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Blocking the HER2 signaling pathway has been an effective strategy in the treatment of HER2‐positive breast cancer. It mainly relies on the use of monoclonal antibodies and tyrosine‐kinase inhibitors. Herein, we present a new strategy, the nano molecularly imprinted polymer (nanoMIP). The nanoMIPs, imprinted using HER2 N‐glycans, could bind almost all HER2 glycans and suppress the dimerization of HER2 with other HER family members, blocking the downstream signaling pathways, thereby inhibiting HER2+ breast cancer growth. In vitro experiments demonstrated that the nanoMIPs specifically targeted HER2+ cells and inhibited cell proliferation by 30 %. In vivo experiments indicated that the mean tumor volume of the nanoMIP‐treated group was only about half of that of the non‐treated groups. This study provides not only a new possibility to treat of HER2+ breast cancer but also new evidence to boost further development of nanoMIPs for cancer therapy. [ABSTRACT FROM AUTHOR]

Blocking the HER2 signaling pathway has been an effective strategy in the treatment of HER2‐positive breast cancer. It mainly relies on the use of monoclonal antibodies and tyrosine‐kinase inhibitors. Herein, we present a new strategy, the nano molecularly imprinted polymer (nanoMIP). The nanoMIPs, imprinted using HER2 N‐glycans, could bind almost all HER2 glycans and suppress the dimerization of HER2 with other HER family members, blocking the downstream signaling pathways, thereby inhibiting HER2+ breast cancer growth. In vitro experiments demonstrated that the nanoMIPs specifically targeted HER2+ cells and inhibited cell proliferation by 30 %. In vivo experiments indicated that the mean tumor volume of the nanoMIP‐treated group was only about half of that of the non‐treated groups. This study provides not only a new possibility to treat of HER2+ breast cancer but also new evidence to boost further development of nanoMIPs for cancer therapy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop an efficient and no pollutants deproteinization method for polysaccharide (AGP) from Arca granosa based on the palygorskite adsorption treatment (PAT). Firstly, the optimal adsorption conditions were obtained by the response surface methodology (RSM) as follows: adsorption for 136 min at 60 °C with the dosage of 0.27 g. Under the optimal conditions, the deproteinization ratio (Dr%), recovery ratio (Rr%) and selectivity coefficient (K C) were 87.35 ± 0.44%, 92.89 ± 0.41% and 12.28 ± 0.64, respectively. Then, the adsorption kinetics and isotherms experiments indicated that the adsorption process was endothermic and spontaneous, and were fitted well by the pseudo-second-order equation and the Freundlich equation, respectively. In addition, compared with the classical Sevag method, the PAT method was proven to be reliable. More importantly, the palygorskite was reusable and the deproteinization process produced no pollutants. These results demonstrated that the PAT method present a highly efficient and environmental friendly technique for the large-scale deproteinization of polysaccharides. An efficient and no pollutants deproteinization method based on the palygorskite adsorption treatment (PAT) was developed successfully. The adsorption conditions, adsorption behaviors, and the reusability were investigated, respectively. In addition, the reliable of the PAT method was studied by compared with the Sevag method. Image 1 • Palygorskite adsorption deproteinization is proven effective and reliable. • Adsorption conditions of palygorskite adsorption treatment (PAT) are optimized. • The fundamental adsorption behaviors of the PAT method are investigated. • The PAT method is no pollutants and suitable for large-scale deproteinization. [ABSTRACT FROM AUTHOR]

Background. Previous studies have demonstrated that acupuncture was an effective alternative for treating major depressive disorders. However, the use of acupuncture for the treatment of postpartum depression remains controversial. This review summarizes the most significant studies in the area of acupuncture treatment for postpartum depression and provides a detailed overview of the efficacy of acupuncture for the treatment of postpartum depression. Methods. We undertook a systematic review of publicly available electronic databases to identify studies that evaluated acupuncture for the treatment of postpartum depression. Our meta-analysis selected randomized controlled trials (RCTs) and quasi-RCTs that reported on the treatment effect of acupuncture on postpartum depression. Results. Eight prospective trials reporting data on postpartum depression were included in our meta-analysis. The results demonstrated that acupuncture treatment could significantly reduce HAMD scores (SMD: -1.08; 95%CI: -2.11 to -0.05; P=0.040). However, with regard to EPDS, clinical response, and serum estradiol levels, pooled analysis suggested no beneficial effects of acupuncture for postpartum women in EPDS (RR: 1.23; 95%CI: 0.90 to 1.67; P=0.195); clinical response (RR: 1.00; 95%CI: 0.89 to 1.12; P=0.969); and the levels of serum estradiol (SMD: 1.96; 95%CI: -0.01 to 3.93; P=0.051). Limitations. First, there was relatively high heterogeneity among the studies, except for clinical response. In order to identify the sources of heterogeneity, we divided the studies into subgroups by way of controls. However, heterogeneity still existed, which suggested that it arose from participants rather than controls. Second, the sample size of the studies was small, causing the power of summary results to be low. This may result in over- or underestimating the interpretation of the results. Third, our analysis used pooled data, which restricted us from performing a more detailed analysis. Conclusions. Our meta-analysis suggested that acupuncture treatment may reduce HAMD scores, while no significant effects on EPDS, clinical response, and serum estradiol levels were observed. [ABSTRACT FROM AUTHOR]

Abstract Background Measures of left ventricular (LV) systolic and diastolic function are known predictors of mortality after repair of tetralogy of Fallot. We aimed to characterise LV reverse remodelling achievable with ramipril therapy. Methods and results A blinded post-hoc analysis of baseline and 6-month follow-up echocardiograms from the APPROPRIATE (ISRCTN: 97515585) randomised double-blinded placebo-controlled trial of ramipril therapy was performed in 64 patients: 32 in ramipril and 32 in placebo group. Tissue Doppler systolic and diastolic myocardial velocities, mitral inflow velocities and time intervals were measured. Left atrial area and left atrial emptying fraction were calculated. There was significant increase in long axis shortening mean (standard deviation); MAPSE [1.9 (4.2) mm vs −0.2 (3.7) mm; p = 0.030], peak lateral systolic velocity; S′ lateral [1.0 (2.0) cm/s vs −0.3 (2.2) cm/s; p = 0.025], peak lateral early diastolic velocity; E′ lateral [0.57 (2.4) cm/s vs −3.3 (3.9) cm/s; p < 0.001], transmitral to lateral mitral annular early diastolic velocity ratio; E/E′ lateral [−0.7 (1.9) vs 1.5 (1.9); p < 0.001] over the study period in the ramipril compared to the placebo group. Significantly higher measurements were observed in the ramipril arm of the subgroup of patients with right ventricular restrictive physiology in terms of peak late diastolic velocity; A [5.9 (13.5) cm/s vs −5.8 (12.5) cm/s; p = 0.041] and early to late diastolic transmitral velocity ratio; E/A [−0.18 (0.42) vs 0.23 (0.48); p = 0.037]. Conclusion Six months' ramipril treatment appears to limit progression of both diastolic and systolic LV function in adults late after tetralogy of Fallot repair. With increased appreciation that even subtle LV disease predicts tetralogy of Fallot outcomes, further clinical trials of drug therapies are justified. Highlights • Left ventricular (LV) function is a known predictor of mortality after tetralogy of Fallot repair. • We aimed to characterise LV reverse remodelling achievable with ramipril therapy. • 6-months' ramipril treatment limits progression of both diastolic and systolic LV function. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Molecular dynamics simulation for representative ALK5-ligand complexes was carried out to reveal their stability. • The field-based QSAR model (Q2 = 0.548, R2training = 0.840, R2test = 0.750) owns good predictive capabilities. • Interaction analysis of ALK5-ligand complexes could provide valuable information about the key residues. Abstract The discovery of drugs relevant to transforming growth factor β (TGF-β) receptor inhibitors have been considered as a considerable challenge during therapy idiopathic pulmonary fibrosis diseases. For the first time, herein we illustrate a field-based quantitative structure-activity relationship (QSAR) model and molecular dynamics (MD) simulations for novel 7-substituted-pyrazolo [4, 3-b] pyridine derivatives with biological activity for the TGF-β receptor, with an attempt of elucidating the 3D structural features that are essential for the activity. Results demonstrate that the field-based model (Q2 = 0.548, R2 training = 0.840, R2 test = 0.750) are acceptable with good predictive capabilities. In addition, MD studies were also carried out on the training set with the aim of exploring their binding modes in the active pocket of TGF-β receptor, resulting in some of the crucial structural fragments which are responsible for inhibitory activity. Therefore, we summarized the following features required for TGF-β receptor inhibition: electronegative in region1, bulky groups in region2 and smaller groups in region3. Based on the model and related information, we hope the above information provides an important insight for understanding the interactions of the inhibitors and TGF-β receptor, which may be useful in discovering novel potent inhibitors. [ABSTRACT FROM AUTHOR]

