Circulating levels of hypoxia-inducible factor-1α and miR-210 are associated with photosensitivity in systemic lupus erythematosus patients

Background: miR-210, a key HypoxamiR, regulates the hypoxia and inflammation-linked hypoxia. Systemic lupus erythematosus (SLE), a chronic autoimmune disease, responsible for many pathological disorders, including photosensitivity. Objective: Finding the correlation between the circulating miR-210/HIF-1α levels and photosensitivity in SLE patients and other SLE-associated pathological complications, in a single-center case control study. Methods: Study population of 104 SLE Egyptian patients with photosensitivity, 32 SLE patients without photosensitivity, and 32 healthy subjects. SLE activity was assessed for all patients by SLE Disease Activity Index (SLEDAI). The clinical complications/manifestations and the hematological/serological analyses were recorded. HIF-α concentration was investigated by ELISA and miR-210 expression was analyzed by qRT-PCR. Results: The results revealed that circulating miR-210 was significantly increased in SLE/photosensitivity than SLE and controls. The additional occurrence of malar rash, oral ulcers, renal disorders or hypertension resulted in a higher expression of miR-210. SLEDAI activity status showed no effect on miR-210. Erythrocyte sedimentation rate, white blood cells, hemoglobin, platelets, the patients age and the disease duration were positively correlated with circulatory miR-210. HIF-α concentration was significantly induced in SLE/photosensitivity than SLE and controls. In SLE/photosensitivity, presence of renal disorders and hypertension resulted in highest HIF-α concentrations. A strong positive correlation was recorded between HIF-α concentration and circulatory miR-210 in SLE/photosensitivity patients (r = 0.886). Conclusion:: The dysregulation of circulating miR-210/ HIF-1α levels in SLE/photosensitivity‎ patients is controlled by the presence of additional pathological complications and supposed that hypoxia pathway might interact positively with the pathogenesis and illness progress of SLE.

Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis

Background The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. Purpose The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. Research Design This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. Results SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls ( p<0.01) and increased in LN more than non-LN group ( p<0.001). SOX2 significantly decreased in patient groups compared to controls ( p<0.001), and was more in LN compared to non-LN group ( p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups ( p<0.001). Conclusion miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P &lt;0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P &lt;0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P &lt;0.05), shortened colonic length (P &lt;0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P &lt;0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P &lt;0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P &lt;0.05), DAI (P &lt;0.05), colonic length and enterocyte apoptosis (P &lt;0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P &lt;0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

Dietary Alaska Pollock Protein Attenuates the Experimental Colitis Induced by Dextran Sulfate Sodium via Regulation of Gut Microbiota and Its Metabolites in Mice

Protein derived from fish has not only nutritional properties but also health-promoting properties. Few studies have examined the effect of dietary Alaska pollock protein (APP) on the anticolitis effect reported to be associated with metabolic syndrome (MetS). This study investigated the effect of APP intake on colitis symptoms, gut microbiota, and its metabolites in the experimental colitis mouse model induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were divided into three groups: (1) DSS-untreated mice fed an American Institute of Nutrition (AIN) 93G diet (protein source is casein), (2) DSS-treated mice fed an AIN93G diet, and (3) DSS-treated mice fed an APP diet. After the mice were fed the diets for 21 days, experimental colitis was induced by three cycles of 2% DSS administration for 5 days followed by washouts over the course of 5 days. APP-reduced body weight loss increased the disease activity index, and elevated spleen weight and alleviated colon length shortening and colonic tissue damage. Furthermore, APP altered the structure and composition of the microbiota and short-chain fatty acids in feces. Since APP intake alleviates experimental colitis induced by DSS administration through alterations in the gut microbiota and its metabolites, we deduced that APP would inhibit MetS progression via colitis suppression.

Protective Effect of Probiotics Isolated from Traditional Fermented Tea Leaves (Miang) from Northern Thailand and Role of Synbiotics in Ameliorating Experimental Ulcerative Colitis in Mice

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.

Salivary anti-nuclear antibody (ANA) mirrors serum ANA in systemic lupus erythematosus

Objectives To assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations. Methods Saliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated. Results Salivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p < 0.001). Among ANA-positive samples, 80.85% exhibited a nuclear ANA pattern, and 42.55% exhibited a cytoplasmic ANA pattern. Salivary IgG-ANA, IgA-ANA, and IgM-ANA levels, as assayed by ELISA, were significantly increased in both active and less active SLE patients compared with healthy controls, and levels of each isotype were significantly correlated with serum ANA titer. Salivary IgM-ANA levels correlated with the physician global assessment (PGA), SLE disease activity index (SLEDAI), and negatively with serum C3 and C4. Salivary IgG-ANA also correlated with erythrocyte sedimentation rate (ESR), SLEDAI, and negatively with serum C3. Conclusion Salivary ANA levels correlate with serum ANA titer, and salivary IgM-ANA and IgG-ANA correlate variably with PGA, SLEDAI, ESR and complement levels. These findings underscore the potential of using salivary ANA and ANA isotypes as surrogates for serum ANA, particularly for future point-of-care applications since saliva is easier to obtain than blood.

