Facile solution-phase synthesis of γ-Mn3O4 hierarchical structures

<p>Abstract</p> <p>Background</p> <p>A lot of effort has been focused on the integration of nanorods/nanowire as building blocks into three-dimensional (3D) complex superstructures. But, the development of simple and effective methods for creating novel assemblies of self-supported patterns of hierarchical architectures to designed materials using a suitable chemical method is important to technology and remains an attractive, but elusive goal.</p> <p>Results</p> <p>The hierarchical structure of Mn₃O₄with radiated spherulitic nanorods was prepared via a simple solution-based coordinated route in the presence of macrocycle polyamine, hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene (CT) with the assistance of thiourea as an additive.</p> <p>Conclusion</p> <p>This approach opens a new and facile route for the morphogenesis of Mn₃O₄material and it might be extended as a novel synthetic method for the synthesis of other inorganic semiconducting nanomaterials such as metal chalcogenide semiconductors with novel morphology and complex form, since it has been shown that thiourea can be used as an effective additive and the number of such water-soluble macrocyclic polyamines also makes it possible to provide various kinds of ligands for different metals in homogeneous water system.</p

Inter-Observer Agreement on Subjects' Race and Race-Informative Characteristics

Health and socioeconomic disparities tend to be experienced along racial and ethnic lines, but investigators are not sure how individuals are assigned to groups, or how consistent this process is. To address these issues, 1,919 orthodontic patient records were examined by at least two observers who estimated each individual's race and the characteristics that influenced each estimate. Agreement regarding race is high for African and European Americans, but not as high for Asian, Hispanic, and Native Americans. The indicator observers most often agreed upon as important in estimating group membership is name, especially for Asian and Hispanic Americans. The observers, who were almost all European American, most often agreed that skin color is an important indicator of race only when they also agreed the subject was European American. This suggests that in a diverse community, light skin color is associated with a particular group, while a range of darker shades can be associated with members of any other group. This research supports comparable studies showing that race estimations in medical records are likely reliable for African and European Americans, but are less so for other groups. Further, these results show that skin color is not consistently the primary indicator of an individual's race, but that other characteristics such as facial features add significant information

Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity

ACE2-Mediated Reduction of Oxidative Stress in the Central Nervous System Is Associated with Improvement of Autonomic Function

Oxidative stress in the central nervous system mediates the increase in sympathetic tone that precedes the development of hypertension. We hypothesized that by transforming Angiotensin-II (AngII) into Ang-(1–7), ACE2 might reduce AngII-mediated oxidative stress in the brain and prevent autonomic dysfunction. To test this hypothesis, a relationship between ACE2 and oxidative stress was first confirmed in a mouse neuroblastoma cell line (Neuro2A cells) treated with AngII and infected with Ad-hACE2. ACE2 overexpression resulted in a reduction of reactive oxygen species (ROS) formation. In vivo, ACE2 knockout (ACE2−/y) mice and non-transgenic (NT) littermates were infused with AngII (10 days) and infected with Ad-hACE2 in the paraventricular nucleus (PVN). Baseline blood pressure (BP), AngII and brain ROS levels were not different between young mice (12 weeks). However, cardiac sympathetic tone, brain NADPH oxidase and SOD activities were significantly increased in ACE2−/y. Post infusion, plasma and brain AngII levels were also significantly higher in ACE2−/y, although BP was similarly increased in both genotypes. ROS formation in the PVN and RVLM was significantly higher in ACE2−/y mice following AngII infusion. Similar phenotypes, i.e. increased oxidative stress, exacerbated dysautonomia and hypertension, were also observed on baseline in mature ACE2−/y mice (48 weeks). ACE2 gene therapy to the PVN reduced AngII-mediated increase in NADPH oxidase activity and normalized cardiac dysautonomia in ACE2−/y mice. Altogether, these data indicate that ACE2 gene deletion promotes age-dependent oxidative stress, autonomic dysfunction and hypertension, while PVN-targeted ACE2 gene therapy decreases ROS formation via NADPH oxidase inhibition and improves autonomic function. Accordingly, ACE2 could represent a new target for the treatment of hypertension-associated dysautonomia and oxidative stress

An Analysis of Enzyme Kinetics Data for Mitochondrial DNA Strand Termination by Nucleoside Reverse Transcription Inhibitors

Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-γ hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-γ) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-γ with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication

Asthma susceptible genes in Chinese population: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population.</p> <p>Methods</p> <p>The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications.</p> <p>Results</p> <p>Seven polymorphisms were found being associated with risk of asthma, namely: <it>A Disintegrin and Metalloprotease 33 </it>(<it>ADAM33</it>) T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73), <it>Angiotensin-Converting Enzyme </it>(<it>ACE</it>) D/I (OR = 3.85, 95%CI: 2.49-5.94), <it>High-affinity IgE receptor β chain </it>(<it>FcεRIβ</it>) -6843G/A (OR = 1.49, 95%CI: 1.01-2.22), <it>Interleukin 13</it>(<it>IL-13</it>) -1923C/T (OR = 2.99, 95%CI: 2.12-4.24), <it>IL-13 </it>-2044A/G (OR = 1.49, 95%CI: 1.07-2.08), <it>Regulated upon Activation, Normal T cell Expressed and Secreted </it>(<it>RANTES</it>) -28C/G (OR = 1.64, 95%CI: 1.09-2.46), <it>Tumor Necrosis Factor-α </it>(<it>TNF-α</it>) -308G/A(OR = 1.42, 95%CI: 1.09, 1.85). After subgroup analysis by age, the <it>ACE </it>D/I, <it>β2-Adrenergic Receptor </it>(<it>β2-AR</it>) -79G/C, <it>TNF-α </it>-308G/A, <it>Interleukin 4 receptor</it>(<it>IL-4R</it>) -1902G/A and <it>IL-13 </it>-1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the <it>ACE </it>D/I, <it>FcεRIβ </it>-6843G/A, <it>TNF-α </it>-308G/A, <it>IL-13 </it>-1923C/T and <it>IL-13 </it>-2044A/G polymorphisms were associated with asthma risk in Chinese adults.</p> <p>Conclusion</p> <p><it>ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R </it>and <it>IL-13 </it>genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.</p

Herbal Medicines for Parkinson's Disease: A Systematic Review of Randomized Controlled Trials

OBJECTIVE: We conducted systematic review to evaluate current evidence of herbal medicines (HMs) for Parkinson's disease (PD). METHODS: Along with hand searches, relevant literatures were located from the electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED, PsycInfo, CNKI, 7 Korean Medical Databases and J-East until August, 2010 without language and publication status. Randomized controlled trials (RCTs), quasi-randomized controlled trials and randomized crossover trials, which evaluate HMs for idiopathic PD were selected for this review. Two independent authors extracted data from the relevant literatures and any disagreement was solved by discussion. RESULTS: From the 3432 of relevant literatures, 64 were included. We failed to suggest overall estimates of treatment effects on PD because of the wide heterogeneity of used herbal recipes and study designs in the included studies. When compared with placebo, specific effects were not observed in favor of HMs definitely. Direct comparison with conventional drugs suggested that there was no evidence of better effect for HMs. Many studies compared combination therapy with single active drugs and combination therapy showed significant improvement in PD related outcomes and decrease in the dose of anti-Parkinson's drugs with low adverse events rate. CONCLUSION: Currently, there is no conclusive evidence about the effectiveness and efficacy of HMs on PD. For establishing clinical evidence of HMs on PD, rigorous RCTs with sufficient statistical power should be promoted in future

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting