Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
BMJ Open ; 14(4): e080303, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38626969

RESUMO

INTRODUCTION: Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3 has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron-folic acid (IFA) with vitamin D3 on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3 on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels. METHODS AND ANALYSIS: This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3 levels will be randomised into the intervention (IFA and vitamin D3 supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks. ETHICS AND DISSEMINATION: Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities. TRIAL REGISTRATION NUMBER: CTRI/2022/05/042775. PROTOCOL VERSION: Version 1.0.


Assuntos
Anemia Ferropriva , Anemia , Humanos , Idoso , Ferro , Colecalciferol/uso terapêutico , Hepcidinas , Suplementos Nutricionais , Ácido Fólico , Anemia/tratamento farmacológico , Anemia/epidemiologia , Vitamina D , Vitaminas/uso terapêutico , Ferritinas , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Calcifediol , Hemoglobinas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Trace Elem Med Biol ; 84: 127429, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38493666

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially protective effect of selenium (Se), but the reports are inconsistent. The objective of the study was to examine the evidence for relation between serum/tissue Se status and CRC. METHOD AND MATERIALS: In this Systematic Review and Meta-Analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum/plasma/whole blood/tissue Se concentrations in CRC patients and controls for articles published till August 2023. Meta-analysis was performed, and study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary mean differences in serum levels of Se between CRC patients and healthy controls, and Se levels between malignant and matched non-malignant tissue specimens were assessed. RESULTS: After initial screening, a total of 24 studies (18 serum and 6 tissue studies) with a pooled total of 2640 participants were included in the meta-analysis. CRC patients had significantly lower serum Se levels than healthy controls, being the difference between the two equal to 3.73 µg/dl (95% CI: 6.85-0.61). However, the heterogeneity was very high, I2= 99% (p < 0.01). Our meta-analysis showed higher Se levels in CRC cancerous specimens than in matched healthy colon tissue: the increase was equal to 0.07 µg/g wet tissue weight (95% CI: 0.06-0.09; p= 0.02). CONCLUSIONS: CRC patients have lower serum and higher colon cancerous tissue Se levels. Some factors, such as Se levels in different tumor grades of CRC need to be further considered for a more conclusive association between Se levels and risk of CRC.

3.
J Trace Elem Med Biol ; 82: 127370, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38159434

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and a public health problem. Several clinical studies have shown that copper (Cu) is involved in carcinogenesis, possibly via cuproptosis, a new form of programmed cell death, but the conclusions from published reports are inconsistent. This study aimed at evaluating the potential of Cu dysregulation as a CRC susceptibility factor. METHODS: In this systematic review and meta-analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum Cu concentrations in CRC patients and controls from articles published till June 2023. The studies included reported measurements of serum/plasma/blood Cu levels. Meta-analyses were performed as well as study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary standardized mean differences (SMDs) and the corresponding 95% confidence intervals (95% CIs) were applied to compare the levels of Cu between CRC patients and controls. RESULTS: 26 studies with a pooled total of9628 participants and 2578 CRC cases were included. The pooled SMD was equal to 0.85 (95% CIs -0.44; 2.14) showing that the CRC patients had higher mean Cu levels than the control subjects, but the difference was not significant (p = 0.185) and the heterogeneity was very high, I2 = 97.9% (95% CIs: 97.5-98.3%; p < 0.001). CONCLUSION: The pooled results were inconclusive, likely due to discordant results and inaccuracy in reporting data of some studies; further research is needed to establish whether Cu dysregulation might contribute to the CRC risk and whether it might reflect different CRC grades.


Assuntos
Neoplasias Colorretais , Cobre , Humanos
4.
J Lab Physicians ; 15(4): 578-582, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37780867

RESUMO

Introduction The collection of blood samples in different vacutainers can affect the result of serum lithium estimation due to the presence of distinct additives in the blood collection vacutainer for enhancing the clot formation process. Due to the low therapeutic index and threat of toxicity of lithium, it is imperative to correctly report the test result. Thus, it has become a challenge for the laboratory physician to estimate lithium in any clinical laboratory setup. Materials and Methods Sample of 100 patients were collected and paired into clot activator vacutainers and plain glass vials. After centrifugation, samples from the paired collection tubes were processed immediately for serum lithium estimation by VITROS 4600 analyzer working on the principle of reflectance photometry. Both the paired tubes were stored at 2 to 8°C and were further analyzed, at 24 and 48 hours, respectively, from the time of their collection. The statistical analysis was done in IBM SPSS software version 23. Results There was a statistically significant differences between the mean of lithium values when processed within 1st hour of collection, obtained from clot activator vacutainers in comparison to glass vials. However, within tube comparison, there was no statistical difference in the lithium values estimated at 1st hour, 24 hours, and 48 hours of collection. Conclusion In this study, lithium values measured by clot-activated vacutainers are found to be lower as compared with values measured through glass vials.

