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Over the past 30 years, there has been an increasing number of documented human infections associated with the protozoan Lophomonas, specifically Lophomonas blattarum, which is considered a relatively rare infection. These infections are primarily associated with states of immune suppression, including those resulting from corticosteroid therapy. We report a 61-year-old female patient with a 20-year medical history of Systemic lupus erythematosus (SLE) who was admitted due to persistent respiratory symptoms that were unresponsive to treatment. The patient was receiving immunosuppressive therapy for SLE. Upon hospitalization, computed tomography of the lungs revealed the presence of centrilobular nodules exhibiting tree-in-bud patterns, as well as bronchiectasis, predominantly in the middle and lower lobes. Subsequently, the patient underwent bronchoscopy, during which a BAL sample was obtained. Microscopic analysis of the sample indicated the presence of L. blattarum. Clinicians often focus on the primary symptoms of SLE, but they must also consider the risk of severe respiratory complications like lophomoniasis. This condition is critical to address in the management of SLE patients, who are immunosuppressed due to the disease's nature and its treatment.
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BACKGROUND: Pompe disease, a rare autosomal recessive disorder, is caused by mutations in the acid α-glucosidase gene. Pompe disease is a congenital metabolic disorder that affects all organs, particularly the striated muscle and nerve cells. Diagnosis is typically confirmed through enzyme assays that reveal reduced acid α-glucosidase activity. Enzyme replacement therapy utilizing human α-glucosidase is an available treatment option. Timely diagnosis and treatment in the early stages of the disease significantly impact the effectiveness of enzyme replacement therapy in enhancing patient condition. Here, we present a case of a patient with Pompe disease diagnosed 20 years after the onset of clinical symptoms. CASE PRESENTATION: A 38-year-old Iranian Baloch woman referred to our rheumatology clinic with progressive muscle weakness presents with a complex medical history. On mechanical ventilation for 12 years, she has endured fatigue and limb weakness since the age of 16, exacerbated following an abortion at 19. Despite undergoing corticosteroid and azathioprine therapies, the suspected diagnosis of inflammatory myopathy did not yield improvement. Hospitalization at 23 due to respiratory failure post-pregnancy led to her continued reliance on a ventilator. A dried blood spot test indicated reduced GAA enzyme activity, confirming a diagnosis of Pompe disease through genetic testing. Treatment with myozyme for 2 years demonstrated limited efficacy, as the patient experienced improved breathing but no significant overall improvement in limb-girdle muscular weakness. This case underscores the challenges and complexities involved in diagnosing and managing rare neuromuscular disorders like Pompe disease. CONCLUSION: Early intervention with enzyme replacement therapy plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients. It is important to note that treatment during advanced stages of the disease may not yield substantial benefits. Nevertheless, enzyme instability and denaturation due to temperature and neutral pH levels, along with limited delivery to disease-relevant tissues, can pose challenges in treatment. However, timely diagnosis of Pompe disease is paramount for its effective management and improved outcomes.
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Terapia de Reemplazo Enzimático , Enfermedad del Almacenamiento de Glucógeno Tipo II , Fuerza Muscular , Humanos , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Femenino , Terapia de Reemplazo Enzimático/métodos , Adulto , Diagnóstico Precoz , alfa-Glucosidasas/uso terapéutico , alfa-Glucosidasas/genética , Resultado del Tratamiento , Debilidad Muscular/tratamiento farmacológicoRESUMEN
The role of Mycobacterium avium subspecies paratuberculosis (MAP) in triggering rheumatoid arthritis (RA) could be a population-specific phenomenon. This study explored the relationship between MAP and RA using serological and molecular techniques; In this case-control study, 239 Iranian participants, including 120 RA patients and 119 controls, were enrolled. The indirect ELISA was designed to diagnose antibodies against MAP3865c125-133 and Zinc transporter 8 (ZnT8)178-186. The Nested-Polymerase Chain Reaction (PCR) detected MAP in blood; The frequency of MAP in RA patients and controls was 31.9% and 12.5%, respectively (P = 0.002). The antibodies against MAP3865c125-133 and ZnT8178-186 were 42.9% and 37% in RA patients and 14.2% and 11.7% in the controls, respectively (P < 0.0001). Interestingly, positive ELISA results in previously diagnosed (PD) RA were more common than newly diagnosed (ND) RA patients (P < 0.05).; The findings showed a higher frequency of MAP and its antibodies in the RA patients than in the controls. This data indicated MAP as one of RA's predisposing factors. Also, this first report implies the high positivity of MAP in Iranian RA patients.
