The Role of Serum Erythropoietin (EPO) and Vascular Endothelial Growth Factor (VEGF) in Pulse Wave Velocity (PWV) Among Hypertensive Patients: A Cross-Sectional Study.

Background and objective While hypertension (HTN) is a major health-related threat globally, it is often an under-reported clinical condition as most of the stage I hypertensive patients do not present with any symptoms. The relationship between endogenous oxygen-sensing protein [erythropoietin (EPO) and vascular endothelial growth factor (VEGF)] levels and vascular stress in hypertensive patients is not fully understood as the mechanistic pathway by which these oxygen-sensing proteins alter the vascular physiology and cause hypertension is still a matter of debate. In light of this, we explored the role of these two proteins in the development of vascular stress including increased pulse wave velocity (PWV). We aimed to examine the correlation between oxygen-sensing proteins and vascular stress markers including PWV in hypertensive patients. Materials and methods We conducted a cross-sectional study involving age-matched participants classified into three groups (group 1: normotensive persons, n=36; group 2: stage I hypertensive patients, n=36; and group 3, stage II hypertensive patients, n=36). Adiposity-related parameters such as waist circumference (WC), hip circumference (HC), BMI, and waist-hip ratio (WHR) were measured. BP was recorded manually in resting posture by using a sphygmomanometer. PWV, which predicts the progression of BP and the development of HTN, was recorded using a periscope, which works based on the oscillometric method. Vascular stress-induced oxidative stress parameters [serum malondialdehyde (MDA) and serum nitric oxide (NO)] were also estimated by using a UV spectrophotometer. Quantitative estimations of oxygen-sensing proteins (serum EPO and serum VEGF) were done by using the ELISA kit method. The results were expressed as mean ± standard deviation (SD). The correlation between the variables was done using Spearman's correlation. A p-value <0.05 was considered statistically significant. Results Adiposity indices and vascular stiffness parameters were found to be significantly (p <0.05) increased in group 2 and group 3 compared to group 1. The levels of serum MDA were found to be significantly (p<0.05) increased in group 2 and group 3 than group 1, whereas the levels of serum NO were significantly (p<0.05) decreased in group 3 and group 2 than group 1. A significant (p<0.05) positive correlation was observed between the PWV and EPO (r=0.492) while a significant (p<0.05) negative correlation was observed between PWV and VEGF (r=-0.406) among the study population. Conclusion The results are indicative of the influence of vascular stress in stage I and II hypertensive patients. Furthermore, the relationship between oxygen-sensing proteins and vascular stress in hypertensive patients has also been established.

Antioxidant therapy for hepatic diseases: a double-edged sword.

Liver diseases are complex conditions, significantly influenced by oxidative stress. This comprehensive review assesses the therapeutic role of antioxidants like l-ascorbic acid and α tocopherol, beta-carotene, various minerals, and plant-based ingredients in mitigating oxidative stress-induced liver diseases. The manuscript delves into the critical influence of genetic and epigenetic factors on disease susceptibility, progression, and response to antioxidant therapy. While animal studies suggest antioxidant efficacy in liver disease treatment, human trials remain inconclusive, and caution is advised due to its possible potential pro-oxidant effects. Moreover, the interactions of antioxidants with other drugs necessitate careful consideration in the management of polypharmacy in liver disease patients. The review underscores the need for further research to establish the clinical benefits of antioxidants with understanding of possible antioxidant toxicities to elucidate the intricate interplay of genetic, epigenetic, and environmental factors in liver diseases. The aim is to foster a better understanding of the knowledge on hepatic disease management with judicial antioxidant therapies.

Protein-protein interaction of LDH and CRP-1 with hematotoxin snake venom proteins of all species of snake: An in silico approach.

