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1.
Chem Biodivers ; 21(6): e202301903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623839

RESUMO

Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor-beta (TGF-ß) signaling pathway, pivotal in breast cancer, is a promising approach. TGF-ß inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation. This study explores naturally occurring flavonoids' interactions with TGF-ß. Using molecular docking against the protein's crystal structure (PDB Id: 1PY5), Gossypin showed the highest docking score and underwent molecular dynamics simulation, revealing complex flexibility and explaining how flavonoids impede TGF-ß signaling in breast cancer. ADMET predictions adhered to Lipinski's rule of Five. Insights into flavonoid-TGF-ß binding offer a novel angle for breast cancer treatment. Flavonoids having a good docking score like gossypin, morin, luteolin and taxifolin shown potent cytotoxic effect on breast cancer cell line, MCF-7. Understanding these interactions could inspire flavonoid-based therapies targeting TGF-ß to halt breast cancer growth. These findings pave the way for personalized, targeted breast cancer therapies, offering hope against this formidable disease.


Assuntos
Neoplasias da Mama , Proliferação de Células , Flavonoides , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fator de Crescimento Transformador beta , Humanos , Flavonoides/farmacologia , Flavonoides/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células MCF-7 , Feminino , Relação Estrutura-Atividade , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Relação Dose-Resposta a Droga
2.
Inflammopharmacology ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767762

RESUMO

A chronic inflammatory condition of the intestine, ulcerative colitis (UC), is challenging to successfully manage once diagnosed. Currently, available medical therapies for UC exhibit minimal efficacy with unacceptable side effects, while inventive biological agents are expensive and yet not well accepted by patients. Discovering more effective and safer treatments to treat UC is therefore essential. One of the primary alkaloids found in Aegle marmelos, aegeline, has anti-inflammatory and antioxidant properties as well as being able to suppress several pro-inflammatory cytokines responsible for inflammation. The study aimed to investigate the effectiveness of aegeline in alleviating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through the NFƙB-mediated NLRP3 inflammasome pathway. Mice were randomly allocated into six groups, Normal control (NC), Model control (MC-TNBS, 2,4,6-trinitrobenzene sulfonic acid), STD (TNBS + sulfasalazine 100 mg/kg), AG1, AG2, and AG3 (TNBS + aegeline 5, 10, 20 mg/kg) respectively. Physical parameters such as a change in body weight, stool consistency, rectal bleeding, colon length, myeloperoxidase (MPO) levels and nitric oxide (NO) levels, and disease activity index (DAI) were assessed and supporting gene expression studies of various pro-inflammatory cytokines and enzymes were evaluated and histopathological changes observed. Administration of aegeline (10, 20 mg/kg) was found to be effective in colon protection by lowering the disease activity score and myeloperoxidase level and improving other physical parameters. Aegeline in high dose significantly downregulated the gene expression of NFƙB, iNOS, COX-2, NLRP3, IL-1ß, and IL-18, conferring great anti-inflammatory potential. Suggestive of the findings, aegeline reduced the damage to the colon by downregulating transcriptional genes and enzymes leading to inflammation and mitigated TNBS-induced colitis probably through the NFƙB-mediated NLRP3 inflammasome pathway.

3.
Curr Microbiol ; 79(5): 152, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397006

RESUMO

The outstanding research outcomes and registrations of myriads of probiotic strains have flooded the health market with various innovative probiotic-based products and their patents. The study of patented formulations of probiotics can give an overall insight into its existing application. A landscaping review of patents for probiotic-based preparations is presented in the current work. The patent search was performed over commercially available patent databased and analysis tool-PatSeer Pro®. Search strings containing words "Formulation" and "Composition" resulted in more than 3700 patents. Landscaping review of 400 + patents from the last 20 years (2000-2020) was performed using the Text-Mining approach. Text-Mining helped to identify 19 technological clusters which represent these patents. These clusters include the patents of probiotic preparations on animal feed, human food, cosmetics, antimicrobial, antidiabetic, arthritis, etc. A review of this massive number of patents unveiled many exciting preparations. Probiotic-based innovative products for depression, diabetes, Parkinson's, tumor, acne, and animal husbandry are reviewed comprehensively. The present work also unravels a few new-flanged products like probiotic layered condoms, products for acute alcoholism, and traditional Chinese medicine with probiotics. The patent landscape of probiotic-based preparations has presented a whole scenario of probiotic-based preparations. It has also revealed many unexplored areas where innovation can be excelled.


