Exploring the pharmacological mechanism of Tripterygium wilfordii hook for treatment of Behcet's disease using network pharmacology and molecular docking.

Tripterygium wilfordii hook (TWH) has been used to treat Behcet's disease (BD) but its underlying mechanism remains unclear. This study aims to explore the mechanism of TWH on BD using network pharmacology and molecular docking. The bioactive constituents of TWH and their corresponding target genes were extracted from the Traditional Chinese Medicine systems pharmacology database and analysis platform. BD target genes were obtained by searching the DisGeNet and GeneCards databases. Gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were conducted to elucidate the function of overlapping genes between TWH and BD target genes. A protein-protein interaction network was constructed using Cytoscape and STRING platforms, and the core target genes were identified from the overlapping genes. Finally, molecular docking was used to assess the binding affinity between the core targets and TWH bioactive constituents. We identified 25 intersection genes related to both TWH and BD and 27 bioactive ingredients of TWH. Through analysis of protein-protein interaction network, 6 core targets (TNF, IFNG, prostaglandin-endoperoxide synthase 2, NOS2, VCAM-1, and interleukin-2) were screened out. Enrichment analysis demonstrated that the antioxidant properties of TWH constituents might play a significant role in their therapeutic effects. Molecular docking revealed high binding affinity between the bioactive constituents of TWH, such as kaempferol, triptolide, 5, 8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin, and their corresponding target genes, suggesting the potential of TWH to treat BD. Our investigation clarified the active components, therapeutic targets of BD in the treatment of TWH and provided a theoretical foundation for further researches.

Biologic therapy in large and small vessels vasculitis, and Behçet's disease: Evidence- and practice-based guidance.

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.

Treat to target in Behcet's disease: Should we follow the paradigm of other systemic rheumatic diseases?

During the last decades the efficacy of biologic agents, mainly of anti-TNFs, in controlling the activity of serious manifestations of Behcet's Disease (BD) has been established. On the other hand, the clinical heterogeneity of BD has precluded the validation of a widely-accepted composite index for disease assessment and for target disease-state definitions, such as low disease activity and remission, and the testing of their implementation in clinical practice. Therefore, in contrast to other systemic rheumatic diseases, a treat-to-target strategy has not yet been developed in BD. There are several challenges towards this approach, including standardization of outcome measures for assessing the disease activity in each-affected organ and construction of a composite disease activity index. The challenges for the development of a treat-to-target strategy and possible solutions are discussed in this position paper, which stemmed from a round table discussion that took place in the 19th International Conference on BD.

Biological therapy for ocular Behçet's disease with off-label drug prescription in Turkey.

OBJECTIVE: The use of biological agents in the treatment of ocular Behçet's disease has recently become more frequent. The use of two agents, infliximab (IFX) and adalimumab (ADA), for the treatment of Behçet's disease requires prior approval by the Turkish Medicines and Medical Devices Agency. We report on a review of such applications with a view to informing on how such agents are used off-label in Turkey. METHODS: Prescriptions for off-label use of IFX or ADA sent from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency in 2018 were evaluated. Demographic data, previous treatment regimens and reasons for referral were extracted from the files of the cases. RESULTS: A total of 662 patients were considered for off-label use of IFX or ADA for the treatment of ocular Behçet's disease. The mean age of the patients was 35.7±10.8 years (range 12-76); 61.5% of patients were men and 38.5% were women. Of the applications, 345 (52.1%) were for IFX and 317 (47.9%) for ADA. Among the referring hospitals, the public university hospitals ranked first, accounting for 77.9% of IFX and 88.6% of ADA prescriptions. Most applications were made after the failure of conventional therapy, which included steroids and immunosuppressive agents. CONCLUSION: IFX and ADA are rarely used as initial therapy. Stepwise treatment is still preferred in the treatment of ocular Behçet's disease in Turkey. Our report informs on the management of this difficult-to-treat condition.

Exploration of Gancao Xiexin decoction for treatment of Behcet disease based on network pharmacology and molecular docking.