Objective: Snake bite-induced elevation of serum LDH and CRP-1 is considered as useful biomarkers of hemotoxic. The snake venom contains proteins and may result in various envenomation such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic, or neurotoxic effects. This in silico study was aimed to screen the snake venom proteins and to find out the most interactive hemotoxic venom protein against LDH and CRP-1 proteins as biomarkers. Materials and Methods: To validate the hypothesis of the prospective interaction of snake venom proteins, molecular docking analysis was used in the current work by deploying a cutting-edge docking program. Snake venom peptides were screened from literature and both peptide as well as target protein were obtained from PDB. HDOCK online server was used for the molecular docking analysis of target proteins with hemotoxic snake venom peptides. Further, the toxicity properties of each docked complex of target proteins were subjected for ADME/T analysis. Results: The selected snake venom peptides were subjected to molecular docking study and the results generated from computational-based approach reveals that all the hematotoxin snake venom proteins are interactive with LDH and CRP-1 peptide. Further, this study indicates that snake venom metalloproteinase (SVMPS) peptide may be considered as the best interactive protein with both LDH and CRP-1 proteins; also, ADME/T screening revealed that all docked complex are safe and follow toxicity properties. Conclusion: This in silico study clearly shows that the greatest interaction of SVMPS peptide with LDH and CRP-1 may be due to strong binding in the active site of the target proteins LDH and CRP-1 with SVMPS. Results, further, confirmed LDH and CRP-1 as potential biomarkers against hemotoxic snake venoms. This study should be validated by in vitro and in vivo analysis as well as specific species snake venom should be assessed. For further studies, SVMPS can be consider as therapeutic point of view.

Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats.

Present study aimed to assess effect of pre-treatment with Mucuna pruriens seed extract and its bioactive molecule(s) on NMDAR and Tau protein gene expression in cerebral ischemic rodent model. Methanol extract of M. pruriens seeds was characterized by HPLC, and ß-sitosterol was isolated by flash chromatography. In vivo studies to observe the effect of pre-treatment (28 days) with methanol extract of M. pruriens seed and ß-sitosterol on the unilateral cerebral ischemic rat model. Cerebral ischemia induced by left common carotid artery occlusion (LCCAO) for 75 min (on day 29) followed by reperfusion for 12 h. Rats (n = 48) divided into four groups. GroupI (control,Untreated + LCCAO)-No pre-treatment + cerebral ischemia; GroupII(ß-sitosterol + Sham)-pre-treatment with ß-sitosterol, 10 mg/kg/day + sham-operated; GroupIII(ß-sitosterol + LCCAO)-pre-treatment with ß-sitosterol, 10 mg/kg/day + cerebral ischemia; GroupIV(methanol extract + LCCAO)-pre-treatment with methanol extract of M. pruriens seeds, 50 mg/kg/day + cerebral ischemia. Neurological deficit score was assessed just before sacrifice. Experimental animals were sacrificed after 12 h reperfusion. Brain histopathology was performed. Gene expression of NMDAR and Tau protein of left cerebral hemisphere (occluded side) was performed by RT-PCR. Results revealed that the neurological deficit score was lower in groups III and IV compared to group I. NMDAR and tau protein mRNA expression in left cerebral hemisphere were upregulated in Group I, downregulated in groups III and IV. Histopathology of left cerebral hemisphere (occluded side) in Group I showed features of ischemic brain damage. Groups III and IV, left cerebral hemisphere showed less ischemic damage compared GroupI. Right cerebral hemisphere showed no areas of ischemia-induced brain changes. Pre-treatment with ß-sitosterol and methanol extract of M. pruriens seeds may reduce ischemic brain injury following unilateral common carotid artery occlusion in rats.

Total Reflection X-ray Fluorescence Analysis of Plasma Elements in Autistic Children from India.

Trace elements are essential for the human body's various physiological processes but if they are present in higher concentration, these elements turn to be toxic and cause adverse effect on physiological processes. Similarly, deficiency of these essential elements also affects physiological processes and leads to abnormal metabolic activities. There is a lot of interest in recent years to know the mystery behind the involvement of trace elements in the metabolic activities of autistic children suspecting that it may be a risk factor in the aetiology of autism. The present study aims to analyse the plasma trace elements in autistic children using the total reflection X-ray fluorescence (TXRF) technique. Plasma samples from 70 autistic children (mean age: 11.5 ± 3.1) were analysed with 70 age- and sex-matched healthy children as controls (mean age: 12 ± 2.5). TXRF analysis revealed the higher concentration of copper (1227.8 ± 17.8), chromium (7.1 ± 2.5), bromine (2695.1 ± 24) and arsenic (126.3 ± 10) and lower concentration of potassium (440.1 ± 25), iron (1039.6 ± 28), zinc (635.7 ± 21), selenium (52.3 ± 8.5), rubidium (1528.9 ± 28) and molybdenum (162,800.8 ± 14) elements in the plasma of autistic children in comparison to healthy controls. Findings of the first study from India suggest these altered concentrations in elements in autistic children over normal healthy children affect the physiological processes and metabolism. Further studies are needed to clarify the association between the altered element concentration and physiology of autism in the North Karnataka population in India.

