Insights into the Age-Dependent Variation in Nutrition-Related Trace Elements in Diabetes Blood Using Total Reflection X-Ray Fluorescence.

The prevalence of diabetes has reached alarming levels in India, making it essential to understand the concentration of nutritional-trace elements (Fe, Cu, Zn, Cr. and Se) in blood samples from diabetic adults. In this study, 208 whole blood samples from diabetic (n = 104) and non-diabetic (n = 104) adults across various age groups were analyzed using total reflection X-ray fluorescence (TXRF) spectroscopy with a sample dilution method. Statistical analysis was performed to assess descriptive statistics and determine a significant correlation between elemental concentrations in the blood samples of diabetic and non-diabetic adults. The mean concentration of nutritional-related trace elements in diabetic blood was as follows: Fe (46 ± 5) > Zn (1.28 ± 0.14) > Cu (0.10 ± 0.01) > Cr (0.05 ± 0.004) > Se (0.013 ± 0.001) in mg/L, respectively. Additionally, this study investigated the influence of nutrition-related trace element concentrations across various age groups such as 25-40 years (young adults), 41-55 years (middle-aged adults), and 56-70 years (older adults). In this investigation, Zn (p < 0.001) and Cr (p < 0.05) concentrations differed significantly between diabetic and non-diabetic adults aged 56-70 years. These findings will help us to understand age-dependent changes in element concentrations, clarify their role in diabetes, and improve risk factor management associated with diabetes.

LncRNA SNHG7 participates in osteosarcoma progression by down-regulating p53 via binding to DNMT1.

OBJECTIVE: This study aims to explore the role of lncRNA SNHG7 in the development of osteosarcoma, and its underlying mechanism. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect SNHG7 expression in tumor tissues and paracancerous tissues harvested from osteosarcoma patients. Meanwhile, the relationship between SNHG7 expression and tumorigenesis was analyzed. The effects of SNHG7 and p53 on cell proliferation, cell cycle and apoptosis were detected by plate cloning and flow cytometry, respectively. The binding relationship between SNHG7 and DNMT1, as well as the regulatory mechanism of DNMT1 on p53, were detected by RIP and ChIP. Western blot was conducted to detect the expression of p53 after the knockdown of SNHG7 in osteosarcoma cells. Rescue experiments were finally conducted to verify whether SNHG7 exerted its biological function by targeting p53. RESULTS: QRT-PCR results demonstrated that the expression of SNHG7 in osteosarcoma tissues was remarkably higher than that in paracancerous tissues. Moreover, SNHG7 expression in osteosarcoma with stage III and IV was higher than those in stage I and II. The inhibition of SNHG7 in osteosarcoma cells U2OS and HOS promoted cell proliferation, arrested cell cycle in the G0/G1 phase and induced apoptosis. RIP and ChIP experiments illustrated that SNHG7 inhibited the expression of p53 by binding to DNMT1. The overexpression of p53 in U2OS cells partially reversed the promoted cell proliferation and apoptosis caused by SNHG7. CONCLUSIONS: Highly expressed SNHG7 can promote the proliferation and inhibit apoptosis of osteosarcoma cells by regulating p53 expression by binding to DNMT1.

In situ oxidation and reduction of triangular nickel nanoplates via environmental transmission electron microscopy.

Understanding the oxidation and reduction mechanisms of transition metals, such as nickel (Ni), is important for their use in industrial applications of catalysis. A powerful technique for investigating the redox reactive species is in situ environmental transmission electron microscopy (ETEM), where oxidation and reduction can be tracked in real time. One particular difficulty in understanding the underlying reactions is understanding the underlying morphology of the starting structure in a reaction, in particular the defects contained in the material, and the exposed surface facets. Here-in, we use a colloidal nanoparticle synthesis in a continuous flow reactor to form nanoplates of nickel coated with oleylamine as a capping agent. We utilise an in situ heating procedure at 300 °C in vacuum to remove the oleylamine ligands, and then oxidise the Ni nanoparticles at 25 °C with 2 Pa oxygen, and follow the nanoparticles initial oxidation. After that, the nanoparticles are oxidised at 200 and 300 °C, making the size of the oxide shell increase to ∼4 nm. The oxide shell could be reduced under 2 Pa hydrogen at 500 °C to its initial size of ∼1 nm. High temperature oxidation encouraged the nanoparticles to form pure NiO nanoparticles, which occurred via the Kirkendall effect leading to hollowing and void formation.

Direct observations of dynamic PtCo interactions in fuel cell catalyst precursors at the atomic level using E(S)TEM.

Reduction reactions in practical bimetallic platinum-cobalt electrode catalyst precursors containing platinum, cobalt and cobalt oxides in hydrogen at 200, 450 and 700 °C for 6 h have been studied in situ using an aberration corrected environmental (scanning) transmission electron microscope (AC E(S)TEM). Little difference was observed in reduction at 200 °C but during and after reduction at 450 °C, small nanoparticles less than 3 nm in diameter with tetragonal PtCo structures were observed and limited Pt3 Co ordering could be seen on the surfaces of larger nanoparticles. During and after reduction at 700 °C, fully ordered Pt3 Co and PtCo nanoparticles larger than 4 nm were produced and the average nanoparticle size almost trebled relative to the fresh precursor. After reduction at 450 and 700 °C, most nanoparticles were disordered platinum/cobalt alloys with fcc structure. After reduction at 700 °C many of the smallest nanoparticles disappeared suggesting Ostwald ripening had occurred. Mechanisms concerning the thermal transformation of mixed cobalt and platinum species are discussed, offering new insights into the creation of bimetallic platinum-cobalt nanoparticles in fuel cell catalysts.

The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis.

OBJECTIVES: Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. METHODS: We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. RESULTS: With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. CONCLUSIONS: This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures.Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452-463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1.

Association of MMP3 genotype with susceptibility to frozen shoulder: a case-control study in a Chinese Han population.

Genetic factors may play an important role in frozen shoulder etiology, which may involve matrix metalloproteinase-3 (MMP3) gene polymorphisms. In this study, we examined single nucleotide polymorphisms in MMP3 for their association with frozen shoulder susceptibility in a Chinese Han population. The rs591058, rs650108, and rs679620 polymorphisms in the MMP3 gene were genotyped in 112 subjects diagnosed as having frozen shoulder and in 143 healthy controls. rs650108 was found to be significantly associated with an increased risk of frozen shoulder. For other single nucleotide polymorphisms, no statistically significant associations with frozen shoulder were found. In conclusion, our data demonstrated that the MMP3 rs650108 variant was significantly associated with increased frozen shoulder susceptibility in a Chinese Han population.

Increased survival and reduced renal injury in MRL/lpr mice treated with a human Fcγ receptor II (CD32) peptide.

Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease affecting many organs. The deposition in kidney tissue of immune complexes and their interaction with macrophages is thought to trigger the inflammatory response leading to glomerulonephritis. It has been demonstrated that inhibition of this interaction in murine models can alleviate the disease. Six synthetic peptides were derived from the membrane-proximal extracellular domain (EC2) of human Fcγ receptor II (huFcγRII). Of these, one peptide, huRII6, was shown to be a potent competitive inhibitor of IgG binding to recombinant FcγRII in vitro. To examine the possible therapeutic impact of huRII6 in vivo, this peptide, or a control, was given by subcutaneous injection to female MRL/lpr mice from weeks 7 to 36, resulting in an enhanced survival rate compared with control-treated animals and a reduction of proteinuria. Histopathological examination of the kidneys showed a reduction in deposition of immune complexes and preservation of structure. Such a functional peptide should prove useful for examining the role of IgG-FcγR interactions in experimental models of disease and may provide for the development of FcR-targeting drugs to treat autoimmune disorders.

Identification of a linear epitope for Fc-binding in the mouse FcγRIII.

Fc receptors are transmembrane proteins, found on the surfaces of immune cells, that aid in the removal of foreign pathogens by binding to antibody-coated targets via the Fc regions of the antibodies. To identify sites on mouse FcgammaRIII (moFcgammaRIII) alpha-chain that bind to the Fc region, peptides derived from the proximal extracellular domain (EC2) of moFcgammaRIII alpha-chain corresponding to the homologous region of human FcgammaRIIIB alpha-chain were synthesized. Binding of mouse IgG to the different peptides was tested by Dot-blot assay. The effective peptide (119)SFFHNEKSVRYH(130) located in the putative C-C' loop of the EC2 domain was found to bind mouse IgG specifically with an affinity of approximately 5.58 x 10(-5) M and inhibit the binding of mouse IgG to the receptor. Such a functional peptide should be very useful for further understanding the IgG-FcgammaR interaction and development of FcR-targeting drugs.

GC/MS method for the determination of adipate plasticizers in ham sausage and its application to kinetic and penetration studies.