BACKGROUND: Based on network pharmacology and molecular docking, this study discusses the potential mechanism of Gancao Xiexin decoction in the treatment of Behçet disease (BD) to provide a more reliable theoretical basis for the treatment of BD. METHODS: The effective components and action targets of Gancao Xiexin decoction were obtained by searching the traditional Chinese medicine systems pharmacology database and analysis platform database, and the genome annotation database platform (GeneCards) database Search BD related targets in Online Mendelian inheritance in man database, pharmacogenetics and pharmacogenomics knowledge base database, therapeutic target database and drugbank database, Venny analysis tool was used to overlap drug targets and disease targets; The "active drug active ingredient target gene" network was constructed with the help of Cytoscape 3.8.2 software, and the protein-protein interaction (PPI) network was constructed with string database; R language was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis; Target prediction based on pubchemp platform. RESULTS: A total of 163 active components were identified, with 730 corresponding targets, including 56 common targets of the active components and BD. GO enrichment analysis yielded 1126 entries for biological processes (BP), 17 entries for cellular components, and 89 entries for molecular functions. The significant items of BP enrichment mainly included reaction to lipopolysaccharide, reaction to bacteria-derived molecules, exogenous apoptosis signal pathways, and biological metabolism processes of reactive oxygen species. KEGG pathway enrichment analysis identified 118 significantly enriched pathways. The molecular docking technology verified that its effective components can effectively bind to the corresponding BD related target proteins. CONCLUSION: Gancao Xiexin decoction synergistically treats BD through multi-component, multi-target, and multi-channel mechanisms, which provides a basis for further study of the active components and mechanism of Gancao Xiexin decoction.

Regulation of NLRP3 inflammasome by zinc supplementation in Behçet's disease patients: A double-blind, randomized placebo-controlled clinical trial.

BACKGROUND: Overproduction of NLRP3 inflammasome complex is one of the causes of Behcet's disease's (BD) auto-inflammatory nature. The aim of current study was to examine the effect of zinc supplementation on NLRP3 inflammasome expression; as well as clinical manifestations of BD. METHODS: In this double-blind parallel placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day elemental zinc) or placebo groups for 12 weeks. The mRNA expression of NLRP3 and caspase-1 in the leukocytes, serum level of zinc and IL-1ß, anthropometric measures, and clinical manifestations of patients were collected at pre- and post-intervention phase. The Iranian Behçet's disease dynamic activity measure (IBDDAM) was scored to measure the treatment effect using the calculation of number needed to treat (NNT). Analysis of covariance was performed to obtain the corresponding effect sizes. RESULTS: Zinc gluconate led to a significant improvement in genital ulcer (P = 0.019). Zinc supplementation decreased NLRP3 and caspase-1 genes expression compared with placebo group (baseline-adjusted P-value = 0.046 for NLRP3 and P-value = 0.003 for caspase-1), even after adjustment for the effect of confounding factors (baseline- and confounders-adjusted P-value = 0.032 for NLRP3 and P-value = 0.004 for caspase-1). Baseline and confounders adjusted effect size demonstrated that zinc was effective in reducing the serum level of IL-1ß (P = 0.046). The NNT [95 %CI] for the rate of IBDDAM improvement was 3 [1.7-8.5]. CONCLUSIONS: Zinc gluconate supplementation (30 mg/day) for a 3-month period can be considered as an adjuvant therapy in alleviating inflammation and genital ulcer among BD patients.

Half-fluence Photodynamic Therapy for Central Serous Chorioretinopathy in a Patient Receiving Corticosteroids for Behçet's Uveitis

Corticosteroid-induced central serous chorioretinopathy (CSCR) has been reported to develop in many intraocular inflammatory diseases and usually resolves spontaneously after discontinuation of corticosteroids. Patients without any improvement may require alternative therapies. In this case report, we present the case of a 35-year-old man with Behçet's disease who had complaints of decreased vision due to CSCR in his left eye while using systemic corticosteroids along with cyclosporine and azathioprine. Half-fluence photodynamic therapy (PDT) was performed because the CSCR did not regress despite discontinuation of systemic corticosteroids. After treatment, his visual acuity increased with complete resolution of the subfoveal fluid. Half-fluence PDT seems to be an effective and safe treatment for patients who develop acute CSCR while under systemic or local corticosteroid therapy for intraocular inflammatory diseases such as Behçet's uveitis and do not improve despite steroid discontinuation.

Immunomodulatory and clinical responses to zinc gluconate supplementation in patients with Behçet's disease: A double-blind, randomized placebo-controlled clinical trial.

