Effect of resveratrol on the biomarkers of oxidative stress and inflammation in monocyte cultures from PBMC’s of patients with myocardial infarction

Globally, one of the major causes of mortality and morbidity is ischemic heart disease (IHD). It has been established that in cardiac disorders, there exists a synergistic correlation between the oxidative stress and inflammatory cytokines. The stabilization and regulation of the oxidative stress and inflammatory cytokines in these patients is essential for the better management of the disease. Hence, the aim of this study was to study the effect of natural antioxidant, resveratrol, on the oxidative stress and inflammatory biomarkers in cultures of monocytes isolated from peripheral blood mononuclear cells (PBMCs) from the patients with myocardial infarction. Monocytes isolated from peripheral blood mononuclear cells (PBMC’s) of patients with myocardial infarction (MI) and healthy controls were employed in culture studies (with and without resveratrol). The 24 h cultures were subjected to evaluation of cytokine/ interleukins levels i.e. TNF-α, IL-1 and IL-6 as well as oxidative stress markers like MDA and Glutathione. The patient’s samples exhibited a significantly decreased level of intramonocyte glutathione as compared to samples of healthy subjects. On the other hand, significantly increased levels of MDA were observed in culture supernatants of monocytes isolated from PBMC’s of patients with MI in comparison to those of healthy controls. A significant degree of amelioration in intramonocyte glutathione levels coupled with decreased MDA levels (culture supernatants) were observed in cultures treated with resveratrol (20 ug/mL). Furthermore, 24 h culture supernatants of untreated patients cells exhibited augmented levels of IL-1, IL-6, and TNF-α. However, co-culturing with resveratrol exhibited a significant decrease in the levels of all the IL-1, IL-6 and TNF-α. Resveratrol—a potent polyphenol from grapes and also a natural antioxidant regulates the oxidative stress and inflammatory biomarkers and may be used as a prophylactic antioxidant in high risk patients.

Factors Associated With Elevated Blood Lead Levels in Children

Objectives: To determine the prevalence and correlates of elevated blood lead level inchildren (6-144 months) of Aligarh. Methods: A hospital-based cross-sectional study wasconducted. Venous blood was obtained for lead estimation and a structured questionnairewas filled. Results: A total of 260 children were enrolled. The prevalence of elevated bloodlead level was 44.2%, seen mostly in children below 5 years of age. Old and deteriorating wallpaints at home was found to be significantly associated with elevated levels. Conclusions:Lead-based house paints are potential source of lead exposure. Meticulous renovation andpainting of the walls with safe paints is desirable

Comparative evaluation of extract of Bacopa monnieri and Mucuna pruriens as neuroprotectant in MPTP model of Parkinson’s disease.

Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in substantia nigra. Treatment of PD has been shifted recently towards herbal medicines.Bacopa monnieri (L.) Wettst. (BM) and Mucuna pruriens (L.) DC (MP) are traditional herbal plants known to have neuroprotective effects due to the presence of bacosides in whole plant extract of Bacopa monnieri (BME) and L-DOPA in MP seed extract (MPE). In this study, the comparative effect of BME and MPE in Parkinsonian mice induced by chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was evaluated. Twenty four Swiss albino mice (35-45 g) were grouped into Control, MPTP, MPTP+BME and MPTP+MPE (6 mice in each). Experimental mice were given 40 mg/kg body wt. BME, 48 mg/kg body wt. MPE treatment was given orally for one month with prior use of 15 mg/kg body wt. of MPTP for 2 wk. After the treatment period, behavioral study was performed and assessment of neuroprotective effect was done via neurochemical analysis, Immunohistochemical parameters studied included functional viability of dopaminergic neurons in substantia nigra by Tyrosine hydroxylase (TH) using monoclonal antibody against TH and apoptotic study through caspase-3 and m-RNA expression of neurogenic gene in substantia nigra region of brain. Treatment with BME or MPE for one month significantly decreased the elevated levels of oxidative stress found in Parkinsonian mice. In behavioral tests, comparative analysis of BME and MPE showed a significant increase in spontaneous locomotor activity and grip strength test. Moreover, it was found that the use of BME considerably improved the tyrosine hydroxylase activity, caspase-3 and expression of neurogenic gene in the substantia nigra region of the brain. The results suggest that BME may provide a better platform for future drug discoveries and novel treatment strategies for PD as compared to MPE.