Assuntos
Probióticos , Animais , Mineração de Dados
4.
J Biomater Sci Polym Ed ; 35(6): 869-879, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38310516

RESUMO

The dressing materials that provide surface protection, bacteriostatic activities, and tissue regeneration are important for the treatment and management of complex wounds. This study aimed to evaluate the wound-healing properties of electrospun nanofibers containing a blend of methylcellulose (MC) and polyvinyl alcohol (PVA). The nanofibers were tested in single-layered (S-NFs) and multilayered (M-NFs) forms (PCL/MC-PVA/PCL). In vitro scratch assay using L929 cells and in vivo experiments on Wistar rats were conducted. The results showed that both S-NFs and M-NFs significantly accelerated wound closure by promoting cell migration. M-NFs demonstrated superior wound healing activity compared to S-NFs. Additionally, M-NFs exhibited faster skin epithelization compared to S-NFs. Histopathological evaluation confirmed the absence of irritation or lesions on the healed wound surface. Overall, the study concluded that these polymeric nanofibers have the potential to be used as self-wound healing dressings. They are safe, non-toxic, biodegradable, and biocompatible.


Assuntos
Nanofibras , Poliésteres , Álcool de Polivinil , Ratos , Animais , Metilcelulose , Ratos Wistar , Bandagens , Antibacterianos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38706351

RESUMO

BACKGROUND: Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells. However, the PD-1/PDL1 interactions are only partially characterized. OBJECTIVE: We aim to comprehend the time-dependent behavior of PD-1 upon its binding with PD-L1. METHOD: The current work focuses on a molecular dynamics simulation (MDs) simulation study of apo and ligand bound PD-1. RESULTS: Our simulation reveals the flexible nature of the PD-1, both in apo and bound form. Moreover, the current study also differentiates the type of strong and weak interactions which could be targeted to overcome the complex formation. CONCLUSION: The current article could provide a valuable structural insight about the target protein (PD-1) and its ligand (PD-L1) which could open new opportunities in developing small molecule inhibitors (SMIs) targeting either PD-1 or PD-L1.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38859789

RESUMO

In underdeveloped nations, tuberculosis (TB) continues to be a major source of morbidity and mortality. The currently available vaccine against tuberculosis in endemic areas is mainly ineffective, which triggers the need for a clinically effective vaccine against tuberculosis. In the present review, we emphasized the impact of genetic variations in the BCG strains, which influence the efficacy of BCG vaccines. We also discussed the current status of BCG vaccines and their potential mechanisms on the modulation of B cells and, thereby, humoral immunity, which trigger immune responses against various intracellular pathogens. Further, we also elaborated upon the pre-clinical and clinical studies demonstrating the efficacy and safety of the vaccines. Moreover, we also presented the putative novel targets such as polysaccharide-induced antibodies for the protection against Mtb, PGRS domain as an important target for Humoral immunity, HLA-E pathway-Target strategy for new TB vaccine, Coronin-1a - Novel player for Mycobacterial survival, IRGM, IFN-I3, an autophagy inducer with Irgm1 serving as a core part in the Tuberculosis vaccine development.

7.
ADMET DMPK ; 12(1): 63-105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560713

RESUMO

Background and Purpose: The blood-brain barrier (BBB), a critical interface of specialized endothelial cells, plays a pivotal role in regulating molecular and ion transport between the central nervous system (CNS) and systemic circulation. Experimental Approach: This review aims to delve into the intricate architecture and functions of the BBB while addressing challenges associated with delivering therapeutics to the brain. Historical milestones and contemporary insights underscore the BBB's significance in protecting the CNS. Key Results: Innovative approaches for enhanced drug transport include intranasal delivery exploiting olfactory and trigeminal pathways, as well as techniques like temporary BBB opening through chemicals, receptors, or focused ultrasound. These avenues hold the potential to reshape conventional drug delivery paradigms and address the limitations posed by the BBB's selectivity. Conclusion: This review underscores the vital role of the BBB in maintaining CNS health and emphasizes the importance of effective drug delivery through this barrier. Nanoparticles emerge as promising candidates to overcome BBB limitations and potentially revolutionize the treatment of CNS disorders. As research progresses, the application of nanomaterials shows immense potential for advancing neurological therapeutics, albeit with careful consideration of safety aspects.

8.
Am J Transl Res ; 15(10): 6148-6158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37969205

RESUMO

INTRODUCTION: In diabetic neuropathy with neurodegeneration (DNN), a serious diabetes consequence, extreme hyperglycemia destroys neurons in the brain and limbs. The main therapies for this condition are glucose control and pain management. Phytopharmacology is thought to be more successful in addressing the pain and blood sugar management issues associated with DNN. The objective of this study was to investigate how Bauhinia variegata (BV) could offer protection against streptozotocin (STZ)-induced diabetic neuropathy. METHODOLOGY: STZ-associated DNN was induced in rats, and these diabetic rats were treated with BV at 200 mg/kg and 400 mg/kg doses for 28 days. Blood glucose (BG), serum nitrite, lipid peroxidation, antioxidants, C-reactive protein, behavioral, and histopathological parameters were assessed. RESULTS: BV dramatically reduced BG and HbA1c levels in diabetic rats, according to the findings. The levels of superoxide dismutase and catalase both rose significantly. Both lipid peroxidation and serum nitrite levels were drastically decreased with BV treatment. In this study, it was found that BV has anti-hyperglycemic and anti-inflammatory effects on DNN. This was shown by a significant drop in C-reactive protein in diabetic rats, which was a key factor in diabetic neuropathy. Thermal hyperalgesia was significantly alleviated after BV therapy, and diabetic rats' pain thresholds improved. CONCLUSION: Present study concluded that BV treatment has excellent glycemic control, a high antioxidant status, and relevant pain-relieving potential in diabetic neuropathy with neurodegeneration by reversing thermal hyperalgesia and decreasing hypeglycemia in diabetic rats.

9.
Am J Transl Res ; 15(9): 5747-5756, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854239

RESUMO

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing significantly due to high amounts of fat and fructose in the diet. Phytochemicals present in herbal plants and nutrients present in food play vital roles in the management of NAFLD. One of these is trans-cinnamic acid (TCA). We are evaluate the role of TCA in NAFLD induced by a high-fat, high-fructose diet. METHODOLOGY: Rats fed a high-fat, high-fructose (HFHF) diet for ten weeks exhibited distinct signs of NAFLD. Rats were given TCA (10 mg/kg, 20 mg/kg, and 40 mg/kg) and pioglitazone (10 mg/kg) for four weeks along with a HFHF diet. At the end, body weight, food intake, liver, lipid measurements, TNF-α, antioxidants, and histopathology were evaluated. RESULTS: TCA significantly decreased serum glutamic-oxaloacetic transaminase and glutamic pyruvic transaminase in rats. Serum cholesterol, triglyceride, and low-density lipid levels were substantially decreased in TCA-treated rats compared to diseased controls. Superoxide dismutase, glutathione, and malondialdehyde were significantly decreased in rats treated with a high dose of TCA (40 mg/kg) compared to HFFD-fed rats. HFFD-fed rats exhibited fatty liver alterations, whereas rats treated with TCA exhibited significantly fewer morphologic changes associated with fatty liver disease. TCA at a high dose exhibited decreased TNF-α levels, thereby decreasing hepatic inflammation. CONCLUSION: TCA proved its role in the treatment of NAFLD by substantially reducing liver enzymes, pro-inflammatory markers (TNF-α), and lipid markers. Inclusion of TCA as a therapeutic regimen alongside diet-based treatment undoubtedly has therapeutic potential in NAFLD and related diseases.

