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This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and the development of antiviral nanomaterials with physical antagonistic features of viral replication checkpoints as such a solution. Our detailed discussion of SARS-CoV-2 replication and pathogenesis highlights four distinct checkpoints, the S protein (ACE2 receptor coupling), the RBD motif (ACE2 receptor coupling), ACE2 coupling, and the S protein cleavage site, as targets for the development of nano-enabled solutions that, for example, prevent viral attachment and fusion with the host cell by either blocking viral RBD/spike proteins or cellular ACE2 receptors. As proof of this concept, we highlight applications of several nanomaterials, such as metal and metal oxide nanoparticles, carbon-based nanoparticles, carbon nanotubes, fullerene, carbon dots, quantum dots, polymeric nanoparticles, lipid-based, polymer-based, lipid-polymer hybrid-based, surface-modified nanoparticles that have already been employed to control viral infections. These nanoparticles were developed to inhibit receptor-mediated host-virus attachments and cell fusion, the uncoating of the virus, viral gene expression, protein synthesis, the assembly of progeny viral particles, and the release of the virion. Moreover, nanomaterials have been used as antiviral drug carriers and vaccines, and nano-enabled sensors have already been shown to enable fast, sensitive, and label-free real-time diagnosis of viral infections. Nano-biosensors could, therefore, also be useful in the remote testing and tracking of patients, while nanocarriers probed with target tissue could facilitate the targeted delivery of antiviral drugs to infected cells, tissues, organs, or systems while avoiding unwanted exposure of non-target tissues. Antiviral nanoparticles can also be applied to sanitizers, clothing, facemasks, and other personal protective equipment to minimize horizontal spread. We believe that the nanotechnology-enabled solutions described in this review will enable us to control repeated SAR-CoV-2 waves caused by antibody escape mutations.
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COVID-19 , Nanotubos de Carbono , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , SARS-CoV-2/genética , Enzima de Conversão de Angiotensina 2/genética , Anticorpos Neutralizantes , Mutação , LipídeosRESUMO
Background: Erythrodermic psoriasis is an acute inflammatory condition presenting as erythema and scaling involving more than 90% of body surface area in patients with a history of psoriasis vulgaris. If not treated promptly, metabolic complications and infections due to acute skin failure can cause significant morbidity and mortality in this condition. Interleukin-17 (IL-17) is considered to be the key player in initiating the inflammatory cascade in psoriasis. IL-17 blockers have been successfully used in the management of psoriasis vulgaris. However, its use in unstable erythrodermic psoriasis is limited to isolated case reports. Methods: We hereby report an observational study of nine patients of unstable psoriatic erythroderma successfully managed with injection secukinumab and followed up over the next 24 months. Results: Nine patients were managed during the study period, and a successful outcome was noted in all the patients. The Psoriasis Area and Severity Index response rate improved by at least 75% from baseline in 33.3% (3/9) at week 4 and improved to 88.9% (8/9) at week 12. None of the patients had a recurrence of erythroderma till 24 months of followup. Conclusion: The study concluded that secukinumab is quick, safe, and efficient in psoriatic erythroderma, and there was no relapse of erythroderma in any of the patients in the 24 months of followup.
