Proteomic and metabolomic analysis of smooth muscle cells derived from the arterial media and adventitial progenitors of apolipoprotein E-deficient mice

We have recently demonstrated that stem cell antigen 1-positive (Sca-1(+)) progenitors exist in the vascular adventitia of apolipoprotein E-deficient (apoE(-/-)) mice and contribute to smooth muscle cell (SMC) accumulation in vein graft atherosclerosis. Using a combined proteomic and metabolomic approach, we now characterize these local progenitors, which participate in the formation of native atherosclerotic lesions in chow-fed apoE(-/-) mice. Unlike Sca-1(+) progenitors from embryonic stem cells, the resident Sca-1(+) stem cell population from the vasculature acquired a mature aortic SMC phenotype after platelet-derived growth factor-BB stimulation. It shared proteomic and metabolomic characteristics of apoE(-/-) SMCs, which were clearly distinct from wild-type SMCs under normoxic and hypoxic conditions. Among the differentially expressed proteins were key enzymes in glucose metabolism, resulting in faster glucose consumption and a compensatory reduction in baseline interleukin-6 secretion. The latter was associated with a marked upregulation of insulin-like growth factor binding proteins (IGFBPs) 3 and 6. Notably, reconstitution of interleukin-6 to levels measured in the conditioned medium of wild-type SMCs attenuated the elevated IGFBP expression in apoE(-/-) SMCs and their vascular progenitors. This coregulation of apoE, interleukin-6, and IGFBPs was replicated in wild-type SMCs from hypercholesterolemic mice and confirmed by silencing apoE expression in SMCs from normocholesterolemic mice. In summary, we provide evidence that Sca-1(+) progenitors contribute to native atherosclerosis in apoE(-/-) mice, that apoE deficiency and hypercholesterolemia alter progenitor cell behavior, and that inflammatory cytokines such as interleukin-6 act as metabolic regulators in SMCs of hyperlipidemic mice.     

Type 2 Diabetes and Anxiety Symptoms Among Women in New Delhi,India

Objectives. We explored the relationship between mental health and type 2 diabetes among women in New Delhi, India, in 2011.Methods. We recruited a convenience sample of 184 diabetic women from 10 public and private clinics. They completed a finger-stick blood test and a questionnaire assessing demographic characteristics, depression and anxiety symptoms, and diabetes-related disabilities restricting their performance of daily tasks. A subsample of 30 women participated in follow-up qualitative interviews at their homes.Results. More than one quarter of our sample of diabetic women reported high levels of anxiety symptoms, whereas 18% reported high levels of depression symptoms. Anxiety symptoms were patterned according to recency of diabetes diagnosis, with 40% of women diagnosed less than 2 years before their interview reporting high anxiety symptom levels, as opposed to 23% of women diagnosed more than 2 years in the past. Depression and anxiety scores differed with respect to their relationship to recency of diagnosis, number of children, blood glucose level, and functional disabilities restricting performance of daily tasks.Conclusions. Screening for anxiety among people with diabetes has been overlooked in the past. Anxiety appears more prevalent than depression, especially during the first 2 years of the disease.Chronic and noncommunicable diseases (CNCDs) are emerging as major research foci in tandem with their increasing global prevalence. In both developed and developing regions of the world, including South Asia, CNCDs are now leading causes of morbidity and mortality.1 With their complicated etiologies, long durations, frequent comorbidities, and lack of “cures,” CNCDs pose unique challenges for global health. In particular, CNCDs can have far-reaching personal and interpersonal effects that are difficult to capture in epidemiological and biomedical studies, yet are crucial to the trajectory of these illnesses. It is therefore necessary to adopt an analytic perspective that embraces the complex natural histories of chronic diseases as well as their potential comorbidities.A particularly well-studied instance of comorbidity is the overlap between type 2 diabetes and depression. This comorbidity has been estimated to affect anywhere from 11% to 71% of individuals with diabetes, depending on the population studied and the diagnostic method used,2–4 and it is strongly associated with physical and mental morbidity and even mortality.2–6 Clinical and epidemiological studies have demonstrated the cyclical nature of diabetes–depression comorbidity,7 and medical social scientists have identified some of the social determinants linking the 2 conditions, including socioeconomic status (SES),8 the social significance of foods and activity patterns,9,10 and gendered social roles.11–13The similarity between depression and anxiety symptoms, etiologies, and methods of diagnosis, as well as their common comorbidity,14 suggests that anxiety should be as great a concern in CNCD comorbidity as depression. Indeed, according to findings from the World Mental Health Survey, diabetes is roughly equally associated with depression and anxiety around the world.15 Yet, with one very recent exception,16 the potential impact of anxiety disorders on diabetes has received much less attention than diabetes–depression comorbidity.Here we detail the findings of an exploratory mixed-method study of type 2 diabetes (hereafter diabetes) and mental health symptoms among women in New Delhi, India, with a special focus on symptoms of anxiety. India is home to the second-largest population of individuals with type 2 diabetes in the world.17 The limited existing evidence suggests that depression and anxiety are also common,18–20 although prevalence studies are few. Little is known about how diabetes and poor mental health co-occur in this setting or about what social determinants might shape their comorbidity.On the basis of the observation that high levels of anxiety symptoms were significantly more prevalent than depression symptoms in our study, we believe that it is important to consider the causes and correlates of anxiety comorbid with diabetes. We propose a socially grounded interpretation of the patterns emerging from our preliminary data and offer suggestions for future research designed to assess the broader applicability of this interpretation for CNCD–anxiety comorbidity in other contexts.     