10.
CNS Neurol Disord Drug Targets ; 22(10): 1462-1471, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36200162

RESUMO

Over the past 20 years, advances in the field of pathogenesis have inspired researchers to look into novel pharmacological therapeutics that are more focused on the pathophysiological events of the disease (AD). This review article discussed the prior use of statins for the prevention of Alzheimer's disease, which can help prevent the disease. Other drugs, such as memantine and donepezil, are available, but they cannot prevent the onset of AD in middle age. Based on available clinical data, the valuable effects of statins are mediated by alteration of ß-amyloid (Aß) and tau metabolism, genetic and lifestyle risk factors, along with other clinical aspects of AD. These findings suggested that using statins in middle age may help to prevent Alzheimer's disease by modifying genetic and non-genetic risk factors in later stages of life. In the present review, we elaborated upon the modification of risk factors and amyloid metabolism in the development and progression of AD and their modulation through atorvastatin. Future directions in the research and treatment of Alzheimer's disease patients include the use of antisense oligonucleotides (ASO) to change target expression, and researchers discovered decreased markers of oxidative stress in tissues affected by tau pathology in response to RNA interference treatment.


Assuntos
Doença de Alzheimer , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Doença de Alzheimer/metabolismo , Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Cognição , Proteínas tau/metabolismo
11.
Am J Clin Exp Urol ; 11(4): 275-292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645617

RESUMO

Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene CYP3A5 associated with Tacrolimus metabolism. Studies focusing on genetic variants in the CYP3A5 gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of CYP3A5 and Tacrolimus metabolism from the PubMed database and clinical trials (www.clinicaltrials.gov). This meta-analysis also assessed the correlation of CYP3A5 genotype (rs776746) with concentration/dose (Co/D) of Tacrolimus in renal transplant patients. The 59 published articles on genetic association of the CYP3A5 on Tacrolimus doses were reviewed for this systematic review. Meta-analysis showed that the Tacrolimus Co/D ratio is significantly lower in the CYP3A5 expressor group as compared with non-expressor in Asian, European as well as in mixed populations at any post-transplant period (P<0.0001). Our study further confirmed that the CYP3A5 variant (rs776746) is clinically relevant for the dose determination of Tacrolimus. Variations in Tacrolimus Co/D have been found to be significantly linked to the patient's CYP3A5 genetic variant (rs776746). The addition of other genetic variants involved in the pharmacokinetic of Tacrolimus may determine efficient regimen for drug dose. Our meta-analysis confirmed that the CYP3A5 genetic variant (rs776746) analysis is relevant in personalizing the Tacrolimus dose determination in renal transplant patients.

12.
Curr Pharm Biotechnol ; 23(14): 1691-1703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507802

RESUMO

This review work discusses the applications of xenobots in drug discovery. These are the world's first tiny robots that are living. Robots are built of metals and other things that benefit humans to solve various issues; however, in this case, small xenobots were built utilizing Xenopus laevis, frog embryonic stem cells in the blastocyte stage. Xenobots were created by combining bioscience, artificial intelligence, and computer science. Artificial intelligence constructs several forms of design in an in vitro, In-silico model, after which software analyzes the structure; the most substantial and most noticeable forms are filtered out. Later in vivo development create the design of the Petri plate using the MMR solution and makes the same form as the in silico approach. Ultimately evaluation done based on the behavior, movement, function, and features of xenobots. Xenobots are employed in medical research, pharmaceutical research to evaluate novel dosage forms, also useful for biotechnological and environmental research. Xenobots can be utilized to cure neurodegenerative disorders such as Alzheimer's, Parkinson's disease, and cancer-related issues because of their selfrepairing properties, which allow them to repair normal damaged cells, and convey drugs to their specific target, and reduce cytotoxicity in mostly malignancy circumstances. In the future, new approaches will be employed to treat chronic illnesses and their complications.