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Artritis Reumatoide , Mycobacterium avium subsp. paratuberculosis , Paratuberculosis , Animales , Humanos , Mycobacterium avium subsp. paratuberculosis/genética , Estudios de Casos y Controles , Irán/epidemiología , Anticuerpos Antibacterianos , Ensayo de Inmunoadsorción Enzimática , Paratuberculosis/diagnósticoRESUMEN
Background: Systemic sclerosis is an autoimmune disease characterised by endothelial dysfunction and fibrosis of the skin and internal organs. Cardiac involvement during systemic sclerosis can be primary or secondary to pulmonary arterial hypertension and renal pathology. Among the disorders in systemic sclerosis, prolongation of QTc time is also associated with more anti-RNA polymerase III antibodies, longer duration, and severity of disease. Methods: This case-control study was performed on 35 patients with systemic scleroderma who filled in the American Society of Rheumatism (ACR / EULAR criteria) and 35 healthy subjects prior to entering the study. Then, the QTc distance was extracted from the electrocardiogram and calculated using the formula. The measured QTc distance in the electrocardiogram, QTc> 440ms in men and QTc> 460ms in women, was defined as QTc long. The patients and the control group then underwent echocardiography, and changes in QTc interval and their relations with echocardiographic findings were evaluated. Results: The results of this study indicated a significant relationship between QTc distance in patients with scleroderma compared with healthy controls. There was also a significant relationship between QTc and Skin Score of patients. However, there was no significant correlation between QTc distance and age, duration of disease, Anti-Centromere, Anti-Scl70, and pulmonary artery pressure. Conclusion: This study concludes that patients with scleroderma are at high risk for cardiac conduction impairment. The only factor that significantly correlated with QTc was the Skin Score of the patients.
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BACKGROUND/OBJECTIVE: Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients. METHODS: In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs). RESULTS: A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of - 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [- 1.34 to 2.11], 0.04 [- 1.61 to 1.69], and 0.41 [- 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs. CONCLUSION: The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03293108 ; Registration date: 2017-09-19.
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Biosimilares Farmacéuticos , Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Biosimilares Farmacéuticos/efectos adversos , Densidad Ósea , Conservadores de la Densidad Ósea/efectos adversos , Denosumab/efectos adversos , Método Doble Ciego , Femenino , Humanos , Osteoporosis Posmenopáusica/tratamiento farmacológicoRESUMEN
BACKGROUND: End-stage renal disease (ESRD) is a condition in which bone turnover and metabolism is impaired; thus, osteoporosis and low bone density are subsequently inevitable. We aimed to determine bone mineral density (BMD) and biochemical markers, and associated factors in hemodialysis (HD) patients. METHODS: Patients aged 30-70 years undergoing HD between 2015 to 2019 were enrolled in this cross-sectional study. BMD measured by dual energy x-ray absorptiometry (DEXA) and biochemical laboratory tests were assessed in 200 patients undergoing HD. Statistical analysis was based on t test, Pearson, regression and Mann-Whitney tests using SPSS 16. RESULTS: Two hundred patients were investigated. Sixty percent of the patients were female. Mean ± SD of participants' age was 58.6 (±11.63) years and mean ± SD for duration of HD was 45.69 (± 43.76) months. Osteoporosis was found in 48% (n=96) and low bone density in 36% (n=76) of our patients. General osteoporosis was more frequent in those undergoing HD for more than 3 years, although not significantly (P=0.093, odds ratio [OR]=0.37). However, regional osteoporosis in hip and femoral neck, but not spine vertebrae, were significantly higher after three years of HD (P=0.036, OR=0.27; P=0.042, OR=0.27; and P=0.344, OR=0.56, respectively). Increased body mass index (BMI) correlated negatively with osteoporosis (P=0.050). CONCLUSION: With increasing age and duration of HD, BMD decreases. Higher BMI was associated with higher bone mass density. Bone density assessment seems to be necessary in patients undergoing HD.
