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This article discusses a study that identified two novel mutations in the TTC37 gene in two Chinese patients with Crohn's disease (CD). These mutations are the first two Asian cases of CD associated with TTC37 mutations. The TTC37 gene is involved in RNA exosome regulation and mutations in this gene have been linked to trichohepatoenteric syndrome and IBD. The study suggests that TTC37 mutations may influence the progression of CD by altering mitochondrial structure and function. Further research is needed to understand the precise mechanisms involved. [Extracted from the article]

Polymerase chain reaction (PCR) is commonly used to detect Listeria monocytogenes , foodborne pathogen. This study conducted in silico genomic analysis to investigate the specificity and binding efficacy of four published pairs of PCR primers targeting Listeria prfA -virulence gene cluster (pVGC) based on Listeria sequences available. We first performed comprehensive genomic analyses of the pVGC, the main pathogenicity island in Listeria spp. In total, 2961 prfA , 642 plcB , 629 mpl , and 1181 hlyA gene sequences were retrieved from the NCBI database. Multiple sequence alignments and phylogenetic trees were generated using unique (non-identical or not-shared) sequences of each represented genes, targeting four pairs of PCR primers published previously, namely 202 prfA , 82 plcB , 150 mpl , and 176 hlyA unique gene sequences. Only the hlyA gene showed strong (over 94%) primer mapping results, while prfA, plcB , and mpl genes showed weak (<50%) matching results. In addition, nucleotide variations were observed at the 3′ end of the primers, indicating non-binding to the targets could potentially cause false-negative results. Thus, we propose designing degenerate primers or multiple PCR primers based on as many isolates as possible to minimize the false-negative risk and reach the aim of low tolerable limits of detection. [ABSTRACT FROM AUTHOR]

Previous studies have revealed that deleterious I ANKZF1 i mutations may disrupt mitochondrial integrity and play a pathogenic role in the development of IBD in human.[5] No other meaningful mutations related to IBD have been identified in the proband. Learning point for clinicians At present, only five mutations of I ANKZF1 i have been identified in patients with inflammatory bowel disease (IBD). Our findings demonstrate the first case of IBD attributed to I ANKZF1 i heterozygous mutation (NM 018089.2: c.1243T>G; p.Leu415Val) in Asia, which expands our understanding of I ANKZF1 i mutations. [Extracted from the article]

Background: Lobectomy is not advocated for papillary thyroid carcinoma (PTC) with high-risk features, although there is no highlevel evidence showing that this is an inferior strategy. This study aimed to examine the association between the extent of surgery and survival of patients with PTC and high-risk features. Methods: Consecutive patients with PTC and at least one high-risk feature treated in 2000-2012 were included in the study. High-risk features were defined as: primary tumour larger than 4 cm, gross extrathyroidal extension, macroscopic multifocality, and confirmed nodal metastasis including pathological lateral neck metastasis (pN1b) or more than five central lymph node metastases. Cox proportional hazards models were employed to measure the association between the extent of surgery and disease-specific survival (DSS) in the whole cohort and in a matched-pair analysis. Results: Among a total of 2059 patients with high-risk features, 1224 underwent lobectomy and 835 had total thyroidectomy. Patients who underwent total thyroidectomy had significantly higher rates of bilateral cancer than those who had a lobectomy (79.4 versus 2.7 per cent respectively), macroscopic multifocality (80.8 versus 32.8 per cent) and bilateral neck metastasis (30.9 versus 3.3 per cent) (all P<0.001). With a median follow-up of 93 months, multivariable analysis showed that the extent of surgery was not associated with DSS in the whole cohort (hazard ratio 1.36, 95 per cent c.i. 0.75 to 2.48; P=0.310). After 1: 1 case-control matching of 528 patients, no significant difference between lobectomy and total thyroidectomy groups was observed with respect to the 10-year DSS rate (94.3 versus 95.2 per cent respectively; P=0.323) or 10-year recurrence-free survival rate (75.8 versus 79.2 per cent; P=0.784). Conclusion: Lobectomy was not associated with significantly worse outcomes for patients with PTC and high-risk features. [ABSTRACT FROM AUTHOR]

Summary: Background: Oxidative stress plays an important role in initiating the destruction of melanocytes, which could be one possible mechanism of vitiligo. PINK1 is an outer membrane protein of mitochondria, which protects many cells from oxidative stress through regulating mitochondrial function. However, the role of PINK1 and its effects on oxidative damage in melanocytes have not been elucidated. Aim: To investigate the expression and effects of PINK1 on oxidative stress in human melanocytes. Methods: Quantitative reverse transcription−PCR and western blot analysis were used to analyse the expression of PINK1 in PIG1 melanocyte and gene downregulation models. Levels of cell viability, cell apoptosis and intracellular reactive oxygen species (ROS), mitochondrial morphology, mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening were measured in PIG1 models transfected with PINK1 small interfering RNA with or without hydrogen peroxide (H2O2). Results: We first observed the expression of PINK1 in human PIG1 melanocytes and found that downregulation of PINK1 made melanocytes more sensitive to oxidative stress induced by H2O2, with more cell apoptosis and increased intracellular ROS. Meanwhile, downregulation of PINK1 caused morphological changes in mitochondria, decreased the MMP and increased MPTP opening. Conclusions: Our study found PINK1 plays an essential role in protecting human melanocytes from oxidative stress. [ABSTRACT FROM AUTHOR]

Summary: The diagnosis of coronavirus 19 (COVID‐19) relies mainly upon viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis; severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐specific antibody detection is convenient, safe and highly sensitive. Immunoglobulin (Ig)M and IgG are commonly used to serologically diagnose COVID‐19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS‐CoV‐2‐specific IgM, IgA and IgG antibodies, identify changes in them based on COVID‐19 severity, and establish the significance of combined antibody detection. COVID‐19 patients, divided into a severe and critical group and a moderate group, and non‐COVID‐19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS‐CoV‐2‐specific IgM, IgA and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results and other data were recorded for all patients. Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are more effective for diagnosing COVID‐19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID‐19 patients than in non‐COVID‐19 patients. IgA and IgG were also higher for severe and critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Detection of SARS‐CoV‐2‐specific combined IgA–IgG antibodies is advantageous in diagnosing COVID‐19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity. [ABSTRACT FROM AUTHOR]