Assuntos
Neoplasias , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Inteligência Artificial , Descoberta de Drogas
13.
Curr Drug Discov Technol ; 19(1): e140122195498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35135461

RESUMO

BACKGROUND: Lung cancer is the leading cause of mortality in India. Adenosine Receptor (AR) has emerged as a novel cancer-specific target. A3AR levels are upregulated in various tumor cells, which may mean that the specific AR may act as a biological marker and target specific ligands leading to cell growth inhibition. AIM: Our aim was to study the efficacy of the adenosine receptor agonist, AB MECA, by in silico (molecular docking) and in vitro (human cancer cells in xenografted mice) studies. METHODS: Molecular docking on the AB-meca and TNF-α was performed using AutoDock. A549 Human lung cancer 2 ×106 cells per microliter per mouse injected via intrabronchial route. Rat TNF-α level was assessed by ELISA method. RESULTS: AB Meca's predicted binding energy (beng) with TNF-α was 97.13 kcal/mol, and the compatible docking result of a small molecular inhibitor with TNF-α native ligand beng was 85.76 kcal/mol. In vivo, a single dose of lung cancer cell A549 is being researched to potentiate tumor development. Doxorubicin and A3AR agonist therapies have lowered TNF-alpha levels that were associated with in silico function. The A3AR Agonist showed myeloprotective effects in the groups treated along with doxorubicin. CONCLUSION: AB MECA's higher binding energy (beng) with TNF-α mediated reduction of tumor growth in our lung cancer in vivo model suggested that it may be an effective therapy for lung cancer.


Assuntos
Agonistas do Receptor A3 de Adenosina , Neoplasias Pulmonares , Adenosina/análogos & derivados , Agonistas do Receptor A3 de Adenosina/farmacologia , Animais , Modelos Animais de Doenças , Doxorrubicina , Xenoenxertos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Ratos , Fator de Necrose Tumoral alfa
14.
Curr Drug Discov Technol ; 18(4): 518-524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32532194

RESUMO

BACKGROUND: Benign prostate hyperplasia [BPH] is an abnormal growth of prostate observed commonly in elderly males. Artemisinin has been reported to reduce the levels of testosterone. OBJECTIVE: This study is designed to evaluate the efficacy of Artemisinin on testosterone propionate [TP] induced benign prostate hyperplasia. MATERIALS AND METHODS: Male Wistar albino rats [n=24] were separated into four groups of six rats each. Group I served as control and distilled water using tween 80 as an emulsifying agent was administered subcutaneously. BPH was induced by testosterone propionate 3mg/kg [Group II], S.C. daily for 28 days. Group III was BPH + Finasteride treated group (10mg/kg orally for 28 days) and BPH + Artemisinin treated group (Group IV) (50 mg/kg orally for 28 days). RESULT: The study results showed significantly high levels of serum prostatic acid phosphatase (PAP), lactate dehydrogenase (LDH) and an elevation in prostate weight and prostatic index in Group II (BPH) when compared with Group I. The histopathological examination showed an increase in the epithelial proliferation of prostatic cells with involutions protruding into the lumen in BPH group when compared to the normal group. Treatment with Artemisinin (50 mg/kg) reduced the levels of PAP, LDH, prostate weight and prostatic index to a significant extent and restored the histoarchitectural features of the cells. CONCLUSION: The present study concludes that Artemisinin is efficacious in testosterone propionate induced BPH. This could be attributed, at least partly, to its anti-inflammatory property or its role in testosterone level reduction or as a Vitamin D receptor modulator.


Assuntos
Anti-Inflamatórios/farmacologia , Artemisininas/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Artemisininas/uso terapêutico , Modelos Animais de Doenças , Humanos , Masculino , Próstata/imunologia , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/patologia , Ratos , Ratos Wistar , Propionato de Testosterona/administração & dosagem , Propionato de Testosterona/toxicidade
15.
Am J Cardiovasc Dis ; 11(5): 601-610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34849291

