace: Alteration in lipid metabolism in cancer-associated cachexia.

    Joshi, Mit / Patel, Bhoomika M

    Molecular and cellular biochemistry

    2022  Volume 477, Issue 6, Page(s) 1709–1723

    Abstract: Cancer cachexia can be defined as a complex metabolic syndrome characterized by weight loss, anorexia, and emaciation due to the wasting of adipose tissue and skeletal muscle. In the last decade, much research has been done to decipher the role of lipid ... ...

    Abstract Cancer cachexia can be defined as a complex metabolic syndrome characterized by weight loss, anorexia, and emaciation due to the wasting of adipose tissue and skeletal muscle. In the last decade, much research has been done to decipher the role of lipid metabolism in cancer cachexia. Tumors, as well as host-derived factors, cause major metabolic changes in the body. Metabolic changes lead to higher energy expenditure by the host. To meet the high energy demand, the host utilizes fat depots stored in adipose tissues by a process known as lipolysis. High catabolic and low anabolic response leads to loss of adipose tissue. A significant insight has been made regarding adipose tissue "browning" bestow on thermogenic activities of adipocytes that result in catabolic energy expenditure. Both lipolysis and WAT browning play an important role in exhaustion adipose tissue. The goal of this review is to summarise what is currently known and about altered lipid metabolism and its utilization in cancer cachexia.
    MeSH term(s) Adipose Tissue, White/metabolism ; Cachexia/etiology ; Cachexia/metabolism ; Energy Metabolism ; Humans ; Lipid Metabolism ; Lipolysis ; Neoplasms/complications ; Neoplasms/metabolism ; Thermogenesis
    Language English
    Publishing date 2022-03-07
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 184833-1
    ISSN 1573-4919 ; 0300-8177
    ISSN (online) 1573-4919
    ISSN 0300-8177
    DOI 10.1007/s11010-022-04398-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Cardiac Complications: The Understudied Aspect of Cancer Cachexia.

    Bora, Vivek / Patel, Bhoomika

    Cardiovascular toxicology

    2022  Volume 22, Issue 3, Page(s) 254–267

    Abstract: The global burden of cancer cachexia is increasing along with drastic increase in cancer patients. Cancer itself leads to cachexia, and cachexia development is associated with events like altered hemodynamics, and reduced functional capacity of the heart ...

    Abstract The global burden of cancer cachexia is increasing along with drastic increase in cancer patients. Cancer itself leads to cachexia, and cachexia development is associated with events like altered hemodynamics, and reduced functional capacity of the heart among others which lead to failure of the heart and are called cardiovascular complications associated with cancer cachexia. In some patients, the anti-cancer therapy also leads to this cardiovascular complications. So, in this review, an attempt is made to understand the mechanisms, pathophysiology of cardiovascular events in cachectic patients. Important processes which cause cardiovascular complications include alterations in the structure of the heart, loss of cardiac mass and functioning, cardiac fibrosis and cardiac remodeling, apoptosis, cardiac muscle atrophy, and mitochondrial alterations. Previously, the available treatment options were limited to nutraceuticals and physical exercise. Recently, studies with some prospective agents that can improve cardiac health have been reported, but whether their action is effective in cardiovascular complications associated with cancer cachexia is not known or are under trial.
    MeSH term(s) Cachexia/complications ; Heart ; Humans ; Muscle, Skeletal ; Neoplasms/complications ; Prospective Studies
    Language English
    Publishing date 2022-02-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2036765-X
    ISSN 1559-0259 ; 1530-7905
    ISSN (online) 1559-0259
    ISSN 1530-7905
    DOI 10.1007/s12012-022-09727-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Sodium orthovanadate exhibits anti-angiogenic, antiapoptotic and blood glucose-lowering effect on colon cancer associated with diabetes.

