Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

AIM: To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non-European population. METHODS: We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next-generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. RESULTS: We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver-operating characteristic curve 0.90 (95% CI 0.83-0.97)]. All children with monogenic diabetes were autoantibody-negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody-positive individuals by eight. CONCLUSIONS: The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course.

Dietary weight loss in insulin-resistant non-obese humans: Metabolic benefits and relationship to adipose cell size.

BACKGROUND AND AIMS: Overweight and obesity increase risk for diabetes and cardiovascular disease, largely through development of insulin resistance. Benefits of dietary weight loss are documented for obese individuals with insulin resistance. Similar benefits have not been shown in overweight individuals. We sought to quantify whether dietary weight loss improves metabolic risk profile in overweight insulin-resistant individuals, and evaluated potential mediators between weight loss and metabolic response. METHODS AND RESULTS: Healthy volunteers with BMI 25-29.9 kg/m2 underwent detailed metabolic phenotyping including insulin-mediated-glucose disposal, fasting/daylong glucose, insulin, triglycerides, FFA, and cholesterol. Subcutaneous fat biopsies were performed for measurement of adipose cell size. After 14 weeks of hypocaloric diet and 2 weeks of weight maintenance, cardiometabolic measures and biopsies were repeated. Changes in weight, % body fat, waist circumference, adipose cell size and FFA were evaluated as predictors of change in insulin resistance. Weight loss (4.3 kg) yielded significant improvements in insulin resistance and all cardiovascular risk markers except glucose, HDL-C, and LDL-C. Improvement in insulin sensitivity was greater among those with <2 vs >2 cardiovascular risk factors at baseline. Decrease in adipose cell size and waist circumference, but not weight or body fat, independently predicted improvement in insulin resistance. CONCLUSIONS: Weight loss yields metabolic health benefits in insulin-resistant overweight adults, even in the absence of classic cardiovascular risk factors. Weight loss-related improvement in insulin sensitivity may be mediated through changes in adipose cell size and/or central distribution of body fat. The insulin-resistant subgroup of overweight individuals should be identified and targeted for dietary weight loss. CLINICAL TRIALS IDENTIFIER: NCT00186459.

Relationship between surrogate estimates and direct measurement of insulin resistance in women with polycystic ovary syndrome.

PURPOSE: To evaluate the relationship between surrogate estimates of insulin resistance and a direct measurement of insulin-mediated glucose uptake women with and without PCOS. METHODS: Retrospective cohort study of 75 PCOS and 118 controls. Fasting plasma glucose and insulin concentrations, insulin resistance as determined by the insulin suppression test, calculation of multiple surrogate estimates of insulin resistance, total and free testosterone concentrations, and correlations between the direct measure and surrogate estimates of insulin resistance were evaluated. RESULT(S): Surrogate markers of insulin resistance were correlated to a variable, but statistically significant degree with the direct measure of insulin resistance in control population and the women with PCOS. There was no correlation between the surrogate estimates of insulin resistance and total or free plasma testosterone concentrations. CONCLUSION(S): The surrogate estimates of insulin resistance evaluated were significantly related to a direct measure of insulin resistance, and this was true of both the control population and women with PCOS. The magnitude of the relationship between the surrogate estimates and the direct measurement was comparable and not significantly altered by androgen levels. Fasting plasma insulin concentration seems to be at least as accurate as any other surrogate estimate, and is by far the simplest.

Antineoplastic influence of nimesulide in chemically induced hepatocellular carcinoma by inhibition of DNA synthesis.

Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150 mg/kg) intraperitoneally. Duration of the in vivo study was 12 weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [3H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE2 effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).

Melastoma malabathricum Linn attenuates complete freund's adjuvant-induced chronic inflammation in Wistar rats via inflammation response.

