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Background Benign prostatic hyperplasia (BPH) is one of the most common illnesses in aging men. Recent studies found that bone morphogenetic protein 5 (BMP5) is upregulated in BPH tissues, however, the role of BMP5 in the development of BPH has not been examined. The current study aims to elucidate the potential roles of BMP5 and related signaling pathways in BPH. Methods Human prostate cell lines (BPH-1, WPMY-1) and human/rat hyperplastic prostate tissues were utilized. Western blot, quantitative real-time polymerase chain reaction, immunofluorescent staining, and immunohistochemical staining were performed. BMP5-silenced and -overexpressed cell models were generated and then cell cycle progression, apoptosis, and proliferation were determined. The epithelial-mesenchymal transition (EMT) was also quantitated. And rescue experiments by BMP/Smad signaling pathway agonist or antagonist were accomplished. Moreover, BPH-related tissue microarray analysis was performed and associations between clinical parameters and expression of BMP5 were analyzed. Results Our study demonstrated that BMP5 was upregulated in human and rat hyperplastic tissues and localized both in the epithelial and stromal compartments of the prostate tissues. E-cadherin was downregulated in hyperplastic tissues, while N-cadherin and vimentin were upregulated. Overexpression of BMP5 enhanced cell proliferation and the EMT process via phosphorylation of Smad1/5/8, while knockdown of BMP5 induced cell cycle arrest at G0/G1 phase and blocked the EMT process. Moreover, a BMP/Smad signaling pathway agonist and antagonist reversed the effects of BMP5 silencing and overexpression, respectively. In addition, BMP5 expression positively correlated with prostate volume and total prostate-specific antigen. Conclusion Our novel data suggest that BMP5 modulated cell proliferation and the EMT process through the BMP/Smad signaling pathway which could contribute to the development of BPH. However, further studies are required to determine the exact mechanism. Our study also indicated that BMP/Smad signaling may be rediscovered as a promising new therapeutic target for the treatment of BPH.

Reactivation of fetal haemoglobin (HbF) expression is an effective way to treat β-thalassaemia and sickle cell anaemia. In the present study, we identified a novel GATA zinc finger domain-containing protein 2A (GATAD2A) mutation, which contributed to the elevation of HbF and ameliorated clinical severity in a patient with β-thalassaemia, by targeted next-generation sequencing. Knockout of GATAD2A led to a significant induction of HbF in both human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) and human cluster of differentiation (CD)34+ cells with a detectable impact on erythroid differentiation. Furthermore, heterozygous knockout of GATAD2A impaired recruitment of chromodomain helicase DNA-binding protein 4 (CHD4) to the methyl-binding domain protein 2 (MBD2)-containing nucleosome remodelling and deacetylation (NuRD) complex. Our present data suggest that mutations causing the haploinsufficiency of GATAD2A might contribute to amelioration of clinical severity in patients with β-thalassaemia.

Background Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin-like growth factor 1 (IGF-1). Methods Human prostate tissues, prostate, and monocyte cell lines (WPMY-1, BPH-1, and THP-1) were used. THP-1 was polarized into several subtypes with cytokines. The expression and localization of IGF-1 and M2 macrophages were determined via immunofluorescent staining, quantitative real-time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF-1 in WPMY-1 and BPH-1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and fibrosis processes were examined. Results The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF-1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF-1 than other subtypes. Knockdown of IGF-1 in WPMY-1 and BPH-1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH-1 cells as well as the fibrotic process in WPMY-1 cells, which was reversible when cocultured with M2a macrophages. Conclusion These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.

Our study aims to explore changes in bladder contractility and the phosphodiesterase type 5 (PDE5) signalling pathway in response to partial bladder outlet obstruction (PBOO). A surgically induced male rat PBOO model and human obstructed bladder tissues were used. Histological changes were examined by H&E and Masson's trichrome staining. Bladder strip contractility was measured via organ bath. The expressions of nitric oxide synthase (NOS) isoforms, PDE5, muscarinic cholinergic receptor (CHRM) isoforms and PDE4 isoforms in bladder were detected by RT‐PCR and Western blotting. The immunolocalization of the PDE5 protein and its functional activity were also determined. PBOO bladder tissue exhibited significant SM hypertrophy and elevated responsiveness to KCl depolarization and the muscarinic receptor agonist carbachol. NOS isoforms, PDE5, CHRM2, CHRM3 and PDE4A were up‐regulated in obstructed bladder tissue, whereas no change in PDE4B and PDE4D isoform expression was observed. With regard to PDE5, it was expressed in the SM bundles of bladder. Interestingly, obstructed bladder exhibited less relaxation responsiveness to sodium nitroprusside (SNP), but an exaggerated PDE5 inhibition effect. The up‐regulation of PDE5 could contribute to the lack of effect on Qmax for benign prostatic hyperplasia/lower urinary tract symptom (BPH/LUTS) patients treated with PDE5 inhibitors. Moreover, PDE5 (with presence of NO) and PDE4 may serve as new therapeutic targets for bladder diseases such as BPH‐induced LUTS and overactive bladder (OAB).

