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Aim: The present study aimed to isolate and characterize chemical compounds from Anthocephalus cadamba Miq. bark and evaluate their anticancer activity by in silico, molecular docking, and in vitro studies. Background: Anthocephalus cadamba is a traditionally used Indian medicinal plant. The anticancer and phytochemical properties of this plant remain unexplored except for a few studies. Objectives: The objective of the study was to evaluate the antiproliferative activity of extract and fractions against breast cancer and prostate cancer cell lines and isolate and characterize active compounds from bio-active guided fractions. Moreover, the anticancer activity of isolated compounds against breast and prostate cancer cell lines was also evaluated, in addition to in silico and molecular docking interactions of isolated compounds with VEGFR2 and PDGFRα target proteins. Methods: The compounds were isolated and purified with the help of repeated column chromatography, and spectral techniques, such as 1D, 2D NMR, and GC-MS/MS, were used to identify and elucidate the structure of the compounds. Moreover, prediction of activity spectra for substances, physiochemical properties, bioactivity radar prediction, bioactivity score, natural-product likeness, ADME, and toxicity parameters of isolated compounds (AC-1 to AC-4) was performed through various in-silico databases and servers. To evaluate the docking interaction profile and binding energies of compounds, three docking tools were utilized, such as AutoDock, AutoDock Vina, and iGEMDOCK, against two targets VEGFR2 and PDGFRα. MD simulation was performed through ligand and receptor molecular dynamic server (LARMD). Results: It was found that the A. cadamba bark chloroform fraction demonstrated a significant inhibitory effect against MDA-MB-231, MCF-7, and PC-3 cells in a dose-time-dependent manner. The bioassay-guided isolation afforded four molecules AC-1 to AC-4 from chloroform fraction. Moreover, the GC-MS/MS profiling identified fourteen new molecules which were not reported earlier from A. cadamba. The in-silico study showed that the isolated compounds (AC-1 to AC-4) followed Lipinski’s rule and had good oral bioavailability. While compound AC-4 had positive bioactivity scores except for kinase inhibitor activity. The ADMET profiling revealed that AC-4 was non-toxic and easily absorbed in the human intestine, and transportable in the blood-brain barrier compared to AC-1, AC-2, AC-3, and standard drug doxorubicin. Molecular docking and MD simulation assessment also signified AC-4 anticancer activity with dual inhibitory action against the target proteins VEGFR2 and PDGFRα amongst the studied compounds. The in vitro cell viability assay of isolated compounds demonstrated that AC-1 showed IC50 (μg/mL) value of 34.96 ±3.91, 47.76±3.80 69.1±4.96, AC-2; 68.26±4.22, 54.03±5.14, >100, AC-3; 35.34±4.14, 51.5±51.5, 70.8±5.25 and AC-4; 44.2±3.57, 24.2±2.67, 51.2±2.54 for MDA-MB-231, MCF-7, and PC-3 cancer cell lines, respectively and compared with standard drug doxorubicin. Moreover, fluorescence microscopy confirmed the apoptogenic property of compounds. We also found that AC-4 exhibited significant intracellular ROS production in breast cancer cells, thereby inducing apoptosis and eventually cell death. Conclusion: In conclusion, A. cadamba afforded four pure molecules AC-1 to AC-4 with the identification of fourteen new compounds. The entire in-silico studies concluded that the AC-4 compound had better oral bioavailability, bioactivity score, and ADMET profile among studied molecules. Molecular docking analysis and MD simulation also supported AC-4 dual inhibitory action against both VEGFR2 and PDGFRα receptors. Moreover, the isolated molecules AC-1, AC-2, AC-3, and AC-4 were found to be active against MDA-MB-231, MCF-7, and PC-3 cancer cells. The molecule AC-4 was found to induce ROS-mediated apoptosis in breast cancer cells. It was found that the anticancer inhibitory potentiality of AC-4 is directed to its molecular stereochemistry which specifically binds to the target proteins of breast cancer cells with no toxicological effect. Therefore, AC-4 is suggested to be an effective aspirant for novel drug design and discovery.

T-cadherin, a special member of cadherin family, expresses with blood circulation involving the heart i.e. CVS. Cadherin is connected with the healthy conditions of an individual and normal functioning of cardio-vascular metabolism. T-cadherin is mainly associated with blood vascular system of human. Previous studies analysed this cadherin been unexpressed within the fat storing tissues i.e. adipose tissue of peri-aortic and peri-coronary, it is present within endothelium as well as in vascularized smooth muscular cells which includes the area nearby coronary vessels and aorta. The area and site of this cadherin is attention-grabbing because it particularly related to atherosclerosis and cardiovascular disease (CVD). T-cadherin - a protein acting as the receptor for low density lipoproteins (LDL). It may act as a special biomarker for atherosclerosis. Previous studies on T-cadherin showed that it has cardio-protective role. Furthermore, research is essential to enumerate the cardio-protective function of T-cadherin. It can be an important therapeutic target in developing new medicine to decrease incident of heart disease and its complications.