Immunogenicity of BNT162b2 mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis on TNF inhibitors

BackgroundScanty data on the immunogenicity of the BNT162b2 vaccine in patients with psoriatic arthritis (PsA) on Tumor Necrosis Factor inhibitors (TNFi) have been published.ObjectiveTo investigate the humoral response to BNT162b2 vaccination patients with PsA on TNFi, comparing immunogenicity with healthy controls.MethodsForty patients with classified PsA on TNFi undergoing vaccination with the BNT162b2 mRNA SARS-CoV-2 vaccine (BioNTech/Pfizer) were enrolled. Fifteen days after the second shot, serum IgG levels against SARS-CoV-2 (Abbott ARCHITECT i2000SR, positivity cut-off 50 AU/mL) were assayed in all patients. Clinimetrics and treatment data were gathered. TNFi treatment was not discontinued throughout the whole period, whereas methotrexate (MTX) was discontinued for 1 week after each shot in those on combination therapy. Sera from healthcare professionals were considered as healthy controls for 1:1 propensity score matching; any of them was taking medication.Student’s t-test and logistic regression were used for investigating differences in immunogenicity between groups and predictors of antibody response.ResultsClinical Disease Activity Index did not change before and after vaccination (7.06±5.23 to 7.10±5.27, p=0.92).Patients with PsA achieved a positive anti-SARS-CoV-2 IgG level with a mean (±SD) of 13794.44±15 815.42 AU/mL. Although lower, the antibody level was not significantly different from matched controls (19227.4±11.8460.45 AU/mL, p=0.08). In the overall sample, those on MTX (12/80, 15%) had a trend toward lower immune response (p=0.07); glucocorticoid therapy (11/80, 13.8%) predicted lower antibody levels (p=0.04).ConclusionsContinuing TNFi in patients with PsA throughout the vaccination did not hamper immunogenicity.

Clinical characteristics and disease patterns of patients with relapsing polychondritis: a retrospective cohort

Background Relapsing polychondritis (RP) is a rare autoimmune disease affected various cartilage, Patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to allocated RP patients into two subgroups by chest computed tomography (CT) and compare the clinical features and disease patterns of each group.Methods A retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Patients were divided into two groups: respiratory involvement group and non-respiratory involvement group according to chest CT.Results In our study, respiratory involvement found in 59.7% (n=43) patients, which had higher rate of costochondritis, fewer rate of Inflammatory eye disease and auricular chondritis than those in non-respiratory involvement. Compared with non-respiratory involvement subgroup, The incidence of pulmonary infection marginally increased and those inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, further subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Finally, 5 patients died during the follow-up in this cohort with a median follow-up time of 6 years (range 3-8 years).Conclusion 59.7% of patients had respiratory involvement according to chest CT findings in our cohort, which had a strong inverse relationship between respiratory and auricular, ocular involvement. Increase inflammatory indexes were not correlated with pulmonary infection, suggesting that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not found significant in two subgroups.

Severity of the acute phase response in experimental ulcerative colitis under conditions of the use of vitamin D3 in a novel rectal suppository

