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ID PMID Title PublicationDate abstract
31903246 Therapeutic issues with, and long-term outcomes of, pulmonary mycobacterial tuberculosis t 2019 Nov BACKGROUND: Real-world data on treatment safety and outcome of pulmonary tuberculosis (PTB) in patients with rheumatic diseases (RDs) are scarce. This study explored the therapeutic issues of standard first-line anti-tuberculosis (TB) medication in patients in whom PTB complicated autoimmune RDs. METHODS: Observational, retrospective study was conducted in an intermediate TB burden area, South Korea. We evaluated the safety profile of, and adherence to, standard first-line anti-TB medication in PTB patients with systemic RD and assessed the long-term treatment outcomes, up to 84 months after treatment completion. RESULTS: We included 37 patients suffering from PTB with RD (case group) and 191 without RD (control group). Rheumatoid arthritis (RA) was the most common RD (24 PTB patients, 64.9%). The frequency of severe adverse drug reactions (ADRs) was significantly higher in the case group than in the control group (36.1% vs. 12.5%, P=0.003). Severe gastrointestinal problems were the most commonly observed ADRs, with a high frequency consistently noted in both groups. Changes in first-line anti-TB medication because of severe ADRs were significantly more frequent in the case group, compared with the control group (19.4% vs. 8.3%, P=0.046). No significant between-group difference was evident in terms of long-term unfavorable outcomes (including relapse and mortality) (5.7% cases vs. 1.2% controls, P=0.146). CONCLUSIONS: Clinicians may encounter difficulties when treating PTB in patients with RD. Despite the favorable long-term outcomes of RD patients, the outcomes of individual patients such as those with systemic lupus erythematosus (SLE) should be interpreted with caution during post-therapy follow-up.
31888660 AliClu - Temporal sequence alignment for clustering longitudinal clinical data. 2019 Dec 30 BACKGROUND: Patient stratification is a critical task in clinical decision making since it can allow physicians to choose treatments in a personalized way. Given the increasing availability of electronic medical records (EMRs) with longitudinal data, one crucial problem is how to efficiently cluster the patients based on the temporal information from medical appointments. In this work, we propose applying the Temporal Needleman-Wunsch (TNW) algorithm to align discrete sequences with the transition time information between symbols. These symbols may correspond to a patient's current therapy, their overall health status, or any other discrete state. The transition time information represents the duration of each of those states. The obtained TNW pairwise scores are then used to perform hierarchical clustering. To find the best number of clusters and assess their stability, a resampling technique is applied. RESULTS: We propose the AliClu, a novel tool for clustering temporal clinical data based on the TNW algorithm coupled with clustering validity assessments through bootstrapping. The AliClu was applied for the analysis of the rheumatoid arthritis EMRs obtained from the Portuguese database of rheumatologic patient visits (Reuma.pt). In particular, the AliClu was used for the analysis of therapy switches, which were coded as letters corresponding to biologic drugs and included their durations before each change occurred. The obtained optimized clusters allow one to stratify the patients based on their temporal therapy profiles and to support the identification of common features for those groups. CONCLUSIONS: The AliClu is a promising computational strategy to analyse longitudinal patient data by providing validated clusters and by unravelling the patterns that exist in clinical outcomes. Patient stratification is performed in an automatic or semi-automatic way, allowing one to tune the alignment, clustering, and validation parameters. The AliClu is freely available at https://github.com/sysbiomed/AliClu.
31784864 Rheumatological publications from Malaysia: a bibliometric study. 2020 Feb OBJECTIVES: To assess the content, authorship and study design of rheumatological publications written by Malaysian authors or about rheumatological conditions in Malaysia. METHODS: The Malaysian Medical Repository (MyMedR), a web-based database of Malaysian health and medical publications, and Scopus were searched to retrieve rheumatological publications from Malaysia, for the period 1950 until 30 June 2019. The type and number of publications in each rheumatological subject area and the overall trend of publication numbers and citations were analysed. RESULTS: 547 publications were found for the time period studied. There was a 27-fold increase in the number of publications from the period up to 1980 compared to 2010-2019. The median number of citations per paper was 5, but unlike the number of publications, there was only a slight increase in the number of citations with time. 84.5% of the papers were cited at least once. The top 3 conditions generating the most publications were systemic lupus erythematosus, 36.7%, followed by rheumatoid arthritis, 17.0%, and osteoporosis, 13.9%. CONCLUSIONS: The number of rheumatological publications in Malaysia have increased over time, especially in the last decade. However, the average number of citations per publications remains low and the majority of publications are in journals with low impact factors. Thus, the quality of rheumatological publications from Malaysia can be further improved.Key Points• There have been only a limited number of bibliometric analysis of rheumatology publications from Asia.• In Malaysia, the number of rheumatology publications has increased over time.• However, there is still room for improvement in terms of the quality of the publications.
