Pregnane X Receptor Polymorphisms and Risk of Inflammatory Bowel Disease: A Meta-Analysis

Background: Pregnane X receptor (PXR) gene polymorphisms have been widely studied in terms of the association with inflammatory bowel disease (IBD), with inconsistent results.

Objective: The present meta-analysis was performed to assess the association between PXR gene polymorphisms and the susceptibility of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).

Methods: PubMed, Wanfang, and CNKI databases were searched for eligible studies before November 1, 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to calculate the various genetic models using either a fixed-effect or a random-effect model. The heterogeneity of the included studies was examined with Cochran Q and I² statistics. Begg’s rank correlation test and Egger’s linear regression test were used to assess the publication bias.

Results: A total of six studies with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene polymorphism had no obvious influence on the risk of IBD in Caucasians. Subgroup analyses based on disease type showed similar results.

Conclusion: Our meta-analysis revealed that PXR gene polymorphism may not be significantly associated with IBD susceptibility. However, the number of original studies was limited and further studies with large samples are needed to verify the results.

Abbreviations: PXR = pregnane X receptor, IBD = inflammatory bowel disease, CD = Crohn’s disease, UC = ulcerative colitis, ORs = pooled odds ratios, 95% CIs = 95% confidence intervals, NOS = Newcastle–Ottawa scale, HWE = Hardy–Weinberg equilibrium.     

Comparison of TGF-β1 and NO production by mesenchymal stem cells isolated from murine lung and adipose tissues

Context: Mesenchymal stem cells (MSCs) are cell sources for tissues regeneration. By secretion of soluble factors including transforming growth factor-β (TGF-β1) and nitric oxide (NO), MSCs are also able to regulate the immune system. MSCs have been disclosed in lung and adipose tissues with insufficient comparison between the tissues.

Objectives: In this study, specific differentiation and the expression of surface antigens as well as TGF-β1 and NO productive levels were compared in murine lung-derived MSCs (LMSCs) and adipose tissue-derived MSCs (ADMSCs).

Materials and methods: MSCs were isolated from murine lung and adipose tissues and cultured. Both cell populations were characterized using multilineage potential and the expression of surface antigenic proteins, CD73, CD105, CD34, CD45, and CD11b. Finally, levels of TGF-β1 and NO were evaluated and compared in ADMSCs and LMSCs.

Results: Expression of CD73 and CD105; lack of the expression of CD34, CD45, and CD11b markers; as well as adipocyte and osteocyte differentiations were detected in both adult stem cells. No significant difference was found in TGF-β1 and NO production between two stem cell populations.

Conclusion: Our data showed that LMSCs and ADMSCs have comparable phenotype and TGF-β1 and NO production.     

Systematic overview of neuroanatomical differences in ADHD: Definitive evidence

Objectives: This article seeks to identify neuroanatomical differences in ADHD through an overview of systematic reviews that report encephalic differences compared to a control group in volume, area, activation likelihood or chemical composition.

Methods: We conducted a systematic search using Cochrane guidelines and PRISMA criteria in PubMed, Scopus, Web of Science, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects.

Results: Results revealed broad encephalic involvement that includes a functional frontal and cingulate hypoactivation and structural differences in corpus callosum, cerebellum and basal nuclei.

Conclusions: ADHD symptoms might be due to a multi-network unbalanced functioning hypothesis.     

Matrix Metalloproteinase-9 rs17576 Gene Polymorphism and Behçet’s Disease: Is There an Association?

Background: Clinical studies have reported a significant association between matrix metalloproteinases (MMP), particularly (MMP-9), and inflammatory diseases including Behçet’s disease (BD).

Purpose: To study the relationship between MMP-9 rs17576 gene polymorphism and the development of BD, and its relation to disease activity among Egyptian patients.

Methods: A total of 100 BD patients and 100 healthy control volunteers were genotyped for MMP-9 rs17576 polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), followed by the confirmation of our results in random subgroups using direct DNA sequencing technique.

Results: The frequency of the GG genotype and G allele was significantly higher in BD patients as compared to the normal controls (p = 0.011, OR 8.61; p = 0.03, OR 1.65, respectively). There was no significant association between the MMP-9 rs17576 polymorphism and the clinical outcomes of BD.

Conclusion: our study suggests a significant association of the MMP-9 rs17576 A/G polymorphism with increased risk of BD development in Egyptian patients.     

Systemic inflammatory immune signatures in a patient with CRB1 linked retinal dystrophy

Background: In this report we describe, for the first time, the activation of the peripheral immune compartment in a patient with a CRB1 linked retinal degenerative disease, masquerading as intermediate uveitis.

Methods: To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators.

