Publications by authors named "R Kumar"

15,745 Publications

Activation of SIRT1 by silibinin improved mitochondrial health and alleviated the oxidative damage in experimental diabetic neuropathy and high glucose-mediated neurotoxicity.

Arch Physiol Biochem 2022 Aug 9:1-17. Epub 2022 Aug 9.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.

Background: Silibinin (SBN), a sirtuin 1 (SIRT1) activator, has been evaluated for its anti-inflammatory activity in many inflammatory diseases. However, its role in diabetes-induced peripheral neuropathy (DPN) remains unknown. The SIRT1 activation convalesces nerve functions by improving mitochondrial biogenesis and mitophagy.

Methods: DPN was induced by streptozotocin (STZ) at a dose of 55 mg/kg, i.p. in the male SD rats whereas neurotoxicity was induced in Neuro2A cells by 30 mM (high glucose) glucose. Neurobehavioural (nerve conduction velocity and nerve blood flow) western blot, immunohistochemistry, and immunocytochemistry were performed to evaluate the protein expression and their cellular localisation.

Results: Two-week SBN treatment improved neurobehavioural symptoms, SIRT1, PGC-1α, and TFAM expression in the sciatic nerve and HG insulted N2A cells. It has also maintained the mitophagy by up-regulating PARL, PINK1, PGAM5, LC3 level and provided antioxidant defence by upregulating Nrf2.

Conclusion: SBN has shown neuroprotective potential in DPN through SIRT1 activation and antioxidant mechanism.
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http://dx.doi.org/10.1080/13813455.2022.2108454DOI Listing
August 2022

Evaluation of cell-free seminal mRNA for the diagnosis of obstruction as the cause of azoospermia in infertile men: A prospective cohort study.

Andrologia 2022 Aug 9:e14364. Epub 2022 Aug 9.

Department of Urology, All India Institute of Medical Sciences, New Delhi, India.

Differentiating obstructive (OA) from non-obstructive (NOA) azoospermia is clinically important in managing infertile men. Classically, the differentiation has been based on clinical, hormonal and histological analysis. Histological tests are invasive and may miss spermatogenic areas. Seminal fluid can serve as a medium to assess the status of spermatogenesis and presence or absence of certain markers can help diagnosing and differentiating azoospermia. We evaluated the role of cell-free seminal markers: DDX4, PRM1 and PRM2 in diagnosing and differentiating between OA and NOA and classifying their subtypes. We observed DDX4 was more sensitive for NOA compared with OA. Among various subtypes of NOA, DDX4 positivity was higher in patients with maturation arrest and hypospermatogenesis compared with Sertoli cell only syndrome. PRM1 and PRM2 had very low positivity rate for any meaningful comparison. Seminal cell-free markers can serve as non-invasive tests in diagnosing and differentiating etiologies of azoospermia but their validity needs to be proved in long-term trials with more refined molecular techniques.
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http://dx.doi.org/10.1111/and.14364DOI Listing
August 2022

Glycaemic control and factors affecting it in type 1 diabetes in children: experience from a tertiary care centre in India.

Pediatr Endocrinol Diabetes Metab 2022 Aug 9. Epub 2022 Aug 9.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: Optimal glycaemic control is essential for the prevention of future micro- and macrovascular complications in type 1 diabetes (T1D). The type of insulin, the type of insulin delivery device, the caregiver's knowledge, the patient's age, duration of diabetes, and self-monitoring of blood glucose affect glycaemic control in type 1 diabetes. In the present study, we analysed glycaemic control and factors affecting it at a tertiary care centre in northern India.

Material And Methods: A retrospective review of records of patients registered between 2015 and 2018 was done. The data on demographic and disease-related factors were collected from the records. The different groups were compared with the t-test, one-way ANOVA, or Kruskal-Wallis test.