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Hypertension is one of the most reported cardiovascular and cerebrovascular diseases with significantly high morbidity and mortality rates. This condition threatens the very existence of human beings. Numerous studies conducted earlier revealed the good therapeutic effect of isorhynchophylline on hypertension since the former regulates the metabolic disorders in neurotransmitters. However, the mechanism behind this action is yet to be deciphered. The current study followed the targeted metabolomics method to investigate the changes in the neurotransmitter level in the hippocampus of spontaneously hypertensive rats (SHRs) after the rats were treated with isorhynchophylline. The authors predicted the metabolic pathways involved in extensively modified neurotransmitters. Further, the expressions of metabolism-key enzymes in mRNA and protein levels were also determined. When treated with isorhynchophylline, it induced notably varying metabolomic profiles of the hippocampus in SHRs. Isorhynchophylline perturbed a total of seven extensively modified neurotransmitters as well as the primarily related pathways such as tyrosine and glutamate metabolism. An increase in the key metabolic enzymes such as DDC, MAO, COMT, TH, and DβH was observed in the SHR group, whereas their levels decreased after treatment with isorhynchophylline. The expression of GAD67 established cross-current validity. So, isorhynchophylline has been proved to have potential therapeutic value to treat hypertension via tyrosine and glutamate metabolism in the hippocampus. Further, the current study also opened new ventures to further investigate the working mechanism of isorhynchophylline in hypertension.

In the present study, the perinatal oral exposure of pregnant mice to 15 and 30mg/kg lithium (lithium chloride) in their drinking water resulted in a significant and dose-dependent reduction in postnatal body weight gain, delays in opening of the eyes and appearance in the body hair fuzz, and deficits in the sensory motor reflexes of the mice pups during weaning period (from the day of birth to postnatal day21). At adolescent and adult ages of the male offspring, a significant and dose-dependent deficit was also observed in their learning capability (at PD25), and cognitive behavior (at PD30-36). Furthermore, a significant and dose-dependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT); non-enzymatic oxidative stress (OS) indices like thiobarbituric acid-reactive substances (TBARS) and total reduced glutathione (GSH); and enzymatic OS indices like glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were observed in the forebrain region of the offspring at post-natal day (PD)7, PD14, PD21, PD30, and PD36. Thus, perinatal lithium exposure can affect the in utero developing fetus, raising the concerns for a potential neurotoxic hazards and a longer lasting cognitive dysfunction. A reduced use of lithium during pregnancy is of crucial importance in preventing lithium -induced neurotoxicity in the offspring.

It is known that miRNA mediates the formation of osteogenesis, but the mechanism by which miRNA let-7a-5p regulates osteogenesis in osteoporosis (OP) is not yet understood. This paper aims to probe into the regulatory mechanism of miRNA let-7a-5p in the development of OP. Fresh femoral trabecular bones of patients with osteoporotic fracture (OP group, n = 25) and non-OP osteoarthritis (Non-OP group, n = 23) who underwent hip replacement in our hospital from December 2016 to December 2019 were collected. The expression and protein levels of miRNA let-7a-5p and V-AKT murine thymoma viral oncogene homolog 3 (RNA KCNQ1OT1) were detected. C2C12 cells were purchased and osteogenic differentiation model was constructed by BMP2 induction. After miRNA let-7a-5p up-regulation or down-regulation by transfection of corresponding mimics and inhibitors, the impacts of miRNA let-7a-5p and RNA KCNQ1OT1 on osteogenic differentiation-related factors (OC, ALP, COL1A1) in C2C12 cells were analyzed. The determination of targeting correlation of miRNA let-7a-5p with RNA KCNQ1OT1 was performed by dual-luciferase reporter (DLR). In OP samples, miRNA let-7a-5p was notably declined while RNA KCNQ1OT1 were remarkably up-regulated. MiRNA let-7a-5p reduced in C2C12 cells as BMP2 treatment proceeded. MiRNA let-7a-5p up-regulation or RNA KCNQ1OT1 down-regulation increased OC, ALP, COL1A1 levels and ALP activity. RNA KCNQ1OT1 was directly targeted to miR-497-5p. RNA KCNQ1OT1 up-regulation weakened the promoting effect of miRNA let-7a-5p up-regulation on osteoblast differentiation. MiRNA let-7a-5p up-regulation can target to reduce RNA KCNQ1OT1 and promote osteoblast differentiation, thereby improving the development of osteoporosis.

