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ID PMID Title PublicationDate abstract
31629819 miR-22 inhibits synovial fibroblasts proliferation and proinflammatory cytokine production 2020 Jan 15 BACKGROUND/AIMS: Rheumatoid arthritis synovial fibroblasts (RASF) play an essential role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the biological effects of miR-22 on RASFs. METHODS: RT-qPCR was used to detect the expressions of miR-22 and SIRT1 in RA synovial tissue. The results of miR-22 on the proliferation of RASF were examined by MTT assay. The effects of miR-22 on the secretion of TNF-α, IL-1β, and IL-6 in RASF were measured by ELISA. Target gene prediction and screening, and luciferase reporter assay were used to testify downstream target genes of miR-22. RT-qPCR and western blotting were used to detect the mRNA and protein expression of SIRT1. RESULTS: miR-22 was significantly decreased in RA synovial tissue, while SIRT1 was significantly increased in RA synovial tissue. Over-expression of miR-22 significantly inhibited the proliferation of RASFs and the secretions of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in RASFs. SIRT1 was identified as a direct target of miR-22. Over-expression of miR-22 reduced the expression level of SIRT1 in RASFs. Over-expression of SIRT1 reversed the effect of miR-22 on the proliferation of RASFs and the secretion of inflammatory cytokines. CONCLUSION: MIR-22 was significantly down-regulated in RASF cells, which affected the secretions of inflammatory cytokines and cell proliferation by regulating SIRT1.
31894573 Innovative Education and Engagement Tools for Rheumatology and Immunology Public Engagemen 2019 Rheumatoid arthritis (RA) affects around 1% of the population, which places a heavy burden on society and has severe consequences for the individuals affected. The early diagnosis and implementation of disease-modifying anti-rheumatic drugs significantly increase the chance of achieving long-term sustained remission. Therefore, raising awareness of RA amongst the general public is important in order to decrease the time of diagnosis of the disease. Augmented reality (AR) can be tremendously valuable in a teaching and learning context, as the coexistence of real and virtual objects aids learners in understanding abstract ideas and complicated spatial relationships. It has also been suggested that it raises motivation in users through interactivity and novelty. In this chapter we explore the use AR in public engagement, and detail the design, development and evaluation of a blended learning experience utilising AR. A set of informative printed posters was produced, enhanced by an accompanying interactive AR application. The main user testing was conducted with 27 participants at a science outreach event at the Glasgow Science Centre. Findings report mean positive attitudes regarding all aspects of the study, highlighting the potential of AR for public engagement with topics such as RA.
31870429 Conferring extracellular matrix affinity enhances local therapeutic efficacy of anti-TNF-Π2019 Dec 23 BACKGROUND: Although disease in a majority of rheumatoid arthritis (RA) patients is often initially limited to one or a few joints, currently approved medications including anti-tumor necrosis factor-α antibody (α-TNF) are injected systemically. Given that α-TNF systemic injection typically does not cure RA and involves risk of treatment-related adverse events, one possible approach to enhance therapeutic efficacy and reduce α-TNF systemic exposure is to retain the antibodies in arthritic joints after local administration. The aim of this study was to evaluate the approach of conferring extracellular matrix (ECM) binding affinity to α-TNF antibodies in a RA model. METHODS: α-TNF was chemically conjugated with a promiscuous ECM-binding peptide derived from placenta growth factor 2 (PlGF-2(123-144)). The binding activity of PlGF-2(123-144)-conjugated α-TNF (PlGF-2(123-144)-α-TNF) against ECM proteins was assessed by ELISA and by immunostaining on human cartilage specimens. The effect of conjugation on antibody function was assessed as a neutralizing activity against osteoclast differentiation. Retention at the injection site and therapeutic efficacy of PlGF-2(123-144)-α-TNF were tested in a collagen antibody-induced arthritis (CAIA) model in the mouse. RESULTS: PlGF-2(123-144) peptide conjugation conferred α-TNF with affinity to ECM proteins without impairment of antigen recognition. PlGF-2(123-144)-α-TNF locally injected at a paw in the CAIA model was retained for at least 96 h at the injection site, whereas unmodified α-TNF was dispersed rapidly after injection. Local treatment with unmodified α-TNF did not suppress the arthritis score relative to isotype controls. By contrast, local administration of PlGF-2(123-144)-α-TNF suppressed arthritis development almost completely in the treated paw even at a 1000× lower dose. CONCLUSION: These data demonstrate that retention of α-TNF in arthritic joints can suppress arthritis development and enhance therapeutic efficacy. This simple bioengineering approach of ECM-binding peptide conjugation offers a powerful and clinically translational approach to treat RA.