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Densidad Ósea , Diálisis Renal , Absorciometría de Fotón , Anciano , Estudios Transversales , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Irán/epidemiología , Vértebras Lumbares , Persona de Mediana EdadRESUMEN
The safety of teriparatide has been studied in various phase III and phase IV trials. However, a postmarketing study of the biosimilar of teriparatide, CinnoPar®, has not been conducted on Iranian patients. This was a phase IV study conducted on osteoporotic patients who received an Iranian teriparatide biosimilar with a dose of 20 µg daily. The primary outcome of this study was to monitor for adverse events (AEs). Effectiveness as the secondary outcome was measured using the EQ-5D quality-of-life questionnaire and back pain Visual Analogue Scale (VAS) score. Among 193 analyzed patients between September 2015 and March 2019, the most common AEs were hypercalcemia (4%), nausea, and pain (3%). No deaths, serious AEs, or other significant AEs occurred in this study. The mean EQ-5D scores decreased after the course of the treatment from 2.3 ± 0.66 at the baseline to 2 ± 0.66. The mean back pain VAS scores also decreased from 4.9 ± 3.6 at baseline to 1.8 ± 2.1 at the end of the study. Both changes were statistically significant (p < 0.001). Consistent with the findings of previous studies and the drug monograph, no new safety concern was observed with this biosimilar teriparatide, and the drug was effective based on the VAS score and EQ-5D in osteoporotic patients.
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The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab's safety and efficacy profile in SSc patients. A systematic online query was performed in PubMed, Scopus, Web of Science, and Embase. The studies on the application of rituximab for patients with SSc were reviewed comprehensively for over two years. In terms of efficacy profile, mRSS, MS, LVEF, sPAP, FVC, DLCO, TLC, FEV, DAS, severity activity, HAQ-DI and SF36 were assessed for organ involvement and quality of life. The level of biological and immunological markers was also evaluated in SSc patients treated with RTX. In total, 24 studies met the criteria. Although they did not have a high quality, they were free from heterogeneity and publication bias. The pooled results revealed a long-term improvement in mRSS and MS. HAQ-DI was improved to 0.78 after 12 months, and DAS was significantly reduced to 0.33, 0.23, and 0.24 following 6, 12, and 24 months of treatment, respectively (p = 0.00 for both parameters). The rest of the parameters remained stable over time in patients with SSc. The pooled analysis of these patients demonstrated that the induction of death, cancer, infection, and infusion were 9, 5, 18 and 10%, respectively. Based on the pooled results of this meta-analysis, rituximab improves skin score and disease indices and stabilizes organ involvement in SSc patients. Rituximab seems to possess reasonable safety, similar to previous data from other autoimmune diseases.
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Esclerodermia Localizada , Esclerodermia Sistémica , Humanos , Calidad de Vida , Rituximab/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , PielRESUMEN
The adsorption behavior of the amino acid, glycine (Gly), via the carboxyl, hydroxyl, and amino groups onto the surfaces of Al12N12 and Al16N16 fullerene-like cages were computationally evaluated by the combination of density functional theory (DFT) and molecular docking studies. It was found that Gly can chemically bond with the Al12N12 and Al16N16 fullerene-like cages as its amino group being more favorable to interact with the aluminum atoms of the adsorbents compared to carboxyl and hydroxyl groups. Oxygen and carbon doping were reported to reduce steric hindrance for Glycine interaction at Al site of Al12ON11/Gly and Al12CN11/Gly complexes. Interaction was further enhanced by oxygen doping due to its greater electron withdrawing effect. Herein, the Al12ON11/Gly complex where two carbonyl groups of Gly are bonded to the aluminum atoms of the Al12N12 fullerene-like cage is the most stable interaction configuration showing ∆adsH and ∆adsG values of -81.74 kcal/mol and -66.21 kcal/mol, respectively. Computational studies also revealed the frequency shifts that occurred due to the interaction process. Molecular docking analysis revealed that the Al12N12/Gly (-11.7 kcal/mol) and the Al12ON11/Gly (-9.2 kcal/mol) complexes have a good binding affinity with protein tumor necrosis factor alpha (TNF-α). TNF-α was implicated as a key cytokine in various diseases, and it has been a validated therapeutic target for the treatment of rheumatoid arthritis. These results suggest that the Al12N12/Gly complex in comparison with the Al16N16/Gly, Al12ON11/Gly, and the Al12CN11/Gly complexes could be efficient inhibitors of TNF-α.
