Generation of two hiPSC lines, (DMBi003-A and DMBi004-A), by reprogramming peripheral blood mononuclear cells and fibroblast-like synoviocytes from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects joints but should be considered as a syndrome that also includes extra-articular manifestations and comorbidities. Human-derived induced pluripotent stem cells (hiPSCs) and their differentiated derivatives may be of special interest in the investigation of complex pathophysiology of RA. In this study, we demonstrate and compare the generation of hiPSC from peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients. Application of three-dimensional cardiac microtissues constructed from RA specific iPSC-derivatives may be a useful approach to investigate RA comorbidities and cardiac protection or toxicity of anti-rheumatic drugs.

Usefulness of noninvasive diagnostic procedures for assessment of methotrexate hepatotoxicity in patients with rheumatoid arthritis.

Methotrexate (MTX) is recommended as a first-line treatment for rheumatoid arthritis (RA). There are no strict guidelines regarding monitoring for liver damage in RA patients. This study aimed to evaluate noninvasive diagnostic procedures in assessing liver fibrosis in RA patients. Ninety-six RA patients were recruited for this study. The procollagen III N-terminal peptide (PIIINP) serum level was measured in all patients. The Enhanced Liver Fibrosis score (ELF-1) was calculated for 82 patients. Transient elastography (TE) was performed in 91 patients, those examined were divided into two groups: a study and control group, comprising patients with and without risk factors for liver fibrosis, respectively. The TE result correlated only with the body mass index-BMI (p < 0.05); there was no correlation with the cumulative MTX dose (p = 0.33). The TE result was significantly higher in those with risk factors for liver fibrosis than in those without risk factors (TE result > = 7.1 kPa 28/42 vs 13/41, HR = 2.103, Mann-Whitney U test, approximately 0.02). There was a positive correlation between the PIIINP level and body weight (p = 0.028), cumulative MTX dose (p = 0.007), RA activity (p = 0.028) and diabetes mellitus (DM) (p = 0.001). There was a positive correlation between the ELF-1 score and age (p < 0.001), cumulative MTX dose (p = 0.007) and RA activity (p < 0.001). The PIIINP level and ELF-1 score are not organ specific, and readings may vary depending on RA activity. TE is organ specific and can be performed by a skilled ultrasonographer might be useful to assess actual liver condition.

Breast Cancer and Arsenic Anticancer Effects: Systematic Review of the Experimental Data from In Vitro Studies.

Arsenic is a known environmental carcinogenic agent. However, under certain circumstances, it may exert anticancer effects. In this systematic review, we aim to provide information on recent developments in studies on arsenic antitumor effects in breast cancer. Research included in the review refers to experimental data from in vitro studies. The data was collected using search terms "breast cancer," "arsenic," and "anticancer" (25.05.2021). Only studies in English and published in the last 10 years were included. The search identified 123 studies from the EBSCOhost, PubMed, and Scopus databases. In the selection process, thirty full-texts were evaluated as eligible for the review. The literature of the last decade provides a lot of information on mechanisms behind anticancer effects of arsenic on breast cancer. Similar to arsenic-induced carcinogenesis, these mechanisms include the activation of the redox system and the increased production of free radicals. Targets of arsenic action are systems of cell membranes, mitochondria, pathways of intracellular transmission, and the genetic apparatus of the cell. Beneficial effects of arsenic use are possible due to significant metabolic differences between cancer and healthy cells. Further efforts are needed in order to establish modes and doses of treatment with arsenic that would provide anticancer activity with minimal toxicity.

The effect of polyunsaturated fatty acids on cardiovascular risk factors and urinary mercury in workers employed at electrolytic production of chlorine.