A GC/MS method was developed and successfully validated for the determination of adipate plasticizers in ham sausage migrated from polyvinylidene chloride (PVDC) packaging film. The sample pretreatment includes liquid extraction, solvent evaporation, and reconstitution before and after solid phase extraction (SPE). For the 5 adipate plasticizers studied, the SPE process with Oasis MAX cartridge showed an extraction efficiency from 85.7% to 106%, and the calibration curves are all linear in the range of 5 to 1000 ng/g with correlation coefficients greater than 0.998. The method proved to be accurate and precise; the average intraday recovery ranges from 85.4% to 114.6% with a %CV value from 2.5 to 11.3, and the average interday recovery from 83.6% to 118.5% with a %CV value from 2.8 to 15.6, respectively, for the adipate plasticizers. The method is sensitive and was effectively applied in the kinetic and penetration studies of the adipate plasticizers migrating from food-grade PVDC packaging film into ham sausage. The experimental data showed that approximately 6.8% of dibutyl adipate (DBA) in the packaging film migrated into the ham sausage in 4 mo and the migration reached the innermost portion of the sausage in 6 mo.

Diversity and divergence among the tribal populations of India.

Tribal populations of the Indian subcontinent have been of longstanding interest to anthropologists and human geneticists. To investigate the relationship of Indian tribes to Indian castes and continental populations, we analyzed 45 unlinked autosomal STR loci in 9 tribal groups, 8 castes, and 18 populations from Africa, Europe and East Asia. South Indian tribal populations demonstrate low within-population heterozygosity (range: 0.54 - 0.69), while tribal populations sampled further north and east have higher heterozygosity (range: 0.69 - 0.74). Genetic distance estimates show that tribal Indians are more closely related to caste Indians than to other major groups. Between-tribe differentiation is high and exceeds that for eight sub-Saharan African populations (4.8% vs. 3.7%). Telugu-speaking populations are less differentiated than non-Telugu speakers (F(ST): 0.029 vs. 0.079), but geographic distance was not predictive of genetic affinity between tribes. South Indian tribes show significant population structure, and individuals can be clustered statistically into groups that correspond with their tribal affiliation. These results are consistent with high levels of genetic drift and isolation in Indian tribal populations, particularly those of South India, and they imply that these populations may be potential candidates for linkage disequilibrium and association mapping.

Autoantibodies to amphiphysin I and amphiphysin II in a patient with sensory-motor neuropathy.

A proportion of patients with peripheral neuropathies has circulating autoantibodies directed against neural antigens. In some cases, autoantibodies may play a pathogenic role. We studied a patient with a progressive sensory-motor axonal neuropathy of unknown etiology, looking for circulating autoantibodies against neural antigens and we showed that the patient's serum contained anti-amphiphysin I (AMP I) and amphiphysin II (AMP II) autoantibodies. A sural nerve biopsy revealed an axonal neuropathy. Indirect immunofluorescence experiments with the patient's serum showed a staining of rat axons due to alpha-AMP I autoantibodies and a specific labelling of cytoplasm and Schmidt-Lanterman incisures of Schwann cells due to alpha-AMP II autoantibodies. In conclusion we identified a patient affected by a sensory-motor neuropathy with autoantibodies against both AMP I and AMP II.

Structural elucidation of microporous and mesoporous catalysts and molecular sieves by high-resolution electron microscopy.

Twenty years ago, one of us embarked (Bursill, L. A.; Lodge, E. A.; Thomas, J. M. Zeolitic structures as revealed by high-resolution electron microscopy. Nature 1980, 286, 111-113) on the study of zeolites (renowned for their electron-beam sensitivity) by high-resolution transmission electron microscopy (HRTEM). In the ensuing years, high-resolution imaging aided by optical diffractometry has yielded details of the open framework structures of a number of new aluminosilicate and aluminophosphate molecular sieves and catalysts. The nature of intergrowth and recurrently twinned structures, as well as new types of structural imperfection in hitherto uncharacterized materials, has also been elucidated. With continued improvements in instrumental development, encompassing higher accelerating voltages, better objective lenses and vacua, computational advances, and the arrival of slow-scan CCD detectors, electron crystallographic methods and HRTEM imaging now enable the ab initio three-dimensional structures of micro- and mesoporous solids, with their occluded structure-directing organic species, to be determined. High-resolution scanning transmission electron microscopy using subnanometric probes provides supplementary structural and ultramicro analytical information and electron spectroscopic imaging (at the attogram level). In its high-angle annular dark-field mode, it is capable of locating and determining the composition of individual nanoparticle catalysts (consisting of just a few atoms) supported on porous hosts.

Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts.

