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1.
Mol Biol Rep ; 49(10): 9749-9758, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35441940

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health concern. Nutritional interventions become a primary concern in managing various diseases, including CKD. Ketogenic diets (KD) are a popular diet and an increasingly used diet for weight loss. MAIN BODY: With the increasing cases of CKD, KD has been proposed as a treatment by many scientists. Several studies have shown that KD can slow down the progression rate of renal abnormalities. Also, this diet is regarded as a safe route for managing CKD. CKD is generally associated with increased inflammation, oxidative stress, fibrosis, autophagy dysfunction, and mitochondrial dysfunction, while all of these can be attenuated by KD. The protective effect of KD is mainly mediated through inhibition of ROS, NF-κB, and p62 signaling. CONCLUSIONS: It is suggested that KD could be considered a new strategy for managing and treating CKD more carefully. This review explores the potential of KD on CKD and the mechanism involved in KD-mediated kidney protection.


Assuntos
Dieta Cetogênica , Insuficiência Renal Crônica , Humanos , NF-kappa B/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio
2.
Nat Commun ; 12(1): 5325, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493733

RESUMO

Distal-less homeobox-1 (DLX1) is a well-established non-invasive biomarker for prostate cancer (PCa) diagnosis, however, its mechanistic underpinnings in disease pathobiology are not known. Here, we reveal the oncogenic role of DLX1 and show that abrogating its function leads to reduced tumorigenesis and metastases. We observed that ~60% of advanced-stage and metastatic patients display higher DLX1 levels. Moreover, ~96% of TMPRSS2-ERG fusion-positive and ~70% of androgen receptor (AR)-positive patients show elevated DLX1, associated with aggressive disease and poor survival. Mechanistically, ERG coordinates with enhancer-bound AR and FOXA1 to drive transcriptional upregulation of DLX1 in ERG-positive background. However, in ERG-negative context, AR/AR-V7 and FOXA1 suffice to upregulate DLX1. Notably, inhibiting ERG/AR-mediated DLX1 transcription using BET inhibitor (BETi) or/and anti-androgen drugs reduce its expression and downstream oncogenic effects. Conclusively, this study establishes DLX1 as a direct-target of ERG/AR with an oncogenic role and demonstrates the clinical significance of BETi and anti-androgens for DLX1-positive patients.


Assuntos
Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Fatores de Transcrição/genética , Transcrição Gênica , Antagonistas de Androgênios/farmacologia , Animais , Azepinas/farmacologia , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos SCID , Metástase Neoplásica , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Regiões Promotoras Genéticas , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Ligação Proteica , Receptores Androgênicos/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Transdução de Sinais , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Regulador Transcricional ERG/genética , Regulador Transcricional ERG/metabolismo , Triazóis/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203830

RESUMO

Insulin is a polypeptide hormone mainly secreted by ß cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.


Assuntos
Doença , Saúde , Insulina/metabolismo , Animais , Humanos , Secreção de Insulina , Fígado/metabolismo , Transdução de Sinais
4.
Heliyon ; 6(12): e05798, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33363261

RESUMO

Honey and its compounds are drawing attention as an effective natural therapy because of its ability to attenuate acute inflammation through enhancing immune response. Several studies have proved its potential healing capability against numerous chronic diseases/conditions, including pulmonary disorders, cardiac disorders, diabetes, hypertension, autophagy dysfunction, bacterial, and fungal infections. More importantly, honey has proved its virucidal effect on several enveloped viruses such as HIV, influenza virus, herpes simplex, and varicella-zoster virus. Honey may be beneficial for patients with COVID-19 which is caused by an enveloped virus SARS-CoV-2 by boosting the host immune system, improving comorbid conditions, and antiviral activities. Moreover, a clinical trial of honey on COVID-19 patients is currently undergoing. In this review, we have tried to summarize the potential benefits of honey and its ingredients in the context of antimicrobial activities, some chronic diseases, and the host immune system. Thus, we have attempted to establish a relationship with honey for the treatment of COVID-19. This review will be helpful to reconsider the insights into the possible potential therapeutic effects of honey in the context of the COVID-19 pandemic. However, the effects of honey on SARS-CoV-2 replication and/or host immune system need to be further investigated by in vitro and in vivo studies.

5.
Lung India ; 26(4): 109-13, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20531991

RESUMO

BACKGROUND: The Revised National Tuberculosis Control programme (RNTCP), India. AIM: To assess the impact of the expansion of the RNTCP in the case detection and treatment outcome. MATERIALS AND METHODS: Reports of patients with tuberculosis (TB) diagnosed and treated under RNTCP from 2001 to 2005 under Bagbazar TB unit (TU), Kolkata, reviewed retrospectively. RESULTS: Of 2814 cases registered between 2001 and 2005, 1268 were new smear-positive pulmonary TB (PTB), 308 were new smear-negative PTB and 536 were new extrapulmonary TB (EPTB). During that period, the new smear-positive case detection rate increased from 41 to 61 per lakh population, the annual total case detection rate increased from 87 to 142 per lakh and the treatment success rate reduced from 90% to 76%. The default and failure rates increased from 7% to 10% and from 3% to 10%, respectively. CONCLUSION: A steady increase was observed in the annual total case detection rate and annual new smear-positive case detection rate from 2001 to 2005, but the 3-month conversion rate and cure rate of new smear-positive patients were progressively decreased. Default rate and treatment failure rate of new smear-positive patients were also increased. So it needs extra attention and evaluation of this disappointing treatment outcome.

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