New Proteins Contributing to Immune Cell Infiltration and Pannus Formation of Synovial Membrane from Arthritis Diseases

An inflamed synovial membrane plays a major role in joint destruction and is characterized by immune cells infiltration and fibroblast proliferation. This proteomic study considers the inflammatory process at the molecular level by analyzing synovial biopsies presenting a histological inflammatory continuum throughout different arthritis joint diseases. Knee synovial biopsies were obtained from osteoarthritis (OA; n = 9), chronic pyrophosphate arthropathy (CPPA; n = 7) or rheumatoid arthritis (RA; n = 8) patients. The histological inflammatory score was determined using a semi-quantitative scale based on synovial hyperplasia, lymphocytes, plasmocytes, neutrophils and macrophages infiltration. Proteomic analysis was performed by liquid chromatography-mass spectrometry (LC-MS/MS). Differentially expressed proteins were confirmed by immunohistochemistry. Out of the 1871 proteins identified and quantified by LC-MS/MS, 10 proteins (LAP3, MANF, LCP1, CTSZ, PTPRC, DNAJB11, EML4, SCARA5, EIF3K, C1orf123) were differentially expressed in the synovial membrane of at least one of the three disease groups (RA, OA and CPPA). Significant increased expression of the seven first proteins was detected in RA and correlated to the histological inflammatory score. Proteomics is therefore a powerful tool that provides a molecular pattern to the classical histology usually applied for synovitis characterization. Except for LCP1, CTSZ and PTPRC, all proteins have never been described in human synovitis.

Bacteriological and pathological investigations on the preputial glands of one-year-old C57BL/6NCrl mice maintained in individually ventilated cages

Spontaneous infections of the preputial glands represent overlooked health problems in mice that could raise welfare concerns and potentially confound scientific experiments. Agents involved in preputial gland infections have rarely been investigated, with opportunistic pathogens of laboratory animals usually detected in inflamed preputial glands. The aim of this study was to investigate the prevalence of bacterial infection in the preputial glands and the relationship between haematological and pathological changes and infection status. We analysed 40 preputial glands from 20 one-year-old C57BL/6NCrl male mice by using bacteriology, haematology and pathology. Bacteria were isolated from 16/20 (80%) mice, for a total of 32/40 (80%) examined preputial glands. Enterobacter cloacae, Pasteurella spp., Klebsiella spp. and Staphylococcus aureus were identified in 35%, 17.5%, 15% and 12.5% of the examined glands, respectively. Preputial gland inflammation was identified in 29/40 (72.5%) glands and was classified as chronic interstitial adenitis in 27 cases and suppurative adenitis in the remaining two glands. No haematological changes were found in mice with infected glands. Histologically, the presence of intralesional bacteria, intraluminal necrotic material, intraluminal keratin accumulation, interstitial inflammatory cell infiltrate and granulocytes (intraluminal and/or interstitial), along with total inflammatory score and total histopathological score, were significantly increased in infected glands and correlated with the bacterial load. Most severe inflammatory changes were identified after S. aureus infection, while ductal hyperkeratosis was significantly increased in glands infected with Klebsiella spp. In conclusion, preputial gland infection was a common event in one-year-old C57BL/6NCrl mice, and bacterial load correlated with pathological findings, while systemic effects were not highlighted by haematology.

Inflammatory potential of diet and bone mineral density in a senior Mediterranean population: a cross-sectional analysis of PREDIMED-Plus study

Purpose Inflammation could play a key role in tissue damage and bone metabolism. The modified dietary inflammatory score (M-DIS) is a validated tool to estimate the inflammatory potential of the diet. In the present study, we evaluate the associations between the M-DIS and bone mineral density (BMD) in a senior Mediterranean population with overweight/obesity and metabolic syndrome. Methods Baseline cross-sectional association between the M-DIS and bone mineral density was assessed in 1134 participants of the multicenter PREDIMED-Plus trial (aged 55–75 with overweight/obesity and metabolic syndrome). BMD was measured using Dual-energy X-ray Absorptiometry scans and participants answered a food frequency questionnaire to determine the M-DIS. BMD was categorized as low BMD when T score was equal or lower than -1 and normal BMD in another case. Associations between BMD and M-DIS were evaluated by using linear and logistic regressions adjusted by other co-variates. Results Participants in the top tertile of the M-DIS had a lower BMD at total femur [β (95% CI) − 0.02 (− 0.04, − 0.01)], trochanter areas [β (95% CI) − 0.03 (− 0.05, − 0.01)] and lumbar spine area [β (95% CI) − 0.03 (− 0.07, 0.01)] (but in the last case, measures were less precise and hence not statistically significant) compared to those in the lower M-DIS tertile. Multiple logistic regression analyses showed that the odds of the total femur and femoral trochanter osteopenia/osteoporosis were higher in participants in the top tertile compared to those in the lowest tertile of M-DIS [OR (95% CI) 1.71 (1.12, 2.64), P for trend 0.015; 2.02 (1.29, 3.21), P for trend 0.002, respectively]. Conclusion A high pro-inflammatory diet, measured by the M-DIS, is associated with lower BMD in a senior Mediterranean population with metabolic syndrome.