Graphene supports in vitro proliferation and osteogenic differentiation of goat adult mesenchymal stem cells: potential for bone tissue engineering

Current treatments for bone loss injuries involve autologous and allogenic bone grafts, metal alloys and ceramics. Although these therapies have proved useful, they suffer from inherent challenges, and hence, an adequate bone replacement therapy has not yet been found. We hypothesize that graphene may be a useful nanoscaffold for mesenchymal stem cells and will promote proliferation and differentiation into bone progenitor cells. In this study, we evaluate graphene, a biocompatible inert nanomaterial, for its effect on in vitro growth and differentiation of goat adult mesenchymal stem cells. Cell proliferation and differentiation are compared between polystyrene‐coated tissue culture plates and graphene‐coated plates. Graphitic materials are cytocompatible and support cell adhesion and proliferation. Importantly, cells seeded on to oxidized graphene films undergo osteogenic differentiation in fetal bovine serum‐containing medium without the addition of any glucocorticoid or specific growth factors. These findings support graphene's potential to act as an osteoinducer and a vehicle to deliver mesenchymal stem cells, and suggest that the combination of graphene and goat mesenchymal stem cells provides a promising construct for bone tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.     

Bone-tissue engineering: complex tunable structural and biological responses to injury,drug delivery,and cell-based therapies

Bone loss and failure of proper bone healing continues to be a significant medical condition in need of solutions that can be implemented successfully both in human and veterinary medicine. This is particularly true when large segmental defects are present, the bone has failed to return to normal form or function, or the healing process is extremely prolonged. Given the inherent complexity of bone tissue – its unique structural, mechanical, and compositional properties, as well as its ability to support various cells – it is difficult to find ideal candidate materials that could be used as the foundation for tissue regeneration from technological platforms. Recently, important developments have been made in the implementation of complex structures built both at the macro- and the nano-level that have been shown to positively impact bone formation and to have the ability to deliver active biological molecules (drugs, growth factors, proteins, cells) for controlled tissue regeneration and the prevention of infection. These materials are diverse, ranging from polymers to ceramics and various composites. This review presents developments in this area with a focus on the role of scaffold structure and chemistry on the biologic processes that influence bone physiology and regeneration.     