BACKGROUND & AIMS: Toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of Behçet's disease (BD). The current study aimed to investigate the effect of zinc supplementation on TLR-2/4 expression and the clinical manifestations of BD. METHODS: In this double-blind placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day) or placebo groups for 12 weeks. Before and after the intervention, the surface and mRNA expression level of TLR-2 and TLR-4 in the leukocytes, serum level of zinc and tumor necrosis factor-α (TNF-α), quality of life, anthropometric measures, and blood pressure of patients were collected. BD activity was studied using the nonocular Iranian Behçet's disease dynamic activity measure (IBDDAM), Behçet's disease current activity form (BDCAF), and total inflammatory activity index (TIAI) at the pre-and post-intervention phases. The effect sizes were compared between two groups using analysis of covariance. RESULTS: There were significant decrease in TLR-2 mRNA (P = 0.038) and protein expression (P = 0.034) and nonocular IBDDAM score (P = 0.046) in the zinc group compared to placebo at the endpoint. The serum level of zinc was increased in the zinc group (P < 0.001). Zinc supplementation significantly decreased the TLR-4 surface (P = 0.012) and mRNA expression (P = 0.028) within the group. However, this decrease was not significant compared to the placebo group. There was no significant difference between the two groups regarding the serum level of TNF-α, BDCAF, TIAI, quality of life, anthropometric measures, and blood pressure (P > 0.05). CONCLUSIONS: The present study revealed that zinc supplementation significantly improved nonocular IBDDAM score and TLR-2 expression in BD patients. GOV REGISTRATION NUMBER: NCT05098678.

Clonal cytopenia of undetermined significance and atypical Behçet's: the importance of zinc.

Atypical Behçet's is recognised in myelodysplastic syndrome (MDS) cases and is associated with trisomy 8. Clonal cytopenia of undetermined significance (CCUS) is recognised as a precursor to MDS. Our case describes the presentation of atypical Behçet's, in association with CCUS, post a Streptococcal infection. A mutation of a zinc finger RNA spliceosome, ZRSR2, is also described. Our patient initially presented with macrocytic anaemia, together with neutropenia and lymphocytopenia on routine monitoring. Later gastrointestinal symptoms together with oral and anal ulcerations developed. He was treated with oral zinc therapy and had resolution of recurrent oral ulcerations and significant reduction in severity of anal ulcerations. The functional impact of ZRSR2 mutation on spliceosome assembly is yet to be defined, but has been previously reported in CCUS with a clinical phenotype of macrocytic anaemia.

Effects of nanocurcumin supplementation on T-helper 17 cells inflammatory response in patients with Behcet's disease: a randomized controlled trial.

OBJECTIVE: Present research was performed to assess the effects of nanocurcumin supplementation on T-helper 17 (Th17) cells inflammatory response in patients with Behcet's disease (BD). METHODS: In this randomized double-blind, placebo-controlled trial, 36 BD subjects were randomly placed into two groups to take 80 mg/day nanocurcumin or placebo for eight weeks. Disease activity, frequency of Th17 cells and expression of related parameters including retinoic acid-related orphan receptor γ (RORγt) transcription factor messenger RNA (mRNA), related microRNAs (miRNAs) such as miRNA-155, miRNA-181, and miRNA-326 as well as proinflammatory cytokines including interleukin (IL)-17 and IL-23 were evaluated. RESULTS: Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Number of Th17 cells decreased significantly in the nanocurcumin group compared to baseline (p = .012) and placebo (p = .047). Moreover, RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 mRNA expression decreased significantly in the nanocurcumin group compared with baseline (p = .004, p = .009, p < .001, p < .001, p < .001, p < .001, respectively) and placebo (p = .002, p = .021, p = .006, p = .035, p < .001, p = .017, respectively). Significant reductions in IL-17 and IL-23 were seen in nanocurcumin group compared with baseline (p = .017 and p = .015) and placebo (p = .047 and p = .048, respectively). Significant reduction in disease activity was observed in nanocurcumin group compared with placebo group (p = .035). CONCLUSION: Nanocurcumin supplementation had favorable effects in improving inflammatory factors and disease activity in BD patients. Additional studies are warranted to suggest nanocurcumin as a safe complementary therapy in BD.HighlightsNanocurcumin supplementation decreased Th17 cells frequency significantly compared with baseline and placebo group.Nanocurcumin supplementation decreased mRNA expression of RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased cell supernatant IL-17 and IL-23 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased disease activity significantly compared to placebo group.

Mutation analysis of the TNFAIP3 in A20 haploinsufficiency: A case report.