Anticancer and Antioxidant activity of Zingiber officinale Roscoe rhizome.

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.

Identification of Anticancer and Antioxidant phytoconstituents from chloroform fraction of Solanum nigrum L. berries using GC-MS/MS analysis.

Solanum nigrum is a traditional Indian plant acclaimed for its medicinal properties since antiquity. Among all plant parts fruit berries have shown to be most pharmacologically active part. In the present investigation, we tried to characterize the bioactive principles of chloroform fraction of S. nigrum (CFSn) fruit berries using GC-MS analysis. We could identify 29 compounds belonging to different chemical classes viz. alkaloids, flavonoids, carbohydrates, glycosides, phytosterols, proteins, phenolic compounds, and saponins. More specifically, we found two novel phenolic compounds, benzoiisovanillin and syringic acid (4-hydroxy-3, 5-dimethoxybenzoic acid), which may be responsible for its pharmacological properties. Our phytochemical investigation of CFSn was well supported by its total phenolic content and antioxidant activity which we evaluated subsequently. Further, we investigated the anticancer activity against breast cancer cell lines (MDA-MB-231 and MCF-7) as well. Our in vitro results indicated that CFSn exhibited significant antiproliferative activity against both these cell lines and due induction of cancer cell death through apoptosis. Our study emphasizes the need for isolation and characterization of specific bioactive compounds of CFSn and determination of their mechanism of action responsible for its anticancer activity in breast cancer cells.

Osteocalcin HindIII gene polymorphism not associated with bone mineral density—A study in North Indian postmenopausal osteoporotic women.

Osteoporosis is an important health problem in India owing to the prevalence of vitamin D deficiency across all ages, low level of awareness and higher risk of complications. This disease is characterized by decreased bone mass, bone strength and higher risk of bone fracture. Here, we investigated association between osteocalcin HindIII gene polymorphism and bone mineral density (BMD) in postmenopausal osteoporotic and postmenopausal healthy North Indian women, possibly the first study of this kind in the aforesaid population. We investigated Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) of osteocalcin HindIII in 254 postmenopausal osteoporotic (56.12±7.004 years) and 254 postmenopausal healthy (55.27±5.93 years) North Indian women. BMD at lumbar spine (L1-L4), femoral neck, hip and forearm was measured by dual energy X-ray absorptiometry (DEXA). The results showed no significant correlation between osteocalcin HindIII gene polymorphism and BMD and we conclude that osteocalcin HindIII gene polymorphism may not have major effects on BMD variation in postmenopausal North Indian women.

PI3K/Akt/mTOR signaling & its regulator tumour suppressor genes PTEN & LKB1 in human uterine leiomyomas.