BACKGROUND: We evaluated the contribution of endogenous and exogenous nitric oxide (NO) in ischaemia reperfusion (IR) injury and histamine release in the isolated guinea pig heart. METHODS: Ischaemia reperfusion was performed in isolated Langendorff perfused guinea pig heart throughout the ligature of the left anterior descending coronary (LAD) artery for 20 min, and following the release of the ligature for a further 20 min. RESULTS: IR promoted a linear release of lactate dehydrogenase (LDH) and a preferential release of histamine in the reperfusion phase. The amount of nitrite (NO2-, one of the breakdown products of NO) released during IR was significantly lower than in the control hearts. These effects were accompanied by an increase in calcium levels and malonyl-dialdehyde (MDA) production in the left ventricle and by a decrease in cardiac mast cell metachromasia. Perfusion of the hearts with two inhibitors of the nitric oxide synthase pathway, namely N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M) or nitroarginine methylester (L-NAME, 10(-5) M) significantly enhanced histamine and LDH release; these effects were attenuated by co-infusion with L-arginine (10(-4) M) but not D-arginine (10(-4) M), while L-arginine (10(-4) M) alone had no effect. Perfusion of the heart with sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1), glyceryl trinitrate (GTN), all at 10(-5) M, reduced histamine release, LDH release, calcium overload and MDA production induced by IR. These effects were amplified by concomitant perfusion with superoxide dismutase (SOD, 50 IU/ml). CONCLUSION: The endogenous production of NO provides significant myocardial protection from IR injury and histamine release. These effects were mimicked by various NO donors.

Modulation of the immunological response of guinea pig mast cells by carbon monoxide.

Challenge of guinea pig mast cells with antigen under aerobic conditions induced the expected release of histamine and led to a significant increase in intracellular calcium ([Ca2+]i) and cyclic adenosine monophosphate (cAMP) levels. Prior exposure to CO decreased the immunological histamine release. This effect was accompanied by a decrease in the levels of [Ca2+]i and by an increase in the cyclic guanosine monophosphate (cGMP) levels. The exposure of mast cells to nitrogen (N2) did not modify the release of histamine. The CO-mediated inhibition of the immunological release of histamine was reversed by the soluble guanylate cyclase inhibitor (1 H-[1.2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and by oxyhaemoglobin (HbO2). Incubation of mast cells for 4 h with hemin, a heme oxygenase (HO) inducer, resulted in an increase in HO activity, measured as bilirubin production. Hemin abated the immunological release of histamine, in similar fashion to exogenous CO, and increased the cGMP levels. These effects were reversed by ODQ and HbO2. It is proposed that CO from an exogenous or endogenous source stimulates guanylyl cyclase and causes cGMP formation which then induces calcium to be sequestrated so that the [Ca2+]i concentration falls and histamine release is inhibited.

Multiple origins of the mtDNA 9-bp deletion in populations of South India.

The origins and genetic affinities of the more than 500 tribal populations living in South Asia are widely disputed. This may reflect differential contributions that continental populations have made to tribal groups in South Asia. We assayed for the presence of the intergenic COII/tRNALys 9-bp deletion in human mtDNA in 646 individuals from 12 caste and 14 tribal populations of South India and compared them to individuals from Africa, Europe, and Asia. The 9-bp deletion is observed in four South Indian tribal populations, the Irula, Yanadi, Siddi, and Maria Gond, and in the Nicobarese. Length polymorphisms of the 9-bp motif are present in the Santal, Khonda Dora, and Jalari, all of whom live in a circumscribed region on the eastern Indian coast. Phylogenetic analyses of mtDNA control region sequence from individuals with the 9-bp deletion indicate that it has arisen independently in some Indian tribal populations. Other 9-bp deletion haplotypes are likely to be of Asian and African origin, implying multiple origins of the 9-bp deletion in South India. These results demonstrate varying genetic affinities of different South Indian tribes to continental populations and underscore the complex histories of the tribal populations living in South Asia.

Interaction between histamine and nitric oxide in rat mast cells and in isolated guinea pig hearts.

BACKGROUND: Histamine and nitric oxide (NO) are present in guinea pig hearts and in rat mast cells (MCs) of the serosal phenotype. Histamine and NO are simultaneously released upon immunological challenge of isolated hearts of actively sensitised guinea pigs. MCs release histamine in response to antigen and NO in response to stirring. This has prompted us to study the interaction between histamine and NO in rat MCs and in guinea pig hearts. METHODS: The experiments have been carried out in isolated purified rat serosal MCs and in isolated perfused guinea pig hearts. The generation of NO by both preparations has been evaluated as nitrites (NO2-) by means of the Griess reaction. RESULTS: Histamine upregulates the generation of NO both in rat MCs and in guinea pig hearts. The effect is abolished by blocking NO synthase and preferentially mimicked by a selective H2-receptor agonist. A selective H3-receptor agonist downregulates the generation of NO in lipopolysaccharide-pretreated MCs and in bradykinin-pretreated guinea pig hearts. CONCLUSION: A mutual relationship between histamine and NO in allergic inflammation could be envisaged.