32421953 Current Developments in Therapeutic Drug Targeting for the Management of Rheumatoid Arthri 2019 Rheumatoid arthritis (RA) is a debilitating condition that results in impairment of joints and ligaments and thus constrained mobility and decreased array of movement. It is a broad expression that encompasses additional 100 very diverse disorders mainly affecting joints. In the field of drug discovery, there is no well-known treatment for RA that can eradicate the disease permanently and alleviate the pain. The common non-targeted treatment approaches leads to serious side effects and systemic complications for RA patients. Therefore, targeted drug delivery systems, strategies, and diverse therapeutic approach for treatment of RA have gained increasing attention in the past few years. However, with the current understandings, researchers aim at accomplishing complete and long-lasting remission by the development of smart formulations/smart drug-delivery systems. Treatment for RA patients can be more efficient and effective utilizing these smart approaches. The present review focuses on the existing novel drug-delivery systems, strategies, and current trends in the treatment of RA.
30932720 Design and development of bioinspired calcium phosphate nanoparticles of MTX: pharmacodyna 2019 Jul The aim of this investigation is the management of rheumatoid arthritis (RA) by developing methotrexate-loaded calcium phosphate nanoparticles (MTX-CAP-NP) and to evaluate pharmacokinetic and pharmacodynamic behavior in adjuvant induced arthritis model. The nanoparticles were synthesized by wet precipitation method and optimized by Box-Behnken experimental design. MTX-CAP-NPs were characterized by TEM, FTIR, DSC and XRD studies. The particle size, zeta potential and entrapment efficiency of the optimized nanoparticles were found to be 204.90 ± 64 nm, -11.58 ± 4.80 mV, and 88.33 ± 3.74%, respectively. TEM, FTIR, DSC and XRD studies revealed that the developed nanoparticles were nearly spherical in shape and the crystalline structure of CAP-NP was not changed after MTX loading. The pharmacokinetic studies revealed that MTX-CAP-NP enhanced bioavailability of MTX by 2.6-fold when compared to marketed formulation (FOLITRAX-10). Under pharmacodynamic evaluation, arthritic assessment, radiography and histopathology studies revealed that CAP has ability to regenerate cartilage and bone therefore, together with MTX, MTX-CAP-NPs have shown significant reduction in disease progression. The overall work demonstrated that the developed nanodelivery system was well tolerated and more effective than the marketed formulation.
31185124 Success Rates of Revision Knee Arthroplasty for Periprosthetic Joint Infection in Rheumato 2019 Sep 1 This study evaluated the success and failure rates as well as the final results following 2-stage revision total knee arthroplasty (TKA) for periprosthetic joint infection (PJI). Particular emphasis was placed on comparing patients with rheumatoid arthritis (RA) and non-RA patients. A total of 140 knees that required 2-stage revision for PJI after TKA were analyzed. Mean patient age at first revision TKA was 67.9 years (range, 43 to 89 years), and mean time from second-stage revision to final follow-up was 53.3 months (range, 26 to 127 months). Thirty-eight of the 140 knees (27.1%) demonstrated recurrence of infection after first 2-stage revision. Of these, 8 required another 2-stage revision, 25 required knee arthrodesis, and 2 required amputation; 3 patients refused further treatment or were lost to follow-up. There was no recurrence of infection. No statistically significant differences were observed between the RA and non-RA groups in terms of success or failure rate (P=.6) according to Diaz-Ledezma and Knee Society Scores (P=.3). These findings indicate reinfection rates and final results were similar in RA and non-RA patients following revision TKA for PJI. [Orthopedics. 2019; 42(5):e472-e476.].
31813912 IgA Vasculitis Developed as an Adverse Effect of Tofacitinib Taken for Rheumatoid Arthriti 2020 Mar 15 Tofacitinib is a new small-molecule inhibitor of the JAK/STAT signaling pathway used to treat rheumatoid arthritis. We herein report a case of IgA vasculitis apparently caused by tofacitinib. A 67-year-old woman with rheumatoid arthritis developed IgA vasculitis after taking tofacitinib for 6 months. She presented with proteinuria and purpura of the lower extremities. Biopsy specimens from her skin and kidney were compatible with IgA vasculitis. Following termination of tofacitinib, the patient completely recovered from the IgA vasculitis. Drug-induced IgA vasculitis has been previously described for anti-tumor necrosis factor-(TNF)α therapies, but this is the first report of this adverse effect with anti-JAK therapy.
