Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating periostin levels in patients with AS: association with clinical and radiographic variables, inflammatory markers and molecules involved in bone formation.

OBJECTIVE The aim of this study was to evaluate serum periostin levels in patients with AS in comparison with healthy controls as well as their association with clinical, inflammatory and radiographic parameters and molecules involved in bone formation. METHODS Serum samples for periostin, total Dickkopf-1 (Dkk-1), sclerostin, VEGF and inflammatory markers were obtained from 65 TNF inhibitor-naive patients with AS. The BASDAI, BASFI, modified Stoke AS Spine Score and BASRI for the spine (BASRI-s) were assessed for each patient. Serum periostin levels were also measured in 36 sex-, age- and BMI-matched controls. RESULTS Serum periostin levels were significantly lower in AS patients compared with controls [234.4 pg/ml (s.e.m. 7.5) vs 291.4 (s.e.m. 8.3), respectively; P < 0.001]. Periostin levels were higher in AS patients with elevated CRP (P = 0.005), high BASDAI (P = 0.014) and low BASRI-s (P = 0.033) and were correlated with BMI (r = -0.304, P = 0.014), ESR (r = 0.395, P = 0.001), CRP (r = 0.413, P = 0.001), BASRI-s (r = -0.242, P = 0.047) and sclerostin (r = -0.280, P = 0.024). In multiple regression analysis, periostin levels were an independent variable of CRP (β = 0.160, P = 0.009) and sclerostin levels (β = -0.311, P = 0.012). CONCLUSION Our data suggest that periostin levels are low in patients with AS. Among AS patients, periostin levels are higher in those with higher disease activity, higher systemic inflammation and less extensive radiographic damage. Periostin is independently associated with CRP and sclerostin levels.
Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis.

OBJECTIVE Histone deacetylase 1 (HDAC1) is highly expressed in the synovium of RA patients. Thus we aimed to investigate a novel HDAC inhibitor (HDACi), NW-21, designed to target HDAC1. The effect of NW-21 on osteoclast formation and activity, cytokine and chemokine expression in vitro and arthritis in mice was assessed. METHODS The effects on human osteoclast formation and activity derived from human blood monocytes stimulated with receptor activator of nuclear factor κB ligand (RANKL) and M-CSF were assessed. The anti-inflammatory activity of NW-21 was assessed using human monocytes stimulated with either TNF-α or lipopolysaccharide for 24 h. mRNA expression of monocyte chemotactic protein 1 (MCP-1), TNF-α, macrophage inflammatory protein 1α (MIP-1α), IL-1 and RANTES (regulated on activation, normal T cell expressed and secreted) was assessed. The effect of NW-21 in the collagen antibody-induced arthritis model was assessed following daily oral administration at 5 mg/kg/day. The HDAC1 inhibitors NW-21 and MS-275 were compared with a broad-acting HDACi, 1179.4b. Effects on inflammation and bone were assessed using paw inflammation scoring, histology and live animal micro-CT. RESULTS NW-21 suppressed osteoclast formation and activity as well as significantly reducing mRNA expression of MCP-1 and MIP-1α in monocytes stimulated by lipopolysaccharide or TNF-α (P < 0.05) in vitro. Only inhibitors that targeted HDAC1 (NW-21 and MS-275) reduced inflammation and bone loss in the arthritis model. CONCLUSION The results indicate that inhibitors targeting HDAC1, such as NW-21 and MS-275, may be useful for treating RA, as such drugs can simultaneously target both inflammation and bone resorption.
Sleep disturbances and neurotoxicity in workers exposed to hydrocarbons. An observational study from Algeria.

BACKGROUND Occupational exposure to solvents may lead to neurotoxicity and sleep disturbances. We aimed to investigate the association of occupational exposure to petroleum-derived hydrocarbons with neurotoxicity and sleep disturbance symptoms. METHODS We included male workers handling/distributing petroleum products (exposed, n = 250) and electricians (non-exposed, n = 250) from two companies in Tlemcen (Algeria). Neurotoxicity was evaluated with the Q-16 questionnaire, and sleep disturbances with the Epworth and the Berlin questionnaires. Multivariable Poisson regression models with robust error variances were applied obtaining risk ratios (RR) and their 95% confidence interval (CI). RESULTS Overall, the prevalence of reported neurotoxicity and sleep disturbance symptoms was higher in exposed than in non-exposed workers. Significant adjusted associations were observed for neurotoxicity, snoring, and excessive sleepiness (RR = 2.2, CI: 1.7-2.8; RR = 1.4; CI: 1.1-1.7; RR = 1.3, CI: 1.2-1.5, respectively). No significant associations were observed with the Epworth score. CONCLUSIONS Our questionnaire-based cross-sectional study suggests that exposure to petroleum-derived hydrocarbons is associated with self-reported sleep disturbances and neurotoxicity symptoms.
Effects of TNF-α and IFN-γ on Nitric Oxide-Induced Neurotoxicity in the Mouse Brain1

The present study investigated the interaction between highly reactive gaseous-free radical NO and cytokines that are produced by activated Th-1 cells on the cerebral immune response and neuronal integrity. CD-1 mice received an intrastriatal infusion of different solutions containing the NO synthase inhibitor N(G)-nitro-l-arginine methylester, NO-releasing substance sodium nitroprusside (SNP), IFN-γ, and/or TNF-α. The solution containing both cytokines caused a profound and transient transcriptional activation of numerous genes encoding proinflammatory proteins in microglial/monocytic cells ipsilateral to infusion site. This increase in gene expression peaked 1 day after the cerebral bolus of cytokines and returned to basal levels from 3 to 7 days post administration. N(G)-nitro-l-arginine methylester further stimulated this immune reaction to IFN-γ and TNF-α, but the brain of these mice failed to exhibit signs of neurodegeneration and demyelination. In contrast, a single bolus of SNP in the striatal region caused neuronal death and demyelination as early as 1 to 3 days following the infusion with the NO donor. This phenomenon was greatly exacerbated by the coadministration of both cytokines, although TNF-α remained the most critical cytokine to enhance the damage of cerebral elements. These data provide evidence that NO has the ability to modulate the immune response, which is not by itself detrimental for the brain. However, SNP-induced NO production together with TNF-α in the cerebral environment are critical events leading to intense neurodegeneration and demyelination in vivo.
Comparison of transgene expression in Aedes aegypti generated by mariner Mos1 transposition and ΦC31 site‐directed recombination

Transgenic mosquitoes generated by transposable elements (TEs) often poorly express transgenes owing to position effects. To avoid these effects, the ΦC31 site‐directed recombination system was used to insert transgenes into a locus favourable for gene expression in Aedes aegypti. We describe phenotypes of mariner Mos1 TE and ΦC31 transgenic mosquitoes expressing the enhanced green fluorescent protein (EGFP) reporter in midguts of blood‐fed females. Mosquitoes of nine TE‐generated lines [estimated transformation frequency (TF): 9.3%] clearly expressed the eye‐specific selection marker but only 2/9 lines robustly expressed the EGFP reporter. The piggyBac TE‐generated ΦC31 docking strain, attP26, supported recombination with attB site containing donors at an estimated TF of 1.7–4.9%. Using a codon‐optimized ΦC31 integrase mutant instead of the ‘wild‐type’ enzyme did not affect TF. Site‐directed recombination of line attP26 with an attB‐containing donor expressing EGFP from the Ae. aegypti carboxypeptidase promoter produced one transgenic line with blood‐fed females expressing the reporter in midgut tissue. Docking strain attP26 also supported robust expression of Flock House virus B2 from the Ae. aegypti polyubiquitin promoter. Our data confirm that eye‐specific selection marker expression alone is not a reliable indicator for robust gene‐of‐interest expression in Ae. aegypti and that the ΦC31 system can ensure predictable transgene expression in this mosquito species.
Cold tolerance and cold‐induced modulation of gene expression in two Drosophila virilis group species with different distributions

The importance of high and low temperature tolerance in adaptation to changing environmental conditions has evoked new interest in modulations in gene expression and metabolism linked with stress tolerance. We investigated the effects of rapid cold hardening and cold acclimatization on the chill coma recovery times of two Drosophila virilis group species, Drosophila montana and D. virilis, with different distributions and utilized a candidate gene approach to trace changes in their gene expression during and after the cold treatments. The study showed that cold acclimatization clearly decreases chill coma recovery times in both species, whereas rapid cold hardening did not have a significant effect. Microarray analysis revealed several genes showing expression changes during different stages of cold response. Amongst the 219 genes studied, two genes showed rather consistent expression changes: hsr‐omega, which was up‐regulated in both study species during cold acclimatization, and Eip71CD, which was down‐regulated in nearly all of the cold treatments. In addition, 29 genes showed expression changes that were more treatment‐ and/or species specific. Overall, different stages of cold response elicited changes mainly in genes involved in heat shock response, circadian rhythm and metabolism.
DNA methylation plays a crucial role during early Nasonia development

Although the role of DNA methylation in insect development is still poorly understood, the number and role of DNA methyltransferases in insects vary strongly between species. DNA methylation appears to be widely present among the social hymenoptera and functional studies in Apis have suggested a crucial role for de novo methylation in a wide variety of developmental processes. The sequencing of three parasitoid Nasonia genomes revealed the presence of three Dnmt1 (Dnmt1a, Dnmt1b and Dnmt1c) genes and one Dnmt2 and Dnmt3 gene, suggesting a role of DNA methylation in Nasonia development. In the present study we show that in Nasonia vitripennis all Dnmt1 messenger RNAs (mRNAs) and Dnmt3 mRNA are maternally provided to the embryo and, of these, Dnmt1a is essential during early embryogenesis. Lowering of maternal Dnmt1a mRNA results in embryonic lethality during the onset of gastrulation. This dependence on maternal Dnmt1a during embryogenesis in an organismal group outside the vertebrates, suggests evolutionary conservation of the function of Dnmt1 during embryogenesis.
Neonatal complications of premature rupture of membranes.

Premature rupture of membranes (PROM) is one of the most common complications of pregnancy that has a major impact on neonatal outcomes. With respect to racial, nutritional and cultural differences between developed and developing countries, this study was conducted to detect the prevalence of neonatal complications following PROM and the role of the duration of rupture of membranes in producing morbidities and mortalities in these neonates in our hospital. Among 2357 pregnant women, we found 163 (6.91%) cases of premature rupture of the fetal membranes in Tehran Vali-e-Asr Hospital during April 2001 to April 2002. Route of delivery was cesarean section in 65.6% of women. Urinary tract infection occured in 1.8%, maternal leukocytosis and fever in 20.2% and 5.5%, chorioamnionitis in 6.1%, fetal tachycardia in 1.2% and olygohydramnios in 4.9%. Gestational age in 138 (86%) of neonates was less than 37 completed weeks. Thirty five infants (21.47%) had respiratory distress syndrome and 33 (20.245%) had clinical sepsis. Pneumonia in 6 (3.7%) and skeletal deformity in 7 (4.294%) were seen. Rupture of membrane of more than 24 hours duration occurred in 71 (43.6%) of the patients. Comparison of morbidities between two groups of neonates and their mothers according to the duration of PROM (less and more than 24 hours ) showed significant differences in NICU admission, olygohydramnios, maternal fever, leukocytosis and chorioamnionitis rates (p 24 hr of PROM with an odds ratio of 2.68 and 2.73, respectively. Positive blood and eye cultures were detected in 16 cases during 72 hours of age. Staphylococcus species, klebsiella, E.coli and streptococcus were the predominant organisms among positive blood cultures. Mortality was seen in 18 (11%) of neonates because of respiratory failure, disseminated intravascular coagulation, septic shock, and a single case of congenital toxoplasmosis. In this study, the prevalence of prematurity, sepsis and prolonged rupture of membrane were higher than previous studies.
Tn Glycosylation of the MUC6 Protein Modulates Its Immunogenicity and Promotes the Induction of Th17-biased T Cell Responses*

The Tn antigen (α-GalNAc-O-Ser/Thr) is one of the most specific human cancer-associated structures. This antigen, together with mucins, the major carriers of O-glycosylated tumor antigens in adenocarcinomas, are being evaluated as anti-cancer immunotherapeutic targets. In particular, the MUC6 protein, which is normally expressed only in gastric tissues, has been detected in intestinal, pulmonary, colorectal, and breast carcinomas. To develop anti-cancer vaccines based on the Tn antigen, we produced MUC6 proteins with different Tn density by using mixtures of recombinant ppGalNAc-T1, -T2, and -T7. The obtained glycoproteins were characterized and analyzed for their immunological properties, as compared with the non-glycosylated MUC6. We show that these various MUC6:Tn glycoproteins were well recognized by both MUC6 and Tn-specific antibodies. However, Tn glycosylation of the MUC6 protein strongly affected their immunogenicity by partially abrogating Th1 cell responses, and promoting IL-17 responses. Moreover, the non-glycosylated MUC6 was more efficiently presented than MUC6:Tn glycoproteins to specific T CD4+ hybridomas, suggesting that Tn glycosylation may affect MUC6 processing or MHC binding of the processed peptides. In conclusion, our results indicate that Tn glycosylation of the MUC6 protein strongly affects its B and T cell immunogenicity, and might favor immune escape of tumor cells.
Residual bacteria in root apices removed by a diagonal root-end resection: a histopathological evaluation.

AIM To assess bacteria in the apical portion of the root end after 45 degrees root-end resection in teeth with persistent periapical lesions. METHODOLOGY The study included 27 apical root segments from patients with persistent periapical lesions. Histological sections of the coronal part of the amputated root segment were stained with Brown and Brenn to detect the presence of bacteria in the main root canal and/or in irregular root spaces and dentinal tubules. The quality of each root canal filling was evaluated using preoperative radiographs of filling, length of root filling as assessed from the distance between its apical end and the radiographic apex, diameter of apical preparation, and presence of apical perforations or deviations from the root canal. Two endodontists, blinded to the bacteriological results, independently evaluated the radiographs. RESULTS Bacteria were present in 23 (85.2%) specimens: five in only the main canal (21.7%), 10 in only the dentinal tubules and irregular spaces (43.5%), and eight in both irregular spaces and dentinal tubules and in the main root canal (34.8%). No correlation was found between the technical quality of the root filling assessed radiographically and bacterial presence in the central canal or irregular areas. CONCLUSIONS Infected irregular areas were found in the root tips of teeth with persistent periapical lesions. This was found regardless of the radiographic quality of the root filling. Diagonal, 45 degrees root-end resection may expose such contaminated irregularities to the periapical tissue.
Effects of Inflammatory Factors on Mesenchymal Stem Cells and Their Role in the Promotion of Tumor Angiogenesis in Colon Cancer*

Mesenchymal stem cells (MSCs), which are modulated by cytokines present in the tumor microenvironment, play an important role in tumor progression. It is well documented that inflammation is an important part of the tumor microenvironment, so we investigated whether stimulation of MSCs by inflammatory cytokines would contribute to their ability to promote tumor growth. We first showed that MSCs could increase C26 colon cancer growth in mice. This growth-promoting effect was further accelerated when the MSCs were pre-stimulated by inflammatory factors IFN-γ and TNF-α. At the same time, we demonstrated that MSCs pre-stimulated by both inflammatory factors could promote tumor angiogenesis in vivo to a greater degree than untreated MSCs or MSCs pre-stimulated by either IFN-γ or TNF-α alone. A hen egg test-chorioallantoic membrane (HET-CAM) assay showed that treatment of MSC-conditioned medium can promote chorioallantoic membrane angiogenesis in vitro, especially treatment with conditioned medium of MSCs pretreated with IFN-γ and TNF-α together. This mechanism of promoting angiogenesis appears to take place via an increase in the expression of vascular endothelial growth factor (VEGF), which itself takes place through an increase in signaling in the hypoxia-inducible factor 1α (HIF-1α)-dependent pathway. Inhibition of HIF-1α in MSCs by siRNA was found to effectively reduce the ability of MSC to affect the growth of colon cancer in vivo in the inflammatory microenviroment. These results indicate that MSCs stimulated by inflammatory cytokines such as IFN-γ and TNF-α in the tumor microenvironment express higher levels of VEGF via the HIF-1α signaling pathway and that these MSCs then enhance tumor angiogenesis, finally leading to colon cancer growth in mice.
Fracture resistance of structurally compromised root filled bovine teeth restored with accessory glass fibre posts.

AIM To evaluate the mechanical behaviour of structurally compromised root filled bovine roots after restoration with accessory glass fibre posts. METHODOLOGY Fifty roots of bovine teeth received conventional post preparations with a cervical diameter of 3.5 mm. The roots were assigned to five groups (n = 10): group MP - cast metal post, group GP - glass fibre post and group AGP - glass fibre post plus accessory glass fibre posts. In groups GP-R and AGP-R (similar to groups GP and AGP), 2 mm of coronal tooth structure were left intact. All groups were subjected to an elastic limit assay and tested in an universal machine for fracture resistance. Repeated measures anova were performed to examine differences in fracture resistance; fracture modes were analysed by Fischer's exact test. RESULTS The mean fracture resistance values (kgf) were 61.8 (MP), 63.1 (GP), 55.5 (AGP), 56 (GP-R) and (53.1) AGP-R. No statistically significant difference was found between groups. The Fisher's exact test indicated significant differences (P < 0.05) in the fracture mode amongst groups MP, GP and AGP, indicating 100%, 50% and 10% of catastrophic fractures, respectively. CONCLUSIONS The use of accessory glass fibre posts affected the fracture mode favorably: 90% of fractures in group AGP were in the coronal third.
Phosphatidylinositol-3-kinase inhibitor LY 294002 blocks Streptococcus mutans-induced interleukin (IL)-6 and IL-8 gene expression in odontoblast-like cells.

AIM To investigate the involvement of the phosphatidylinositol-3-kinase (PI3K) in interleukin-6 (IL-6) and interleukin-8 (IL-8) gene expression in odontoblast-like cells when exposed to heat-killed Streptococcus mutans. METHODOLOGY Cultured human odontoblast-like cells (Dulbecco's modified Eagle's medium) were pre-treated with a specific inhibitor for PI3K (LY 294002) and subsequently stimulated with heat-killed S. mutans for 6 and 24 h. After stimulation, RNA was extracted from the cells and cDNA synthesis was performed. Gene expression of IL-6 and IL-8 was analysed by real-time polymerase chain reaction and normalized to the gene expression of beta-actin. Cell survival was determined for stimulation experiments. RESULTS The gene expression of IL-6 and IL-8 was significantly increased in response to heat-killed S. mutans (P = 0.002 and P < 0.001, respectively). After 6 h, the mRNA expression of IL-6 and IL-8 was significantly higher than after 24 h of stimulation (P = 0.019 and P < 0.001, respectively). Pre-treatment with the inhibitor LY 294002 blocked the induced gene expression of IL-6 and IL-8 (P = 0.002 and P < 0.001, respectively). No differences in viable cell counts were found after stimulation with heat-killed S. mutans and/or pre-treatment with LY 294002 compared with the unstimulated control. CONCLUSION Gene expression of IL-6 and IL-8 was induced by heat-killed S. mutans via signalling pathways mediated by PI3K. These findings indicate that odontoblasts respond to cariogenic bacteria with increased gene expression of pro-inflammatory mediators and hence participate in immune processes.
Chronic contagious ovine digital dermatitis-like lesions in a Scottish flock

apparently new, severe condition (Figs. 1-7) first described in 1997. While CODD is reported to present a different clinical picture from virulent footrot (Fig. 8) and white line lesions (Fig. 9) there are few convincing published images. The isolation of spirochaetes resembling those involved in digital dermatitis in cattle from some, but not all, suspected clinical cases in sheep has led to the adoption of the current name. However, the isolation of the same spirochaetes from apparently normal feet, and the occurrence of mixed infections of ovine foot lesions with the causal agents of virulent foot-rot, provide ample opportunity for confusion. This report describes severe lameness of several months’ duration in a group of ten Cheviot ewes in poor body condition presenting with CODD-like lesions.
Ex vivo evaluation of dye penetration associated with various dentine bonding agents in conjunction with different irrigation solutions used within the pulp chamber.

AIM To compare the effect of sodium hypochlorite (NaOCl), chlorhexidine, povidone iodine and sodium ascorbate on dye penetration associated with various dentine adhesives used within the pulp chamber. METHODOLOGY One hundred and sixteen mandibular molar teeth were divided into eight groups of 12 teeth each by irrigation regimen and adhesive system. The roof of pulp chambers and roots were removed under water cooling. The pulp chambers in the experimental groups were irrigated with 5.25% NaOCl, 0.2% chlorhexidine, 5% w/v povidone iodine or 5.25% NaOCl followed by sodium ascorbate and restored with Surefil using either Prime & Bond NT or Xeno III with each irrigation regimen. Twenty teeth were used as control specimens in which no disinfectant was used before bonding. Ten teeth from each group were immersed in 2% methylene blue dye and assessed for dye penetration. The data were statistically analysed by Kruskal-Wallis and Mann-Whitney U-tests. Two samples in each group were observed under scanning electron microscopy for interfacial gap evaluation. RESULTS No significant difference was found in dye leakage between control and groups with 5.25% NaOCl pretreatment with both adhesive systems. Chlorhexidine and povidone iodine pretreatment resulted in significantly less dye penetration with Xeno III as compared with Prime & Bond NT. Sodium ascorbate treatment following NaOCl application significantly reduced microleakage and improved the marginal adaptation with both adhesive systems. CONCLUSIONS The type of irrigant affected the sealing ability of bonding agents inside the pulp chamber and was material specific. Xeno III had less dye penetration with CHX and povidone iodine whilst sodium ascorbate pretreatment after NaOCl reduced dye penetration with both PBNT and Xeno III.