BACKGROUND: Natural products use for arthritis treatment is gaining importance in the medical worldt. Various studies reports medical importance of Melastoma malabathricum Linn. (MM) (Melastomataceae), also known as "putki," has a broad range of health benefits, for its free radical scavenging constituents. The current investigation scrutinizes the antioxidant and anti-inflammatory effect of MM against adjuvant-induced arthritis in experimental rats. METHODS: High-performance thin layer chromatography (HPTLC) was used for estimation of phytochemical-constituents present in the MM extract. Protective effect of MM extract in Wistar rats was estimated using CFA-induced model. The rats were divided into different groups with six rats in each group. All animals received oral administration of MM and indomethacin for 28 days. The body weight and arthritic score were scrutinized at regular intervals. At the end of experimental protocol, the rats were sacrificed, and blood samples were used for antioxidant, hematological parameters, pro-inflammatory and inflammatory mediator, respectively. Histopathological observation was used to evaluate the protective effect of MM extract. RESULT & DISCUSSION: Current study confirmed the preventive effect of MM against adjuvant-induced paw edema, paw redness and arthritic progression. MM significantly (P < 0.001) modulated the oxidative stress parameters as well as hematological parameter induced by CFA. The result also altered the distorted level of proinflammatory mediators and inflammatory mediator, which further reinforce the implication of MM in CFA induced arthritis. Histological analyses of joints of rats showed a reduction in the synovial hyperplasia and mononuclear infiltration in the MM treated group which provides evidence for the antiarthritic effect of MM. CONCLUSION: From above parameters our study states that the MM is capable of restraining the alteration produced via adjuvant-induced arthritis in aminals. The repressing effect of MM could be attributed, at least in part, to antioxidant, hematological and anti-inflammatory effect. Figure Caption: Melastoma Malabathricum Linn Attenuates Complete Freund's Adjuvant-Induced Chronic Inflammation in Wistar rats by Inflammation Response.

Quantification of cells with specific phenotypes II: determination of CD4 expression level on reconstituted lyophilized human PBMC labelled with anti-CD4 FITC antibody.

This report focuses on the characterization of CD4 expression level in terms of equivalent number of reference fluorophores (ERF). Twelve different flow cytometer platforms across sixteen laboratories were utilized in this study. As a first step the participants were asked to calibrate the fluorescein isothiocyanate (FITC) channel of each flow cytometer using commercially available calibration standard consisting of five populations of microspheres. Each population had an assigned value of equivalent fluorescein fluorophores (EFF denotes a special case of the generic term ERF with FITC as the reference fluorophore). The EFF values were assigned at the National Institute of Standards and Technology (NIST). A surface-labelled lyophilized cell preparation was provided by the National Institute of Biological Standards and Control (NIBSC), using human peripheral blood mononuclear cells (PBMC) pre-labeled with a FITC conjugated anti-CD4 monoclonal antibody. Three PBMC sample vials, provided to each participant, were used for the CD4 expression analysis. The PBMC are purported to have a fixed number of surface CD4 receptors. On the basis of the microsphere calibration, the EFF value of the PBMC samples was measured to characterize the population average CD4 expression level of the PBMC preparations. Both the results of data analysis performed by each participant and the results of centralized analysis of all participants' raw data are reported. Centralized analysis gave a mean EFF value of 22,300 and an uncertainty of 750, corresponding to 3.3% (level of confidence 68%) of the mean EFF value. The next step will entail the measurement of the ERF values of the lyophilized PBMC stained with labels for other fluorescence channels. The ultimate goal is to show that lyophilized PBMC is a suitable biological reference cell material for multicolor flow cytometry and that it can be used to present multicolor flow cytometry measurements in terms of ABC (antibodies bound per cell) units.

Effect of liraglutide administration and a calorie-restricted diet on lipoprotein profile in overweight/obese persons with prediabetes.