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Fulerenos , Glicina , Adsorción , Antiinflamatorios/farmacología , Simulación del Acoplamiento MolecularRESUMEN
Defect in T lymphocyte homeostasis could implicate initiation and development of rheumatoid arthritis (RA). Since PD-1 plays a key role in the regulation of T lymphocytes, its expression pattern in various CD8+ T cell subsets could be so effective in RA pathogenesis. Here, we investigated the expression of PD-1 and CXCR3 on CD8+CD28- T cells in association with the IFN-γ levels in patients with RA. A total of 42 RA patients, including 10 newly-diagnosed (ND) and 32 relapsed (RL) cases and also 20 healthy donors were enrolled. Phenotypic characterization of CD8+ T cells derived from peripheral blood (PB) and synovial fluid (SF) was performed by flow cytometry. The plasma and SF IFN-γ levels were also assessed by ELISA. The frequency of CD8+CD28- T cells showed no significant differences between patients and controls while its higher levels were observed in PB, versus SF of RL patients. Relapsed patients also showed higher CXCR3 and especially PD-1 expression on their CD8+CD28- T cells. The IFN-γ concentration was elevated in SF of ND patients while its plasma level was significantly lower in RL subgroup than controls. Although PD-1 could induce immune suppression in effector T cells, it is upregulated during inflammation and its overexpression on CD8+CD28- T cells within inflammatory synovium is associated with severity of disease in our cohort of RA patients.
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Artritis Reumatoide/metabolismo , Antígenos CD28/metabolismo , Linfocitos T CD8-positivos/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Membrana Sinovial/metabolismo , Sinovitis/metabolismo , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Biomarcadores/metabolismo , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Receptores CXCR3/metabolismo , Recurrencia , Membrana Sinovial/inmunología , Sinovitis/diagnóstico , Sinovitis/inmunologíaRESUMEN
BACKGROUND: Relapses and flares with delayed wound healing are among the main symptoms of systemic lupus erythematosus (SLE), a rheumatic autoimmune disease. The orientation of immune responses in SLE disease depends on the function of the population of macrophages. This study investigated the effect of indole-3-carbinol (I3C) on transcriptional profiling of macrophage-derived monocytes (MDMs) in four stages of the wound-healing process. METHODS: In the first phase of study, MDMs were generated from peripheral blood mononuclear cells of three new SLE cases (unmedicated) and two healthy controls. The cases and controls were then divided into I3C treated and untreated groups after 24 hours of exposure to I3C. Single-end RNA sequencing was performed using an Illumina NextSeq 500 platform. After comprehensive analysis among differentially expressed genes, CDKN1A, FN1 and MMP15 were validated by quantitative real-time polymerase chain reaction as upregulated ranked genes involved in wound-healing stages. RESULTS: The RNA sequencing analysis of treated cases and treated controls versus untreated cases and untreated controls (group 3 vs. group 4) revealed upregulation of various genes, for example: C1S, C1R, IGKV1-5, IGKV4-1, SERPING1, IGLC1 and IGLC2 in coagulation; ADAM19, CEACAM1 and CEACAM8 in M2 reprogramming; IRS1, FN1, THBS1 and LIMS2 in extracellular matrix organization; and STAT1, THBS1 and ATP2A3 in the proliferation stage of wound healing. CONCLUSIONS: The results showed that treatment with I3C could modulate the gene expression involved in wound healing in SLE cases and healthy controls.