Graphical abstract Alleviation of silver nanoparticle-induced sexual behavior and testicular parameters dysfunction in male mice by yttrium oxide nanoparticles. Gasem Mohammad Abu-Taweel, Hani Manssor Albetran, Mohsen Ghaleb Al-Mutary, Mohammad Ahmad, It Meng Low., Highlights • Exposure to silver nanoparticles decreased the weight of the reproductive organs, sexual behavior, oxidative defense parameters, sperm count and their motility in male mice. • In addition, serum testosterone, apoptotic germ cells and testicular histology were also disrupted due to silver nanoparticles. • Yttrium oxide nanoparticles have protective effects on sexual behavior and spermatotoxicity induced by silver nanoparticles in male mice. • The toxicity of silver nanoparticles altered testicular functions that were effectively ameliorated by yttrium oxide nanoparticles., Silver nanoparticles (Ag-NPs) can easily cross through the blood-testis barrier and encourage reproductive dysfunction. This study investigated the protective effects of yttrium oxide nanoparticles (YO-NPs) on sexual behavior and spermatotoxicity induced by Ag-NPs in male mice. Twenty-four male mice were separated into four groups and injected intraperitoneally once a week as the following: group I (Ag-NPs at the dose of 40 mg/kg), group II (YO-NPs at the dose of 40 mg/kg), group III (Ag + YO NPs at the doses of 40 mg/kg, each) and group IV (control; distilled water). After 35 days of the injections, the sexual behavior, oxidative parameters in testis, sperm parameters, serum testosterone, apoptotic germ cells and testicular histology were evaluated. Our findings showed that Ag-NPs decreased the weight of the reproductive organs, sexual behavior, oxidative defense parameters, sperm count and motility of male mice. In addition, the apoptotic cells in testicular cross-sections and TBARS level increased after Ag-NPs exposure when compared to other groups. However, the YO-NPs had protective effects in the studied parameters of testicles and minimized the Ag-NPs toxicity in male mice. In conclusion, the results revealed that the toxicity of Ag-NPS altered testicular functions in male mice that were effectively ameliorated by YO-NPs.

To examine and evaluate the efficacy of the spectrum of psychological and behavioral intercession as a novel treatment regime to address the necessity of Schizophrenia affected patients. A sum of 148 individuals with the first episode of Schizophrenia enrolled in the trial. Patients admitted in our medium-sized hospital with symptoms of schizophrenia were scrutinized carefully and selected for the intercession trial. Total selected individuals were bifurcated into two groups based on guidelines prescribed in the intervention model. Control group or standard care group (SCG) was treated with usual medications and nursing measures of psychiatry practices. Experimental Group (EG) was conferred with enriched psychological strategy and behavioral modules to tackle and satisfy their specific needs. Various methods such as positive and negative syndrome scale (PANSS), several disability screening schedule (SDGSS), satisfaction with life scale (SWLS), global assessment scale (GAS) and finally rate of recurrence of disease were evaluated and analyzed. Efficacy of psychological and behavioral intercession on psychotic domine is proved to be effective, and a novel strategy and it is significantly reducing positive and negative psychological symptoms in the experimental group was observed attributing to the intercession. Moreover, a drastic attenuation in the rate of recurrence of disease was supporting a long term efficiency of intercession. Conducting intervention on psychological and behavioral approach has explored novel treatment outcomes, targeted schizophrenia patients effectively.

Introduction Childhood and adolescence require adequate amount of micronutrients for normal growth and development. The primary objective of study was to assess the prevalence of deficiencies of Vitamins (Vitamin A, 25 Hydroxy Vitamin D, Vitamin B12 and Folate) and minerals (Calcium, Zinc, Selenium and Iron), among urban school going children aged 6–11 and 12–16 years in ten cities of India. Secondary objective was to find the association between micronutrient deficiencies with sociodemographic and anthropometric indicators. Methods A multi-center cross-sectional study was conducted across India. Participants in the age groups of 6 to 11 years (group 1) and 12 to 16 years (group 2) were selected from randomly chosen schools from each center. Data on socio economic status, anthropometric measures was collected. Blood samples were collected for biochemical analysis of micronutrients. Point estimates and 95% confidence intervals was used to assess the prevalence of deficiencies. Associations were observed using chi square, student t test and ANOVA test. Results From April 2019 to February 2020, 2428 participants (1235 in group 1 and 1193 group 2) were recruited from 60 schools across ten cites. The prevalence of calcium and iron deficiency was 59.9% and 49.4% respectively. 25 Hydroxy Vitamin D deficiency was seen in 39.7% and vitamin B12 in 33.4% of subjects. Folate, Selenium and Zinc were deficient in 22.2%, 10.4% and 6.8% of subjects respectively. Vitamin A deficiency least (1.6%). Anemia was prevalent in 17.6% subjects and was more common among females. Conclusion One or more micronutrient deficiencies are found in almost one half of school going children in urban area. Hence efforts must be made to combat these on priority. Trial registration number CTRI/2019/02/017783.

Diabetic nephropathy (DN) is a chronic complication of both type 1 and type 2 diabetes. However, there is still inadequate understanding of the exact mechanism related to progressive diabetic renal disease. The GLUT-1 XbaI gene polymorphism in the glucose transporter has been suggested in the development of DN. However, its association with T2DM and DN is controversial and has not been established in different ethnic populations. To enhance the understanding of GLUT-1 XbaI gene polymorphism in the context of T2DM and DN. We investigated the possible genetic association of GLUT-1 XbaI polymorphism with T2DM and DN in North Indian population. 100 T2DM patients and 100 patients of DN with 100 healthy controls were included in the study. GLUT-1 XbaI polymorphism was determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). The obtained data showed no significant association between GLUT-1 XbaI gene polymorphism with T2DM and DN leading us to conclude that GLUT-1 XbaI gene polymorphism may not have major effects on T2DM and DN in North Indian population.