BACKGROUND AND AIMS: To evaluate the effects of 14 weeks of liraglutide plus modest caloric restriction on lipid/lipoprotein metabolism in overweight/obese persons with prediabetes. METHODS AND RESULTS: Volunteers with prediabetes followed a calorie-restricted diet (-500 Kcal/day) plus liraglutide (n = 23) or placebo (n = 27) for 14 weeks. The groups were similar in age (58 ± 7 vs. 58 ± 8 years) and body mass index (31.9 ± 2.8 vs. 31.9 ± 3.5 kg/m(2)). A comprehensive lipid/lipoprotein profile was obtained before and after intervention using vertical auto profile (VAP). Weight loss was greater in the liraglutide group than in the placebo group (6.9 vs. 3.3 kg, p < 0.001), as was the fall in fasting plasma glucose concentration (9.9 mg/dL vs. 0.3 mg/dL, p < 0.001). VAP analysis revealed multiple improvements in lipid/lipoprotein metabolism in liraglutide-treated compared with placebo-treated volunteers, including decreases in concentrations of total cholesterol, low-density lipoprotein cholesterol and several of its subclasses, triglyceride, and non-high-density cholesterol. The liraglutide-treated group also had a significant shift away from small, dense low-density lipoprotein-particles, as well as decreases in apolipoprotein B concentration and ratio of apolipoprotein B/apolipoprotein A-1. There were no significant changes in the lipoprotein profile in the placebo-treated group. CONCLUSION: Treatment with liraglutide plus modest calorie restriction led to enhanced weight loss, a decrease in fasting plasma glucose concentration, and improvement in multiple aspects of lipid/lipoprotein metabolism associated with increased cardiovascular disease (CVD) risk. The significant clinical benefit associated with liraglutide-assisted weight loss in a group at high risk for CVD - obese/overweight individuals with prediabetes - as seen in our pilot study, suggests that this approach deserves further study.

Malvidin attenuates behavioral and inhibits the TNF-α/Caspase-3/Nrf-2 expression in rotenone-induced Parkinson's disease in rats: insights from molecular docking.

OBJECTIVE: Malvidin is a natural, biologically active polyphenol found in several fruits. It exhibits several therapeutic benefits; however, limited studies are available on its effects on neurodegenerative clinical conditions, including Parkinson's disease. The study aimed to investigate the therapeutic properties of malvidin on rotenone-triggered Parkinson's disease in an animal model. MATERIALS AND METHODS: To determine the effects of malvidin, rotenone (1.5 mg/kg) was injected subcutaneously into Wistar rats for 21 days, followed by a dose of malvidin (200 and 100 mg/kg). Behavioral tests were performed on the experimental animals before sacrifice. On the 22nd day of the experiment, biochemical tests were performed, including superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT). The activity of neurotransmitters and their metabolites, including acetylcholine (ACh), acetylcholinesterase (AChE), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) along with neuroinflammatory markers including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor- α (TNF-α), and nuclear factor erythroid 2-related factor 2 (Nrf-2) were estimated. Moreover, the level of the apoptotic marker, caspase-3, was also estimated. In addition, molecular docking was performed. RESULTS: The administration of rotenone resulted in oxidative stress, cholinergic imbalances, dopaminergic alternations, and increased expression of inflammatory compounds. The docking analysis revealed that malvidin displayed a favorable binding affinity for AChE, showcasing a binding energy of -9.329 Kcal/mol. CONCLUSIONS: The investigation concludes that malvidin exhibits neuroprotective effects due to its curative effects against inflammation and oxidative stress. These findings suggest that malvidin possesses therapeutic potential against rotenone-triggered behavioral, oxidative, and inflammatory abnormalities in rodents.

Butin attenuates behavioral disorders via cholinergic/BDNF/Caspase-3 pathway in scopolamine-evoked memory deficits in rats.

OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.

Fustin alleviates lipopolysaccharide-induced anxiety-depression-like performances by modulation of oxidative stress/neuroinflammatory markers/ NF-κB/caspase-3/BDNF expression in rodents.