Clinical profile of hemophilia B patients from Karnataka.

Background: The most prevalent severe inherited hemorrhagic condition is hemophilia, which means "love of blood." Hemophilia A and B are caused by a lack or malfunction of the factor VIII and factor IX proteins. Objective: The present study is to determine the prevalence and clinical profile of hereditary coagulation disorder, particularly hemophilia B, in Karnataka. Methods: The study comprised 150 HB patients with a mean age of 25, nmale = 148 and nfemale = 2. The samples were collected from hemophilia societies across Karnataka. The detailed history of HB patients was recorded in a predesigned Performa regarding family history, age, time of first bleed, site of the bleed, and bleeding history. Result: In our study cohort, the majority of the 58 (38.7%) cases belong to 21-30 years of age. The mean age of onset was 2.0 ± 1.0 years in severe, 7.5 ± 2.8 0 years in moderate, and 10.0 ± 3.5 years in mild HB patients. Out of 150 HB cases, 102 (68%) cases were diagnosed as severe, 30 (20%) as moderate, and 18 (12%) as mild. Mean factor IX levels were 0.6 ± 0.2, 2.5 ± 1.3, and 8.0 ± 2.6 in the severe, moderate, and mild group, respectively. A family history of bleeding was observed in 97 [64.7%] HB patients. Forty-seven (32.3%) HB patients had a history of consanguinity. The most common initial site of bleed was in joints in 86 [57.3%]. Conclusion: The present study is one of the fewer studies from Karnataka studying the demographic and clinicopathological features of hemophilia B. Early diagnosis can be only helpful with knowledge of spectral presentation of hemophilia B in a local population.

Analysis of Genetic Variations in Connexin 26 ( GJB2 ) Gene among Nonsyndromic Hearing Impairment: Familial Study.

Objective The goal of this research was to investigate the gap junction beta 2 ( GJB2 ) gene mutations associated with nonsyndromic hearing loss individuals in North Karnataka, India. Materials and Methods For this study, patients with sensorineural genetic hearing abnormalities and a family history of deafness were included. A total of 35 patients from 20 families have been included in the study. The patient's DNA was isolated from peripheral blood samples. The GJB2 gene coding region was analyzed through Sanger sequencing. Results There is no changes in the first exon of the GJB2 gene. Nine different variants were recorded in second exon of the targeted gene. W24X and W77X are two nonsense mutations and three polymorphisms viz. R127H, V153I, and I33T were reported along with four 3'-UTR variants. A total (9/20) of 45% of families have been identified with mutations in the targeted gene. Conclusion GJB2 mutations were identified in 19 deaf-mute patients (19/35), and 13 patients were homozygous for the mutations identified in our study cohort. In our study, W24X mutation was found to be the pathogenic with a high percentage, prompting further evaluation of the other genes, along with the study of additional genetic or external causes in the families, which is essential.

Efficacy of BAINS Circuit in Treating Critically Ill Hypoxemic COVID-19 Patients During the Second Wave of the Pandemic in India.

BACKGROUND: The COVID-19 pandemic has encouraged doctors to look for novel ways of treating patients with respiratory failure due to the limited availability of ventilators and highflow nasal cannula. The study aims to assess the efficacy of using the Bains circuit as an alternative to HFNC and NIV as life-saving tools in patients with respiratory failure during the second wave of the COVID-19 pandemic in India. METHODS: This is a prospective interventional study carried out in the intensive care unit of Shri B.M Patil Medical College Hospital and Research Centre, Vijayapur, India, from May 2021 to June 2021. All patients (n=90) with respiratory failure not responding to therapy with an oxygen mask were included. Patients were placed on Bain circuits, one end connected to a non-invasive ventilation mask fitted to the face of the patients, and the other end connected to a central oxygen port. Patients' vital parameters were assessed on an hourly basis. The blood gas analyses were done before and after using Bains. RESULTS: The study showed diabetes (33.4%), hypertension (22.2%), and diabetes with hypertension (11.1%) as comorbid factors among the ICU admitted patients. The results from the arterial blood gas analyses showed a statistically significant increase in Sp02 (%) and a decrease in respiratory rate (cycles/min) in the patients after being kept on Bains (p<0.05). Further, it showed that 72% of ICU patients with 70-79% Sp02 had a recovery by using Bains. The overall outcome of ICU admitted COVID-19 patients on Bains showed that 38.9% of patients improved and were shifted to 02/NRBM masks. CONCLUSION: The study highlights a novel concept of using the Bains circuit as an effective alternative to HFNC and NIV for oxygenation in critically ill COVID-19 patients during scarcity of NIV and HFNC at the peak of the pandemic.