INTRODUCTION: Haploinsufficiency of A20 (HA20) is a novel genetic disease presented by Zhou et al in 2016. A20 is a protein encoded by TNFAIP3. Loss-of-function mutation in TNFAIP3 will trigger a new autoinflammatory disease: HA20. HA20-affected patients may develop a wide range of clinical manifestations, such as Behcet disease, rheumatoid arthritis, rheumatic fever, juvenile idiopathic arthritis, and systemic lupus erythematosus. HA20 is rarely reported, thus remaining far from thoroughly understood. Sixty-one cases of HA20 have been reported worldwide, among which 29 cases were diagnosed with Behcet disease ultimately. Moreover, 3 cases have been reported in China, which was the first report of HA20 characterized by Behcet disease. A comprehensive understanding of the pathogenic genes of HA20 could help us apply targeted therapy as soon as possible to improve patients' survival rates. PATIENT CONCERNS: A 2-year-old 3-month-old child was presented to our hospital with recurrent infectious enteritis and stomatitis. DIAGNOSIS: Genetic mutations were detected immediately, and a novel pathogenic mutation was found in TNFAIP3. A heterozygous mutation (c.436-437deTC) located at TNFAIP3 was confirmed. The present research indicated that the TNFAIP3 mutation of c.436-437deTC (p.L147Qfs∗7) accounted for familial Behcet-like autoinflammatory syndrome in the child suffering from HA20, while no variation in this locus was found in her parents. INTERVENTIONS: Symptomatic treatments including oral administration of prednisone (12.5 mg/d) and iron supplement were performed, and repeated infection was no longer observed in the child. Pain and activity limitation was found in the knee joints. The treatment regimen was adjusted to oral prednisone (12.5 mg/dose, 2 doses/d) and subcutaneous injection of rhTNFR:Fc (12.5 mg/week).Outcomes: At the last follow-up, the limbs' activities were normal, the inflammatory indicators were reduced or within the normal range. The prednisone dose was reduced to 7.5 mg/d, while the dose of rhTNFR:Fc was not changed. CONCLUSION: We have identified a novel pathogenic HA20 mutation. In this article, 1 case was analyzed in-depth in terms of clinical manifestations of the patient and new sources of such a novel disease, which might improve our understanding of this disease.

Herbal Medicine for Behçet's Disease: A Systematic Review and Meta-Analysis.

Patients with Behçet's disease often use complementary and alternative medicine for treating their symptoms, and herbal medicine is one of the options. This systematic review provides updated clinical evidence of the effectiveness of herbal medicine for the treatment of Behçet's disease (BD). We searched eleven electronic databases from inception to March 2020. All randomized controlled trials (RCTs) or quasi-RCTs of BD treatment with herbal medicine decoctions were included. We used the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias and the grading of recommendations assessment, development and evaluation (GRADE) approach to assess the certainty of evidence (CoE). Albatross plot was also used to present the direction of effect observed. Eight studies were included. The risk of bias was unclear or low. The methodological quality was low or very low. Seven RCTs showed significant effects of herbal medicine on the total response rate (Risk ratio, RR 1.26, 95% CI 1.09 to 1.45, seven studies, very low CoE). Four RCTs showed favorable effects of herbal medicine on the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level compared with drug therapy. Herbal medicine favorably affected the ESR (MD -5.56, 95% CI -9.99 to -1.12, p = 0.01, I2 = 96%, five studies, very low CoE). However, herbal medicine did not have a superior effect on CRP. Two RCTs reported that herbal medicine significantly decreased the recurrence rate after three months of follow-up (RR 0.23, 95% CI 0.09 to 0.63, two studies, low CoE). Our findings suggest that herbal medicine is effective in treating BD. However, the included studies had a poor methodological quality and some limitations. Well-designed clinical trials with large sample sizes are needed.

[Behçet's Syndrome]. / Behçet-Syndrom.

Behçet's syndrome (BS) is classified as a variable vessel vasculitis. The clinical picture is very diverse and usually requires interdisciplinary collaboration. Pathogenetically, BS seems to take a middle position between a polygenic autoinflammatory disease and an autoimmune disease. New EULAR recommendations were issued in 2018. The therapy depends on which organs are most affected. Since 2016, adalimumab has been approved for the treatment of posterior ocular involvement. Infliximab, interferon a2a, interleukin-1 antagonists and apremilast may be alternative therapies.