31733367 Comparative United States autoimmune disease rates for 2010-2016 by sex, geographic region 2020 Jan PURPOSE: AIDs may disproportionately impact specific racial groups, but autoimmune (AID) prevalence information by minority racial group is sparse for many AIDs. The objective of this analysis was to supplement previously published AID prevalence rates by providing information on race rate ratios (minority race populations compared to Caucasian populations) in the United States. Preliminary to estimating race rate ratios, contemporary US-specific, health care utilization-based AID prevalence rates and female-to-male ratios were estimated and compared to previously published AID prevalence rates. METHODS: We used a large national electronic medical record database of 52 million individuals to estimate age-adjusted direct standardized rates for 22 AIDs for 2010 through 2016 by gender, race, and US census division. These were compared to previously published estimates. RESULTS: Female-to-male ratios were comparable with published studies. Almost all observed Multiracial AID rates were significantly higher than Caucasian rates, as well as 9 of 22 AID rates observed among Native Americans and 8 of 22 AID rates estimated among African-American patients. Regional variation was noted: highest African-American systemic lupus erythematosus rates were observed in the West North Central and South Atlantic divisions, highest African-American multiple sclerosis rates in the South Atlantic and Pacific divisions, and highest Native American rheumatoid arthritis rates in the West North Central, Mountain, and Pacific divisions. CONCLUSIONS: Substantial AID heterogeneity exists by race and by geographic area. An important research area is further exploring factors related to heterogeneity such as potential interactions between genetic susceptibility and environmental factors.
31721311 The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and fa 2020 Jan Several cytokines signalling via Janus Kinase (JAK) proteins have been implicated in the pathogenesis of immune-mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). Tofacitinib, a small JAK inhibitor, is approved for the treatment of RA and has demonstrated good efficacy in psoriasis phase III clinical trials. In this work, we analysed the in vitro effects of tofacitinib on the functions of human dendritic cells (DCs) and macrophages. When assessing the effects of tofacitinib on monocyte-derived DCs, we observed reduced differentiation of monocytes into immature DCs, as evidenced by a decreased transcription of CD209 and CD80. Phenotype assessment in the presence of tofacitinib suggested a switch towards a M1-like macrophage phenotype, as evidenced by the expression of M1 markers such as iNOS, as well as cytokines typically expressed by M1 cells, including IL-12 and IL-23. Of note, Arginase1 and CD200R, typically expressed by M2 cells, were absent on tofacitinib-treated DCs. Furthermore, tofacitinib affected the response of differentiated DCs to maturation stimuli such as LPS and IFNγ, resulting in a partial up-regulation of IL-23 and down-regulation of IL-12, as assessed by qPCR. When investigating macrophage development, we found that tofacitinib inhibited the ability of monocytes to differentiate and polarize into regulatory M2 macrophages, while rather enhancing the ability to develop into inflammatory M1-like macrophages, as evidenced by decreased expression of the M2 marker CD200R and enhanced production of IL-12 and IL-23. In conclusion, tofacitinib impacts the differentiation of human DCs and macrophages, it particularly favours generation of M1-like pro-inflammatory macrophages.
31516977 The risk factors and an evidence-based protocol for the management of persistent wound dra 2019 Sep BACKGROUND: Persistent wound drainage (PWD) is one of the major risk factors for periprosthetic joint infections (PJIs), arguably the most dreaded complication after total joint arthroplasty (TJA). The aim of this study was to identify the risk factors for PWD and provide a stepwise management protocol for it. METHODS: A retrospective review of 4873 TJAs was performed. After determining patients with PWD, a logistic regression model was designed to identify the risk factors using Charlson and Elixhauser comorbidity indexes. Finally, the protocol that was instituted for the management of PWD and its success rate was presented. RESULTS: The prevalence of PWD was 6.2% (302 of 4873). Of these, 196 did not require any surgical interventions, and drainage stopped with local wound care. 106 patients required surgical intervention, of which, 64 underwent superficial irrigation and debridement and 42 underwent deep irrigation and debridement with modular components exchange. Patients with PWD had significantly higher rates of PJI (odds ratio [OR]: 16.9; 95% confidence interval [CI]: 9.1-31.6). Risks factors were diabetes (OR: 21.2; 95% CI: 12.8-25.1), morbid obesity (OR: 17.3; 95% CI: 14.7-21.5), rheumatoid arthritis (OR: 14.2; 95% CI: 11.7-16.5), chronic alcohol use (OR: 4.3; 95% CI: 2.3-6.1), hypothyroidism (OR: 2.8; 95% CI: 1.3-4.2), and female gender (OR: 1.9; 95% CI: 1.1-2.2). CONCLUSIONS: Several modifiable risk factors of PWD were identified. Surgeons must be cognizant of these comorbidities and optimize patients' general health before an elective TJA. Our results demonstrated that PWD ceased in about 65% of the patients with local wound care measures alone. Patients with PWD were at substantially higher risk for PJI.
31466263 Regulated hAAT Expression from a Novel rAAV Vector and Its Application in the Prevention o 2019 Aug 28 We, and others, have previously achieved high and sustained levels of transgene expression from viral vectors, such as recombinant adeno-associated virus (rAAV). However, regulatable transgene expression may be preferred in gene therapy for diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis (RA), in which the timing and dosing of the therapeutic gene product play critical roles. In the present study, we generated a positive feedback regulation system for human alpha 1 antitrypsin (hAAT) expression in the rAAV vector. We performed quantitative kinetics studies in vitro and in vivo demonstrating that this vector system can mediate high levels of inducible transgene expression. Transgene induction could be tailored to occur rapidly or gradually, depending on the dose of the inducing drug, doxycycline (Dox). Conversely, after withdrawal of Dox, the silencing of transgene expression occurred slowly over the course of several weeks. Importantly, rAAV delivery of inducible hAAT significantly prevented T1D development in non-obese diabetic (NOD) mice. These results indicate that this Dox-inducible vector system may facilitate the fine-tuning of transgene expression, particularly for hAAT treatment of human autoimmune diseases, including T1D.
31235653 The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inf 2019 Jul Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of seemingly unrelated conditions, such as multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel diseases, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus. Despite differing etiologies, these diseases share common inflammatory pathways, which lead to damage in primary target organs and frequently to a plethora of systemic effects as well. The purinergic signaling complex comprising extracellular nucleotides and nucleosides and their receptors, the P2 and P1 purinergic receptors, respectively, as well as catabolic enzymes and nucleoside transporters is a major regulatory system in the body. The purinergic signaling complex can regulate the development and course of IMIDs. Here we provide a comprehensive review on the role of purinergic signaling in controlling immunity, inflammation, and organ function in IMIDs. In addition, we discuss the possible therapeutic applications of drugs acting on purinergic pathways, which have been entering clinical development, to manage patients suffering from IMIDs.
31077015 Where Is Dopamine and how do Immune Cells See it?: Dopamine-Mediated Immune Cell Function 2020 Mar Dopamine is well recognized as a neurotransmitter in the brain, and regulates critical functions in a variety of peripheral systems. Growing research has also shown that dopamine acts as an important regulator of immune function. Many immune cells express dopamine receptors and other dopamine related proteins, enabling them to actively respond to dopamine and suggesting that dopaminergic immunoregulation is an important part of proper immune function. A detailed understanding of the physiological concentrations of dopamine in specific regions of the human body, particularly in peripheral systems, is critical to the development of hypotheses and experiments examining the effects of physiologically relevant dopamine concentrations on immune cells. Unfortunately, the dopamine concentrations to which these immune cells would be exposed in different anatomical regions are not clear. To address this issue, this comprehensive review details the current information regarding concentrations of dopamine found in both the central nervous system and in many regions of the periphery. In addition, we discuss the immune cells present in each region, and how these could interact with dopamine in each compartment described. Finally, the review briefly addresses how changes in these dopamine concentrations could influence immune cell dysfunction in several disease states including Parkinson's disease, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, as well as the collection of pathologies, cognitive and motor symptoms associated with HIV infection in the central nervous system, known as NeuroHIV. These data will improve our understanding of the interactions between the dopaminergic and immune systems during both homeostatic function and in disease, clarify the effects of existing dopaminergic drugs and promote the creation of new therapeutic strategies based on manipulating immune function through dopaminergic signaling. Graphical Abstract.
