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Background: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.Presentation Of the Hypothesis: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.Testing the Hypothesis: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis.Implications Of the Hypothesis: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy. [ABSTRACT FROM AUTHOR]

The role of the aspartate residues Asp193, Asp217, Asp228, Asp234, Asp236, Asp238, Asp438, and Asp461 of a truncated Bacillus sp. strain TS-23 α-amylase (BACΔNC) was investigated by site-directed mutagenesis. These residues were replaced with Asn to generate D193N, D217N, D228N, D234N, D236N, D238N, D438N, and D461N, respectively. Parental and mutant amylases were purified to homogeneity by nickel-chelated chromatography, and the purified enzymes had a molecular mass of approximately 54 kDa. The amylolytic activity of purified BACΔNC was abolished completely upon the addition of 15 mM EDTA. D438N and D461N were very similar to BACΔNC in terms of specific activity, temperature–activity profiles, and kinetic parameters, whereas the remaining mutant enzymes showed a dramatic reduction in both catalytic efficiency ( kcat/ KM) and thermostability. Compared with BACΔNC, measurement of intrinsic tryptophan fluorescence revealed the minor alterations of the microenvironment of aromatic amino acid residues in all of mutant enzymes. Far-UV circular dichroism spectra were nearly identical for the parental and mutant enzymes, but D193N, D217N, D228N, D234N, D236N, and D238N exhibited a different sensitivity towards temperature-induced denaturation. This implicates that the rigidity of the enzyme has been changed as the consequence of Asp193, Asp217, Asp228, Asp234, Asp236, and Asp238 mutations. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer.Methods: qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan-Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial-mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo.Results: Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo.Conclusions: These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21-LZTFL1-EMT axis might be a promising strategy in breast cancer therapy.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Conducting randomized controlled trials on traditional Chinese non-drug therapies has been limited by factors such as patient preference to specific treatment modality. The aim of this study is to investigate the feasibility of applying a partially randomized patient preference (PRPP) trial model in evaluating the efficacy of two types of traditional Chinese medicine therapies, acupuncture and cupping, for fibromyalgia while accounting for patients' preference of either therapeutic modality.Methods: This protocol was approved by the Institutional Ethics Committee of affiliated Dongfang Hospital, Beijing University of Chinese Medicine (approval number: 2013052104-2). One hundred participants with fibromyalgia will be included in this study. Diagnosis of fibromyalgia will be based on the American College of Rheumatology criteria. Before treatment, participants will be interviewed for their preference toward acupuncture or cupping therapy. Fifty participants with no preference will be randomly assigned to one of the two groups and another 50 participants with strong preference to either acupuncture or cupping will receive what they choose. For acupuncture and cupping therapy, the main acupoints used will be tender points (Ashi). Treatment will be three times a week for 5 consecutive weeks with a follow-up period of 12 weeks. Outcome measures will be qualitative (patient expectation and satisfaction) and quantitative (pain intensity, quality of life, depression assessment).Trial Registration Number: NCT01869712 (in clinicaltrials.gov, on 22nd May 2013). [ABSTRACT FROM AUTHOR]

Background: Air pollution has been extensively and consistently linked with mortality. However, no study has investigated the health effects of air pollution on length of survival among diagnosed respiratory cancer patients.Methods: In this study, we conducted a population-based study to investigate if air pollution exposure has adverse effects on survival time of respiratory cancer cases in Los Angeles (LA), CA and Honolulu, HI. We selected all White respiratory cancer patients in the two study areas from the 1992-2008 Surveillance Epidemiology and End Results cancer data. Death from respiratory cancer and length of survival were the main outcomes.Results: Kaplan-Meier survival analysis shows that all respiratory cancer cases exposed to high air pollution referring to the individuals from LA had a significantly shorter survival time than the low pollution exposure group referring to those from Honolulu without adjusting for other covariates (p <0.0001). Moreover, the results from the Cox Proportional-Hazards models suggest that exposure to particles less than 10 micrometers in diameter (PM10) was associated with an increased risk of cancer death (HR = 1.48, 95% CI: 1.44-1.52 per 10 μg/m3 increase in PM10) after adjusting for demographic factors and cancer characteristics. Similar results were observed for particles less than 2.5 micrometers in diameter and ozone.Conclusion: Our study indicates that air pollution may have deleterious effects on the length of survival among White respiratory cancer patients. This study calls for attention to preventive effort from air pollution for this susceptible population in standard cancer patient care. The findings from this study warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: This report aims to study the relationship between sarcopenia of elderly in community and inflammatory factors IL-6 and TNF-α., Methods: A total of 441 elders who undertook physical examinations were included into this study. The age of these subjects were >60, in which 235 subjects were male and 206 subjects were female. According to the diagnostic standards of sarcopenia set by EWGSOP and AWGS, these subjects were divided into two groups: sarcopenia, and non-sarcopenia groups. The living habits, disease status, biochemical indexes, and levels of IL-6 and TNF-α of these subjects were investigated., Results: The morbidity rate of sarcopenia was 17.02% in male subjects and 18.9% in female subjects. In elderly subjects >80 years old, morbidity rate was 25.3% in male subjects and 35.1% in female subjects. The history of smoking in patients with sarcopenia was long, and their regular exercise history was short (P < 0.01). Furthermore, differences in handgrip strength (HG), fat-free mass (FFM), bone mineral content (BMC), plasma albumin (ALB) and serum creatinine (Cr), and body fat content (FAT) in patients between the sarcopenia and non-sarcopenia groups were statistically significant (P < 0.05). Moreover, differences in IL-6 and TNF-α levels between these two groups were statistically significant (P < 0.05). In addition, BMI was positively correlated to TNF-α levels, and ALB was negatively correlated to IL-6; while BMI and VFA were positively correlated to TNF-α levels, and SMM, HDL-C, Hb, HG were negatively correlated to IL-6 level (P < 0.05). Multiple linear regression analysis suggested plasma ALB and BMI were the independent risk factors of TNF-α, while VFA was the independent risk factor of IL-6., Conclusions: The onset of sarcopenia was associated with poor exercise habits, disease history, and nutritional status. The emergence of sarcopenia was accompanied by increased levels of inflammation factors TNF-α and IL-6. Plasma albumin, BMI, and VFA were inflammatory factor predictors of TNF and IL-6.