Correlation between clarithromycin resistance, virulence factors and clinical characteristics of the disease in Helicobacter pylori infected patients in Shahrekord, Southwest Iran

The purpose of this study was to determine the mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from biopsy samples that were collected from the endoscopic ward of Shahrekord Hajar teaching Hospital and also to study the frequency of virulence factor and their correlation and pathological findings with clarithromycin resistance during the years 2019–2020. In this cross-sectional descriptive study, 152 patients with Helicobacter pylori infection were considered, and then, two common A2142G and A2143G mutations in the 23SrRNA gene associated with resistance were analyzed by Real-time PCR (Taq man). The presence of vacA, iceA1, iceA2, cagA, babA2, and oipA virulence genes was investigated by PCR and electrophoresis in 8% polyacrylamide gel. Then, data were analyzed using the relevant statistical tests. In this study, the frequency of Helicobacter pylori was 76% and the frequency of mutant isolates was 57.2%. The frequencies of A2142G and A2143G point mutations were 42.1% and 28.3%. There was a significant correlation among oipA, vacA, and iceA1 virulence factors, type of disease, chronic inflammatory score, and glandular atrophy with the antibiotic resistance to clarithromycin. There was no significant correlation between the age and sex of the patients with antibiotic resistance. According to the results of this study, it seems that the use of clarithromycin to combat this bacterium should be limited.

Efficacy of bubaline blood derived fibrin glue in silk ligature-induced acute periodontitis in Wistar rats

Background and Aim: Fibrin forms in the coagulation process, enhancing local hemostatic properties and promoting wound healing. The study aimed to evaluate the efficacy of bubaline-derived fibrin glue in silk ligature-induced periodontitis rats. Materials and Methods: Bubaline blood–derived fibrin glue was prepared using cryoprecipitation and cryocentrifugation. Periodontitis was induced in rats by placing 5-0 silk ligatures around the mandibular first molars. The animals were divided into two groups: (1) Non-treatment and (2) bubaline fibrin glue–treated groups. Plaque, gingival inflammation, and mobility index were scored on days 1, 7, and 14 after intervention. Histological examinations were performed. The mRNA expression of inflammatory cytokines and growth factors was evaluated using a real-time polymerase chain reaction. Ligature-induced periodontitis was confirmed by the increase in inflammatory cell infiltration as well as histological bone and attachment loss. Results: Compared to the non-treatment group, bubaline fibrin glue application reduced mononuclear cell infiltration into periodontal tissues corresponding to the reduction of collagen destruction. On days 7 and 14 after intervention, the inflammatory score and histological attachment loss were significantly lower in the bubaline fibrin glue–treated group than in the non-treatment group. A significant reduction in histological bone loss was observed in the treated group on day 7. Bubaline fibrin glue application led to a significant reduction of Tnfa and Il1b mRNA levels, while an increased expression of Pdgfa, Tgfb1, and Il10 was observed compared with the control. Conclusion: Bubaline fibrin glue could be beneficial in periodontitis treatment aiming to reduce inflammation and delay the progression of periodontal disease.

Abstract MP13: Evaluation Of The Effect Of Low Grade Inflammation And Hypertension On The Development Of White Matter Lesions

Introduction: The risk of degenerative disease development is closely linked to persistent and continuous systemic inflammation. Although relationships between chronic low-grade inflammation (LGI) measurements and the progression of cardiovascular diseases are becoming established, the burden of the cardio-pathology and LGI on the central nervous system has not been fully investigated. Specifically, there is limited data on how hypertension (HTN) and related LGI impact white matter lesion (WML) pathogenesis. Methods: We examined 448 subjects with a mean age of 69.3 ± 7.4 years, with 62% of the cohort being women (n=276), and 45% having hypertension (n=200). Components of the LGI score included white blood cell count, albumin levels, platelet counts, and granulocyte/lymphocyte ratio, modified after. Larger LGI scores represented an increase in measured LGI intensity at that time point. MR images were obtained on a 3T system using fluid attenuation inversion recovery (FLAIR) sequence. WML burden was ascertained using Fazekas scale, done separately for both deep WML and periventricular WML. Summated score of greater than or equal to 4 was considered high overall WML burden. Results: It was found that subjects with hypertension had significantly higher LGI score when compared to subjects without hypertension after accounting for sex and BMI (F=4.8, p=0.03). Using logistic regression. we found that LGI score was related to higher WML burden (p=0.047) within the entire cohort. However, further analyses have shown that this finding was driven by the normotensive group, in which the relationship between higher WML burden and respective LGI score was significant (p=0.007). This was not the case among hypertensive subjects. Conclusion: It is clear from the data presented that a relationship between LGI and hypertension exists, confirming that inflammation is an underlying process in cardiovascular pathogenesis. However, LGI scores were related to WML in only normotensive cohorts. We offer that the effects of chronic HTN (related to higher inflammatory score itself ) overshadow the effect of LGI among hypertensive subjects. It is worth emphasizing that even in subjects without HTN white matter damage is related to LGI

Procollagen I N-terminal peptide correlates with inflammation on sacroiliac joint magnetic resonance imaging in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis: A cross-sectional study

ABSTRACT Objectives To identify disease activity scores and biomarkers that reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Methods Patients who had AS and nr-axSpA were enrolled. All the patients underwent SIJ MRI. SpondyloArthritis Research Consortium of Canada (SPARCC) method was used to score bone marrow edema in the inflammatory lesions on MRI. Radiographic assessment of the spine was performed using modified Stoke Ankylosing Spondylitis Spine Score. Clinical variables, inflammatory markers, serum alkaline phosphatase, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX-I), and procollagen I N-terminal peptide (PINP) were measured. Correlation analysis between MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables was performed. Results Thirty-five patients had AS and 36had nr-axSpA. Significant differences were noted between the AS group and the nr-axSpA group in terms of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR, ASDAS-CRP, PINP, and SPARCC (p < .001, p = .004, p < .001, p < .001, p = .030, p < .001, respectively). MRI-determined SIJ inflammatory scores correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), OC, CTX-I, and PINP in AS (p = .036, p = .023, p = .002, p = .041, p = .004, respectively) and correlated with ESR, CRP, ASDAS-ESR, ASDAS-CRP, BASDAI, and BASFI in nr-axSpA (p = .003, p = .002, p < .001, p < .001, p = .010, p = .007, respectively). Multivariate analysis showed that PINP exhibited a positive correlation independent of the MRI inflammatory score and that age exhibited a negative correlation independent of the MRI inflammatory score. Conclusions In AS, PINP and age independently correlated with active inflammation on SIJ MRI. PINP may be useful as a marker of objective inflammation in AS.

Inflammatory Potential of the Diet and Incidence of Crohn’s Disease and Ulcerative Colitis in the EPIC-Spain Cohort

Diet may influence the development of inflammatory bowel disease through the modulation of inflammation. We investigated whether the inflammatory potential of the diet is associated with the risk of Crohn’s disease (CD) and ulcerative colitis (UC) in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The study included 32,633 participants aged 29–69 years. The inflammatory potential of the diet was measured by using an inflammatory score of the diet (ISD) based on a baseline dietary history questionnaire. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 21 years (674,547 person-years) of follow-up, 32 and 57 participants developed CD and UC, respectively. In multivariable analysis, a one-standard deviation (SD) increment in the ISD (two-unit increase) was associated with a higher risk of CD (HR of 1.71; 95% CI: 1.05–2.80; p = 0.031). By contrast, ISD was not associated with UC (HR for one-SD increment of 0.89; 95% CI: 0.66–1.19; p = 0.436). Our results suggest that consuming a more pro-inflammatory diet may contribute to the risk of CD, supporting that a healthy diet might be beneficial in its prevention. Further, larger studies are needed to verify these findings.