Aims: Antibiotic adjuvants can give a second life to the antibiotics to which bacteria are highly resistant. We evaluated the antimicrobial effects of extracts from Pithecellobium clypearia against methicillin‐resistant Staphylococcus aureus (MRSA) and also the potential for synergy with several antibiotics. Methods and Results: For this study, four extracts from P. clypearia were tested on MRSA using the broth microdilution method for activity assessment. The ethyl acetate fraction (S20b) had the strongest antibacterial activity against MRSA among the fractions tested. In all, 14 compounds such as gallic acid and luteolin in S20b were analysed by UFLC‐Q‐TOF‐MS/MS. S20b combined with erythromycin showed synergy effects against MRSA and combined with ceftriaxone sodium and levofloxacin showed additive effects against MRSA. Electron microscopy showed that extract S20b damaged the MRSA cell wall and K+ efflux measurements indicated that extract S20b increased cell membrane permeability. Moreover, S20b suppression of PBP2a expression was assessed by Western blot. Furthermore, an in vivo study was used to investigate the therapeutic potential of S20b based on a mouse pneumonia model. Conclusions: The in vitro study results have shown that S20b not only inhibits MRSA growth directly but also reduces the resistance of MRSA to the evaluated antibacterial agents. Based on the in vivo study, it can be concluded that S20b can treat pneumonia in the mouse model. Significance and Impact of the Study: This study is the first research to demonstrate that S20b can inhibit MRSA growth and reduce drug resistance of clinical isolates to antibiotics. S20b has the potential to be used as a therapeutic agent against MRSA and treatment for MRSA pneumonia. [ABSTRACT FROM AUTHOR]

Summary: Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease‐2019 (COVID‐19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID‐19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C‐reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)‐2R, IL‐6, IL‐8, IL‐10 and tumor necrosis factor (TNF)‐α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL‐2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL‐2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL‐2R/lymphocytes were superior compared with other markers for the identification of COVID‐19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL‐2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease‐deteriorated patients, which might be correlated with the outcome of COVID‐19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL‐2R/lymphocyte was a prominent biomarker for early identification of severe COVID‐19 and predicting the clinical progression of the disease. [ABSTRACT FROM AUTHOR]

Summary: Background: Epidermal barrier dysfunction is the initial event in the development of atopic dermatitis (AD). Recent studies have identified a crucial role for the aryl hydrocarbon receptor (AHR) in controlling the gene expression of filaggrin and other skin barrier proteins, suggesting an underlying association between AHR and AD pathogenesis. Aim: To investigate the role of AHR gene polymorphisms in the susceptibility to AD and in AD‐associated phenotypes. Methods: We enrolled 487 patients with AD, 210 patients with psoriasis and 226 healthy controls (HCs) from the Han Chinese population, and genotyped two AHR single‐nucleotide polymorphisms (rs10249788 and rs2066853) by PCR and subsequent DNA sequencing. Results: The AHR rs10249788 and rs2066853 polymorphisms were found in both sets of patients (AD and psoriasis) and in HCs, but no significant differences were detected in genotype or allele frequencies between the three groups. However, patients with AD with the rs10249788 (CT/TT) or rs2066853 (AG + AA) genotype were more likely to have severe dry skin scores. In the stratification analysis, the AHR rs2066853 (AG + AA) and rs10249788 (CT + TT) genotypes could predict a higher risk of severe dry skin phenotypes in the male, early‐onset and allergic rhinitis subgroups. Furthermore, the combined rs10249788 (CT + TT) and rs2066853 (AG + AA) genotypes led to a higher risk for severe dry skin in patients with AD. Conclusion: AHR polymorphisms are not associated with the risk of AD; however, they may predict a dry skin phenotype in patients with AD. [ABSTRACT FROM AUTHOR]

Study Question: Can of Clinical Genetics, Maastricht University Medical Centre, Maastricht kisspeptin and its analogues regulate the motility of human decidual stromal cells and what intracellular signaling pathways are involved?Summary Answer: Kisspeptin analogue-mediated cell motility in human decidual stromal cells via the focal adhesion kinase (FAK)-steroid receptor coactivator (Src) pathway suggesting that kisspeptin may modulate embryo implantation and decidual programming in human pregnancy.What Is Known Already: The extravillous trophoblast invades the maternal decidua during embryo implantation and placentation. The motile behavior and invasive potential of decidual stromal cells regulate embryo implantation and programming of human pregnancy.Study Design, Size, Duration: Human decidual stromal cells were isolated from healthy women undergoing elective termination of a normal pregnancy at 6- to 12-week gestation, after informed consent.Participants/materials, Setting, Methods: Kisspeptin analogues were synthetic peptides. Cell motility was estimated by an invasion and migration assay. Immunoblot analysis was performed to investigate the expression of kisspeptin receptor and the effects of kisspeptin analogues on the phosphorylation of FAK and Src. Small interfering RNAs (siRNAs) were used to knock down the expression of kisspeptin receptor, FAK, Src, matrix metallo-proteinases (MMPs) 2 and 9, and extracellular signal-regulated protein kinase (ERK) 1/2.Main Results and the Role Of Chance: The kisspeptin receptor was expressed in human decidual stromal cells. Kisspeptin agonist decreased, but antagonist increased, cell motility. Kisspeptin agonist decreased the phosphorylation of FAK and Src tyrosine kinases, whereas antagonist increased it. These effects on phosphorylation were abolished by kisspeptin receptor siRNA. The activation of cell motility by kisspeptin analogues was suppressed by siRNA knockdown of endogenous FAK (decreased 66%), Src (decreased 60%), kisspeptin receptor (decreased 26%), MMP-2 (decreased 36%), MMP-9 (decreased 23%), and ERK 1/2 inhibitor (decreased 27%).Limitations, Reasons For Caution: Human decidual stromal cells were obtained from women having terminations after 6-12 weeks of pregnancy and differences in timing could affect their properties.Wider Implications Of the Findings: Kisspeptin acting within the endometrium has a potential modulatory role on embryo implantation and decidual programming of human pregnancy.Study Funding/competing Interest(s): This work was supported by grant NSC-104-2314-B-182A-146-MY2 (to H.-M.W.) from the Ministry of Science and Technology, Taiwan, and grants CMRPG3E0401 and CMRPG3E0402 (to H.-M.W.). This work was also supported by grants from the Canadian Institutes of Health Research to P.C.K.L. P.C.K.L. is the recipient of a Child & Family Research Institute Distinguished Investigator Award. The authors have no conflicts of interest to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Aims: Genotype VII Newcastle disease (ND) is one of the most epidemic and serious infectious diseases in the poultry industry. A novel vaccine targeting VII Newcastle disease virus (NDV) is still proving elusive. Methods and Results: In this study, we constructed regulated delayed lysis Salmonella strains expressing either a fusion protein (F) alone under an eukaryotic CMV promoter or together with chicken IL‐18 (chIL‐18) as a molecular adjuvant under prokaryotic Ptrc promoter, named pYL1 and pYL23 respectively. Oral immunization with recombinant strains induced NDV‐specific serum IgG antibodies in both pYL1‐ and pYL23‐immunized chickens. The presence of chIL‐18 significantly increased lymphocyte proliferation in immunized chickens, as well as the percentages of CD3+CD4+ and CD3+CD8+ T cells in serum, even if a statistically significant difference did not exist. After a virulent challenge, pYL23 immunization provided about 80% protection at day 10 postinfection, compared with 60% of protection offered by pYL1 immunization and 100% protection in the inactivated vaccine group, indicating the enhanced immune response provided by chIL‐18, which was also confirmed by histochemical analysis. Conclusions: Recombinant lysis Salmonella‐vectored DNA vaccine could provide us a novel potential option for controlling NDV infection. Significance and Impact of the Study: This study took use of a regulated delayed lysis Salmonella vector for the design of an orally administrated vaccine against NDV. [ABSTRACT FROM AUTHOR]

