Clinical and Experimental Obstetrics & Gynecology, May 26, 2023
Background: Breast cancer (BC) is the most common malignancy and the leading cause of mortality a... more Background: Breast cancer (BC) is the most common malignancy and the leading cause of mortality among women. Various diagnostic tools for early diagnosis and tumor progression detection have helped patients receive precise and timely treatment. This meta-analysis aims to evaluate the accuracy of abbreviated magnetic resonance imaging (ABB-MRI) data in the diagnosis of BC. Methods: The Preferred Reporting Items for Systematic Reviews and Comparative Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guidelines were followed to perform the meta-analysis. Data from articles published in the last 5 years reporting ABB-MRI as a diagnostic tool were collected by searching the relevant databases using multiple subject keywords and free words. Meta-Disc 1.4 software was used to analyze the data and plot the relevant graphs. Results: We identified 1250 articles while searching the relevant electronic databases. After removing duplicate studies and data, the titles and abstracts of 1149 studies were reviewed. A total of 18 publications that satisfied the inclusion criteria were finally included in the meta-analysis. The calculated pooled specificity and sensitivity were 0.90 and 0.87, respectively. This study confirms the ABB-MRI protocol's high diagnostic sensitivity and specificity in malignant breast cancer detection. Conclusions: Abbreviated MRI seems to function as a useful supplement because it is highly sensitive and specific, on par with the full MRI scan, as shown in multiple independent studies as well as this pooled analysis. These findings confirm the utility of ABB-MRI in the accurate detection of malignant BC lesions in high-risk women that cannot be detected by mammography or ultrasound.
Abstract Molecular imaging has emerged as one of the major areas of research in medical diagnosti... more Abstract Molecular imaging has emerged as one of the major areas of research in medical diagnostics by facilitating timely diagnosis and identification of disease progression and providing relevant insights into pathological processes. Imaging modalities often used by clinicians for 3D cancer staging include computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. Nanoparticulate probes have shown remarkable improvements in medical detection and imaging over single molecule-based contrast agents. Owing to their small size and prolonged circulation time due to lymphatic drainage, nanoparticles display better enhanced permeability and retention effects in solid tumors as well as contrast agents, presenting outstanding contrast. The present chapter will provide insights about applications and limits of nanoparticle-based contrast agents, their advantages, structure, and composition of nanoparticles for biomedical imaging fabricated by surface modification or by using core/shell structures with the examples discussed for each category.
Alzheimer's disease (AD), a neurodegenerative disorder, is the most common form of dementia in th... more Alzheimer's disease (AD), a neurodegenerative disorder, is the most common form of dementia in the elderly individuals. Among the pathogenic mechanisms in AD, chronic systemic inflammation is described and characterized by massive production of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs), which may contribute to an altered immune response and exacerbation of neurodegeneration. Studies have also reported increased double-stranded RNA-dependent protein kinase (PKR) activation in the PBMCs of patients with AD. Interestingly, PKR could be involved in NF-κB activation, leading to production of a wide range of cytokines. We proposed to decrease proinflammatory cytokines production and release by treating the PBMCs in 25 patients with AD with a specific inhibitor of PKR. Our results showed that PKR inhibition greatly decreased tumor necrosis factor α, interleukin (IL)-1α, IL-1β, and IL-6 production and release but did not affect the chemokine RANTES. Moreover, inhibition of the proinflammatory factors was correlated with prevention of caspase-3 activation. These results indicated that specific inhibition of PKR at the peripheral level might decrease the inflammatory response in AD.