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Even today methotrexate (MTX) remains the backbone of psoriasis management in dermatological practice. The widespread usage as well as over the counter availability of drug in India has led to frequent incidents of overdosing, resulting in toxicity. However, there is a lack of large size, comprehensive study in literature emphasizing upon reasons behind drug toxicity, clinical manifestations, and various management aspects. The present study aims to evaluate risk factors, clinical features, and suggest best management protocol based upon our experience in the management of MTX toxicity. A multicentric, retrospective study was conducted including all cases of psoriasis who were treated for MTX toxicity in the last 5 years. Complete information including demographic details, drug history, detailed clinical evaluation, laboratory parameters, management protocol, and outcome were studied and analyzed. A total of 21 patients of psoriasis with MTX toxicity were included, of which 20 had mucocutaneous ulcerations and hematological abnormalities were found in 76% patients. All cases were treated with folinic acid and 85% patients recovered within 7-14 days. Three out of 21 patients succumbed to their illness despite the best possible treatment. Overdosing was found to be the most common cause (66%) of drug toxicity, either inadvertent or due to self-medication. Patients must be counseled regarding course of the disease, drug regimen, and dreaded side effects prior to initiating the drug. In case the symptoms of toxicity appear, a prompt medical advice must be sought.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metotrexato , Psoríase , Humanos , Índia , Leucovorina/uso terapêutico , Metotrexato/toxicidade , Psoríase/tratamento farmacológico , Estudos RetrospectivosRESUMO
Cholera outbreaks currently account for 1.3 to 4.0 million cases and cause between 21 000 and 143 000 deaths worldwide. Cholera is preventable by proper sanitization and immunization; however, in many developing nations such as India, cholera disease is endemic. The surveillance system in India does not adequately capture the actual number of cases. As a result, it is important to utilize limited public health resources correctly in India and other developing counties more effectively to reach vulnerable communities. In this study, we analyze how studies make sense of cholera transmission and spread in India from 1996 to 2015. Furthermore, we analyze how a more sensitive surveillance system can contribute to cholera eradication by giving rise to outbreak preparedness.
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Cólera/epidemiologia , Cólera/prevenção & controle , Doenças Endêmicas , Vacinação , Cólera/transmissão , Vacinas contra Cólera , Surtos de Doenças , Humanos , Índia/epidemiologia , Vigilância da População , Saúde PúblicaRESUMO
A role of Retinol Binding Protein-4 (RBP4) in insulin resistance is widely studied. However, there is paucity of information on its receptor viz., Stimulated by Retinoic Acid-6 (STRA6) with insulin resistance. To address this, we investigated the regulation of RBP4/STRA6 expression in 3T3-L1 adipocytes exposed to glucolipotoxicity (GLT) and in visceral adipose tissue (VAT) from high fat diet (HFD) fed insulin-resistant rats. 3T3-L1 adipocytes were subjected to GLT and other experimental maneuvers with and without vildagliptin or metformin. Real-time PCR and western-blot experiments were performed to analyze RBP4, STRA6, PPARγ gene and protein expression. Adipored staining and glucose uptake assay were performed to evaluate lipid and glucose metabolism. Oral glucose tolerance test (OGTT) and Insulin Tolerance Test (ITT) were performed to determine the extent of insulin resistance in HFD fed male Wistar rats. Total serum RBP4 was measured by quantitative sandwich enzyme-linked immunosorbent assay kit. Adipocytes under GLT exhibited significantly increased RBP4/STRA6 expressions and decreased insulin sensitivity/glucose uptake. Vildagliptin and metformin not only restored the above but also decreased the expression of IL-6, NFκB, SOCS-3 along with lipid accumulation. Furthermore, HFD fed rats exhibited significantly increased serum levels of RBP4 along with VAT expression of RBP4, STRA6, PPARγ, IL-6. These molecules were significantly altered by the vildagliptin/ metformin treatment. We conclude that RBP4/STRA6 pathway is primarily involved in mediating inflammation and insulin resistance in adipocytes and visceral adipose tissues under glucolipotoxicity and in insulin resistant rats.
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Hipoglicemiantes/administração & dosagem , Resistência à Insulina , Proteínas de Membrana/metabolismo , Metformina/administração & dosagem , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vildagliptina/administração & dosagem , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Glucose/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Palmitatos/farmacologia , Ratos , Ratos Wistar , Proteínas Plasmáticas de Ligação ao Retinol/genéticaRESUMO
Since the onset of the present pandemic, effect of the novel corona virus on other infectious conditions continues to be investigated. Although the immunological responses to SARS-Cov-2 infection have been elaborated extensively, they fail to explain, variations in its clinical manifestations and its interaction with other diseases. Hansen's disease is known to present as a complex immunological response to the lepra bacilli, resulting in its varied spectral manifestations. An interaction between these two infectious agents, hence, may affect Hansen's disease. We came across six cases of Hansen's disease who developed COVID19 co-infection. This series presents their clinical course and outcome, during the period of co-infection. All cases were followed up for a minimum eight-week period thereafter. In all these cases the active phase of coronavirus infection had no effect on Hansen's disease and those on prednisolone for their lepra reaction had a more favorable outcome, with two cases manifesting exacerbation of their lepra reactions in the follow period.
