Shailendra Dwivedi | King George's Medical University (original) (raw)

Papers by Shailendra Dwivedi

Abstract Gene therapy, or the use of genetic entities after manipulation for disease management, ... more Abstract Gene therapy, or the use of genetic entities after manipulation for disease management, is derived from advances in genetics, molecular biology, clinical medicine, and human genomics. Molecular medicine, the application of molecular biological techniques to disease treatment and diagnosis, is derived from the development of human organ transplantation, pharmacotherapy, and elucidation of the human genome. The promise of gene therapy, permanent reversal or amelioration of disease symptoms without dependence on a long-lasting intake of drugs, has come within reach because of these conceptual and technical advances in molecular biology. The incidents came at a time when technical advances in the manipulation of DNA had led to widespread testing of gene-based therapies. Gene therapy is generally categorized as either in vivo, in which the gene is delivered directly into recipient cells in the site of target, or ex vivo, in which the gene of interest is inserted in vitro into a targeted cell population (usually stem cells or fibroblasts) and the cells are delivered to the desired site in vivo. These two gene delivery strategies are usually termed “in vivo gene delivery” and “cell-mediated gene delivery,” respectively. Since the beginning of the first gene therapy (clinical trial), i.e., approximately 25 years ago, the field of human gene therapy has gone through numerous successions of ups and downs. Gene therapy has made a profound impact not only in the treatment of genetic disease such as sickle cell anemia as single gene disorder but also open new vistas in neurological diseases, cardiovascular diseases, and cancer; hence, we have started looking at human diseases as a whole.

Indian Journal of Clinical Biochemistry, Mar 21, 2023

Indian Journal of Clinical Biochemistry, Jan 13, 2023

Clinica Chimica Acta, Jun 1, 2019

Research Square (Research Square), May 13, 2021

The current study determined levels of in ammatory cytokines TNF-α, IL-6, IL-10 and immune-regula... more The current study determined levels of in ammatory cytokines TNF-α, IL-6, IL-10 and immune-regulatory miR-155 and miR-187 expressions in chronic opiate abuse. Adults (n = 48), meeting the 5th Edition of the DSM criteria regarding opioid use disorder, and healthy controls (n = 46) were included in the study. Serum samples were analysed for in ammatory cytokines IL-10, IL-6, TNF-α using ELISA and PBMCs processed for miRNA expression using SybrGreen chemistry. Cases showed signi cantly raised IL-10 and TNF-α and reduced IL-6. Using RNU6 for normalization, dose-dependent corresponding upregulation of miR-155-5p and downregulation of miR-187-5p were evident at opiate dose > 1500 gm/day, with a corresponding increase of TNF-α and IL-10. MiR-155 showed a signi cant negative correlation with IL-6 and TNF-α; miR-187 showed a signi cant positive association with TNF-α at > 1000 g/day consumption. Therefore, increasing consumption of opium probably enhances in ammation leading to immunomodulation and aberrant expression of has-miR-155-5p and has-miR-187-5p in opiate abusers.

Indian Journal of Clinical Biochemistry, Jun 6, 2018

Lack of cardiometabolic profile data based on severity of opiate dependence for opiate abusers. T... more Lack of cardiometabolic profile data based on severity of opiate dependence for opiate abusers. The study aimed to evaluate the effect severity of opiate abuse on the cardiometabolic profile of male opiate abusers without comorbidities. The study included 30 healthy controls (HCs), 90 prospective chronic opiate (opium and heroin) abusers, with and without co-dependence of smoking and tobaccochewing. The subjects were categorized based on severity of opiate dependence questionnaire (SODQ) and metabolic syndrome (MS) based on NCEP ATP-III criteria and fasting blood samples analyzed for sugar, insulin, insulin resistance (IR), lipid profile, Hs-CRP and total antioxidant capacity (TAC). There was higher prevalence of MS in opiate abusers as compared to HCs. Majority of the patients fell in grade 2 and 3 of severity. There was significant difference across groups for WHR (p \ 0.001), SBP (p \ 0.03), FBS (p \ 0.001), insulin (p \ 0.02), IR (p \ 0.03) and TAC (p \ 0.01). Multiple regression analysis of SODQ grades 2 and 3 independently predicted TAC by Hs-CRP (p = 0.032 and 0.042). There was a significant correlation of TAC with serum insulin, IR and Hs-CRP in SODQ grade 2 and serum insulin and Hs-CRP in SODQ grade 3. Chronic opiate abuse is not benign and predisposes abusers to cardiometabolic risk with increasing severity of dependence, owing to oxidative stress and chronic lowgrade inflammation.