ACS pharmacology & translational science, Mar 9, 2022
Sodium-dependent glucose cotransporter 2 inhibitors (SGLT2) are recently approved drugs for the t... more Sodium-dependent glucose cotransporter 2 inhibitors (SGLT2) are recently approved drugs for the treatment of diabetes that regulate blood glucose levels by inhibiting reabsorption of glucose and sodium in the proximal tubules of the kidney. SGLT2 inhibitors have also shown cardiovascular (CV) benefits in diabetic patients. However, the therapeutic efficacy of SGLT2 inhibitors with respect to CV disease needs further investigation. Thus, the aim of the present study was to examine the effects of SGLT2 inhibitors, canagliflozin (CANA) and dapagliflozin (DAPA) in vitro under glucolipotoxic condition by treating cultured cardiomyocytes (H9C2) with high glucose (HG) and high lipid, palmitic acid (PA), to investigate whether inhibition of sodium glucose cotransporter could prevent any harmful effects of glucolipotoxicity in these cells. SGLT1 expression was measured by immunofluorescence staining and quantitative polymerase chain reaction. Oxidative stress and apoptosis were measured by flow cytometry. Hypertrophy was measured by hematoxylin and eosin (H&E) and crystal violet staining. A significant increase in SGLT1 expression was observed in HG- and PA-treated cardiomyocytes. Also, a significant increase in reactive oxygen species generation and apoptosis was observed in HG+PA-treated cultured cardiomyocytes. HG- and PA-treated cardiomyocytes developed significant structural alterations. All these effects of HG and PA were attenuated by CANA and DAPA. In conclusion, our study demonstrates upregulation of SGLT1 induces oxidative stress and apoptosis in cultured cardiomyocytes. Thus, inhibition of SGLT1 may be used as a possible approach for the treatment of CVD in diabetic patients.
Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferre... more Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug t...
Role of genetic, environmental, and hormonal factors in the progression of PCOS: A review
Journal of Reproductive Healthcare and Medicine
Polycystic ovary syndrome (PCOS) can be mainly defined as a gynecological problem accompanied by ... more Polycystic ovary syndrome (PCOS) can be mainly defined as a gynecological problem accompanied by an endocrine disturbance in females and can be seen mainly during their menstruation age. Worldwide PCOS prevalence ranges between 6% and 10%. Many of the risk factors are responsible for the pathogenesis of PCOS. Environmental factors such as environmental toxins and obesity play a major role in the occurrence of PCOS, followed by the hormonal disturbance in androgen levels, that is, hyperandrogenism, and insulin levels, that is, hyperinsulinemia. The previous studies have suggested that there is a major contribution of genetics in the etiology of PCOS. However, there is no strong evidence about the mode of inheritance of PCOS. It has been seen that there is a strong correlation between environmental, hormonal, and genetic factors which follow a vicious cycle in the development of PCOS that leads to ovarian dysfunction, metabolic syndrome, that is, metabolic abnormalities include insuli...
Evaluation of newly identified Ikaros family zinc finger 1 loci in colorectal cancer
Journal of Cancer Research and Therapeutics, 2021
Aim: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 ... more Aim: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 (IKZF1) gene with the risk of colorectal cancer (CRC) within the population of Jammu and Kashmir (J and K). Materials and Methods: The variant rs6964823 of the IKZF1 gene was genotyped using the TaqMan allele discrimination assay for 578 individuals (182 CRC cases and 396 healthy controls). The association of single-nucleotide polymorphisms with the disease was evaluated using logistic regression. Results: It was observed that the variant rs6964823 (IKZF1) showed a significant association with an adjusted allelic odds ratio (OR) of 1.74 (1.34–2.27) at 95% confidence interval (CI), P ≤ 0.05. The dominant model (AA + AG vs. GG) was also applied, where the adjusted OR was 3.096 (2.011–4.76) at 95% CI, P > 0.05. Conclusions: It was found that the variant rs6964823 of the IKZF1 gene is associated with a higher risk of CRC within the population of J and K.
Most living organisms have in their genome a sizable proportion of DNA sequences capable of mobil... more Most living organisms have in their genome a sizable proportion of DNA sequences capable of mobilization; these sequences are commonly referred to as transposons, transposable elements (TEs), or jumping genes. Although long thought to have no biological significance, advances in DNA sequencing and analytical technologies have enabled precise characterization of TEs and confirmed their ubiquitous presence across all forms of life. These findings have ignited intense debates over their biological significance. The available evidence now supports the notion that TEs exert major influence over many biological aspects of organismal life. Transposable elements contribute significantly to the evolution of the genome by giving rise to genetic variations in both active and passive modes. Due to their intrinsic nature of mobility within the genome, TEs primarily cause gene disruption and large-scale genomic alterations including inversions, deletions, and duplications. Besides genomic instabi...