Background & objectives: Despite their high occurrence and associated significant level of morbidity manifesting as spectrum of clinical symptoms, the pathogenesis of uterine leiomyomas (ULs) remains unclear. We investigated expression profile of tumour suppressor genes PTEN (phosphatase and tensin homolog deleted on chromosome ten) and LKB1 (liver kinase B1), and key signaling components of P13K (phosphatidylinositol 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) pathway in leiomyomas and adjacent normal myometrium in women of reproductive age, to explore the possibility of targeting this pathway for future therapeutic implications. Methods: Real time PCR (qPCR) was used to quantify relative gene expression levels of PTEN, Akt1, Akt2, mTOR, LKB1 and VEGFA (vascular endothelial growth factor A) in leiomyoma as compared to adjacent normal myometrium. Immunohistochemistry was subsequently performed to analyze expression of PTEN, phospho-Akt, phospho-mTOR, phospho-S6, LKB1 and VEGFA in leiomyoma and adjacent normal myometrium. Results: Significant upregulation of PTEN (2.52 fold; P=0.03) and LKB1 (3.93 fold; P=0.01), and downregulation of VEGFA (2.95 fold; P=0.01) genes were observed in leiomyoma as compared to normal myometrium. Transcript levels of Akt1, Akt2 and mTOR did not vary significantly between leiomyoma and myometrium. An increased immunoexpression of PTEN (P=0.015) and LKB1 (P<0.001) and decreased expression of VEGFA (P=0.01) was observed in leiomyoma as compared to myometrium. Immunostaining for activated (phosphorylated) Akt, mTOR and S6 was absent or low in majority of leiomyoma and myometrium. Interpretation & conclusions: Upregulation of PTEN and LKB1 in concert with negative or low levels of activated Akt, mTOR and S6 indicates that PI3K/Akt/mTOR pathway may not play a significant role in pathogenesis of leiomyoma.

Effect of Pre-treatment Nutritional Status, Folate and Vitamin B12 Levels on Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia.

Objective: To evaluate pre-treatment undernutrition, and folate and B12 deficiency in children with acute lymphoblastic leukemia, and their correlation with complications and outcome of induction chemotherapy. Design: Observational study. Setting: Tertiary care teaching hospital in Northern India. Participants: 50 children with acute lymphoblastic leukemia. Procedure: Children were assessed for nutritional status (Weight for age Z-score, serum albumin, folate and B12) at presentation, and were followed-up during induction for bone marrow response, counts and outcome. Folate and B12 were repeated twice at monthly intervals after induction. Univariate and multivariate analyses were done to determine the association of nutritional parameters with the outcome variables. Results: Baseline undernutrition was observed in 66%, hypoalbuminemia in 32.6%, folate deficiency in 41.3% and B12 deficiency in 36.9% of included children. Significant decline in folate levels was noted on serial assays during chemotherapy (P=0.001). Folate deficient children had higher risk for delayed marrow recovery and counts on day 14 (P=0.007 and P=0.001). Hypoalbuminemia (P=0.04), B12 deficiency (P=0.001) and folate (P=0.03) deficiency were associated with toxic deaths during induction. Conclusion: Baseline nutritional deficiencies negatively influence the outcome and occurrence of complications during induction chemotherapy in children with acute lymphoblastic leukemia.

Hypolipidemic Activity Of Cassia Tora Seeds In Hyperlipidemic Rats

The hypolipidemic activity of Cassia tora (Chakvat, Chakunda) (Family: Caesalpiniaceae) seeds extract has been studied in two hyperlipidemic models of rat. These are triton injected and cholesterol rich HFD fed model of hyperlipidemia. In triton WR-1339 induced hyperlipidemia, feeding with root extract (500 mg/ kg body wt/ day p.o. ) exerted lipid lowering effect as assessed by reversal of plasma levels of total cholesterol (TC), phospholipids (PL), triglyceride (TG) and reactivation of Post Heparin Lipolytic Activity (PHLA) of plasma. The other model was fed with cholesterol rich HFD and seeds extract of Cassia tora (500 mg/ kg body wt/ day p.o.) simultaneously for 30 days. This also caused lowering of lipid levels in plasma and liver homogenate and reactivation of plasma post heparin lipolytic activity, hepatic total lipoprotein lipase activity. The hypolipidemic activity of Cassia tora seeds was compared with a standard drug guggulipid (200 mg/ kg body wt/ day p.o.), a known lipid lowering drug in both models.

MicroRNAs and Their Role in Bone Remodeling and Pathogenesis.