OBJECTIVES: While inorganic mercury is being gradually withdrawn from industry, environmental exposure to mercury is recognized as one of the greatest present toxicological problems. The aim of this study was to evaluate the effect of polyunsaturated fatty acids (PUFAs) supplementation on selected cardiovascular risk factors and the urinary mercury (Hg-U) concentration in workers occupationally exposed to mercury vapor. MATERIAL AND METHODS: Overall, 38 workers of an electrolyzer hall (Hg-U: 46.6±35.7 µg/g creatinine) and a control group of 60 employees not exposed to Hg (Hg-U: 4.3±15.5 µg/g creatinine) were included in a clinical cross-over study. Clinical and laboratory tests were carried out 4 times: before and after a 3-month period of PUFAs supplementation (1000 mg daily), then after a 3-month break, and then after another 3-month period of PUFAs supplementation. RESULTS: The baseline heart rate (HR) and serum triglyceride levels were higher in the Hg-exposed workers than in the controls, whereas systolic blood pressure (SBP) and cholesterol (C) levels exceeded normal values in both groups. There was a positive correlation between high-density lipoprotein 3 cholesterol (HDL3-C) and Hg-U levels. The PUFAs use was associated with a decrease in both HR and SBP. After the first stage of supplementation, a decrease in the Hg-U concentration was observed. In a multivariate logistic regression model, decreases in Hg-U were associated only with exposure to mercury; ORΔHg = 0.562 (95% CI: 0.323-0.979), p < 0.042. After the second 3-month period of PUFAs supplementation, a significant association between HDL3-C and a Hg-U decrease was shown: ORHDL3 = 1.222 (95% CI: 1.01-1.46), p < 0.033. CONCLUSIONS: In the workers exposed to mercury vapor, PUFAs supplementation led to some beneficial effects on HR and SBP. The first stage of supplementation was associated with a decrease in Hg-U in which HDL3 metabolism probably plays an important role. Int J Occup Med Environ Health. 2021;34(4):551-64.

Urinary leucine aminopeptidase 3 in population environmentally exposed to airborne arsenic.

INTRODUCTION: Environmental arsenic contamination is a major toxicological problem worldwide due to its carcinogenic and nephrotoxic potential. AIM: The purpose of this observational study was to determine the suspected association between urinary arsenic (uAs) and urinary leucine (or leucyl) aminopeptidase 3 (uLAP3) to evaluate uLAP3 as a candidate biomarker of exposure to airborne arsenic. MATERIALS AND METHODS: A total of 918 adults occupationally and/or environmentally exposed to airborne arsenic were enrolled in the study. Baseline information (age; sex; history of smoking; alcohol, fish and seafood consumption) was gathered. Total uAs concentrations [µg/L] of 918 subjects, as well as the sum of arsenic species (ΣiAs) in 259 subjects, were obtained. Urinary LAP3 was measured by an immune-enzymatic assay using an ELISA kit. Urinary creatinine concentration was assessed with the IB/lAB/1289 research protocol (version II, 2015-09-17). The values of uAs and uLAP3 were recalculated per unit of creatinine. The association between uAs and uLAP3 was assessed using a logistic regression model adjusted for confounders. RESULTS: The study identified a positive correlation between the logarithm of uAs and the logarithm of uLAP3 in the study population (r = 0.1737, p < 0.0000) and between urinary creatinine and uLAP3 concentration not adjusted for creatinine level (r = 0.1871, p < 0.001). In the logistic regression model, there was also an association between increased (≥15 µg/L) uAs and decreased (below the 25th quartile) uLAP3 [OR uLAP3 = 1.22 (95% CI 1.03 to 1.44, p < 0.02)]. CONCLUSIONS: These data suggest that urinary LAP3 may be a potential biomarker of arsenic exposure, which warrants further study.

Imaging in polymyalgia rheumatica: which technique to use?

Polymyalgia rheumatica (PM) is an inflammatory rheumatic disorder characterised by pain and stiffness, mainly in the neck, shoulders, and pelvic girdle and possible association with giant cell arteritis. Currently, there is no diagnostic gold standard for PM, however, an extensive assessment of patients' inflammatory status aided by imaging evaluation is crucial for disease stratification. Many imaging techniques study PM features and their possible complications or associations with giant cell arteritis: radiography, ultrasound, scintigraphy, magnetic resonance imaging, and positron emission tomography/computed tomography. Each one has different advantages and disadvantages. The aim of this review is to clarify the current uses of imaging in PM for diagnosis and follow-up through a literature review of the last 10 years.

Pathophysiology of hyperuricemia and its clinical significance - a narrative review.