Objective: Objective: To understand role of mitochondrial (mt) mutations in genes regulating oxid... more Objective: Objective: To understand role of mitochondrial (mt) mutations in genes regulating oxidative phosphorylation (OXPHOS) in pathogenesis of male infertility. Infertility affects approximately 15% of couples trying to conceive. Infertility is frequently attributed to defects of sperm motility and number. Mitochondrion and mitochondrial DNA (mtDNA) play an important role in variety of physiological process. They control the oxidative energy supply and thus are central to growth, development and differentiation. Mitochondrial function is controlled by a Þ ne-tuned crosstalk between mtDNA and nuclear DNA (nDNA). As mitochondria supply energy by OXPHOS, any mutation in mtDNA disrupts adenosine triphosphate (ATP) production and thus result in an impaired spermatogenesis and impaired ß agellar movement. As sperm midpiece has few mtDNA copies, thus enhanced number of mutant mtDNA results in early phenotypic defect which manifest as spermatogenic arrest or asthenozoospermia. Oxidative stress and mtDNA mutations are positively correlated and mutations in mitochondrial genome (mt genome) are implicated in the lowered fertilising capacity of the sperm and affects the reproductive potential of an individual. Materials and Methods: Materials and Methods: A thorough review of articles in the last 15 years was cited with reference to the below-mentioned keywords. The articles considered discuss the role of mt genome in the normal functioning of sperm and the factors associated with mt mutations and impact of these mutations on the reproductive potential. Results: Results: Sperm motility is a very important factor for the fertilisation of ova. The energy requirements of sperm are therefore very critical for sperm. Mutations in the mitochondrial genes as COX II, ATPase 6 and 8 play an important role and disrupts ATP production affecting the spermatogenesis and sperm motility. Therefore, the aberrations in mt genome are an important etiopatholgy of male infertility. Conclusion: Conclusion: In the context of male infertility, mt mutations, generation of reactive oxygen species and lowered antioxidant capacity are interlinked and constitute a uniÞ ed pathogenic molecular mechanism. In the era of assisted reproduction technique (ART), it is very important to distinguish between mutations in nuclear and mitochondrial genomes in sperm, as mtDNA mutations are better diagnostic and prognostic markers in infertile men opting for ART.
Ovarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most c... more Ovarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most common cancers among women. The aim of the study is to unravel the genetic factors associated with OC and the extent of genetic heterogeneity in the populations of Jammu and Kashmir (J&K).Using the high throughput Agena MassARRAY platform, present case control study was designed which comprises 200 histopathological confirmed OC patients and 400 age and ethnicity matched healthy controls to ascertain the association of previously reported eleven single nucleotide polymorphisms (SNPs) spread over ten genes (DNMT3A,
Publisher Correction: High fructose and streptozotocin induced diabetic impairments are mitigated by Indirubin‑3‑hydrazone via downregulation of PKR pathway in Wistar rats
Phytochemicals in Clinical Studies: Current Perspective
Natural plants and their derived products are effective against various diseases for their preven... more Natural plants and their derived products are effective against various diseases for their prevention and treatment for several years. Availability of synthetic drugs with faster and selective responses against various diseases decreased the use of herbal products. However, due to adverse side effects of synthetic drugs, in the last few years, the clinical use of plant-derived medicines has been exponentially increased in developing as well as developed countries due to their easy availability, low cost, and least toxicity. Therefore, in recent years, several human trials have been done to analyze the toxicology, pharmacokinetics, and biologically effective dose of phytochemicals against cancer, diabetes, and bacterial and viral diseases for their clinical application. In the present book chapter, we have discussed the clinical studies on phytochemicals against several diseases including diabetes, cancer, and diseases associated with microbial infections including women health probl...