30945150 Arthroscopic release for the severely stiff elbow. 2020 Apr BACKGROUND: Arthroscopic release for the stiff elbow has been widely used, but there are no reports limited to severe stiffness. The purpose of this study was to investigate the outcomes of severe cases. MATERIALS AND METHODS: Ten patients with 10 severely stiff elbows defined by a limited arc of ≤ 60° underwent this arthroscopic release. Causes of stiffness were post-traumatic stiffness (one patient), osteoarthritis (three patients), and rheumatoid arthritis (six patients). Using arthroscopy, the capsule contracture and the intra-articular fibrosis were removed and the impinging osteophyte and part of the radial head were resected. For four patients with preoperative ulnar nerve symptoms or contracture of the posterior oblique ligament of the medial collateral ligament, mini-open ulnar nerve neurolysis and release of the posterior oblique ligament were performed. Patients were followed up for an average of 24 months. RESULTS: Arthroscopic release could be performed without any intraoperative complications. Range of motion for the elbow significantly improved from 95° of flexion and - 55° of extension to 109° of flexion and - 32° of extension. The Mayo Elbow Performance Score also improved from 56 points to 80 points. Two patients underwent a second arthroscopic surgery and gained further arc of motion. One patient showed osteophyte reformation and needed revision open surgery 1 year after the initial surgery. CONCLUSIONS: Arthroscopic release for the severely stiff elbow could improve range of motion. Careful attention should be given during surgery to avoid complications such as intramuscular bleeding or nerve damage.
30674376 Elucidating the risk factors for chronic obstructive pulmonary disease: an umbrella review 2019 Jan 1 Chronic obstructive pulmonary disease (COPD) is commonly attributed to smoking, and other potential risk factors are ignored. We aimed to critically appraise the epidemiological credibility of the risk factors for COPD that have been examined in published meta-analyses. We performed a systematic search to capture systematic reviews and meta-analyses of observational studies on environmental factors and biomarkers for risk of COPD. We applied a set of standardised methodological criteria based on the level of statistical significance, sample size, between-study heterogeneity and statistical biases. Our search yielded 11 eligible papers, including 18 meta-analyses on environmental factors or biomarkers for COPD risk, and eight eligible papers with systematic reviews only. Eleven associations achieved statistical significance at P < 0.001 and six associations at P < 1 × 10(-6). Thirteen associations presented an I²  50%, while six associations had evidence of small-study effects and/or excess significance bias. History of tuberculosis or rheumatoid arthritis, exposure to biomass fuels, tobacco smoking and second hand smoking were supported by high epidemiological credibility for an increased risk of COPD. Furthermore, highly suggestive evidence was found for increased levels of serum C-reactive protein, and serum fibrinogen in COPD patients compared with healthy controls. To summarise, our approach suggests that, while a proportion of COPD patients are non-smokers, only a narrow range of risk factors not related to smoking have been studied for an association with COPD. There is also a need to decipher possible protective factors in COPD pathogenesis given that more than a half of ever-smokers do not develop COPD.
30666652 Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases 2019 Aug Type 1 regulatory T (Tr1) cell is a special type of T regulatory cells with surface molecular markers such as lymphocyte-activation gene 3 and CD49b. A key property of Tr1 cells is the capability to produce high-level interleukin 10 (IL-10) upon activation, in a FOXP3-independent manner. The immunosuppressive function of IL-10 producing Tr1 cells has been extensively studied for many years. Autoimmune diseases (AIDs) are conditions in which the immune system breaks down and starts to attack the body. AIDs include inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis (MS), type 1 diabetes mellitus, Greaves' disease, and so forth. In recent years, more and more studies have documented that the number of Tr1 cells is decreased and the function is inhibited in a variety of AIDs, among which MS is the most widely studied. The protocol for engineering Tr1 cell therapy has been established and is gradually being used in clinical practice in recent years. Tr1 cell therapy has been proven to be safe and effective, but it is mainly involved in myeloid leukemia, graft versus host disease currently. Its therapeutic role in AIDs still needs to be further explored. In this study, we will summarize the research advances of Tr1 cells in AIDs, which will provide useful information for treating AIDs through Tr1 cell therapy in the future.
30588552 Clinical features of hypertrophic pachymeningitis in a center survey. 2019 Mar BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.
