A dominant strain of Elizabethkingia anophelis emerged from a hospital water system to cause a three-year outbreak in a respiratory care center.

BACKGROUND: Elizabethkingia species are ubiquitous bacteria but uncommonly cause human infection. An outbreak of Elizabethkingia anophelis bacteraemia was observed in a respiratory care center of a tertiary hospital in Taiwan from 2015 to 2018. METHODS: Clinical and environmental isolates were collected for the outbreak investigation. Pulsed-field gel electrophoresis (PFGE) and complete-genome sequencing were conducted to elucidate the mechanism of transmission. FINDINGS: The three-year outbreak involved 26 patients with E. anophelis bacteraemia and the incidence significantly increased during the outbreak period compared with that observed from 2010 to 2014 (P<0.05). All 26 clinical isolates during the outbreak period belonged to a cluster by PFGE analysis. In contrast, the PFGE pattern was heterogeneous among comparative historical strains. Hospital tap water was highly contaminated by Elizabethkingia species (18/34, 52.9%); among that, five E. anophelis belonged to the outbreak cluster (5/18, 27.8%). As for the inanimate surface survey, 3.4% sites (4/117) revealed positive growth of E. anophelis including two from feeding tubes/bags and two from sputum suction regulators. All four isolates belonged to the outbreak clone. The outbreak strain had no apparent relationship to currently known E. anophelis strains worldwide through complete-genome sequencing analysis. Specific infection control strategies aimed at water source control and environmental disinfection were implemented subsequently and the outbreak ended in mid-2018. CONCLUSIONS: A specific E. anophelis strain was identified from a three-year outbreak. The elucidation of the mechanism of dominance and intra-hospital transmission is crucial for development of corresponsive infection control policies and outbreak control.

Reperfusion using lactate Ringer's mixture partially eliminates IGF II receptor involved cardiac damage caused by hemorrhagic shock in diabetic rats.

Diabetes is a metabolic disorder that damages many organs. We investigated the effects of reperfusion using lactate Ringer's solution (LR) in a diabetic animal model. Eight-week-old rats were divided into groups: control, hemorrhagic shock induced (HS), diabetes mellitus (DM), DM plus HS (DM + HS) and DM rats that received LR after HS (DM + HS + LR). HS was induced by withdrawing blood from the femoral artery and arterial pressure was maintained at 40 mm Hg for 1 h. Animals were perfused with either withdrawn blood or LR. Rats were sacrificed and hearts were collected from all groups. Histopathological studies were performed using left ventricles and western blotting analysis was performed using protein extracted from the left ventricle. Using the TUNEL assay, we found more apoptotic cells in the DM + HS group compared to the control group, whereas in animals resuscitated with LR, the number of apoptotic cells was reduced. Western blotting showed a significant reduction in apoptotic markers, cyt c, cas 9 and cas 3, and increased survival markers, pPI3K and pAKT, in the DM + HS + LR group. Reperfusion with LR may have therapeutic effects on trauma induced HS by blocking the IGF II R facilitated apoptosis pathway in diabetic rats.

Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report.

We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.

Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover.

Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously, consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicate that TH/PINK1/Parkin pathway has a critical role in protecting hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of TH facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T3 constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.

The risk of lower gastrointestinal bleeding in low-dose aspirin users.

BACKGROUND: Aspirin increases the risk of gastrointestinal bleeding. AIM: To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users. METHODS: Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers. RESULTS: A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB. CONCLUSIONS: The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

PURPOSE: Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. METHODS: In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. RESULTS: Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. CONCLUSION: Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts.

Systematic review: effect of psychiatric symptoms on return to work after occupational injury.

BACKGROUND: Although post-traumatic stress disorder (PTSD) and depression are commonly observed following injury, few studies have focused on the effect of psychiatric symptoms on return to work (RTW) following occupational injury. AIMS: To determine the impact of psychiatric symptoms on RTW after occupational injury. METHODS: PubMed (1980-2014), MEDLINE (1980-2014) and PsycINFO (1980-2014) databases were examined with linked fields of research in February 2015. Reference lists of eligible articles were also searched. Cohort, case-control, cross-sectional studies and intervention studies were selected according to predefined criteria. Evidence was synthesized qualitatively according to the Downs and Black and Crombie checklist. The standard checklist was used to assess the methodological quality of each study by two reviewers. RESULTS: Five of the 56 records met the inclusion and exclusion criteria. After occupational injury, the rates of RTW after the injuries varied widely, ranging from 31 to 63%. PTSD symptoms and depressive symptoms appeared to be negatively associated with RTW. CONCLUSIONS: Currently, the evidence is insufficient to draw conclusions about the effects of psychiatric symptoms on RTW after occupational injury and more studies are needed. Future studies with large sample sizes are warranted to determine the prevalence of RTW and to detect the psychiatric factors.

