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This study was conducted to determine the possible effects of long-term exogenous kisspeptin and its antagonist P234 on serum, liver and adipose tissue fatty acids (FA) profiles, as well as body weight, in female rats. Kisspeptin (50 pmol) and P234 (1 nmol) were administrated to the weaned Sprague-Dawley female rats by an intracerebroventricular injection from the 26th postnatal day to the 60th postnatal day. Percentages of the serum total saturated FA (∑SFA) and total monounsaturated FA (∑MUFA) were lower in the kisspeptin group. In the adipose tissue, ∑SFA was lower and total unsaturated FA higher in the P234 group. Moreover, long-term central kisspeptin injection caused a decrease in the body weight. When compared to the kisspeptin group, the final body weights were higher in the P234 and kisspeptin + P234 groups. According to our results, we suggest that kisspeptin has a regulatory role in FA metabolism and regulation of body weight.

Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide and imposing heavy economic burdens to societies. Currently, only symptomatic treatments are available for patients, but there is ongoing research on potential therapies that can modify the course of disease. The main objective of this work is to identify and explore the challenges surrounding decision modeling for economic evaluation of interventions for AD.

This article discusses the challenges in modeling the natural history of disease, particularly regarding the selection of disease progression and outcome measures, the inclusion of biomarker status in models, and the approach to model mortality. Challenges stemming from the use of long-term assumptions regarding treatment effects and the need for real-world evidence to fill data gaps are discussed. Lastly, the overwhelming economic impact of disease and the challenges in estimating these costs for modeling are addressed.

Value assessment frameworks need to be reconsidered in order to demonstrate the full benefit of new disease-modifying therapies spanning beyond the scope of health systems. Data collection efforts that expand the evidence base, upon which economic models are based, will reduce the uncertainties surrounding the long-term outcomes of interventions in AD.

Value assessment frameworks need to be reconsidered in order to demonstrate the full benefit of new disease-modifying therapies spanning beyond the scope of health systems. Data collection efforts that expand the evidence base, upon which economic models are based, will reduce the uncertainties surrounding the long-term outcomes of interventions in AD.Birth season is an important risk factor for several cancers; for example, anatomic subsite risk factors for gastric cancer differ substantially by when patients were born. In this population-based retrospective study, we explored the relationship between birth season and gastric cancer of different anatomical sites, focusing on gastric cancer patients who were registered at the Beijing Institute for Cancer Research from 2003 to 2012. In total, 19,668 patients were divided into three groups according to the anatomical site of the primary lesion cardia (n = 3911), noncardia (n = 5383) and unknown (n = 10,374). The 5383 patients in the noncardia group were further subdivided into the following subgroups fundus (n = 455), corpus (n = 902), greater curvature (n = 110), lesser curvature (n = 512), antrum (n = 2635), pylorus (n = 106) and overlapping (n = 663). Finally, all gastric cancer cases, the three major groups, and the seven noncardia subgroups were, respectively, compared with inpatients from the Dongzhimen Hospital of Beijing from 2003 to 2013. A logistic regression method with sex and age as control factors was used to evaluate the relationship between birth season and gastric cancer with the level for statistical significance set at P .05). This study demonstrated that gastric cancer is related to birth season. For people born in summer, the risk of developing gastric cancer was comparatively lower than for people born in winter. Seasonal differences in immune function and maternal nutrition status during pregnancy may explain these findings; however, further large-scale prospective studies will be required to validate these findings.

To prepare α-(8-quinolinyloxy) monosubstituted phthalocyanine zinc nanosuspension (ZnPc-NS) for photodynamic therapy by intravenous administration.

The formulation and preparation technology of ZnPc-NS were assessed by particle size using the precipitation-high pressure homogenization method. The efficacy of ZnPc-NS was evaluated based on particle size, zeta potential, sedimentation ratio, TEM imaging, stability assessment, photodynamic activity and safety.

The content, average particle size, polydispersity and photodegradation constant of ZnPc-NS were 0.2 mg/ml, 219.7 ± 7.41 nm, 0.19 ± 0.02 and 0.006, respectively. The photosensitization rate of singlet oxygen (

O

) of the ZnPc-NS was three times higher than that of the ZnPc DMF solution. ZnPc-NS exhibited optimal antitumor activity in HepG2 cells under light exposure and low photo- and non-light-associated toxicity in HELFX cells. In addition, low hemolysis and vascular stimulation were evident in the experiments performed.

The ZnPc-NS exhibited optimal stability, faster photosensitization rate of

O

, and optimal antitumor activity and safety than the ZnPc DMF solution, which could provide potential support for further research and development.

The ZnPc-NS exhibited optimal stability, faster photosensitization rate of 1O2, and optimal antitumor activity and safety than the ZnPc DMF solution, which could provide potential support for further research and development.Glutathione reductase (GR), an essential antioxidant enzyme against oxidative stress, has become an attractive drug target for the development of anticancer and antimalarial drugs. Avasimibe in vitro In this regard, we evaluated the naturally occurring isothiocyanates as promising GR inhibitors and elucidated the mechanism of action. It was found that benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) inhibited yeast GR (yGR) and human GR (hGR) in a time- and concentration-dependent manner. The Ki and kinact of BITC against yGR were determined to be 259.87 µM and 0.0266 min-1, respectively. The GR inhibition occurred only in the presence of NADPH and persisted after extensive dialysis. The tandem mass spectrometric analysis revealed that Cys61 rather than Cys66 at the active site of yGR was mono-benzyl thiocarbamoylated by BITC. Inhibition of intracellular GR by BITC and PEITC in cultured cancer cells was also observed. BITC and PEITC were evaluated as competitive and irreversible inhibitors of GR.