The present study was aimed to assess the correlation between transplacental transfer of xenobiotics and resulting biochemical alterations (including genotoxicity and oxidative stress) in non-occupational pregnant women of North India along with the effect on pregnancy outcomes. Maternal and cord blood samples were collected from 221 healthy mother-infant couples and divided according to their gestational age and birth weight. Genotoxic effects in mother and cord blood were examined using comet assay. The quantitative determination of Organo-chlorine pesticides in blood serum of study population was carried out using gas chromatography-mass spectrometry (GC-MS). Notably higher Organo-chlorine pesticides levels were observed in maternal blood of preterm than term subjects for almost all of the compounds detected, with the maximum concentration found for aldrin (3.26 mg/l) in maternal blood and dieldrin (2.69 mg/l) in cord blood. The results showed a significant increment in olive tail moment, tail full length, catalase, super-oxide dismutase, and malondialdehyde levels whereas lower glutathione reductase and peroxidase were found in preterm babies when compared with term group and it varied in the order: maternal blood > cord blood. A clear trend was observed for preterm babies with their lower birth weight and cesarean mode of delivery. Therefore, reduction in birth weight in newborns may be the consequence of increased oxidative damage and genotoxicity brought about by pesticides and these markers could be employed for early detection of pesticides related ailments and toxicities. To the best of our knowledge, this was a pioneering study and it may help to increase our knowledge with regard to xenobiotic exposure in biological system and the need for stringent guidelines for agricultural use of pesticides.

Chlamydia trachomatis has a say on the target gene i.e., modulating the expression of target gene in the host so that it is given protection from the immune cells and so its survival and replication are not arrested by the host. The current study reports a wide range of C. trachomatis proteins that target the cellular as well as sub-cellular components of the host in gynecologic malignancy. Various bioinformatics tools was used to conduct an in-depth analysis on nuclear and eukaryotic sub cellular localization signal to find the sequences of the predicted proteins of C. trachomatis strain G. A total of 411 proteins was identified with 79.54% maximum expected accuracy and 51.02% least expected accuracy. There were uneven prediction of proteins along with redundancies between BaCeILo and HSLpred in the determination of sub-cellular localization of the CT proteins. The highest molecular weight proteins (>80 kDa) were observed to be the targeted proteins to nucleus of host cell. There was no constant patterns observed in the values of isoelectric point (pI) in case of mitochondrial targeting. The expression of eight proteins were significant with different fold changes. The in-silico study provided much detailed insights for further research in gynecological cancer. However, further experiments should be conducted to validate the specificity and confirmatory roles played by these predicted proteins in carcinogenesis.

Tumor necrosis factor-alpha (TNF-α) are considered as a pro inflammatory and interleukin-10 (IL-10) anti inflammatory have been shown to predict the risk of incident of coronary artery disease (CAD). The polymorphism at promoter of TNF-α and IL-10 has been shown to increase transcriptional activity of the gene and play a important role in patho physiology of CAD. Aim of present study is to examine the impact of the TNF-α and IL-10 variant allele on various markers of the CAD and to study its relation with circulating TNF-α and IL-10 levels.The -308 G/A-238 G/A of TNF-α and -1082 G/A-819 C/T of IL-10 gene polymorphism has been studied in 301 diagnosed CAD subjects (Age 51.50 ± 9.28; BMI 25.30 ± 3.58) and 305 healthy controls (Age 51.57 ± 9.50; BMI 24.06 ± 7.26). These polymorphism of TNF-α and IL-10 were detected by real time PCR by using Taqman SNP genotyping assay. Furthermore serum TNF-alpha and IL-10 levels were also measured by ELISA.Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p 0.05). On allele contrast, significant association with susceptibility to CAD was detected with polymorphisms in TNF-α -308 G/A, that variant genotype GA + AA (dominant model) (p = 0.030: OR = 1.61: 95% CI = 1.06-2.44) and variant allele (A) (p = 0.006: OR = 1.71: 95% CI = 1.17-2.51) of TNF-α 308 G/A gene was significant highly observed in the cases as compared to control group. Furthermore, variant genotype CT + TT (dominant model) (p = 0.004: OR = 1.62: 95% CI = 1.17-2.24) and variant allele (T) (p 0.001: OR = 1.49: 95% CI = 1.17-1.89) of IL-10 -819 C/T gene was significant highly observed in the cases as compared to control group.Our results suggest that the TNF-α G-308A polymorphism independently associated with DBP, cholesterol, triglyceride, LDL, TNF-α and IL-10 levels which may be leads to the development of coronary artery disease of North Indians.

The present study intends to compare the influence of pre-treatment with nanoparticles of curcumin (Cr-NPS), chitosan (Ch-NPS) and nanocomposites chitosan-curcumin (CC-NPS) on cadmium (Cd)-induced oxidative damage in the liver, kidneys, and blood indices in Swiss strain adult male mice. The pretreated mice with Cr-NPS, Ch-NPS, and CC-NPS were exposed to Cd (10mg/kg) for three weeks. The non-enzymatic Oxidative Stress (OS) indices like lipid peroxides (TBARS), reduced total glutathione (GSH), enzymatic OS indices like catalase (CAT), glutathione S-transferase (GST) and superoxide dismutase (SOD) were estimated together with some blood indices. Cadmium was able to induce a significant increase in TBARS and a significant decrease in GSH, GST, CAT and SOD levels in all the tissues, which were pretreated with nanocomposite. Furthermore, the blood indices like counts of red and white blood cells, platelets, hemoglobin and packed cell volume were also depleted due to Cd exposure but remained unaffected and kept under normal levels in pretreated mice group. The results indicate that Cr-NPS, Ch-NPS, and CC-NPS may act as natural antioxidants and when compared among the three, CC-NPS appears to be the best antioxidant.

