Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation.

Autoreactive inflammatory CD4+ T cells, such as T helper (Th)1 and Th17 subtypes, have been found to associate with the pathogenesis of autoimmune disorders. On the other hand, CD4+ Foxp3+ T regulatory (Treg) cells are crucial for the immune tolerance and have a critical role in the suppression of the excessive immune and inflammatory response promoted by these Th cells. In contrast, dendritic cells (DCs) and macrophages are immune cells that through their inflammatory functions promote autoreactive T-cell responses in autoimmune conditions. In recent years, there has been increasing attention to exploring effective immunomodulatory or anti-inflammatory agents from the herbal collection of traditional medicine. Berberine, an isoquinoline alkaloid, is one of the main active ingredients extracted from medicinal herbs and has been shown to exert various biological and pharmacological effects that are suggested to be mainly attributed to its anti-inflammatory and immunomodulatory properties. Several lines of experimental study have recently investigated the therapeutic potential of berberine for treating autoimmune conditions in animal models of human autoimmune diseases. Here, we aimed to seek mechanisms underlying immunomodulatory and anti-inflammatory effects of berberine on autoreactive inflammatory responses in autoimmune conditions. Reported data reveal that berberine can directly suppress functions and differentiation of pro-inflammatory Th1 and Th17 cells, and indirectly decrease Th cell-mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as Tregs, DCs and macrophages.

Humoral and cellular immune response to Buerger's disease.

OBJECTIVE: Thromboangiitis obliterans is a nonatherosclerotic occlusive disease, affecting small to moderate sized arteries of the upper and lower extremities, leading to progressive inflammation and clot formation. However, the role of humoral and cell-mediated immunity in the development of this disease has not been clearly identified. The present study was intended to investigate the humoral and cellular immune response in patients with Buerger's disease with different disease severity. METHODS: In an observational study, 80 male patients with Buerger's disease were included and categorized into three groups (mild, moderate, and severe) based on clinical manifestations. After blood sampling, cellular phenotypes were determined, and erythrocyte sedimentation rate, immunoglobulins (Ig) A, M, G, and E, as well as C3 and C4 components of the complement system and complement hemolytic activity (CH50) were measured. RESULTS: The mean age of the patient was 42.85 ± 8.39 years. Pulse abnormality, cold intolerance, and claudication were the most common symptoms. Eleven (13.75%), 46 (57.50%), and 23 (28.75%) patients had mild, moderate, and severe symptoms. Regression analyses showed that the presence of severe symptoms was significantly associated with elevated erythrocyte sedimentation rate and C4 levels (p < 0.05). CONCLUSION: Buerger's disease in severe cases was associated with increased erythrocyte sedimentation rate and abnormal C4 levels. The alterations in these inflammatory biomarkers might be due to a secondary inflammatory response to the presence of ulcer or gangrene and the inflammatory process in patients with severe symptoms.

Cytokine Analysis in Patients with Different Stages of Thromboangiitis Obliterans.

BACKGROUND: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases. OBJECTIVE: The changes in transforming growth factor ß (TGFß), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptoms were investigated in this research. METHODS: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital, from the year 2012 to 2016. They were then categorized into three groups: Mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFß, IL6, TNFα, and IFNγwere determined by the ELISA method and compared among the groups. RESULTS: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFß and IL6 were dysregulated as the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant (p > 0.05). In the multiple logistic regression model, increased TNFα levels were seen in the presence of moderate symptoms as compared to the severe ones (p < 0.05). CONCLUSION: It could be concluded that TNFα, as part of the defining cytokineproduction profile of T helper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.

Differences in autoimmunity factors based on the activity of thromboangiitis obliterans.

OBJECTIVE: The treatment of Buerger's disease (BD) presents a medical problem as its etiology is still unclear. In this study, our objective was to evaluate the serum levels of autoimmune markers in patients with different clinical features of BD. METHODS: In this study, 80 BD patients were categorized in three groups using a cross-sectional design: migratory thrombophlebitis, cold sensitivity, and skin discoloration (mild symptoms); chronic ulcers, claudication, and burning pain of the feet at night (moderate symptoms); pain at rest and spontaneous gangrene (severe symptoms). Enzyme-linked immunosorbent assay was performed to measure antibodies against immunoglobulin M rheumatoid factor (IgM RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptide (anti-CCP), antiphospholipid antibodies (APA), anti-cardiolipin antibodies (ACLA), anti-double stranded DNA (anti-dsDNA), and extractable nuclear antigen (ENA) profile. RESULTS: Patients with severe symptoms showed the lowest age (p=0.031), ESR (p<0.001), and highest prevalence of ischemia (p<0.001). In all the patients, the serum levels of ANA and IgM RF were higher than 1 U and 15 IU/mL, respectively. However, the progression of the disease from mild to moderate did not affect these markers significantly (p>0.05). Other markers were negative in patients with BD. CONCLUSION: The findings of this study indicate that BD may closely be correlated to transient autoimmune phenomena, despite the fact that further research is required to investigate how transient unspecific autoimmune reactions contribute to the BD pathogenesis.

