The effects of swimming and lactate on the release of testosterone were examined in male rats. During in vivo experiments, male rats were catheterized via the right jugular vein and blood was collected at 0, 10, 15, 30, and 60 min following the exercise, or they were catheterized via the right jugular vein and the left femoral vein and blood was collected at 0, 2, 5, 10, 15, 30, 60, and 120 min after a 10-min infusion at lactate (13 mg.kg-1.min-1). Trunk blood and blood from the testicular vein were also collected after 10 min of swimming or water immersion. In an in vitro experiment, testicular fragments were challenged with lactate (0.01-10 mM) and/or human chorionic gonadotropin (hCG; 0.5 IU.mL-1), and the mediobasal hypothalamus (MBH) was challenged with lactate (8 mM). The post-exercise levels of plasma lactate and testosterone at 10, 15, and 30 min were higher than resting levels. Plasma luteinizing hormone (LH) was increased following 30 min of swimming. Administration of lactate or hCG increased in a dose dependent manner testicular cyclic adenosine 3':5' monophosphate (cAMP) and testosterone release. Plasma testosterone increased after swimming and lactate infusion. Incubation of MBH with lactate increased the gonadotropin-releasing hormone (GnRH) level in the medium. These results suggest that the increased plasma testosterone levels in male rats during exercise is at least partially a result of a direct and LH-independent stimulatory effect of lactate on the secretion of testosterone by increasing testicular cAMP production. Swim-elevated plasma LH may be a result of a rise of GnRH caused by lactate.

MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT) from women with polycystic ovary syndrome (PCOS) or controls with insulin resistance (IR) revealed a differentially expressed microRNA (miRNA) profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4) expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3′ untranslated region (3′UTR). In conclusion, in AT miR-223 is an IR-related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders.

BackgroundA malignant tracheoesophageal/bronchoesophageal fistula (TEF) is a life-threatening complication of esophageal squamous cell carcinoma. A feeding gastrostomy/jejunostomy had been the most common treatment method for patients with TEF before the era of stenting. The aim of this retrospective study is to compare the prognosis of esophageal squamous cell carcinoma patients with TEF treated with an esophageal metallic stent to those treated with a feeding gastrostomy/jejunostomy.MethodsWe retrospectively reviewed a total of 1011 patients with esophageal squamous cell carcinoma between 1996 and 2011 at Kaohsiung Chang Gung Memorial Hospital, and 86 patients with TEF (8.5%) were identified. The overall survival and other clinical data were compared between 30 patients treated with an esophageal metallic stent and 35 patients treated with a feeding gastrostomy/jejunostomy.ResultsAmong the 65 patients receiving either an esophageal metallic stent or a feeding gastrostomy/jejunostomy, univariate analysis showed that treatment modality with an esophageal metallic stent (P = 0.007) and radiotherapy treatment after fistula diagnosis (P = 0.04) were predictive of superior overall survival. In the multivariate comparison, treatment modality with an esophageal metallic stent (P = 0.026, odds ratio: 1.859) represented the independent predictive factor of superior overall survival. There were no significant differences between groups in mean decrease in serum albumin or mean body weight loss. Compared to the feeding gastrostomy/jejunostomy group, a significantly higher proportion of patients in the stenting group (53% versus 14%, P = 0.001) were able to receive chemotherapy within 30 days after fistula diagnosis, indicating better infection control in the stenting group.ConclusionsCompared with a feeding gastrostomy/jejunostomy, an esophageal metallic stent significantly improves overall survival in patients with malignant TEF in our retrospective analysis. Esophageal metallic stent placement may be considered the first-line of treatment for patients with malignant TEF.

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BackgroundAntrodia cinnamomea (AC) is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers. Few clinical studies have reported its application and efficiency in therapeutic chemotherapy strategies. We performed a double-blind, randomized clinical study to investigate whether AC given for 30 days had acceptable safety and efficacy in advanced cancer patients receiving chemotherapy.MethodsPatients with advanced and/or metastatic adenocarcinoma, performance status (PS) 0–2, and adequate organ function who had previously been treated with standard chemotherapy were randomly assigned to receive routine chemotherapy regimens with AC (20 ml twice daily) orally for 30 days or placebo. The primary endpoint was 6-month overall survival (OS); the secondary endpoints were disease control rate (DCR), quality of life (QoL), adverse event (AE), and biochemical features within 30 days of treatment.ResultsFrom August 2010 to July 2012, 37 subjects with gastric, lung, liver, breast, and colorectal cancer (17 in the AC group, 20 in the placebo group) were enrolled in the study. Disease progression was the primary cause of death in 4 (33.3 %) AC and 8 (66.7 %) placebo recipients. Mean OSs were 5.4 months for the AC group and 5.0 months for the placebo group (p = 0.340), and the DCRs were 41.2 and 55 %, respectively (p = 0.33). Most hematologic, liver, or kidney functions did not differ significantly between the two groups, but platelet counts were lower in the AC group than in the placebo group (p = 0.02). QoL assessments were similar in the two groups, except that the AC group showed significant improvements in quality of sleep (p = 0.04).ConclusionsAlthough we found a lower mortality rate and longer mean OS in the AC group than in the control group, A. cinnamomea combined with chemotherapy was not shown to improve the outcome of advanced cancer patients, possibly due to the small sample size. In fact, the combination may present a potential risk of lowered platelet counts. Adequately powered clinical trials will be necessary to address this question.Trial registrationClinicalTrials.gov NCT01287286.

Recently, voice conversion (VC) has been widely studied. Many VC systems use disentangle-based learning techniques to separate the speaker and the linguistic content information from a speech signal. Subsequently, they convert the voice by changing the speaker information to that of the target speaker. To prevent the speaker information from leaking into the content embeddings, previous works either reduce the dimension or quantize the content embedding as a strong information bottleneck. These mechanisms somehow hurt the synthesis quality. In this work, we propose AGAIN-VC, an innovative VC system using Activation Guidance and Adaptive Instance Normalization. AGAIN-VC is an auto-encoder-based model, comprising of a single encoder and a decoder. With a proper activation as an information bottleneck on content embeddings, the trade-off between the synthesis quality and the speaker similarity of the converted speech is improved drastically. This one-shot VC system obtains the best performance regardless of the subjective or objective evaluations.

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