REV3L Gene Variants rs1002481, rs462779, and rs465646 Lead to Increased Susceptibility Towards Non-Small Cell Lung Cancer in the Population of Jammu and Kashmir
Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer accounti... more Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer accounting for 80–85% of all lung cancer cases. Various genetic studies have tried to reveal the association of REV3L (Protein reversion less 3-like) gene mutations with cancer, including lung cancer but no such study has been carried out in the population of Jammu and Kashmir (J&K).Methods: The selected REV3L variants were genotyped using the TaqMan allele discrimination assay in 550 subjects (203 NSCLC patients and 347 healthy controls). The association of variants was evaluated by logistic regression.Results: Out of the four REV3L variants genotyped, we found rs1002481, rs462779, and rs465646 significantly associated with NSCLC risk with an Odds Ratio (OR) of 3.5 (1.98–6.3 at 95% CI ), p value = 0.00002; OR = 4.4 (1.8–10.4 at 95% CI ), p value = 0.00075; and OR = 2.4 (1.47–4.008 at 95% CI ), p value = 0.00053, respectively.Conclusion: Our data suggest a strong association of variants rs100248...
High fructose and streptozotocin induced diabetic impairments are mitigated by Indirubin-3-hydrazone via downregulation of PKR pathway in Wistar rats
Metabolic disorders are becoming more common in young population due to increased consumption of ... more Metabolic disorders are becoming more common in young population due to increased consumption of carbohydrate rich diet, lack of physical activity and stress. Fructose is used as a sweetener in many carbonated beverages and is a known inducer of oxidative stress and hypertension. Up-regulation of the double-stranded RNA-dependent protein kinase (PKR) causes impairment in insulin signaling pathway and metabolic dysfunctions in type 2 diabetes mellitus. In the present study we investigated the role of PKR and associated pathways in high fructose (HF) and streptozotocin (STZ) induced diabetes and whether indirubin-3-hydrazone (IHZ), a novel PKR inhibitor can reverse the HF and STZ induced diabetic impairments in Wistar rats. Diabetes was induced by feeding rats 20% high fructose in drinking water for 6 weeks and by giving a single dose of STZ (35 mg/kg., i.p) at the end of week 5. Glucose and lipid levels were measured by using assay kits. Expression of PKR and its downstream genes wer...
Clinical and Experimental Obstetrics & Gynecology, May 26, 2023
Background: Breast cancer (BC) is the most common malignancy and the leading cause of mortality a... more Background: Breast cancer (BC) is the most common malignancy and the leading cause of mortality among women. Various diagnostic tools for early diagnosis and tumor progression detection have helped patients receive precise and timely treatment. This meta-analysis aims to evaluate the accuracy of abbreviated magnetic resonance imaging (ABB-MRI) data in the diagnosis of BC. Methods: The Preferred Reporting Items for Systematic Reviews and Comparative Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guidelines were followed to perform the meta-analysis. Data from articles published in the last 5 years reporting ABB-MRI as a diagnostic tool were collected by searching the relevant databases using multiple subject keywords and free words. Meta-Disc 1.4 software was used to analyze the data and plot the relevant graphs. Results: We identified 1250 articles while searching the relevant electronic databases. After removing duplicate studies and data, the titles and abstracts of 1149 studies were reviewed. A total of 18 publications that satisfied the inclusion criteria were finally included in the meta-analysis. The calculated pooled specificity and sensitivity were 0.90 and 0.87, respectively. This study confirms the ABB-MRI protocol's high diagnostic sensitivity and specificity in malignant breast cancer detection. Conclusions: Abbreviated MRI seems to function as a useful supplement because it is highly sensitive and specific, on par with the full MRI scan, as shown in multiple independent studies as well as this pooled analysis. These findings confirm the utility of ABB-MRI in the accurate detection of malignant BC lesions in high-risk women that cannot be detected by mammography or ultrasound.
Abstract Molecular imaging has emerged as one of the major areas of research in medical diagnosti... more Abstract Molecular imaging has emerged as one of the major areas of research in medical diagnostics by facilitating timely diagnosis and identification of disease progression and providing relevant insights into pathological processes. Imaging modalities often used by clinicians for 3D cancer staging include computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. Nanoparticulate probes have shown remarkable improvements in medical detection and imaging over single molecule-based contrast agents. Owing to their small size and prolonged circulation time due to lymphatic drainage, nanoparticles display better enhanced permeability and retention effects in solid tumors as well as contrast agents, presenting outstanding contrast. The present chapter will provide insights about applications and limits of nanoparticle-based contrast agents, their advantages, structure, and composition of nanoparticles for biomedical imaging fabricated by surface modification or by using core/shell structures with the examples discussed for each category.
