Health disparities in systemic lupus erythematosus-a narrative review.

PURPOSE OF REVIEW: To describe root causes of health disparities by reviewing studies on incidence and outcomes of systemic lupus erythematosus (SLE) related to ethnic, race, gender, or socioeconomic differences and to propose solutions. RECENT FINDINGS: SLE outcomes have steadily improved over the past 40 years but are not uniformly distributed across various racial and ethnic groups. Belonging to racial and ethnic minority has been cited as a risk factor for more severe disease and poor outcome in SLE. Population-based registries have demonstrated that Black patients with SLE have significantly lower life expectancy compared to White patients. Lower socioeconomic status has been shown to be one of the strongest predictors of progression to end stage renal disease in lupus nephritis. An association between patient experiences of racial discrimination, increased SLE activity, and damage has also been described. The lack of representation of marginalized communities in lupus clinical trials further perpetuates these disparities. To that end, the goal of a rheumatology workforce that resembles the patients it treats has emerged as one of many solutions to current shortfalls in care. Disparities in SLE incidence, treatment, and outcomes have now been well established. The root causes of these disparities are multifactorial including genetic, epigenetic, and socioeconomic. The underrepresentation of marginalized communities in lupus clinical trials further worsen these disparities. Efforts have been made recently to address disparities in a more comprehensive manner, but systemic causes of disparities must be acknowledged and political will is required for a sustained positive change.

Chemical component and in vitro protective effects of Matricaria chamomilla (L.) against lipopolysaccharide insult.

ETHNOPHARMACOLOGICAL RELEVANCE: Chamomile (Matricaria chamomilla L.) is a popular herbal tea for the treatment of hepatitis and cholecystitis in traditional Uygur medicines. AIM OF THE STUDY: To investigate the anti-inflammatory activity and chemical composition of M. chamomilla, and clarify its molecular mechanism. MATERIALS AND METHODS: M. chamomilla was extracted with 75% ethanol and then extracted with different solvents to obtain five fractions, namely petroleum ether fraction (EOPE), dichloromethane fraction (EOD), ethyl acetate fraction (EOEA), n-butanol fraction (EOB), and water fraction (EOW). Cytotoxicity and the effect on the nitric oxide (NO) production of RAW264.7 cells induced by LPS of the five fractions were screened, and the most active one (EOD) was selected for further investigations. The components of EOD were identified by LC-MS/MS analysis in combination with comparison of retention time and UV absorption with authentic compounds by HPLC. In addition, five most abundant compounds of EOD were isolation by column chromatography and semi-preparative HPLC and their structures were further confirmed by HRMS and NMR data analysis and comparison with data in literatures. Then the underlying anti-inflammatory mechanism of EOD were predicted through Network pharmacology using the identified compounds from EOD, and further verified by Western Blot and ELISA experiments. RESULTS: EOD showed the most significant inhibition ratio against NO in RAW264.7 cells without toxicity among the tested five fractions. Thirty-seven compounds including flavonoid-O-glycoside, flavonoid aglycone, methylated flavonoid aglycone, phenolic acid, coumarin, sesquiterpene, and triterpene were identified from EOD by LC-MS/MS and comparison with authentic compounds. The five most abundant compounds in EOD were isolated and determined to be axillarin (26), tricin (30), chrysoeriol (31), centaureidin (33) and chrysosplenetin (35). IL-6, NF-κB, ERK1 and ERK2 cascade, TNF were the most important anti-inflammatory targets of EOD predicted by Network pharmacology. Western Blot and ELISA experiments revealed that EOD significantly decreased the protein expression levels of inflammatory factors (PGE2, MCP-1, IL-6, TNF-α), iNOS, COX-2, NF-κB (p-P65 and p-IκBα), MAPKs (p-p38, p-ERK and p-JNK), and increased the protein expression levels of Nrf2, HO-1 and CYP2E1. In addition, EOD blocked the p65 protein into the nucleus and promoted the nuclear translocation of Nrf2 in RAW264.7 cells induced by LPS. CONCLUSION: M. chamomilla exerted anti-inflammatory effect via NF-κB, MAPK and Nrf2/HO-1 pathways. It could be further applied as a safe anti-inflammatory agent from natural source.

Comprehensive network analysis to identify the molecular pathogenesis of pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PAH) is a chronic progressive disease that may lead to right heart failure and eventually death. At present, great progress had been achieved in the treatment of pulmonary hypertension. However, pulmonary hypertension cannot be fundamentally cured, and its pathogenesis is still unclear. METHODS: A multifactor-driven dysfunction module of pulmonary hypertension has been constructed in order to explore its potential pathogenesis. We performed differential expression analysis, coexpression analysis, enrichment analysis and hypergeometric test to calculate the potential regulatory effects of multiple factors on the module. RESULTS: Four modules and corresponding hub genes were identified. In addition, we also obtained a series of ncRNA (MALAT1 and miR-17-5p) and transcription factor (HIF1A). Network analysis revealed that MALAT1, NFKB1 and RELA targeting IL1B of module 4 and IL6 of module 1 to participate in the occurrence and development of pulmonary hypertension through Toll-like receptor signaling pathway. CONCLUSIONS: It is necessary to identify disease-related disorders by integrating multiple regulatory factors. The regulatory network may play an important role in PAH. The results not only provided new methods and ideas for follow-up research, but also helps researchers to have a deeper understanding of potential pathogenesis for PAH.

Pattern and Correlates of Hypomagnesemia Among Subset of Diabetes Mellitus.

BACKGROUND: Nowadays, there is an accumulated data about the relation between hypomagnesemia (low Serum Mg level < 0.7 mmol/l) and diabetes. OBJECTIVE: In this study, we aimed to determine the prevalence of hypomagnesemia in a carefully diagnosed diabetes patients and to show how some factors could contribute to the prevalence of low serum Mg level among the population under study. METHODS: In short, 62 patients of both type 1 and 2, who attended AL-Sadir medical city/ diabetes and endocrinology centre during the period of the study were included in the study. A detailed history was taken and participants were informed verbally about the procedure of this study. Serum magnesium and creatinine were measured using standardized methods. RESULTS: The overall prevalence of the hypomagnesemia, among diabetic population involved in this study, was 29.03 % and it was nearly similar in male (29.41 %) and female (28.57 %). The means(SD) of serum Mg level were similar in type 1 and type 2 diabetic patients. Other difference in prevalence among other characteristics has been reported. Within all participants, gender (r = -0.02), fasting blood glucose (r = -0.514) and metformin use (r = -0.014) were negatively correlated with serum Mg level, in contrast to other variables, which were positively correlated. While among type 1 DM, age (r= 0.193), serum creatinine (r= 0.031) and insulin use (r= 0.217) were positively correlated with serum Mg level. In contrast, others were negatively correlated. In type 2 DM, age (r = -0.283) and fasting blood glucose (r = -0.496) were negatively correlated with serum Mg level. On the other hand, other variables were positively correlated with serum Mg level. CONCLUSION: Hypomagnesemia prevalence was detected in nearly one-third of the diabetic population, which is quite high prevalence. Some factors have shown to play an essential role in this prevalence. A large study is warranted to address this issue.

Changes in mucin 1 expression in a rat model of allergic airway inflammation.

PURPOSE: To explore the distribution and expressional changes of mucin 1 (Muc1) in airway of rats with allergic airway inflammation. MATERIALS AND METHODS: Ovalbumin (OVA) was used to induce acute allergic inflammation in male Wistar rats. The distributions and expressions of Muc1 in lungs of normal and model rats were assessed by immunohistochemical staining and western blotting, respectively. RESULTS: Immunohistochemical staining showed that Muc1 distributed in airway epithelial cells with ciliates, but not those nonciliated cells. Mucin 1 protein expression in the lung was increased during the development of allergic airway inflammation when compared with the normal rats. CONCLUSION: Mucin 1 distributes in the airway epithelial cells with ciliates and the expressional increase of Muc1 in lung may imply its functions on allergic inflammatory episodes.

Anthropometric measurements in children having transfusion-dependent beta thalassemia.

OBJECTIVES: The aim of this study was to determine the anthropometric measurements in transfusion-dependent ß-thalassemia children in Pakistan. The secondary aim was to correlate serum ferritin with the physical growth. METHODS: We enrolled 367 children (aged 5-17 years) with transfusion-dependent beta-thalassemia major in the study. Anthropometric measurements, serum ferritin levels, and pre-transfusion hemoglobin levels were measured. Serum ferritin was correlated with the height z-score for age. RESULTS: Laboratory evaluation showed that patients had significantly low mean pre-transfusion hemoglobin of 7.66 ±â€…1.34 g/dl (range 2.5-10.5) and high median (Q3-Q1) serum ferritin of 5012 ng/ml (6829-3532). The median (Q3-Q1) height-for-age z-score of children was low at -2.69 and (-1.46 to -3.80) and 65.4% children had stunted growth (height for age z-score <-2). There was a significant negative correlation between height for age z-score and serum ferritin levels (p < 0.000). Stunting of growth began early during 5-10 years of age but increased markedly with the progress of time. CONCLUSIONS: The study showed that children with beta thalassemia major had delayed physical growth possibly secondary to iron overload. Effective and early iron chelation is needed for preventing growth failure in transfusion-dependent beta thalassemia.

Randomized, double-blind, placebo-controlled superiority trial of the Yiqigubiao pill for the treatment of patients with chronic obstructive pulmonary disease at a stable stage.

In traditional Chinese medicine (TCM), the Yiqigubiao pill is commonly used to enhance physical fitness. The current clinical trial was designed to evaluate the efficacy and safety of the Yiqigubiao pill as an adjuvant therapy for patients with stable chronic obstructive pulmonary disease (COPD). The current trial was a randomized, double-blind, placebo-controlled superiority trial. The participants were recruited from outpatients at the Traditional Chinese Medicine Hospital affiliated with Xinjiang Medical University (Ürümqi, China) between February and September 2012. All participants were patients with stable COPD that were randomized to the Yiqigubiao pill (YQGB; n=84) or placebo (Pb; n=87) groups. The occurrences of acute exacerbation (AE) of COPD during the trial were recorded. Lung function value assessments, scoring of life quality and exercise endurance, arterial blood gas analysis and serum inflammatory cytokines level determination were performed prior to and throughout the study. A total of 139 participants completed the intervention and 132 participants completed the study. The interval between the initial intervention and the first AECOPD was greater in the YQGB group compared with the Pb group (P<0.01). The incidence rate of AECOPD was lower in the YQGB group than in the Pb group (P<0.01). Subsequent to the intervention or at the end of the study, the 6-min walking distance difference was longer in the YQGB group compared with the Pb group (P<0.01). The scores reflecting life quality decline became lower in the YQGB group (P<0.01). The serum levels of proinflammatory factors were downregulated to a greater extent in the YQGB group compared with the Pb group. Thus, the Yiqigubiao pill is an efficient and safe adjuvant therapy for the treatment of stable patients with COPD.

Use of aquaporins 1 and 5 levels as a diagnostic marker in mild-to-moderate adult-onset asthma.

Characteristic features of asthma include airway inflammation and hyperactivity, mucus hypersecretion, mucosal edema, and airway remodeling. These features could be due to pathological water transport across pulmonary epithelia and aquaporins (AQPs) have recently been isolated as key proteins in fluid transportation in the human respiratory tract. We aimed to evaluate the role of aquaporins in the pathogenesis of asthma and their possible use a diagnostic marker of the disease. A total of 110 hospitalized and outpatients with mild to moderate adult-onset asthma were invited to participate in this study and 34 submitted an induced sputum sample adequate for analysis. The amount of AQP1, AQP5 and MUC5AC were measured with ELISA assay. The amount of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 in both serum and sputum were measured with Cytometry Bead Array (CBA kit). Our results suggest that sputum AQP5, AQP1 and MUC5AC are all in a good correlation (r=0.498 between AQP5 and AQP1, r=0.529 and r=0.661 between MUC5AC and AQP5 or AQP1, respectively, all P<0.05). The AUC value for AQP1 and AQP5 to diagnose asthma were 0.729 and 0.745, respectively. In conclusion, water homeostasis plays an important role in maintaining adequate fluid transportation within the lung and is involved in the pathogenesis of asthma. Our results suggest that AQP may influence pulmonary physiology that their dysfunction can contribute to pulmonary pathogenesis, such as asthma. Moreover, their quantification could serve as biomarkers for the diagnosis of asthma.

Echinococcus granulosus infection reduces airway inflammation of mice likely through enhancing IL-10 and down-regulation of IL-5 and IL-17A.

BACKGROUND: Cystic echinococcosis (CE) is a near cosmopolitan zoonosis caused by the larval stage of the dog tapeworm Echinococcus granulosus. E. granulosus infection induces a polarized T-helper type 2 (Th2) systematic immune response in its intermediate hosts. However, it is not known whether the infection modulates lung inflammation by regulating local immune response. In this study, we examined the effects of E. granulosus infection on mouse ovalbumin (OVA)-induced asthma model. METHODS: BALB/c mice were intraperitoneally transplanted with 50 small E. granulosus cysts cultured in vitro. At 3 months post-inoculation, the mice were sensitized and challenged with ovalbumin (OVA). For histopathological studies, hematoxylin eosin and periodic acid schiff staining was used to examine the inflammatory cells infiltration and goblet cells hyperplasia, respectively. Cytokine levels were measured by mouse cytometric bead array (CBA) Kit and quantitative RT-PCR and other molecular biological approaches. Airway hyperresponsiveness was assessed in response to increasing doses of methacholine. Serum immunoglobulins were determined by ELISA. RESULTS: E. granulosus infection significantly increased Th2 and Treg cytokine levels in serum and lung tissues, but down-regulated the expression of IL-5 in the lungs and IL-17A in serum and lung tissues of asthmatic mice sensitized and challenged with OVA. Histological staining of lung tissues showed that E. granulosus infection significantly reduced the severity of OVA-induced airway inflammation including reduction of eosinophil cell infiltration and mucus production. The E. granulosus infection also reduced eosinophil accumulation induced by OVA in bronchoalveolar lavage fluid (BALF) and also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. CONCLUSIONS: E. granulosus infection remarkably reduces the severity of OVA-induced airway inflammation likely through enhancing IL-10 and down-regulation of IL-5 and IL-17A.

Expression of aquaporins in the lungs of mice with acute injury caused by LPS treatment.

The aim of the present study was to investigate the expression of aquaporin 1 (AQP1) and AQP5 in the lungs of mice with acute injury induced by LPS treatment. In the study, the concentrations of cytokines were all significantly increased in the BALF of mice received LPS at 12h and 24h (P<0.001). The lung wet/dry weight ratios (W/D) and total protein content in BALF were also increased in the mice treated with LPS (P<0.001). Interestingly the expression of AQP1 and AQP5 was significantly decreased (P<0.05) compared with these in the control mice, while TUNEL positive cells were increased. However, the AQP5 expression was significantly higher at 24h that it at 12h in the control mice. Our results showed that decreased AQP expression was associated with the increased inflammatory factors, as well as apoptotic cells. The increased expression of AQP5 at 24h in control mice might be due to its regulation in transcellular water reabsorption.

Changes in water channel aquaporin 1 and aquaporin 5 in the small airways and the alveoli in a rat asthma model.

OBJECTIVES: To examine changes in aquaporin 1 (AQP1) and aquaporin 5 (AQP5) in the small airways and alveoli in a rat asthma model. METHOD: Forty Wistar rats were randomly divided into a control group and an ovalbumin (OVA) sensitization asthma model group. The distribution and expression of AQP1 and AQP5 in lung tissues were analyzed using immunohistochemistry (IHC), quantified the staining intensity by assessing integrated optical densities (IOD), and Western blotting (WB). RESULTS: IHC showed AQP1 was mainly distributed in sub-epithelial microvascular endothelial cells (MECs) and red blood cells. IOD values showed, in the asthma model group, the expression of AQP1 in alveolar MECs was lower than that in the control group (P<0.05); However, AQP1 expression in small airways sub-epithelial was higher than in the control group (P<0.05). The WB indicated that AQP1 expression in the asthma model group was 57% lower than in the control group (P<0.05). AQP5 was mainly distributed in the non-ciliated epithelial cells of the small airways and the apical membranes of type I and type II epithelial cells. IOD values showed, in asthma model group, the expression of AQP5 increased in small airways epithelium (P<0.05), and decreased in alveolar epithelium (P<0.05). The WB showed a 36% reduction in AQP5 expression compared with the control group (P<0.05). CONCLUSION: AQP1 and AQP5 increased in small airways in rats with experimentally induced asthma, indicating that they may be involved in the formation of submucosal edema and mucus hypersecretion. Decreased AQP1 and AQP5 in pulmonary alveoli may be related to increased alveolar liquid viscosity and the formation of mucus plugs.

Evidences of lateral gene transfer between archaea and pathogenic bacteria.

Acquisition of new genetic material through horizontal gene transfer has been shown to be an important feature in the evolution of many pathogenic bacteria. Changes in the genetic repertoire, occurring through gene acquisition and deletion, are the major events underlying the emergence and evolution of bacterial pathogens. However, horizontal gene transfer across the domains i.e. archaea and bacteria is not so common. In this context, we explore events of horizontal gene transfer between archaea and bacteria. In order to determine whether the acquisition of archaeal genes by lateral gene transfer is an important feature in the evolutionary history of the pathogenic bacteria, we have developed a scheme of stepwise eliminations that identifies archaeal-like genes in various bacterial genomes. We report the presence of 9 genes of archaeal origin in the genomes of various bacteria, a subset of which is also unique to the pathogenic members and are not found in respective non-pathogenic counterparts. We believe that these genes, having been retained in the respective genomes through selective advantage, have key functions in the organism's biology and may play a role in pathogenesis.