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COVID-19 , Coinfecção , Hanseníase , Coinfecção/tratamento farmacológico , Humanos , SARS-CoV-2RESUMO
Manipur, one of the northeastern states of India, lies on the ancient silk route and serves as a meeting point between Southeast Asia and South Asia. The origin and migration histories of Naga and Kuki tribal populations are not clearly understood. Moreover, Kukis have been traced to two different ancestries, which has created confusion among the people. The present study examined genomic affinities and differentiation of the Naga and Kuki tribal populations of Manipur, Northeast India. Twenty autosomal markers (8 Alu insertion-deletions, 12 restriction-fragment-length polymorphisms) were analyzed. Findings show genetic differences between Naga and Kuki tribal populations with respect to the allele distribution pattern, which was substantiated by genetic differentiation (GST = 5.2%) and molecular variance (AMOVA), where the highest percentage of among-group variances was observed between Naga and Kuki tribal groups (7.09%). However, genetic similarities with respect to allele distribution patterns in most of the loci were seen among their respective groups (Rongmei and Inpui, Thadou and Vaiphei). Rongmei and Inpui tribal populations (Naga group) belong to the Naga-Bodo linguistic group, and Thadou and Vaiphei (Kuki group) belong to the Northern Kuki-Chin linguistic group, suggesting that genetic similarities may not be independent of linguistic affinities. Despite differential genetic affinities, both Naga and Kuki tribal populations in Manipur show more proximity with Southeast Asian populations and Northeast Indian populations than with other Indian populations and global populations taken for comparison.
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Povo Asiático , Genômica , Ásia , Povo Asiático/genética , Etnicidade/genética , Frequência do Gene , Variação Genética/genética , Genética Populacional , Humanos , ÍndiaRESUMO
Enzymes are highly efficient and selective biocatalysts, present in the living beings. They exist in enormous varieties in terms of the types of reactions catalyzed by them for instance oxidation-reduction, group transfers within the molecules or between the molecules, hydrolysis, isomerization, ligation, bond cleavage, and bond formation. Besides, enzyme based catalyses are performed with much higher fidelity, under mild reaction conditions and are highly efficient in terms of number of steps, giving them an edge over their chemical counter parts. The unique characteristics of enzymes makes them highly applicable fora number of chemical transformation reactions in pharmaceutical industries, such as group protection and deprotection, selective acylation and deacylation, selective hydrolysis, deracemization, kinetic resolution of racemic mixtures, esterification, transesterification, and many others. In this review, an overview of the enzymes, their production and their applications in pharmaceutical syntheses and enzyme therapies are presented with diagrams, reaction schemes and table for easy understanding of the readers.
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Enzimas/química , Preparações Farmacêuticas , Catálise , Esterificação , Hidrólise , Cinética , Oxirredução , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/químicaRESUMO
The introduction of antiretroviral therapy (ART) has substantially improved the survival of persons infected with HIV. In India, the aggregated HIV prevalence among transgender (TG) community was found 7.5%. West Bengal, with over 30,000 TG population recorded HIV prevalence of 4.8%. The qualitative study was conducted in 2019 with the objective to explore the motivating factors for adherence to ART treatment among TG people living with HIV (PLHIV) in an ART center. Respondents were motivated PLHIVs on ART with suitable treatment adherence recorded. Data were inductively analyzed, using thematic analysis, to identify themes central to ART adherence. Five themes emerged with prime acknowledgment of respondents that ART medication is lifelong for their survival with receiving support. Notwithstanding the chronic nature of the disease, TG PLHIV patient stands a better chance of maintaining treatment adherence if they are involved in treatment plans with their community-based members' helping as peer navigators.