Optimizando el manejo de la uveítis con agentes biológicos en Chile del 2020 / Optimizing uveitis management with biological agents in Chile in 2020

Los agentes biológicos han irrumpido como una alternativa eficaz en el tratamiento de las uveítis no-infecciosas, especialmente en cuadros refractarios a inmunosupresores convencionales, con buena tolerancia y rápido efecto. Hay patologías como la enfermedad de Behçet en que incluso pueden estar indicados como tratamiento de primera línea. Este artículo ayudará a reconocer las patologías específicas donde presentan mayor eficacia, entrega herramientas para escoger el agente más adecuado para cada paciente y sugiere estrategias para evitar la pérdida de control de la enfermedad en el largo plazo.

Biological therapies have emerged as an effective option for the treatment of non-infectious uveitis, especially in refractive cases to conventional immunosup-pressive drugs. They are fast-acting, well tolerated, and can be considered as first-line agents for the treatment of certain uveitis like in Behçet ́s disease. This article will aid in identifying the uveitis syndromes where biological therapy is more effective, help choosing the most appropriate agent for a particular case and offer suggestions on how to keep long-term disease control.

[Use of biotherapy in the management of Behçet's disease in a department of internal medicine]. / Recours à la biothérapie dans la prise en charge de la maladie de Behçet dans un service de médecine interne.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic disease responsible for occlusive vasculitis with arterial, venous and capillary involvement. The aim of this study was to determine the frequency and the features associated with the use of biotherapy in the management of patients followed in our department for BD. METHODS: This is a retrospective study of patients medical records followed for BD in a department of internal medicine from January 2005 to August 2018. RESULTS: A total of 41 patients were included with a mean age at diagnosis of 42.5±12.1 years (range 16 to 63) and a sex ratio men/women of 1.05. Oral and/or genital aphtosis was present in 70.7% of the patients. Other lesions were: ocular (78.0%), articular (46.3%), cutaneous (41.5%), central neurological (34.1%), vascular (26.8%), digestive (7.3%), pericardial (2.4%) and epididymal (2.4%). A biotherapy, interferon α and monoclonal antibodies, was used in 15 patients (36.6%), after failure of conventional treatments. The monoclonal antibodies were anti-TNFα (infliximab, adalimumab, certolizumab and golimumab) except in one patient for whom ustekinumab was used. Biotherapy was used in 46.9% of the patients with ocular involvement and never used in those patients without ocular involvement (P=0.01). CONCLUSION: Biotherapy is effective and represents a solution to the failures of conventional treatments in severe forms of Behçet's disease with ocular involvement.

A review of Behcet's disease from the perspectives of both Western and Chinese medicine.

Behcet's disease is a condition with a complicated and unclear etiology that comprises multi-systemic, chronic, inflammatory vasculitis. Behcet's disease can affect every tissue and organ in the body, and is characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, and other manifestations. The incidence of Behcet's disease has a distinct regional specificity, and is most prevalent along the Silk Road, a route that stretched between the Mediterranean, Middle East and Far East. This article reviews the recent literature to evaluate the prevalence, clinical manifestations, pathogenesis and mechanism, and current treatments of Behcet's disease. Furthermore, the etiology of Behcet's disease will be evaluated from the aspect of Traditional Chinese Medicine (TCM) syndrome differentiation. As Behcet's disease is complex and intractable, its treatment warrants further research. Traditionally, Behcet's disease is treated with Western Medicine (WM) via medications that act locally and systemically; this WM treatment protocol usually has a good effect, but relapse can occur after reducing the dosage. Thus, it may be ideal to treat Behcet's disease via a combination of WM and TCM. Recent studies have indicated that such a combination of Chinese and Western treatments has a better effect than either treatment alone. The aim of the present review is to describe the clinical features of Behcet's disease, and to outline its possible pathogenesis in terms of both TCM and WM. Based on these findings, the present review proposes a Behcet's disease treatment protocol composed of a combination of Chinese and WM that can effectively improve the occurrence of relapse caused by the reduction of the dosage of Western medication.

Herbal medicine (Gancao Xiexin decoction) for Behcet disease: A systematic review protocol.

