Association between VDR polymorphisms and multiple sclerosis: systematic review and updated meta-analysis of case-control studies.

Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.

Demonstration of low energy proton radiography on an 11-MeV cyclotron.

Lens focused proton radiograph on thin objects is demonstrated using an 11-MeV proton cyclotron at China Academy of Engineering Physics. The proton beam exiting from the tested objects is focused onto the image plane by a magnetic lens system mitigating image blur caused by multiple Coulomb scattering. Both simulations and experiments show that clear images can be obtained with a lens system for the objects with thickness up to 2.7 × 10-2 g/cm2 and the error for the areal density measurement is measured to be less than 2.3%. For the objects with thickness between 2.7 × 10-3 g/cm2 and 2.7 × 10-2 g/cm2, 100-200 µm of spatial resolution is achieved.

The Influence of Different Solvents on Systemic Sclerosis: An Updated Meta-analysis of 14 Case-Control Studies.

BACKGROUND: Several studies have collected detailed data to examine which specific solvents account for the association between solvents and risk of systemic sclerosis (SSc). These studies generally reported elevated risks associated with many of the specific solvents examined, such as toluene, xylene, and trichloroethylene. The previous meta-analysis was not able to conduct separate analyses for specific solvent subtypes. OBJECTIVE: The aims of the new meta-analysis were to investigate a more comprehensive estimate and to consider the effect of different solvents on SSc. METHODS: We searched PubMed, Biosis Previews, China National Knowledge Infrastructure, and Wanfang for all articles published before July 2015. Fourteen case-control studies (1657 patients and 3838 controls) were included. The quality of studies was scored according to the Newcastle-Ottawa scale. The final odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed- or random-effects model according to heterogeneity test. Publication bias was assessed using Begg test. RESULTS: The risk of SSc was significantly different among sex, age, and exposure assessment methods. Separate analyses for specific solvent subtypes indicated that SSc was associated with aromatic solvents (OR, 2.72; 95% CI, 1.21-6.09), trichloroethylene (OR, 2.07; 95% CI, 1.34-3.17), halogenated solvents (OR, 1.49; 95% CI, 1.12-1.99), and ketones (OR, 4.20; 95% CI, 2.19-8.06). CONCLUSIONS: Exposure to identified types solvents does seem to be a risk factor for developing SSc. Needed efforts to decrease such exposures are discussed.

Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

High expression of Naa10p associates with lymph node metastasis and predicts favorable prognosis of oral squamous cell carcinoma.

N-a-Acetyltransferase 10 protein (Naa10p) is a potential prognostic biomarker and a modulator of several types of cancer. Despite the efforts to elucidate the relationship between Naa10p expression and clinical prognosis, little is known about its expression and role in human oral squamous cell carcinoma (OSCC). In this study, we firstly detected the mRNA and protein levels of Naa10p in 10 paired OSCC tissue samples and found Naa10p was frequently overexpressed in the tumor tissues of patients with OSCC. Further detection by immunohistochemistry was used to examine Naa10p expression in 124 OSCC tumor specimens by tissue microarray (TMA), and a relative high level of Naa10p protein expression was found in 98 out of 124 cases (79.03 %). Additional analyses illustrated that Naa10p expression inversely correlated with clinical stage (p = 0.047), degree of lymph node status (p = 0.020), differentiation (p = 0.022), and recurrence (p = 0.016) of patients with OSCC. The survival analysis showed that patients with Naa10p-positive expression had a better prognosis for disease-free survival (DFS) or overall survival (OS) than those with Naa10p-negative expression (p = 0.003 for both). Furthermore, we assessed the effect of Naa10p knockdown on motility of oral cancer cells in vitro, and the results showed that Naa10p inhibit cell wound healing, migration, and invasion. In summary, our study illustrated that the expression of Naa10p had a potential value for predicting the progression of OSCC and prognosis of OSCC patients.

Erythropoietin attenuates Alzheimer-like memory impairments and pathological changes induced by amyloid ß42 in mice.

Amyloid beta (Aß) is a key molecule in the neurodegenerative progression of Alzheimer׳s disease (AD). It is critical to develop a treatment that can arrest the Aß-induced pathologic progression of AD. Erythropoietin (EPO) has various protective effects in the nervous system. However, the effect of EPO on Aß-induced Alzheimer-like cognitive deficits and pathological changes remains unclear. In the present study, we observed that the treatment of mice with EPO (1000 IU/kg) attenuated Aß42-induced cognitive deficits and tau hyperphosphorylation at multiple AD-related sites through the regulation of glycogen synthase kinase-3ß (GSK-3ß). We also observed that EPO attenuated the Aß42-induced mitochondrial dysfunction and apoptosis in brain. These results indicate a potential role for EPO in AD therapy.

Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis.

OBJECTIVE: The aim of this paper is to review the anti-inflammatory cytokines IL-4 and IL-13 and their receptor signals; we discuss new insight into their possible roles in systemic sclerosis (SSc) and their overlapping function in SSc. INTRODUCTION: SSc is a connective tissue disease characterized by fibrosis. The exact etiology of SSc is unknown, and no therapy has been proved effective in modifying its course. Recently the roles of IL-4 and IL-13 in the development of SSc have been extensively considered. The possible roles of IL-4 and IL-13, especially their overlapping function, in SSc are not well documented. METHODS: A literature survey was performed using a PubMed database search to gather complete information regarding IL-4 and IL-13 and their role in inflammation. RESULTS AND CONCLUSIONS: The participation of complex pathways of IL-4 and IL-13 in the process of inflammation and fibrosis action in SSc is still not very clear, and some pathogenesis of regulation found in vitro needs to be further proved. There is still more work which could be done to achieve useful developments with therapeutic benefit in SSc.

The association between vibration and vascular injury in rheumatic diseases: a review of the literature.

Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.

The epidemiology of alcohol consumption and multiple sclerosis: a review.

Alcohol consumption is accounted for a large proportion in patients with multiple sclerosis (MS) and may be a modifiable lifestyle factor that affects the risk of developing the disease. The epidemiological studies about the association between MS and alcohol consumption have got corresponding studies during the last decade. It has been suggested that alcohol consumption was associated with mood disorders, disability and even onset of MS, but a common theme is lacking. To make an understanding of the effect of alcohol consumption on MS, the related epidemiological evidence and potential mechanisms are reviewed.

Association of interleukin 1 family with systemic sclerosis.

Systemic sclerosis is a connective tissue disease characterized with fibrosis of skin and/or internal organs, and its specific pathological mechanism remains incompletely understood. IL-1 family, whose biological properties are typically pro-inflammatory and pro-fibrosis, has been associated with systemic sclerosis (SSc). Interleukin (IL)-1 family has 11 members, IL-1α, IL-1ß, IL-1Ra, IL-18, IL-33, IL-36α, IL-36ß, IL-36γ, IL-36Ra, IL-37, and IL-38. With the exception of IL-1Ra and IL-36Ra, each member has its own receptor signal. Abnormal expression of IL-1 and its potential role in the fibrosis process have been probed earliest, as well as its gene polymorphisms with SSc. IL-33 and IL-18 have also been discussed in the recent years, and IL-33 may contribute to the fibrosis of SSc, while IL-18 remains to be researched to confirm its role in fibrosis process. There is a lack of studies on the association of the other members of the IL-1 family, which might provide us the future study area; much more efforts need to be put on this matter.

Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases.

INTRODUCTION: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. AREAS COVERED: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. EXPERT OPINION: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.

The risk of cancer development in systemic sclerosis: a meta-analysis.

OBJECTIVES: Systemic sclerosis is a multi-system disorder of connective tissue characterized by Raynaud's phenomenon and fibrosis of various organs. The risk of development of cancer in systemic sclerosis (SSc) has been extensively investigated with inconclusive results. To shed some light on the controversy, we conducted a meta-analysis of all published articles linking SSc to the risk of cancer development. METHODS: Relevant electronic databases were searched for English-language studies characterizing the association of cancers in patients with SSc. Standardized incidence rate (SIR) with its 95% confidence interval (CI) of each study was combined using a fixed/random effect model. RESULTS: A total of seven papers including 7183 SSc patients were identified, of which 7 reported the SIR for lung cancer, 4 for non-Hodgkin's lymphoma (NHL) and 4 for hematopoietic cancer and 7 for breast cancer. Compared with the general population, the combined SIR was 3.14 (95% CI: 2.02-4.89), 2.68 (95% CI: 1.58-4.56), 2.57 (95% CI: 1.79-3.68) and 1.09 (95% CI: 0.86-1.38), respectively. Significant heterogeneity was observed in lung cancer group (Q=26.13, P<0.001, I(2)=77%). Potential publication bias was absent. CONCLUSIONS: This present meta-analysis demonstrated an increased risk of lung, non-Hodgkin's lymphoma and hematopoietic cancers among patients with SSc, but not for breast cancer. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

[The changes of ghrelin, growth hormone, growth hormone releasing hormone and their clinical significances in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the changes of plasma ghrelin, growth hormone (GH) and growth hormone releasing hormone (GHRH) and gastric ghrelin in patients with chronic obstructive pulmonary disease (COPD) and to explore their clinical significances. METHODS: Plasma ghrelin, GH, GHRH, TNFα, IL-6 and C reactive protein (CRP) were measured in 40 COPD patients and 20 controls with chronic bronchitis. Correlated factors of plasma ghrelin, TNFα, IL-6, CRP were analyzed. Body composition was assessed with bioelectrical impedance analysis. The expression of gastric ghrelin in patients with COPD was detected. RESULTS: Plasma ghrelin was higher in the underweight patients than in the normal weight patients and in the controls [(1.78 ± 0.46) ng/L, (1.39 ± 0.46) ng/L, (1.36 ± 0.39) ng/L, respectively]. Plasma GH was lower in the underweight patients than in the normal weight patients and in the controls [(4.12 ± 0.83) µg/L, (5.17 ± 0.72)µg/L, (6.49 ± 1.13) µg/L, respectively]. Plasma GHRH was lower in the underweight patients than in the normal weight patients and in the controls [(20.43 ± 4.41) ng/L, (23.47 ± 3.97) ng/L, (27.48 ± 10.06) ng/L, respectively]. Plasma ghrelin was higher in the underweight patients than in the controls (P < 0.01). Plasma ghrelin was higher in the underweight patients than in the normal weight patients with COPD. Plasma ghrelin (log transformed) was negatively correlated with BMI and percentage of body fat in the COPD patients. Plasma GHRH was positively correlated with ghrelin in the underweight patients (r = 0.515, P < 0.05), while no correlation was found between plasma GH and ghrelin in the underweight patients (r = 0.415, P > 0.05). Plasma ghrelin was positively correlated with TNFα and IL-6 in the underweight patients. The gastric expression of ghrelin showed no evident difference between the patients with COPD and the controls. CONCLUSIONS: The plasma GH in COPD patients may not be correlated with ghrelin. The plasma ghrelin level may be a useful indicator for malnutrition in COPD patients. Plasma ghrelin might be involved in the pathogenesis of CODP by affecting the body energy metabolism.

Matrix metalloproteinases: a review of their structure and role in systemic sclerosis.

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

MicroRNA-29: a potential therapeutic target for systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic autoimmune disease of unknown cause characterized by microvasculopathy, fibroblast activation, and excessive production of collagen, causing tissue and organ damage. Effective medical treatment for SSc is lacking because the etiology and pathogenesis of SSc are not fully understood. MicroRNAs (miRNAs) are endogenous, regulatory, single-stranded, noncoding RNAs that negatively modulate gene expression by either promoting the degradation of mRNA or down-regulating the protein production by translational repression. Among them, miRNA-29 is recently discovered as a class of miRNAs which is related to fibrotic disease. Numerous evidences have confirmed that miRNA-29 involved in the expression of extracellular matrix (ECM) and regulated organ fibrosis. These findings revealed a potential and appealing role for miRNA-29 as SSc therapeutic targets. AREAS COVERED: This review provides a comprehensive view on the biogenesis and functions of miRNAs. We also discuss the aberrant expression of miRNA-29 in SSc, and summarize current understanding of miRNA-29 involved in the process of fibrosis. Finally, we discuss the therapeutic potential of targeting miRNA-29 in SSc. EXPERT OPINION: Although the exact pathogenesis of SSc still remains to be clarified, Targeting miRNA-29 may serve as a promising therapy strategy.