Mercury and its derivatives even in small concentration may cause a major human health problem. Though not reported in detail, there are various aquatic bacterial species that produce small quantities of methyl mercury (MM) growing under aerobic conditions. Consumption of food derived from sources contaminated with such bacteria within therapeutic doses and exposure to different forms of MM compounds through such sources may induce substantial toxic effects. In the present study, the perinatal oral exposure of pregnant mice to two strains of mercury resistant bacteria (MRB), Aeromonas KSU5 MRB and KSU6 MRB resulted in a significant reduction in postnatal body weight gain, delays in the opening of the eyes and appearance in the body hair fuzz, and deficits in the developing sensory motor reflexes in the mice pups during their weaning period on post-natal day (PD)7, PD14 and PD21. A significant and MM producing concentration-dependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT); non-enzymatic oxidative stress (OS) indices like thiobarbituric acid-reactive substances (TBARS) and total reduced glutathione (GSH); and enzymatic OS indices like glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were observed in the forebrain region of the offspring at weaning period (PD7, PD14, and PD21), at adolescent age (PD30), and at adult age (PD36). Thus, perinatal exposure to MRB can affect developing fetus, raising the concerns for it's potential neurotoxic hazards. A reduced exposure to mercury during pregnancy is of crucial importance in preventing mercury-induced neurotoxicity in the offspring.

The microRNA (miR)-183-5p is expressed at high level in the majority of cancer. The purpose of present study was to investigate the role of oncogenic miR-183-5p in prostate cancer (PCa) as biomarker. We carried out our experiment in 50 prostate cancer patients and 40 patients of benign prostatic hyperplasia (BPH) and 40 adjacent controls tissue. The expression of miR-183-5p was evaluated through reverse transcription qualitative polymerase chain reaction. We found that the expression of miR-183-5p in PCa tissue was significantly up regulated as compared to BPH patients and adjacent normal tissues as control. Additionally, miR-183 expression was correlated with higher prostate-specific antigen, higher Gleason Score and metastatic condition. A receiver operating characteristic curve analysis revealed that miR-183-5p distinguished PCa patients from BPH patients and also from control. In conclusion, our data suggest that oncogenic miR-183-5p may be useful as a new tissue specific diagnostic biomarker in prostate cancer.

This study was undertaken to uncover the regulatory role of lycopene in targeting lipopolysaccharide (LPS) induced oxidative stress and inflammatory cascades and subsequent regulation of proprotein convertase subtilisin/kexin type-9 (PCSK-9) expression via sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor-1α (HNF-1α). Further, protein-protein interaction (PPI) studies for Lycopene-Apo-CIII complex against lipoprotein lipase (LPL) were also performed to assess its regulatory role behind the enhanced circulatory TG/TRLs clearance. Lycopene treatment down-regulated hepatocyte PCSK-9 expression via down-regulation of HNF-1α, whereas, LDL-receptor (LDL-R) was up-regulated by subsequent up-regulation of SREBP-2. PPI studies showed that lycopene diminishes the affinity of Apo-CIII to complex with LPL (ΔG: −917.1 Kcal/mol) resulting in increased LPL functionality and TRLs clearance. Moreover, lycopene also ameliorated LPS stimulated oxidative-stress via enhanced total antioxidant and HDL associated PON-1 activity in addition to down-regulate the expression and plasma level of inflammatory mediators. Based on above findings, we concluded that lycopene exhibits dual role in targeting LPS induced oxidative stress and hypertriglyceridemia via down-regulation of PCSK-9, making greater no. of surface LDL-R available for LPS processing and clearance, as well as increased LPL activity through inhibition of Apo-CIII.

A lot of research investigations, conducted in the recent years, establishes that microRNAs (miRNAs) have an important role in keeping both growth and metastasis of Ovarian Epithelial Carcinoma (OEC) under control. However, the clinical and functional role of miR-130a-3p in OEC is yet to be explored. Through quantitative reaction i.e., qRT-PCR, the expression of miR-130a-3p was assessed in tissues and cell lines of OEC patients. This analysis determined the relationship between the expression of miR-130a-3p and its clinicopathology with the overall survival rate of OEC patients. The author made use of cell counting analysis (CCK8) and in vitro flow cytometry to understand the functional and biological impact of miR-130a-3p expression. In comparison with neighboring normal tissues, the expression of miR-130a-3p was found to be lower in 7 OEC samples. Few reasons are cited for this scenario i.e., low expression of miR-130a-3p, such as low overall OEC patient survival rate, incidence of FIGO and metastasis of lymph nodes. miR-130a-3p has been found as an independent candidate for predicting the prognosis of OEC patients, as per Multivariate Cox research. When miR-130a-3p is over-expressed, as per the enhanced mechanism, it prevents both cell proliferation and cell cycle production in OEC. The current study findings emphasize that miR-130a-3p can be leveraged as a biomarker of prognosis and possibly as a target in the treatment of OEC.