BACKGROUND: Behcet disease (BD) is a systemic vasculitis that causes blood vessel inflammation throughout body and no cure exists. The purpose of this review is to evaluate the safety and efficacy of Gancao Xiexin Decoction (GCXX) in the treatment of BD and provide a clinical reference for the treatment of the refractory disease. METHODS: First, the researcher will retrieve the following database based on the established search strategy: MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), China National Knowledge Infrastructure, Wanfang, VIP (Journal Integration Platform). The quality of the literature will be evaluated according to Cochrane's handbook and review inclusion criteria. Data will be extracted and data of sufficient homogeneity was combined using Review Manager (RevMan) software V5.3.5. RESULTS: This study will provide a high quality synthesis of herbal medicine (Gancao Xiexin decoction) for Behcet disease. CONCLUSIONS: The conclusion of our systematic review will provide evidence to judge whether herbal medicine (Gancao Xiexin decoction) for Behcet disease is an effective intervention for patient with menopausal women. TRIAL REGISTRATION NUMBER: PROSPERO CRD 42018104099.

Behçet syndrome: effects of Pycnogenol® supplementation during regression phases.

BACKGROUND: The aim of this comparative registry study was to evaluate the supplementation with Pycnogenol® in subjects with Behçet syndrome (BS) with symptoms impairing their quality of life despite being in a remitting phase of the disease. METHODS: Thirty-four patients with a confirmed diagnosis of BS were divided into the control group (without supplement) or the active group, in this specific case using Pycnogenol® (Horphag Research LTD) supplement at the daily dose of 150 mg (50 mg tid) for 4 weeks. RESULTS: All subjects receiving Pycnogenol® reported a significant decrease in symptoms, such as burning/pain due to dryness and ulcerations (P<0.05). In addition, Pycnogenol® showed important anti-inflammatory activity by decreasing ESR, leucocytosis and Pathergy Test response. CONCLUSIONS: Pycnogenol® may be a useful supplementation for the management of BS.

Effectiveness and safety of Glycyrrhizae Decoction for Purging Stomach-Fire in Behcet disease patients: Study protocol for a randomized controlled and double-blinding trail.

BACKGROUND: Behcet disease (BD) is a worldwide-occurred autoimmune disorder and currently lack of optional successful treatment. An ancient traditional Chinese medical formula called Glycyrrhizae Decoction for Purging Stomach-Fire (GDPSF) was recorded and nowadays has been observed to be effective for BD patients. However, the strict randomized controlled and double-blinding trail is needed to further assess this alternative medicine. METHODS: To ascertain the potential effects and safety of GDPSF for BD patients and to determine whether combination application of GDPSF and thalidomide could possibly reduce the side effects and increase effectiveness for BD management, we will conduct a randomized, double blind, controlled clinical trial. Patients enrolled will be randomly assigned into 3 groups: GDPSF group, thalidomide group, and integrative group (treated by both GDPSF and thalidomide). Participants will receive treatment for 6 months and accept a 12 months follow-up. Before and after treatment, clinical manifestations, blood tests, thalidomide dosage, remission levels, quality of life, and satisfactory levels will be assessed. The data of assessments on each group before and after treatments will be collected and analyzed through historical control, while between groups through intergroup control. Then statistical analysis will be applied to assess the effects and safety. DISCUSSION: This study protocol will assess the effects and safety of GDPSF for BD patients GDPSF. Combination application of GDPSF and thalidomide might be a new integrative medical method for BD patients. TRIAL REGISTRATION: Chinese Clinical Registry (ChiCTR-ONC-16009621) on Oct. 2016 http://www.chictr.org.cn/showproj.aspx?proj=16395.

Panax Notoginseng Saponin Controls IL-17 Expression in Helper T Cells.

PURPOSE: Panax Notoginseng, a traditional Chinese medicine, is known as an anti-inflammatory herb. However, the molecular mechanism by which it controls helper T cell mediated immune responses is largely unknown. METHODS: Naive CD4+ T cells isolated from healthy donors, patients with Behcet's disease, and C57BL/6 mice were polarized into Th1, Th17, and Treg cells. Proliferation and cytokine expression were measured in these cells with the presence or absence of Panax Notoginseng saponins (PNS). Genomewide expression profiles of Th1, Th17, and Treg cells were assessed using Affymetrix microarray analysis. RESULTS: We found that PNS control the proliferation and differentiation of Th17 cells by globally downregulating the expression of inflammatory cytokines and cell cycle genes. CONCLUSIONS: These findings demonstrated that PNS function as an anti-inflammatory agent through directly targeting Th17 cell mediated immune response.