Involvement of epigenetics and microRNA-29b in the urethane induced inception and establishment of mouse lung tumors

Epigenetic changes are correlated with tumor development showing aberrations in DNA methylation and histone modifications. To find the early changes, we evaluated the epigenetic events from early to late stage of the urethane induced lung tumor development in mouse model and tried to correlate the molecular events with the progression of tumor. We addressed the hypothesis by examining the tumor development, status of DNMTs, HDACs and MBDs, DNA methylation and expression of microRNA-29b during 1 to 36 weeks after urethane exposure that included the period before and after the tumor appearance. Tumors did not appear after 1 or 4 weeks but well defined tumors appeared after 12 weeks and larger tumors appeared at 36 weeks which was prevented by IP6. DNMT1, DNMT3a and DNMT3b were upregulated after urethane exposure at the time of no tumor till the tumor developed and showed its upregulated functional activity. DNMTs are shown to be the targets of microRNA-29b and we showed that microRNA-29b was downregulated in the line of DNMT upregulation. HDAC, the histone modifier, also showed progressive upregulation. Periodic increase in methyl binding proteins, MBD2, supported the expression of gene silencing pathways in terms of the downregulation of tumor suppressor genes, p16 and MLH1. All these molecular alterations were protected in the presence of IP6. Our results showed that the key steps of epigenetics, DNMTs, mir29b, and HDAC1, are altered both before and after the development of tumors.     

Incidence of total knee and hip replacement for osteoarthritis in relation to the metabolic syndrome and its components: A prospective cohort study

Objective

To examine whether components of metabolic syndrome (MetS), either singly or additively, were associated with the incidence of severe knee and hip OA, and whether these associations were independent of obesity assessed by body mass index (BMI).

Methods

Twenty thousand, four hundred and thirty participants who had blood lipids, anthropometric and blood pressure measurements during 2003–2007 were selected from the Melbourne Collaborative Cohort Study. MetS was defined as central obesity assessed by waist circumference and any two of raised triglyceride level, reduced HDL cholesterol level, hypertension or impaired fasting glycaemia. The incidence of total knee and hip replacement was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.

Results

Six hundred and sixty participants had knee OA and 562 had hip OA. After adjustment for age, gender, country of birth, education, physical activity and BMI, central obesity [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.25–2.01] and hypertension (1.24, 1.05–1.48) were associated with increased risk of knee OA. The accumulation of MetS components was associated with knee OA risk, independent of BMI: one component, 2.12 (1.15–3.91); two components, 2.92 (1.60–5.33) and three or more components, 3.09 (1.68–5.69). No statistically significant associations were observed for hip OA.

Conclusion

Cumulative number of MetS components and central obesity and hypertension were associated with increased risk of severe knee OA, independent of BMI. No associations were observed with severe hip OA. These findings suggest that the pathogenesis of knee and hip OA differ and that targeting the management of MetS may reduce the risk of knee OA.     

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.     

Bio-nanoparticle assembly: a potent on-site biolarvicidal agent against mosquito vectors

Background: Vector-borne diseases such as malaria, dengue, yellow fever, encephalitis and filariasis are considered serious human health concerns in the field of medical entomology. Controlling the population of mosquito vectors is one of the best strategies for combating such vector-borne diseases. However, the use of synthetic insecticides for longer periods of time increases mosquito resistance to the insecticides. Recently, the search for new environmentally friendly and efficient insecticides has attracted major attention globally. With the evolution of material sciences, researchers have reported the effective control of such diseases using various sustainable resources. The present investigation demonstrates a potent on-site biolarvicidal agent against different mosquito vectors such as Aedes albopictus, Anopheles stephensi and Culex quinquefasciatus. Methods: Stable and photo-induced colloidal silver nanoparticles were generated via the surface functionalization of the root extract of Cyprus rotundas. Characterizations of the nanoparticles were performed using assorted techniques, such as UV-visible spectroscopy, FTIR spectroscopy, DLS and HRTEM. The bioefficacy of the synthesized nanoparticles was investigated against different species of mosquito larvae through the evaluation of their life history trait studies, fecundity and hatchability rate of the treated larvae. Histopathological and polymerase chain reaction-random amplified polymorphic DNA (RAPD) analyses of the treated larvae were also examined to establish the cellular damage. Results: The synthesized nanoparticles showed remarkable larvicidal activity against mosquito larvae in a very low concentration range (0.001–1.00) mg L⁻¹. The histopathological study confirmed that the present nanoparticles could easily enter the cuticle membrane of mosquito larvae and subsequently obliterate their complete intestinal system. Furthermore, RAPD analysis of the treated larvae could assess the damage of the DNA banding pattern. Conclusion: The present work demonstrates a potent biolarvicidal agent using sustainable bioresources of the aqueous Cyprus rotundas root extract. The results showed that the synthesized nanoparticles were stable under different physiological conditions such as temperature and photo-induced oxidation. The effectiveness of these materials against mosquito larvae was quantified at very low dose concentrations. The present biolarvicidal agent can be considered as an environmentally benign material to control the mosquito vectors with an immense potential for on-site field applications.