OBJECTIVE: Anxiety and depression are common psychiatric disorders that affect millions of people worldwide. Lipopolysaccharide (LPS) is a bacterial endotoxin that has been demonstrated to cause depression and anxiety-like behaviors in animal models. Fustin is a flavonoid found in various plant species that have been reported to have neuroprotective effects. The study proposed the evaluation of fustin's impact on anxiety and depression in LPS-injected rats. MATERIALS AND METHODS: The efficacy of fustin in higher and lower doses was studied by administering a single dose of LPS-injected anxiety/depression in rodents. Behavioral models like the elevated plus maze test, open field test, marble burying test, force swimming test, tail suspension test, and hyperemotionality behavior were performed to evaluate anxiety/depression in rodents. The neuroinflammatory markers such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), apoptosis marker caspase-3, and brain-derived neurotrophic factor (BDNF) were also measured as a part of the study. Additionally, biochemical markers of oxidative stress, such as malonaldehyde (MDA) and antioxidants, including superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and nitric oxide (NO), were also evaluated. RESULTS: LPS administration resulted in significant (p<0.001) changes in behavior tests and biochemical markers including IL-1ß, IL-6, NF-κB, TNF-α, NO, caspase-3, BDNF, MDA, CAT, SOD, and GSH. In contrast, treating the rats with fustin significantly improved the behavior tests and restored the changes in biochemical markers. CONCLUSIONS: The current work established the efficacy of fustin with its therapeutic impact on depression and anxiety-like behaviors in rodent experimental models through its modulation of apoptosis markers, oxidative stress, and neuroinflammation.

Protective effect of sterubin against neurochemical and behavioral impairments in rotenone-induced Parkinson's disease.

This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.

Organoleptic characteristics and compositional profile of meat of growing Japanese quail fed different levels of poultry byproducts compost.

The poultry industry generates a lot of waste, including dead birds, manure, and poultry litter. Poultry waste should never be disposed of improperly because it can seriously harm the environment. The waste can be recycled as a feedstock for use in poultry feed by composting the litter and deceased birds. The compositional profile and organoleptic properties of the meat of growing Japanese quail were examined over the course of a 4-week trial to ascertain the effect of adding compost to the diet. In a completely randomized design (CRD), 1200 newly hatched quail chicks (Coturnix coturnix japonica) were divided into five treatment groups (diets with 0, 2.5, 5, 7.5, and 10% compost), each consisting of 40 birds with six replicates. The addition of compost to the diet had no noticeable effects on the organoleptic qualities of appearance, color, aroma, taste, texture, juiciness, tenderness, and acceptability (P>0.05). The compositional profile characteristics for chicks given compost at any level compared to chicks fed the control diet showed no differences (P>0.05). These findings suggest that the sensory characteristics and compositional profile of growing meat quails can be maintained when fed diets including up to 10% compost.

Assessing effect of feeding poultry byproducts compost on organoleptic characteristics and compositional profile of meat of broiler chickens.

Large amounts of waste, including dead birds, manure, and poultry litter, are produced by the poultry industry. Poultry waste should be disposed of properly to avoid major pollution and health risks. Composting litter and dead birds could be an option to recycle the waste and use in poultry feed. A study was conducted to investigate the effects of feeding composted poultry waste on the organoleptic qualities and compositional profile of the meat of broiler chickens. A total of 300 day-old broiler chicks (500-Cobb) were randomly allocated to five treatment groups replicated six times with 10 birds each, under a completely randomized design (CRD). Five iso-caloric and iso-nitrogenous diets including composted poultry byproducts at concentrations of 0, 2.5, 5, 7.5, and 10% were fed ad libitum to the birds from day 0 to day 35. The sensory grading and meat composition profile of 500 Cobb broiler chickens were tested at 35 days of age. The findings showed that there were no variations in the sensory profiles of the meat from birds given various diets (P>0.05). Although the results were somewhat lower for the chicks fed compost-containing diets than for the control group, this difference was deemed to be insignificant (P>0.05). Similarly, there were no variations in the compositional profile values of the meat between meat from birds fed various diets (P>0.05). These findings imply that broiler chickens may be raised on diets containing up to 10% poultry byproduct compost without any negative impacts on the meat's sensory quality or composition. Additionally, using compost into broiler diets may help to lower the cost of feed.

Protective effect of barbigerone against ethanol-induced ulcers via the interleukins/ICAM-1/Bcl-2 pathway.