MicroRNAs, a class of post-transcriptional gene expression regulators that bind to complementary sequences in the 3’ UTR or 5’ UTR of mRNAs have recently been detected in human body fluids including peripheral blood plasma as extracellular nuclease resistant entities. It is now clear that the biogenesis and functions of microRNAs are related to the molecular mechanisms of various clinical diseases and they can potentially regulate every aspect of cellular activity. This review will highlight our current understanding of microRNA biogenesis and their mechanisms of action. It will also summarize recent works on the role of microRNAs in bone remodeling including angiogenesis, osteoblast and osteoclast differentiation and in various bone related pathologies. An in-depth understanding of the roles of these regulatory mRNAs in the skeleton will be critical for the development of new therapeutics aimed on bone remodeling including fracture repair and bone-related diseases.

A case of oligoasthenoteratozoospermia with AZFc deletion and persistent oxidative stress.

Y-chromosomal microdeletions are associated with severe oligozoospermia or azoospermia. AZFc microdeletions have been always associated with severe oligozoospermia or azoospermia with a rare occurrence in individuals with other infertility phenotypes. We report here a rare case of an infertile man carrying AZFc deletion, whose semen picture is oligoasthenoteratozoospermia complexed with seminal oxidative stress. Anti-oxidant therapy could make no change in either oxidative stress biomarker levels of semen, seminal parameters or serum hormone levels. Therefore, oligoasthenoteratozoospermia in the present case correlates with AZFc deletion, and high content of abnormal sperm eventually might be responsible for persistently elevated reactive oxygen species levels. Understanding the function of genes in AZFc region could help decipher the exact cause of the phenotype in such cases.

Abnormality of Circadian Rhythm of Serum Melatonin and Other Biochemical Parameters in Fibromyalgia Syndrome.

Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body’s circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels.

Hypolipidemic and antioxidant activity of Anthocephalus indicus (Kadam) root extract.

The present study was carried out to explore the anti-diabetic, anti-dyslipoproteinemic and anti-oxidant activities of Anthocephalus indicus root extract in alloxan-induced (150 mg/kg body wt.) diabetic rats. A marked increase in plasma levels of glucose and lipid peroxides accompanied with an elevation in the lipids and apoprotein levels of serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) following decrease in lipid and protein constituents of high density lipoprotein (HDL) were observed. The alterations in lipoprotein pattern was associated with inhibition of lipolytic and antioxidant enzymes. Oral administration of root extract (500 mg/kg body wt.) for 30 days in dyslipidemic animals resulted in significant decrease in plasma glucose, total cholesterol, phospholipids, triglyceride and lipid peroxides. The decrease of lipids and apoprotein levels of VLDL and LDL were followed by stimulation of plasma post-heparin lipolytic activity and lecithin cholesterol acyltransferase as well as hepatic superoxide dismutase and catalase activities. Lipid and apoprotein levels of HDL were also recovered partially on treatment with root extract.

Hypolipidemic activity of Hibiscus rosa sinensis root in rats.

The hypolipidemic activity of Hibiscus rosa sinensis (family Malvaceae) root extract was studied on triton and cholesterol-rich high fat diet (HFD) induced models of hyperlipidemia in rats. In triton WR-1339-induced hyperlipidemia, feeding with root extract (500 mg/kg body wt/day p.o.) exerted lipid-lowering effect, as assessed by reversal of plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) and reactivation of post-heparin lipolytic activity (PHLA) of plasma. The other model was fed with cholesterol-rich HFD and root extract (500 mg/kg body wt/ day p.o.) simultaneously for 30 days. This also caused lowering of lipid levels in plasma and liver homogenate and reactivation of plasma PHLA and hepatic total lipoprotein lipase activity. The hypolipidemic activity of Hibiscus rosa sinensis root was compared with a standard drug guggulipid (200 mg/kg body wt/day p.o.), a known lipid- lowering agent in both models. Histopathological findings in rat liver supported the protective role of H. rosa sinensis root extract in preventing cholesterol-rich HFD-induced hepatic steatosis.