5.
Front Cell Infect Microbiol ; 13: 1179885, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457957

RESUMO

Background: Human monkeypox (mpox) disease is a multicountry outbreak driven by human-human transmission which has resulted in an international public health emergency. However, there is limited evidence on the positivity rate of skin lesions for mpox viral DNA. We aim to fill this gap by estimating the pooled positivity rate of skin samples with mpox viral DNA from mpox patients globally. Methods: In this systematic review and meta-analysis, seven databases and several preprint servers have been extensively searched until 17 January 2023 according to a prospectively registered protocol (PROSPERO: CRD42023392505). Articles including the positivity rate of skin samples with mpox viral DNA in mpox-confirmed patients were considered eligible. After a quality assessment, a random-effect meta-analysis was used for pooled prevalence. To explore and resolve heterogeneity, we used statistical methods for outlier detection, influence analysis, and sensitivity analysis. Findings: Among the 331 articles retrieved after deduplication, 14 studies were finally included. The pooled positivity rate of the skin samples was 98.77% (95% CI: 94.74%-99.72%). After the removal of an influential outlier, I 2 for heterogeneity dropped from 92.5% to 10.8%. Meta-regression did not reveal any significant moderator. Conclusion/interpretation: The present findings reinforce that skin lesions act as a reservoir of mpox viral DNA and contribute to a high infectivity risk. This may be a prevailing basis of prompt transmission during the current multicountry outbreak and also needs further investigation. The present imperative outcome may benefit in producing valuable preventive and management procedures in an appropriate health strategy.


Assuntos
DNA Viral , Mpox , Humanos , Mpox/epidemiologia , Prevalência , Bases de Dados Factuais , Surtos de Doenças
6.
Med Sci Educ ; 33(2): 339-342, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37261029

RESUMO

Here, we have systematically developed a blueprint for the biochemistry theory assessment of phase I MBBS students in India which we have been using for both formative and summative assessments for the past 2 academic years. The blueprint has ensured the content validity and construct reliability and fairness of the assessment.

7.
Viruses ; 15(6)2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37376686

RESUMO

Despite monkeypox (mpox) being a public health emergency, there is limited knowledge about the risk of infectivity from skin viral loads during mpox infection. Thus, the aim of this study was to estimate cutaneous viral loads among mpox patients globally. Several databases, including Cochrane, EBSCOHost, EMBASE, ProQuest, PubMed, Scopus, and Web of Science, and preprint servers were searched concerning skin mpox viral loads in confirmed mpox subjects. In this systematic review and meta-analysis, a total of 331 articles were initially screened after the removal of duplicate entries. A total of nine articles were included in the systematic review and meta-analysis for the overall estimation of viral loads (Ct) using a random-effect model. The pooled cutaneous mpox viral load (lower Ct) was 21.71 (95% CI: 20.68-22.75) with a majority of positivity rates being 100%, highlighting a higher infectivity risk from skin lesions. The current results strongly support that skin mpox viral loads may be a dominant source of rapid transmission during current multi-national outbreaks. This important finding can help in constructing useful measures in relevant health policy.