Results: The levels of various pro-inflammatory immune mediators (including MIF, TSLP, CCL2/MCP-1, CXCL9, CXCL10, IFN-β, IL-6, IL-17, IL-21, IL-22, and IL-23) were elevated in serum at the first time point, and decreased under immunosuppressive treatment. In parallel, the frequency of activated (CD86+) CD1c+ myeloid dendritic cells in blood was proportional to the central foveal thickness measured by optical coherence tomography.

Conclusions: These observations challenge the current view on the distinct pathophysiology of retinal degenerative and retinal inflammatory conditions in this patient.     

Correlation of Proteinuria with Podocyte Foot Process Effacement in IgA Nephropathy: An Ultrastructural Study

Background: Proteinuria is an uncommon clinical manifestation of IgA nephropathy and is usually seen in cases with severe lesions like endocapillary proliferation. However, it is occasionally seen even with cases with mild glomerular manifestations and may even be of nephrotic range.

Predictor: Podocyte foot process effacement.

Outcome: Severity of proteinuria.

Measurements: Podocyte foot process effacement was measured. Morphometric analysis was performed on transmission electron microscope images using a computerized digital photomicrograph system (BioWizard 4.2 Image analysis software, New Delhi, India). Proteinuria was measured quantitatively assigned into five grades.

Results: It was found that as the extent of proteinuria increased, the effacement ratio also increased, and this was most significant between “no” proteinuria and the rest of the categories.

Conclusion: Nephrotic presentation in IgA nephropathy is a known phenomenon and in certain cases may show near normal glomerular morphology with severe foot process effacement on EM being the only significant finding to explain the proteinuria. Proteinuria in these cases shows a significant correlation with degree of foot process effacement. Renal biopsy is important in these cases because they are known to have a better prognosis and are usually steroid responsive.     

Natural Killer Cell Subsets and Their Functional Activity in Behçet’s Disease

Background: Behçet’s disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented.

Objectives: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD.

Patients and methods: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects. BD patients were divided into two groups according to their frequencies of oral ulcerations. NK cell cytotoxicity was determined using CD107a expression and a CFSE-based cytotoxicity test. Expression of NK cell receptors and surface markers and the intracellular IL-5, IL-10, IL-17, and IFN-γ levels in CD16⁺ NK cells were assessed by flow cytometry.

Results: Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells.

Conclusion: Increases in NK1/NK2 ratio and CD16⁺IFN-γ⁺ NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells.     

Harpagoside-induced anaphylactic reaction in an IgE-independent manner both in vitro and in vivo

Background: Harpagoside (HAR) is an active component of Scrophularia ningpoensis (SN), which has anti-inflammatory and anti-immune effects. SN is used widely in China to treat various diseases. Recently, SN has been used as a traditional Chinese medicine injection and used clinically. However, allergic responses to these injections are frequently reported.

Aim: We examined whether the main component of SN, HAR, is associated with the allergic reaction to SN.

Methods: This study assessed the effects of HAR in mice and mast cell activation to characterize its anaphylactic effects and underlying mechanisms. Mice hindpaw swelling, serum allergy factor detection, enzyme-linked immunosorbent assays, and degranulation assays were performed to measure allergic mediators both in vivo and in vitro.

Results: The present study indicated that HAR induced paw swelling, interleukin-6, inositol triphosphate, tumor necrosis factor-α, and histamine increases in mice. Our in vitro data also showed that HAR induced β-hexosaminidase, inositol triphosphate, and interleukin-6 release, leading to mast cell degranulation. In contrast, neither C48/80 nor HAR induced local anaphylaxis in STOCK Kit^W-sh/HNihrJaeBsmJNju mice.

Conclusions: HAR is a potential sensitization compound in SN, and these results provide information for the safe clinical use of SN.     

The timing of mandibular tooth formation in two African groups

Background: Ethnic differences in the timing of human tooth development are unclear.

Aim: To describe similarities and differences in the timing of tooth formation in two groups of Sudanese children and young adults.

Subjects and methods: The sample consisted of healthy individuals from Khartoum, Sudan, aged 2–23 years. The Northern group was of Arab origin (848 males, 802 females) and the Western group was of African origin (846 males, 402 females). Each mandibular left permanent tooth from first incisor to third molar was assessed from dental radiographs into one of 15 development stages. Mean ages at entry for 306 tooth stages were calculated using probit regression in males/females in each group and compared using a t-test.

Results: Mean ages were not significantly different in most tooth stage comparisons between ethnic groups for both males (61/75) and females (56/76), despite a tendency of earlier mean ages in the Western group. Mean ages for most tooth stage comparisons between males and females (137/155) were not significantly different within ethnic groups suggesting low sexual dimorphism.

Conclusion: The mean ages of most mandibular tooth formation stages were generally not significantly different between ethnic groups or between males and females in this study.     

Discriminating between first- and second-order cognition in first-episode paranoid schizophrenia*

Introduction: An impairment of visually perceiving backward masked stimuli is commonly observed in patients with schizophrenia, yet it is unclear whether this impairment is the result of a deficiency in first or higher order processing and for which subtypes of schizophrenia it is present.

Methods: Here, we compare identification (first order) and metacognitive (higher order) performance in a visual masking paradigm between a highly homogenous group of young first-episode patients diagnosed with paranoid schizophrenia (N?=?11) to that of carefully matched healthy controls (N?=?13).

Results: We find no difference across groups in first-order performance, but find a difference in metacognitive performance, particularly for stimuli with relatively high visibility.

Conclusions: These results indicate that the masking deficit is present in first-episode patients with paranoid schizophrenia, but that it is primarily an impairment of metacognition.     

Alu insertion polymorphisms in the African Sahel and the origin of Fulani pastoralists

Background: The origin of Western African pastoralism, represented today by the Fulani nomads, has been a highly debated issue for the past decades, and has not yet been conclusively resolved.

Aim: This study focused on Alu polymorphisms in sedentary and nomadic populations across the African Sahel to investigate patterns of diversity that can complement the existing results and contribute to resolving issues concerning the origin of West African pastoralism.

Subjects and methods: A new dataset of 21 Alu biallelic markers covering a substantial part of the African Sahel has been analysed jointly with several published North African populations.

Results: Interestingly, with regard to Alu variation, the relationship of Fulani pastoralists to North Africans is not as evident as was earlier revealed by studies of uniparental loci such as mtDNA and NRY. Alu insertions point rather to an affinity of Fulani pastoralists to Eastern Africans also leading a pastoral lifestyle.

Conclusions: It is suggested that contemporary Fulani pastoralists might be descendants of an ancestral Eastern African population that, while crossing the Sahara in the Holocene, admixed slightly with a population of Eurasian (as evidenced by uniparental polymorphisms) ancestry. It seems that, in the Fulani pastoralists, Alu elements reflect more ancient genetic relationships than do uniparental genetic systems.     

Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery Disease

Background: Natural killer (NK) cells are the potential modulators of inflammatory reactions that exert several unique biological effects and could lead to future adverse events of coronary artery disease (CAD).

Hypothesis: The purpose of this study was to find out the possible association of modulation in NK cell, TNK cells, T cells, B cells, and tumor necrosis factor alpha (TNF-α) in CAD patients and various forms of myocardial infarction.

Methods: The present study included total 190 subjects (98 confirmed CAD patients both men and women and 92 healthy control individuals). Serum concentration of TNF-α was measured by ELISA method. For the measurement of various immune cells, viz., NK cell, TNK cells, T cells, and B cells, flow-cytometric analysis was performed.

Results: A significant reduction by 15% (P < 0.001) in CD16/CD56 NK cells was observed in CAD patients. Moreover, non-ST segment elevation myocardial infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI), unstable angina (UA), and combined UA + NSTEMI group also showed a significant decline in NK cells compared with control individuals. CD16/CD56/CD3 TNK cells showed a significant reduction in CAD, NSTEMI, STEMI, and UA categories. However, UA + NSTEMI group did not show any significant change in TNK cells. On the other hand, the level of TNF-α was found to be significantly elevated in CAD, STEMI, and UA groups. NSTEMI and combined UA + NSTEMI group did not show any significant change in TNF-α level.

Conclusion: Current study provides an insight toward the association of immune cells and inflammation with CAD.     

Secular trends in cranial morphological traits: a socioeconomic perspective of change and sexual dimorphism in North Americans 1849–1960

Background: The human body has undergone significant changes in stature and other areas, which reflect secular trends associated with socioeconomics.

Aim: To analyse cranial morphological traits for deciphering if they are subject to secular trends.

Subjects and methods: Two documented skeletal collections were sampled for a total of 525 individuals from 1849–1960. Cranial morphological traits were scored and input into time series statistics (logistic regression).

Results: In females, nuchal crests have enlarged, while glabella has decreased. In males, supraorbital margins have dulled, while glabella decreased. Sexual dimorphism increased in supraorbital margins.

Conclusion: The patterns in the data here reflect those found in other areas of the skeleton, namely height, as regards to secular trends. These findings can be extended to stature and cranial changes that parallel socioeconomic trends during the Industrial Revolution, antebellum period and after.     

A monoclonal antibody against CD86 and its protection in a murine lupus nephritis model of chronic graft-versus-host disease

Context: Lupus nephritis is the most common complication that causes the death of systemic lupus erythematosus patients. CD28/CTLA4 and their ligands CD80 or CD86 costimulatory pathway play a pivotal role in autoimmune disease and organ transplantation.

Objectives: We generated a monoclonal antibody (clone 1D1) against human CD86 (1D1) that could recognize both human and mouse CD86, and blocked the CD86/CD28 costimulatory pathway with our mAb on a murine lupus nephritis model induced with chronic graft-versus-host disease (cGVHD).

Materials and methods: Experimental lupus nephritis mice were induced with cGVHD, and splenocyte population were analyzed by flow cytometry. Autoantibodies and proteinuria were detected to evaluate the severity of lupus nephritis. The change of histopathology was observed by microscopy, fluorescence microscopy and electron microscopy.

Results: we successfully generated a monoclonal antibody against human CD86(1D1). 1D1 mAb could recognize not only human CD86, but also mouse CD86. 1D1 was applied to the cGVHD-induced experimental lupus nephritis model, and our study found the production of ANA and anti-dsDNA in the 1D1-treated group was lower than those in IgG-treated group after four weeks. The pathological injure of kidney in the 1D1-treated group was lighten than that in IgG-treated group.

Discussion and conclusions: Our data showed that blockade of CD86/CD28 with 1D1 induced a significant remission of proteinuria, production of autoantibodies, immune complex deposition and renal parenchyma lesions in experimental mice. Anti-CD86 Abs might be a potential method for immune therapy in autoimmune diseases and transplantation.     

Leprosy in a Lombard-Avar cemetery in central Italy (Campochiaro,Molise, 6th–8th century AD): ancient DNA evidence and demography

Background: The study of past infectious diseases increases knowledge of the presence, impact and spread of pathogens within ancient populations.

Aim: Polymerase chain reaction (PCR) was used to examine bones for the presence of Mycobacterium leprae ancient DNA (aDNA) as, even when leprosy is present, bony changes are not always pathognomonic of the disease. This study also examined the demographic profile of this population and compared it with two other populations to investigate any changes in mortality trends between different infectious diseases and between the pre-antibiotic and antibiotic eras.

Subjects and methods: The individuals were from a site in Central Italy (6th–8th CE) and were examined for the presence of Mycobacterium leprae aDNA. In addition, an abridged life mortality table was constructed.

Results: Two individuals had typical leprosy palaeopathology, and one was positive for Mycobacterium leprae aDNA. However, the demographic profile shows a mortality curve similar to that of the standard, in contrast to a population that had been subjected to bubonic plague.

Conclusions: This study shows that, in the historical population with leprosy, the risk factors for health seem to be constant and distributed across all age classes, similar to what is found today in the antibiotic era. There were no peaks of mortality equivalent to those found in fatal diseases such as the plague, probably due to the long clinical course of leprosy.     

ALK protein expression in pulmonary adenocarcinoma of Tunisian patients

Background. It is now necessary to determine ALK status in order to use targeted therapy. Aim: herein, we assess immunohistochemical profile of ALK protein in a series of Tunisian patients with pulmonary adenocarcinoma.

Materials and Methods. ALK protein expression was studied applying the D5F3 antibody with a fully automated Ventana CDx technique on a series of 19 patients.

Results. Positive ALK expression was found in one case (5.2%) corresponding to a papillary adenocarcinoma which showed a strong granular and homogenous cytoplasmic staining. The patient was a 30-years-old woman.

Conclusion. The frequency of positive ALK expression based on immunohistochemistry in our series was similar to that reported in the world literature.     

Immune Profiling of T Cells Infiltrating Vitreous Humor in Tubercular Uveitis

Purpose: To assess cellular composition and local cytokine response in vitreous humor of tubercular uveitis.

Methods: Cells were collected from vitreous cassettes and peripheral blood of 8 tubercular uveitis and 5 control subjects, undergoing vitrectomy and analyzed by flow cytometry for cellular composition, activation status, proinflammatory cytokine expression, and uptake of TLR9 ligand, CpG ODN 2216.

Results: CD3 + T cells with equal proportion of CD4+ and CD8 + T cells formed major fraction of infiltrating cells. The vitreous humor showed higher expression of recent activation marker, CD69, and proinflammatory cytokines, IFN-γ and IL-17A, in CD4 + T cells as compared to peripheral blood. Lastly, intraocular CD4 + T cells showed reduced uptake of ODN 2216 than peripheral blood.

Conclusions: Our results indicate that local antigenic stimuli trigger T cell infiltration and activation of CD4 + T cells that are hyporesponsive to TLR9 stimulation. These infiltrating T cells might be responsible in further aggravating ocular inflammation.