iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer.

The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted ß-TrCP-dependent degradation of NRF2 in a glucocorticoid receptor- and a glycogen synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative stress and strongly suppressed the anchorage-independent growth of tumors with KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in combination with rapamycin strongly inhibited the in vitro and in vivo growth of tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for cancers with high NRF2 activity. We also proposed that the use CP and rapamycin in combination could be a potential therapeutic strategy for tumors harboring both KEAP1 and LKB1 mutations.

Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice.

In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7ΔCD11c mice when compared with Atg7f/f mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7ΔCD11c mice compared with those of control Atg7f/f mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7ΔCD11c mice, B6 mice transferred with fecal microbiota of Atg7ΔCD11c mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.

The impact of depression and somatic symptoms on treatment outcomes in patients with chronic prostatitis/chronic pelvic pain syndrome: a preliminary study in a naturalistic treatment setting.

AIM: The aim of this study was to evaluate the impact of depression and somatic symptoms on treatment outcomes in Korean male patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) attending a routine clinical practice. METHODS: This was a 12-week prospective observational study (n = 80). The Korean version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS, the Korean version of the Patient Health Questionnaire-9 (PHQ-9) to assess depression, the Korean version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatisation and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D), specifically the EQ-5D utility index and the EQ-5D visual analogue scale (EQ-5D VAS), to assess quality of life, were utilised and given at baseline and week 12. The primary and secondary end-points in this study were changes in the NIH-CPSI total score from baseline to week 12 according to depression and somatisation. RESULTS: The change in NIH-CPSI total score was significantly higher in those without depression than in those with depression (p = 0.003), with a magnitude of difference of 2.8. The responder rate (a ≥ 4 point decrease in NIH-CPSI total score from baseline) was significantly higher in those without depression (42.9%) than in those with depression (17.2%, p = 0.023). However, significant differences were not observed between the two groups in the other outcome measures or in all study outcomes between subjects with or without somatisation. A logistic regression analysis revealed that the presence or absence of depression may be a principal predictor of response to treatment. CONCLUSION: These preliminary results indicate that depression may have a negative impact on treatment outcome and is a likely predictor of response to treatment in patients with CP/CPPS. However, additional studies with adequate power and improved design are necessary to further support the present findings.

Greater osteoporosis educational outreach is desirable among Chinese immigrants in Chinatown, Chicago.

UNLABELLED: Osteoporosis beliefs were assessed in immigrant Chinese women in Chinatown, Chicago. Results from a survey utilizing the Osteoporosis Health Belief Scale showed that women expressed concern about osteoporosis but lacked both knowledge of preventive care and health motivation. INTRODUCTION: The objective of this study was to assess osteoporosis beliefs in immigrant Chinese women in Chinatown, Chicago. METHODS: In a community-based health fair, osteoporosis knowledge and self-efficacy among postmenopausal Chinese immigrants were assessed using the translated Osteoporosis Health Belief Scale. Bone mineral density (BMD) was assessed with calcaneal ultrasound. RESULTS: The study population included 94 women with mean age of 51 +/- 9 years, mean length of residence in the United States of 9 +/- 7 years, and 73% (n = 76) of whom were recent immigrants. Women expressed concern about the seriousness of osteoporosis and their relative susceptibility to osteoporosis. In particular, women with a prior fracture reported higher seriousness to osteoporosis. Nonetheless, women exhibited low health motivation and low awareness of the benefits of calcium and exercise. Bone densitometry results corresponded to a T score of -1.2 +/- 1.5. Multiple regression analysis revealed that a younger age and longer length of residence in the USA were associated with higher BMD. CONCLUSION: Chinese immigrant women in Chicago exhibit concern regarding osteoporosis, but are unaware of the benefits of calcium and exercise, and exhibit low health motivation. Chinese women in Chinatown lack necessary knowledge about osteoporosis to develop adequate self-efficacy. Public health initiatives should be undertaken among recent immigrant Chinese women.

Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys.