Aim Dasatinib is a small molecule tyrosine kinase inhibitor with multiple targets including kit, PDGFR, and SRC. This prospective study evaluated the efficacy and safety of dasatinib as third‐line treatment for gastrointestinal stromal tumors (GIST). Methods The study enrolled adult patients (≥18 years of age) with histologically confirmed unresectable and/or metastatic GIST whose disease progressed despite imatinib and sunitinib therapy. Dasatinib (50 mg twice daily) was given orally for 1 week and escalated to 70 mg twice daily orally. The primary endpoint was to the 3‐month progression‐free survival (PFS) rate. Blood samples were acquired before dasatinib therapy for examination of gene mutations by next‐generation sequencing (NGS). Results From May 2016 to June 2018, 58 patients from 9 Chinese medical centers were enrolled in this study. The 3‐month PFS rate was 53.4% and the median overall survival (OS) was 14.0 months. Neither primary nor secondary gene mutations predicted the efficacy of dasatinib. Wild‐type GIST patients had longer PFS (5.5 months). The most common adverse events were anemia, proteinuria, fatigue, neutropenia, and diarrhea. The concordance of KIT/PDGFRA mutation was 61.9% between tissue and peripheral blood samples and additional KIT mutations were detected in the peripheral blood samples in 28.6% of the patients. Some SNV and CNV such as ATRX, TP53, TEKT4, STK11, SDHC, and CDKN2C related to tumor signaling pathways were detected. Patients with TP53 mutations and SDHC and TMEM127 gene copy number loss had longer OS. Conclusion Dasatinib has modest antitumor activity with tolerable toxicities in patients with metastatic GISTs who have failed imatinib and sunitinib therapy., This is the first prospective trial to evaluate the efficacy of dasatinib in third line treatment of GIST and reached the expected primary endpoint. The results of NGS ananlysis and liquid biopsy are also very important to clinical practice.

Background Arginase plays key roles in methyl jasmonate (MeJA)-mediated quality maintenance in vegetables and fruits. MeJA treatment induced the Arginase 2 (SlARG2) expression, which is one of the most important encoding genes of arginase. In addition, the treatment with MeJA induced resistance to pathogenic infection in many plants. However, the functions of SlARG2 in MeJA-induced defense to Botrytis cinerea are unclear. In our work, control and SlARG2-silenced tomato fruits (Solanum lycopersicum) were treated with 0.05 mmoL L-1 MeJA before storage to assay the roles of SlARG2 in MeJA-induced defense responses to Botrytis cinerea. Results Our results indicated that MeJA treatment induced both pathogenesis-related gene expression (PR1, PR2a, PR2b and PR3b), and the activity of defense-related enzymes, as well as upregulated arginine metabolism. Compared to control fruits, the treatment with MeJA also induced the activity of arginase, arginine decarboxylase (ADC) and ornithine aminotransferase (OAT), and expression of SlARG2, SlADC, ornithine decarboxylase (SlODC) and SlOAT, and consequently increased the accumulation of arginine, proline, glutamate, putrescine and spermine. However, the induction effects by MeJA were significantly reduced in fruits in which SlARG2 was silenced and severe disease symptoms were observed. Conclusion MeJA fumigation could inhibit disease development by inducing pathogenesis-related gene expression (PR1, PR2a, PR2b and PR3b) and defense-related enzymes activity, as well as upregulated arginine metabolism. In addition, SlARG2 silencing could inhibit the functions of MeJA in inducing the accumulation of the above substances. Overall, our study provided strong evidence that SlARG2 was essential for MeJA-induced tomato fruit defense responses to Botrytis cinerea. © 2020 Society of Chemical Industry.

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with significant phenotypic alterations in vascular smooth muscle cells (VSMCs). Gasdermin D (GSDMD) is a pore-forming effector of pyroptosis. In this study, the role of VSMC-specific GSDMD in the phenotypic alteration of VSMCs and AAA formation is determined. Single-cell transcriptome analyses reveal Gsdmd upregulation in aortic VSMCs in angiotensin (Ang) II-induced AAA. VSMC-specific Gsdmd deletion ameliorates Ang II-induced AAA in apolipoprotein E (ApoE)

To gain in-depth insights into the relevant exposed crystal planes for the photocatalytic performance of perovskite-structured oxides, SrSnO3 nanocrystals with different microstructures were synthesized and their photocatalytic activity for the degradation of simulated dye was investigated. The as-obtained orthorhombic SrSnO3 nanorods with exposed {001} crystal planes showed higher photocatalytic activity for decomposing methylene blue than that of SrSnO3 nanoribbons with exposed {111} crystal planes. The surface atomic configurations revealed that the quantity of SnO2 overlayer on the {001} crystal facets is slightly greater than that on {111} crystal planes, which results in exposed {001} crystal facets of the SrSnO3 nanorods that can exhibit better activity in the photocatalytic process, due to fewer lattice defects, which act as traps for photogenerated charge carriers to decrease the recombination of photoexcited electrons and holes. This originated from narrowing of the crystal face distance and slight variation of the unit cell parameters; the crystallographic axis became shorter and the value of lattice strain became smaller. As a result, SrSnO3 nanocrystals exhibited different surface behavior under post-treatment conditions and exhibited variation in the photocatalytic properties. The findings reported herein highlight the importance of probing the properties of surface facets in the evaluation of the photocatalytic performance of ternary metal oxides.

Background: In the present study, we investigated the role of ornithine decarboxylase (ODC) in the methyl jasmonate (MeJA)-regulated postharvest quality maintenance of Agaricus bisporus (J. E. Kange) Imbach button mushrooms by pretreating mushrooms with a specific irreversible inhibitor called α-difluoromethylornithine (DFMO) before exposure to MeJA vapor.; Results: Mushrooms were treated with 0 or 100 µmol L-1 MeJA or a combination of 120 µmol L-1 DFMO and 100 µmol L-1 MeJA, respectively, before storage at 4 °C for 21 days. Treatment with MeJA alone induced the increase in ODC activity whereas this effect was greatly suppressed by pretreatment with DFMO. α-Difluoromethylornithine strongly attenuated the effect of MeJA on decreasing cap opening, slowing the decline rate of soluble protein and total sugar, and accumulating total phenolics and flavonoids. α-Difluoromethylornithine pretreatment also counteracted the ability of MeJA to inhibit polyphenol oxidase and lipoxygenase activities, and malondialdehyde production, and to stimulate superoxide dismutase and catalase activities. It also largely downregulated MeJA-induced accumulation of free putrescine (Put).; Conclusion: These results reveal that ODC is involved in MeJA-regulated postharvest quality retention of button mushrooms, and this involvement is likely to be associated with Put levels. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Postharvest diseases result in major losses in fruits. Tomato is susceptible to postharvest rot caused by Botrytis cinerea and is regarded as a good model system to study postharvest disease and quality deterioration in fruit. To develop a safe and effective technique to alleviate disease and maintain fruit quality, the effects of methyl salicylate (MeSA) and 1-methylcyclopropene (1-MCP) either separately or combined on quality and gray mold caused by B. cinerea in tomato fruit were investigated.; Results: The results showed that application of MeSA (0.05 mmol L-1 ) delayed fruit ripening and reduced gray mold. Compared with MeSA treatment, 1-MCP (0.5 µL L-1 ) effectively delayed fruit ripening. Further, MeSA combined with 1-MCP treatment was more effective in inhibiting fungal decay during storage than MeSA treatment alone. The combined treatment not only enhanced pathogenesis-related protein 1 (PR1) expression, activities of defense enzymes and total phenolic content but also inhibited the increase in electrical conductivity and malondialdehyde content. The combined treatment was also more effective in retaining firmness, color change and titratable acidity content than MeSA treatment alone.; Conclusion: MeSA combined with 1-MCP treatment was a useful technique to maintain quality and alleviate gray mold in postharvest tomato fruit during storage. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

The bioactive lipid sphingosine‐1‐phosphate (S1P) regulates smooth muscle (SM) contractility predominantly via three G protein‐coupled receptors. The S1P1 receptor is associated with nitric oxide (NO)‐mediated SM relaxation, while S1P2 & S1P3 receptors are linked to SM contraction via activation of the Rho‐kinase pathway. This study is to determine testosterone (T) modulating the expression and functional activity of S1P receptors in corpus cavernosum (CC). Adult male Sprague‐Dawley rats were randomly divided into three groups: sham‐operated controls, surgical castration and T supplemented group. Serum S1P levels were detected by high‐performance liquid chromatography. The expression of S1P1‐3 receptors and sphingosine kinases was detected by real‐time RT‐PCR. In vitro organ bath contractility and in vivo intracavernous pressure (ICP) measurement were also performed. T deprivation significantly decreased ICP rise. Meanwhile, surgical castration induced a significant increase in serum S1P level and the expression of S1P2‐3 receptors by twofold (P

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell–cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1–mediated firm adhesion of neutrophils that regulate VE-cadherin’s role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2–containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1–SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1–VE-cadherin association and promoted VE-cadherin–actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2—via association with ICAM-1—mediates ICAM-1–induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.—Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1–VE-cadherin interaction.

Adult hippocampal neurogenesis is essential for learning and memory, and its dysfunction is involved in neurodegenerative diseases. However, the molecular mechanisms underlying adult hippocampal neurogenesis are still largely unknown. Our previous studies indicated that the transcription factor Brn4 was upregulated and promoted neuronal differentiation of neural stem cells (NSCs) in the surgically denervated hippocampus in rats. In this study, we use high-throughput RNA sequencing to explore the molecular mechanisms underlying the enhancement of adult hippocampal neurogenesis induced by lentivirus-mediated Brn4 overexpression in vivo. After 10 days of the lentivirus injection, we found that the expression levels of genes related to neuronal development and maturation were significantly increased and the expression levels of genes related to NSC maintenance were significantly decreased, indicating enhanced neurogenesis in the hippocampus after Brn4 overexpression. Through RNA sequencing, we found that 658 genes were differentially expressed in the Brn4-overexpressed hippocampi compared with GFP-overexpressed controls. Many of these differentially expressed genes are involved in NSC division and differentiation. By using quantitative real-time PCR, we validated the expression changes of three genes, including Ctbp2, Notch2, and Gli1, all of which are reported to play key roles in neuronal differentiation of NSCs. Importantly, the expression levels of Ctbp2 and Notch2 were also significantly changed in the hippocampus of Brn4 KO mice, which indicates that the expression levels of Ctbp2 and Notch2 may be directly regulated by Brn4. Our current study provides a solid foundation for further investigation and identifies Ctbp2 and Notch2 as possible downstream targets of Brn4. © 2017 Wiley Periodicals, Inc.

The RIN transcription factor is one of the MADS box family members and predominantly controls fruit ripening. In this study, effort was made to demonstrate the regulation network of RIN transcription factor during tomato fruit ripening and softening. Novel RIN target genes were identified by proteomics, electrophoresis mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis.; Results: Over 700 protein spots were achieved by two-dimensional gel electrophoresis, and 42 proteins were successfully identified. Among them, 1-aminocyclopropane-1-carboxylate oxidase (LeACO4, ethylene synthesis, spot 3) and α-galactosidase-like isoform 2 (α-Gal, cell wall metabolism, spot 26) exhibited varied expression levels in different tomato fruits. Particularly high expression levels of LeACO4 and α-Gal were observed in wild type but not in the rin mutant. Additionally, CArG box, a RIN-binding site, was discovered in the promoter regions of both LeACO4 and α-Gal genes, suggesting that RIN possibly directly regulates their transcriptions, and this assumption was further confirmed by EMSA and ChIP assay.; Conclusion: Functional annotations of RIN target genes demonstrated the specific role of RIN in the process of fruit ripening and softening, especially in cell wall degradation and ethylene biosynthesis. This study will further illuminate the mechanism of tomato ripening and softening. © 2016 Society of Chemical Industry.; © 2016 Society of Chemical Industry.

Introduction Neurofibrillary pathology of abnormally hyperphosphorylated tau (P-tau) is a hallmark of Alzheimer's disease (AD) and other tauopathies. Tau pathology can be experimentally induced and propagated. However, what induces the prion-like transmission character to tau and produces morphologically distinct tau lesions remains elusive. Methods We investigated the role of hyperphosphorylation in the spread of tau pathology in hTau transgenic mice. Results We found that intrahippocampal injection with AD P-tau, but not nonphosphorylated tau, produced numerous P-tau tangles and neuropil threads locally and in neocortex lateral to injection and upstream to the hippocampus. Dephosphorylation of AD P-tau with protein phosphatase-2A dramatically reduced and switched tau pathology from neurofibrillary tangles to argyrophilic grain-like morphology. Conclusions Our findings show that abnormal hyperphosphorylation of tau determines the spread and morphology of tau lesions and that the propagation of tau pathology takes place both locally and in axonally connected areas and highlight tau hyperphosphorylation as a potential drug target.

BACKGROUND Prostatitis is one of the most common urological problems afflicting adult men. The etiology and pathogenesis of nonbacterial prostatitis, which accounts for 90–95% of cases, is largely unknown. As serum proteins often indicate the overall pathologic status of patients, we hypothesized that protein biomarkers of prostatitis might be identified by comparing the serum proteomes of patients with and without nonbacterial prostatitis. METHODS All untreated samples were collected from subjects attending the Fangchenggang Area Male Health and Examination Survey (FAMHES). We profiled pooled serum samples from four carefully selected groups of patients (n = 10/group) representing the various categories of nonbacterial prostatitis (IIIa, IIIb, and IV) and matched healthy controls using a mass spectrometry-based 4-plex iTRAQ proteomic approach. More than 160 samples were validated by ELISA. RESULTS Overall, 69 proteins were identified. Among them, 42, 52, and 37 proteins were identified with differential expression in Category IIIa, IIIb, and IV prostatitis, respectively. The 19 common proteins were related to immunity and defense, ion binding, transport, and proteolysis. Two zinc-binding proteins, superoxide dismutase 3 (SOD3), and carbonic anhydrase I (CA1), were significantly higher in all types of prostatitis than in the control. A receiver operating characteristic curve estimated sensitivities of 50.4 and 68.1% and specificities of 92.1 and 83.8% for CA1 and SOD3, respectively, in detecting nonbacterial prostatitis. The serum CA1 concentration was inversely correlated to the zinc concentration in expressed-prostatic secretions. CONCLUSIONS Our findings suggest that SOD3 and CA1 are potential diagnostic markers of nonbacterial prostatitis, although further large-scale studies are required. The molecular profiles of nonbacterial prostatitis pathogenesis may lay a foundation for discovery of new therapies. Prostate 75:1538–1555, 2015. © 2015 Wiley Periodicals, Inc.

Introduction Our purpose is to investigate whether polymorphisms of 102 T/C and -1438A/G in 5HTR2A are associated with Tourette syndrome (TS) in Chinese Han population. Methods A total of 178 TS trios were recruited in this study. After the allelic and genotypic distributions of two polymorphisms were genotyped using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), we compared their genetic distributions with what is expected with Hardy–Weinberg to explore whether there might be an association of these polymorphisms with TS by haplotype relative risk (HRR) and transmission disequilibrium test (TDT) statistics. Results Our results showed that no significant associations were found between the HTR2A 102 T/C and -1438A/G polymorphisms and TS (for HTR2A 102 T/C: TDT = 2.041, df = 1, P = 0.175; HRR = 1.468, χ2 = 1.905, P = 0.168, 95% confidence interval: 0.850–2.535; for HTR2A: -1438A/G, TDT = 0.093, df = 1, P = 0.819; HRR = 0.965, χ2 = 0.018, P = 0.894, 95% confidence interval: 0.574–1.624). Discussion Our study suggested that the HTR2A 102T/C and -1438A/G polymorphisms may not be associated with susceptibility to TS, and thus do not play a major role in the development of TS in the Chinese Han population. However, these results need to be confirmed in a larger sample collected from different populations.

Stromal derived factor-1α (SDF-1α), a critical chemokine that promotes cell homing to target tissues, was presumed to be involved in the traumatic brain injury cortex. In this study, we determined the expression of SDF-1α in the hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA showed that mRNA transcription and SDF-1α proteins increased significantly after FF transection. In vitro, the expression of SDF-1α in radial glial cells (RGCs) incubated with deafferented hippocampus extracts was observed to be greater than in those incubated with normal hippocampus extracts. The co-culture of neural progenitor cells (NPCs) and RGCs indicated that the extracts of deafferented hippocampus induced more NPCs migrating toward RGCs than the normal extracts. Suppression or overexpression of SDF-1α in RGCs markedly either decreased or increased, respectively, the migration of NPCs. These results suggest that after FF transection, SDF-1α in the deafferented hippocampus was upregulated and might play an important role in RGC induction of NPC migration; therefore, SDF-1α is a target for additional research for determining new therapy for brain injuries.

Background We attempted to clarify the association between dopamine receptor D4 (DRD4) 48-bp variable number of tandem repeats (VNTR) polymorphism and Tourette's syndrome. Methods The DRD4 48-bp VNTR polymorphism was genotyped in 291 Tourette's syndrome patients (including 218 trios) and 405 controls. Chi-square and transmission disequilibrium test analysis were used to compare genetic distributions. We retrieved related studies in a meta-analysis to clarify the role of 2-repeat and 4-repeat alleles in the pathogenesis. Results Obvious genotype and allele distribution differences were observed between patients and healthy controls for both 2-repeat and 4-repeat alleles. This was verified using transmission disequilibrium test analysis. Meta-analysis showed strong associations in both the total population and the Asian population. Conclusions The DRD4 48-bp VNTR polymorphism appears to be associated with Tourette's syndrome, with the 2-repeat allele performing a protective role and the 4-repeat allele a nonprotective role in the genesis of the disease. © 2014 International Parkinson and Movement Disorder Society

Micro-sized ZnO crystals with different shapes have been successfully synthesized by a simple solvothermal reaction in glycol-water binary solution or citrate solution. The morphology and size of the ZnO are strongly depended on synthetic environment. The growth of ZnO crystals with tunable shape was controlled by a suppressed crystal growth of the nonpolar plane and polar plane, due to the Tris selectively adsorbed on the different plane facets. Systematic reactions in the presence of different environments were conducted to control the formation of various well-shaped ZnO crystals. In addition, the porous three-dimensional microspheres possess larger surface area, which make it improving the mechanical properties of polymer compound. The mechanical properties of ZnO reinforced polyhydroxyalkanoates (PHA) composites have been tremendously improved. The elongation to break and ultimate tensile strength are increased by 41.2 and 56% compared with the pure PHA, respectively. The Young's modulus of the composites is also further improved. The results demonstrate the effectiveness of ZnO as reinforcement applications in polymer composites. POLYM. COMPOS., 35:1701–1706, 2014. © 2014 Society of Plastics Engineers

The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation.

BACKGROUND To understand whether arginine catabolism might be involved in hot air (HA)-induced chilling tolerance mechanism in tomato fruit, we investigated the effect of HA treatment on endogenous arginine catabolism in relation to chilling injury. RESULTS Tomato fruit were harvested at mature green stage and treated with HA at 38°C for 12 h and then stored at 2°C for 21 days. The effects of HA treatment on fruit chilling injury and gene expression levels or enzyme activity, and metabolites related to arginine catabolism were evaluated. HA treatment reduced the chilling injury symptoms of tomato fruit and enhanced the accumulation of endogenous polyamines, especially putrescine and proline. This accumulation is associated with the increased transcript levels of genes encoding arginase (LeARG1 and LeARG2), arginine decarboxylase (LeADC), ornithine decarboxylase (LeODC) and ornithine aminotransferase (LeOAT) at most sampling times. However, HA treatment had little effect on nitric oxide synthase activity and nitric oxide concentration. CONCLUSION These results revealed that the reduction in chilling injury by HA treatment may be due to the accumulation of putrescine and proline induced primarily by activating the catabolism of endogenous arginine. © 2013 Society of Chemical Industry

What's known on the subject? and What does the study add? Partial urethral obstruction (PUO), a common urologic pathology in men and children, can be associated with detrusor overactivity (DO), but the exact molecular mechanisms responsible for the altered contractile phenotypes have not been fully elucidated. Our study is the first to determine by direct patch-clamp current measurement that PUO, to recapitulate many of the pathological characteristics of benign prostatic hyperplasia (BPH), is associated with an approximate 5-fold decrease in bladder myocyte Maxi-K channel activity. Similar to others we report a 40% decrease in Maxi-K α subunit expression which correlates with the observed decrease in Maxi-K activity, but uniquely as much as a 5-fold increase in expression of Maxi-K β subunit which we hypothesize may be a compensatory response. Based upon our previous finding of increased detrusor overactivity (DO) in similar male PUO rats, we suggest the Maxi-K channel as a therapeutic target to treat BPH associated lower urinary tract symptoms (LUTS). OBJECTIVES • To examine the effect of partial urethral obstruction (PUO) on bladder smooth muscle outward potassium current and the contribution of the large-conductance calcium-activated potassium (Maxi-K, BKCa) channel to this activity in smooth muscle cells isolated from bladders of sham-operated and PUO male rats using whole-cell patch clamp recording techniques. • To determine the effect of PUO on the expression of the Maxi-K channel α and β1 subunits and in vitro detrusor contractility. MATERIALS AND METHODS • Twenty adult male Sprague–Dawley rats were divided equally into two groups and subjected to surgical ligation of the urethra (PUO) or sham surgery (SHAM). • After 2 weeks, the detrusors from PUO and SHAM rats were used for molecular analyses (mRNA and protein quantification of Maxi-K subunits) or organ bath contractility studies, or myocytes were isolated for conventional whole-cell patch clamp analyses. RESULTS • PUO increased bladder mass 2.5-fold and detrusor strips exhibited a more tonic-type contraction and increased contractility compared with controls (SHAM). • Iberiotoxin (300 nM) sensitive Maxi-K channel current comprised about 40% of the outward whole-cell current in SHAM bladders but only about 8% in PUO bladders. • Expression of the α subunit of the Maxi-K channel was significantly decreased ∼40% while the expression of the β1 subunit was increased ∼2-fold at the mRNA level. The increase in β1 expression was confirmed by Western blotting. CONCLUSIONS • Our findings show that obstruction of the rat bladder is associated with decreased Maxi-K channel activity of bladder smooth muscle cells, determined via direct current measurement. • Increased expression of the β1 subunit points to a compensatory reaction to decreased Maxi-K channel activity. • Maxi-K channel openers or gene therapy may therefore provide therapeutic benefit for the overactive bladder.

Self-assembled In (Indium)-doped ZnS nanowire bundles were synthesized via a thermal evaporation method without using any template. Vapor - solid homoepitaxial growth was found to be the key reason for the formation of close-packed nanowire bundles grown on the surface of microscale sphere-shaped ZnS crystal. X-ray diffraction (XRD), selected area electron diffraction (SAED), and transmission electron microscopy (TEM) analysis demonstrate that the In-doped ZnS nanowires have the cubic structure, and there are numerous stacking faults along the direction. Photoluminescence (PL) spectrum shows that the spectrum mainly includes two parts: a weak violet emission band centering at about 380 nm and a strong green emission band centering at about 510 nm. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

OBJECTIVE To investigate the in vitro and in vivo effects of blebbistatin (a small cell-permeable molecule with high affinity and selectivity toward the myosin II contractile molecule) on bladder smooth muscle (SM) contractility, as antimuscarinic therapy is only 65-75% effective in treating overactive bladder (OAB) and is associated with considerable side-effects, with a < 25% continuation rate at 1 year. MATERIALS AND METHODS Bladder and aortic strips from adult male rats, and human bladder strips obtained from open prostatectomy, were used for organ-bath studies of blebbistatin. Awake cystometry was also used in rats in both the presence and absence of intravesically delivered blebbistatin. RESULTS Blebbistatin dose-dependently and completely relaxed both KCl- and carbachol-induced rat detrusor and endothelin-1-induced human bladder contraction. Pre-incubation with 10 µm blebbistatin attenuated carbachol responsiveness by ≈ 65% while blocking electrical field stimulation-induced bladder contraction reaching 50% inhibition at 32 Hz. The basal tone and amplitude of spontaneous contraction were also significantly diminished. Urodynamic variables were obviously altered by intravesical infusion with blebbistatin. CONCLUSION Our novel data show that blebbistatin strongly relaxes both rat and human bladder contraction induced by various physiological stimuli. Coupled with our in vivo data showing that nanomole doses of blebbistatin significantly alter urodynamic variables to produce a less active bladder, our results suggest the possibility of intravesically administered blebbistatin binding at myosin II being developed as a therapeutic treatment for OAB via a novel targeting of the SM contractile apparatus.

NSCs (neural stem cells) provide a powerful research tool for the design and discovery of new approaches to cell replacement therapy during brain repair. However, the usefulness of this tool has been particularly obstructed by limited neuronal differentiation of NSCs. Brn-4, a member of the POU domain family of transcription factors, has been previously implicated in the development of neurons by expression analysis. Here, we directly investigated the effects of Brn-4 on the neuronal differentiation and development of NSCs derived from the E13 rat midbrain. We found that Brn-4 knockdown in NSCs resulted in a significant decrease of MAP-2-positive neurons with immature morphology. Overexpression of Brn-4 in NSCs markedly increased the production and maturation of newborn neurons. These results suggest that Brn-4 has a critical role in the neuronal differentiation of mesencephalic NSCs and the maturation of newborn neurons. Brn-4 may be utilized to manipulate NSCs for gene and cell therapy of several neurological diseases.

BACKGROUND: Arginase, which plays an important role in regulating the metabolism of L-arginine (Arg) in mammalian cells, has been reported to be involved in stress responses in higher plants. In view of the well-established roles of polyamines, nitric oxide and proline in plant tolerance to chilling stress, arginase may play an important role in fruit chilling tolerance by regulating the metabolism of Arg. However, the current information available on this is very limited. RESULTS: Cherry tomatoes (Lycopersicon esculentum cv.Messina) at the mature green stage were treated with Arg or Nω -hydroxy-nor-L-arginine (nor-NOHA) and analysed for chilling injury, electrolyte leakage, malondialdehyde and proline contents and arginase and antioxidant enzyme (superoxide dismutase, catalase, peroxidaseand ascorbate peroxidase) activities during cold storage. The effects of low temperature on the transcriptional levels of two arginase genes (LeARG1 and LeARG2) were also evaluated. LeARG1 and LeARG2 expression and arginase activity were significantly induced by low temperature. Compared with the control, Arg treatment alleviated fruit chilling injury, reduced electrolyte leakage, malondialdehyde content and peroxidaseactivity and increased other parameters. Treatment with nor-NOHA caused the opposite effects. CONCLUSION: Up-regulation of arginase activity and gene expression may be a chilling tolerance strategy in cherry tomato fruit. Inhibition of chilling-induced arginase activity could aggravate chilling injury and oxidation damage. Arginase appears to play an important role in the chilling resistance process of cherry tomato fruit induced by Arg. Copyright © 2010 Society of Chemical Industry

Poly(hexane succinate) (PHS) was designed as an alternative type of polyester plasticizer for the modification of poly(vinyl chloride) (PVC). The plasticizing effect of PHS was studied and compared with the traditional dioctyl phthalate (DOP) plasticizer. The results show that the PVC plasticized by PHS had the lowest tensile strength of 15.3 MPa and the highest elongation at break of 105.1% when 35 phr PHS was added. It also exhibited a lower glass-transition temperature than PVC plasticized by DOP (PVC–DOP); this could be explained by the improvement of free volume for the amorphous part of PVC enhanced by high-molecular-weight PHS. The migration-resistant properties of PVC–PHS was greatly superior to those of PVC–DOP. All of these results illustrate that PHS had a higher plasticizing efficiency than DOP for PVC. PHS could be used as an alternative plasticizer to remove the potential health risks of phthalates migrating out during applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46388.

OBJECTIVES To examine the effect of partial urethral obstruction (PUO) on the sphingosine-1-phosphate (S1P, a bioactive lipid shown to modulate smooth muscle, SM) pathway in the bladders of male rats, and to determine the effect of PUO on the RhoA/Rho-kinase (ROK) pathway, and whether there is a molecular cross-talk with the S1P pathways associated with bladder overactivity (S1P1-S1P3, where S1P1 is associated with nitric oxide-mediated SM relaxation, and S1P2 and S1P3 receptors are associated more with SM contraction via the ROK pathway). MATERIALS AND METHODS In all, 20 male rats were divided into two groups and underwent PUO or a sham operation (control). After 2 weeks all rats were killed humanely and bladder specimens used for in vitro organ-bath physiological contractility studies, and for mRNA and protein analyses of major S1P/ROK pathway constituents via real-time polymerase chain reaction and Western blotting, respectively. In addition, early-passage SM cells were transfected with recombinant sphingosine kinase (SPHK, the enzyme that converts sphingosine to S1P). RESULTS Bladders from PUO rats had greater mRNA expression of the S1P2 and S1P3 receptors, as well as SPHK1, than the sham controls (4.78, 2.04 and 2.72 times, respectively). PUO rats also had significantly greater expression of RhoA and ROKα (1.76 and 2.19 times, respectively). Western blotting and organ-bath contractility studies showed similar changes at the protein and in vitro functional level, with an increased contractility of bladder strips from PUO rats to exogenous S1P. Transfection of SPHK into isolated SM cells increased ROK expression. CONCLUSIONS We show for the first time that the S1P signalling pathway is significantly upregulated in response to PUO in male rats at both the molecular and in vitro functional levels, correlating with an activation of the RhoA/ROK pathway. Further, we provide novel data that SPHK overexpression increases ROK expression in vitro, suggesting a novel hypothesis of S1P-induced bladder overactivity in the mechanism for PUO-induced bladder dysfunction and the S1P signalling pathway as a possible therapeutic target for bladder overactivity.

The authors developed a simple solvothermal route to synthesis of PbS nanocrystals in the mild binary mixed solvent made of diethylenetriamine (DETA) and water. Two kinds of PbS nanostructures (dice-like and cubic) have been successfully synthesized in the binary mixed solvothermal system at 150 °C by changing the sulfur source. The products were characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM). The results show that the as-prepared dice-like PbS crystals have a hole on each of their faces. To elucidate the relationship between reaction systems and the morphologies of the final products, the authors also investigated the crystal growth by using different sulfur source. Based on the experimental results, the possible growth mechanism of the dice-like PbS crystals was proposed.

Complex nanomaterial-film-metal substrate architectures, which are composed of ZnS nanorods, island-like ZnS film and Zn foil, have been formed via a simple vapor deposition route. The growth of the complex nanostructures is initiated by the preferred formation of ZnS film, and ZnS nanorods branches out from ZnS film flows a liquid-phase epitaxial growth mode. The ZnS nanorod is switched to an angle, which may be attributed to the sudden change of vapor pressure and temperature reduction by the end of vapor deposition process. The room-temperature photoluminescence spectrum shows that complex ZnS nanostructures have a strong blue emission band centered at about 423 nm and a weak broad green emission band centered at about 515 nm. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)