Genetic variations of CD36 and low platelet CD36 expression - a risk factor for lipemic plasma donation in Taiwanese apheresis donors.

BACKGROUND: New CD36 mutations are constantly being identified, although no study has specifically targeted a Taiwanese population. CD36 deficiency can result in dyslipid state and slow clearance of chylomicron. This could be linked to more frequent lipemic donations. STUDY DESIGN AND METHODS: We used flow cytometric methods to study the CD36 deficiency in 640 regular volunteer platelet apheresis donors from Taipei blood centre. The coding exons of CD36 gene were sequenced in CD36-deficient individuals, and the allele frequencies of CD36 variants were determined in the larger population by mutation-specific PCR and oligonucleotide hybridization. Visual inspection of lipemic plasma was routinely performed on samples taken before commencement of apheresis. Individuals found to have lipemic plasma are deferred until next donation. We investigated the link between positive lipemic deferral record and low platelet CD36 expression status. RESULTS: We found four donors (0·6%) with type I CD36 deficiency (both platelets and monocytes CD36(null) ) and six (1·0%) with type II CD36 deficiency (PLT: CD36(null) , monocyte: CD36(low) ). Six CD36 genetic variants were identified, two of them were novel, all but one are found exclusively in CD36(null) and CD36(low) expressors. Subjects with CD36 genetic variants also displayed deficient or reduced CD36 on monocytes. Donors with null or low PLT CD36 expression were more likely to have a lipemic deferral record than control subjects with normal PLT CD36 expression (X(2) = 27·36, odds ratio = 2·6, 95% conference interval: 1·8-3·8, P < 0·0001). CONCLUSION: Through this study, we established a donor registry to supply CD36-negative platelets for patients in need.

Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells.

We have assessed the impact of α-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson's disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of α-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson's disease progression, particularly in the context of bioenergetic dysfunction.

Migraine is associated with a higher risk of transient global amnesia: a nationwide cohort study.

BACKGROUND AND PURPOSE: The association between migraine and transient global amnesia (TGA) is not determined. Only two clinic-based studies showed that TGA patients had a higher frequency of migraine history. Our population-based study aimed to investigate whether migraine patients were associated with a higher risk of developing TGA. METHODS: Patients with migraine aged ≥18 years were identified from the Taiwan National Health Insurance Research Database between 2005 and 2009. Each migraine patient was randomly matched to one subject without migraine or other headache disorders based on age, sex and cardiovascular comorbidities. Patients with antecedent stroke, epilepsy or TGA were excluded. Both cohorts were followed up until the end of 2010. The incidence rates of TGA were compared and risk factors were identified. RESULTS: A total of 158 301 patients in the migraine cohort and 158 301 patients in the matched control cohort were enrolled. During a mean follow-up of 3.0 years (range 0-6 years), the migraine cohort had a greater risk of developing TGA than the control cohort [7.59 vs. 3.06 per 100 000 person-years, incidence rate ratio (IRR) = 2.48, P = 0.002]. Compared with the matched cohort, only female migraine patients aged 40-60 years showed a significantly higher risk of TGA [IRR = 3.18 (1.31-8.82), P = 0.005]. Of note, the incidence rates did not differ between migraine patients with and without aura. CONCLUSIONS: This population-based study demonstrates that migraine is associated with an increased risk of TGA, particularly in female patients aged 40-60 years.

Inhibitive effects of mulberry leaf-related extracts on cell adhesion and inflammatory response in human aortic endothelial cells.

Effects of mulberry leaf-related extracts (MLREs) on hydrogen peroxide-induced DNA damage in human lymphocytes and on inflammatory signaling pathways in human aortic endothelial cells (HAECs) were studied. The tested MLREs were rich in flavonols, especially bombyx faces tea (BT) in quercetin and kaempferol. Polyphenols, flavonoids, and anthocyanidin also abounded in BT. The best trolox equivalent antioxidant capacity (TEAC) was generated from the acidic methanolic extracts of BT. Acidic methanolic and water extracts of mulberry leaf tea (MT), mulberry leaf (M), and BT significantly inhibited DNA oxidative damage to lymphocytes based on the comet assay as compared to the H2O2-treated group. TNF- α -induced monocyte-endothelial cell adhesion was significantly suppressed by MLREs. Additionally, nuclear factor kappa B (NF- κ B) expression was significantly reduced by BT and MT. Significant reductions were also observed in both NF- κ B and activator protein (AP)-1 DNA binding by MLREs. Significant increases in peroxisome proliferator-activated receptor (PPAR) α and γ DNA binding by MLREs were also detected in M and MT extracts, but no evidence for PPAR α DNA binding in 50 µ g/mL MT extract was found. Apparently, MLREs can provide distinct cytoprotective mechanisms that may contribute to its putative beneficial effects on suppressing endothelial responses to cytokines during inflammation.

Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells.

MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.

Cardiac iron measurement and iron chelation therapy in patients with ß thalassaemia major: experience from Taiwan.

BACKGROUND: The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian ß-thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload. METHODS: We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia. RESULTS AND CONCLUSION: In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL(-1) (compared with ≤2500 ng mL(-1) ). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = -0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = -0·07, P = 0·52) or of the risk of developing arrhythmia.

Liver transplantation in patients infected with gram-negative bacteria: non-Acinetobacter baumannii and Acinetobacter baumannii.

BACKGROUND: The current study investigated risk factor related to gram-negative bacterial (GNB) infection by Acinetobacter baumannii and non-A baumannii groups, in liver transplantation (OLT) recipients. MATERIALS AND METHODS: All patients with OLT and their living donors were analyzed retrospectively. After excluding those with Gram-positive and fungal infections 89 patients remained in the study including 59 who were noninfected and 30 with GNB infection. The risk factors for GNB infection were classified into the preoperative versus the postoperative periods. RESULTS: GNB-infected patients were classified as non-A baumannii versus A baumannii (15 patients per group). A significant difference was observed in the numbers of intensive care and hospitalized days, hemodialysis requirement, and reoperation frequency compared with the noninfected group. Infection also correlated with hospital mortality, overall survival, and Model for End-Stage Liver Disease (MELD) scores with significance upon univariate but only the last feature on multivariate analysis. CONCLUSIONS: Preoperative MELD scores were more likely to be higher among the non-A baumannii compared with the A baumannii-infected group. However, the 1-year survival of the A baumannii-infected subjects was lower than that of the non-A baumannii infected group.

Thyroid hormone suppresses cell proliferation through endoglin-mediated promotion of p21 stability.

Hypothyroidism has been associated with significantly elevated risk for hepatocellular carcinoma (HCC), although the precise underlying mechanisms remain unknown at present. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. Endoglin is a T3/TR candidate target gene identified from our previous studies. Here, we demonstrated that T3 positively regulates endoglin mRNA and protein levels, both in vitro and in vivo. The thyroid hormone response elements of endoglin were identified at positions -2114/-2004 and -2032/-1973 of the promoter region using the electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Endoglin was downregulated in the subgroups of HCC patients and significantly associated with histology grade (negative association, P=0.001), and this expression level was significantly associated with TRα1 in these HCC patients. Our results clearly indicate that p21 is involved in T3-mediated suppression of cell proliferation. Knock down of endoglin expression in HCC cells facilitated p21 polyubiquitination and promoted cell proliferation in the presence of T3. The data collectively suggest that T3/TR signaling suppresses cell proliferation by upregulating endoglin, in turn, affecting p21 stability. The results indicate that endoglin has a suppressor role to inhibit cell proliferation in HCC cell lines.

The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis.

Only a few studies have investigated the use of PCT in the diagnosis of bone and joint infection, and these studies have had relatively small sample sizes. We performed a systematic review and meta-analysis of the diagnostic performance of serum procalcitonin (PCT) in the identification of osteomyelitis and septic arthritis in patients who present with fever and orthopedic symptoms. EMBASE, MEDLINE, and Cochrane databases and the reference lists of relevant articles were searched, with no language restrictions, through February 2012. All original studies that reported the use of serum PCT alone or in comparison with other biomarkers for diagnosis of osteomyelitis and septic arthritis were included. Seven studies qualified for inclusion. These studies enrolled a total of 583 patients with suspected bone or joint infection, 131 of whom had confirmed osteomyelitis or septic arthritis. Analysis of the PCT data indicated a bivariate pooled sensitivity of 0.67 (95 % CI: 0.37-0.88), specificity of 0.90 (95 % CI: 0.78-0.96), a positive likelihood ratio (LR+) of 6.48 (95 % CI: 2.28-14.6), and a negative likelihood ratio (LR-) of 0.37 (95 % CI: 0.16-0.84). Use of a lower PCT cut-off value (0.2-0.3 ng/mL) improved the LR + to 6.66 and the LR- to 0.15. Analysis of the three studies that also measured serum C-reactive protein (CRP) indicated that CRP had an LR + of 1.39 (95 % CI: 1.17-1.65) and an LR- of 0.40 (95 % CI: 0.12-1.36). Our results indicate that PCT may be more suitable as an aid for rule-in diagnosis rather than for exclusion of septic arthritis or osteomyelitis and that use of a lower cut-off value for serum PCT may improve its diagnostic performance.

PPARγ regulates the mitochondrial dysfunction in human neural stem cells with tumor necrosis factor alpha.

Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated transcription factors, and its ligands are known to control many physiological and pathological conditions. The hypothesis of our study was that the PPARγ agonist (rosiglitazone) could mediate tumor necrosis factor alpha (TNFα) related to the regulation of human neural stem cells (hNSCs), by which TNFα possibly fulfills important roles in neuronal impairment. The results show that PPARγ mediates the cell viability of hNSCs via the downregulation of the activity of caspase 3, indicating that this rescue effect of PPARγ could improve the reduced levels of two mitochondrial regulators, adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) in the hNSCs with TNFα. The stimulation of mitochondrial function by PPARγ was associated with activation of the PPAR coactivator1 alpha (PGC1α) pathway by up-regulation of oxidative defense and mitochondrial systems. The above protective effects appeared to be exerted by a direct activation of the rosiglitazone, because it protected hNSCs from TNFα-evoked oxidative stress and mitochondrial deficiency. Here we show that the rosiglitazone protects hNSCs against Aß-induced apoptosis and promotes cell survival. These findings extend our understanding of the central role of PPARγ in TNFα-related neuronal impairment, which probably increases risks of neurodegenerative diseases. The anti-inflammatory effects of PPARγ in the hNSCs with TNFα, and the involved mechanisms were also characterized.

Effects of tendon viscoelasticity in Achilles tendinosis on explosive performance and clinical severity in athletes.

The aim was to compare viscoelastic properties of Achilles tendons between legs in elite athletes with unilateral tendinosis, and to investigate relationships between the properties and explosive performance and clinical severity. Seventeen male athletes (mean ± standard deviation age, 27.3 ± 2.0 years) who had unilateral, chronic middle-portion tendinopathy of the Achilles tendon were assessed by the Victorian Institute of Sport Assessment questionnaire, measurements of tendon viscoelastic properties, voluntary electromechanical delay (EMD), normalized rate of force development (RFD), and one-leg hopping distance. Compared with the non-injured leg, the tendinopathic leg showed reduced tendon stiffness (-19.2%. P < 0.001), greater mechanical hysteresis (+21.2%, P = 0.004), lower elastic energy storage and release (-14.2%, P = 0.002 and -19.1%, P < 0.001), lower normalized RFD at one-fourth (-16.3%, P = 0.02), 2/4 (-17.3%, P = 0.006), and three-fourths maximal voluntary contraction (-13.7%, P = 0.02), longer soleus and medial gastrocnemius voluntary EMD (+26.9%, P = 0.009 and +24.0%, P = 0.004), and shorter hopping distances (-34.1%, P < 0.001). Tendon stiffness was correlated with normalized RFD, voluntary EMD in the medial gastrocnemius, and hopping distances (r ranged from -0.35 to 0.64, P < 0.05). Hysteresis was correlated to the soleus voluntary EMD and hopping distances (r = 0.42 and -0.39, P < 0.05). We concluded that altered tendon viscoelastic properties in Achilles tendinosis affect explosive performance in athletes.

Thyroid hormone receptors promote metastasis of human hepatoma cells via regulation of TRAIL.

Although accumulating evidence has confirmed the important roles of thyroid hormone (T(3)) and its receptors (TRs) in tumor progression, the specific functions of TRs in carcinogenesis remain unclear. In the present study, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was directly upregulated by T(3) in TR-overexpressing hepatoma cell lines. TRAIL is an apoptotic inducer, but it can nonetheless trigger non-apoptotic signals favoring tumorigenesis in apoptosis-resistant cancer cells. We found that TR-overexpressing hepatoma cells treated with T(3) were apoptosis resistant, even when TRAIL was upregulated. This apoptotic resistance may be attributable to simultaneous upregulation of Bcl-xL by T(3), because (1) knockdown of T(3)-induced Bcl-xL expression suppressed T(3)-mediated protection against apoptosis, and (2) overexpression of Bcl-xL further protected hepatoma cells from TRAIL-induced apoptotic death, consequently leading to TRAIL-promoted metastasis of hepatoma cells. Moreover, T(3)-enhanced metastasis in vivo was repressed by the treatment of TRAIL-blocking antibody. Notably, TRAIL was highly expressed in a subset of hepatocellular carcinoma (HCC) patients, and this high-level expression was significantly correlated with that of TRs in these HCC tissues. Together, our findings provide evidence for the existence of a novel mechanistic link between increased TR and TRAIL levels in HCC. Thus, TRs induce TRAIL expression, and TRAIL thus synthesized acts in concert with simultaneously synthesized Bcl-xL to promote metastasis, but not apoptosis.