Objective(s): Diabetes mellitus (DM) is a widespread metabolic disorder worldwide. Clinical physicians have found diabetic patients have mild to middle cognitive dysfunction and an alteration of brain monoaminergic function. This study explored the change in various patterns of behavioral models and brain monoamine function under streptozotocin (STZ)-induced type 1 diabetes. Materials and Methods: We established a type 1 DM model via intravenous injection with STZ (65 mg/kg) in rats. Three weeks after the STZ injection, various behavioral measurements including the inhibitory avoidance test, active avoidance test and Morris water maze were conducted. Finally, all rats were dissected and the concentrations of monoamines and their metabolites in cortex and hippocampus were measured by high performance liquid chromatography with electrochemical detection. Results: We found that STZ induced type 1 diabetes (hyperglycemia and lack of insulin) in rats. STZinduced diabetic rats had cognitive impairment in acquisition sessions and long-term retention of the active avoidance test. STZ-induced diabetic rats also had cognitive impairment in spatial learning, reference and working memory of the Morris water maze. STZ significantly reduced concentrations of norepinephrine (NE) in the cortex and dopamine (DA) in the hippocampus, but increased concentrations of DA and serotonin (5-HT) in the cortex 35 days after injection. The concentration of 5-HT in the hippocampus was also significantly increased. Conclusion: The data suggested that this cognitive impairment after a short-term period of STZ injection might be related to cortical NE dysfunction, differential alteration of cortical and hippocampal DA function, and brain 5-HT hyperfunction. [ABSTRACT FROM AUTHOR]

Background: To systematically review and assess the efficacy and safety of hydroxychloroquine (HCQ) for treating primary Sjogren's syndrome (pSS).Methods: Five electronic databases (Pubmed, EMBASE, Web of science, Ovid, Cochrane Library) were searched for randomized controlled trials and retrospective or prospective studies published in English that reported the effect of HCQ on pSS. The subjective symptoms (sicca symptoms, fatigue and pain) and the objective indexes (erythrocyte sedimentation rate and Schirmer test) were assessed as main outcome measures. A meta-analysis and descriptive study on the efficacy and safety of HCQ were conducted. The estimate of the effect of HCQ treatment was expressed as a proportion together with 95% confidence interval, and plotted on a forest plot.Results: Four trials with totals of 215 SS patients, including two randomized controlled trials, one double blind crossover trial and one retrospective open-label study, were analyzed in this review. For dry mouth and dry eyes, the effectiveness of HCQ treatment was essentially the same as placebo treatment. For fatigue, the effectiveness of HCQ was lower than placebo. The efficacy of HCQ in treating pain associated with pSS was superior to that of the placebo. There was no significant difference between HCQ-treated groups and controls in terms of Schirmer test results, but HCQ could reduce the erythrocyte sedimentation rate compare with placebo. A descriptive safety assessment showed that gastrointestinal adverse effects were the most common adverse effects associated with HCQ.Conclusions: This systematic review showed that there is no significant difference between HCQ and placebo in the treatment of dry mouth and dry eye in pSS. Well-designed, randomized, controlled trials are needed to provide higher-quality evidence to confirm our findings, and future studies should focus on some other index or extraglandular measures, such as cutaneous manifestations, to further explore the therapeutic effect of HCQ in pSS. [ABSTRACT FROM AUTHOR]

Background: Gastric epithelial hyper-proliferation was reported in patients with Helicobacter pylori (H. pylori)-infected gastric mucosa with intestinal metaplasia (IM) changes. In patients with gastric ulcer (GU) and IM, the GU may have a different healing rate in comparison to patients without IM. This study aimed to compare the difference in GU healing between H. pylori-infected patients with IM and those without IM.Methods: We retrospectively analyzed patients at the Keelung Chung Gung Memorial Hospital during the period from March 2005 to January 2011. The inclusion criteria were: 1) endoscopic findings of GU and biopsy histological examination plus rapid urease test indicating H. pylori infection; 2) gastric IM adjacent to a GU but with no atrophic gastritis changes; 3) patients receiving H. pylori eradication triple therapy and 8 weeks of maintenance therapy with a proton pump inhibitor; and 4) patients receiving follow-up endoscopy within the 3rd and the 4th months after treatment.Results: In total, 327 patients with GU and H. pylori infection (136 with IM and 191 without IM) were included. Patients with IM had a higher GU healing rate than those without IM (91.9% vs. 84.3%, P = 0.040). Multivariate logistical regression analysis revealed that failure of H. pylori eradication (Odds = 4.013, 95% CI: 1.840-8.951, P < 0.001) and gastric IM (Odds = 0.369, 95% CI: 0.168-0.812, P = 0.013) were the predictors of non-healing GU following treatment.Conclusions: Patient with gastric IM change may have a higher GU healing rate than those without gastric IM. However, successful H. pylori eradication is a more important factor for GU healing than gastric IM. [ABSTRACT FROM AUTHOR]

This retrospective study tested the feasibility of decitabine (DAC) plus intermediate-dose cytarabine (ID-AraC) followed by HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs) infusion as consolidation treatment for older patients with acute myeloid leukemia (AML) in first complete remission (CR). A total of 23 patients received this regimen for 3 cycles (D-GPBSCs group), and the outcome was compared with that of 19 patients treated with repeated cycles of ID-AraC chemotherapy (chemo group). The two regimens were well tolerated. The median recovery times for neutrophils and platelets were shorter in D-GPBSCs group than in chemo group (p<.05). No graft-versus-host disease (GVHD) was observed in D-GPBSCs group. The 2-year leukemia-free survival (LFS) and overall survival (OS) were better in D-GPBSCs group (51.6 and 55.4%) than in chemo group (27.1 and 34.2%) (p = .047 and p = .056). These data suggest that DAC and ID-AraC followed by GPBSCs as a consolidation regimen may be a safe and promising option for older patients with AML. [ABSTRACT FROM AUTHOR]

