Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
34262360 Incidental Finding of Elevated Serum Cartilage Oligomeric Matrix Protein (sCOMP) in Knee O 2021 BACKGROUND: The clinical utility of cartilage oligomeric matrix protein (COMP) as a diagnostic and prognostic biomarker is currently under intense study. COMP has been associated primarily with musculoskeletal disorders such as rheumatoid and osteoarthritis (OA) or muscular and ligament trauma. Aside from its established role as a biomarker of arthritis, an increasing number of studies have also suggested the role of COMP in tumorigenesis, based on findings of its expression in breast, prostate, and colon cancers. CASE PRESENTATION: We described the case of a 61-year-old man with knee osteoarthritis and was prescribed physical therapy and a course of prolotherapy injection. We found elevated sCOMP levels in our patient (twice higher than average). After a month of follow-up, he was diagnosed with colorectal cancer. CONCLUSION: It makes us wonder about other conditions of the patients. There is no standard COMP parameter to differentiate OA patients from colorectal cancer patients, but it considers the increase is higher in colorectal cancer patients. We suggest to clinicians who use the COMP level to monitor OA condition to be aware of other conditions when the level is much higher than average OA patients.
34201946 Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independen 2021 Jun 25 We recently reported that increased serum adiponectin was associated with rheumatoid arthritis (RA) risk in subjects with obesity. We hereby aim to determine if other adipokines associate with RA risk and if the association between adiponectin and RA is independent of other adipokines. Two nested-case control studies were performed in two different cohorts: 82 participants of the Swedish Obese Subjects (SOS) study who developed RA during follow-up matched with 410 controls, and 88 matched pairs from the Medical Biobank of Northern Sweden. Baseline levels of circulating adipokines were measured using ELISA. In a multivariable analysis in the SOS cohort, higher adiponectin was associated with an increased risk of RA independently of other adipokines (OR for RA risk: 1.06, 95% CI: 1.01-1.12, p = 0.02). No association between leptin, resistin, and visfatin levels and the risk of RA was detected. In the cohort from the Medical Biobank of Northern Sweden, higher adiponectin was associated with an increased risk of RA only in participants with overweight/obesity (OR: 1.17, 95% CI: 1.01-1.36, p = 0.03), independently of other adipokines. Our results show that in individuals with overweight/obesity, higher circulating levels of adiponectin, but not leptin, resistin, or visfatin, were associated with an increased RA risk.
34716485 Evaluation of the balance function before and after total knee arthroplasty using Berg bal 2021 Oct 30 INTRODUCTION: The purpose of this study was to evaluate balance function before and after total knee arthroplasty (TKA) using Berg balance scale (BBS). The study also aimed to identify factors associated with balance impairment. MATERIALS AND METHODS: Ninety-three knees in 90 patients were prospectively evaluated using their BBS scores, passive knee extension/flexion angles, Visual analogue scale for pain scores, hip-knee-ankle angles, and knee extensor/flexor muscle strengths before and after TKA. A total BBS score of less than 45 indicates an enhanced risk of multiple falls. Multivariate logistic regression models were performed to elucidate factors associated with post-operative BBS score. RESULTS: A significant difference in mean pre- and post-operative BBS scores were noted (49.3 ± 6.4 vs. 52.2 ± 4.7) (p < 0.05). The percentage of pre- and post-operative BBS scores less than 45 were 20% and 10% (p < 0.05). Rheumatoid Arthritis (RA), lower pre-operative BBS score, and larger post-operative knee flexion contracture were significantly associated with lower post-operative BBS score (p < 0.01). The post-operative knee flexion contracture greater than 10° was significantly associated with substantially high odds of post-operative BBS scores less than 45 (Odds ratio 7.6; 95% confidential interval 1.69-34.17). CONCLUSIONS: While TKA significantly improved BBS scores, 10% of the patients remained at a risk for multiple falls. RA, lower pre-operative BBS score, and post-operative knee flexion contracture greater than 10° retained balance impairment even after TKA.