Цель - изучение влияния витамина D3 в составе оригинальных ректальных суппозиториев на выраженность острофазового ответа при экспериментальном язвенном колите Методика. Эксперимент выполнен на 49 половозрелых крысах-самцах Wistar. Язвенный колит (ЯК) моделировали двухэтапным (накожным, а затем ректальным) применением 3% спиртового раствора оксазолона. Оригинальные суппозитории на основе смеси полиэтиленгликолей массой 300 мг, содержащие 1500 ME витамина D3, вводили per rectum каждые 12 ч в течение 6 сут. Исследования проводили на 2-е, 4-е и 6-е сут заболевания. Клиническую картину оценивали по адаптированной для крыс шкале Disease activity index (DAI) с учетом массы тела, консистенции и наличия крови в каловых массах. Количество лейкоцитов и нейтрофилов определяли на гематологическом анализаторе и в мазках крови. Функциональную активность нейтрофилов исследовали по поглощению частиц монодисперсного латекса в спонтанном и индуцированном НСТ-тесте. Концентрацию в сыворотке крови C-реактивного белка (С-РБ), IL-6 и IL-8 определяли с помощью иммуноферментного анализа, экспрессию TNF-α в стенке толстой кишки - иммуногистохимическим методом. Результаты. При экспериментальном ЯК на 2-е, 4-е и 6-е сут наряду с прогрессивным повышением DAI зафиксированы изменения показателей острофазового ответа (ООФ): увеличивается экспрессия в толстой кишке TNF-α с максимальным уровнем на 4-е и 6-е сут, повышается концентрация в сыворотке крови IL-6 с максимальным уровнем на 4-е, IL-8 - на 6-е сут; в сыворотке возрастает концентрация С-РБ максимально на 6-е сут, в крови увеличивается общее количество лейкоцитов, число палочкоядерных и сегментоядерных нейтрофилов с максимальным уровнем на 2-е и 4-е сут. Возрастает поглотительная и НСТ-редуцирующая способность нейтрофилов крови с максимальными значениями на 4-е и 6-е сут эксперимента. Применение при экспериментальном ЯК ректальных суппозиториев с витамином D3 приводит на 4-е и 6-е сут наблюдения к снижению DAI, экспрессии TNF-α в толстой кишке и количества нейтрофилов, на 2-е, 4-е и 6-е сут - к уменьшению концентрации IL-6 и С-РБ в сыворотке, поглотительной и НСТ-редуцирующей способности нейтрофилов крови, на 6-е сут - к снижению концентрации IL-8 в сыворотке и общего количества лейкоцитов в крови. Заключение. Применение при экспериментальном ЯК оригинальных ректальных суппозиториев с витамином D3 приводит к снижению индекса активности болезни. Выраженность клинических проявлений ослабевает по мере снижения экспрессии в кишке TNF-α, снижения концентрации в сыворотке IL-6, количества в крови лейкоцитов и нейтрофилов, уменьшения НСТ-редуцирующей способности нейтрофилов. Aim. To study the effect of vitamin D3 in rectal suppositories on severity of the acute phase response (APR) in experimental ulcerative colitis (UC). Methods. Experiments were performed on 49 mature male Wistar rats. UC was induced by cutaneous followed by rectal applications of a 3% oxazolone alcohol solution. Novel polyethylene glycol suppositories (300 mg) containing 1500 IU of vitamin D3 were injected per rectum every 12 hrs for 6 days. Data were collected on days 2, 4, and 6 of UC. The clinical picture was assessed according to the Disease Activity Index (DAI) scale adapted for rats, taking into account body weight, consistency of, and the presence of blood in the feces. The number of blood leukocytes and neutrophils was determined on a hematological analyzer and in blood smears. The functional activity of neutrophils isolated from the blood was evaluated by the absorption of monodisperse latex particles and with the spontaneous and induced NBT test. Serum concentrations of C-reactive protein (CRP), IL-6 and IL-8 were measured by enzyme immunoassay. TNF-α expression in the colon wall was measured by an immunohistochemical method. Results. The following changes in APR variables along with a progressive increase in DAI were recorded on days 2, 4, and 6. Expression of colon TNF-α increased, with maximal values on days 4 and 6. Serum IL-6 increased and reached a maximal value on day 4; and serum IL-8 increased, with a maximum on day 6. Serum CRP increased, with a maximum on day 6. The total number of blood leukocytes and the number of stab and segmented neutrophils increased, with maximal values on days 2 and 4. The absorption and NBT-reducing ability of blood neutrophils increased, with maximal values on days 4 and 6. The use of rectal suppositories with vitamin D3 in experimental UC resulted in decreases in DAI, colon TNF-α expression, and the number of blood neutrophils on days 4 and 6; decreases in serum concentrations of IL-6 and CRP, and the absorption and NBT-reducing ability of blood neutrophils on days 2, 4, and 6; and decreases in the serum concentration of IL-8 and in the total number of blood leukocytes on day 6. Severity of clinical manifestations was alleviated with decreases in the expression of colon TNF-α, the serum concentration of IL-6, the number of blood leukocytes and neutrophils, and the NBT-reducing ability of neutrophils decreases. Conclusion. Application of the original rectal suppositories with vitamin D3 every 12 hours in experimental UC leads to a decrease in the disease activity index. The severity of clinical manifestations weakens as TNF-α expression, serum IL-6 concentration, number of leukocytes and neutrophils in blood, and decrease of neutrophil NST-reducing capacity decrease.

Repeatability and Reliability of the Rheumatoid Arthritis Foot Disease Activity Index in Spanish Patients: A Transcultural Adaptation

Background: The Rheumatoid Arthritis Foot Disease Activity Index (RADAI-F5) questionnaire, based on five questions, is used to assess the severity of rheumatoid arthritis disease in the foot. Nowadays, RADAI-F5 has been validated in different languages; however a Spanish version was lacking. Therefore, the purpose of this research was to translate and validate the Spanish version (RADAI-F5-es). Methods: A cross-cultural translation of the RADAI-F5 questionnaire was performed from English to Spanish. To validate its use, 50 subjects with rheumatoid arthritis who responded to the translated questionnaire two times in an interval of less than 3 months were selected in order to verify the psychometric properties. Results: Excellent agreement between the two versions according to the Cronbach’s α was shown. Five domains with regards to arthritis activity in foot joint tenderness and swelling, foot arthritis pain, general foot health and joint stiffness were added together to obtain the total score. Excellent retest reliability was shown for the total score. Test/retest reliability was excellent for joint stiffness on awakening and foot arthritis pain domains. There were no significant differences among any domains (p > 0.05). There were no statistically significant differences (p = 0.000) for the mean ± standard deviations (SD) between pre- and post-tests (98.09 ± 15.42) [93.75–102.43] and 97.96 ± 13.88 [94.5–101.86] points, respectively). Bland–Altman plots or clinically pertinent variations were not statistically significantly different. Conclusions: The RADAI-F5-es is considered a valid and strong tool with adequate repeatability in the Spanish community.