World Journal of Stem Cells

Indian Journal of Clinical Biochemistry

Inflammation, 2022

Substance use disorders are known to be associated with inflammation. However, the dynamics of in... more Substance use disorders are known to be associated with inflammation. However, the dynamics of inflammatory cytokines and microRNA in chronic opium use is yet unexplored. The current study determined the levels of inflammatory cytokines TNF-α, IL-6, IL-10 and immune-regulatory miR-155 and miR-187 expressions in chronic opioid use disorder. Adults ( n = 48) meeting the 5th Edition of the DSM criteria regarding opioid use disorder and healthy controls ( n = 46) were included in the study. Inflammatory cytokines IL-10, IL-6, and TNF-α were analyzed from serum samples, and peripheral blood mononuclear cells processed for miRNA expression. Cases showed significantly raised IL-10 and TNF-α and reduced IL-6. Dose-dependent upregulation of miR-155-5p and miR-187-5p was evident at opium dose >1500 g/month, with a corresponding increase of TNF-α and IL-10. MiR-155 showed a significant positive correlation with IL-6 and TNF-α levels, while miR-187 showed a significant negative association with TNF-α at ≥1000 g/month consumption. Therefore, increasing consumption of opium probably enhances inflammation leading to immunomodulation and aberrant expression of hsa-miR-155-5p and hsa-miR-187-5p in opioid use disorder.

Precision Medicine in Cancers and Non-Communicable Diseases, 2018

Molecular Diagnostics in Cancer Patients, 2019

Ovarian cancer is a heterogeneous disease that influences women worldwide, is diagnosed at an adv... more Ovarian cancer is a heterogeneous disease that influences women worldwide, is diagnosed at an advanced stage in most patients, and has no effective screening tests for initial detection. The incidence of this cancer is 225,500 diagnoses per year worldwide, and it is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis. Therefore, better management strategies are needed to improve outcomes for women with advanced ovarian cancer.

Single-Cell Omics, 2019

Abstract The dynamics and heterogeneity of breast cancer undergoing clonal evolution produce cell... more Abstract The dynamics and heterogeneity of breast cancer undergoing clonal evolution produce cells with varying degrees of drug resistance and metastatic potential. Breast cancer is well known for different clinical behaviors and patient outcomes, in spite of common histopathological features at diagnosis. Currently, single-cell analysis has made remarkable advances, overshadowing the problem of heterogeneity linked with huge populations. Rapid progression in sequencing methods now permits unbiased, high-output, and high-resolution interpretation of heterogeneity from individual cells within a population. Conventional treatment strategies for individual patients are directed by the presence and absence of expression pattern of the estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor 2 (HER2). Though such approaches for clinical classification have usefulness in selection of targeted therapies and short-term patient responses, they are unable to predict long-term survival. In any phenotypic alterations, like breast cancer disease, the molecular signature has proven its significance, as we know that an individual cell's state is controlled at diverse levels, such as DNA, RNA, and protein, by a multifaceted interplay of intrinsic biomolecule pathways existing in the organism and extrinsic stimuli such as the ambient environment. Thus for comprehensive understanding, complete profiling of a single-cell requires synchronous investigations from different levels (multiomics) to circumvent incomplete information produced from single-cells. In this chapter, initially we present current updates on the various methods available to explore omics and then we focus on omics (i.e., genomics, transcriptomics, epigenomics, proteomics, and metabolomics) data available from various studies that can be used for better management of breast cancer patients.

Annals of Oncology, 2018

peripheral neuropathy was assessed by the investigator and confirmed by the other medical oncolog... more peripheral neuropathy was assessed by the investigator and confirmed by the other medical oncologists according to CTCAE version 4.0. Result: Of 84 patients who received paclitaxel, 25 received neoadjuvant, and 59 received adjuvant chemotherapy. Median age of the patients was 50 years (range 27-74). 38 of the patients had peripheral neuropathy over grade 2, and 46 of them had under grade 1. The serum samples before treatment of those patients were randomly divided to training set and test set (2:1). 3 formulas with combination of four miRNAs were found to be able to predict peripheral neuropathy (PNmiR sets). PNmiR sets had a sensitivity, specificity and accuracy over 75% in the test cohort. It should be noted that one of the four miRNAs, which constructs two of the three formulas, represents the drug-transporter protein P-glycoprotein, potentially promoting paclitaxel resistance. Conclusion: The combination of four miRNAs (PNmiR set) measured from serum can be used to predict peripheral neuropathy by paclitaxel-contained chemotherapy. One of the potential miRNAs suggests the relation with metabolism of paclitaxel. O2 À 8 À 5 Prognostic value of subtype changes after neoadjuvant chemotherapy in primary breast cancer

Cell and tissue research, Jan 16, 2015

Growth/differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor b... more Growth/differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor beta (TGF-β) superfamily. It is widely distributed in the nervous system, where it has been shown to play an important role in neuronal maintenance. The present study investigates the role of endogenous GDF-15 in sciatic nerve (SN) lesions using wild-type (WT) and GDF-15 knock-out (KO) mice. SN of 5-6-month-old mice were crushed or transected. Dorsal root ganglia (DRG) and nerve tissue were analyzed at different time points from 6 h to 9 weeks post-lesion. Both crush and transection induced GDF-15 mRNA and protein in the distal portion of the nerve, with a peak at day 7. DRG neuron death did not significantly differ between the genotypes; similarly, remyelination of regenerating axons was not affected by the genotype. Alternative macrophage activation and macrophage recruitment were more pronounced in the KO nerve. Protrusion speed of axons was similar in the two genotypes but WT axons sh...