Hyperuricemia, i.e. increased serum uric acid (UA) concentration, is a common problem in clinical practice. While there are clear guidelines concerning management of symptomatic hyperuricemia in acute conditions such as gout, urolithiasis or acute urate nephropathy, less is known about their secondary prevention. Moreover, despite the ongoing debate on the role of UA in the pathogenesis of chronic kidney disease, hypertension, cardiovascular disease and heart failure, the management of asymptomatic hyperuricemia in patients with these chronic conditions is still mainly up to physicians' judgement. Individual considerations should always be taken into account when prescribing urate-lowering therapy. In this narrative review study, we attempt to present current trends concerning treatment of patients with either symptomatic or asymptomatic hyperuricemia in the light of the available knowledge on the role of hyperuricemia in the development of gout, renal, cardiovascular and other diseases.

Relapsing polychondritis - analysis of symptoms and criteria.

OBJECTIVES: Relapsing polychondritis (RP) is a rare disease characterised by recurrent inflammation of the cartilaginous structures and proteoglycan-rich organs. The aim of this case series study is to share the 10-year clinical experience of our department in diagnosing RP patients in the context of data from available published studies. MATERIAL AND METHODS: A retrospective case analysis of 10 patients with symptoms of RP, hospitalised at the Department of Rheumatology and Internal Diseases of Wroclaw University Hospital between January 2008 and December 2018. RESULTS: Nine out of 10 patients fulfilled at least one of the three sets of the diagnostic criteria. The mean age (±standard deviation) at diagnosis was 54.4 ±13.3 years and ranged from 32 to 73 years. The symptoms suggestive of the RP diagnosis were mainly inflammation of the pinna (in 80% of patients) and laryngeal stenosis (in 20% of patients). The mean age at which initial symptoms were observed was 52.3 ±12.0 years and ranged from 31 to 69 years. Auricular chondritis was the first manifestation of the disease in 40% of cases (two women and two men) laryngeal chondritis in 20%, nasal chondritis in 10%, and bronchial stenosis in 10%. Other initial symptoms were polyarthritis, which was present in 10% of cases (male) and general symptoms observed in 10%. CONCLUSIONS: A thorough analysis of the entire medical history with specific questions about the occurrence of the manifestations of the disease in the past leads to the diagnosis of RP. The RP also should be considered in differential diagnosis of respiratory track narrowings. It is very useful to apply the three sets of criteria simultaneously in the diagnostic process.

Immunohistochemical and ultrastructural analysis of sporadic inclusion body myositis: a case series.

Sporadic inclusion body myositis (s-IBM) is a progressive, skeletal muscle disease with poor prognosis. However, establishing the final diagnosis is difficult because of the lack of clear biomarkers in the blood serum and very slow development of clinical symptoms. Moreover, most other organs function normally without any disturbance. Here, in patients with this untreatable disease, we have underlined the importance of immunohistochemical and ultrastructural assessment of skeletal muscle in patients diagnosed with s-IBM. The goal of this study was to identify the distribution of specific antigens and to determine morphological features in order to localize pathological protein aggregates, rimmed vacuoles, and loss of myofibrils, which are key elements in the diagnosis of s-IBM. All studied patients were between 48 and 83 years of age and were hospitalized in the Department of Rheumatology and Internal Medicine between 2011 and 2016. Anamneses revealed an accelerated progression of muscle atrophy, weakness of limb muscles, and difficulties with climbing stairs. Based on histopathology and transmission electron microscopy examination, inflammatory infiltrations consisting of mononuclear cells, severe atrophy and focal necrosis of myofibers, splitting of myofilaments, myelinoid bodies and rimmed vacuoles were observed. Primary antibodies directed against CD3, CD8, CD68, cN1A, beta-amyloid, Tau protein and apolipoprotein B made it possible to identify types of cells within infiltrations as well as the protein deposits within myofibers. Using a combination of immunohistochemistry and electron microscopy methods, we were able to establish the correct final diagnosis and to implement a specific treatment to inhibit disease progression.

Interstitial lung disease in systemic sclerosis: challenges in early diagnosis and management.

Interstitial lung disease (ILD) is a group of lung diseases characterized by thickening of the interstitium surrounding pulmonary alveolar walls. It is related to specific radiographic features in lung imaging and/or the presence of restrictive disorders in pulmonary function tests (PFTs). ILD is one of the leading causes of death in systemic sclerosis patients. Major risk factors of ILD associated with SSc (SSc-ILD) include male sex, diffuse type of cutaneous SSc and presence of anti-Scl-70 antibodies. SSc-ILD is challenging to diagnose at an early stage as the symptoms are non-specific. The greatest risk of its development is during the 4-5 years after the initial diagnosis of systemic sclerosis. Clinical vigilance at the time, including regular pulmonary function tests and/or high-resolution com-puted tomography (HRCT), is needed. The aim of this paper is to summarize the current knowledge on early diagnostic methods and progression risk factors for SSc-ILD.