30870218 Opioid use in rheumatoid arthritis: trends, efficacy, safety, and best practices. 2019 May PURPOSE OF REVIEW: The opioid epidemic remains prominent in both the medical literature and popular media. Rheumatologists are among the physicians at the forefront of the epidemic because of the prominent role of pain in rheumatoid arthritis (RA) and the limited options for treatment of pain. The purpose of this review is to provide an update on the trends of opioid use among patients with RA, to discuss the various mechanisms of RA pain, review the available evidence for opioid efficacy in RA, and to promote a guideline for best practices in opioid prescribing. RECENT FINDINGS: Recent cohort studies have estimated that up to 40% of patients with RA are regular users of opioids, and the effects of disease-modifying antirheumatic drugs are minimal in reducing opioid use. Although the literature supports the efficacy of short-term opioids for the improvement in pain, long-term use is associated with reduced efficacy and increased safety concerns. SUMMARY: Although the data supporting the use of long-term opioid use in patients with RA is poor, rheumatologists can adhere to best practices for determining when and if initiation of opioids is appropriate. Identification of the nature of the pain can help determine the appropriate course of treatment.
31232832 The Gut Microbiome in Inflammatory Bowel Disease: Lessons Learned From Other Immune-Mediat 2019 Jul There is a growing appreciation for the role of the gut microbiome in human health and disease. Aided by advances in sequencing technologies and analytical methods, recent research has shown the healthy gut microbiome to possess considerable diversity and functional capacity. Dysbiosis of the gut microbiota is believed to be involved in the pathogenesis of not only diseases that primarily affect the gastrointestinal tract but also other less obvious diseases, including neurologic, rheumatologic, metabolic, hepatic, and other illnesses. Chronic immune-mediated inflammatory diseases (IMIDs) represent a group of diseases that share many underlying etiological factors including genetics, aberrant immunological responses, and environmental factors. Gut dysbiosis has been reported to be common to IMIDs as a whole, and much effort is currently being directed toward elucidating microbiome-mediated disease mechanisms and their implications for causality. In this review, we discuss gut microbiome studies in several IMIDs and show how these studies can inform our understanding of the role of the gut microbiome in inflammatory bowel disease.
30557129 Frailty in seropositive rheumatoid arthritis patients of working age: a cross-sectional st 2019 Jul OBJECTIVES: The prevalence of frailty has been widely researched in the elderly population. However, data about people of working age are scarce. The aim of this paper was to assess the prevalence of prefrailty and frailty in rheumatoid arthritis (RA) patients of working age, and to assess factors associated with prefrailty/frailty. METHODS: In this monocentric cross-sectional study, 100 RA patients aged 18-65 years were included. Frailty was measured with the Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI) and disease activity with the Clinical Disease Activity Index (CDAI). In addition, disease duration (years), pain intensity (visual analogue scale) and employment status were also assessed. RESULTS: Fifty-five percent were robust, 30% prefrail and 15% were frail. Eighty-nine of the prefrail/frail individuals suffered from exhaustion. Compared to robust individuals, the prefrail/frail individuals had significantly higher median scores in disease activity [4.0 (Q25-Q75: 0-10) vs. 11 (Q25-Q75: 6-18)] and pain intensity [3.0 (Q25-Q75: 2.0-4.0) vs. 4.0 (Q25-Q75: 2.8-6.3)] and a higher rate of unemployment [31% vs. 53%]. In the multivariable analysis, higher disease activity (ß=0.444; p<0.001), unemployment (ß=0.243; p=0.005), higher pain intensity (ß=0.186; p=0.060) and longer disease duration (ß=0.181; p=0.020) were associated with a higher frailty score. CONCLUSIONS: Frailty is common in RA patients, even those of working age. As the prevalence of frailty increases with age, it is important to take this syndrome into account in younger persons and to take action to counteract frailty.
31647605 First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and to 2020 Feb Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first-in-human, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n = 56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3 mg/kg), or subcutaneous iscalimab (3 mg/kg), or placebo. Rheumatoid arthritis patients (n = 20) received single doses of intravenous iscalimab (10 or 30 mg/kg) or placebo. Iscalimab exhibited target-mediated drug disposition resulting in dose-dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3-0.4 µg/mL. In subjects receiving 3 mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154-induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40-CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases.