    Patel, Kruti / Bora, Vivek / Patel, Bhoomika

    Cancer chemotherapy and pharmacology

    2023  Volume 93, Issue 1, Page(s) 55–70

    Abstract: Background: The presence of type 2 diabetes mellitus increases the risk of developing the colon cancer. The main objective of this study was to determine the role of sodium orthovanadate (SOV) in colon cancer associated with diabetes mellitus by ... ...

    Abstract Background: The presence of type 2 diabetes mellitus increases the risk of developing the colon cancer. The main objective of this study was to determine the role of sodium orthovanadate (SOV) in colon cancer associated with diabetes mellitus by targeting the competitive inhibition of PTP1B.
    Methods: For in vivo study, high fat diet with low dose streptozotocin model was used for inducing the diabetes mellitus. Colon cancer was induced by injecting 1,2-dimethylhydrazine (25 mg/kg, sc) twice a week. TNM staging and immunohistochemistry (IHC) was carried out for colon cancer tissues. In vitro studies like MTT assay, clonogenic assay, rhodamine-123 dye assay and annexin V-FITC assay using flow cytometry were performed on HCT-116 cell line. CAM assay was performed to examine the anti-angiogenic effect of the drug.
    Results: Sodium orthovanadate reduces the blood glucose level and tumor parameters in the animals. In vitro studies revealed that SOV decreased cell proliferation dose dependently. In addition, SOV induced apoptosis as depicted from rhodamine-123 dye assay and annexin V-FITC assay using flow cytometry as well as p53 IHC staining. SOV showed reduced angiogenesis effect on eggs which was depicted from CAM assay and also from CD34 and E-cadherin IHC staining.
    Conclusions: Our data suggest that SOV exhibits protective role in colon cancer associated with diabetes mellitus. SOV exhibits anti-proliferative, anti-angiogenic and apoptotic inducing effects hence can be considered for therapeutic switching in diabetic colon cancer.
    MeSH term(s) Animals ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Vanadates/pharmacology ; Vanadates/therapeutic use ; Colonic Neoplasms/pathology ; Apoptosis ; Rhodamines/pharmacology ; Rhodamines/therapeutic use
    Chemical Substances Blood Glucose ; Vanadates (3WHH0066W5) ; Rhodamines
    Language English
    Publishing date 2023-09-27
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-023-04596-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: PROTACs: Novel approach for cancer breakdown by breaking proteins.

    Memon, Humera / Patel, Bhoomika M

    Life sciences

    2022  Volume 300, Page(s) 120577

    Abstract: Ubiquitination defects have been reported in various diseases, including neurodegenerative diseases, metabolic disorders and cancer. Balance between degradation and synthesis of the proteins to treat cancer can be managed by designing a chimeric molecule, ...

    Abstract Ubiquitination defects have been reported in various diseases, including neurodegenerative diseases, metabolic disorders and cancer. Balance between degradation and synthesis of the proteins to treat cancer can be managed by designing a chimeric molecule, known as Proteolysis Targeting Chimeric molecule (Lee, Kim et al. 2021). Proteolysis-targeting chimeras (PROTACs) acts as a tool for conducting therapeutic intervention. It eradicates or reduces the proteins that are responsible for causing diseases. Each PROTAC contains a target warhead, an E3 ligand and a linker. E3 ligases are recruited by these bifunctional molecules, and the Ubiquitin (Ub) Proteasome System (UPS) is used to target the degradation of specific proteins. As compared to inhibition, this degradation offers several advantages in the drug resistance, selectivity, and potency. Thus, numerous small molecule PROTACs are identified so far. In this review, the development of PROTACs, historical milestones, the biological mechanism, advantages and recent progress, and role of PROTAC in prostate cancer, breast cancer, non-hodgkin lymphoma, multiple myeloma, and malignant peripheral nerve sheath tumors are summarized.
    MeSH term(s) Humans ; Neoplasms ; Proteasome Endopeptidase Complex/metabolism ; Proteins/metabolism ; Proteolysis ; Recombinant Fusion Proteins ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Proteins ; Recombinant Fusion Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2022-04-26
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2022.120577
    Database MEDical Literature Analysis and Retrieval System OnLINE

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