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Antirretrovirais/uso terapêutico , Infecções por HIV/epidemiologia , Adesão à Medicação/psicologia , Motivação , Pessoas Transgênero/psicologia , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Pesquisa Qualitativa , Apoio Social , Fatores Socioeconômicos , Adulto JovemRESUMO
Interferon regulatory factor-1 (IRF-1) is a tumor suppressor gene, which encodes a mammalian transcription factor that serves various vital functions in a cell, such as cell cycle regulation, immunomodulation, and antiviral response. We report full-length human IRF-1 cDNA cloning and expression in E. coli/BL21 cells with complete solubilisation of recombinant protein. We cloned the gene by the RT-PCR technique using ORF-specific primers followed by expression of recombinant IRF-1 in E. coli under GST fusion system. The profound expression of recombinant protein was observed after inducing with 0.5 mM IPTG for 3 h at 37 °C. We observed few degradation products of low molecular mass along with full-length fusion protein. We successfully minimized the formation of low molecular mass degradation products of GST-huIRF-1 protein at 16 °C. Simultaneously, we achieved the expression of recombinant protein in soluble fraction of E. coli/BL21 cells at 20 °C with higher yield, which is crucial to the study of the biological functions of any protein. We further confirmed it by the immunoblotting technique using anti-IRF-1 and anti-GST antibodies under the induction of E. coli cells harboring the IRF-1 recombinant plasmid after sonicated and fractioned fractions. This work will serve as a platform for characterizing the recombinant protein that may pave the way to understand molecular mechanism of tumour suppression caused by this molecule.
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Fator Regulador 1 de Interferon/biossíntese , Fator Regulador 1 de Interferon/química , Clonagem Molecular/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Glutationa Transferase/biossíntese , Glutationa Transferase/genética , Humanos , Fator Regulador 1 de Interferon/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes/genética , SolubilidadeRESUMO
BACKGROUND: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. METHODS: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2 nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. RESULTS: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. CONCLUSION: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.
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Cério/química , Nanopartículas Metálicas/uso terapêutico , Substâncias Protetoras/química , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Caspase 3/metabolismo , Quimiocina CXCL2/metabolismo , Quimiocinas/metabolismo , Imunoensaio , L-Lactato Desidrogenase/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Nanopartículas Metálicas/química , Mioglobina/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Proteína X Associada a bcl-2/metabolismoRESUMO
Optical internal urethrotomy (OIU) is the most common procedure performed for short segment bulbar urethral stricture worldwide. This procedure most commonly performed using Sachse's cold knife. Various perioperative complications of internal urethrotomy have been described in literature including bleeding, urinary tract infection, extravasation of fluid, incontinence, impotence, and recurrence of stricture. Here we report a unique complication of breakage of Sachse knife blade intraoperatively and its endoscopic management.
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Falha de Equipamento , Complicações Intraoperatórias/etiologia , Instrumentos Cirúrgicos , Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/instrumentação , Adulto , Cistoscopia/métodos , Fluoroscopia/métodos , Humanos , Complicações Intraoperatórias/cirurgia , Masculino , Uretra/diagnóstico por imagem , Uretra/cirurgiaRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. After further consultation with the experts conducting research in the area of XRD and FTIR spectrum, it has been concluded that the appropriate action for this case is the full retraction of the article from the Journal of Environmental Management. The rationale for this decision is what the journal has concluded to be the fabrication of data associated with Figure 2a in the manuscript which shows three distinct areas in the noise patters with unusual similarities to be considered as coincidental. The data presented in Figure 2a jeopardizes the quality of the manuscript and the conclusions drawn based on the data presented in Figure 2.