Chest injury is one of the most frequent causes of death and complications in different societies. The search for a marker of lung injury is desirable for diagnosis and prognosis. This study was conducted to assess the serum level of Von Willebrand factor (VWF) and Clara cell secretory protein (CC16) as biomarker in traumatic lung injuries for diagnostic and prognostic significance. We evaluated the demographic data of all patients of chest injury presenting to the department. Mode of injury, any intervention, and outcome were evaluated. The level of the VWF and CC16 was assessed as per protocol. The duration of this study was 1 year. The total number of patients was 96. The mean age of patients was 40.84 ± 9.89 (range 14–70 years). Male to female ratio was 5.4:1. There was a statistically significant association of VWF with diagnosis of patient. Markedly elevated levels of VWF were associated with high mortality rates (p = 0.002). The level of VWF was markedly raised in patient having duration of hospital stay more than 2 weeks (p = 0.001). There was a statistically significant association of CC16 with diagnosis of patient. Markedly elevated level of CC16 was associated with high mortality rates (p = 0.001). The level of CCI6 was markedly raised in patients having duration of hospital stay more than 2 weeks (p = 0.001). VWF and CC16 appear to be useful markers for thoracic trauma. They may also be helpful for the prognosis of the patient. Further studies evaluating their role may substantiate our efforts.

Background & objectives: Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (− 330A>C) gene polymorphisms with the susceptibility to oral cancer. Methods: The SNP in IL-2 (−330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated. >Results: IL-2 (−330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; PC) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. >Interpretation & conclusions: Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (−330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

Background: Oxidant-antioxidant imbalance forms a prime component in pathogenesis of chronic obstructive pulmonary disease (COPD). Studies of oxidative stress markers in South Asians were sparse. Methods: One hundred and eighty COPD patients and eighty healthy nonsmokers were enrolled in the study. Serum malondialdehyde (MDA) and iron levels were estimated for oxidative stress. Three antioxidant markers evaluated-catalase, superoxide dismutase (SOD), and serum copper. Patients on antioxidant therapy and with sepsis and chronic illness were excluded from the study. Results: The mean age of COPD patients was 59.29 ± 10.3 years. Serum levels of MDA and iron were significantly higher in COPD patients compared to controls (5.21 ± 1.9 vs. 0.71 ± 0.29 nmol MDA/ml, P = 0.0001 and 69.85 ± 85.49 vs. 79.32 ± 24.39 μg/dl, P = 0.0001, respectively). Mean level of all antioxidant enzymes catalase, SOD, and copper were significantly diminished in cases when compared to control population (P = 0.001). Levels of MDA and iron were found to be significantly elevated in higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes (III, IV) when compared to lower GOLD Classes (I, II). The levels of serum antioxidants were significantly depleted in higher GOLD grades too. COPD patients who were male and smoked had significantly higher levels of oxidants and depleted antioxidant levels compared to female and nonsmoking compatriots. Serum MDA levels negatively correlated with forced expiratory volume 1 s and forced vital capacity (r = −0.19 and r = −0.21, P ≤ 0.01). The presence of a cough significantly correlated with higher levels of MDA and iron (P = 0.001). The levels of MDA negatively correlated with SOD and catalase levels. Conclusion: Oxidative markers (MDA and iron) are higher whereas antioxidants (catalase, copper, and SOD) are significantly reduced in patients of COPD. Serum MDA levels correlate with lung functions and disease severity.

The inevitable development of chemoresistance and unmanageable side effects are the major therapeutic challenges in management of breast cancer imposing an urgent need for identification of novel therapeutic agents. In the present investigation, we report anti-proliferative activity of chloroform fraction of Tinospora cordifolia (TcCF), an Ayurvedic medicinal plant, on breast cancer cells. We found that TcCF inhibited growth of breast cancer cells, MDA-MB-231 and MCF-7. More interestingly, we observed TcCF treatment increased intra-cellular ROS levels, altered expression of pro and anti-apoptotic genes, decreased colony formation ability and induced apoptosis in breast cancer cells. We also found that inhibition of ROS abrogated TcCF induced apoptosis in breast cancer cells, emphasizing the role ROS in TcCF induced breast cancer cell death. Furthermore, we identified the presence of pharmacologically active compounds like rutin and quercetin which account for the anti-cancer property of TcCF against breast cancer cells. These data show TcCF is a promising anti-cancer agent against breast cancer cells.

