Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

Background. Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles. HLA-E are non-classical MHC class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis. Objectives: To analyze the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27 positive AS patients and healthy controls (HC) bearing the AS-associated, B*2705 and the non-AS-associated, B*2709 allele. Methods: The level of surface expression of HLA-E molecules on CD14 positive peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27 negative HC, using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3-CD56+ NK cells. Results. HLA-E expression in CD14 positive cells was significantly higher in AS patients (587.0 IQR 424-830) compared to B*2705 HC (389 IQR 251.3-440.5, p=0.0007), B*2709 HC (294.5 IQR 209.5-422, p=0.0004) and HLA-B27 negative HC (380 IQR 197.3-515.0, p=0.01). A higher number of NK cells expressing NKG2A compared to NKG2C was found in all cohort analysed as well as a higher cell surface density. Conclusion: The higher surface level of HLA-E molecules in AS patients compared to HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis accounting for the previously reported association between HLA-E and AS

Spa therapy induces clinical improvement and protein changes in patients with chronic back pain

This study is primarily aimed at assessing serum changes on a large panel of proteins in patients with chronic back pain following spa therapy, as well as evaluating different spa therapy regimens as a preliminary exploratory clinical study. Sixty-six patients with chronic back pain secondary to osteoarthritis were randomly enrolled and treated with daily mud packs and bicarbonate-alkaline mineral water baths, or a thermal hydrotherapy rehabilitation scheme, the combination of the two regimens or usual medication only (control group), for two weeks. Clinical variables were evaluated at baseline, after 2 and 12 weeks. One thousand serum proteins were tested before and after a two-week mud bath therapy. All spa treatment groups showed clinical benefit as determined by improvements in VAS pain, Roland Morris disability questionnaire and neck disability index at both time points. The following serum proteins were found greatly increased (≥2.5 fold) after spa treatment: inhibin beta A subunit (INHBA), activin A receptor type 2B (ACVR2B), angiopoietin-1 (ANGPT1), beta-2-microglobulin (B2M), growth differentiation factor 10 (GDF10), C-X-C motif chemokine ligand 5 (CXCL5), fibroblast growth factor 2 (FGF2), fibroblast growth factor 12 (FGF12), oxidized low density lipoprotein receptor 1 (OLR1), matrix metallopeptidase 13 (MMP13). Three proteins were found greatly decreased (≤0.65 fold): apolipoprotein C-III (Apoc3), interleukin 23 alpha subunit p19 (IL23A) and syndecan-1 (SDC1). Spa therapy was confirmed as beneficial for chronic back pain and proved to induce changes in proteins involved in functions such as gene expression modulation, differentiation, angiogenesis, tissue repair, acute and chronic inflammatory response

The impact of COVID-19 lockdown on admission to gynecological emergency departments: Results from a multicenter Italian study

Objective: To evaluate the impact of the COVID-19 lockdown on admissions to gynecological emergency departments (ED) of three Italian university hospitals with different rates of COVID-19 incidence. Methods: A retrospective study was conducted in the gynecological EDs of Modena (Emilia-Romagna), Sassari and Cagliari (Sardinia) regarding all admissions to gynecological EDs during November 1 to 30, 2019, and March 11 to April 9, 2020 (lockdown period). Results: A total of 691 women (mean age 38.3 \ub1 14.3 years) who were admitted to the gynecological EDs were included. The relative decrease in women evaluated from March 11 to April 9, 2020, was 1256.6% (95% confidence interval [CI] 52.2\u201361.1). Time spent in the ED was also significantly shorter during this period (P=0.02) in comparison to November 1 to 30, 2019. The most evident decrease was observed for pelvic pain ( 1268.9% [95% CI 60.3\u201376.7]; 1291 cases). The management of women suggests a more effective use of the ED, with higher rates of hospitalization (P=0.001) and recourse to emergent surgeries (P=0.005) and lower rates of discharge to home (P=0.03). Conclusion: The COVID-19 lockdown greatly reduced the rate of admission to gynecological EDs, but the real emergencies were filtered from the more deferrable ones

Diastereoselective additions of organometallic reagents to (SFc)-2-p-tolylsulfanylferrocene carboxyaldehyde and to (SFc)-2-p-tolylsulfanyl ferrocenyl imines. Synthesis of new central and planar chiral ferrocenyl alcohols and amines

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Epigenetics, stem cells, and autophagy: Exploring a path involving miRNA

MiRNAs, a small family of non-coding RNA, are now emerging as regulators of stem cell pluripotency, differentiation, and autophagy, thus controlling stem cell behavior. Stem cells are undifferentiated elements capable to acquire specific phenotype under different kind of stimuli, being a main tool for regenerative medicine. Within this context, we have previously shown that stem cells isolated from Wharton jelly multipotent stem cells (WJ-MSCs) exhibit gender differences in the expression of the stemness related gene OCT4 and the epigenetic modulator gene DNA-Methyltransferase (DNMT1). Here, we further analyze this gender difference, evaluating adipogenic and osteogenic differentiation potential, autophagic process, and expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived from males and females. These miRNAs were selected since they are involved in OCT4 and DNMT1 gene expression, and in stem cell differentiation. Our results indicate a difference in the regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in male WJ-MSCs as compared to female cells. Moreover, no difference was detected in the expression of the two-differentiation regulating miRNA (miR-145 and miR-185). Taken together, our results highlight a different behavior of WJ-MSCs from males and females, disclosing the chance to better understand cellular processes as autophagy and stemness, usable for future clinical applications

The role of HLA-B27 molecules in the pathogenesis of ankylosing spondylitis

Ankylosing Spondylitis (AS) is characterised by the strongest association with an HLA antigen ever described for any disease. It represents therefore the ideal model for the understanding of the link between immune-mediated diseases and the HLA system. The role of HLA-B27 in the pathogenesis of AS will be discussed focusing on the recently described higher expression of these molecules in patients with AS compared with healthy controls

Postpartum ovarian vein thrombosis after cesarean delivery: a case report

<p>Abstract</p> <p>Introduction</p> <p>Postpartum ovarian vein thrombosis is an uncommon complication; incidence varies between 0.002% and 0.05%. It most often occurs during the 2–15 days following delivery.</p> <p>Case presentation</p> <p>A 22-year-old pregnant woman at term presented to hospital with uterine contractions, abdominal pain, nausea and vomiting. After delivery an ovarian vein thrombosis was diagnosed.</p> <p>Conclusion</p> <p>Low-molecular weight heparin with broad-spectrum antibiotics are the accepted therapy in non-complicated cases of postpartum ovarian vein thrombosis.</p