34100976 Pulsed electromagnetic field (PEMF) as an adjunct therapy for pain management in interstit 2022 Mar INTRODUCTION AND HYPOTHESIS: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often experience chronic pelvic and even systemic pain that can be difficult to clinically manage. Pulsed electromagnetic field (PEMF) therapy, a non-invasive strategy that has shown significant efficacy for pain reduction in other chronic pain conditions, may provide benefit for pain management in patients with IC/BPS. METHODS: PEMF delivery to patients occurs via a bio-electromagnetic-energy device which consists of a flexible mat (180 × 50 cm) that the patient lies on for systemic, full-body delivery and/or a flexible pad (50 × 15 cm) for targeted delivery to a specific body region (e.g., pelvic area). The duration of individual sessions, number of sessions per day, total number of sessions, and follow-up observation period vary between previously published studies. Positive outcomes are typically reported as a significant reduction in visual analog scale (VAS) pain score and functional improvement assessed using validated questionnaires specific to the condition under study. RESULTS AND CONCLUSIONS: The use of PEMF has been evaluated as a therapeutic strategy for pain management in several clinical scenarios. Randomized, double-blinded, placebo-controlled trials have reported positive efficacy and safety profiles when PEMF was used to treat non-specific low back pain, patellofemoral pain syndrome, chronic post-operative pain, osteoarthritis-related pain, rheumatoid arthritis-related pain, and fibromyalgia-related pain. Based on these positive outcomes in a variety of pain conditions, clinical trials to evaluate whether PEMF can provide a safe, non-invasive therapeutic approach to improve symptoms of chronic pain and fatigue in patients with IC/BPS are warranted.
34055335 Psycho-sensory relationships in chronic pain. 2021 May BACKGROUND: Psychological variables contribute to pain- and injury-related outcomes. We examined the hypothesis that anatomical spread and intensity of persistent pain relate to anxiety-related variables: generalised anxiety, fear of pain and pain catastrophising. METHODS: An online survey was used to gather data from 413 women with persistent pain (low back pain, n = 139; fibromyalgia syndrome, n = 95; neck pain, n = 55; whiplash, n = 41; rheumatoid arthritis, n = 37; migraine, n = 46). The spread and intensity of pain were assessed using the McGill pain chart and a Numerical Rating Scale. A Bayesian Structural Equation Model assessed if the intensity and spread of pain increased with anxiety-related variables. Men were also surveyed (n = 80), but the sample size was only sufficient for analysing if their data were consistent with the model for women. RESULTS: Across subgroups of women, one standard deviation increase in catastrophising, generalised anxiety and fear corresponded to 27%, 7% and -1% additional pain areas and a 1.1, 0 and -0.1 change in pain intensity (on 0-10 scale), respectively. Overall, our clinical significance criterion - a 30% shift in pain variable in relation to one standard deviation increase in psychological variable - was not met. However, in subgroups it was met for pain spread (low back pain, neck pain and migraine) and pain intensity (migraine and neck pain) in relation to pain catastrophising. The model generally had low goodness-of-fit to men. CONCLUSION: These data support a meaningful relationship between some anxiety-related variables and pain in women for some conditions. Since the model did not consistently fit the men, we may conclude that the relationships are moderated by sex. Clinician attention to psychological variables as potential contributing factors can be justified; however, research is needed to understand the relationship and whether psychological treatment can reduce pain.
33780902 Chloroquine and hydroxychloroquine ototoxicity; potential implications for SARS-CoV-2 trea 2021 Sep INTRODUCTION: Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria; they have been considered for off-label and compassionate use in several countries against moderate to severe cases of COVID-19 and there's actually a massive demand of these two drugs. The aim of this paper is to briefly review the published literature, summarizing evidences about audiological implications after CQ and HCQ treatment. METHODS: We conducted a review of the literature on Medline and Pubmed platforms from 27th May 2020 to 30 May 2020. We combined MeSH terms of "chloroquine", "hydroxychloroquine", "ototoxicity", "hearing loss", "tinnitus", "deafness" and "hearing". Publications with relevant data were included. Selected data (authors, country and year; sample size; study design; audiological side effects) were extracted and summarized in a table. RESULTS: Of 45 initial studies, 14 met inclusion criteria. The authors found xix cases of HCQ ototoxicity; Tinnitus was reported in 2 cases, and it was found to be reversible or irreversible. Sensorineural hearing loss after HCQ use was reported in 7 patients; it was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. Eight papers reporting CQ ototoxicity were; tinnitus was not reported by any authors. Sensorineural hearing loss after taking CQ was reported in 6 patients; it was found to be irreversible after discontinuation of CQ in 5 patients. One patient showed abnormal gait after a single intramuscular injection of CQ. Thirteen patients' Auditory Brainstem Response (ABR) were found to be abnormal, but they resolved after CQ discontinuation. CONCLUSIONS: CQ and HCQ related ototoxicity is widely reported in the literature although the pathophysiological mechanism is not well known. Current data are not sufficient enough to support the use of CQ and HCQ as therapy for COVID-19, but considering the growing demand for these two drugs and the number of people around the world who have taken and will take CQ and HCQ, it must necessarily consider the clinical and social impact of long term audiological side effects.
33775907 Efficacy of Allogeneic Hematopoietic Cell Transplantation for Autoimmune Diseases. 2021 Jun Allogeneic hematopoietic cell transplantation (HCT) may be efficacious for autoimmune diseases (AIDs), but its efficacy for individual AIDs is unknown. Factors influencing the likelihood of relapse for each AID are also unknown. This study aimed to determine the likelihood of relapse for each common AID and to generate hypotheses about factors influencing the likelihood of relapse. We reviewed charts of adult patients with nonhematologic AIDs who had undergone HCT in Alberta (n = 21) and patients described in the literature (n = 67). We used stringent inclusion criteria to minimize the inclusion of patients whose AID may have been cured before transplantation. We also used stringent definitions of AID relapse and remission. AID relapsed in 2 of 9 patients (22%) with lupus, in 4 of 12 (33%) with rheumatoid arthritis (RA), in 0 of 4 (0%) with systemic sclerosis (SSc), in 3 of 16 (19%) with psoriasis, in 1 of 12 (8%) with Behçet's disease (BD), in 1 of 15 (7%) with Crohn's disease (CD), in 0 of 5 (0%) with ulcerative colitis (UC), in 4 of 8 (50%) with multiple sclerosis (MS), and in 3 of 3 (100%) with type 1 diabetes mellitus (T1DM). Among highly informative patients (followed for >1 year after discontinuation of immunosuppressive therapy if no relapse, or donor AID status known if relapse), relapse occurred in 0 of 3 patients with lupus, in 2 of 7 with RA, in 0 of 2 with SSc, in 3 of 6 with psoriasis, in 0 of 3 with BD, in 0 of 10 with CD, in 0 of 3 with UC, in 2 of 3 with MS, and in 2 of 2 with T1DM. There appeared to be no associations between AID relapse and low intensity of pretransplantation chemoradiotherapy, multiple lines of AID therapy (surrogate for AID refractoriness) except perhaps for lupus, absence of serotherapy for graft-versus-host disease (GVHD) prophylaxis, lack of GVHD except perhaps for lupus, or incomplete donor chimerism. Even though remission commonly occurs after HCT in lupus, RA, SSc, psoriasis, BD, CD, and UC, HCT is efficacious for only a subset of patients. The efficacy appears to be unrelated to pretransplantation therapy, GVHD, or chimerism. Large studies are needed to determine the characteristics of patients likely to benefit from HCT for each AID.
33632287 Clinical guidance for podiatrists in the management of foot problems in rheumatic disorder 2021 Feb 25 BACKGROUND: Foot and ankle problems are common in rheumatic disorders and often lead to pain and limitations in functioning, affecting quality of life. There appears to be large variability in the management of foot problems in rheumatic disorders across podiatrists. To increase uniformity and quality of podiatry care for rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis (SpA), and gout a clinical protocol has been developed. RESEARCH OBJECTIVES: [1] to evaluate an educational programme to train podiatrists in the use of the protocol and [2] to explore barriers and facilitators for the use of the protocol in daily practice. METHOD: This study used a mixed method design and included 32 podiatrists in the Netherlands. An educational programme was developed and provided to train the podiatrists in the use of the protocol. They thereafter received a digital questionnaire to evaluate the educational programme. Subsequently, podiatrists used the protocol for three months in their practice. Facilitators and barriers that they experienced in the use of the protocol were determined by a questionnaire. Semi-structured interviews were held to get more in-depth understanding. RESULTS: The mean satisfaction with the educational programme was 7.6 (SD 1.11), on a 11 point scale. Practical knowledge on joint palpation, programme variation and the use of practice cases were valued most. The protocol appeared to provide support in the diagnosis, treatment and evaluation of foot problems in rheumatic disorders and the treatment recommendations were clear and understandable. The main barrier for use of the protocol was time. The protocol has not yet been implemented in the electronic patient file, which makes it more time consuming. Other experienced barriers were the reimbursement for the treatment and financial compensation. CONCLUSIONS: The educational programme concerning the clinical protocol for foot problems in rheumatic disorders appears to be helpful for podiatrists. Podiatrists perceived the protocol as being supportive during patient management. Barriers for use of the protocol were identified and should be addressed prior to large scale implementation. Whether the protocol is also beneficial for patients, needs to be determined in future research.
33460504 More than just protein building blocks: how amino acids and related metabolic pathways fue 2021 Jun Macrophages represent the first line of defence in innate immune responses and additionally serve important functions for the regulation of host inflammation and tissue homeostasis. The M1/M2 model describes the two extremes of macrophage polarization states, which can be induced by multiple stimuli, most notably by LPS/IFN-γ and IL-4/IL-13. Historically, the expression of two genes encoding for enzymes, which use the same amino acid as their substrate, iNOS and ARG1, has been used to define classically activated M1 (iNOS) and alternatively activated M2 (ARG1) macrophages. This 'arginine dichotomy' has recently become a matter of debate; however, in parallel with the emerging field of immunometabolism there is accumulating evidence that these two enzymes and their related metabolites are fundamentally involved in the intrinsic regulation of macrophage polarization and function. The aim of this review is to highlight recent advances in macrophage biology and immunometabolism with a specific focus on amino acid metabolism and their related metabolic pathways: iNOS/ARG1 (arginine), TCA cycle and OXPHOS (glutamine) as well as the one-carbon metabolism (serine, glycine).
33452837 Is implant surgery a risk factor for osteonecrosis of the jaw in older adult patients with 2021 Apr OBJECTIVES: This study aimed to investigate the association between dental implant therapy and osteonecrosis of the jaw (ONJ) in osteoporotic patients and the relationship between tooth extraction, dental implantation, and ONJ. MATERIAL AND METHODS: This retrospective cohort study used the Customized Health Information Data from the National Health Insurance Corporation in South Korea. The study population included patients older than 70 years with a history of osteoporosis; the cases included patients who had undergone dental implant surgery between July 2014 and July 2016 with specific procedure codes. The case and control cohorts were stratified by tooth extraction because it was the strongest risk factor to consider in this study. Each group of patients was matched using the propensity score. To investigate the relationship between dental implants and ONJ, a Cox proportional hazard model was applied to socio-economic factors, comorbidities, and bisphosphonates (BPs). All analyses were conducted using SAS statistical software. RESULTS: Based on the fully adjusted model, the propensity score-matched osteoporosis patients with dental implants had a 0.51 times hazard ratio of osteonecrosis. On the contrary, tooth extraction was associated with a higher risk of ONJ (HR = 5.89). The patients with rheumatoid arthritis (RA) and those using BPs had a higher HR, respectively, 6.80 and 4.09 HR (p < .001). CONCLUSIONS: Dental implantation was not a risk factor and patients with implants show rather lower ratios. However, older osteoporotic Korean patients who had undergone tooth extraction had higher risks of ONJ. A significantly higher risk of ONJ was associated with RA and BPs as well.