The role of diet in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic connective tissue disease which develops in the course of an autoimmune inflammatory process triggered by environmental factors in a genetically predisposed person. One of the environmental factors is the diet. RA patients' adherence to a healthy diet remains low, despite plentiful data confirming positive effects of some foods, e.g. fish rich in n-3 polyunsaturated fatty acids (PUFAs), as well as the negative influence of unhealthy eating patterns, such as high consumption of fats and sugars, on RA incidence, activity and treatment response. In this review, we present current knowledge on the role of diet in rheumatoid arthritis, including dietary factors' preventive/promoting influence on RA development, as well as their impact on RA activity. We hope this article will aid and encourage clinicians to recommend a relevant dietary intervention to their RA patients.

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia.

BACKGROUND: Linseed oil has cardio-protective effects. However, its antihypertensive action has not yet been well characterised. AIM: The primary purpose of the study was to evaluate the effect of short-term dietary supplementation with linseed oil on blood pressure (BP) and lipid metabolism in patients with mild hypercholesterolaemia. The secondary aim was to assess the effect of linseed oil on nitric oxide pathway and selected serum trace metals. METHODS: 150 volunteers: 43 men (49.9 ± 11.5 years) and 107 women (53.2 ± 10.3 years), diagnosed with mild hyper-cholesterolaemia, were assessed prospectively for BP and lipid levels, before and after lipid-lowering diet plus linseed oil supplementation at a dose of 15 mL daily for four weeks (study groups) or four-weekly lipid-lowering diet (control group). Multivariate logistic regression analysis was used to determine the effect of linseed oil on BP after adjustment for age, sex, height, body weight, body mass index, smoking status, and alcohol consumption. RESULTS: Supplementation with linseed oil significantly decreased low-density lipoprotein (LDL)- and non-high-density lipo-protein (HDL) cholesterol, and increased HDL- and HDL3- cholesterol levels. Additionally, linseed oil decreased diastolic BP in men (95% confidence interval [CI]: -6.0 to -1.1, p < 0.006), whereas in women linseed oil reduced (p < 0.001) systolic BP (-3.6 mmHg; 95% CI: -5.8 to -1.5) as well as diastolic BP (-4 mmHg; 95% CI: -5.8 to -2.1). Women with higher BP displayed an increase in serum L-arginine level (p < 0.01). In the logistic regression model oil consumption was associated with a decrease in mean BP (adjusted odds ratio 3.85; 95% CI 1.32-11.33). CONCLUSIONS: Our findings confirm the benefit of short-term linseed oil use in mild hypercholesterolaemia, particularly in patients with increased blood pressure.

Postprandial decrease in LDL-cholesterol in men with metabolic syndrome.

BACKGROUND: In some epidemiological studies, blood lipids are determined at non-fasting state, which may impact cardiovascular risk estimation. The aim of this study was to evaluate postprandial LDL-C changes in men with newly diagnosed metabolic syndrome (MetSy). METHODS: 36 male patients were examined: 12 men with and 24 men without MetSy. The fat tolerance test was performed before and after a three-month hypolipidemic treatment. Serum lipids were measured using routine methods, lipid peroxides (LPO) colorimetrically, apolipoproteins A-I, B, and hsCRP immunoturbidimetrically. RESULTS: The postprandial increase in triglycerides was associated with a decrease in LDL-C and a small decrease in apo B. In men with MetSy, the mean change in LDL-C (-19.5 ± 2.3 mg/dl) was greater than in healthy men (-5.7 ± 3.8 mg/dl). All lipid changes (ΔTG, ΔLDL-C and ΔLPO) were linearly dependent on the postprandial non-LDL-cholesterol. After three months of hypolipidemic treatment, in all men with MetSy, the apoB/apoA-I ratio remained the same as before the therapy. CONCLUSION: In men diagnosed with MetSy, postprandial decreases in LDL-cholesterol may cause underestimation of cardiovascular risk. After three months of hypolipidemic treatment, there was only a partial reduction in this risk, as the apoB/apoA-I ratio remained the same.