Interplay of Oxidative Stress and Nitric Oxide Synthase Gene Expression on Cardiovascular Responses in Preeclampsia / Interação do estresse oxidativo e da expressão dos genes das óxido nítrico sintases nas respostas cardiovasculares na pré-eclâmpsia

Abstract Objective To assess the influence of oxidative stress on the gene expression of nitric oxide synthases (NOS 3 and NOS 2) and, hence, the cardiovascular responses in preeclampsia. Methods This was a case control study in which patients with preeclampsia (PE group) and normal pregnancy controls (NP group) were included according to the guidelines of the American College of Obstetricians and Gynecologists (ACOG). The serum levels of malondialdehyde (MDA), total antioxidant capacity, and nitric oxide (NO) were estimated, and the heart rate andmean arterial pressure were recorded. The gene profiling of NOS3 and NOS2 was performed through real-time polymerase chain reaction (RT-PCR). The statistical analysis was performed using the Student t-test, and values of p<0.05 were considered statistically significant. Results The serum levels of malondialdehyde were increased (p<0.0001), and the total antioxidant capacity was reduced in the PE group (p=0.034), indicating oxidative stress. In the PE group, themean arterial pressure was significantly higher (p<0.0001), but the serum levels of NO did not show a statistically significant reduction (p=0.20). The gene expression profiling of NOS3 and NOS2 revealed a down regulation in the PE group by 8.49 and 51.05 times respectively. Conclusion Oxidative stress may lead to endothelial dysfunction, which could result in increased mean arterial pressure. Nitric oxide may play a role in this mechanism, but interactions with other vasoactive /biological substances cannot be overlooked, as the gene expression of NOS3 and NOS2 has been reduced.

Resumo Objetivo Avaliar a influência do estresse oxidativo na expressão genética das óxido nítrico sintases (nitric oxide synthases, NOS, em inglês; NOS 3 e NOS 2) e, consequentemente, nas respostas cardiovasculares na pré-eclâmpsia. Métodos Este foi um estudo caso-controle no qual pacientes com pré-eclâmpsia (grupo PE) e controles comgravidez normal (grupo GN) foramincluídos de acordo com as diretrizes do American College of Obstetricians and Gynecologists (ACOG). Foram estimados os níveis séricos de malondialdeído (MDA) da capacidade antioxidante total, e de óxido nítrico (nitric oxide, NO, em inglês). A frequência cardíaca e a pressão arterial média foram registradas. O perfil genético da NOS3 e da NOS2 foi feito por reação em cadeia de polimerase em tempo real (real-time polymerase chain reaction, RT-PCR, em inglês). A análise estatística foi feita utilizando-se o teste t de Student, e valores de p<0,05 foram considerados estatisticamente significativos. Resultados Os níveis séricos de malondialdeído sérico estavam aumentados (p<0,0001), e a capacidade antioxidante total, reduzida no grupo PE (p=0,034), o que indicava estresse oxidativo. No grupo PE, a pressão arterial média era significativamente maior (p<0,0001), mas os níveis séricos de NO não demostraram redução estatisticamente significativa (p=0,20). O perfil de expressão genética da NOS3 e da NOS2 revelou uma regulação negativa no grupo PE de 8,49 e 51,05 vezes, respectivamente. Conclusão O estresse oxidativo pode levar à disfunção endotelial, o que pode resultar em aumento da pressão arterialmédia. O NO pode desempenhar umpapel neste mecanismo, mas as interações com outras substâncias vasoativas/biológicas não podem ser negligenciadas, uma vez que a expressão genética da NOS3 e da NOS2 foi reduzida.

Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India.

Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population. Aim The present study hypothesized that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [ NLGN4Y ] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India. Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid. Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [ NLGN4Y ] gene especially in the male predominance of autism in Indian autistic population.

Interplay of Oxidative Stress and Nitric Oxide Synthase Gene Expression on Cardiovascular Responses in Preeclampsia.

OBJECTIVE: To assess the influence of oxidative stress on the gene expression of nitric oxide synthases (NOS 3 and NOS 2) and, hence, the cardiovascular responses in preeclampsia. METHODS: This was a case control study in which patients with preeclampsia (PE group) and normal pregnancy controls (NP group) were included according to the guidelines of the American College of Obstetricians and Gynecologists (ACOG). The serum levels of malondialdehyde (MDA), total antioxidant capacity, and nitric oxide (NO) were estimated, and the heart rate and mean arterial pressure were recorded. The gene profiling of NOS3 and NOS2 was performed through real-time polymerase chain reaction (RT-PCR). The statistical analysis was performed using the Student t-test, and values of p < 0.05 were considered statistically significant. RESULTS: The serum levels of malondialdehyde were increased (p < 0.0001), and the total antioxidant capacity was reduced in the PE group (p = 0.034), indicating oxidative stress. In the PE group, the mean arterial pressure was significantly higher (p < 0.0001), but the serum levels of NO did not show a statistically significant reduction (p = 0.20). The gene expression profiling of NOS3 and NOS2 revealed a down regulation in the PE group by 8.49 and 51.05 times respectively. CONCLUSION: Oxidative stress may lead to endothelial dysfunction, which could result in increased mean arterial pressure. Nitric oxide may play a role in this mechanism, but interactions with other vasoactive /biological substances cannot be overlooked, as the gene expression of NOS3 and NOS2 has been reduced.

OBJETIVO: Avaliar a influência do estresse oxidativo na expressão genética das óxido nítrico sintases (nitric oxide synthases, NOS, em inglês; NOS 3 e NOS 2) e, consequentemente, nas respostas cardiovasculares na pré-eclâmpsia. MéTODOS: Este foi um estudo caso-controle no qual pacientes com pré-eclâmpsia (grupo PE) e controles com gravidez normal (grupo GN) foram incluídos de acordo com as diretrizes do American College of Obstetricians and Gynecologists (ACOG). Foram estimados os níveis séricos de malondialdeído (MDA) da capacidade antioxidante total, e de óxido nítrico (nitric oxide, NO, em inglês). A frequência cardíaca e a pressão arterial média foram registradas. O perfil genético da NOS3 e da NOS2 foi feito por reação em cadeia de polimerase em tempo real (real-time polymerase chain reaction, RT-PCR, em inglês). A análise estatística foi feita utilizando-se o teste t de Student, e valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Os níveis séricos de malondialdeído sérico estavam aumentados (p < 0,0001), e a capacidade antioxidante total, reduzida no grupo PE (p = 0,034), o que indicava estresse oxidativo. No grupo PE, a pressão arterial média era significativamente maior (p < 0,0001), mas os níveis séricos de NO não demostraram redução estatisticamente significativa (p = 0,20). O perfil de expressão genética da NOS3 e da NOS2 revelou uma regulação negativa no grupo PE de 8,49 e 51,05 vezes, respectivamente. CONCLUSãO: O estresse oxidativo pode levar à disfunção endotelial, o que pode resultar em aumento da pressão arterial média. O NO pode desempenhar um papel neste mecanismo, mas as interações com outras substâncias vasoativas/biológicas não podem ser negligenciadas, uma vez que a expressão genética da NOS3 e da NOS2 foi reduzida.

Screening and Development of Transglutaminase-2 Inhibitors and their Derivative as Anti-lung Cancer Agent by in silico and in vitro Approaches.

AIM: This study aimed at screening and development of TG2 inhibitors as anti lung cancer agent. BACKGROUND: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from the transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative diseases, and also cancer. OBJECTIVE: The proposed study focused on screening potent inhibitors of TG2 by in-silico method and synthesize their derivative as well as analyse its activity by utilizing an in-vitro approach. MATERIALS AND METHODS: Molecular docking studies have been carried out on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction while possessing the least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines using cytotoxicity studies. RESULTS: The results of the present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein, so this derivative of cystamine was formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecules proved to be good cytotoxic agents against A549 lung cancer (875.10, 553.22 µg/ml), respectively. Further, their activity needs to be validated on TG2 expressing lung cancer. CONCLUSION: Cystamine and its derivative can act as a potential therapeutic target for lung cancer but its activity should be further validated on TG2 expressing lung cancer.

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India.