MiR-20a has been previously reported to participate in the development of various human diseases. However, the role of miR-20a in the pathology of atherosclerosis remains elusive. The present study aimed to reveal the relationship between miR-20a expression and atherosclerosis using in vitro cell model. The expression level of miR-20a was detected in human aortic endothelial cells (HAECs) under Ox-LDL exposure. Meanwhile, the regulatory effects of miR-20a on predicted targets (TLR4 and TXNIP) were also determined. Moreover, the levels of key proteins and inflammatory mediators in TLR4 and NLRP3 signaling were detected to further confirm the regulatory effects of miR-20a. We found that miR-20a expression was repressed under Ox-LDL condition, and both TLR4 and TXNIP acted as regulatory targets of miR-20a. Overexpressed miR-20a reduced ROS generation under Ox-LDL treatment, and this effect was restored by forced expression of TLR4. Moreover, key molecules (including MyD88, TRIF, phosphorylated NF-κB (p65), NLRP3, ASC, cleaved caspase-1, ICAM-1 and IL-1β) in TLR4 and NLRP3 signaling were significantly repressed under miR-20a overexpression. In conclusion, miR-20a could negatively regulate TLR4 and NLRP3 signaling to protect HAECs from inflammatory injuries, which provides a new insight into the inhibition of atherosclerotic development. [ABSTRACT FROM AUTHOR]

Background There has been no effective treatment for acute ischemic stroke (AIS) patients who presented to the Emergency Department > 4.5 h without a visible arterial occlusion on the neurovascular imaging studies. In this study, we aimed to investigate whether intravenous antiplatelet agent tirofiban was safe and potentially effective in AIS patients who had no visible arterial occlusion and was outside of treatment window for Alteplase. The goal of this study was to collect preliminary data to plan a future phase II study. Method Twenty-five patients received intravenous tirofiban therapy. The safety outcomes were assessed by the incidence of symptomatic intracerebral hemorrhage (sICH), systematic bleeding and mortality. Efficacy outcomes were evaluated with National Institutes of Health Stroke Scale (NIHSS) score at day 7 (or discharge) and modified Rankin Scale (mRS) at 90 days. Outcomes for these patients were compared with a historical age-gender-admission-NIHSS matched cohort treated with aspirin and/or clopidogrel. Results The rate of intracerebral hemorrhage, systematic bleedings, and death were not found in both groups. At day 7 or discharge, the neurological function improved significantly in both treatment groups. However, the NIHSS score was lower in tirofiban group compared with the control group (2 vs. 3, p = 0.045). At 3 months, more patients in tirofiban group had favorable outcomes (mRS 0–1) compared with control group (84% vs. 52%; adjusted odds ratio: 10.57; 95% CI: 1.54–72.33; p = 0.016). Conclusions Intravenous tirofiban appears to be safe and potentially effective for the ischemic stroke patients with no artery occlusion on neurovascular imaging studies and being out of the window for thrombolytic therapy. A next logic step is to plan for a phase II study. [ABSTRACT FROM AUTHOR]

Objective Few studies have concentrated on the sagittal alignment of lumbar disc herniation ( LDH), especially the parameters of the pelvis, and controversy exists about whether pelvic morphology is involved in the pathogenesis of LDH. The present study analyzed the characteristics of the sagittal alignment in young Chinese LDH patients and explored the impact of pelvic morphology on the pathogenesis of LDH. Methods A retrospective analysis was conducted on 100 young patients with LDH (69 men and 31 women, aged 18-35 years), and the clinical and imaging findings met the criteria for the diagnosis of LDH. The control group included 100 asymptomatic volunteers with matching age and gender. Coronal and sagittal parameters were measured on the anteroposterior and lateral radiographs of the whole spine, including lumbar lordosis ( LL), pelvic incidence ( PI), sacral slope ( SS), pelvic tilt ( PT), thoracic kyphosis ( TK), and sagittal balance ( SVA). The cases were classified into four types by the apex position of lumbar lordosis (type I, L5 or the L4-5 intervertebral space; type II, bottom or middle of L4; type III, upper part of L4 or the intervertebral space between L3 and L4; type IV, L3 or more high level), and divided into three groups by PI; namely, a low PI group ( PI < 40°), a medium PI group (40° ≤ PI < 50°), and a high PI group ( PI ≥ 50°). The sagittal parameters, especially PI, were compared between the LDH group and the control group. Correlations between the parameters in the LDH group were analyzed. Results The PI value of the LDH group was not different from that of the control group (46.1° ± 10.0° vs 47.2° ± 8.8°, P > 0.05). The LDH group showed lower average LL, SS, and TK ( P < 0.01), as well as higher PT and SVA compared with the control group ( P < 0.01). The LL (34.4° ± 15.3° vs 50.8° ± 10.2°) and SVA (21.6 ± 53.6 mm vs − 18.4 ± 32.8 mm) showed a significant difference ( P < 0.01); LL was correlated with PI, SS, PT, TK and SVA ( P < 0.01); and SVA was also correlated with the parameters above ( P < 0.01) except PI ( P > 0.05), and the lordosis apex tended to be higher. The distributions of PI groups between the LDH group and the control group were not different. Pairwise correlations were found among LL, PI, SS, and PT. In addition, TK and SVA were correlated with LL, SS, and PT. Conclusions There is no difference in PI between young Chinese patients with lumbar disc herniation and the normal population. Young LDH patients may present flat lumbar and thoracic curves, as well as lower sacral slope. The anteversion sagittal imbalance is regulated by both the spine and the pelvis. [ABSTRACT FROM AUTHOR]

However, anti-eczema therapy did not improve itching and skin condition. The significant improvement of blisters and the associated itching with dupilumab suggests a novel treatment option for BP. The eczema-like skin lesions and all blisters had resolved (Figure 1D-F,I,J) and the itch score decreased to 2 of 10 after 6 weeks of dupilumab treatment. [Extracted from the article]

Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy. [ABSTRACT FROM AUTHOR]

The development of combinational anti-tumor therapy is of great value. Here, the thermal-sensitive and hepatic tumor cell targeting peptide-A54 modified polymer, A54-poly(ethylene glycol)-g-poly(acrylamide-co-acrylonitrile) (A54-PEG-g-p(AAm-co-AN)) can self-assemble into an 80 nm-sized micelle, which shows a thermal-sensitive behavior with an upper critical solution temperature (UCST) of 43 °C. This self-assembled and targeted A54-PEG-g-p(AAm-co-AN) micelle can co-encapsulate anti-tumor drug doxorubicin (DOX) and magnetic nanoparticles (MNPs) taking advantage of the hydrophobic core of the core-shell micellar structure, when the temperature is lower than 43 °C. A much higher accumulation of the MNPs@A54-PEG-g-p(AAm-co-AN) to the tumor navigated by the A54 targeting peptide is achieved. Due to the thermal-agent effect of the accumulated MNPs in tumor, the mild microwave (8 W) applied afterwards specifically elevates the local tumor temperature by 13 °C, compared to 6 °C without MNPs accumulation in 30 min. The greater temperature rise resulted from the thermal-agent effect of MNPs doesn't only activate the drug release inside tumor cells, but also achieve an augmented hyperthermia. A mild microwave activated, chemo-thermal combinational tumor therapy is thus developed. [ABSTRACT FROM AUTHOR]

Background/Aims: We examined the factors associated with blood pressure variability in a multi-ethnicity prospective study in China to gain more evidence to guide the prevention and management of hypertension through risk factor intervention. Methods: A total of 318 consecutive adult subjects aged 29-94 years with suspected or known hypertension were enrolled in this study. Blood pressure variability measurements were based on ambulatory blood pressure monitoring. To measure short-term reading-to-reading blood pressure variability in this study, we used the standard deviation(SD) of the blood pressure to estimate the blood pressure variability. Results: The SDs of the blood pressure in this study ranged from 5.425 to 32.25, with a median of 10.81 (quartile range, 8.90-12.46). No significant difference regarding the level distribution of blood pressure variability was found across the various ethnicities. Spearman correlation analyses indicated that the SD of blood pressure was positively correlated with DSBP (r=0.302, p=<0.001), NSBP (r=0.383, p=<0.001), NDBP (r=0.230, p=<0.001), and FBG (r=0.129, p=0.023) and was negatively correlated with triglyceride (r=-0.289, p=<0.001), CR (r=-0.242, p=<0.001), HDL-C (r=-0.230, p=<0.001), LDL-C (r=-0.186, p=0.001), and apolipoprotein B levels (r=-0.157, p=0.006). Multiple linear regression analysis indicated that triglycerides (β=-0.217, p=<0.001), NSBP (β=0.174, p=0.003), FBG (β=0.128, p=0.024), DDBP (β=-0.128, p=0.022), and apolipoprotein A (β=-0.116, p=0.036) were significantly and independently associated with the blood pressure variability. Conclusions: In this study, blood pressure variability was significantly associated with not only blood pressure levels but also patient demographic, clinical and biochemical characteristics. [ABSTRACT FROM AUTHOR]

Objective:Although several previous studies have examined the efficacy of sertraline in the treatment of posttraumatic stress disorder (PTSD), none involved Chinese PTSD patients. This study aimed to evaluate sertraline efficacy and adverse events in Chinese patients with PTSD over 12 weeks. Methods:In total, 72 PTSD patients were randomly assigned to receive sertraline (135 mg daily) or a placebo for 12 weeks. Impact of Event Scale-Revised subscores constituted the primary outcome, with Clinical Global Impression Scale-Severity scores and adverse events as secondary outcomes. Results:Sixty-five subjects completed the study, and their data were included in the final analysis. Sertraline showed greater efficacy in enhancing Impact of Event Scale-Revised and Clinical Global Impression Scale-Severity scores at 6 and 12 weeks relative to that of the placebo. The most common adverse event was nausea, which occurred in 12 (33.3%) and 8 (22.2%) patients in the sertraline and placebo groups, respectively. No sertraline-related deaths were recorded. Conclusions:In summary, we demonstrated that 12 weeks of sertraline was efficacious and well-tolerated in Chinese patients with PTSD. [ABSTRACT FROM PUBLISHER]

Background aims. Pulmonary fibrosis induced by irradiation is a significant problem of radiotherapy in cancer patients. Extracellular superoxide dismutase (SOD3) is found to be predominantly and highly expressed in the extracellular matrix of lung and plays a pivotal role against oxidative damage. Early administration of mesenchymal stromal cells (MSCs) has been demonstrated to reduce fibrosis of damaged lung. However, injection of MSCs at a later stage would be involved in fibrosis development. The present study aimed to determine whether injection of human umbilical cord-derived MSCs (UC-MSCs) over-expressing SOD3 at the established fibrosis stage would have beneficial effects in a mice model of radiation pulmonary fibrosis. Methods. Herein, pulmonary fibrosis in mice was induced using Cobalt-60 (60Co) irradiator with 20 Gy, followed by intravenous injection of UC-MSCs, transduced or not to express SOD3 at 2 h (early delivery) and 60 day (late delivery) post-irradiation, respectively. Results. Our results demonstrated that the early administration of UC-MSCs could attenuate the microscopic damage, reduce collagen deposition, inhibit (myo)fibroblast proliferation, reduce inflammatory cell infiltration, protect alveolar type II (AE2) cell injury, prevent oxidative stress and increase antioxidant status, and reduce profibrotic cytokine level in serum. Furthermore, the early treatment with SOD3-infected UC-MSCs resulted in better improvement. However, we failed to observe the therapeutic effects of UC-MSCs, transduced to express SOD3, during established fibrosis. Conclusion. Altogether, our results demonstrated that the early treatment with UC-MSCs alone significantly reduced radiation pulmonary fibrosis in mice through paracrine effects, with further improvement by administration of SOD3-infected UC-MSCs, suggesting that SOD3-infected UC-MSCs may be a potential cell-based gene therapy to treat clinical radiation pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

We herein evaluated the antibacterial effect of curry plant EO, a natural antibacterial agent, on B. cereus. The curry plant EO was encapsulated into liposomes to improve the chemical stability of EO and its active time. By a thin-film dispersion method, soy lecithin, in combination with cholesterol, were used to prepare liposomes at various curry plant EO concentrations. The optimal formula for preparing liposome is a curry plant EO concentration of 5.0 mg/ml. The average particle size of liposomes containing curry plant EO was 196.6 nm with a PDI of 0.218 and the entrapment efficiency was 56.34%. The optimal liposomes containing curry plant EO gave a zeta potential of −31.1 mV. Besides, liposome-encapsulated curry plant EO exhibited efficient antimicrobial activity for B. cereus in rice. Practical applications As a natural and safe antibacterial agent, curry plant EO shows an excellent antibacterial effect on B. cereus in rice. The concept in the present study may be useful in the future to deliver a variety of antimicrobials for the treatment of various infections caused by bacteria or other organisms. Hence, the antimicrobial agent has broad prospect in the field of food preservation. [ABSTRACT FROM AUTHOR]

Aim: Biliary atresia (BA) has preponderance in Asian populations with Kasai portoenterostomy (KP) regarded as the first-line standard of care. Yet reports from Southeast Asia remain scant. This study reviews the demographics, short- and medium-term outcomes for our cohort, and evaluates prognostic factors for outcome.Methods: All patients diagnosed with BA between January 1997 and December 2013 were included. Clinical data were obtained from medical records. Jaundice clearance was defined as total bilirubin < 20 µmol/L within 6 months after KP. Two-year and 5-year native liver survival (NLS) were determined. Prognostic factors examined included gender, ethnicity, associated anomalies, age at KP, post-KP cholangitis and clearance of jaundice within 6 months.Results: Of 58 patients studied, 31(53.4%) were male. Median age at time of KP was 53 days (range: 28-127). Ethnic distribution showed 32 (55.2%) Chinese, 16 (27.6%) Malays and 10 (17.2%) others. Twenty-one (36.2%) patients achieved jaundice clearance by 6 months. Two-year NLS rate was 36 out of 50 (72%), while 5-year NLS rate was 16 out of 35 (45.7%). Only clearance of jaundice within 6 months had a significant association with NLS (P = 0.006). All other factors showed no significant impact on outcome.Conclusions: Our short- and medium-term outcomes after KP for BA are comparable with those reported by most international centres. However, prognostic factors such as age at KP, cholangitis episodes and associated anomalies did not show significant correlation; only clearance of jaundice within 6 months was significantly predictive of NLS. [ABSTRACT FROM AUTHOR]

The cell-surface glycoprotein CD56 has three major isoforms that play important roles in cell adhesion and signaling, which may promote cell proliferation, differentiation, survival, or migration. It is an important molecule in normal kidney development and acts as a key marker in Wilms tumor stem and progenitor cells. Here, we review the structural and genetic features of the CD56 glycoprotein, and summarize its roles in the normal versus diseased metanephric blastema. We discuss areas of CD56-related research that may complement or improve existing Wilms tumor treatment strategies, including the antibody-drug conjugate lorvotuzumab mertansine that binds to CD56. [ABSTRACT FROM PUBLISHER]

Background Antipsychotic agents are well known for their arrhythmigenic effect on ventricular arrhythmia. Though a few case reports observed the occurrence of atrial fibrillation (AF) after antipsychotic exposure, information about their implication in AF is limited. Methods Based on the National Health Insurance Database in Taiwan, we conducted a nested case-control study to investigate the relationship between antipsychotics and AF. From 2001 to 2010, a total of 34,053 cases of AF and 34,919 matched controls were enrolled. Antipsychotic exposure was measured and binding affinity to neurotransmitter receptors was calculated. Both medical and psychiatric comorbidities were identified and adjusted in multivariate logistic regression analysis. Results Current antipsychotic use was associated with a 17% increased risk of AF relative to nonusers (adjusted OR: 1.17, 95% CI: 1.10–1.26). A dose-dependent relationship of antipsychotic exposure and AF risk was observed ( P for trend < 0.001). Antipsychotics with higher binding affinity to muscarinic M2 receptors were associated with a higher incidence of AF. In subgroup analysis, subjects with preexisting hypertension, diabetes, or coronary artery diseases were at greater risk of developing AF following antipsychotic exposure. Conclusion Antipsychotic exposure was associated with increased risk of AF, especially for agents with higher cardiac muscarinic receptor binding affinity. Physicians should monitor the occurrence of new-onset AF, and strictly control underlying medical risk factors while prescribing antipsychotic agents to high-risk populations. [ABSTRACT FROM AUTHOR]

The study was aimed to investigate the effect of melatonin on the development potential of mouse MII oocytes after cryopreservation. Mouse MII oocytes were subjected first to vitrification/warming and 2 h of in vitro culture (phase 1), then to parthenogenetic activation (PA) followed by in vitro culture of parthenogenetic embryos (phase 2). Different concentrations of melatonin (0, 10 −9 , 10 −6 mol/L) were added to the medium during either phase 1, phase 2 or both phases. The fresh oocytes were used as control. When melatonin was used during both phases, 10 −9 mol/L melatonin-treated group showed similar rates of cleavage and 4-cell embryo development compared with control, which were significantly higher than those of melatonin-free group, while the rates in either 10 −6 mol/L melatonin-treated or melatonin-free groups were significantly lower than that in control. When 10 −9 mol/L melatonin was added during either phase 1 or phase 2, both cleavage and 4-cell embryo development rates of either group were significantly lower than those of control. After oocyte vitrification/warming and PA, the ROS levels increased significantly and maternal-to-zygotic transition (MZT) related genes ( Dcp1a , Dcp2 , Hspa1a , Eif1ax , Pou5f1 , Sox2 ) expression were disorganized. However, after 10 −9 mol/L melatonin supplementation, the ROS levels decreased significantly compared with melatonin-free group, and the gene expressions were almost recovered to normal level of control group. These results demonstrated that 10 −9 mol/L melatonin supplementation could increase the developmental potential of vitrified-warmed mouse MII oocytes, which may result from ROS scavenging activities and recovery of normal levels of the expressions of MZT-related genes. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is a frequent form of focal intractable epilepsy in adults, but the specific mechanism underlying the epileptogenesis of TLE is still unknown. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) (the murine homolog gene called paired immunoglobulin-like receptor B, or PirB), participates in the process of synaptic plasticity and neurite growth in the central nervous system (CNS), suggesting a potential role of LILRB2 in epilepsy. However, the expression pattern of LILRB2 and the downstream molecular signal in intractable TLE remains poorly understood. In the present study, western blotting and immunohistochemistry results showed that LILRB2 expression was upregulated in the temporal neocortex of patients with TLE. Moreover, protein levels of LILRB2 negatively correlated with the frequency of seizures in TLE patients. In the pilocarpine-induced C57BL/6 mouse model, PirB upregulation in the hippocampus began 12 h after status epilepticus (SE), reached a peak at 7 days and then maintained a significantly high level until day 60. Similarly, we found a remarkable increase in PirB expression at 1 day, 7 days and30days post-SE in the temporal cortex. Double-labeled immunofluorescence showed that LILRB2/PirB were highly expressed in neurons and astrocytes but not microglia. In addition, protein levels of POSH, SHROOM3, ROCK1 and ROCK2, the important downstream factors of the LILRB2 pathway, were significantly increased in the epileptic foci of TLE patients and located on the NeuN-positive neurons and GFAP-positive astrocytes. Taken together, our results indicate that LILRB2/PirB may be involved in the process of TLE. [ABSTRACT FROM AUTHOR]

Context Combination of chemotherapy and nucleic acid therapy generally take advantage of drugs anti-tumor activity together with DNA capacity to transfect cancer cells, showing great promise in cancer treatment. However, effective co-delivery of drugs and DNA in a single carrier for cancer treatment remains a challenge. Objective This study aimed to design a tumor targeted, pH sensitive nanocarriers for the co-delivery of gene and drug. Materials and methods Hyaluronic acid – acid sensitive linker – 1,2-distearoyl phosphatideylethanolamine copolymers (HA-as-DSPE) were synthesized. HA-as-DSPE modified, paclitaxel and pDNA loaded solid lipid nanoparticles (HA-PTX/pDNA SLN) was prepared. The physicochemical properties like morphology, size, and zeta potential as well as release properties were evaluated. The ability and therapeutic effects of the novel system for the co-delivery of PTX and pDNA were demonstrated in vitro and in vivo . Results In vitro experiments and in vivo animal studies both confirmed that the HA-PTX/pDNA SLN system could promote the inhibition of tumor, at the same time deliver and transfect gene into the cancer cells. Discussion and conclusion Highest efficiency achieved by HA-PTX/pDNA SLN might result from the HA ligands that targeted the receptors on the cancer cells, the enhanced cellular uptake by the SLN formulations and also the pH sensitive bound of the carriers let the drug release more in the tumor cells. It could be concluded that HA-PTX/pDNA SLN could be used as a promising delivery system for drug and gene combination therapy [ABSTRACT FROM AUTHOR]

In recent years, great strides have been made toward the development of immune cell‐based therapies in the treatment of refractory malignancies. Primary T cells and NK cells armed with chimeric antigen receptors have achieved tremendous clinical success especially in patients with leukaemia and lymphoma. However, the autologous origin of these effector cells means that a single batch of laboriously engineered cells treats only a certain patient, leading to high cost, ununiform product quality, and risk of delay in treatment, and therefore results in restricted accessibility of these therapies to the overwhelming majority of the patients. Addressing these tricky obstacles calls for the development of universal immune cell products that can be provided 'off the shelf' in a large amount. Pluripotent stem cells (PSCs), owing to their unique capacity of self‐renewal and the potential of multi‐lineage differentiation, offer an unlimited cell source to generate uniform and scalable engineered immune cells. This review discusses the major advances in the development of PSC‐derived immune cell differentiation approaches and their therapeutic potential in treating both hematologic malignancies and solid tumours. We also consider the potency of PSC‐derived immune cells as an alternative therapeutic strategy for other diseases, such as autoimmune diseases, fibrosis, infections, et al. [ABSTRACT FROM AUTHOR]

As a non-invasive visualization technique, photoluminescence imaging (PLI) has found its huge value in many biological applications associated with intracellular process monitoring and early and accurate diagnosis of diseases. PLI can also be combined with therapeutics to build imaging-guided theragnostic platforms for achieving early and precise treatment of diseases. Photodynamic therapy (PDT) as a quintessential phototheranostics technology has gained great benefits from the combination with PLI. Recently, aggregation-induced emission (AIE)-active materials have emerged as one of the most promising bioimaging and phototheranostic agents. Most of AIEgens, however, need to be chemically engineered to form versatile nanocomposites with improved their photophysical property, photochemical activity, biocompatibility, etc. In this review, we focus on three categories of AIE-active nanocomposites and highlight their application progresses in the intracellular biological process monitoring and PLI-guided PDT. We hope this review can guide further development of AIE-active nanocomposites and promote their practical applications for monitoring intracellular biological processes and imaging-guided PDT. [ABSTRACT FROM AUTHOR]

Background Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. Objective To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2). Methods Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n = 64) as a cerebral I/R injury model. In the MCAO + CUR group, the rats were administered curcumin (300 mg/kg BW, i.p.) at 30 min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24 h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry. Results Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO + CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression. Conclusion The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB. [ABSTRACT FROM AUTHOR]

The aim of this study is to compare the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU) and ureteroscopic holmium laser lithotripsy (UHLL) as two minimally invasive procedures in managing obstructive upper ureteral calculi with concurrent urinary tract infections (UTI). The retrospective study included 189 patients who underwent unilateral obstructive upper ureteral stones with concurrent UTI from January 2007 to November 2014 at our institution. Patients received RPLU (81 cases) or UHLL (108 cases). All patients received preoperative anti-infection treatment (indwelling ureteral stent and/or preoperative antibiotics). Collected data, including sex, age, stone size, success rate, operation duration, post-operation hospitalization time, and post-operation complications, were compared. All patients were followed up for more than 6 months after surgeries, and no ureterostenosis occurred. The study included 189 patients, 41 (21.7 %) females and 148 (78.3 %) males with a medium age of 52 years (range 22-81 years). All surgeries were successfully performed without conversion to open surgery. Stone size in the RPLU group was larger than that of the UHLL group (16.1 ± 1.4 vs. 10.4 ± 1.6 mm, P = 0.012). Operative duration (P = 0.009) and hospitalization time (P < 0.001) in the UHLL group were significantly shorter than those in the RPLU group, whereas stone clearance rate was significantly higher in the RPLU group (100 vs. 88.9 %, P = 0.002). Of note, postoperative fever was more common in patients treated with UHLL (15 cases) versus RPLU (4 cases) (13.9 vs. 4.9 %, P = 0.043). Moreover, in the UHLL group, three patients without a preoperative indwelling ureteral stent were complicated with sepsis, which was not seen in RPLU group. In our study, the safety and stone clearance rate of RPLU are better than those of UHLL in the treatment of unilateral upper ureteric calculi with concurrent UTI. Preoperative antibiotics and indwelling ureteral stent may reduce the risk of postoperative infections. [ABSTRACT FROM AUTHOR]

Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines and food additives in China. Comparing with the extensive uses and active researches of P. notoginseng and its products, the side effect and probable toxicity were rare. 25-Methoxydammarane-3,12,20-triol (25-OCH 3 -PPD), a novel dammarane-type triterpene sapogenin that was first isolated from the extract of P. notoginseng , was proven to have strong antitumor activities against prostate cancer, breast cancer and lung cancer. The aim of the present study was to investigate the potential subchronic toxicity of 25-OCH 3 -PPD after it was repeatedly orally administered to Sprague–Dawley rats (5/sex/group/each time-point) at dose levels of 0, 150, 300 or 600 mg/kg/day for 13 weeks and 4-week recovery. No mortality and treatment-related toxicity effects were observed as a result of the administration of 25-OCH 3 -PPD at any dose level (150, 300 and 600 mg/kg) for 92 consecutive days. Although there were some statistical changes, such as increased weights in female rats and decreased organ weights and coefficients of the liver, spleen, kidney, and adrenal gland compared with the control group at the corresponding time, the autopsy and histopathological examination of the target organs did not show any abnormal responses. As a result, 25-OCH 3 -PPD was well tolerated by SD rat at doses of up to 600 mg/kg and that it is a potential candidate for therapeutic use. [ABSTRACT FROM AUTHOR]

This study consisted of a single centre randomised controlled trial with two parallel arms: an acupuncture group (n=20) with 27 affected eyes and a sham group (n=20) with 23 affected eyes. Participants in the acupuncture group received acupuncture treatment once daily, three times weekly for four weeks. Participants assigned to the control group received sham acupuncture, the same protocol as that used for the acupuncture group but without insertion of needles into the skin. The primary outcome measure was the cervical range of motion (CROM) score. Secondary outcome measures were the palpebral fissure size, response rate, and adverse events. All 40 participants completed the study. In the comparison of acupuncture and sham acupuncture, a significant difference was observed between acupuncture and sham acupuncture in CROM score (21.37±15.16 and 32.21±19.54, resp.) (P<0.05) and palpebral fissure size (7.19±2.94 and 5.41±2.45, resp.) (P<0.05). Response rate was also significantly different in the acupuncture group (P<0.05). No adverse events were reported in both groups in this study. In summary, it was demonstrated that acupuncture had a feasibility positive effect on oculomotor paralysis. [ABSTRACT FROM AUTHOR]

Background: Jian-Pi-Zhi-Dong Decoction (JPZDD) is a dedicated treatment of Tourette syndrome (TS). The balance of neurotransmitters in the cortico-striato-pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu) and γ-aminobutyric acid (GABA) and their receptors in a TS rat model. Materials and methods: Rats were divided into four groups (n=12 each). TS was induced in three of the groups by injecting them with 3,3'-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia) or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D-aspartate receptor 1 and GABAA receptor (GABAAR) were observed using Western blot and real-time polymerase chain reaction. Results: Tia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the mRNA expression, only Tia reduced the expression of N-methyl-D-aspartate receptor 1, compared with the model group. Conclusion: JPZDD could alleviate impairments in behavior and dysfunctional signaling by downregulating GABAAR in the striatum. We suggest that this acts to maintain the balance of Glu and GABA. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common malignant bone tumor. In recent years, although a lot of research in the mechanism of osteosarcoma development and metastasis had been done, the molecular mechanisms are still elusive. MicroRNAs (miRs), as small noncoding RNA sequences, are dysregulated in various diseases, including cancer, negatively modulating the target genes expression by posttranscriptional repression. MicroRNA-143 (miR-143) has been reported to be reduced in cancers, including pituitary, colorectal, prostate cancer and cervical. We were aimed to detect the effects of miR-143 on osteosarcoma cell invasion and migration as well as to indicate the potential molecular mechanisms by which miR-143 regulated osteosarcoma. After miR-143 transfection, the cancer cells migration and invasion were examined. And Western blot, RT-PCR, flow cytometry and immunochemistry assays were performed to analyze the role of miR-143 in osteosarcoma progression. The results suggested that miR-143 expressed lessly in osteosarcoma cell lines and could suppress cell migration and invasion in U2-OS and MG-63 cells. To our knowledge, it was the first time to target Bcl-2 directly to explore the underlying mechanism by which miR-143 performed its role to induce apoptosis in tumor cells, thus improving osteosarcoma progression. The present study indicated that miR-143 could inhibit Bcl-2 expression, causing Caspas3 activation, thus inducing apoptosis in osteosarcoma cells. MiR-143 may therefore sreve as a potential biomarker for osteosarcoma, and the regulation of its expression might be a novel therapeutic strategy for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Aim The objective of this study was to investigate the effects of urotensin II (UII) treatment on the proliferation and collagen synthesis of cultured rat pulmonary arterial smooth muscle cells (PASMCs) and to explore whether these effects are mediated by mitogen-activated protein kinase (MAPK) signaling pathways and early growth response 1 (Egr-1). Methods The proliferation of cultured PASMCs stimulated with different doses of UII was detected by BrdU incorporation. The mRNA expression levels of procollagen I (procol I), procollagen III (procol III), extracellular regulated protein kinase 1/2 (ERK1/2), stress-stimulated protein kinase (Sapk), p38 MAPK (p38), and Egr-1 mRNA in cultured PASMCs after treatment with UII, the UII-specific antagonist urantide, and the ERK1/2 inhibitor PD98059 were detected by real-time polymerase chain reaction (PCR), and the protein expression levels of procol I, procol III, phosphorylated (p)-ERK1/2, p-Sapk, p-p38, and Egr-1 were detected by Western blotting. Results Treatment with UII increased the proliferation of cultured PASMCs in a dose-dependent manner (P < 0.05). However, treatment with urantide and PD98059 inhibited the promoting effect of UII on PASMC proliferation (P < 0.05). Real-time PCR analysis showed that UII up-regulated the expression of procol I, procol III, ERK1/2, Sapk, and Egr-1 mRNA (P < 0.05), but not p38 mRNA. However, the up-regulating effect of UII was inhibited by PD98059 and urantide. Western blotting analysis showed that UII increased the synthesis of collagen I, collagen III, p-ERK1/2, p-Sapk, and Egr-1, and these effects also were inhibited by PD98059 and urantide (P < 0.05). Conclusions Egr-1 participates in the UII-mediated proliferation and collagen synthesis of cultured rat PASMCs via activation of the ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

A Ru(II) polypyridyl complex [Ru(bpy) 2 (HMSPIP)](ClO 4 ) 2 ( 1 ) (bpy = 2,2′-bipyridine, HMSPIP = 2-(4-methylsulfonyl)phenyl-1H-imidazo[4,5- f ][1,10] phenanthroline) was synthesized. The IC 50 value of the complex against human hepatocellular cell BEL-7402 is 21.6 ± 2.7 μM. The complex shows no cytotoxic activity toward human lung adenocarcinoma cell A549, human osteosarcoma cell MG-63 and human breast cancer cell SK-BR-3 cells. It is easily for complex 1 to be taken up by BEL-7402 cells. The complex can enhance the reactive oxygen species (ROS) levels and induce the decrease in the mitochondrial membrane potential. The complex inhibits the cell growth in BEL-7402 cells at G2/M phase. Complex 1 can regulate the expression of Bcl-2 family proteins. The results show that the complex induces apoptosis of BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Aims: Gestational diabetes mellitus (GDM) is a complex disease induced by a combination of genetic factors and environmental exposures. Growing evidence suggests that common single nucleotide polymorphisms within miRNA-binding sites (miR-binding SNPs) contribute to the development of various diseases. However, the roles of miR-binding SNPs in GDM have not been fully elucidated. The CDKN2A/B genes have been identified as two of the strongest genetic determinants for diabetes risk. The aim of the study was to first investigate the associations between miR-binding SNPs of CDKN2A/B, GDM susceptibility, and quantitative metabolism traits. Methods: Three miR-binding SNPs of CDKN2A/B gene (rs1063192, rs3217992, and rs3088440) were selected and genotyped using TaqMan allelic discrimination assays in 839 cases of GDM and 900 controls. Results: The CC genotype of CDKN2B rs1063192, which is located in the hsa-miR-323b-5p binding site, was significantly associated with GDM [OR 1.418 (1.143, 1.908); p = 0.003]. The C allele of rs1063192 occurred with significantly higher frequency in GDM [OR 1.22 (1.03, 1.44); p = 0.021]. The rs1063192 genotype CC exhibited increased glucose levels at 1 h and 3 h, as well as higher insulin levels at 3 h during an OGTT compared with the control TT genotype ( p < 0.05). We also found that the rs1063192 CC genotype was associated with lower total cholesterol and LDL cholesterol levels ( p < 0.05). Conclusions: The CC genotype of CDKN2B rs1063192 in the hsa-miR-323b-5p binding site increased the risk of GDM in pregnant Chinese Han women. Importantly, our study provides evidence that miR-binding SNPs are a novel source of GDM susceptibility loci. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of urgent percutaneous nephrolithotomy (PNL) for acute kidney injury secondary to bilateral upper urinary stones in infants. Methods: A total of seven infants (five boys and two girls), aged from 5 to 12 months, underwent urgent PNL for calculus anuria from September 2011 to March 2013. The initial blood test revealed acute renal injury in all infants. After correcting electrolyte imbalance and acid-base status through medical treatment in a short time without dialysis, all urgent PNL procedures were performed with 16F percutaneous access and small-diameter nephroscopes designed specifically for pediatric surgery on the side with the more dilated pelvis. Stones were fragmented with a pneumatic lithotripter. Results: Stones were completely removed from the operative side kidneys. The operating time ranged from 35 to 57 min. Blood BUN, serum creatinine, and electrolyte levels returned to normal on postoperative 36 h. There were no major perioperative or postoperative complications and deaths. Conclusions: When performed by experienced endourologists, urgent PNL is a safe and effective procedure in infants for acute kidney injury secondary to bilateral upper urinary stones. [ABSTRACT FROM AUTHOR]

Intervertebral disc (IVD) disease, a most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to investigate the potential of Tanshinone IIA (TSA) for the treatment of IVD disease, through exploring its anti-inflammatory and anti-catabolic activities in both in vitro IVD cell culture and in vivo animal models. After the inflammatory response was induced in IVD cells by IL-1β, the activity and expression of inflammatory mediators, and potentially involved pathways were investigated in the presence or absence of TSA. The p38-MAPK inhibitor, SB239063, was also used to investigate the involvement of the MAPK signaling pathway in the observed effects. Meanwhile, the analgesic properties of TSA were analyzed by the von Frey filament test in Sprague–Dawley rats. Our results indicated that TSA significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, probably by modulation of the activity of interleukin-1 receptor-associated kinase 1 (IRAK-1) and its downstream effectors p38, JNK and NF-κB. Our current study strongly demonstrates the potential of TSA for the treatment of inflammation and followed pain in degenerative disc disease. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a helminthic disease that affects more than 200 million people. An effective vaccine would be a major step towards eliminating the disease. Studies suggest that T follicular helper (Tfh) cells provide help to B cells to generate the long-term humoral immunity, which would be a crucial component of successful vaccines. Thus, understanding the biological characteristics of Tfh cells in patients with schistosomiasis, which has never been explored, is essential for vaccine design. Methodology/Principal Findings: In this study, we investigated the biological characteristics of peripheral memory Tfh cells in schistosomiasis patients by flow cytometry. Our data showed that the frequencies of total and activated peripheral memory Tfh cells in patients were significantly increased during Schistosoma japonicum infection. Moreover, Tfh2 cells, which were reported to be a specific subpopulation to facilitate the generation of protective antibodies, were increased more greatly than other subpopulations of total peripheral memory Tfh cells in patients with schistosomiasis japonica. More importantly, our result showed significant correlations of the percentage of Tfh2 cells with both the frequency of plasma cells and the level of IgG antibody. In addition, our results showed that the percentage of T follicular regulatory (Tfr) cells was also increased in patients with schistosomiasis. Conclusions/Significance: Our report is the first characterization of peripheral memory Tfh cells in schistosomasis patients, which not only provides potential targets to improve immune response to vaccination, but also is important for the development of vaccination strategies to control schistosomiasis. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer''s disease (AD) is an irreversible, progressive brain disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptides deposition are found to be correlated with dementia progression in patients with AD. However, little is known about the simultaneous effects of glucocorticoids and Aβ on learning and memory impairment and its mechanism. In this study, 12-month-old male rats were chronically treated with Aβ25–35 (10μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg) for 14 days to investigate the effects of DEX and Aβ25–35 treatment on learning and memory impairments, pathological changes, neuronal ultrastructure, amyloid precursor protein (APP) processing and neuronal cell apoptosis. Our results showed that DEX or Aβ25–35 treatment alone for 14 days had caused slight damage on learning and memory impairments and hippocampal neurons, but damages were significantly increased with DEX+Aβ25–35 treatment. And the mRNA levels of the APP, β-secretase and caspase 3 were significantly increased after DEX+Aβ25–35 treatment. The immunohistochemistry demonstrated that APP, Aβ1–40, caspase 3 and cytochrome c in hippocampus CA1 were significantly increased. Furthermore, Hoechst 33258 staining and Aβ1–40 ELISA results showed that DEX+Aβ25–35 treatment induced hippocampus CA1 neuron apoptosis and increased the level of Aβ1–40. The results suggest that the simultaneous effects of GCs and Aβ may have important roles in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy may increase the toxicity of Aβ and have cumulative impacts on the course of AD development and progression. [Copyright &y& Elsevier]

Oral lichen planus (OLP) is a chronic inflammatory disease, has prolonged courses, repeated attacks and resistance to treatment. The traditional narrow spectrum UVB treatment has an established efficacy on skin lichen planus, and high safety. However, most of ultraviolet phototherapy devices have a huge volume, thereby cannot be used in the treatment of OLP. Lymphocytic infiltration is evident in the lesions of lichen planus, and the direct irradiation of 308-nm excimer laser can induce apoptosis of the T lymphocytes in skin lesions, thereby has a unique therapeutic effect on the diseases involving T lymphocytes. This study aims to investigate the efficacy of 308-nm excimer laser in the treatment of OLP. A total of six OLP patients were enrolled into this study, and further pathological diagnosis was conducted, then 308-nm excimer laser was used in the treatment. The efficacy of 308-nm excimer laser in the treatment of OLP was satisfactory. The clinical symptoms of five patients were significantly improved. In two patients, the erosion surface based on congestion and the surrounding white spots completely disappeared, and clinical recovery was achieved. Three patients achieved partial remission, that is, the erosion surface healed, congestion and white spot area shrunk by more than 1/2 of the primary skin lesions. In the remaining one patient, the erosion surface had not completely healed after treatment, and congestion and white spot area shrunk by less than 1/2 of the primary skin lesions. Only one patients had developed mild pain during the treatment, and this symptom alleviated by itself. The 308-nm excimer laser therapy can serve as a safe and effective treatment for OLP. [ABSTRACT FROM AUTHOR]

Chondrosarcoma is the second most common type of primary bone malignancy following up osteosarcoma, characterized by resistance to conventional chemotherapeutic agents and radiation regimens. The p160 family members steroid receptor coactivator-1 and -3 (SRC-1 and SRC-3) have been implied in the regulation of cancer growth, migration, invasion, metastasis and chemotherapeutic resistance; but we still lack detailed information about the levels of SRCs in chondrosarcoma. In this study, expression of SRC-1 and SRC-3 in chondrosarcoma was examined by immunohistochemistry with tissue microarrays; the four score system (0, 1, 2 and 3) was used to evaluate the staining. The results showed that there were no gender-, site- or age-differences regarding the expression of SRC-1 or SRC-3 ( p > 0.05); organ (bone or cartilage) -differences were only detected for SRC-1 but not SRC-3 ( p < 0.05). Significant higher levels of SRC-1 and SRC-3 were detected in MDC and PDC when compared to WDC. Our study clearly demonstrated differentiation-dependant expression of SRC-1 and SRC-3 in chondrosarcoma, may be novel targets for the prognosis and/or treatment of chondrosarcoma, would have opened a new avenue and established foundation for studying chondrosarcoma. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone (DHEA) and its ester form, DHEA-S, are the most abundant steroids in human plasma. Our previous studies showed that DHEA protects against osteoarthritis (OA). The aim of this paper was to explore the possible mechanisms that underlie DHEA-mediated protection against OA. We tested the expression of β-catenin, it was increased significantly in OA. Rabbit cartilage was treated with various concentrations of DHEA in both IL-1β-induced rabbit chondrocytes and in rabbit cartilage from the anterior cruciate ligament transaction-induced OA model. We found DHEA decreased the expression of β-catenin. Then we further activated Wnt/β-catenin signaling by β-catenin transfection and inactivated it by the inhibitor Dickkopf1 in chondrocytes to reveal its role in the pathogenesis of OA. It turns out the protective effect of DHEA was significantly decreased when Wnt/β-catenin signaling was activated, while inactivating Wnt/β-catenin signaling enhanced the effects of DHEA. Therefore, we hypothesize that DHEA probably exerted its chondroprotective effect by regulating Wnt/β-catenin signaling. Our findings demonstrate the critical role of Wnt/β-catenin signaling in DHEA-mediated protection against OA. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNA) have been implicated in the resistance of tumors to chemotherapy. However, little is known about miRNA expression in bromocriptine-resistant prolactinomas. In this study, 23 prolactinoma samples were classified as bromocriptine-sensitive or -resistant according to the clinical definition of bromocriptine resistance, and their miRNA expression profiles were determined using Solexa sequencing. We found 41 miRNAs that were differentially expressed between the two groups, and 12 of these were validated by stem-loop qRT-PCR. Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas. Furthermore, silencing of mir-93 significantly increased the sensitivity of MMQ cells to dopamine agonist treatment. Mir-93 directly affected p21 expression in MMQ cells by targeting the 3′-UTR. Our study is the first to identify a miRNA expression profile associated with bromocriptine-resistant prolactinoma. [ABSTRACT FROM AUTHOR]

Abstract: This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4′-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2–6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1–6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1–10μM. Among them, compounds 1 and 2 were the most active at 1μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells. [Copyright &y& Elsevier]

Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS) in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Chylothorax is a pathologic condition defined by an accumulation of lymphatic fluid, the chyle, in the thorax. Postoperative chylothorax is a potentially lethal complication, with a reported mortality rate of 15.4%–25%. Patients and methods: Esophageal cancer patients hospitalized for elective radical esophagectomy by thoracotomy (n = 10,574) were consecutively enrolled between January 1996 and December 2011. Patients (n = 306) who experienced post-esophagectomy chylothorax were assigned to a 48-h (group A, n = 186) or to a 2-wk (group B, n = 120) conservative treatment regimen. For patients with a daily chylothorax output >1000 mL, thoracic duct ligation (TDL) was performed by thoracotomy. Measured outcomes included frequency of TDL, overall and treatment-specific morbidity and mortality rates, and the rate of chylothorax recurrence. Results: A total of 171 patients (171 of 306 [55.9%]) underwent TDL. A larger proportion of patients in group A required TDL compared with group B (72.6% versus 30.0%, P < 0.001). Group A had a significantly higher rate of overall morbidity compared with group B (31.7% versus 19.2%, P = 0.02). Moreover, the overall mortality rate was significantly higher in group A (14.0% versus 4.2%, P = 0.006). Chylothorax recurred in nine patients (9 of 306 [2.9%]), and there was no difference between the two groups (3.2% versus 2.5%, P = 1.000). Conclusions: The 2-wk regimen reduced the requirement for TDL and the overall morbidity and mortality rates compared with the 48-h regimen. Importantly, this regimen does not increase the risk of chylothorax recurrence. [Copyright &y& Elsevier]

Abstract: The Notch pathway is a cell signaling pathway determining initial specification and subsequent cell fate in the inner ear. Previous studies have suggested that new hair cells (HCs) can be regenerated in the inner ear by manipulating the Notch pathway. In the present study, delivery of siRNA to Hes1 and Hes5 using a transfection reagent or siRNA to Hes1 encapsulated within poly(lactide-co-glycolide acid) (PLGA) nanoparticles increased HC numbers in non-toxin treated organotypic cultures of cochleae and maculae of postnatal day 3 mouse pups. An increase in HCs was also observed in cultured cochleae and maculae of mouse pups pre-conditioned with a HC toxin (4-hydroxy-2-nonenal or neomycin) and then treated with the various siRNA formulations. Treating cochleae with siRNA to Hes1 associated with a transfection reagent or siRNA to Hes1 delivered by PLGA nanoparticles decreased Hes1 mRNA and up-regulated Atoh1 mRNA expression allowing supporting cells (SCs) to acquire a HC fate. Experiments using cochleae and maculae of p27kip1/-GFP transgenic mouse pups demonstrated that newly generated HCs trans-differentiated from SCs. Furthermore, PLGA nanoparticles are non-toxic to inner ear tissue, readily taken up by cells within the tissue of interest, and present a synthetic delivery system that is a safe alternative to viral vectors. These results indicate that when delivered using a suitable vehicle, Hes siRNAs are potential therapeutic molecules that may have the capacity to regenerate new HCs in the inner ear and possibly restore human hearing and balance function. [Copyright &y& Elsevier]