OBJECTIVE: The objective of the study was to assess the protective effects of barbigerone in ethanol-induced gastric ulcers in rats. MATERIALS AND METHODS: Male Wistar rats (180±20 g) were used in the study (n=06). The rats were randomly divided into different groups, i.e., the normal group, ethanol control, and barbigerone 10 and 20 mg/kg group. Various biochemical parameters were assessed - total acidity and pH values, oxidative stress biomarkers such as superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT) along with markers, i.e., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, intercellular adhesion molecule-1 (ICAM-1) and expression of B-Cell Leukemia/Lymphoma 2 (Bcl-2). Also, histopathology was performed. RESULTS: Treatment with barbigerone in the ethanol-induced-ulcer rats restored the levels of biochemical parameters such as SOD, GSH, MDA, CAT, and markers expression, including TNF-α, IL-6, IL-1ß, ICAM-1, and Bcl-2 with protected against cellular necrosis. CONCLUSIONS: Barbigerone protective effects can be attributed to its ability to reduce oxidative stress and inflammation, as well as promote gastroprotection against ethanol-induced ulcers in rats.

Adiposity indices in the prediction of metabolic abnormalities associated with cardiovascular disease in non-diabetic adults.

BACKGROUND AND AIMS: The prevalence of insulin resistance and cardiovascular disease (CVD) increases with degree of obesity. Whether measurements of generalized and abdominal obesity differ in the ability to predict changes associated with increased CVD risk is widely debated. We compared the prevalence of metabolic abnormalities in 275 women and 204 men stratified by categories of body mass index (BMI) and waist circumference (WC), and assessed the ability of these adiposity indices in combination with metabolic risk variables to predict insulin resistance. METHODS AND RESULTS: Healthy, non-diabetic volunteers underwent measurements of BMI, WC, blood pressure, fasting plasma glucose (FPG), lipoprotein concentrations, and direct quantification of insulin-mediated glucose uptake. Insulin resistance was defined as the top tertile of steady-state plasma glucose (SSPG) concentrations. BMI and WC were highly correlated (P < 0.001) in both women and men. Abnormal SSPG and triglyceride concentrations were associated with increasing adiposity by either index in both genders. Among women, abnormal FPG and high density lipoprotein cholesterol (HDL-C) concentrations were associated with increasing BMI and WC. In men, abnormal HDL-C was associated with increasing BMI only. Elevated systolic blood pressure (SBP) was associated with increasing BMI in both genders. The odds of insulin resistance were greatest in women with elevated FPG and triglycerides (4.5-fold). In men, the best predictors were BMI and SBP, and WC and HDL-C (3-fold). CONCLUSION: BMI is at least comparable to WC in stratifying individuals for prevalence of metabolic abnormalities associated with increased CVD risk and predicting insulin resistance.

Multi-layer PDMS films having antifouling property for biomedical applications.

Poly(dimethylsiloxane) (PDMS) elastomer is now a well-known material for packaging implantable biomedical micro-devices owing to unique bulk properties such as biocompatibility, low toxicity, excellent rheological properties, good flexibility, and mechanical stability. Despite the desirable bulk characteristics, PDMS is generally regarded as a high-flux material for oxygen and water vapor to penetrate compared with other polymeric barrier materials, which is related to the defect-induced penetration through the packaging coating prepared by the traditional deposition techniques. Besides, its hydrophobic nature causes serious fouling problems and limits the practical application of PDMS-based devices. In this work, the performance of silicone thin films as a packaging layer was improved by the fabrication of the roller-casted multiple thin layers to minimize a defect-induced failure. To confer hydrophilicity and cell fouling resistance, high-density and well-defined poly(oligo(ethylene glycol) methacrylate) (POEGMA) brushes were tethered via the surface-initiated atom transfer radical polymerization (SI-ATRP) technique on the roller-casted multiple thin PDMS layers. The characteristics of fabricated substrates were determined by static water contact angle measurement, X-ray photoelectron spectroscopy, and attenuated total reflection-Fourier transform infrared spectroscopy. In vitro cell behavior of POEGMA-grafted PDMS substrates was evaluated to examine cell-fouling resistance.

Interconnected porous nanofibrous gelatin scaffolds prepared via a combined thermally induced phase separation/particulate leaching method.