Indian Journal of Clinical Biochemistry, 2022

Diabetic Retinopathy (DR), a debilitating microvascular complication of diabetes, is one of the l... more Diabetic Retinopathy (DR), a debilitating microvascular complication of diabetes, is one of the leading cause of blindness. However, the pathogenesis of this disease is not fully understood. Few Studies have reported the role of MicroRNA (miRNA), which is deregulated or altered in many diseases. Further, few pathways linked genes which have been suggested to be regulated by miRNAs, may play an important role in the regulation of glucose homeostasis and eventually may contribute to the establishment of DR. However, the roles of microRNAs (miRNAs) in DR are still not very clear. In current review, we explored various findings of scientific database demonstrating the role of miRNA in the progression and development of Diabetic Retinopathy.

Indian Journal of Clinical Biochemistry, 2020

The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, the cause of c... more The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, the cause of coronavirus disease (COVID-19), has influenced health globally. So far, there are no established management options and prophylaxis for those who have been exposed to SARS-CoV-2, and those who develop COVID-19. Documented scientific evidences in similar viral outbreaks in past suggested few therapy regimens. These rather have not shown promising results in management of current pandemic. So, in the current review, we are exploring novel treatment strategies and therapies that are being explored and are in clinical and preclinical stages of research. To explore more about the same, we directed our search towards stem cell based, DNA based, or RNA based vaccines against COVID-19 under development by various universities, institutes or pharmaceutical companies. The current scientific literature and database search were performed by exploring various Trials registry (NIH: https:// clinicaltrials.gov/ and https://www.coronavirus.gov) and Chinese clinical trial registry http://www.chictr.org.cn/) and for preclinical trials various University, Institutions, Pharmaceutical companies websites and news bulletins along with google search were checked routinely from 3rd March 2020 to 16 May 2020. The term ''Stem Cell therapy and COVID-19'', ''Mesenchymal stem cell and corona 2019 virus'', ''DNA Vaccines and COVID-19, RNA Vaccines and COVID-19'' and ''Cell-based therapy with SARS-CoV-2, University/Institutions and COVID-19 research'' were used. The vaccine trials (Stem Cells/DNA/ RNA) which were cancelled were not included in this review. Similarly, few others like repurposing of drugs, Nano Vaccines, other miscellaneous trials of Herbs, Music therapy etc., were also excluded. In the present review, we have included the various novel therapies like stem cell therapy, DNA or RNA vaccines which are under development and if proven successful may have a lasting impact on the health industry. Keywords Stem cell based vaccine Á DNA vaccine Á RNA vaccine Á Nucleic acid based vaccines Á Viral disease Á COVID-19

Applied Molecular Biotechnology, 2016

Indian Journal of Clinical Biochemistry, 2015

Deficiency or excess of certain trace elements has been considered as risk factor for prostate ca... more Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann-Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.

Andrology, 2014

The aim of this review was to provide current scenario linking obesity and male fertility. Obesit... more The aim of this review was to provide current scenario linking obesity and male fertility. Obesity has been linked to male fertility because of lifestyle changes, internal hormonal environment alterations, and sperm genetic factors. A few studies assessing the impact of obesity on sperm genetic factor have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm genetic factor and obesity. There are emerging facts that obesity negatively affects male reproductive potential not only by reducing sperm quality, but in particular it alters the physical and molecular structure of germ cells in the testes and ultimately affects the maturity and function of sperm cells. Inhibition of microRNA in the male pronucleus of fertilized zygotes produces offspring of phenotypes of variable severity depending on miRNAs ratios. Hence, these RNAs have a role in the oocyte development during fertilization and in embryo development, fetal survival, and offspring phenotype. It has been reported that the miRNA profile is altered in spermatozoa of obese males, however, the impact of these changes in fertilization and embryo health remains as yet not known.

IntroductionMethylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) ... more IntroductionMethylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the key enzymes of the folate pathway, which involved in the DNA methylation. DNA methylation may affect the stability and integrity of DNA, that supposed to play a pivotal role in carcinogenesis. So, we aimed to investigate the association ofMTHFRC677T andMTRRA66G gene polymorphisms with susceptibility to prostate cancer in North Indian population. We also performed meta-analyses of published literatures on these polymorphisms to evaluate their association with prostate cancer.MethodsWe genotypedMTHFRC677T andMTRRA66G gene polymorphisms in 147 prostate cancer cases and 147 healthy controls using PCR-RFLP methods. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for risk estimation. For meta-analysis different databases were searched and all statistical analysis were performed using Open Meta-Analyst software.ResultsThe present case control study revealed that the...