31739706 Physical activity in rheumatoid arthritis: relationship to cardiovascular risk factors, su 2020 Mar Objective: To investigate associations between physical activity and risk factors for cardiovascular disease (CVD), subclinical atherosclerosis, and disease activity in patients with early and long-standing rheumatoid arthritis (RA).Method: This cross-sectional study included 84 patients with early and 37 with long-standing RA (disease duration, mean ± sd: 1.4 ± 0.4 and 16.3 ± 2.3 years, respectively). Physical activity was measured using a combined accelerometer and heart-rate monitor. Further assessments were disease activity (erythrocyte sedimentation rate, Disease Activity Score in 28 joints), functional ability (Health Assessment Questionnaire), risk factors for CVD (blood lipids, i.e. triglycerides, high-density lipoprotein, low-density lipoprotein; blood glucose, blood pressure, sleeping heart rate, waist circumference, body mass index, and body fat), and subclinical atherosclerosis (pulse-wave velocity, augmentation index, and carotid intima-media thickness).Results: Physical activity variables did not differ between patients with early and long-standing RA. However, 37% of the patients with early and 43% of those with long-standing RA did not reach the World Health Organization's recommended levels of moderate to vigorous physical activity (MVPA). In a final multiple regression model, adjusted for age, gender, disease duration, and activity monitor wear time, higher total physical activity was associated with lower body fat and higher functional ability. With the same adjustments, more time spent in MVPA was associated with lower high-density lipoprotein and lower sleeping heart rate.Conclusions: Physical activity was associated with more favourable risk factors for CVD. However, many patients were physically inactive, stressing the importance of promoting physical activity in RA.
30769038 Aleurites moluccanus and its main active constituent, the flavonoid 2″-O-rhamnosylswerti 2019 May 10 ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general, and the nut oil had been topically applied to treat arthritis and other joint pain, however the seeds are classified as toxic for oral use. AIM: Faced with the need for new alternative to treat the symptoms and modify rheumatoid arthritis (RA) the aim of this work was to evaluate the effects of A. moluccanus' leaves dried extract in rats and mice submitted to complete Freund adjuvant (CFA)-induced RA. MATERIAL AND METHODS: Wistar Rats and Swiss mice were submitted to CFA-induced RA in the right hindpaw. They received A. moluccanus extract (orally; p.o.), dexamethasone (subcutaneously), 2″-O-rhamnosylswertisin (p.o.) or vehicle (p.o.), from the 14th day after the CFA injection for up to 8 days. The mechanical hypersensitivity was evaluated using the von Frey filaments and the paw-oedema was measured using a plethysmometer. The rats' injected hindpaw was used to perform the histological analysis. RESULTS: A. moluccanus was able to significantly reduce the mechanical hypersensitivity in both ipsi- and contralateral hindpaws of mice injected with CFA, in a dose dependent manner. Furthermore, the paw-oedema was progressively reduced by A. moluccanus. Similar results were obtained for the positive-control drug dexamethasone and the isolated compound 2″-O-rhamnosylswertisin. Besides the effects mentioned above, the extract was also effective to repair the joint damage in CFA-induced RA rats, including reduction of fibrosis, cartilage degradation and bone erosion scores. CONCLUSION: These results together with the literature data reinforce the anti-hypersensitivity and anti-inflammatory activity of A. moluccanus extract. Part of the observed effects is due to the presence of the compound 2″-O-rhamnosylswertisin. The fact that the extract acted as a disease modifier point this herbal product as a promisor and safe tool to treat RA and other associated chronic diseases.
31005814 Ethanolic extract of Kaempferia parviflora interrupts the mechanisms-associated rheumatoid 2019 Jun BACKGROUND: Kaempferia parviflora Wall. ex Baker (KP) has long been used in traditional medicine to treat various diseases because active compounds in rhizome extracts are important anti-inflammatory agents. PURPOSE: This study aims to investigate the effects of an ethanolic extract of KP on the molecular mechanisms associated with rheumatoid arthritis (RA), which was induced by a combination of proinflammatory cytokines (IL-1β or TNF-α with IL-17A) in a human synovial sarcoma cell line (SW982) culture model. METHODS: SW982 cells pretreated with cytokines were incubated with KP extract at 3-30 µg/ml, or three major compounds of KP (5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, and 3,5,7,3',4'-pentamethoxyflavone) for up to 72 h. Dexamethasone was used as positive control. RA-associated genes and inflammatory products were measured in parallel with cell death genes. Apoptosis by flow cytometry and migration assay were also analyzed. Western blotting was used to examine the effects on intracellular signaling mechanisms. RESULTS: KP extract markedly reduced the expression of genes and levels of proinflammatory cytokines, inflammatory mediators, and matrix-degraded enzymes, but neither induced apoptosis nor altered the cell cycle. Its major constituents differently exerted suppressive effects on inflammatory genes. The KP extract downregulated the expression of genes associated with autophagosome and necroptosome formations. The extract also inhibited cell migration, reduced the mRNA expression of cadherin-11, and selectively reduced the phosphorylation of p38 MAPK, STAT1, and STAT3 signaling molecules, but did not interfere with the NF-κB pathway. CONCLUSION: These results suggest that the anti-arthritic potential of KP extract results from anti-inflammation and anti-migration via the suppression of the cytokines-induced p38/STAT1 and STAT3 pathways.