Assuntos
Monkeypox virus , Mpox , Humanos , Mpox/epidemiologia , Carga Viral , Pele , Bases de Dados Factuais
8.
Indian J Community Med ; 48(2): 297-303, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37323731

RESUMO

Background: Children suffering from allergic rhinitis (AR) in their earlier days of life, not receiving proper treatment, subsequently develop asthma. To sensitize the first-year medical undergraduates about AR by implementing pediatric allergic rhinitis (PAR) module as a part of their attitude, ethics, and communication (AETCOM) curriculum. Materials and Methods: Triangulation type of mixed method study was conducted from January 2021 to June 2021 among 125 first-year medical undergraduate students. The PAR module communication checklist was developed and validated by an interprofessional (IP) team. Twenty multiple-choice questions (MCQs) were framed for both pretest and posttest cognitive assessment of the students. The pretest assessment was done (first 15 min) followed by the teaching of the PAR module (30 min), and lastly the posttest assessment along with open-ended feedback (last 15 min). Objective Structured Clinical Examination (OSCE) communication checklist along with the guidelines was given to the observer during the student-patient encounter to score the learner and to assess the communication skill. Apart from descriptive analysis, paired t-test and content analysis were done. Results: A statistically significant difference in the mean scores before and after the PAR module and communication checklist (P < 0.001). Majority (78/81, 96%) of the students favored this module, while (28/81) 34.6% suggested modifications. Most of the parent's feedback was good about the student's communication skill in terms of empathy (118), behavior (107), and greet (125); however, 33 parents were about the opinion of difficulties in closing the session, 17 parents commented about student's language problem and 27 about feedback. Conclusion: The PAR module should be taught in the current medical curriculum as a part of AETCOM in the foundation course as early clinical exposure with some modifications in the existing module.

10.
Biomedicines ; 11(3)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36979702

RESUMO

A series of Michael adducts of malononitrile and sulfonamide chalcones were synthesized, characterized, and evaluated for their antifilarial activity. Out of 14 compounds, N-(4-(4,4-dicyano-3-p-tolylbutanoyl)phenyl)benzenesulfonamide showed favorable drug-likeness properties with marked antifilarial effects at micro-molar dosages. Apoptosis in Brugia malayi microfilariae was confirmed by EB/AO staining, MTT assay, and cytoplasmic cytochrome c ELISA. Since chalcone and folate synthesis pathways share the same substrate, we hypothesize a structural analogy-based inhibition of folate metabolism by this compound. Molecular docking against a pre-validated BmDHFR protein showed more favorable thermodynamic parameters than a positive control, epicatechin-3-gallate. The compound significantly suppressed the DHFR activity in a parasite extract in vitro. Our hypothesis is also supported by a significant reversal of DHFR inhibition by folate addition, which indicated a plausible mechanism of competitive inhibition. These results demonstrate that targeting filarial folate metabolism through DHFR with consequent apoptosis induction might be rewarding for therapeutic intervention. This study reveals a novel rationale of the structural analogy-based competitive inhibition of DHFR by Michael adducts of sulfonamide chalcones.

11.
Biomater Sci ; 11(10): 3574-3588, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37000481

RESUMO

To address the obstacles in insulin protein homeostasis leading to the formation of neurotoxic amyloid plaques associated with different diseases, herein we have synthesized block copolymers using the reversible addition-fragmentation chain transfer (RAFT) polymerization method, composed of tert-butoxycarbonyl (Boc) protected leucine and acetyl (Ac) protected glucose pendant moieties, respectively. Selective or dual deprotection of Boc- and Ac-groups from leucine and/or glucose moieties resulted in amphiphilic polymers, which self-assembled into nanoaggregates in aqueous medium, confirmed by critical aggregation concentration (CAC) determination, dynamic light scattering (DLS) and transmission electron microscopy (TEM). These glycopolymeric nanoassemblies were used to study the inhibition rates of insulin fibrillation and were found to impede the fibrillation of the insulin protein. Using several biophysical techniques, we observed that hydrophobic, electrostatic, and hydrogen bonding interactions were responsible for binding the insulin monomer/oligomer with various glycopolymeric aggregates, inhibiting insulin fibrillation. Tyrosine (Tyr) and Nile red (NR) fluorescence measurements manifested the hydrophobic interactions, whereas temperature-dependent fluorescence and isothermal titration calorimetry (ITC) measurements revealed respectively the hydrogen bonding and electrostatic interactions involved in the inhibition process of insulin amyloid formation. Molecular dynamics simulations further confirmed the involvement of different interactions among polymer-protein residues in averting the fibrillation process.