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Bentonita/química , Corantes/química , Violeta Genciana/química , Poluentes Químicos da Água/química , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Ácidos Sulfúricos/química , Suspensões , Temperatura , Purificação da Água/métodosRESUMO
Epidermal growth factor receptor (EGFR) and its downstream elements are overexpressed in most cases of the head and neck squamous cell carcinoma. This study investigated the expression pattern of key proteins linked to the EGFR pathway in laryngeal carcinoma patients with a history of cannabis smoking. We selected 83 male glottic cancer patients, aged between 45 to 75 years with three distinct populations-nonsmoker, cigarette smoker, and cannabis smoker. Immunohistochemical staining was performed for EGFR, protein kinase B (PKB or Akt), nuclear factor kappa B p50 (NF-ÐB), and cyclooxygenase-2 (COX-2) followed by boolean scoring for statistical analysis. Experimental data showed upregulation of the selected EGFR cascade in tumor cells, stromal expression of EGFR, and nuclear localization of COX-2 in metaplastic gland cells of laryngeal cancer tissue sample. Statistical analyses indicated that overexpression of the EGFR cascade is significantly correlated to cannabis smoking. Cannabis smokers had higher expression (p < 0.01) of these onco-proteins with respect to both nonsmokers as well as cigarette smokers. Risk factor analysis showed high risk of these proteins expression in age <60 years (odds ratio (OR) > 1.5) as the lower age group had relatively higher number of cannabis smokers. This study provides evidence for a direct association between cannabis smoking and increased risk of laryngeal cancer. Higher expression of the EGFR cascade in cannabis smokers revealed that cannabis smoking may be a major cause for the early onset of aggressive laryngeal cancer.
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Ciclo-Oxigenase 2/biossíntese , Receptores ErbB/biossíntese , Neoplasias Laríngeas/genética , Subunidade p50 de NF-kappa B/biossíntese , Proteína Oncogênica v-akt/biossíntese , Idoso , Ciclo-Oxigenase 2/genética , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Laríngeas/induzido quimicamente , Neoplasias Laríngeas/patologia , Masculino , Fumar Maconha/efeitos adversos , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Proteína Oncogênica v-akt/genética , Fatores de Risco , Transdução de Sinais/efeitos dos fármacosRESUMO
Plants, herbivores and parasitoids affect each other directly and indirectly; however, feedback effects mediated by host plant traits have rarely been demonstrated in these tritrophic interactions. Brood-site pollination mutualisms (e.g. those involving figs and fig wasps) represent specialised tritrophic communities where the progeny of mutualistic pollinators and of non-mutualistic gallers (both herbivores) together with that of their parasitoids develop within enclosed inflorescences called syconia (hence termed brood-sites or microcosms). Plant reproductive phenology (which affects temporal brood-site availability) and inflorescence size (representing brood-site size) are plant traits that could affect reproductive resources, and hence relationships between trees, pollinators and non-pollinating wasps. Analysing wasp and seed contents of syconia, we examined direct, indirect, trophic and non-trophic relationships within the interaction web of the fig-fig wasp community of Ficus racemosa in the context of brood site size and availability. We demonstrate that in addition to direct resource competition and predator-prey (host-parasitoid) interactions, these communities display exploitative or apparent competition and trait-mediated indirect interactions. Inflorescence size and plant reproductive phenology impacted plant-herbivore and plant-parasitoid associations. These plant traits also influenced herbivore-herbivore and herbivore-parasitoid relationships via indirect effects. Most importantly, we found a reciprocal effect between within-tree reproductive asynchrony and fig wasp progeny abundances per syconium that drives a positive feedback cycle within the system. The impact of a multitrophic feedback cycle within a community built around a mutualistic core highlights the need for a holistic view of plant-herbivore-parasitoid interactions in the community ecology of mutualisms.