The present work demonstrates a potent and stable biolarvicidal agent using sustainable bioresources. The synthesized nanomaterials can control the mosquito vectors at a very low concentration range (0.01–1.00 mg L⁻¹) for on-site field applications.     

The effectiveness of early mobilization after tendon transfers in the hand: A systematic review

Study DesignSystematic review.IntroductionOver the past decade, early mobilization (initiated within a week) has become an increasing trend in postoperative rehabilitation after tendon transfer surgery in the hand. However, there are no published reviews summarizing the effectiveness of early mobilization protocols in comparison with conventional immobilization in tendon transfer rehabilitation.PurposeTo systematically review available evidence on the effectiveness of early mobilization protocols to conventional immobilization protocol after tendon transfers in the hand.MethodsA literature search of the Cochrane Library, PubMed, PEDro, EMBASE, and CINAHL databases was conducted (1980 to date). Randomized controlled trials (RCTs), case–control, and other study designs were included. Six articles were eligible for inclusion in the analysis (five RCTs and one retrospective study) and 260 articles that did not meet inclusion criteria were excluded. Level of evidence (Center for Evidence-based Medicine) and methodological quality (Structured Effectiveness Quality Evaluation Scale [SEQES] score) of each study were assessed by two independent reviewers.ResultsThis review found three high quality trials (SEQES score: 35–43 of 48), with level 1b and 2b evidence, supporting early mobilization of tendon transfers. The literature reports reduced total cost, total rehabilitation time, and demonstrates that early mobilization is a safe approach with no incidence of tendon ruptures or insertion pull out. In the initial phase of rehabilitation, outcomes like range of motion, grip strength, pinch strength, total active motion of digits, deformity correction, and tendon transfer integration were significantly superior with early mobilization compared with immobilization. However, in the long term, these outcomes were similar in both the groups, suggesting that early mobilization protocol improves hand function in the initial phase of rehabilitation (four weeks) and the long-term results (two months to one year) are equivalent to immobilization.ConclusionsBased on a limited number of small studies, there is evidence of short-term benefit for early mobilization, but inconclusive findings for longer-term outcomes. Until the body of evidence increases, clinicians should consider the clinical context, their experience in optimizing patient outcomes after surgery, and the patient's preferences when selecting between early and late mobilization after tendon transfer.Level of Evidence2a.     

Risk of renal cell carcinoma and polymorphism in phase I xenobiotic metabolizing CYP1A1 and CYP2D6 enzymes

The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease. The CYP1A1 (val) “variant” genotype, which contains at least 1 copy of the CYP1A1 variant alleles, was found to be associated with a 2.03-fold [GG ver. AA/AG, unadjusted OR = 2.03; 95%CI = 1.233–3.342; P = 0.005] increase in the risk of RCC. There was also a significant association (p^trend = 0.034) between higher frequency of RCC subjects containing at least of copy of the CYP1A1 (val) “variant” genotype with III or IV Fuhrman's grade. Whereas, the CYP2D6 polymorphism did not show any association with RCC risk [TT ver. CT/CC, unadjusted OR = 95%CI = 1.233–3.342; P = 0.005]. There was a significant association (p^trend = 0.001) between the poor metabolizer CYP2D6 (TT) and progression towards higher pathological stage of RCC. Our data demonstrate for the first time a significant association between pharmacogenetic polymorphisms of CYP1A1 and risk of RCC development in the Indian population. The findings suggest that inter-individual variation in the phase I metabolic enzymes involved in the fictionalization and detoxification of specific xenobiotics is an important susceptibility factor for development and progression of RCC in Indians.     

Population-based Studies of Childhood Disability in Developing Countries

This article reports the main health status differences between a representative sample of homeless people and an at-risk for homelessness group consisting of people who use services for the homeless such as soup kitchens and public baths but have and maintain a home. The variables analyzed include health problems by system, risk habits and behaviors, substance use, alcohol problems, general health status, suicidal thoughts and perceived health status. Because of the gender differences between groups, the data were analyzed independently for men and women. The results show that the homeless have worse health status compared with the at-risk group. Homeless men had significantly more risk habits and behaviors, substance use, and mental health problems. Homeless women had similar tendencies, although they also had significantly more general health illnesses (by systems and over the past year). Almost no differences were found in drug use (especially alcohol use) or in mental health—except for depression, which was significant. These results shed light on new data regarding the correlation between homelessness and health issues.     

Total antioxidant and oxidant status of plasma and renal tissue of cisplatin-induced nephrotoxic rats: protection by floral extracts of Calendula officinalis Linn.

The present study was aimed to determine the total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of plasma and renal tissue in cisplatin (cDDP) induced nephrotoxic rats and its protection by treatments with floral extracts of Calendula officinalis Linn. Treatment with cDDP elevated (p?p?C. officinalis along with cDDP restored (p?>?0.05) CR, albumin, TOS, GSH and activities of antioxidant enzymes in blood and renal tissue. Ethanolic extract treatments reduced (p?C. officinalis protect cDDP induced nephrotoxicity by restoring antioxidant system of the renal tissue.