BACKGROUND: Hemophilia B (HB) is an X-linked bleeding disorder resulting from coagulation factor IX defects. Over 3,000 pathogenic, HB-associated mutations in the F9 gene have been identified. We aimed to investigate the role of F9 variants in 150 HB patients using sequencing technology. METHODS: F9 gene sequences were amplified from peripheral blood-derived DNA and sequenced on an Applied Biosystems (ABI) 3500 Sanger sequencing platform. Functional and structural predictions of mutant FIX were analyzed. RESULTS: Among 150 HB patients, 102 (68%), 30 (20%), and 18 (12%) suffered from severe, moderate, and mild HB, respectively. Genetic analysis identified 16 mutations, including 3 novel mutations. Nine mutations (7 missense and 2 stop-gain) were found to be pathogenic. Only 3 mutations (c.127C＞T, c.470G＞A, and c.1070G＞A) were associated with different severities. While 2 mutations were associated with mild HB cases (c.304C＞T and c.580A＞G), 2 (c.195G＞A and c.1385A＞G) and 3 mutations (c.223C＞T, c.1187G＞A, and c.1232G＞A) resulted in moderate and severe disease, respectively. Additionally, 1 mutation each was associated with mild-moderate (c.*1110A＞G) and mild-severe HB disease (c.197A＞T), 4 mutations were associated with moderate-severe HB cases (c.314A＞G, c.198A＞T, c.676C＞T, and c.1094C＞A). FIX concentrations were lower in the mutated group (5.5±2.5% vs. 8.0±2.5%). Novel p.E66D and p.S365 mutations were predicted to be pathogenic based on changes in FIX structure and function. CONCLUSION: Novel single nucleotide polymorphisms (SNPs) largely contributed to the pathogenesis of HB. Our study strongly suggests that population-based genetic screening will be particularly helpful to identify risk prediction and carrier detection tools for Indian HB patients.

Structural analysis and prediction of potent bioactive molecule for eNOS protein through molecular docking.

Reactive oxygen species by uncoupled eNOS is linked to endothelial dysfunction. Ellagic acid (EA), a polyphenol possesses numerous biological activities including radical scavenging. whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels remains unknown. Molecular docking provides an initial model of protein and molecular interactions in various physiological and/or pathological functions. To identify a eNOS modulatory biomolecule through molecular docking as possible vascular protective agent. On the basis of binding affinities and other physicochemical features, a molecular docking-based approach was used to classify and evaluate eNOS binding micronutrients found in natural sources, Lipinski's rule was used taking into account their adsorption, delivery, metabolism, and excretion (ADME). An insilico approach focused on the ligand-protein interaction technique to determine the therapeutic potential of certain phytochemical-based drugs for the vascular remodelling.20 bioactive molecules were screened, docking analysis on human eNOS proteins was performed. The best poses for target protein was established based on binding energy and inhibition constant. EA and caffeine acid are the strongest candidates for eNOS protein functional norms. This provides a novel insight into the interaction properties of known human eNOS protein with EA and used as a therapeutic agent in various pathologies. Predicting interaction of ellagic acid with eNOS protein by molecular docking in endothelial dysfunction.

Terminalia arjuna supplementation ameliorates high fat diet-induced oxidative stress in nephrotoxic rats.

OBJECTIVES: Dietary high fat possibly causes oxidative stress; also it makes deleterious effect on kidney functions and land up in lipotoxicity in renal tissue. Lipotoxicity is the pathological situation where lipid Peroxidation occurs and generates reactive oxygen species (ROS). Overproduction of ROS than antioxidant present in tissues cause oxidative stress. Terminalia arjuna is found to be potential antioxidant that counteract oxidative stress and possibly maintain glomerular integrity. METHODS: Ethanolic extract of T. arjuna (ETO) was prepared and phytochemical analysis was done. Rats were divided into four groups, having six rats in each group as following; group 1-Control (20% fat); group 2 (ETO 100 mg/kg/b.wt); group 3 (30% fat) and group 4 (30% fat + ETO 100 mg/kg/b.wt). Dietary and ETO supplementation were continued for 21 days. Gravimetric, kidney functions (blood urea and serum creatinine) and oxidative stress markers like MDA, SOD and GSH were evaluated. Histopathological analysis was done on kidney along with measurement of glomerular integrity. Morphometrical analysis of glomerular integrity was evaluated by measuring glomerular length, width, glomerular area and Bowman's capsule radius. One way ANOVA was done for analysis of data. RESULTS: Blood urea and serum creatinine levels were significantly higher in high fat fed rats indicating renal dysfunction. High fat diet showed significant increase in MDA, decrease in SOD and GSH in rats fed with high fat diet, which indicate generation of oxidative stress. Supplementation of ETO showed amelioratic effect against high fat diet induced renal dysfunction and oxidative stress. Histopathological findings were significantly corroborated with morphometrical analysis of glomerular integrity. CONCLUSIONS: Ethanolic extracts of T. arjuna supplementation found to be beneficial against high fat induced renal alterations in terms of functions and architecture.