Background: Developmental ethanol (EtOH) exposure can cause lifelong behavioral hyperactivity, cognitive deficits, emotional dysregulation, and more. However, co-treatment with lithium (Li) on the day of EtOH exposure prevents many of the impairments. Methods: Experimental groups of pregnant mice were exposed to EtOH (20% v/v solution at a dose of 2.5 g/kg) in their drinking water and the animals were treated with Li (15 and 30 mg/kg) through IP injection on gestational days14, 16, 18, and 20, and post-natal days (PD) 3, 5, 7, and 9. All treatments with EtOH and exposure to Li doses to pregnant mice started on gestational day 14 and continued until post-natal day 9 (PD9). The effects on some developing morphological indices, nerve reflexes during weaning age, and various cognitive dysfunctions at adolescent ages and biochemical changes in the brain tissue indices of below-mentioned neurotransmitters and oxidative stress in post-natal developing offspring at adolescent age, were studied. Results: Perinatal exposure to EtOH in pregnant mice resulted in several postnatal developing and morphological indices in the developing male pups during their weaning period, like gain in their body weight, delay in appearance of their body hair fuzz and opening of their eyes, and disruptions in their developing motor reflexes. Discussion: During adolescent age, a significant deficit in their learning capability and cognitive behavior, decline in the neurochemical DA and 5-HT in their brain and some indices of oxidative stress TBARS, GSH, GST, CAT, and SOD was observed. Conclusion: These results indicate that Li ameliorates significantly and dose-dependently EtOH induced developmental toxicities like morphological developments and dysfunctions in cognitive retention and oxidative stress on a long-term basis in brain tissue. However, further detailed studies are required for the clinical use of as an ameliorating agent for perinatal EtOH induced dysfunctions.

Prostate cancer is an ideal tumor model for heterogeneity in almost every aspect. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and research settings. In this chapter, we summarize the main aspects of prostate cancer and its molecular diagnosis at different levels, with special attention given to the spatial heterogeneity within the prostate, and to understand its morphological heterogeneity, with respect to tumor grading and modern classifications. Prostate-specific antigen (PSA) screening is associated with a decline in prostate cancer related mortality. However, screening has also lead to over diagnosis and overtreatment of clinically insignificant tumors. Newly, certain national guidelines (eg, US Preventive Services Task Force) have recommended against PSA screening, which may lead to a reverse-stage migration, even though many prostate tumors are indolent at presentation, others are aggressive and are appropriate targets for treatment interventions. Molecular markers may help in discrimination of indolent and aggressive tumors, at the time of diagnosis.

Radioprotective effects of Resveratrol is well known in normal cells exposed to the damaging effects of ionizing radiation however, its potential radioprotective effect on ovarian follicle formation and development is still uncertain. Astonishingly, it has been reported that PARP contributed to the pathogenesis of immune-mediated ovarian injury. In this paper, Resveratrol was tested for its inflammatory, anti-cervical carcinoma activity, and checked its targets poly (ADP-ribose) polymerase 1 (PARP-1) induced premature ovarian failure with a potent enzymatic modulatory activity. Through high-throughput virtual screening method, Resveratrol was screened to find its target. That the compound strongly inhibited cervical carcinoma HT-3 cell. The cell proliferation was evaluated by an CCK-8 assay, and the cell apoptosis was assessed by a flow cytometry. Rat model of premature ovarian failure was used to introduce resveratrol preparation and rtPCR was done to measure expression of apoptosis related markers. We report resveratrol as a potential target for PARP-1 and its modulator from a high-throughput virtual screening method. Resveratrol was measured its anti-cervical carcinoma activity by using an CCK-8 assay, which suggested that the compound strongly inhibited HT-3 cell proliferation, the IC50 value is 0.65 μM. In addition, the compound induced HT-3 cell apoptosis in a dose-response manner. Resveratrol preserves the entire ovarian follicle pool manifested by increasing serum anti-Mullerian hormone (AMH) levels. Study suggest that resveratrol restored ovarian function through increasing AMH levels, and diminishing ovarian inflammation, predominantly modulation of PPAR-1 and inhibition of inflammatory cytokines. Resveratrol was identified targets for PARP-1 from a high-throughput virtual screening method, strongly inhibited PARP-1 protein and HT-3 cell proliferation. Resveratrol is a promising PARP-1 modulator with anti-cervical carcinoma activity, which deserves further investigation.

Background and Objectives: Insulin action of reducing blood glucose has been found to be enhanced by trace elements. Material and Methods: This was a cross sectional study including 150 patients with Type 2 Diabetes Mellitus (T2DM) and 50 controls. Serum concentrations of zinc, copper, chromium, selenium and magnesium was measured by colorimetric kit. Fasting Blood Glucose and Glycated Haemoglobin (HbA1c) were assayed using the standard kit. Results: Out of 150 patients, 85.4% (n = 128) of the cases had uncontrolled blood sugar with HbA1c ≥7 and only 14.6% (n = 22) had good control of blood sugar with HbA1c