To mimic the fibrous architecture of collagen, the nanofibrous gelatin scaffolds are fabricated employing a thermally induced phase separation (TIPS) technique. The influences of processing parameters, including polymer concentration and solvent mixture composition on the scaffold microstructure are investigated. However, using the TIPS technique, a limited pore size range is generally obtained. To yield the well-interconnected macroporous structures with equiaxed pores and nanofibrous architectures, the TIPS technique is combined with particulate leaching. The macroporous structure of produced scaffolds duplicates the predefined three-dimensional template structure. The homogenous macrostructure with well-interconnected equiaxed pores and no particular orientation is created. Modulating the size and shape of microspheres has precise control over porosity, pore size, and interconnection of the matrix. Because of the well-interconnected macroporous nanofibrous structure, the useful applications of these scaffolds in the tissue engineering field are expected.

Chemopreventive effects of Melastoma malabathricum L. extract in mammary tumor model via inhibition of oxidative stress and inflammatory cytokines.

The objective of this study was to evaluate the anticancer effects of Melstoma malabathricum L. (MM) MDA-MB-231 human breast cancer and in vivo mammary tumor model and decipher the potential mechanism. The phyto-constituents in the extract have been identified by liquid chromatography-mass spectrometry (LC-MS). The anti-cancer activity of MM extract was tested on MDA-MB-231 human breast cancer cells. Chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was used for the induction of breast cancer in rodents. Burden, volume, tumor incidence, pro-inflammatory cytokines, antioxidant parameters and mitochondrial parameters were estimated. Histological analysis was determined in mammary gland, vagina, uterus, heart, liver, lung and renal tissues. LC-MS showed the 21 phyto-constituents present in the extract of MM. MM extract showed the potent cytotoxicity against MDA-MB-231 cells and exhibited the IC50 value (14.6 µM). MM extract significantly decreased the body weight and altered the organ weight such as ovary, uterus, liver, spleen, lungs, renal, adrenal and brain tissue. MM extract significantly down-regulated the tumor incidence, tumor burden and average tumor weight at dose dependently manner. MM extract significantly altered the antioxidants activity in term of augmented the level of superoxide dismutase (SOD), catalase (CAT) and suppressed the level of malonaldehyde (MDA); pro-inflammatory cytokines levels such as reduced the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) in the serum, hepatic and mammary gland tissue in DMBA induced mammary gland tumor rats. MM extract significantly (P < 0.001) enhanced the activity of mitochondrial parameters include Isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), Malate dehydrogenase (MDH) and alpha-keto glutaraldehyde dehydrogenase (α-KGDH). The histopathological finding exhibited that MM extract has a marked reduced effect on mammary glands, mammary gland, vagina, uterus, heart, liver, lung and renal.These data provide the scientific evidence that MM extract might be used as a traditional medicine to cure the breast cancer.

Pioglitazone decreases postprandial accumulation of remnant lipoproteins in insulin-resistant smokers.

BACKGROUND: Fasting hypertriglyceridaemia has been reported to occur commonly in cigarette smokers and is thought to increase cardiovascular disease (CVD) risk in these individuals. More recently, it has been suggested that an increase in non-fasting triglycerides, rather than fasting hypertriglyceridaemia, is an independent CVD risk factor. METHODS: In this study, we divided 24 smokers into insulin-resistant (IR) and insulin-sensitive (IS) groups by determining their steady-state plasma glucose concentrations during the insulin suppression test and compared fasting and daylong postprandial accumulation of total triglycerides and remnant lipoprotein (RLP) concentrations, before and after 3 months of pioglitazone (PIO) administration. RESULTS: The two groups were similar in age, body mass index, race and gender distribution, but differed dramatically in insulin sensitivity. Baseline fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride concentrations were significantly higher in the IR smokers (p=0.01 to <0.01). Insulin resistance [corrected] and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p=0.05 to 0.01) [corrected] in PIO-treated IR smokers, without any significant increase in weight instead of insulin sensitivity and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p = 0.05 to, 0.01) in PIO-treated IR smokers, without any significant increase in weight. [corrected] CONCLUSIONS: The postprandial accumulation of RLP particles is increased in the IR subset of smokers and is likely to contribute to the increased CVD risk in these individuals. Furthermore, PIO administration provides a possible therapeutic approach to decreasing postprandial lipaemia and CVD risk in IR smokers who are unwilling or unable to stop smoking.