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Indoles/farmacología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/genética , Macrófagos/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Adulto , Estudios de Casos y Controles , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Fibronectinas/genética , Perfilación de la Expresión Génica , Humanos , Indoles/uso terapéutico , Macrófagos/metabolismo , Masculino , Metaloproteinasa 15 de la Matriz/genética , Persona de Mediana Edad , Análisis de Secuencia de ARN , Transducción de Señal/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Inflammation is a common feature of type 2 diabetes (T2D). Inflammatory cytokines increase in patients with type 2 diabetes, metabolic syndrome, and heart disease. Various types of cells can produce inflammatory cytokines and then release them into the bloodstream, where their complex interactions with target tissues raise a tissue-specific immune response. This review focused on C-reactive protein (CRP), tumor necrosis factor (TNF)-α as an inflammatory cytokine, and adiponectin produced by adipose tissues. Despite the major role of cytokines in the development of T2D, further studies are required to investigate the possible effects of the macronutrient composition of diet on these cytokines.
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Citocinas/biosíntesis , Diabetes Mellitus Tipo 2/inmunología , Dieta/efectos adversos , Inflamación/inmunología , Adiponectina/biosíntesis , Animales , Proteína C-Reactiva/biosíntesis , Humanos , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Acute myocardial infarction (AMI) is one of the leading causes of morbidity worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species, and so forth. One of the processes that gets activated in response to I/R injury is autophagy. Indeed, autophagy acts as a "double-edged sword" in the pathology of myocardial I/R injury and there is a controversy about autophagy being beneficial or detrimental. On the basis of the autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy.
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Autofagia , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Animales , Fármacos Cardiovasculares/uso terapéutico , Humanos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The present work reports the adsorption of serine in the neutral and zwitterionic forms on the pure and Pt-decorated B12N12 fullerenes by means of density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations. The binding energy of serine over the fullerene has been studied through its hydroxyl (-OH), carboxyl (-COOH), and amine (-NH2) functional groups. Based on our analysis, the binding energy of serine in zwitterionic form (F: -1.52â¯eV) on B12N12 fullerene is less stable than that of the neutral form (C: -1.61â¯eV) using the M06-2X functional. Our results indicated that the most stable chemisorption state for serine is through its amine group (I: -2.49â¯eV) interacting with the Pt-decorated B12N12 fullerene in comparison with the carbonyl group (J: -1.92â¯eV). The conductivity of the B12N12 and Pt-decorated B12N12 fullerenes is influenced by the energy band gap variation when serine is adsorbed upon the outer surface of fullerenes. Understanding the adsorption of serine on B12N12 and Pt-decorated B12N12 fullerenes provide fundamental knowledge for future applications in biomolecules and metal surfaces.
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Fulerenos/química , Nanopartículas/química , Platino (Metal)/química , Serina/química , Adsorción , Electrones , Conformación Molecular , Fenómenos Ópticos , Espectrofotometría Infrarroja , Electricidad Estática , TermodinámicaRESUMEN
In this study, we evaluated the effect of the Celecoxib (CXB) adsorption on the electronic and optical properties of B12N12 fullerene by using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations with the M06-2X functional and the 6-311+G** basis set. The calculated adsorption energies of CXB with the B12N12 fullerene was evaluated at Tâ¯=â¯298.15â¯K in the vacuum and solvent (water) environments with the M06-2X functional. UV absorption and IR spectra were calculated and studied in order to identify the most important changes happening as a consequence of interactions between CXB and B12N12 fullerene. The results revealed that the adsorption of the CXB molecule from its NH2 head on the B12N12 is more favorable than those of the SO2 and NH groups in the gas and solvent environments. It is anticipated that the applied B12N12 fullerene could be suitable as a biomedical carrier for the delivery of CXB drug.