30470476 The systematic case-referent method. 2019 Apr The systematic case-referent method is a special case-referent design originally developed for pharmacoepidemiologic research purposes. It consists in the systematic collection of series of incident cases of various disorders and the assembling of a general reference pool, from which "controls" are secondarily selected to be matched to specific cases. Both series are collected independently from each other and with no a priori hypothesis to be investigated. The reference pool can be either general or limited to a subpopulation, representative of the source population of the cases. Based on clinical recruitment of cases and referents, the design allows a very high specificity of diagnosis and documentation of clinical variables. All cases and referents are systematically documented on all treatments received before the incidence of the cases or before identification of referents. This documentation is done preferentially using objective sources assembled independently (linkage to claims data, medical records, pharmacy records, prescription records, hospital discharge letters). It can be completed with patients' interviews using standardised research tools, in particular for over-the-counter drug use and self-medication, and for the documentation of adherence to treatment and specific time-windows of exposure. Likewise, all cases and all referents are systematically documented on a series of risk factors, which are common to most epidemiological studies and are not hypothesis-dependent. Whenever the documentation of a confounding factor specific to the disease at hand is necessary, additional questionnaires can be applied to all or a sample of patients. The method has been successfully implemented for the pharmacoepidemiologic study of myocardial infarction, stroke, lupus, multiple sclerosis, rheumatoid arthritis, Guillain Barré syndrome, idiopathic thrombocytopenic purpura, type 1 diabetes mellitus, suicide attempts, breast cancer, and other disorders, for the analysis of the risk or preventing action of NSAIDs, statins, antiplatelet agents, anticoagulants, insulins, vaccines and other drugs.
30421793 Autoantibodies to killer cell immunoglobulin-like receptor 3DL1 in patients with systemic 2019 Mar A genetic variant of the killer immunoglobulin-like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA) and 17 healthy control subjects for anti-KIR3DL1 activity by an enzyme-linked immunosorbent assay (ELISA) using recombinant KIR3DL1-enhanced green fluorescent protein (EGFP) and EGFP proteins. Anti-KIR3DL1 antibodies were detected in 22 (79%) of the 28 patients with SLE, whereas they were present in only three (27%) of the 11 patients with RA examined. Notably, 10 (91%) of the 11 samples from patients with SLE prior to therapy had anti-KIR3DL1 antibodies. None of the samples from healthy donors were positive for the antibodies. Here, we report the presence of anti-KIR3DL1 antibodies in the sera of patients with SLE for the first time. Anti-KIR3DL1 autoantibodies may be involved in the pathogenesis of autoimmune diseases.
30412715 Autophagy protects against redox-active trace metal-induced cell death in rabbit synovial 2019 Jan 1 Reactive oxygen species (ROS) are implicated to play a role in initiating rheumatoid arthritis (RA) pathogenesis. We have investigated the mechanism(s) by which essential redox-active trace metals (RATM) may induce cell proliferation and cell death in rabbit synovial fibroblasts. These fibroblast-like synovial (FLS) cells, which express Toll-like receptor 4 (TLR4), were used as a model system that plays a role in potentially initiating RA through oxidative stress. Potassium peroxychromate (PPC, [Cr(5+)]), ferrous chloride (FeCl(2), [Fe(2+)]), and cuprous chloride (CuCl, [Cu(+)]) in the indicated valency states were used as exogenous pro-oxidants that can induce oxidative stress through TLR4 coupled activation that also causes HMGB1 release. We measured the proliferation index (PI) of FLS, and examined the effect of RATM oxidants on apoptosis and autophagy by fluorescence cell-sorting flow cytometry (FC). Cell cycle was analysed by FC and autophagy-related protein expression levels were measured by western blot. Our data showed that as RATM as prooxidants increased intracellular ROS (iROS) that can induce oxidative stress. Whereas iROS increased PI in FLS, these reactive species also protected cells against apoptosis by inducing autophagy. Our results indicate that ROS/TLR4-coupled activation may contribute to the pathogenesis of RA in FLS by induction of autophagy. The signalling pathway by which inflammation and its tissue destructive sequel may occur in RA underlies the need for developing therapeutic agents that can inhibit release of tissue-damaging high mobility group box 1 (HMGB1), cytokines, and possess both trace metal chelating capacity and oxidant scavenging properties in a directed combinatorial therapy for RA.