RESUMO

BACKGROUND: Hypertension is most common prevailing cardiovascular disease worldwide. In this condition the effectiveness and safety of already available and many time-tested medications should be regularly reviewed. METHODOLOGY: Ethical approval of study was obtained from human research ethics committee of the hospital. 180 patients were enrolled with three groups of antihypertensive medication groups as calcium channel blocker (amlodipine), beta blocker (metoprolol) and angiotensin receptor blocker (telmisartan) over a span of eight months. The data was obtained from week zero to twelve (SBP: Systolic Blood Pressure and DBP: Diastolic Blood Pressure). Safety of Beta blocker, calcium channel blocker and angiotensin receptor blocker were investigated. RESULTS: Comparison of efficacy between the beta blocker, calcium channel blocker and angiotensin blocker receptor blocker were shown to be non-significant. It indicated that all drug therapies have the same successful reduction of SBP (P-0.4819). No significant adverse reactions were observed in either class of the medicines. CONCLUSION: The study showed the efficacy of Calcium Channel Blocker, Beta Blocker and Angiotensin Receptor Blocker in reduction of SBP & DBP was same, while Calcium Channel Blockers were superior to other two medications.

16.
Rev Recent Clin Trials ; 16(3): 242-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33267765

RESUMO

OBJECTIVE: Immediately after the outbreak of nCoV, many clinical trials are registered for COVID-19. The numbers of registrations are now raising inordinately. It is challenging to understand which research areas are explored in this massive pool of clinical studies. If such information can be compiled, then it is easy to explore new research studies for possible contributions in COVID-19 research. METHODS: In the present work, a text-mining technique of artificial intelligence is utilized to map the research domains explored through the clinical trials of COVID-19. With the help of the open-- source and graphical user interface-based tool, 3007 clinical trials are analyzed here. The dataset is acquired from the international clinical trial registry platform of WHO. With the help of hierarchical cluster analysis, the clinical trials were grouped according to their common research studies. These clusters are analyzed manually using their word clouds for understanding the scientific area of a particular cluster. The scientific fields of clinical studies are comprehensively reviewed and discussed based on this analysis. RESULTS: More than three-thousand clinical trials are grouped in 212 clusters by hierarchical cluster analysis. Manual intervention of these clusters using their individual word-cloud helped to identify various scientific areas which are explored in COVID19 related clinical studies. CONCLUSION: The text-mining is an easy and fastest way to explore many registered clinical trials. In our study, thirteen major clusters or research areas were identified in which the majority of clinical trials were registered. Many other uncategorized clinical studies were also identified as "miscellaneous studies". The clinical trials within the individual cluster were studied, and their research purposes are compiled comprehensively in the present work.


Assuntos
COVID-19 , Ensaios Clínicos como Assunto , Mineração de Dados , Inteligência Artificial , Análise por Conglomerados , Humanos
17.
J Cardiovasc Pharmacol ; 54(6): 502-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19738487

RESUMO

We have studied the effect of 8-week treatment with spironolactone (20 mg*kg(-1)*day(-1)) on cardiovascular complications associated with streptozotocin (STZ)-diabetic rats. Wistar rats were made diabetic with STZ (45 mg/kg, intravenously). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzyme, and C-reactive protein levels; reduction in heart rate; and cardiac hypertrophy. Chronic treatment with spironolactone significantly prevented STZ-induced bradycardia, hypertension, and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly reduced the elevated cholesterol, very-low-density lipoprotein, and triglyceride levels and increased the lower high-density lipoprotein-cholesterol levels in diabetic rats. Furthermore, spironolactone also produced a significant reduction in the elevated creatinine levels, C-reactive protein, and levels of lactate dehydrogenase and creatinine kinase. It also produced beneficial effect in diabetic rats by preventing cardiac hypertrophy as evident from decrease in left ventricular collagen levels, cardiac hypertrophy index, and left ventricular hypertrophy index. Our data suggest that spironolactone prevents not only the STZ-induced metabolic abnormalities but also cardiovascular complications.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Espironolactona/uso terapêutico , Animais , Sangue/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Peso Corporal/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Proteínas de Transporte/sangue , Colesterol/sangue , Colágeno/metabolismo , Creatina Quinase/sangue , Creatinina/sangue , Complicações do Diabetes/sangue , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/patologia , Insulina/sangue , Lipoproteínas/sangue , Ratos , Ratos Wistar , Espironolactona/farmacologia , Estreptozocina/farmacologia , Triglicerídeos/sangue
18.
Indian J Pharmacol ; 47(6): 610-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26729951

RESUMO

OBJECTIVE: Ficus racemosa (FR) is one of the herbs mentioned in the scriptures of the Ayurveda as Udumbara with high medicinal value. The objective of this study was to estimate the protective effect of FR against streptozotocin (STZ) induced diabetic neuropathy with neurodegeneration (DNN). MATERIALS AND METHODS: Diabetes was induced in Wistar rats with STZ and were divided into six groups namely diabetic vehicle control, FR (four) and glibenclamide (one) treated rats; while one group was of normal control rats. After the 4(th) week of diabetes, induction treatment was started for further 28 days (5(th) to 8(th) week) with FR aqueous extract (250 mg/kg and 500 mg/kg) and ethanolic extract (200 mg/kg and 400 mg/kg). Investigation of DNN was carried out through biochemical and behavioral parameter assessment in rats. RESULTS: Study showed a significant fall in glycosylated hemoglobin (HbA1c) and blood glucose level by the treatment of FR in diabetic rats. Antioxidant potential of FR showed a great rise in superoxide dismutase, catalase content and reduction observed in serum nitrite level; while significant fall in lipid peroxidation level and of C-reactive protein was observed in FR treated diabetic rats. Further FR treated diabetic rats also showed marked improvement in tail flick latency, pain threshold, the rise in locomotion and fall latency period. CONCLUSION: Treatment with FR shows protection in the multiple pathways of DNN by improving blood glucose, HbA1c, biochemical, and behavioral parameters, which suggest the protective role of FR in the reversal of DNN.


Assuntos
Antioxidantes/uso terapêutico , Neuropatias Diabéticas/prevenção & controle , Ficus/química , Hipoglicemiantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/metabolismo , Relação Dose-Resposta a Droga , Etnofarmacologia , Hemoglobinas Glicadas/análise , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ayurveda , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/isolamento & purificação , Casca de Planta/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Caules de Planta/química , Distribuição Aleatória , Ratos Wistar , Testes de Toxicidade Aguda
19.
J Basic Clin Pharm ; 4(4): 82-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24808678

RESUMO

INTRODUCTION: Diabetes mellitus is on alarming rise in India. Drug utilization studies help to identify the adherence to standard treatment guidelines and to evaluate the rational drug usage. OBJECTIVE: To study prescription pattern, calculate the cost of antidiabetic drugs and to evaluate the adherence to treatment guidelines in diabetic patients attending the medicine outpatient department in a tertiary care teaching hospital. MATERIALS AND METHODS: A prospective observational study was carried out for a period of 5 months. The diabetic patients who visited the medicine outdoor department were included. Demographic data and complete prescription details were recorded in the structured case record form. Cost of the drug therapy was calculated from the patient's bills. Indian Council for Medical research guidelines-2005 for diabetes management was used to evaluate the adherence. RESULTS: A total of 250 patients were enrolled in the study with mean age 57.91 ± 9.37. Out of 250 patients 126 (50.4%) were male and rest were female. A total of 1,391 drugs were prescribed, with mean of 5.56 ± 2.52 drugs and out of which 539 drugs were antidiabetics with mean of 2.18 ± 0.96. In monotherapy, metformin was frequently 218 (40.45%) prescribed. Glimepiride and metformin was the most frequently prescribed in 119 (76.28%) out of 156 antidiabetic drug combinations. Most commonly used drugs other than antidiabetics were aspirin 146 (18.9%) and atorvastatin 119 (15.41%). Mean cost of therapy for a month for a diabetic patient was 354.60 ± 305.72 INR. Majority 209 (83.6%) of prescriptions was in accordance to guidelines. CONCLUSION: Metformin was the most frequently prescribed drug in the diabetes patient. Metformin and glimeperide being the most frequent combination used. Majority of the prescriptions followed standard guidelines.

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