Para-Clinical and Immunological Evaluation in Buerger's Disease as a Suspected Autoimmune Disease: Case Series.

BACKGROUND: Autoimmunity causes the loss of normal immune homeostasis and involves the presence of autoantibodies and inflammation. Thromboangiitis obliterans or Buerger's disease (BD) refers to a type of vascular obstructive syndrome, with tobacco exposure accounting for disease formation and progression. However, the current understanding of autoimmunity is unclear in the context of BD, and the scientific findings are not enough to support autoimmune mechanisms. This study was aimed at investigating autoimmunity factors in patients with BD. METHODS: Clinical and experimental examinations were performed on 80 patients with BD. The diagnostic work-up for autoimmunity was composed of IgM rheumatoid factor (RF), anti-nuclear antibodies (ANA), The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (CCP) antibodies, Antiphospholipid antibodies (APA), Anti-cardiolipin antibodies (ACLA), anti-double-stranded DNA (ds-DNA), and extractable nuclear antigen (ENA) profile. Immunomarkers were detected using the quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: Raynaud's phenomenon (84.93%), cold sensitivity (76.25%), and claudication (73.75%) were the most common symptoms in the BD patients. Also, 64.29% represented with high ANA levels and positive RF, while 42.11% were found with increased ANA and ESR levels. The ANA/RF positive BD patients had ESR> 15 mm/hr and a high prevalence of cold sensitivity, claudication, and Raynaud's phenomenon (p> 0.05). CONCLUSION: There is a possibility of a non-specific autoimmune disposition among BD patients. RF and ANA could be considered for predicting disease progression.

Tumor Necrosis Factor-α and Interleukin-1-ß Polymorphisms in Pre-Eclampsia.

BACKGROUND: Pre-eclampsia is the most common critical condition during pregnancy. Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1ß) increase in pregnant women with pre-eclampsia, compared to normal pregnant women. OBJECTIVE: To investigate the polymorphisms of IL-1ß (C+3954T), TNF-α (G-308A), and (G-238A) in pre-eclemptic women in northeastern Iran. METHODS: This study was conducted on 153 pre-eclamptic women (case group) and 150 healthy pregnant women (control group), admitted to Ghaem and Imam Reza hospitals of Mashhad, Iran. IL-1ß (C+3954T), TNF- α (G-238A) and TNF-α (G-308A) gene polymorphisms in the promoter region were screened by polymerase chain reaction. Data were analyzed, using SPSS version 16.0. RESULTS: The mean age of the participants in the case and control groups was 28.2 ± 6.1 and 27.1 ± 6.3 years, respectively (P=0.68). The frequency of G-308A polymorphism was significantly higher in the case group, compared to the control group (p<0.001). However, no significant relationship was found between IL-1ß genotype and pre-eclampsia (p=0.39). The frequency of TNF- α (G-238A) AA genotype was significantly higher in the case group, while GG genotype was less frequently detected in the case group, compared to the control group (p<0.001 for both genotypes). Moreover, the frequencies of AA genotypes of -238 TNF-α and G-308A polymorphisms were significantly higher in the case group, compared to the control group (p<0.001). CONCLUSION: The significant correlation between inflammation promoting genotypes of TNF-α and pre-eclampsia is noteworthy and provides evidence on the contribution of immune related genes in this disease.

Comparison of body mass index in children of two different regions of welfare.

Socioeconomic basis of children obesity is of high importance for preventive policies. This study aimed to compare the prevalence of obesity among children living in two different levels of welfare regions in Mashhad northeast of Iran. A total of 625 primary school girls and boys aged 78-127 months were randomly selected, and values of their body mass index (BMI) were measured. The prevalence of both overweight and obesity were higher among students of enriched area in comparison with that of resource restricted (P<0.05).The prevalence of overweight concerns in urban and rural areas. These results highlight the relation between socio-economic status and prevalence of obesity among children.

Serum selenium concentration in Mashhad prisoners, Iran.

OBJECTIVES: To determine the serum selenium concentration among prisoners in the central jail of Mashhad, Northeast of Iran. METHODS: In a cross-section study, a sample of 435 prisoners (387 men [34.5±10 years] and 48 women [36.4±11 years]) recruited during May 2008 to June 2008 from Mashhad Central Prison, Mashhad, Iran, using multistage sampling method, proportionate to gender, age groups and kind of crime. Serum level of selenium was assessed using atomic absorption spectrophotometer. RESULTS: The mean of serum selenium concentration was 121±20 ug/l. Prevalence of selenium deficiency was 9.7% in selected sample. The selenium deficiency was more prevalent in women than men (25.5% versus 7.8%, p=0.00). Age distribution of serum selenium level had a different pattern among men and women. While in men serum selenium level on average was least in those aged 50 and over, in women, serum selenium did not change with age. Body mass index (BMI) and weight change had no relations. CONCLUSION: Results of this study suggest that selenium status of the prisoners in Mashhad central prison is of concern. Women may be at higher risk for selenium deficiency. These results have implications for officials in charge with prisoners and health policy makers.