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At 3 years of follow-up, among obese patients with uncontrolled type 2 diabetes who were randomly assigned to receive intensive medical therapy with or without bariatric surgery, significantly more patients in the surgery groups achieved glycemic control. Bariatric surgery has recently emerged as a potentially useful treatment for type 2 diabetes mellitus. 1 Observational studies 2 – 5 and randomized, controlled trials 6 – 10 have shown that procedures including Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding, and biliopancreatic diversion significantly improve glycemic control and favorably affect cardiovascular risk factors. In the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, we found that 1 year after randomization, gastric bypass and sleeve gastrectomy were superior to intensive medical therapy alone in achieving glycemic control and reducing cardiovascular risk factors while decreasing dependency on pharmacotherapy for diabetes management. 7 Although bariatric surgery yields . . .

Cancer stem cells (CSCs) have been suggested as responsible for the initiation and progression of cancers. Octamer-binding transcription factor 4 (Oct4) is an important regulator of embryonic stem cell fate. Here, we investigated whether Oct4 regulates stemness of head and neck squamous carcinoma (HNSC) CSCs. Our study showed that ectopic expression of Oct4 promotes tumor growth through cyclin E activation, increases chemoresistance through ABCC6 expression and enhances tumor invasion through slug expression. Also, Oct4 dedifferentiates differentiated HNSC cells to CSC-like cells. Furthermore, Oct4 high  HNSC CSCs have more stem cell-like traits compared with Oct4 low cells, such as self-renewal, stem cell markers' expression, chemoresistance, invasion capacity and xenograft tumorigeneity in vitro and in vivo . In addition, knockdown of Oct4 led to markedly lower HNSC CSC stemness. Finally, there was a significant correlation between Oct4 expression and survival of 119 HNSC patients. Collectively, these data suggest that Oct4 may be a critical regulator of HNSC CSCs and its targeting may be potentially valuable in the treatment of HNSC CSCs.

Coronary-artery dissections account for less than 1% of acute myocardial infarctions, occur most commonly in women and most often between the ages of 47 and 53 years, may be associated with an underlying disorder such as fibromuscular dysplasia and other noncoronary arterial abnormalities, and are usually treated medically.

Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ-transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-κB (NF-κB) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes ( bcl-2 , X-chromosome inhibitor of apoptosis protein ( IAP ), cellular IAP and cellular FADD-like IL-1β-converting enzyme-inhibitory protein , cyclin D ), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes ( caspase-3 and -9 , bax ) increased. In tumor, spleen and blood, the number of cytotoxic CD8 + T cells and CD57 + natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-κB and STAT3 in vitro . In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.

Proneurogenic compounds have recently shown promise in some mouse models of Alzheimer’s pathology. Antagonists at Group II metabotropic glutamate receptors (Group II mGluR: mGlu 2 , mGlu 3 ) are reported to stimulate neurogenesis. Agonists at those receptors trigger γ-secretase-inhibitor-sensitive biogenesis of Aβ42 peptides from isolated synaptic terminals, which is selectively suppressed by antagonist pretreatment. We have assessed the therapeutic potential of chronic pharmacological inhibition of Group II mGluR in Dutch APP (Alzheimer’s amyloid precursor protein E693Q) transgenic mice that accumulate Dutch amyloid-β (Aβ) oligomers but never develop Aβ plaques. BCI-838 is a clinically well-tolerated, orally bioavailable, investigational prodrug that delivers to the brain BCI-632, the active Group II mGluR antagonist metabolite. Dutch Aβ-oligomer-forming APP transgenic mice (APP E693Q) were dosed with BCI-838 for 3 months. Chronic treatment with BCI-838 was associated with reversal of transgene-related amnestic behavior, reduction in anxiety, reduction in levels of brain Aβ monomers and oligomers, and stimulation of hippocampal neurogenesis. Group II mGluR inhibition may offer a unique package of relevant properties as an Alzheimer’s disease therapeutic or prophylactic by providing both attenuation of neuropathology and stimulation of repair.

Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT–PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo . Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.

Rigid polyurethane foam (RPUF)/glass fiber composites have been fabricated from glass fiber, polymeric 4,4′-di-phenylmethane diisocyanate (PMDI) and polypropylene glycols (PPG) using HFC 365mfc as blowing agent. Thermal conductivity, glass transition and decomposition temperatures as well as the mechanical strengths of the foam increased with the addition of glass fiber. This indicates that an optimum fiber content should depend on the balance between the mechanical reinforcement and thermal insulation.The results were interpreted in terms of cell size, closed cell content, density, fiber dispersion and a simple series model for heat transfer of the composite foam.

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including Aβ42 and γ-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae . We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including α-synuclein (α-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS , and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion ( HTT gene; htt-103Q). Latrepirdine effects on α-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wild-type mice. Latrepirdine only protected yeast against the cytotoxicity associated with α-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of α-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate α-syn accumulation in transgenic mouse models of α-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust pro-autophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.

Ginseng is beneficial for many aspects of human physiology, including sexual function. In this study, we have evaluated the efficacy and safety of an extract of ginseng berry, which has a ginsenoside profile distinct from other parts of the plant, on sexual function in men with erectile dysfunction. In all, 119 men with mild-to-moderate ED participated in a multicenter, randomized, double-blind, parallel, placebo-controlled clinical study. They were administered 4 tablets of either standardized Korean ginseng berry (SKGB, 350 mg ginseng berry extract per tablet), or placebo, daily, for 8 weeks. Efficacy was assessed with the International Index of Erectile Function (IIEF)-15 and premature ejaculation diagnostic tool (PEDT) at the end of the 4th and 8th week. We observed that the total and each of the individual domain scores of IIEF-15 increased from 40.95±7.05 to 46.19±12.69 significantly in the SKGB by the 8th week ( P <0.05). The erectile function domain of IIEF changed slightly from 17.17±2.57 to 18.59±5.99 in the SKGB group by the 8th week ( P <0.05). In addition, PEDT scores significantly improved from 9.14±4.57 to 7.97±4.4 and 7.53±4.26 in the SKGB group after 4 and 8 weeks of treatment ( P <0.05). Safety markers including hormone and lipid in the blood were assessed at the end of the 4th and 8th week and they remained unchanged. Oral administration of the SKGB extract improved all domains of sexual function. It can be used as an alternative medicine to improve sexual life in men with sexual dysfunction.