Assuntos
Insulina , Polímeros , Insulina/química , Leucina , Polímeros/química , Simulação de Dinâmica Molecular
12.
Vaccines (Basel) ; 10(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36016123

RESUMO

Human lymphatic filariae have evolved numerous immune evasion strategies to secure their long-term survival in a host. These strategies include regulation of pattern recognition receptors, mimicry with host glycans and immune molecules, manipulation of innate and adaptive immune cells, induction of apoptosis in effector immune cells, and neutralization of free radicals. This creates an anti-inflammatory and immunoregulatory milieu in the host: a modified Th2 immune response. Therefore, targeting filarial immunomodulators and manipulating the filariae-driven immune system against the filariae can be a potential therapeutic and prophylactic strategy. Filariae-derived immunosuppression can also be exploited to treat other inflammatory diseases and immunopathologic states of parasitic diseases, such as cerebral malaria, and to prevent leishmaniasis. This paper reviews immunomodulatory mechanisms acquired by these filariae for their own survival and their potential application in the development of novel therapeutic approaches against parasitic and inflammatory diseases. Insight into the intricate network of host immune-parasite interactions would aid in the development of effective immune-therapeutic options for both infectious and immune-pathological diseases.

13.
Biomater Sci ; 10(13): 3466-3479, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35670569

RESUMO

To develop anti-amyloidogenic inhibitors for ameliorating the treatment of diabetes, herein, we have synthesised amphiphilic block copolymers with side-chain fatty acid (FA) moieties via reversible addition fragmentation chain-transfer (RAFT) polymerization. We addressed the unexplored role of FA pendants in the FA-tethered block copolymers (FABC) towards modulating the insulin fibrillation process with the aid of different biophysical techniques. Experimental findings established that FABC micelles can elongate the lag phase time to a greater extent and exhibit significant inhibitory potencies, with the more pronounced effect observed in stearic acid-based polymeric micelles (SABC475). Furthermore, conformational modulation using circular dichroism spectroscopic measurements demonstrates their potential role as effective inhibitors of insulin fibrils through reducing the ß-sheet contents. Interestingly, the FABC micelles can also disintegrate the matured fibrils and effectively diminish the fibril induced toxicity. Hydrophobic interaction and hydrogen (H) bonding are the two major driving forces that are equally responsible for the almost complete prevention of insulin aggregated species. Theoretical simulation results further support our experimental observations in explaining the inhibitory rate of the insulin fibrillation process in the presence of different FABC micelles. Overall, we envision that the reported study will provide a novel path to develop a new class of anti-amyloid polymeric inhibitors.


Assuntos
Insulinas , Micelas , Portadores de Fármacos/química , Ácidos Graxos , Polímeros/química
14.
Phytother Res ; 36(6): 2394-2415, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35393674

RESUMO

The interim results of the large, multinational trials on coronavirus disease 2019 (COVID-19) using a combination of antiviral drugs appear to have little to no effect on the 28-day mortality or the in-hospital course. Therefore, there is a still vivid interest in finding alternate re-purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin's possible therapeutic/prophylaxis efficacy against severe acute respiratory syndrome coronavirus (SARS-CoV) as well as comorbidities like chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, coagulopathy, and hypertension. Currently, 14 interventional clinical trials are underway assessing the efficacy of quercetin along with other antiviral drugs/nutritional supplements as prophylaxis/treatment option against COVID-19. The present review is tempting to suggest that, based on circumstantial scientific evidence and preliminary clinical data, the flavonoid quercetin can ameliorate COVID-19 infection and symptoms acting in concert on two parallel and independent paths: inhibiting key factors responsible for SARS-CoV-2 infections and mitigating the clinical manifestations of the disease in patients with comorbid conditions. Despite the broad therapeutic properties of quercetin, further high power randomized clinical trials are needed to firmly establish its clinical efficacy against COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Antivirais/uso terapêutico , Suplementos Nutricionais , Humanos , Quercetina/uso terapêutico , Recompensa , SARS-CoV-2
15.
J Family Med Prim Care ; 11(12): 7857-7862, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36994052

RESUMO

Introduction: Raising trend of cardiovascular diseases (CVD) in developing countries created a platform for exploring the sociodemographic nexus in search of underlying cause. Aim and Objectives: The precise aim of the study is to detect any possible association of social determinants and metabolic derangement with CVDs risk, particularly focusing on comparative analysis of the data to decipher the most significant factor(s), if any among the studied parameters contributing toward prediction of such cardiometabolic risk in linked with insulin resistance. Results: In the present study, it was found that 2% of the studied population had high risk, and 13.3% had intermediate risk of developing cardiovascular events in next 10 years. Results also showed that estimated CVD risk was significantly higher in males with central obesity and age more >60 years as key determinants showing more insulin resistance at lower cut-off. Conclusion: This study also strongly suggests need to revise the cut-off values for HOMA index in defining insulin resistance to rural population with active the life style and need of redefining new targeted preventive health care planning.

16.
Biomacromolecules ; 22(11): 4833-4845, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34674527

RESUMO

To understand the effect of cholic acid (CA)-based charge variable polymeric architectures on modulating the insulin aggregation process, herein, we have designed side-chain cholate-containing charge variable polymers. Three different types of copolymers from 2-(methacryloyloxy)ethyl cholate with anionic or cationic or neutral units have been synthesized by reversible addition-fragmentation chain transfer polymerization. The effects of these copolymers on the insulin fibrillation process was studied by multiple biophysical approaches including different types of spectroscopic and microscopic analyses. Interestingly, the CA-based cationic polymer (CP-10) was observed to inhibit the insulin fibrillation process in a dose-dependent manner and to act as an effective anti-amyloidogenic agent. Corresponding anionic (AP-10) and neutral (NP-10) copolymers with cholate pendants remained insignificant in controlling the aggregation process. Tyrosine fluorescence assays and Nile red fluorescence measurements demonstrate the role of hydrophobic interaction to explain the inhibitory potencies of CP-10. Furthermore, circular dichroism spectroscopic measurements were carried out to explore the secondary structural changes of insulin fibrils in the presence of cationic polymers with and without cholate moieties. Isothermal titration calorimetry measurements revealed the involvement of electrostatic polar interaction between the CA-based cationic polymer and insulin at different stages of fibrillation. Overall, this work demonstrates the efficacy of the CA-based cationic polymer in controlling the insulin aggregation process and provides a novel dimension to the studies on protein aggregation.


Assuntos
Insulina , Polímeros , Cátions , Ácido Cólico , Polimerização
17.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166228, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311079

RESUMO

Breast cancer stem cells (CSCs) are distinct CD44+-subpopulations that are involved in metastasis and chemoresistance. However, the underlying molecular mechanism of CD44 in breast CSCs-mediated tumorigenesis remains elusive. We observed high CD44 expression in advanced-stage clinical breast tumor samples. CD44 activation in breast CSCs sorted from various triple negative breast cancer (TNBC) cell lines induced proliferation, migration, invasion, mammosphere formation that were reversed in presence of inhibitor, 4-methyl umbelliferone or CD44 silencing. CD44 activation in breast CSCs induced Src, Akt, and nuclear translocation of pSTAT3. PCR arrays revealed differential expression of a metabolic gene, Lipoprotein lipase (LPL), and transcription factor, SNAI3. Differential transcriptional regulation of LPL by pSTAT3 and SNAI3 was confirmed by promoter-reporter and chromatin immunoprecipitation analysis. Orthotopic xenograft murine breast tumor model revealed high tumorigenicity of CD24-/CD44+-breast CSCs as compared with CD24+-breast cancer cells. Furthermore, stable breast CSCs-CD44 shRNA and/or intratumoral administration of Tetrahydrolipstatin (LPL inhibitor) abrogated tumor progression and neoangiogenesis. Thus, LPL serves as a potential target for an efficacious therapeutics against aggressive breast cancer.


Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , Receptores de Hialuronatos/metabolismo , Lipase Lipoproteica/genética , Células-Tronco Neoplásicas/patologia , Animais , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinogênese/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Receptores de Hialuronatos/genética , Lipase Lipoproteica/antagonistas & inibidores , Camundongos , Orlistate/farmacologia , Orlistate/uso terapêutico , Fosforilação , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Results Chem ; 3: 100148, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34150487