Losartan-induced attenuation of blood pressure in L-NAME hypertensive rats is associated with reversal of the enhanced expression of Gi alpha proteins

OBJECTIVE: We have previously reported that hearts from N-[omega]-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats exhibited an enhanced expression of Gi proteins. Since, losartan, an AT1 receptor antagonist, has been shown to attenuate the L-NAME-induced increase in blood pressure, we undertook the present studies to evaluate whether losartan-induced decreased blood pressure in this model of hypertension is associated with attenuation of enhanced expression of Gi proteins and adenylyl cyclase signalling. METHODS: L-NAME (70 mg/kg body weight) and losartan (10 mg/kg body weight), alone or in combination, were given orally to Sprague-Dawley rats for 4 weeks. The control rats received only plain tap water. The levels of inhibitory guanine nucleotide regulatory proteins (Gi alpha-2 and Gi alpha-3) and stimulatory (Gs alpha) proteins and Gi alpha mRNA in hearts were determined by immunoblotting and Northern blotting, respectively. Adenylyl cyclase activity was determined by measuring [32P]cAMP formation from [32P]ATP. RESULTS: Systolic blood pressure was enhanced in L-NAME-treated rats compared to control rats (164 +/- 5.2 versus 105 +/- 2 mmHg; n = 30), and was significantly attenuated by losartan treatment (164 +/- 5.2 mmHg versus 120 +/- 2.5 mmHg; n = 30). The expression of Gi alpha-2 and Gi alpha-3 proteins and their mRNA, which was enhanced in L-NAME-treated rats, was reversed by losartan treatment. However, losartan alone did not alter the levels of Gs alpha or Gi alpha proteins. In addition, the stimulatory effects of guanosine 5'-gamma-thiotriphosphate (GTPgammaS), isoproterenol, 5'-N-ethylcarboxamideadenosine (NECA), glucagon, forskolin (FSK) and sodium fluoride (NaF) on adenylyl cyclase, which were diminished in L-NAME-treated rats, were reversed by losartan treatment. Furthermore, the inhibition of forskolin-stimulated enzyme activity by low concentrations of GTPgammaS (receptor-independent Gi functions), which was significantly enhanced in L-NAME-treated rats, was attenuated by losartan treatment. In addition, losartan was able to reverse the attenuated receptor-mediated inhibitions of adenylyl cyclase by oxotremorine and angiotensin II towards control. CONCLUSIONS: These results suggest the implication of AT1 receptors in enhanced expression of Gi alpha proteins and increased blood pressure in L-NAME-induced hypertension.     

High prevalence of obesity among nursing personnel working in tertiary care hospital

Aim

To find out the prevalence of obesity and glucose intolerance among nurses working in tertiary care hospital.

Prevalence of double diabetes in youth onset diabetes patients from east Delhi and neighboring NCR region

Background

It is being increasingly reported that some of the youth onset diabetes patients cannot be classified clearly as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) based on usual criteria and the term double diabetes (DD) coined for these cases.

Status of TIM-1 exon 4 haplotypes and CD4+T cell counts in HIV-1 seroprevalent North Indians

The TIM (T cell/transmembrane, immunoglobulin and mucin) proteins are crucial regulators of Th1/Th2 immune responses and have been implicated in several diseases including HIV-1/AIDS. The TIM1 exon 4 that codes for mucin domain is highly diverse, with sequence variants associated with varying phenotypes. In this study, TIM1 exon 4 was sequenced among 227 HIV-1 seroprevalent and 288 healthy non infected individuals from North Indian population and haplotypes established. A novel but rare haplotype D1^∗ was identified among the healthy and differed from D1 by a synonymous substitution G>T at Thr208Thr. The TIM1 haplotype diversity showed no association with susceptibility to HIV-1 infection. The seroprevalent individuals carrying D3A had relatively higher median CD4+T cell counts (368/μl) than those without (313/μl; p = 0.02). A comparison of CD4+T counts between D3-A individuals on ART or ART naïve did not show any significant difference plausibly due to confounding nature of ART and other factors.     

Volatile compounds reveal age: a study of volatile organic compounds released by Chrysomya rufifacies immatures

International Journal of Legal Medicine - Age determination of insects collected from vertebrate remains is an essential step in estimating time since colonization as related to the post-mortem...