Molecular alteration in the Gap Junction Beta 2 (GJB2) gene associated with non-syndromic sensorineural hearing impairment.

Non-syndromic sensory neural hearing defect is one of the genetic diseases inherited from parents to offerings. The autosomal recessive form affects a large population worldwide and has become a major concern in the social and professional lives of many people. There are many factors and genes which are involved in hearing loss but the Gap Junction Beta 2 (GJB2) gene which encodes the connexin 26 protein, is a major cause of non-syndromic recessive deafness (NSRD). This study aims to record and analyze GJB2 gene mutations in the hearing-impaired population of North Karnataka, India. In this study, we included 368 congenitally hearing-impaired children from North Karnataka, India, under 18 years of age. After thorough clinical examinations, patient's history and proper audiological results, peripheral blood samples were collected and subjected to genetic analysis. We recorded that 54.8% of the NSRD cases have an autosomal recessive mutation in the coding region of the GJB2 gene. The frequency of W24X (25%) mutation was found to be high in the present study population. From this study we can suggest that, identifying this mutation in new-borns definitely helps in the early diagnosis of hearing loss.

Genetic analysis of the postsynaptic transmembrane X-linked neuroligin 3 gene in autism.

Autism is a complex neurodevelopmental disorder, the prevalence of which has increased drastically in India in recent years. Neuroligin is a type I transmembrane protein that plays a crucial role in synaptogenesis. Alterations in synaptic genes are most commonly implicated in autism and other cognitive disorders. The present study investigated the neuroligin 3 gene in the Indian autistic population by sequencing and in silico pathogenicity prediction of molecular changes. In total, 108 clinically described individuals with autism were included from the North Karnataka region of India, along with 150 age-, sex-, and ethnicity-matched healthy controls. Genomic DNA was extracted from peripheral blood, and exonic regions were sequenced. The functional and structural effects of variants of the neuroligin 3 protein were predicted. One coding sequence variant (a missense variant) and four non-coding variants (two 5'-untranslated region [UTR] variants and two 3'-UTR variants) were recorded. The novel missense variant was found in 25% of the autistic population. The C/C genotype of c.551T>C was significantly more common in autistic children than in controls (p = 0.001), and a significantly increased risk of autism (24.7-fold) was associated with this genotype (p = 0.001). The missense variant showed pathogenic effects and high evolutionary conservation over the functions of the neuroligin 3 protein. In the present study, we reported a novel missense variant, V184A, which causes abnormal neuroligin 3 and was found with high frequency in the Indian autistic population. Therefore, neuroligin is a candidate gene for future molecular investigations and functional analysis in the Indian autistic population.

Hypoxia and its preconditioning on cardiac and vascular remodelling in experimental animals.

Since oxygen (O2) is indispensable for mammalian life, every cell in the body is endowed with mechanisms to detect and to respond to changes in the O2 levels in the microenvironment. The heart and the brain are the two most vital, life-supporting organs requiring a continuous supply of O2 to sustain their high metabolic rate. On being challenged with hypoxia, maintenance of O2 supply to these organs even at the cost of others becomes a priority. This review describes the cardiovascular, skeletal muscle vascular, pulmonary vascular and cerebrovascular remodelling in face of chronic mild hypoxia exposure and the underlying mechanisms, with special reference to the role of oxidative stress, hypoxia signalling, autonomic nervous mechanisms. The significance of the normalized wall index (NWI) in assessing the remodelling of the vessels particularly of the intramyocardial coronary artery has been underscored. The review also highlights the basic concepts of hypoxic preconditioning and the subsequent protection of the brain against an acute ischemic insult in preclinical studies hinting towards its possible therapeutic potential in the management of ischemic stroke.