Background: Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are frequent in low-grade gliomas and secondary glioblastomas (sGBM). Because they yield the same oncometabolite, D-2-hydroxyglutarate, they are often treated as equivalent and pooled. The objective of this study was to provide insight into the differences between IDH1 and IDH2 mutant gliomas., Methods: To investigate the different clinical and molecular characterization between IDH1 mutant and IDH2 mutant gliomas, we studied 811 patients with IDH1 mutations, IDH2 mutations and IDH1/2 wild-type. In addition, whole-transcriptome sequencing and DNA methylation data were used to assess the distribution of genetic changes in IDH1 and IDH2 mutant gliomas in a Chinese population-based cohort., Results: Among 811 gliomas in our cohort, 448 cases (55.2%) harbored an IDH1 mutation, 18 cases (2.2%) harbored an IDH2 mutation and 345 cases (42.6%) harbored an IDH1/2 wild-type. We found that IDH1 and IDH2 are mutually exclusive in gliomas, and IDH2 mutations are mutually exclusive with PTEN, P53 and ATRX mutations. Patients with IDH2 mutations had a higher frequency of 1p/19q co-deletion (p < 0.05) than IDH1 mutant patients. In addition, a Gene Set Enrichment Analysis (GSEA) showed that IDH2 mutant gliomas were associated with the oxidative phosphorylation gene set, and the four most representative biological processes for genes commonly altered by hypermethylation in IDH2 mutant gliomas were the regulation of cell proliferation, cell motion, cell migration and response to hypoxia. Patients with IDH2 mutant gliomas exhibited longer Overall survival (OS) (p < 0.05) and longer Progression-free survival (PFS) (p < 0.05) than patients with IDH1/2 wild-type gliomas. However, their OS and PFS did not differ from that of IDH1 mutant patients., Conclusions: Our study revealed an intrinsic distinction between IDH1 and IDH2 mutant gliomas, and these mutations should be considered separately because their differences could have implications for the diagnosis and treatment of IDH1/2 mutant gliomas.

Although the original US porcine epidemic diarrhea virus (PEDV) was confirmed as highly virulent by multiple studies, the virulence of spike-insertion deletion (S-INDEL) PEDV strains is undefined. In this study, 3-4 day-old conventional suckling piglets were inoculated with S-INDEL PEDV Iowa106 (4 pig litters) to study its virulence. Two litters of age-matched piglets were inoculated with either the original US PEDV PC21A or mock as positive and negative controls, respectively. Subsequently, all pigs were challenged with the original US PEDV PC21A on 21-29 days post-inoculation (dpi) to assess cross-protection. All S-INDEL Iowa106- and the original US PC21A-inoculated piglets developed diarrhea. However, the severity of clinical signs, mortality (0-75%) and fecal PEDV RNA shedding titers varied among the four S-INDEL Iowa106-inoculated litters. Compared with the original PC21A, piglets euthanized/died acutely from S-INDEL Iowa106 infection had relatively milder villous atrophy, lower antigen scores and more limited intestinal infection. Two of four S-INDEL Iowa106-infected sows and the original PC21A-infected sow showed anorexia and watery diarrhea for 1-4 days. After the original PC21A challenge, a subset (13/16) of S-INDEL Iowa106-inoculated piglets developed diarrhea, whereas all (5/5) and no (0/4) pigs in the mock and original PC21A-inoculated pigs had diarrhea, respectively. Our results suggest that the virulence of S-INDEL PEDV Iowa106 was less than the original US PEDV PC21A in suckling pigs, with 100% morbidity and 18% (6/33) overall (0-75%) mortality in suckling pigs depending on factors such as the sow's health and lactation and the piglets' birth weight. Prior infection by S-INDEL Iowa106 provided partial cross-protection to piglets against the original PC21A challenge at 21-29 dpi.