This study aims to explore the association between functional health literacy and awareness for, beliefs, and attitudes of patients with colorectal cancer (CRC) and CRC screening test in Riyadh, Saudi Arabia. A total of 256 participants from two different tertiary level hospitals in Riyadh, Saudi Arabia were recruited in this study. The participants were interviewed by a trained researcher between October and December 2015. All respondents answered a three-part questionnaire which included demographic data, questions related to CRC awareness, attitude, behaviour, and short Test of Functional Health Literacy in Adults (STOFHLA). More than half of the participants had an inadequate awareness of functional health literacy skills (FHLS), 16.4 % had marginal of FHLS awareness and 17.6 % had adequate awareness about FHLS as assessed by the STOFHLA. Overall, the majority of the participants in both marginal and adequate aware groups showed a limited awareness about colorectal cancer screening and testing. A significant association was found on awareness of the patients about frequencies that they should have been tested for colorectal cancer and functional health literacy. No significant association was found between functional health literacy as assessed by STOFHLA and concerns of Faecal Occult Blood Test (FOBT) (p = 0.384) and sigmoidoscopy or colonoscopy might cause embarrassment (p = 0.089), harm (p = 0.917), and pain (p = 0.849). The present study revealed a low level of health literacy among Saudi adults in Riyadh region. Although the level of literacy was low, the bigger concern is that of the poor awareness and beliefs of Saudi adults about CRC and CRC screening.

Oral squamous cell carcinoma (OSCC) occurrence appears to be the number one among all cancers in India. Folate is a methyl donor during DNA methylation, as it provides substrate for methylenetetrahydrofolate reductase (MTHFR) to convert 5,10-MTHF to 5-MTHF and subsequently metabolizes it to methionine. The purpose of this study was to identify MTHFR C677T gene polymorphism in patients with OSCC. A total of 350 OSCC cases and 350 healthy controls participated in this study. MTHFR C677T single-nucleotide polymorphism was evaluated by PCR-RFLP. In the present study, MTHFR gene 677CC, CT, and TT genotype frequencies of the total OSCC cases were 74.8; 19.4 and 5.71; and 88.5, 9.42, and 2.0 % in controls. The average frequency of the MTHFR 677T allele was 15.4 % in OSCC cases compared to 6.71 % in the controls. The CT genotype occurrence prevailed more in patients than controls in contrast to TT genotype, although both the genotypes were statistically significant for OSCC. Moreover, we found that T allele was significant in cases of smoking and tobacco chewing. In this study, we found that the homozygous mutant T allele appeared to have significantly higher risk of OSCC especially in late stages and therefore supporting in OSCC susceptibility and its progression.

Injury to the spinal cord results in immediate physical damage (primary injury) followed by a prolonged posttraumatic inflammatory disorder (secondary injury). The present study aimed to investigate the neuroprotective effects of minocycline and FK506 (Tacrolimus) individually and in combination on recovery from experimental spinal cord injury (SCI). Young adult male rats were subjected to experimental SCI by weight compression method. Minocycline (50mg/kg) and FK506 (1mg/kg) were administered orally in combination and individually to the SCI group daily for three weeks. During these three weeks, the recovery was measured using behavioral motor parameters (including BBB, Tarlov and other scorings) every other day for 29days after SCI. Thereafter, the animals were sacrificed and the segment of the spinal cord centered at the injury site was removed for the histopathological studies as well as for biochemical analysis of monoamines such as 5-hydroxytryptamine (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) and some oxidative stress indices, such as thiobarbituric acid-reactive substances (TBARS), total glutathione (GSH) and myeloperoxidase (MPO). All behavioral results indicated that both drugs induced significant recovery from SCI with respect to time. The biochemical and histopathological results supported the behavioral findings, revealing significant recovery in the regeneration of the injured spinal tissues, the monoamine levels, and the oxidative stress indices. Overall, the effects of the tested drugs for SCI recovery were as follows: FK506+minocycline>minocycline>FK506 in all studied parameters. Thus, minocycline and FK506 may prove to be a potential therapy cocktail to treat acute SCI. However, further studies are warranted.

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

Dietary components present in foods, spices and herbs are source of natural compounds viz. phenols, flavonoids, tocopherols, ascorbic acid and carotenoids with potential benefits. Ginger is one such herb commonly used throughout the world as a spice for dietary as well as medicinal purpose since ancient period. Here, we investigated the methanolic extract of Zingiber officinale rhizome (ZOME) for anticancer activity against human cervical cancer HeLa cells and breast cancer MDA-MB-231 cells and antioxidant activity using 1,1-diphenyl-2-picryl hydroxyl (DPPH) scavenging assay, 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS) cation decolorization test. Antiproliferative activity was substantiated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assay for cell viability and cell proliferation, Hoechst staining was performed to examine apoptosis. Our results demonstrated that ZOME inhibited the proliferation and colony formation in HeLa and MDA-MB-231 cells, in a dose- and time-dependent manner and induced typical changes in nuclear morphology, chromatin condensation and fragmentation, membrane shrinkage and blebbing in both cells indicated apoptotic property of Z. officinale. ZOME exhibited potent antiradical activity against DPPH and ABTS. On the basis of the results of the present study, it may be suggested that Z. officinale has promising anticancer and antioxidant properties. Since, Z officinale has been commonly used throughout the world as a spice for dietary as well as for medicinal purposes since prehistoric times. Therefore, enriched use of Z. officinale as dietary material could be recommended in ethno-medicine for the management of cervical and breast cancers. Moreover, further studies are needed to isolate and characterize the potent compounds for further adjuvant therapy against such malignancies.