Results: The mean age at the time of evaluation was 10.43 ±4.04 years (2-21 years), and the mean disease duration was 46.61 ±28.49 months (16-141 months). Most of the patients were prepubertal and using a basal-bolus regimen. The mean glycated haemoglobin (HbA1c ) was 7.96 ±1.46%, but only 24% had HbA1c below the International Society of Paediatric and Adolescent Diabetes (ISPAD) recommended desirable level of below 7%. Forty-six patients suffered one or more micro-macrovascular complications, and dyslipidaemia was the most common complication. Children with a longer duration of disease (8.39 ±1.42% vs. 7.59 ±1.65%), an episode of DKA (diabetes ketoacidosis) within a year of evaluation (9.19 ±2.54% vs. 7.93 ±1.39%), lower maternal (8.22 ±1.37% vs. 7.56 ±1.45%) and paternal education (8.26 ±1.67% vs. 7.78 ±1.30%), and hyperthyroid state (9.43 ±2.28% vs. 7.91 ±1.45%) had higher HbA1c.

Conclusions: Better diabetes education focusing on parents with lower education strata and children with longer disease duration and poor compliance can help improve glycaemic control in developing countries like India.
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http://dx.doi.org/10.5114/pedm.2022.118326DOI Listing
August 2022

Lipid-Polymer Hybrid "Particle-in-Particle" Nanostructure Gene Delivery Platform Explored for Lyophilizable DNA and mRNA COVID-19 Vaccines.

Adv Funct Mater 2022 Jul 22:2204462. Epub 2022 Jul 22.

Department of Chemical and Materials Engineering New Jersey Institute of Technology Newark NJ 07102 USA.

SARS-CoV-2 has led to a worldwide pandemic, catastrophically impacting public health and the global economy. Herein, a new class of lipid-modified polymer poly (β-amino esters) (L-PBAEs) is developed via enzyme-catalyzed esterification and further formulation of the L-PBAEs with poly(d,l-lactide-coglycolide)--poly(ethylene glycol) (PLGA-PEG) leads to self-assembly into a "particle-in-particle" (PNP) nanostructure for gene delivery. Out of 24 PNP candidates, the top-performing PNP/C12-PBAE nanoparticles efficiently deliver both DNA and mRNA in vitro and in vivo, presenting enhanced transfection efficacy, sustained gene release behavior, and excellent stability for at least 12 months of storage at -20 °C after lyophilization without loss of transfection efficacy. Encapsulated with spike encoded plasmid DNA and mRNA, the lipid-modified polymeric PNP COVID-19 vaccines successfully elicit spike-specific antibodies and Th1-biased T cell immune responses in immunized mice even after 12 months of lyophilized storage at -20 °C. This newly developed lipid-polymer hybrid PNP nanoparticle system demonstrates a new strategy for both plasmid DNA and mRNA delivery with the capability of long-term lyophilized storage.
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http://dx.doi.org/10.1002/adfm.202204462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349454PMC
July 2022

Treatment strategies for HIV infection with emphasis on role of CRISPR/Cas9 gene: Success so far and road ahead.

Eur J Pharmacol 2022 Aug 5:175173. Epub 2022 Aug 5.

School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India; Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia. Electronic address:

Advances in biotechnology have led to improving human health with number of novel approaches to mitigate life-threatening diseases such as human immunodeficiency virus (HIV) infection, cancer, and neurodegenerative diseases. In the case of HIV, the damage caused by the retrovirus to the immune system leads to opportunistic infection as well as an elevated risk of autoimmune disease and cancer. Furthermore, clinical symptoms associated with the virus itself may arise. Antiretroviral drug therapy using reverse transcriptase inhibitors, protease inhibitors, fusion inhibitor, chemokine receptor 5 antagonist and integrase strand transfer inhibitors have shown promising results in treating HIV infection and available in market in the form of various dosage forms. However, they are unable to completely cure the disease because of complexity in pathogenesis of HIV. In addition, these drugs have some limitations of poor solubility, permeability or, poor receptor binding capacity. To overcome these drawbacks, many novel drug delivery systems for the drugs belonging to above mentioned categories have been developed. The possibility of treating HIV infection using CRISPR-Cas9 gene editing has been found in 2015. This provided a new area of research to the scientists who are working towards alternative treatment strategies for HIV infections. The present article describes about various treatment strategies used to treat HIV infections with special emphasis on the role of CRISPR/Cas9 gene-based technology. The potential benefits of specific epigenetic modification in the c-c chemokine receptor 5 gene (CCR5) via various delivery methods are also highlighted.
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http://dx.doi.org/10.1016/j.ejphar.2022.175173DOI Listing
August 2022
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