Alzheimer's disease (AD), a neurodegenerative disorder, is the most common form of dementia in th... more Alzheimer's disease (AD), a neurodegenerative disorder, is the most common form of dementia in the elderly individuals. Among the pathogenic mechanisms in AD, chronic systemic inflammation is described and characterized by massive production of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs), which may contribute to an altered immune response and exacerbation of neurodegeneration. Studies have also reported increased double-stranded RNA-dependent protein kinase (PKR) activation in the PBMCs of patients with AD. Interestingly, PKR could be involved in NF-κB activation, leading to production of a wide range of cytokines. We proposed to decrease proinflammatory cytokines production and release by treating the PBMCs in 25 patients with AD with a specific inhibitor of PKR. Our results showed that PKR inhibition greatly decreased tumor necrosis factor α, interleukin (IL)-1α, IL-1β, and IL-6 production and release but did not affect the chemokine RANTES. Moreover, inhibition of the proinflammatory factors was correlated with prevention of caspase-3 activation. These results indicated that specific inhibition of PKR at the peripheral level might decrease the inflammatory response in AD.
ACS pharmacology & translational science, Mar 9, 2022
Sodium-dependent glucose cotransporter 2 inhibitors (SGLT2) are recently approved drugs for the t... more Sodium-dependent glucose cotransporter 2 inhibitors (SGLT2) are recently approved drugs for the treatment of diabetes that regulate blood glucose levels by inhibiting reabsorption of glucose and sodium in the proximal tubules of the kidney. SGLT2 inhibitors have also shown cardiovascular (CV) benefits in diabetic patients. However, the therapeutic efficacy of SGLT2 inhibitors with respect to CV disease needs further investigation. Thus, the aim of the present study was to examine the effects of SGLT2 inhibitors, canagliflozin (CANA) and dapagliflozin (DAPA) in vitro under glucolipotoxic condition by treating cultured cardiomyocytes (H9C2) with high glucose (HG) and high lipid, palmitic acid (PA), to investigate whether inhibition of sodium glucose cotransporter could prevent any harmful effects of glucolipotoxicity in these cells. SGLT1 expression was measured by immunofluorescence staining and quantitative polymerase chain reaction. Oxidative stress and apoptosis were measured by flow cytometry. Hypertrophy was measured by hematoxylin and eosin (H&E) and crystal violet staining. A significant increase in SGLT1 expression was observed in HG- and PA-treated cardiomyocytes. Also, a significant increase in reactive oxygen species generation and apoptosis was observed in HG+PA-treated cultured cardiomyocytes. HG- and PA-treated cardiomyocytes developed significant structural alterations. All these effects of HG and PA were attenuated by CANA and DAPA. In conclusion, our study demonstrates upregulation of SGLT1 induces oxidative stress and apoptosis in cultured cardiomyocytes. Thus, inhibition of SGLT1 may be used as a possible approach for the treatment of CVD in diabetic patients.
Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferre... more Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug t...
Role of genetic, environmental, and hormonal factors in the progression of PCOS: A review
Journal of Reproductive Healthcare and Medicine
Polycystic ovary syndrome (PCOS) can be mainly defined as a gynecological problem accompanied by ... more Polycystic ovary syndrome (PCOS) can be mainly defined as a gynecological problem accompanied by an endocrine disturbance in females and can be seen mainly during their menstruation age. Worldwide PCOS prevalence ranges between 6% and 10%. Many of the risk factors are responsible for the pathogenesis of PCOS. Environmental factors such as environmental toxins and obesity play a major role in the occurrence of PCOS, followed by the hormonal disturbance in androgen levels, that is, hyperandrogenism, and insulin levels, that is, hyperinsulinemia. The previous studies have suggested that there is a major contribution of genetics in the etiology of PCOS. However, there is no strong evidence about the mode of inheritance of PCOS. It has been seen that there is a strong correlation between environmental, hormonal, and genetic factors which follow a vicious cycle in the development of PCOS that leads to ovarian dysfunction, metabolic syndrome, that is, metabolic abnormalities include insuli...