Background Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. Aim To investigate the gender difference of BrS in Han Chinese. Design We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. Methods Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. Results The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P  =   0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P  <   0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P  =   0.049), which was mainly attributed to syncope (P  <   0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P  =   0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P  =   0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P  =   0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P  =   0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. Conclusion Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females. [ABSTRACT FROM AUTHOR]

The aim of this study was to produce lactobionic acid from lactose by a new Pycnoporus sp. SYBC‐L10 strain. Recently, studies on enzymatic production of lactobionic acid mostly focus on cellobiose dehydrogenase from Sclerotium rolfsii CBS 191·62 and laccase from Trametes pubescens MB 89 oxidize lactose to lactobionic acid with redox mediators. In this study, we converted lactose to lactobionic acid by shaking flask fermentation without exogenous mediator in the reaction mixture. In this bioconversion process, lactose is efficiently converted into lactobionic acid with a specific productivity of up to 3·1 g l−1 h−1 and 96% yield. 3‐Hydroxyanthranilic acid added externally to the reaction mixture can obviously accelerate the conversion of lactose to lactobionic acid. The results showed that 3‐hydroxyanthranilic acid produced by the fungus itself is an important influencing factor in this bioconversion process. This study presents the first attempt to efficiently produce lactobionic acid by white‐rot fungi, suggesting definite potential for Pycnoporus to produce lactobionic acid. Significance and Impact of the Study: Lactobionic acid has been applied to a wide range of applications in pharmaceutical, food, nanotechnology and chemical industries. Here, an attempt was done to produce lactobionic acid from lactose using the cellobiose dehydrogenase‐3‐HAA‐laccase system in a fermentation system. After a survey of other methods to produce lactobionic acid by cellobiose dehydrogenase, this study explores a new and significant perspective for the production of lactobionic acid. Significance and Impact of the Study: Lactobionic acid has been applied to a wide range of applications in pharmaceutical, food, nanotechnology and chemical industries. Here, an attempt was done to produce lactobionic acid from lactose using the cellobiose dehydrogenase‐3‐HAA‐laccase system in a fermentation system. After a survey of other methods to produce lactobionic acid by cellobiose dehydrogenase, this study explores a new and significant perspective for the production of lactobionic acid. [ABSTRACT FROM AUTHOR]

Summary: Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide‐binding, oligomerization domain (NOD)‐like receptor family, pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2‐biased response. In this study, VDR–/– mice and WT (WT) mice were used. Th2 cell differentiation between VDR–/– mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR–/– mice. The VDR–/–CD4+ T cells were prone to Th2 polarization. VDR–/– mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR–/– mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to investigate the association between the single‐nucleotide polymorphisms (SNPs) of the interleukin 22 (IL‐22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL‐22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL‐22 level of serum was assessed by enzyme‐linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22–4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20‐3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30–7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35–7·85, P = 0·009). In addition, the concentration of IL‐22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL‐22. [ABSTRACT FROM AUTHOR]

Background Sudden cardiac death (SCD) occurs in a broad spectrum of cardiac pathologies and is an important cause of mortality in the general population. Idiopathic ventricular fibrillation (IVF) is a rare but important factor resulting in SCD. It is diagnosed in a resuscitated cardiac arrest victim underlying unknown cause, with documented ventricular fibrillation. Previous studies have demonstrated that mutations in dipeptidyl aminopeptidase-like protein-6 (DPP6) and cardiac sodium channel Nav1.5 (SCN5A) are the most important genetic factors involve in IVF. Aim By using whole sequencing to identify the genetic lesion of a family with suspicious idiopathic ventricular fibrillation Design Prospective genetic study. Methods In this study, we employed whole-exome sequencing in combination with arrhythmia-related gene filtering to identify the genetic lesion for a family suffering from suspicious IVF, syncope and SCD. We then generated the plasmids of DPP6 -pcDNA3.1+ (WT and c.1578G>C/p.Q526H). Kv4.3 -pcDNA3.1+ was co-transfected together with/without DPP6 -pcDNA3.1+ (WT and/or c.1578G>C/p.Q526H) into HEK293 cells to perform the patch clamp experiments. Results A novel missense mutation (c.1578G>C/p.Q526H) of DPP6 was identified and co-segregated with affected patients in this family. Patch clamp experiments suggested that this novel mutation might result in a gain of function and disturb the efflux of potassium ion. Conclusion Our study not only reported the second missense mutation of DPP6 in heart disease and expanded the spectrum of DPP6 mutations, but also contribute to the genetic diagnosis and counseling of families with suspicious IVF, syncope and SCD. [ABSTRACT FROM AUTHOR]

Summary: Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which around one in 20 affected individuals show autosomal dominant inheritance. In such cases there may be gain‐of‐function mutations in CARD14, encoding caspase recruitment domain‐containing protein 14 (CARD14), which activates the noncanonical nuclear factor (NF)‐κB pathway, thereby promoting cutaneous inflammation. Here we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins 12 and 23, in both patients. A 49‐year‐old woman and her 20‐year‐old son had lifelong, generalized, patchy erythematous scale with a few islands of sparing, as well as minor nail ridging and mild palmoplantar keratoderma, features consistent with generalized PRP. Topical steroids, phototherapy and oral retinoids proved ineffective. Following informed consent, Sanger sequencing of CARD14 in both individuals revealed a new heterozygous single‐nucleotide transversion in exon 4, c.356T>G, resulting in the missense mutation p.Met119Arg. Ustekinumab, at a dose of 45 mg every 12 weeks, brought about a significant physical and emotional improvement in both the mother and son within a few days of the initial dose, which was sustained on maintenance dosing. This report highlights the therapeutic potential of biologics that downregulate NF‐κB signalling in familial PRP with mutations in CARD14. [ABSTRACT FROM AUTHOR]

Background Few studies have examined the association between psoriasis and glomerulonephritis ( GN) as well as chronic kidney disease ( CKD). Objectives To determine the risk of CKD in patients with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis. Methods We identified 4344 patients with psoriasis for the study cohort and randomly selected 13 032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD. Results After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow-up period [hazard ratio ( HR) 1·28; 95% confidence interval ( CI) 1·14-1·44]. The increased incidence of GN in patients with psoriasis ( HR 1·50, 95% CI 1·24-1·81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis ( HR 1·62 vs. 1·26). Among drugs, nonsteroidal anti-inflammatory drugs ( NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1·69, 95% CI 1·14-2·49). Conclusions Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Objective: To assess the iodine nutritional status and investigate the prevalence of thyroid diseases in a community population in Chengdu, China. Methods: Eighty school-age children were randomly selected for measurements of urinary iodine concentration. A total of 1500 residents over the age of 18 who had lived in Chengdu for more than 5 years were selected by stratified cluster sampling. Serum thyroid hormone concentrations and thyroid autoantibodies were measured, and thyroid ultrasonography was performed. Results: The median urine iodine concentration was 184 mg/l in school-age children. The prevalence of clinical hyperthyroidism, subclinical hyperthyroidism, clinical hypothyroidism and subclinical hypothyroidism was 0.97%, 1.95%, 0.90% and 5.55%, respectively. The prevalence of thyroid autoantibodies and thyroid nodules was 15.82% and 16.87%, respectively. The prevalence of clinical hyper- and hypothyroidism was greater in females than in males (P< 0.05). The prevalence of subclinical hyper- and hypothyroidism, thyroid nodules and thyroid autoantibodies increased significantly with age (P< 0.05). The rate of new abnormal TSH was 9.37%, and the average serum Thyroid Stimulating Hormone (TSH) concentrations increased with age. When TSH >0.71 mU/l, the prevalence of positive TPOAb and/or TgAb increased significantly with rising concentrations of TSH (P< 0.05); however, the prevalence of thyroid nodules did not increase with escalating concentrations of TSH (P =0.09). Conclusion: Subclinical thyroid diseases, especially subclinical hypothyroidism and thyroid nodules, are common in an iodine sufficient area. Females and the elderly might benefit from routine screening for thyroid diseases, followed by appropriate detection and treatment. [ABSTRACT FROM AUTHOR]

Cysteine phytase is the main phytate-degrading enzyme of ruminant animals. To explore the genetic diversity and dynamic expression profile of cysteine phytase in sheep rumen during a feeding cycle, four transcript (0, 4, 9 and 16 h after feeding) and one DNA (9 h after feeding) clone libraries were constructed, respectively. A total of 46 distinct gene fragments were identified, and most of these sequences had low identities (<60%) with known phytases. Great divergence was found in the constitution and abundance of genes at the genome and transcriptional levels, and the transcript data are more reliable to reflect the information of functional genes. Phylogenetic analysis indicated that the genes from uncultured bacteria instead of Firmicutes played the major phytate-degrading role. Further comparative analysis revealed the dynamic constitution of cysteine phytase genes in rumen at different time points. Significance and Impact of the Study Ruminal phytases, that are cysteine phytases, are novel in sequences and functions. Great divergence in the constitution and abundance of cysteine phytase genes at the genome and transcriptional levels suggested that transcript data are more reliable to reflect the information of functional genes. Phylogenetic and rarefaction analyses indicated that the cysteine phytase genes from uncultured bacteria instead of Firmicutes play the major phytate-degrading role in rumen, and their constitution is dynamic at different time points. This study provides a new insight into ruminal cysteine phytase genes and undermines their expression profiles over a whole feeding cycle. [ABSTRACT FROM AUTHOR]

We hypothesized that the aberrant expression of microRNAs ( miRNAs) in rheumatoid arthritis ( RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor ( RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed insulin-like growth factor-1 receptor ( IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein ( CREB) protein expression by Western blotting. The protein expression of IGF-1 R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin ( IL)-10 production by activated normal T cells, but not RA T cells. The transfection of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Background In recent years, increasing attention has been focused on the skin hypopigmentation that develops after the initiation of imatinib mesylate therapy in patients with chronic myeloid leukaemia ( CML). Aim To understand the underlying mechanism of this hypopigmentation effect, and to explore the possibility of using imatinib in the treatment of pigmentation disorders. Methods We examined the effects of imatinib on the proliferation, apoptosis, melanin content and melanogenic activity of human primary epidermal melanocytes. The responsible molecular events were also investigated in a mechanism study. Results We found that imatinib led to a dramatic decrease in total melanin content in cultured melanocytes, by affecting melanocyte number and/or melanogenesis in a dose-dependent manner. This inhibition of melanogenesis was due to suppressed expression of tyrosinase and microphthalmia-associated transcription factor ( Mi TF). Furthermore, stem cell factor ( SCF)-stimulated c- Kit activation and melanocyte proliferation were completely abrogated by imatinib. Conclusions Inactivation of c- Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. These results also support using imatinib as a clinical depigmentation agent when dosage being carefully determined. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate the ability of Cp G7909 adjuvant to enhance immunogenicity and protective efficacy of a subunit vaccine composed of ESAT6- Ag85 A fusion protein ( Pe685a) of Mycobacterium tuberculosis. Methods and Results ELISA was used to detect specific antibody and IFN-γ expression in sera; ELISPOT, to detect IFN-γ expression in splenocytes; MTT assay and FACS, to detect T-lymphocytes proliferation in spleens; and RT- PCR, to detect cytokines expression in lungs of mice after immunization. Bacterial load and histopathological lesions in lungs or spleens of mice challenged with Myco. tuberculosis H37 Rv strain were analysed. Compared with incomplete Freund's adjuvant, induced more potent production of Pe685a-specific Ig G2a/ Ig G1 antibody and higher expression of IFN-γ in sera, stimulated more generation of antigen-specific IFN-γ-secreting splenocytes, enhanced frequencies of CD3+ CD4+ and CD3+ CD8+ T-lymphocytes in spleen and increased transcription of TNF-α, IFN-γ, IL-6 and TLR9 in lung. However, lower bacterial load in lung and less severe lung pathology were not observed in Cp G7909 group mice. Conclusions Cp G7909 is able to enhance immunological effects of Pe685a subunit vaccine, but does not confer significant protective efficacy against Myco. tuberculosis infection. Significance and Impact of the Study Cp G7909 as an adjuvant of subunit vaccine against Myco. tuberculosis is worthy of further investigation. [ABSTRACT FROM AUTHOR]

Background The most common indications for surgery for patients with ileocolic Crohn's disease are fibrostenotic or perforating disease. The objective was to compare surgical outcomes of patients with perforating versus non-perforating disease following ileocolic resection. Methods This was a retrospective review of all patients who had their first ileocolic resection between 1990 and 2010, identified from a prospectively maintained inflammatory bowel disease database. Demographic information, preoperative medication, intraoperative findings and postoperative outcome data were collected. Outcomes in patients who had an abscess drained before surgery or were found to have a fistula or abscess at surgery or at pathology were compared with outcomes in all others. Results A total of 434 patients (56·2 per cent women) were included, 293 with perforating and 141 with non-perforating disease. Median age, tobacco use, and preoperative steroid and biological agent use were similar in the two groups. Forty patients (13·7 per cent) in the perforating group had abscesses drained before surgery and 251 patients had at least one fistula, most commonly to the sigmoid colon. Patients with perforating disease were more likely to require preoperative total parenteral nutrition, need another resection, have an ileostomy and a longer mean postoperative stay, and less likely to undergo a laparoscopic procedure. Patients in this group also developed more postoperative abscesses or leaks (4·8 versus 0 per cent; P = 0·006). The reoperation rate was similar (3·1 versus 0·7 per cent; P = 0·178). Conclusion Patients with penetrating Crohn's disease are more likely to require a more complex procedure, and an ileostomy, and to a have longer postoperative stay. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a well-known Gram-negative pyogenic pathogen that can cause various types of infection. Liver abscesses caused by community-acquired K. pneumoniae infection are commonly reported in Taiwan, especially in people with diabetes mellitus. Meningococcal bacteraemia can present as disseminated pustules and leucocytoclastic vasculitis, but it has rarely been seen in patients with K. pneumoniae infection. To date, there are only two reports in the English literature about K. pneumoniae bacteraemia presenting as generalized pustulosis. We report a third case, occurring in a Taiwanese woman with a community-acquired K. pneumoniae liver abscess leading to sepsis and generalized pustules, complicated by cutaneous leucocytoclastic vasculitis. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis ( AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of micro RNAs (mi RNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 mi RNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction ( PCR). Thirteen mi RNAs were found potentially differential expression. After validation, we confirmed that mi R-16, mi R-221 and let-7i were over-expressed in AS T cells and the expression of mi R-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index ( BASRI) of lumbar spine in AS patients. The protein molecules regulated by mi R-16, mi R-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 ( TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the m RNA expression of interferon ( IFN)-γ was elevated in AS T cells. Lipopolysaccharide ( LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti- CD3+anti- CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti- CD3+anti- CD28+ lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti- CD3+anti- CD28+ LPS-stimulated AS T cells. In conclusion, we found that mi R-16, mi R-221 and let-7i were over-expressed in AS T cells, but only mi R-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 ( IFN-γ) immune response in T cells. [ABSTRACT FROM AUTHOR]

Objective: To assess the effective dose of the liver C-arm computed tomography (CT) scan during hepatic arterial embolisation sur- gery with clinical dose-area product (DAP) data from Taiwan. Methods: The experiment used two kinds of phantoms: RANDO® Man and RANDO Woman (The Phantom Laboratory, Salem, NY), embedded with thermoluminescent dosemeters at locations according to the International Commission on Radiological Protection 103 report. The conversion factors of DAP to effective doses for males and females, respectively, were obtained. The clinical DAP data of liver C-arm CT scan during hepatic arterial embolisation surgery were collected in a hospital in Taiwan. Results: There were 125 liver transarterial embolisation therapy cases, including 94 males and 31 females, from February 2009 to June 2010. C-arm CT was used 38 times for males and 17 times for females. The corresponding average and standard devia- tion of clinical DAP were 61.0±6.6 Gy cm2 and 52.2±8.3 Gy cm2, respectively. Conclusion: The DAP of RANDO Man and RANDO Woman phantoms simply scanned by C-arm CT are much lower than that of patients. After consideration of the clinical DAP of patients, the effective doses of a liver C-arm CT scan recommended for males and females in Taiwan are 11.5±2.3mSv and 11.3±3.0 mSv, respectively. Advances in knowledge: The conversion factors of DAP to effective doses for males and females are 0.19±0.03mSvGy-1cm-2 and 0.22±0.05mSvGy-1cm-2. Only if the actual DAP value of a patient scan is multiplied by the conversion factor can the correct effective dose be determined. [ABSTRACT FROM AUTHOR]

Aims To elucidate the impact of CO2 fixation, nitrate reduction and temperature on selenium reduction by a newly identified acetogenic bacterium, Clostridium sp. BXM. Methods and Results A series of culture experiments were designed to evaluate the impact of temperature, CO2 fixation and nitrate reduction on the rate and extent of selenium reduction by strain BXM. The products of selenium reduction, CO2 fixation and nitrate reduction were determined. Molecular analysis was performed to identify the functional genes involved in the selenium reduction process. CO2 may have enhanced the activity of hydrogenase I and/or the level of cytochrome b, thus increasing selenium reduction. Nitrate may inhibit selenium reduction due to its higher reduction potential and/or by decreasing selenite/selenate reductase activity. The suitable temperature was 37 and 30°C for selenite reduction under anaerobic and aerobic conditions, respectively. The optimum temperature was 30°C for selenate reduction under both anaerobic and aerobic conditions. CO2 fixation and nitrate reduction by Clostridium sp. BXM stimulated each other. Conclusions Clostridium sp. BXM was capable of reducing up to 36-94% of 1 mmol l−1 selenate and selenite under anaerobic or aerobic conditions over 15 days. The strain might be used for the precipitation of Se from highly selenium-contaminated water or sediments. Significance and Impact of the Study The findings contribute to the current understanding about the role that micro-organisms play in the detoxification of toxic selenium compounds in paddy soils. Micro-organisms in paddy soils can influence selenium accumulation in rice grain and hence human selenium intake. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus ( SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of micro RNAs ( miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human mi RNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed mi RNAs using real-time polymerase chain reaction ( PCR). Then, the expression of m RNAs regulated by these aberrant-expressed mi RNAs was detected using real-time PCR. Finally, mi RNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these mi RNAs. The initial analysis indicated that seven mi RNAs, including mi R-145, mi R-224, mi R-513-5p, mi R-150, mi R-516a-5p, miR-483-5p and mi R-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed mi R-145 and over-expressed mi R-224 were noted. We further found that STAT1 m RNA targeted by mi R-145 was over-expressed and apoptosis inhibitory protein 5 ( API5) m RNA targeted by mi R-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with mi R-145 suppressed STAT1 and mi R-224 transfection suppressed API5 protein expression. Over-expression of mi R-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that mi R-145 and mi R-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These mi RNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 ( STAT)-1 expression in patients with SLE. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the response of sarcoplasmic proteins in bovine LM to low-voltage electrical stimulation (ES; 80 V, 35 s) after dressing and its contribution to meat tenderization at an early postmortem time. Proteome analysis showed that ES resulted in decreased (P < 0.05) phosphorylation of creatine kinase M chain, fructose bisphosphate aldolase C-A, β-enolase, and pyruvate kinase at 3 h postmortem. Zymography indicated an earlier (P < 0.05) activation of μ-calpain in ES muscles. Free lysosomal cathepsin B and L activity increased faster (P < 0.05) in ES muscles up to 24 h. Immunohistochemistry and transmission electron microscopy further indicated that lysosomal enzymes were released at an early postmortem time. Electrical stimulation also induced ultrastructural disruption of sarcomeres. In addition, ES accelerated (P < 0.05) the depletion of ATP, creatine phosphate, and glycogen, as well as a pH decline and the more preferred pH/temperature decline mode. Finally, ES accelerated meat tenderization, resulting in lesser (P < 0.05) shear force values than the control over the testing time. A possible relationship was suggested between a change in the phosphorylation of energy metabolic enzymes and the postmortem tenderization of beef. Our results suggested the possible importance of the activation of μ-calpain, phosphorylation of sarcoplasmic proteins, and release of lysosomal enzymes for ES-induced tenderization of beef muscle. [ABSTRACT FROM AUTHOR]

Summary Abnormal Ca2+-mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca2+ signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca2+ level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca2+ influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca2+ channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca2+-calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a fatal disease with great public health impact worldwide. Heme oxygenase (HO)-1 has recently been reported as an important player in tumor angiogenesis and metastasis. However, the role of HO-1 in liver cancer metastasis is unclear. In this study, we explored genetic differences and downstream signal transduction pathways of HO-1 in liver cancer cell lines. HO-1 wild-type and mutant cell lines were generated from human liver cancer cell line HepG2. The overexpression of wild-type HO-1 decreased the migration of HepG2 cells. In contrast, the overexpression of mutant HO-1G143H increased the migration of the cancer cells. Interleukin (IL)-6 is one of the major downstream molecules that mediated this process because IL-6 expression and migration are suppressed by HO-1 and increased when HO-1 is knocked down by shRNA. In addition, we demonstrated carbon monoxide (CO) and p38MAPK are the cofactors in this signal pathway. In vivo animal model demonstrated HO-1 inhibited the tumor growth. In conclusion, in vitro and in vivo data show HO-1 inhibits the human HCC cells migration and tumor growth by suppressing the expression of IL-6. The heme degradation product CO is a cofactor in this process and inhibits p38MAPK phosphorylation. [ABSTRACT FROM AUTHOR]

Cutaneous adverse drug reactions (CADRs) are common skin adverse reactions associated with drugs. To assess recent trends in CADRs and the drugs associated with them, using data from the past 5 years in the largest single database available on a hospital-based population in China. All clinical records of inpatients admitted with a diagnosis of CADR to the Dermatology Ward, Huashan Hospital from January 2004 to December 2008 were retrospectively studied. In the 734 patients, the three most common types of CADRs were nonsevere reactions, erythema multiforme (EM)-like eruptions ( n = 255), urticaria ( n = 192) and exanthematous reactions ( n = 159), followed by three severe reactions: Stevens-Johnson syndrome ( n = 58), toxic epidermal necrolysis ( n = 29) and exfoliative dermatitis ( n = 22). The most common single drug associated with the development of all drug eruptions was allopurinol, followed by amoxicillin, cephalosporins, antiepileptic agents and antipyretic/analgesic agents. However, the most common single drugs associated with severe reactions were antiepileptic agents, followed by allopurinol, antipyretic/analgesic agents and cephalosporins. In contrast to patients with nonsevere reactions, patients with severe reactions were more likely to be male ( P < 0.001) and to have a greater mean age of onset ( P < 0.001), a longer latency period ( P < 0.001) and a longer duration of hospitalization ( P < 0.001). In contrast to previous studies, we found allopurinol to be the most common single drug associated with CADRs followed by antibiotics (amoxicillin and cephalosporins), and antiepileptic, especially carbamazepine. A higher incidence of EM-like eruptions and urticaria was also seen. [ABSTRACT FROM AUTHOR]

To improve the yield and productivity of docosahexaenoic acid (DHA) by Schizochytrium sp. in terms of the analysis of microbial physiology. A two-stage oxygen supply control strategy, aimed at achieving high concentration and high productivity of DHA, was proposed. At the first 40 h, Ka was controlled at 150·1 h to obtain high μ for cell growth, subsequently Ka was controlled at 88·5 h to maintain high q for high DHA accumulation. Finally, the maximum lipid, DHA content and DHA productivity reached 46·6, 17·7 g l and 111 mg l h, which were 43·83%, 63·88% and 32·14% over the best results controlled by constant Ka. This paper described a two-stage oxygen supply control strategy based on the kinetic analysis for efficient DHA fermentation by Schizochytrium sp. This study showed the advantage of two-stage control strategy in terms of microbial physiology. As Ka is a scaling-up parameter, the idea developed in this paper could be scaled-up to industrial process and applied to other industrial biotechnological processes to achieve both high product concentration and high productivity. [ABSTRACT FROM AUTHOR]

Aims: To examine the potential use of hemicellulose hydrolysate (HH) for the production of chitosan by Rhizopus oryzae and investigate the influence of contents in HH on mycelia growth and chitosan synthesis. Methods and Results: Compared to xylose medium, HH enhanced mycelia growth, chitosan content and production of R. oryzae by 10·2, 64·5 and 82·1%, respectively. During sulfuric acid hydrolysis of corn straw, sugars (glucose, galactose, etc) and inhibitors (formic acid, acetic acid and furfural) were generated. Acetic acid (2·14 g l−1) and formic acid (0·83 g l−1) were stimulative, while furfural (0·55 g l−1) was inhibitory. Inhibitors, at different concentrations, increased the mycelia growth and chitosan production by 24·5–37·8 and 60·1–207·1%. Conclusions: HH of corn straw is a good source for chitosan production. Inhibitors in HH, at proper concentrations, can enhance chitosan production greatly. Significance and Impact of the Study: This work for the first time reported chitosan production from HH. Chitosan production can be greatly enhanced by cheap chemicals such as inhibitors in HH. [ABSTRACT FROM AUTHOR]

Background: A putative tumor suppressor gene at chromosome 10p15, which contains KLF6 and other genes, is predicted to be lost during melanoma development, and its identity is unknown. In this study, we investigated the biological roles and identity of this tumor suppressor gene. [ABSTRACT FROM PUBLISHER]

Aims: To increase the fruit body production of Cordyceps guangdongensis, selected cultivation conditions, especially nutritional parameters were optimized. Methods and Results: Cordyceps guangdongensis was inoculated on potato dextrose agar slants with pH values from 4·5 to 9·0 and cultivated in artificial media with different carbon and nitrogen supplements. Primordium formation in C. guangdongensis was favoured by slightly acidic conditions. Fruit body yields and biological efficiency (BE) recorded were all highest in cultures of C. guangdongensis supplemented with sucrose and KNO3 as carbon and nitrogen supplements, respectively. Highest fruit body yields and BE values were recorded with C : N ratio of 12 : 1. The optimal medium consisted of (g l−1) 20·0 sucrose, 4·0 soya bean powder, 5·0 beef extract and 10·0 KNO3. Cultivation experiments using this medium confirmed its reliability; 18·35% of BE was obtained, compared with a calculated maximum BE of 18·65% based on orthogonal test data. Conclusions: Cordyceps guangdongensis preferred sucrose and potassium nitrate as best carbon and nitrogen supplements. It produced satisfying yield of fruit body with optimized medium. Significance and Impact of the Study: Optimized artificial cultivation conditions could promote the yield of C. guangdongensis and decreased the cost of production. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the degree of radiation-induced trismus after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From 2003 to 2004, 17 non-metastatic NPC patients treated with parotid-sparing IMRT were enrolled. The maximal interincisal distance (MID) was measured to represent the maximum mouth opening. All 17 patients had both pre- and post-IMRT measurements taken, and the normalized MID (post-IMRT MID/pre-IMRT MID) was analysed to evaluate the percentage decrease in MID after IMRT. The median follow-up time was 20.5 months. One patient had nodal failure and was successfully salvaged with radiotherapy. All 17 patients were alive without cancer at the last followup. The average MID before IMRT was 46.2 mm (standard deviation (SD), 8.6 mm). The average MID at 12 months post-IMRT was 45.4 mm (SD, 8.9 mm). The averages of normalized MID were 94% (SD, 3.9%) at 5 months post-IMRT and 98.1% (SD, 4.2%) at 12 months post-IMRT. Based on the satisfactory preservation of normalized MID (average of 98.1% at 12 months post-IMRT), we demonstrate that IMRT reduces radiation-induced trismus in NPC patients. The recovery of normalized MID exists in the period from 5-12 months post-IMRT. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) can induce both tolergenic as well as effective immune responses in the lung. Pulmonary DCs producing interleukin (IL)-10 mediated tolerance induced by respiratory exposure to antigen. IL-10 is an important immunosuppressive cytokine, which inhibits maturation and function of DC. To assess whether IL-10 producing DCs can exert the tolergenic effect through the differentiation of regulatory T cells, bone marrow derived DCs were genetically modified by IL-10 expressing adenovirus. IL-10 gene modified DCs (Ad-IL-10-DC) displayed a characteristic phenotype of immature DCs. Here we showed that in vitro repetitive stimulation of naïve DO11·10 CD4+ T cells with Ad-IL-10-DCs resulted in a development of IL-10 producing T-cell regulatory cells. These T cells could not proliferate well but also lost their ability to produce interferon-γ upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naïve CD4+ T cells in a dose-dependent manner. Our findings demonstrated that IL-10 producing DCs had the potential to induce the differentiation of Tr1-like cells and suggested their therapeutic use. [ABSTRACT FROM AUTHOR]

The Chaoshan littoral is located in a high-incidence area of esophageal cancer in the south of China. In this study, a new esophageal cancer cell line CSEC was established from a 47-year-old female Chinese patient in this district. The biological characters of the cultured cells were investigated, including morphology, ultrastructure, growth kinetic features, tumorigenicity, expression of tumor-associated antigen and cytogenetic features. CSEC cell line grew continuously with a doubling time of 39.5 h and had been passaged over 80 times. The CSEC cells possessed features of squamous epithelial cells with cytokeratin indicated by immunohistochemical staining and tonofilaments and desmosomes revealed by electron microscopy. Tumorigenicity to severe combined immunodeficient mice was confirmed and the tumors developed revealed well-differentiated squamous cell carcinoma, similar to the origin tumor from which the cell line derived. The cytogenetic analysis demonstrated hypertetraploid karyotypes. Chromosome structure aberrations were common and complicated. Immunohistochemical staining showed that CSEC cells were infected with HPV and over-expressed p53. In summary, the CSEC cell line is a well-differentiated esophageal squamous cell carcinoma cell line from a high-incidence area in southern China. It may provide a useful model for the pathogenesis and therapeutic research of esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, such as glutamic acid decarboxylase 65 (GAD65), for which islet transplantation is a promising therapy. Therefore, the generation of tolerance aiming at both alloantigen and GAD65 will help therapeutic intervention greatly in T1D. In this study, we tested the effect of programmed death-1 ligands (PD-L1)-transfected dendritic cells (DC) loaded with GAD65 on the alloresponse and GAD65-reactive lymphocyte response. The DC2·4 cell line was transfected with PD-L1 and co-cultured with GAD65. BALB-c mice were primed, respectively, by intraperitoneal injection with GAD65, PD-L1-transfected- or non-transfected DC (PD-L1/DC or DC), and PD-L1-transfected- or non-transfected DC loaded with GAD65 (PD-L1/DC/GAD65 or DC/GAD65). Splenocytes of treated mice were isolated and restimulated in vitro with GAD65 or the various DC populations above being used as stimulators, respectively. In the mixed lymphocyte reaction, DC/GAD65 were able to stimulate both allogeneic and GAD65-reactive lymphocytes. However, PD-L1/DC/GAD65 were poorer than DC/GAD65 at activating the GAD65-reactive lymphocyte response. Further, although PD-L1/DC could inhibit the alloresponse, PD-L1/DC/GAD65 were more effective at down-regulating the GAD65-reactive lymphocyte response. More importantly, PD-L1/DC/GAD65-primed lymphocytes exhibited the weakest proliferation when again restimulated in vitro by PD-L1/DC/GAD65. Additionally, PD-L1/DC/GAD65 down-regulated interferon-γ and up-regulated interleukin-10 production by activated lymphocytes. Therefore, combined stimulation in vivo and in vitro by PD-L1/DC/GAD65 could inhibit both the alloresponse and the GAD65-reactive lymphocyte response, which may contribute to controlling diabetes and islet transplant rejection. [ABSTRACT FROM AUTHOR]

The approval of collagenase clostridium histolyticum (collagenase) in 2014 provided a novel nonsurgical option for the treatment of Peyronie's disease (PD), which significantly changed the overall treatment paradigm for PD. A longitudinal analysis was performed of patients newly diagnosed with PD undergoing first-time treatment with collagenase, penile surgery, or other treatment from January 1, 2011 through December 31, 2017. Trends demonstrated stable annual rates of new PD diagnoses and associated surgical procedures following collagenase approval, while collagenase use increased notably over the same time period. [Extracted from the article]

The lethal and sublethal effects of tebufenozide on the survival, development, and reproduction of a field strain of tufted apple bud moth, Platynota idaeusalis (Walker) (Lepidoptera: Tortricidae), were assessed by feeding first and third instars tebufenozide-treated diet until pupation. Larval mortality was 27.4 and 44.7% at 0.1 and 0.2 ppm for first instars and 21.9 and 57.8% at 0.2 and 0.4 ppm for third instars, respectively. Treated larvae exhibited higher pupal mortalities, lower pupal weights, and generally more deformed adults than untreated larvae. Larval development was not affected by tebufenozide when neonates were exposed, but development was accelerated slightly at 0.4 ppm for both males and females when third instars were exposed. All treatments produced sex ratios biased toward males. When paired with either treated or untreated males, females resulting from neonates treated at 0.2 ppm and from third instars treated at both 0.2 and 0.4 ppm laid from 37 to 65% fewer eggs. A reduction in fertility was only found when third instars were treated at the higher 0.4 ppm rate. These results suggest that tebufenozide can exhibit a significant effect on the population dynamics of the tufted apple bud moth. [ABSTRACT FROM AUTHOR]

The conformational change and associated aggregation of β amyloid (Aβ) with or without metals is the main cause of Alzheimers' disease (AD). In order to further understand the effects of Aβ and its associated metals on the aggregation mechanism, the influence of Aβ conformation on the metal affinity and aggregation was investigated using circular dichroism (CD) spectroscopy. The Aβ conformation is dependent on pH and trifluoroethanol (TFE). The binding of metals to Aβ was found to be dependent on the Aβ conformation. The aggregation induced by Aβ itself or its associated metals is completely diminished for Aβ in 40% TFE. Only in 5% and 25% TFE can Aβ undergo an α-helix to β-sheet aggregation, which involve a three-state mechanism for the metal-free state, and a two-state transition for the metal-bound state, respectively. The aggregation-inducing activity of metals is in the order, Cu2+ > Fe3+ ≥ Al3+ > Zn2+. [ABSTRACT FROM PUBLISHER]

Objectives: To compare the cephalometric landmark identification on softcopy and hardcopy of direct digital cephalography acquired by a storage-phosphor (SP) imaging system. Methods: Ten digital cephalograms and their conventional counterpart, hardcopy on a transparent blue film, were obtained by a SP imaging system and a dye sublimation printer. Twelve orthodontic residents identified 19 cephalometric landmarks on monitor-displayed SP digital images with computer-aided method and on their hardcopies with conventional method. The x- and y-coordinates for each landmark, indicating the horizontal and vertical positions, were analysed to assess the reliability of landmark identification and evaluate the concordance of the landmark locations in softcopy and hardcopy of SP digital cephalometric radiography. Results: For each of the 19 landmarks, the location differences as well as the horizontal and vertical components were statistically significant between SP digital cephalometric radiography and its hardcopy. Smaller interobserver errors on SP digital images than those on their hardcopies were noted for all the landmarks, except point Go in vertical direction. The scatter-plots demonstrate the characteristic distribution of the interobserver error in both horizontal and vertical directions. Generally, the dispersion of interobserver error on SP digital cephalometric radiography is less than that on its hardcopy with conventional method. Conclusions: The SP digital cephalometric radiography could yield better or comparable level of performance in landmark identification as its hardcopy, except point Go in vertical direction. [ABSTRACT FROM AUTHOR]

SUMMARY Myeloid (CD11c+ ) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-α MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14+ macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro . In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-γ, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-γ on moDC. moDC cultured with MS CSF induced a higher production of IFN-γ from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses. [ABSTRACT FROM AUTHOR]

Summary Sclerosing perineurioma is a rare, recently described variant of perineurioma that tends to affect the fingers and palms of adolescents or young adults. The process typically presents as a painless, well-circumscribed, unencapsulated nodule involving subcutis or reticular dermis. To our knowledge, all of the previously reported sclerosing perineuriomas were solitary. Hence, we report a 16-year-old boy, without stigmata of neurofibromatosis, who developed one sclerosing perineurioma in the right palm and another on the left index finger. Microscopically, tumours at both sites revealed small epithelioid and plump spindle cells with trabecular, whorled, or Indian file growth pattern enmeshed within extensively hyalinizing stroma. Immunohistochemically, the tumour cells showed strong reactivity for EMA but negative staining for S-100 and neurofilament. Ultrastructually, the tumour cells in both lesions exhibited features of perineurial cells, including discontinuous external basal lamina, occasional pinocytotic vesicles, and encirclement of abundant collagen fibrils by the interdigitating cytoplasmic processes. This case confirms the fact that sclerosing perineurioma is not always solitary. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most prevalent cancer in males in the United States. Standard therapy relies on removing, or blocking the actions of, androgens. In most cases, this therapy results in a regression of the cancer because the prostate and most primary prostate tumors depend on androgens for growth and the avoidance of apoptosis. However, a portion of the cancers eventually relapse, at which point they are termed "androgen refractory" and can no longer be cured by conventional therapy of any type. The precise molecular events that lead from androgen-sensitive prostate cancer to androgen-refractory prostate cancer are, therefore, of great interest. This review seeks to identify specific molecular events that may be linked directly to the progression to androgen-refractory cancer. Some of the mechanisms appear to involve the androgen receptor (AR) directly and include mutations in, or amplification of, the AR gene in a manner that allows the AR to respond to low doses of androgens, other steroids, or antiandrogens. In a less direct manner, coactivators may increase the sensitivity of the AR to androgens and even other nonandrogenic substances through a number of mechanisms. Additional indirect mechanisms that do not result from mutation of the AR may involve activation of the AR by peptide growth factors or cytokines or may involve bypassing the AR entirely via other cellular pathways. Identification of the role of these mechanisms in the progression to androgen-refractory prostate cancer is critical for developing therapies capable of curing this disease. [ABSTRACT FROM AUTHOR]