31410215 Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 2019 Purpose: Methotrexate (MTX) is a first-line drug for rheumatoid arthritis (RA)therapy. However, MTX monotherapy often results in irreversible joint damage due to its slow onset of action and long duration. microRNA-124 (miR-124) has shown direct bone protection activity against RA. A co-delivery system for MTX and microRNA combination may provide therapeutic synergy. Methods: Methotrexate-conjugated polymer hybrid micelles (M-PHMs) were prepared by self-assembly of two functional amphiphilic polymers (MTX-PEI-LA and mPEG-LA) at an optimized weight ratio. Incorporation of microRNA was achieved through electrostatic interactions between microRNA and cationic polymer MTX-PEI-LA. Cellular uptake, endosome escape, biodistribution, and therapeutic efficacy of M-PHMs/miR-124 complexes were investigated and evaluated in RAW264.7 cells and a rat adjuvant-induced arthritis (AIA) model. Results: M-PHMs/miR-124 complexes exhibited folate receptor-mediated uptake in activated RAW264.7 cells. miR-124 was able to escape from the endosome and down-regulate nuclear factor of activated T cells cytoplasmic1 (NFATc1). M-PHMs/miR-124 complexes accumulated in inflamed joints of AIA rats and showed superior therapeutic efficacy through both anti-inflammatory effect and direct bone protective effect. Combination of miR-124 and MTX in these micelles induced disease remission. Conclusions: M-PHMs/miR-124 was highly effective against RA through therapeutic synergy. Additional studies are warranted to further investigate its therapeutic potential and delineate its mechanisms of action.
30620286 Attitudes about principle of autonomy in Hispanic patients from a dynamic early rheumatoid 2019 Jul OBJECTIVES: In 2004, we began assembling an incidental cohort of patients with recent-onset rheumatoid arthritis (RA). In February 2018, we performed a cross-sectional study with the objective to investigate patients' attitudes/knowledge regarding the autonomy principle. METHODS: Patients currently attending the cohort (n=146) were invited to participate. A 4-dimensional questionnaire was administered, and a rheumatologic evaluation performed in the 143 patients who agreed to participate. Dimension-4 (D-4) included 7 multiple-choice (strongly agree-strongly disagree) sentences, 3 of which were related to patients' rights/obligations about health-related decisions (group-1), and 4 additional sentences challenged physician's recommendations (group-2). The D-4 score was considered a surrogate of knowledge autonomy (KA). Additionally, the surveyor scored KA with a Likert scale (poor, borderline and superior), and a cut-off point for poor KA was set using Borderline methodology. Mann-Whitney U-tests and logistic regression analysis were used. The study received IRB approval. RESULTS: At the time the questionnaire was administered, mean (±SD) patient age was 46.9 (±13.6) years, and median (interquartile range) cohort follow-up time was 8.8 (4.3-11.9) years. Fifty-one patients (35.6%) had poor KA; increased age (OR: 0.97, 95% CI: 1.004-1.063, p=0.023) was associated with better KA. Patients more frequently agreed-strongly agreed with group-1 sentences than they did with group-2 sentences (86.7% vs. 58%, p≤0.001). The results were reproduced in the subpopulations with sufficient KA (98.9% vs. 88%, p=0.007) and poor KA for patients in whom the gap was extreme (64.9% vs. 3.9%, p≤0.001). CONCLUSIONS: Hispanic RA patients' sense of autonomy suggests paternalism in the physician-patient relationship.
31454097 CD4+ count-dependent concentration-effect relationship of rituximab in rheumatoid arthriti 2019 Dec AIMS: Rituximab is approved in rheumatoid arthritis (RA). A substantial decrease in CD4+ count was observed in responders after a single cycle of treatment. This study aimed to describe and quantifying the influence of CD4+ count depletion on the concentration-response relationship of rituximab in RA patients. METHODS: In this retrospective monocentric observational study, 52 patients were assessed. Repeated measurements of rituximab concentrations (pharmacokinetics), CD4+ counts (biomarker) and disease activity score in 28 joints (DAS28, clinical response) were made. Rituximab pharmacokinetics was described using a 2-compartment model, and CD4+ cell counts and DAS28 measurements were described using indirect turnover and direct Emax pharmacokinetic-pharmacodynamic models, respectively. Delay between rituximab concentrations and responses was accounted for by including biophase compartments. RESULTS: Elimination half-life of rituximab was 18 days. The pharmacokinetic-pharmacodynamic model showed that DAS28 response to rituximab was partly associated with CD4+ cell depletion. At 6 months, a deeper DAS28 decrease was observed in patients when CD4+ cell count is decreased: median [interquartile range] of DAS28 was 3.7 [2.9-4.4] and 4.5 [3.7-5.3] in patients with and without CD4+ decrease, respectively. CONCLUSIONS: This is the first study to quantify the relationship between rituximab concentrations, CD4+ count and DAS28 in RA patients. This model showed that approximately 75% of patients had CD4+ count decrease, and that the clinical improvement is 2-fold higher in patients with CD4+ cells decrease than in others.
30551432 Molecular modulators of celastrol as the keystones for its diverse pharmacological activit 2019 Jan In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
31322028 Increased risk of osteoporotic fractures in Swedish patients with rheumatoid arthritis des 2019 Nov Objective: To study the difference in incidence and risk of fragility fractures between rheumatoid arthritis (RA) patients followed up early in the disease and the general population in Sweden; and the fracture risk changes in RA patients diagnosed in the 1990s and 2000s because of earlier, more potent pharmacological treatment in the later period.Method: Patients with early RA were recruited from the BARFOT cohort, a Swedish multicentre observational study of early RA patients (n = 2557). All patients fulfilled 1987 American College of Rheumatology criteria and were included between 1992 and 2006. Each patient was matched by gender, age, and residential area with four controls from the general population (n = 10 228). Fractures of forearm, upper arm, and hip were identified by ICD-9 and ICD-10 codes through Swedish national medical registries.Results: During follow-up of 12.9 ± 4.7 years (mean ± sd), 14% (n = 470) of RA patients and 11% (n = 1418) of controls experienced a fracture (p < 0.001). When dividing the patients and controls into two groups according to inclusion period, an 8 year follow-up time was used. RA patients included in the 1990s had a higher incidence rate (IR) of hip and other fractures. RA patients included in the 2000s had a higher IR of all fracture sites. The hazard ratio of fractures was 1.4 in the total RA cohort, and the risk was increased in both the 1990s and 2000s.Conclusion: We observed an increased risk of fragility fractures in RA patients diagnosed in both the 1990s and 2000s, despite patients in the 2000s obtaining potent pharmacological treatment early in the disease.
30289986 Functional and phenotypic heterogeneity of Th17 cells in health and disease. 2019 Jan BACKGROUND: Th17 cells have nonredundant roles in maintaining immunity, particularly at mucosal surfaces. These roles are achieved principally through the production of cytokines and the recruitment of other immune cells to maintain the integrity of mucosal barriers and prevent the dissemination of microorganisms. Th17 cells are heterogeneous and exhibit a considerable degree of plasticity. This allows these cells to respond to changing environmental challenges. However, Th17 cells also play pro-inflammatory roles in chronic autoimmune diseases. The trigger(s) that initiate these Th17 responses in chronic autoimmune diseases remain unclear. DESIGN: In this report, we provide an overview of studies involving animal models, patient data, genome wide association studies and clinical trials targeting IL-17 for treatment of patients to gain a better understanding of the pathogenic roles of Th17 cells play in a range of autoimmune diseases. RESULTS: The report sheds light on likely triggers that initiate or perpetuate Th17 responses that promote chronic inflammation and autoimmunity. The divergent effects of tumour necrosis factor alpha blockade on Th17 cells in patients, is explored. Furthermore, we highlight the role of Th17 cells in inducing autoreactive B cells, leading to autoantibody production. Pathogenic bacterial species can change Th17 cell phenotype and responses. These findings provide insights into how Th17 cells could be induced to promoting autoimmune disease pathogenesis. CONCLUSION: This article provides an overview of the distinct roles Th17 cells play in maintaining immunity at mucosal surfaces and in skin mucosa and how their functional flexibility could be linked with chronic inflammation in autoimmune rheumatic diseases.