Evaluation of newly identified Ikaros family zinc finger 1 loci in colorectal cancer
Journal of Cancer Research and Therapeutics, 2021
Aim: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 ... more Aim: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 (IKZF1) gene with the risk of colorectal cancer (CRC) within the population of Jammu and Kashmir (J and K). Materials and Methods: The variant rs6964823 of the IKZF1 gene was genotyped using the TaqMan allele discrimination assay for 578 individuals (182 CRC cases and 396 healthy controls). The association of single-nucleotide polymorphisms with the disease was evaluated using logistic regression. Results: It was observed that the variant rs6964823 (IKZF1) showed a significant association with an adjusted allelic odds ratio (OR) of 1.74 (1.34–2.27) at 95% confidence interval (CI), P ≤ 0.05. The dominant model (AA + AG vs. GG) was also applied, where the adjusted OR was 3.096 (2.011–4.76) at 95% CI, P > 0.05. Conclusions: It was found that the variant rs6964823 of the IKZF1 gene is associated with a higher risk of CRC within the population of J and K.
Most living organisms have in their genome a sizable proportion of DNA sequences capable of mobil... more Most living organisms have in their genome a sizable proportion of DNA sequences capable of mobilization; these sequences are commonly referred to as transposons, transposable elements (TEs), or jumping genes. Although long thought to have no biological significance, advances in DNA sequencing and analytical technologies have enabled precise characterization of TEs and confirmed their ubiquitous presence across all forms of life. These findings have ignited intense debates over their biological significance. The available evidence now supports the notion that TEs exert major influence over many biological aspects of organismal life. Transposable elements contribute significantly to the evolution of the genome by giving rise to genetic variations in both active and passive modes. Due to their intrinsic nature of mobility within the genome, TEs primarily cause gene disruption and large-scale genomic alterations including inversions, deletions, and duplications. Besides genomic instabi...
Objective: Objective: To understand role of mitochondrial (mt) mutations in genes regulating oxid... more Objective: Objective: To understand role of mitochondrial (mt) mutations in genes regulating oxidative phosphorylation (OXPHOS) in pathogenesis of male infertility. Infertility affects approximately 15% of couples trying to conceive. Infertility is frequently attributed to defects of sperm motility and number. Mitochondrion and mitochondrial DNA (mtDNA) play an important role in variety of physiological process. They control the oxidative energy supply and thus are central to growth, development and differentiation. Mitochondrial function is controlled by a Þ ne-tuned crosstalk between mtDNA and nuclear DNA (nDNA). As mitochondria supply energy by OXPHOS, any mutation in mtDNA disrupts adenosine triphosphate (ATP) production and thus result in an impaired spermatogenesis and impaired ß agellar movement. As sperm midpiece has few mtDNA copies, thus enhanced number of mutant mtDNA results in early phenotypic defect which manifest as spermatogenic arrest or asthenozoospermia. Oxidative stress and mtDNA mutations are positively correlated and mutations in mitochondrial genome (mt genome) are implicated in the lowered fertilising capacity of the sperm and affects the reproductive potential of an individual. Materials and Methods: Materials and Methods: A thorough review of articles in the last 15 years was cited with reference to the below-mentioned keywords. The articles considered discuss the role of mt genome in the normal functioning of sperm and the factors associated with mt mutations and impact of these mutations on the reproductive potential. Results: Results: Sperm motility is a very important factor for the fertilisation of ova. The energy requirements of sperm are therefore very critical for sperm. Mutations in the mitochondrial genes as COX II, ATPase 6 and 8 play an important role and disrupts ATP production affecting the spermatogenesis and sperm motility. Therefore, the aberrations in mt genome are an important etiopatholgy of male infertility. Conclusion: Conclusion: In the context of male infertility, mt mutations, generation of reactive oxygen species and lowered antioxidant capacity are interlinked and constitute a uniÞ ed pathogenic molecular mechanism. In the era of assisted reproduction technique (ART), it is very important to distinguish between mutations in nuclear and mitochondrial genomes in sperm, as mtDNA mutations are better diagnostic and prognostic markers in infertile men opting for ART.
Ovarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most c... more Ovarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most common cancers among women. The aim of the study is to unravel the genetic factors associated with OC and the extent of genetic heterogeneity in the populations of Jammu and Kashmir (J&K).Using the high throughput Agena MassARRAY platform, present case control study was designed which comprises 200 histopathological confirmed OC patients and 400 age and ethnicity matched healthy controls to ascertain the association of previously reported eleven single nucleotide polymorphisms (SNPs) spread over ten genes (DNMT3A,
Publisher Correction: High fructose and streptozotocin induced diabetic impairments are mitigated by Indirubin‑3‑hydrazone via downregulation of PKR pathway in Wistar rats
Phytochemicals in Clinical Studies: Current Perspective
Natural plants and their derived products are effective against various diseases for their preven... more Natural plants and their derived products are effective against various diseases for their prevention and treatment for several years. Availability of synthetic drugs with faster and selective responses against various diseases decreased the use of herbal products. However, due to adverse side effects of synthetic drugs, in the last few years, the clinical use of plant-derived medicines has been exponentially increased in developing as well as developed countries due to their easy availability, low cost, and least toxicity. Therefore, in recent years, several human trials have been done to analyze the toxicology, pharmacokinetics, and biologically effective dose of phytochemicals against cancer, diabetes, and bacterial and viral diseases for their clinical application. In the present book chapter, we have discussed the clinical studies on phytochemicals against several diseases including diabetes, cancer, and diseases associated with microbial infections including women health probl...
REV3L Gene Variants rs1002481, rs462779, and rs465646 Lead to Increased Susceptibility Towards Non-Small Cell Lung Cancer in the Population of Jammu and Kashmir
Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer accounti... more Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer accounting for 80–85% of all lung cancer cases. Various genetic studies have tried to reveal the association of REV3L (Protein reversion less 3-like) gene mutations with cancer, including lung cancer but no such study has been carried out in the population of Jammu and Kashmir (J&K).Methods: The selected REV3L variants were genotyped using the TaqMan allele discrimination assay in 550 subjects (203 NSCLC patients and 347 healthy controls). The association of variants was evaluated by logistic regression.Results: Out of the four REV3L variants genotyped, we found rs1002481, rs462779, and rs465646 significantly associated with NSCLC risk with an Odds Ratio (OR) of 3.5 (1.98–6.3 at 95% CI ), p value = 0.00002; OR = 4.4 (1.8–10.4 at 95% CI ), p value = 0.00075; and OR = 2.4 (1.47–4.008 at 95% CI ), p value = 0.00053, respectively.Conclusion: Our data suggest a strong association of variants rs100248...
High fructose and streptozotocin induced diabetic impairments are mitigated by Indirubin-3-hydrazone via downregulation of PKR pathway in Wistar rats
Metabolic disorders are becoming more common in young population due to increased consumption of ... more Metabolic disorders are becoming more common in young population due to increased consumption of carbohydrate rich diet, lack of physical activity and stress. Fructose is used as a sweetener in many carbonated beverages and is a known inducer of oxidative stress and hypertension. Up-regulation of the double-stranded RNA-dependent protein kinase (PKR) causes impairment in insulin signaling pathway and metabolic dysfunctions in type 2 diabetes mellitus. In the present study we investigated the role of PKR and associated pathways in high fructose (HF) and streptozotocin (STZ) induced diabetes and whether indirubin-3-hydrazone (IHZ), a novel PKR inhibitor can reverse the HF and STZ induced diabetic impairments in Wistar rats. Diabetes was induced by feeding rats 20% high fructose in drinking water for 6 weeks and by giving a single dose of STZ (35 mg/kg., i.p) at the end of week 5. Glucose and lipid levels were measured by using assay kits. Expression of PKR and its downstream genes wer...
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Papers by Audesh Bhat