RESUMO

The world's largest randomized control trial against COVID-19 using remdesivir, hydroxychloroquine, lopinavir and interferon-ß1a appeared to have little or no effect on hospitalized COVID-19 patients. This has again led to search for alternate re-purposed drugs and/or effective "add-on" nutritional supplementation, which can complement or enhance the therapeutic effect of re-purposed drug. Focus has been shifted to therapeutic targets of severe acute respiratory syndrome coronavirus (SARS-CoV-2), which includes specific enzymes and regulators of lipid metabolism. Very recently, fenofibrate (cholesterol-lowering drug), suppressed the SARS-CoV-2 replication and pathogenesis by affecting the pathways of lipid metabolism in lung cells of COVID-19 patients. A preclinical study has shown synergistic effect of quercetin (a flavonoid) and fenofibrate in reducing the cholesterol content, which might be useful in COVID-19 treatment. Based on the scientific literature, use of quercetin and fenofibrate in COVID-19 seems meaningful in pharmaceutical and biomedical research, and warrants basic, experimental and clinical studies. In this article, we have summarized the contemporary findings about drug fenofibrate and its effect on membrane synthesis of COVID-19 virus along with emphasizing on possible synergistic effects of quercetin with fenofibrate.

19.
Acta Parasitol ; 66(4): 1212-1221, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33884574

RESUMO

PURPOSE: Silver nanoparticles (AgNPs) mediated apoptosis is well-known but its rationale is yet to be elucidated. This study explored the mechanistic underpinning of the apoptosis in the Brugia malayi parasitic model. METHOD: Silver nanoparticles were synthesized and tested against B. malayi microfilariae (Mf) to explore the role of oxidative and nitrosative stress in its apoptotic effect. RESULTS: AgNPs caused significant decrease in reduced glutathione (GSH) level and increase in both protein carbonylation and nitric oxide (NO) level indicating oxidative as well as nitrosative stress. Both GSH and nitric oxide synthase (NOS) inhibitors exhibited marked reversal. Nanoparticles and NO-donor in combination but not the NO-donor alone showed significant antiparasitic effect implying the requisite of combined oxidative and nitrosative stress to induce apoptosis. Synthetically prepared peroxynitrite from NaNO2 to H2O2 showed marked antiparasitic effect in very low dose which could be achieved neither by NaNO2 or H2O2 alone. GSH reversed the effect of peroxynitrite similar to its specific inhibitor, acetaminophen. GSH also reversed the plummet in mitochondrial oxygen consumption by AgNPs. CONCLUSION: We conclude that apoptosis by AgNPs is possibly mediated through peroxynitrite dependent depletion of GSH; this provides a significant insight into the pharmacological as well as toxicological impact of AgNPs.


Assuntos
Brugia Malayi , Nanopartículas Metálicas , Animais , Peróxido de Hidrogênio/toxicidade , Estresse Nitrosativo , Estresse Oxidativo , Prata/farmacologia
20.
Biochem Mol Biol Educ ; 49(3): 457-463, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33660917

RESUMO

Objectively Structured Clinical/Practical Examination (OSCE/OSPE) has been the backbone of the assessment system of graduate medical education for over three decades. We have developed an electronic Objectively Structured Practical Examination (e-OSPE) in Medical Biochemistry using the freely available Google forms to mitigate the academic disruption posed by COVID-19 pandemic in our resource-poor setting. Ten e-OSPE stations created, interlinked, and time-restricted. Fifty undergraduate students appeared for the e-OSPE examination on a prefixed date and time. Learner feedback was collected immediately after the completion of the examination. Facilitator feedback was also collected. Students' mean scores in e-OSPE and traditional OSPE were 78.15% and 74.56%, respectively. Their difference was not statistically significant (paired t-test two-tailed p-value 0.0979). Thus, the results of e-OSPE are reliable as compared to traditional OSPE. Bland Altman Plot revealed 92% of students had scores that were in the agreeable limit of both traditional OSPE and e-OSPE. Both the learners and facilitators were in consensus that the online format of e-OSPE is a good alternative for assessment (0.67 and 0.82); their experience was good (0.72 and 0.92) and conduction was well organized (0.73 and 0.86). Several suggestions were also received to make e-OSPE even more effective. In conclusion, this pilot study showed e-OSPE can be an effective alternative to traditional OSPE when "in-person" evaluation is not possible such as in the current era of COVID-19 even in resource-limited settings.


Assuntos
Bioquímica/educação , Educação a Distância , Educação de Graduação em Medicina/normas , Avaliação Educacional/métodos , Avaliação Educacional/normas , COVID-19/epidemiologia , Currículo , Humanos , Índia/epidemiologia , Sistemas On-Line , Pandemias , Projetos Piloto , SARS-CoV-2 , Estudantes de Medicina , Interface Usuário-Computador
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA