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Excessive immune‐mediated inflammatory reaction plays a deleterious role in ventricular remodelling after myocardial infarction (MI). Interleukin (IL)‐38 is a newly characterized cytokine of the IL‐1 family and has been reported to exert a protective effect in some autoimmune diseases. However, its role in cardiac remodelling post‐MI remains unknown. In this study, we found that the expression of IL‐38 was increased in infarcted heart after MI induced in C57BL/6 mice by permanent ligation of the left anterior descending artery. In addition, our data showed that ventricular remodelling after MI was significantly ameliorated after recombinant IL‐38 injection in mice. This amelioration was demonstrated by better cardiac function, restricted inflammatory response, attenuated myocardial injury and decreased myocardial fibrosis. Our results in vitro revealed that IL‐38 affects the phenotype of dendritic cells (DCs) and IL‐38 plus troponin I (TNI)‐treated tolerogenic DCs dampened adaptive immune response when co‐cultured with CD4+T cells. In conclusion, IL‐38 plays a protective effect in ventricular remodelling post‐MI, one possibility by influencing DCs to attenuate inflammatory response. Therefore, targeting IL‐38 may hold a new therapeutic potential in treating MI.

Acupuncture may be beneficial for patients with mild hypertension, but the evidence is not convincing. We aimed to examine the effect of acupuncture on blood pressure (BP) reduction in patients with mild hypertension. We conducted a multicenter, single‐blind, sham‐controlled, randomized trial in eleven hospitals in China. The trial included 428 patients with systolic blood pressure (SBP) from 140 to 159 mm Hg and/or with diastolic blood pressure (DBP) from 90 to 99 mm Hg. The patients were randomly assigned to receive 18 sessions of affected meridian acupuncture (n = 107) or non‐affected meridian acupuncture (n = 107) or sham acupuncture (n = 107) during 6 weeks, or to stay in a waiting‐list control (n = 107). All patients received 24‐hour ambulatory blood pressure monitoring at weeks 6, 9, and 12. We included 415 participants in the intention‐to‐treat analysis. The two acupuncture groups were pooled in the analysis, since they had no difference in all outcomes. SBP decreased at week 6 in acupuncture group vs sham acupuncture vs waiting‐list group (7.2 ± 11.0 mm Hg vs 4.1 ± 11.5 mm Hg vs 4.1 ± 13.2 mm Hg); acupuncture was not superior to sham acupuncture (mean difference 2.7 mm Hg, 95% CI 0.4 to 5.9, adjusted P = 0.103) or waiting‐list control (2.9 mm Hg, 95% CI −0.2 to 6.0, adjusted P = 0.078). However, acupuncture was superior to sham acupuncture (3.3 mm Hg, 95% CI 0.2 to 6.3, adjusted P = 0.035) and waiting‐list control (4.8 mm Hg, 95% CI 1.8 to 7.8, P

Background Infective endocarditis (IE) is uncommon in childhood. Its associated epidemiological characteristics in patients with congenital heart disease (CHD) remain unclear. Methods The study population included children born in Taiwan during the years 1997 to 2005 who were diagnosed as having CHD before 3years of age. All children were followed up until the end year of 2010, the diagnosis of infective endocarditis, or death. The demographic characteristics of patients with and without IE, the invasive procedures performed during 6months before the index date, the prophylactic antibiotics related to dental procedures, and in-hospital mortality were collected. Results Information of 24,729 children with CHD were retrieved for our analysis and 237 patients with newly diagnosed IE were identified. The incidence rate of IE in all CHD lesions was 11.13 per 10,000person-years. Taking ASD for reference, the following CHD lesions were at risk for IE: cyanotic CHD (adjusted OR, 9.58; 95% confidence interval, 5.38–17.05), endocardial cushion defect (ECD) (8.01; 2.73–23.50), Left-sided lesions (4.36; 1.90–10.01) and VSD (2.93; 1.64–5.23). Patients who underwent procedures have a higher risk of acquiring IE which include central venous catheter (CVC) insertion (3.17; 2.36–4.27), cardiac catheterization (3.74; 2.67–5.22), open-heart surgery (2.47; 1.61–3.77), valve surgery (3.20; 1.70–6.02), and shunt surgery (7.43; 2.36–23.41). However, dental procedures did not increase the risk of IE, irrespective of antibiotic usage. Conclusions The risk of IE varies markedly among CHD lesions in our study. Invasive heart procedures but not dental procedures, are more significantly associated with IE among children with CHD.

Dermatomyositis or polymyositis as a paraneoplastic syndrome of hepatocellular carcinoma (HCC) is an uncommon event. Few cases have been reported in the literature. We herein report the case of a 55-year-old man with chronic hepatitis B and alcoholism who presented with skin rash. Abdominal computed tomography revealed multiple hypervascular liver tumors consistent with HCC. He subsequently developed dysphagia with proximal limb weakness. Laboratory tests and electromyography demonstrated inflammatory myopathy. We therefore diagnosed the patient with HCC-induced dermatomyositis. Prednisolone and anti-viral therapy were administered; however, the patient died two months later due to the progression of the disease. We review the cases of HCC-induced dermatomyositis and polymyositis in the literature.

Cyberbullying has emerged as a new threat to adolescents’ well-being in modern society; yet, little is known about adolescents’ alternative views on this virtual form of aggression. This study investigated Taiwanese students’ misconceptions about cyberbullying and the logics behind. We first surveyed 8,547 students nationwide (4th–12th grades) on potential misconceptions. Then, we administrated 6 focus group interviews to further explore students’ adverse beliefs on justifying cyberbullying, not reporting, and disseminating cyberbullying contents. We also found that students did not associate cyberbullying with anonymity as past research suggested. These findings extend the existing knowledge about cyberbullying in school-age youth in East Asian contexts and could lead to appropriate and effective intervention and prevention.

Neutrophils infiltration in liver is one of the typical histological characteristics of nonalcoholic steatohepatitis (NASH) in both animal models and human subjects. This study was aimed to investigate the role of neutrophils in the process of NASH and its underling mechanisms. C57BL/6J mice were fed with either standard chow (SC) or methionine/choline-deficient (MCD) diet for 1, 2, 4, 8 weeks, respectively. C57BL/6J APOE(-/-) mice were fed with SC or high-fat high-cholesterol (HFHC) diet. Anti-Ly6G antibody was employed to deplete neutrophils and sivelestat was used to inhibit neutrophil elastase (NE). MCD-diet-receiving mice with neutrophil depletion had much lower serum ALT activity, liver inflammation, and mRNA levels of proinflammatory genes in the early stage of NASH (1 and 2 weeks) when compared to non-neutrophil-depleted mice. NE inhibitor sivelestat could recapitulate the effects of neutrophil depletion in APOE(-/-) mice fed with HFHC diet. As the disease progressed (4 and 8 weeks), neutrophil depletion did not lower serum ALT levels and liver lesions due to activation of Kupffer cells. Finally, we found neutrophils also affected anti-inflammation cytokine interleukin-1 receptor antagonist mRNA expression. Neutrophils play a crucial role in the early stage of NASH via NE.

To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice.Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR.Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P0.05).CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.

An imbalance between neutrophil elastase (NE) and its inhibitor α1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.

The long-term prophylactic effects of acupuncture for migraine are uncertain.To investigate the long-term effects of true acupuncture compared with sham acupuncture and being placed in a waiting-list control group for migraine prophylaxis.This was a 24-week randomized clinical trial (4 weeks of treatment followed by 20 weeks of follow-up). Participants were randomly assigned to true acupuncture, sham acupuncture, or a waiting-list control group. The trial was conducted from October 2012 to September 2014 in outpatient settings at 3 clinical sites in China. A total of 249 participants 18 to 65 years old with migraine without aura based on the criteria of the International Headache Society, with migraine occurring 2 to 8 times per month.Participants in the true acupuncture and sham acupuncture groups received treatment 5 days per week for 4 weeks for a total of 20 sessions. Participants in the waiting-list group did not receive acupuncture but were informed that 20 sessions of acupuncture would be provided free of charge at the end of the trial.Participants used diaries to record migraine attacks. The primary outcome was the change in the frequency of migraine attacks from baseline to week 16. Secondary outcome measures included the migraine days, average headache severity, and medication intake every 4 weeks within 24 weeks.A total of 249 participants 18 to 65 years old were enrolled, and 245 were included in the intention-to-treat analyses. One hundred eighty-nine (77.1%) were women. Baseline characteristics were comparable across the 3 groups. The mean (SD) change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization (P .001); the mean (SD) frequency of attacks decreased in the true acupuncture group by 3.2 (2.1), in the sham acupuncture group by 2.1 (2.5), and the waiting-list group by 1.4 (2.5); a greater reduction was observed in the true acupuncture than in the sham acupuncture group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = .002) and in the true acupuncture vs waiting-list group (difference of 1.8 attacks; 95% CI, 1.1-2.5; P .001). Sham acupuncture was not statistically different from the waiting-list group (difference of 0.7 attacks; 95% CI, -0.1 to 1.4; P = .07).Among patients with migraine without aura, true acupuncture may be associated with long-term reduction in migraine recurrence compared with sham acupuncture or assigned to a waiting list.clinicaltrials.gov Identifier: NCT01687660.

Establish the model of mouse with chronic hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD).Take 100 HBV transgenic, BALB/c mice of 4 weeks old, with each gender half. Then pick out 70 mice in one group to feed high-fat feed and the rest to feed normal feed. At the end of week 16, random kill 10 mice of high-fat, then liver tissue and serological detection target identification model is established in this paper. After that, divide the mice into model group and comparison group with 30 mice in each group. Feed model group with high-fat feed, comparison group with normal feed and normal group with normal feed till week 72 (including previous 16 weeks). Kill 10 mice of each group at the end of week 24, 48 and 72 respectively, fully automatic biochemical instrument detection of serum ALT, AST, TC, TG, FBG, fluorescence quantitative PCR method to detect HBV-DNA, chemiluminescence detection of HBsAg, liver biopsy after HE staining to evaluate histology change, observe mice model of dynamic evolution.(1) Feed high fat feed after 16 weeks, mice's weight, serum ALT, AST, TC, TG, FBG and blood biochemical indicators increased, HBV-DNA positive, liver HE staining obviously big blister fatty degeneration of liver cells and within the lobule lymphocytes infiltration, NAFLD activity score (NAS) getting close to NASH, the model of chronic HBV carries with NAFLD mouse built successfully. (2) The TC and TG values of model group in each period were higher than that of comparison group and normal group. (3) In week 24 and 72, HBV-DNA values of each group are obvious different from the other two groups and the difference can be applied to statistical significance (P0.05). (4) In week 48 and 72, NAS of each group are obvious different from the other two groups and the difference can be applied to statistical significance (P0.05).(1) Chronic HBV carries with NAFLD mice model can be established by HBV transgenic mice fed by high fat feed. (2) NAFLD accelerates the liver disease of the mice carrying HBV to some extent.

To investigate the expression of F4/80, NF-kappaB, p-AKT, AKT in the liver of nonalcoholic fatty liver disease (NAFLD) mice. To determine the role of Kupffer cells (KCs) in the development of NASH (non-alcoholic steatohepatitis), and understand the pathogenic mechanism of NASH.Five C3H/HeN mice fed with normal diet were served as controls, while fifteen fed with high fat, high fructose, high fat combined fructose diet respectively for 16 weeks were as NAFLD mice models. The liver inflammation and hepatic damage were examined, and the expression of F4/80, NF-Kb, p-AKT, AKT and the content of lipid in the liver were also detected.Chronic intake of high fat and 30% fructose solution caused a significant increase in hepatic steatosis in animals in comparison to water controls. Liver F4/80 and NF-kappaB were significantly higher in high fat and high fat combined fructose diet fed mice than that in controls (P0.01, P0.01), F4/80 protein were higher in high fat diet treated mice than those in fructose and high fat combined fructose groups (P0.01, P0.01). Markers of insulin resistance (e. g, hepatic phospho-AKT, AKT) were only altered in fructose-fed or high fat combined fructose animals (P0.01, P0.01).High fat and fructose diet may induce NAFLD in C3H/HeN mice. Kupffer cells and signal pathway proteins were activated, and they may play key roles in the initiation and progression of NASH.

Brown adipose tissue plays the dominant role in response to cold acclimatization through its capacity to produce heat. To demonstrate the cellular function for thermogenesis induced by cold acclimation in the brown adipose tissue of obese Zucker rats, we examined the changes for the area as well as the Na, K, Cl, and Ca concentrations in the mitochondria of brown adipocytes after the warm (25 degrees C, WG) and the cold acclimations (10 degrees C, CG). Moreover, the respiratory quotients (RQs) of these rats were measured. After the acclimations, the RQ in the CG was decreased and the oxygen consumption increased. A morphometric analysis of electron micrographs of brown adipocytes from the two groups of rats showed a marked increase in the area of the mitochondria in the CG. An electron probe X-ray microanalysis showed an increase in the Ca concentration and decreases in the Na and K concentrations in the matrix of the mitochondria of the cells in the CG. These results suggest that the reduction in the RQ of obese Zucker rats acclimated to cold is the consequence of the metabolism of a large quantity of lipid in the brown adipocytes. Our data also indicate that the observed change in the mitochondrial area and the increase for Ca in the mitochondria were associated with the cold-induced thermogenesis in brown adipocytes of obese Zucker rats.

Background The instant-treatment effect of acupuncture for patients with migraines has been corroborated in numerous studies. However, most diseases are chronic and tend to recur, so the long-term effect of acupuncture can verify the existence of sustained efficacy or the placebo effect. Evaluating the efficacy of acupuncture in the prophylaxis of migraine without aura (MWoA) in China is also important because such studies are lacking. Methods This trial is a multicenter, prospective, pragmatic randomized controlled clinical trial. We will randomly allocate 249 participants to three groups of 83. Patients in the individualized acupoint group will be treated with individualized acupuncture point prescriptions. The non-acupoint control group will undergo insertion of acupuncture needles at four bilateral non-points in locations not corresponding to acupuncture points. The waiting-list control group will not undergo treatment but instead will receive 20 acupuncture treatments for free after a waiting period of 24 weeks. Participants in the individualized acupoint group and non-acupoint control group will receive 20 sessions over four weeks and then all participants will receive 20 weeks of follow-up. Discussion The results of our trial will help to supply evidence for the long-term acupuncture effect for MWoA in a long follow-up period, and special attention will be paid to comparison with the placebo effect. Trial registration The trial was registered at ClinicalTrials.gov (NCT01687660) on 18 September 2012.

Objectives The aim of this study was to evaluate the incidence of amputation among patients with diabetic foot ulcer (DFU) and risk factors for amputations. Methods This is a retrospective study of 450 inpatients treated in a multi-discipline based diabetic centre, 306th Hospital of PLA during the period of January 2000–September 2009. Hospital admission and discharge information including patient profile, grade of DFU, co-morbidities and complications, laboratory data and final outcome were collected. The risk factors for amputation were determined using univariate and stepwise logistic regression analysis. Results The overall amputation rate among DFU was 21.5%. Significant univariate risk factors for amputation were peripheral vascular disease (PVD), white blood cell (WBC) counts, neutrophil granulocyte percentage, hemoglobin, triglyceride, cholesterol, LDL-C, HDL-C and serum sCRP. Upon stepwise logistic regression analysis, only PVD (odds ratio 4.529, 95% CI 1.500–13.676), WBC (odds ratio 1.146, 95% CI 1.075–1.222), sCRP (odds ratio 1.041, 95% CI 1.002–1.082) and triglyceride (odds ratio −0.488, 95% CI 0.433–0.869) were significant risk factors. Conclusions The risk factors for amputation were presence of PVD, increased WBC, sCRP and decreased triglyceride.

To observe the effect of acupuncture on quality of life (QOL) in post-ischemic stroke patients with dysphagia.Sixty-six patients with dysphagia were randomly assigned to 3 groups, the 23 patients in the electro-acupuncture (EA) group treated by EA, 18 in the control group received rehabilitation training combined with acupoint percutaneous electric stimulation, and 25 in the acupoint token puncturing (TP) group received rehabilitation training combined with acupoint TP, once every day for 20 days in total. Changes in QOL scale specified for dysphagia of patients before and after treatment were compared.The total effective rate was 69.6% in the EA group, 50.0% in the control group and 64.0% in the TP group with insignificant difference among them (P0.05), but the improvements dealing with patients' general condition, time for taking food, frequency of uneasiness, emotion, appetite, social intercourse ability, fatigue, sleep and mental health, etc. in the EA group were superior to those in the other two groups (P0.05).Acupuncture could improve the QOL of patients with dysphagia after ischemic stroke.

To investigate the immunobiology of Rpf domain from Micrococcus luteus.BALB/c mice were immunized with Rpf domain three times at 2-week interval. ELISA was used to detect the title of the anti-Rpf domain antibody titer in the immunized mice sera. The spleen lymphocytes of the immunized mice were separated and the stimulation index (SI) was measured by MTT colorimetry. The levels of secreted IFN-gamma, IL-10 and IL-12 upon specific antigen stimulation was detected by ELISA. The Rpf domain immunized BALB/c mice were intravenously infected with 10(5) CFU MTB H37Rv. The number of CFU in the spleens was determined four weeks after final injection.The titer of the specific antibody in sera of the immunized BALB/c mice was 1:128 000. The SI of Rpf domain immunized group (2.10+/-0.12) was significantly higher than that of saline immunized group (0.90+/-0.21). The lever of IFN-gamma, IL-10 and IL-12 levels in culture supernatant of spleen lymphocytes from the fusion protein immunized mice was (1 126+/-36) ng/L, (368+/-13) ng/L and (289+/-14) ng/L, respectively, which was markedly higher than that of saline immunized group (P0.01). Compared with normal saline immunized mice (6.64+/-0.13) four weeks after final injection, dramatic reduction in MTB replication was observed in the spleen (5.03+/-0.11) from the BALB/c mice immunized with fusion proteins.Rpf domain can be used as a candidate for a new TB vaccine.

To study the incidence and the risk factors of dysphagia after ischemic stroke in Chengdu City, China.Review was made with unified questionnaire on dysphagia after ischemic stroke in 563 patients from four hospitals, from January to December 2005. Over 20 risk factors related to dysphagia after ischemic stroke were analyzed by logistic regression.The total incidence of dysphagia after ischemic stroke was 13.3% in Chengdu. Data from logistic regression analysis indicated that gender, morbidity frequency, basal nuclei, periventricular lesion, hypertension, pneumonia, hyperlipemia, cervical spondylosisi, internal carotid artherosclerosis were closely related to dysphagia after ischemic stroke,with OR values as 0.416, 0.489, 0.327, 0.454, 2.187, 2.146, 0.352, 0.242 and 0.273 respectively.The total incidence was lower than literature published from home and abroad. Gender, morbidity frequency, basal nuclei, periventricular lesion, hypertension, pneumonia, hyperlipemia, cervical spondylosisi and internal carotid artherosclerosis seemed to be risk factors to dysphagia after ischemic stroke.

To study murine humoral and cellular immune response induced by fusion protein ESAT6-CFP10 and to examine its protective efficacy against M. tuberculosis (MTB) in mice.BALB/c mice were immunized subcutaneously on the back with fusion protein ESAT6-CFP10 that was transferred to nitro cellulose (NC) membrane beforehand. Stimulation index (SI) of the spleen lymphocytes of the immunized mice was measured by MTT colorimetry. The level of IFN-gamma and IL-2 and CTL upon antigen-specific stimulation were detected. The vaccinated BALB/c mice were intravenously infected with MTB H37Rv (10(5) CFU/mouse). Four weeks later the number of CFU in spleens was determined.The titer of serum specific antibody in BALB/c mice immunized with fusion protein ESAT6-CFP10 was 1:6,400. The SI of fusion protein immunized group (1.90+/-0.15) was significantly higher than that of saline-immunized group (0.9+/-0.15). The level of IFN-gamma and IL-2 induced by the fusion protein was 1.792+/-19 ng/L and 0.211+/-11 ng/L respectively, which was significantly higher than that of saline-immunized group and lower than that of BCG-immunized group. The specific killing activity of splenocytes was 36%. Compared with the saline-immunized mice (bacterial load was 6.51+/-0.13), MTB number (bacterial load was 5.24+/-0.15) was reduced dramatically in the spleens of BALB/c mice immunized with the fusion protein, but the protective efficacy of the mice immunized with BCG was higher than that of ESAT6-CFP10 vaccinated group.Fusion protein ESAT6-CFP10 can be used as a candidate for novel vaccines.

To elucidate the role of muscle glycogen storage on regulation of GLUT4 protein expression and whole-body glucose tolerance, muscle glycogen level was manipulated by exercise and insulin administration. Sixty Sprague-Dawley rats were evenly separated into three groups: control (CON), immediately after exercise (EX0), and 16 h after exercise (EX16). Rats from each group were further divided into two groups: saline- and insulin-injected. The 2-day exercise protocol consisted of 2 bouts of 3-h swimming with 45-min rest for each day, which effectively depleted glycogen in both red gastrocnemius (RG) and plantaris muscles. EX0 rats were sacrificed immediately after the last bout of exercise on second day. CON and EX16 rats were intubated with 1 g/kg glucose solution following exercise and recovery for 16 h before muscle tissue collection. Insulin (0.5 microU/kg) or saline was injected daily at the time when glucose was intubated. Insulin injection elevated muscle glycogen levels substantially in both muscles above saline-injected group at CON and EX16. With previous day insulin injection, EX0 preserved greater amount of postexercise glycogen above their saline-injected control. In the saline-injected rats, EX16 significantly increased GLUT4 protein level above CON, concurrent with muscle glycogen supercompensation. Insulin injection for EX16 rats significantly enhanced muscle glycogen level above their saline-injected control, but the increases in muscle GLUT4 protein and whole-body glucose tolerance were attenuated. In conclusion, the new finding of the study was that glycogen overload by postexercise insulin administration significantly abolished the exercise-induced increases in GLUT4 protein and glucose tolerance.

Quantitative structure–activity relationships (QSAR) for a series of new trichostatin A (TSA)-like hydroxamic acids for the inhibition of cell proliferation of the PC-3 cell line have been developed using molecular descriptors from Qikprop and electronic structure calculations. The best regression model shows that the PM3 atomic charge on the carbonyl carbon in the CONHOH moiety(Qco), globularity (Glob), and the hydrophilic component of the solvent-accessible surface area (FISA) describe the IC50 of 19 inhibitors of the PC-3 cell line with activities ranging over five orders of magnitude with an R2=0.92 and F=59.2. This information will be helpful in the further design of novel anticancer drugs for treatment of prostate cancer and other diseases affected by HDAC inhibition.

A series of unsaturated steroids bearing a 3-carboxy substituent has been prepared and assayed in vitro as inhibitors of human and rat prostatic steroid 5 alpha-reductase (EC 1.3.1.30). It is proposed that the observed tight binding of the 3-androstene-3-carboxylic acids is due to mimicry of a putative, high-energy, enzyme-bound enolate intermediate formed during the NADPH-dependent conjugate reduction of testosterone by steroid 5 alpha-reductase. These compounds were prepared through palladium(0)-catalyzed carbomethoxylations of enol (trifluoromethyl)sulfonates derived from 3-keto precursors. Modification of A and B ring unsaturation and substitution at C-3, -4, -6, and -11 was explored. Mono- and dialkylcarboxamides were employed as 17 beta side chains to enhance inhibitory activity with the human enzyme.