Her-2/neu is a well-characterized tumor-associated antigen, the overexpression of which in human carcinomas correlates with a poor prognosis. Here, we evaluated Her-2/neu-specific humoral and cellular immune responses in immunized monkeys after immunization with nonreplicating adenovirus (AdHM) expressing the extracellular and transmembrane domain of human Her-2/neu (HM) and/or naked DNA vaccine (pHM-hGM-CSF) expressing human granulocyte-macrophage colony-stimulating factor together with HM. Priming of monkeys with AdHM generated Her-2/neu-specific long-lasting antibody production. Furthermore, these Her-2/neu-specific antibodies produced by AdHM immunization, some of which shared epitope specificity with Herceptin, were able to induce antibody-dependent cellular cytotoxicity against Her-2-expressing target cells. Cellular immune responses were elicited in all monkeys immunized with Her-2/neu-expressing vaccine; interferon-gamma was secreted when these splenocytes were restimulated with Her-2/neu-expressing autologous cells, and immunization with AdHM induced Her-2/neu-specific lymphoproliferative responses. Further, immunization with pHM-hGM-CSF before AdHM immunization noticeably enhanced cytotoxic T-lymphocyte activity. In addition, we observed no abnormalities that would indicate that the genetic vaccines had toxic effects in the immunized monkeys. Thus, we can conclude that our genetic vaccines efficiently elicited Her-2/neu-specific humoral and cellular immune responses without causing severe adverse effects in nonhuman primates and that as such they warrant further clinical investigation.

Targeting and immobilization of bioactive peptides on dentin matrix.

The regeneration of structurally/functionally competent tooth root cementum is a critical step for the successful restoration of periodontal attachment. In this study, we tested whether a poly-glutamic acid-rich domain and glutamine-containing transglutaminase substrate can be used to target biologically active peptides to the mineralized root matrix and to bind such peptides covalently to the organic matrix. As a biologically active model molecule, the integrin-binding motif, RGD, was used. The effects of immobilization of such synthetic peptides to the dentin matrix on cementoblastic adhesion in vitro and cementogenesis in vivo were studied. In vitro, cementoblastic adhesion improved significantly when the dentin surface contained covalently bound peptides. In vivo, this bound peptide significantly increased cementum formation compared with that attained in control conditions. Transglutaminase-catalyzed covalent binding of bioactive peptides targeted to mineralized collagenous dentin matrix via the poly-glutamate domain can be readily achieved. This approach offers potential for clinical use in periodontal regeneration.

Growth of well-aligned ZnO nanorods using auge catalyst by vapor phase transportation.

Well-aligned ZnO nanorods have been achieved using new alloy (AuGe) catalyst. Zn powder was used as a source material and it was transported in a horizontal tube furnace onto an AuGe deposited Si substrates. The structural and optical properties of ZnO nanorods were characterized by scanning electron microscopy, high resolution X-ray diffraction, and photoluminescence. ZnO nanorods grown at 650 degrees C on 53 nm thick AuGe layer show uniform shape with the length of 8 +/- 0.5 microm and the diameter of 150 +/- 5 nm. Also, the tilting angle of ZnO nanorods (+/- 5.5 degrees) is confirmed by HRXRD. High structural quality of the nanorods is conformed by the photoluminescence measurement. All samples show strong UV emission without considerable deep level emission. However, weak deep level emission appears at high (700 degrees C) temperature due to the increase of oxygen desertion.

The shape control of ZnO based nanostructures.

Tetrapod-shape ZnO nanostructures are formed on Si substrates by vapor phase transportation method. The effects of two important growth parameters, growth temperature and VI/II ratio, are investigated. The growth temperature is varied in the range from 600 degrees C to 900 degrees C to control the vapor pressure of group II-element and the formation process of nanostructures. VI/II ratio was changed by adjusting the flux of carrier gas which affects indirectly the supplying rate of group VI-element. From the scanning electron microscopy (SEM), systematic variation of shape including cluster, rod, wire and tetrapod was observed. ZnO tetrapods, formed at 800 degrees C under the carrier gas flux of 0.5 cc/mm2 min, show considerably uniform shape with 100 nm thick and 1-1.5 microm long legs. Also stoichiometric composition (O/Zn - 1) was observed without any second phase structures. While, the decrease of growth temperature and the increase of carrier gas flux, results in the irregular shaped nanostructures with non-stoichiometric composition. The excellent luminescence properties, strong excitonic UV emission at 3.25 eV without deep level emission, indicate that the high crystalline quality tetrapod structures can be formed at the optimized growth conditions.