31680207 Biologic therapy in the idiopathic inflammatory myopathies. 2020 Feb The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases resulting from inflammation of muscle and manifesting as weakness, though a range of extra-muscular manifestations are observed. These are often correlated closely with disease subtype and the presence of myositis-specific/myositis-associated antibodies. IIM are notoriously difficult to treat and often refractory to glucocorticoid therapy and synthetic immunosuppressants. Both the innate and adaptive immune systems are implicated in the pathogenesis of IIM. A growing understanding of the key cytokines as well as the cell-mediated and antibody effectors of disease has identified multiple potential targets for biologic therapy. The most widely used of these is B-cell depletion via rituximab though the tumour necrosis factor inhibitors and other biologic therapies used in diseases such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis have also been trialled. This review summarises the literature thus far on biologic therapy in IIM, highlighting both the significant trials that influence current treatment regimens and also the continuing need for further research to inform more effective therapies.
31638197 miR‑222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeti 2019 Dec Intervertebral disc degeneration (IDD) is characterized by abnormal induction of apoptosis in intervertebral disc nucleus pulposus (NP) cells. Previous studies indicated that miR‑222 was upregulated in patients with rheumatoid arthritis. However, the effects of miR‑222 in IDD remain unclear. The present study aimed to demonstrate the role of miR‑222 in NP cells. The levels of miR‑222 in patients with IDD were measured by reverse transcription‑quantitative PCR. Cell Counting Kit‑8 and western blotting assays were used to detect cell proliferation and apoptosis‑associated protein levels, respectively. In addition, luciferase reporter assays were performed to validate the predicted target genes of miR‑222. miR‑222 was significantly upregulated in patients with IDD. Overexpression of miR‑222 inhibited cell proliferation and induced cell apoptosis. Moreover, overexpression of miR‑222 resulted in an upregulation in the levels of Bax and cleaved caspase 3, and a downregulation in the levels of Bcl‑2 in NP cells. The luciferase reporter assays demonstrated that Bcl‑2 is a target of miR‑222. Furthermore, overexpression of miR‑222 increased the levels of cytochrome c, apoptotic protease activating factor‑1 and cleaved caspase 9 in NP cells. Conversely, downregulation of miR‑222 could promote the proliferation of NP cells. The present data demonstrated that miR‑222 induced apoptosis in NP cells by directly targeting Bcl‑2. Therefore, miR‑222 may act as a potential therapeutic target for the treatment of IDD.
31615316 Should isoniazid prophylaxis be prescribed to the patients under tumor necrosis factor-alp 2020 Dec INTRODUCTION: The aim of this study was to present the follow-up results of 110 patients who were given anti-tumor necrosis factor alpha (TNF-α) therapy for rheumatic and dermatologic diseases in a country with a high rates of active and latent tuberculosis bacillus infection. MATERIAL AND METHODS: Between February 2008 and January 2015, 110 cases in the age range of 23-77 who are using anti-TNF-α were included in the study retro-prospectively. RESULTS: 52.7% of them (n = 58) were male. The most common diagnoses were rheumatoid arthritis (42.7%) and ankylosing spondylitis (38.2%). Most frequently given treatment were infliximab 37.3% and etanercept 30.9%, respectively. The 65 patients whose first tuberculin skin test (TST) value "5 mm and above" was started daily 300 mg INH prophylaxis for 9 months but 3 patients had not been started because of refusing treatment. In only one case chemoprophylaxis has had to be interrupted because of high liver function test due to the INH prophylaxis. TST conversion was observed in 14 patients. Further follow-up, it was observed that 4 patients had TST's positivity. Isoniazide (INH) prophylaxis was started these 18 patients (42.9%). Although INH prophylaxis has been given in two patients, they developed active tuberculosis in follow-up. CONCLUSION: Considering the INH resistance in our country, all patients especially the ones with residual lesion and history of previous exposure, should be followed up closely during the anti-TNF-α treatment.
31610201 A review for the anti-inflammatory effects of paeoniflorin in inflammatory disorders. 2019 Nov 15 Inflammatory disorders result from abnormal immune response and their incidence has increased recently. Thus, there is an urgent need to discover new treatments for inflammatory disorders. In recent years, the natural products contained in Chinese herbs have attracted much attention worldwide owing to their anti-inflammatory effects. Paeoniflorin (PF) is a bioactive compound purified from the Chinese herb Paeonia lactiflora and reports have recently emerged suggesting the great potential of P. lactiflora as an agent to counter inflammatory disorders. The anti-inflammatory effects of PF have been revealed by in vitro studies and in vivo animal experiments of different inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and asthma. This review systematically describes the recent progress of studies on the mechanism of PF and its therapeutic potential in inflammatory disorders.