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Ficus/fisiologia , Polinização , Vespas/fisiologia , Animais , Ficus/crescimento & desenvolvimento , Ficus/parasitologia , Herbivoria , Interações Hospedeiro-Parasita , Inflorescência/crescimento & desenvolvimento , Inflorescência/fisiologia , Fenótipo , Reprodução/genética , Sementes/genética , SimbioseRESUMO
OBJECTIVE: Retinol binding protein 4 (RBP4) has been implicated in metabolic disorders including type 2 diabetes mellitus (T2DM), but few studies have looked at transthyretin (TTR) with which RBP4 is normally bound to in the circulation. We report on the systemic levels of RBP4 and TTR and their associations with insulin resistance, obesity, prediabetes, and T2DM in Asian Indians. METHODS: Age-matched individuals with normal glucose tolerance (NGT, n = 90), impaired glucose tolerance (IGT, n = 70) and T2DM (n = 90) were recruited from the Chennai Urban Rural Epidemiology Study (CURES). Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Circulatory RBP4 and TTR levels (in µg/mL) were highest in T2DM (RBP4: 13 ± 3.9, TTR: 832 ± 310) followed by IGT (RBP4: 10.5 ± 3.2; TTR: 720 ± 214) compared to NGT (RBP4: 8.7 ± 2.5; TTR: 551 ± 185; P<.001). Compared to nonobese NGT individuals, obese NGT, nonobese T2DM, and obese T2DM had higher RBP4 (8.1 vs. 10.6, 12.1, and 13.2 µg/mL, P<.01) and TTR levels (478 vs. 737, 777, and 900 µg/mL, P<.01). RBP4 but not TTR was significantly (P<.001) correlated with insulin resistance even among NGT subjects. In regression analysis, RBP4 and TTR showed significant associations with T2DM after adjusting for confounders (RBP4 odds ratio [OR]: 1.107, 95% confidence interval [CI]: 1.008-1.216; TTR OR: 1.342, 95% CI: 1.165-1.547). CONCLUSION: Circulatory levels of RBP4 and TTR showed a significant associations with glucose intolerance, obesity, T2DM and RBP4 additionally, with insulin resistance.
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Diabetes Mellitus Tipo 2/sangue , Intolerância à Glucose/sangue , Resistência à Insulina/fisiologia , Obesidade/sangue , Pré-Albumina/metabolismo , Estado Pré-Diabético/sangue , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adulto , Idoso , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y). METHODS: We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and monocyte chemotactic protein-1 [MCP-1]) across groups. RESULTS: Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 µg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 µg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-α levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM. CONCLUSION: In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.
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Adipocinas/sangue , Povo Asiático/estatística & dados numéricos , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Mediadores da Inflamação/sangue , Obesidade/sangue , Adolescente , Adulto , Idade de Início , Criança , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Índia/epidemiologia , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: There is a need to identify biomarkers for gestational diabetes mellitus (GDM). Recently the soluble pro-renin receptor (s[Pro]RR) has been shown to be associated with GDM. We investigated the association of s(Pro) RR levels in Asian Indians with GDM. METHODS: We recruited 222 pregnant females, 147 without GDM (non-GDM) and 75 with GDM visiting antenatal clinics in Tamilnadu in South India. We included singleton pregnancy and excluded those with pre-existing diabetes mellitus or hypertension. Oral glucose tolerance tests (OGTTs) were performed, and GDM was diagnosed using the International Association of Diabetes and Pregnancy Study Group criteria. s(Pro)RR was measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves were used to identify s(Pro) RR cut-off points to identify GDM. RESULTS: The mean levels of the s(Pro)RR were significantly higher in subjects with GDM (34.0 ± 12 ng/mL, P<.001) compared to non-GDM (21.4 ± 6.5 ng/mL). The proportions of subjects with GDM were 11 (15%) in the first tertile of s(Pro)RR (<19.61 ng/mL), 20 (27%) in the second (19.62-26.8 ng/mL), and 44 (59%) in the third tertile (>26.8 ng/mL). In multiple logistic regression analysis, s(Pro)RR showed a significant association with GDM (odds ratio [OR]: 1.201, 95% confidence interval [CI]: 1.065-1.355, P = .003) after adjusting for potential confounders. A s(Pro)RR cut-off of 23.3 ng/mL had a C statistic of 0.828 (95% CI: 0.738-0.918, P<.001), sensitivity of 68%, and specificity of 70% to identify GDM. CONCLUSIONS: s(Pro)RR levels are higher in females with GDM, and this could be used as a potential biomarker.