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Celecoxib/química , Fulerenos/química , Espectroscopía de Fotoelectrones/métodos , Adsorción , Celecoxib/análisis , Fulerenos/análisis , Espectrofotometría Infrarroja/métodos , VibraciónRESUMEN
The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (p<0.01). In correlation with this finding, IL-17 and IL-6 cytokines in RA patients also increased (p<0.01). The Th1 cells in RA patients were less than healthy group (p<0.05) and showed negative correlation with disease activity (r=-0.328, p<0.01). Dual Th17/Th1 cell only in new cases of RA were more than healthy control groups (p<0.01). The Th1/Th17 ratio in RA patients is statistically different with healthy control group (p<0.01) and it has negative correlation with disease activity (r=-264, p<0.05). The levels of ACPA and RF were increased with disease progression. Decreasing of Th1/Th17 ratio in RA patient suggested a new paradigm in the field of autoimmune disease and indicated that imbalance or plasticity between these subsets can be important in progress, diagnosis and therapy of RA disease.
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Artritis Reumatoide/inmunología , Subgrupos de Linfocitos T/inmunología , Células TH1/inmunología , Células Th17/inmunología , Adulto , Anciano , Anticuerpos Antiproteína Citrulinada/sangre , Diferenciación Celular , Plasticidad de la Célula , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. MATERIALS AND METHODS: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. RESULTS: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after 24 hr; however, PGZ 400 µM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. CONCLUSION: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.
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BACKGROUND: Interstitial lung disease (ILD) is a type of pulmonary manifestation in patients with rheumatoid arthritis (RA). Mostly RA-ILD has no symptoms and is only diagnosed by clinical examination, pulmonary function test (PFT), and high-resolution computed tomography (HRCT); hence it seems that the diagnosis of pulmonary involvement in early stages of RA is of great importance. Therefore, we decided to answer this question whether the evaluation of RA patients without pulmonary symptoms using methods such as PFT and HRCT are justifiable and reasonable or not. METHODS: We conducted a cross-sectional study in a referral rheumatology clinic in Razi hospital of Rasht, Iran. Forty-four consecutive patients, diagnosed with RA, were enrolled. Physical examination of the joints was performed by an rheumatologist. The activity of RA was evaluated in all patients by Disease Activity Score 28. An expert pulmonologist performed the respiratory examination in all participants. Then, all subjects were referred for chest X-ray, PFT, and HRCT of lungs. RESULTS: Patients included in this study, 9 (20.45%) males and 35 (79.55%) females, were 21-73 years old and their mean age was 49 ± 13 years. Significant relation between PFT and respiratory complaints was observed (P = 0.016). PFT had significant relation with respiratory examinations (P = 0.009). Our results indicated a significant relation between disease activity rate and PFT (P = 0.038). While HRCT had any significant relation with above items. CONCLUSION: We concluded, using PFT in the respiratory assessment of RA patients can be limited to persons with high disease activity, respiratory complaints, and positive findings in the clinical respiratory examination.
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BACKGROUND Different clinical and epidemiological studies using dual-energy X-ray absorptiometry have shown an increased prevalence of low bone mineral density in patients with inflammatory bowel diseases. The aim of this study was to assess the correlation between bone density and the disease activity in patients with ulcerative colitis. METHODS In this cross-sectional study, 52 patients with ulcerative colitis (duration of the disease less than 5 years) were invited to our research center, Golestan province, northeast of Iran, during February 2012 up to August 2012. A demographic checklist and Simple Clinical Colitis Activity Index was completed for each patients and 5 cc of blood sample was taken after obtaining the informed consent. We used colorimetry method for measuring serum calcium, UV method for serum phosphorus and ELISA for serum vitamin D. Dual-energy X-ray absorptiometry was done to evaluate the bone density. Data analysis was done using SPSS software version 16. Normality of data was assessed using Kolmogorov- Smirnov test. T and ANOVA tests were used if data had normal distribution. Mann-Whitney U or Kruskal-Wallis tests were used for the remaining data. Correlation between qualitative variables was evaluated by Chi-square test. RESULTS The mean (±SD) age and disease activity of the patients were 37.72 (±12.18) years and 4.78 (±1.98), respectively. There were no correlation between disease activity and mean age. Low bone density was seen in 30.8%, 11.5%, and 15.4% in spine, femur neck, and hip, respectively. There was no relationship between Z-score of total hip, spine, and femur neck with disease activity, age, and duration of disease (p>0.05). CONCLUSION Our results showed an acceptable rate of low bone density in patients with ulcerative colitis without any correlation with the disease activity index.