33441153 QALY league table of Iran: a practical method for better resource allocation. 2021 Jan 13 BACKGROUND: The limited health care resources cannot meet all the demands of the society. Thus, decision makers have to choose feasible interventions and reject the others. We aimed to collect and summarize the results of all cost utility analysis studies that were conducted in Iran and develop a Quality Adjusted Life Year (QALY) league table. METHODS: A systematic mapping review was conducted to identify all cost utility analysis studies done in Iran and then map them in a table. PubMed, Embase, Cochrane library, Web of Science, as well as Iranian databases like Iran Medex, SID, Magiran, and Barakat Knowledge Network System were all searched for articles published from the inception of the databases to January 2020. Additionally, Cost per QALY or Incremental Cost Utility Ratio (ICUR) were collected from all studies. The Joanna Briggs checklist was used to assess quality appraisal. RESULTS: In total, 51 cost-utility studies were included in the final analysis, out of which 14 studies were on cancer, six studies on coronary heart diseases. Two studies, each on hemophilia, multiple sclerosis and rheumatoid arthritis. The rest were on various other diseases. Markov model was the commonest one which has been applied to in 45% of the reviewed studies. Discount rates ranged from zero to 7.2%. The cost per QALY ranged from $ 0.144 in radiography costs for patients with some orthopedic problems to $ 4,551,521 for immune tolerance induction (ITI) therapy in hemophilia patients. High heterogeneity was revealed; therefore, it would be biased to rank interventions based on reported cost per QALY or ICUR. CONCLUSIONS: However, it is instructive and informative to collect all economic evaluation studies and summarize them in a table. The information on the table would in turn be used to redirect resources for efficient allocation. in general, it was revealed that preventive programs are cost effective interventions from different perspectives in Iran.
33038496 Patient risk factors for acromial stress fractures after reverse shoulder arthroplasty: a 2021 Jul BACKGROUND: Despite the growing recognition of acromial stress fractures (ASFs) after reverse total shoulder arthroplasty (RTSA), most of the current data are derived from single-center studies with limited generalizability. This multicenter study investigated the incidence of ASFs after RTSA and identified preoperative patient characteristics associated with their occurrence. METHODS: Using 2 institutional registries from different regions of the United States, we identified 1479 patients undergoing either primary or revision RTSA between 2013 and 2018 with minimum 3-month follow-up. ASFs were defined as radiographic evidence of an acromial or scapular spine fracture with clinical symptoms (eg, tenderness over the acromion or scapular spine). Multivariable logistic regression was performed to identify preoperative patient factors associated with the development of ASFs. RESULTS: Overall, 54 (3.7%) patients were diagnosed with an ASF after RTSA. Patient-related factors independently associated with the development of an ASF included female sex (odds ratio [OR], 2.21 reference: male; 95% confidence interval [CI], 1.03-4.74; P < .05), rheumatoid arthritis (OR, 2.30; 95% CI, 1.02-5.16; P < .05), osteoporosis (OR, 2.55; 95% CI, 1.24-5.21; P < .05), a diagnosis of degenerative joint disease with rotator cuff tear (OR, 4.74 reference: degenerative joint disease without rotator cuff tear; 95% CI, 1.84-12.23; P < .05), and fracture malunion/nonunion (OR, 5.21; 95% CI, 1.20-22.76; P < .05). CONCLUSIONS: The non-negligible percentage of ASFs that occur after RTSA is associated with the diagnoses of rotator cuff dysfunction and chronic fracture sequelae in female patients with suboptimal bone health. This information can be used to counsel patients and set expectations about potential setbacks in recovery.
32902896 Differing Progression to Posterior Glottic Stenosis in Autoimmune and Idiopathic Subglotti 2021 Aug OBJECTIVES/HYPOTHESIS: We sought to characterize rates of progression to posterior glottic stenosis (PGS) from autoimmune or idiopathic subglottic stenosis. STUDY DESIGN: This was a retrospective review. METHODS: Patients from a tertiary-care laryngology practice over a 10-year period with autoimmune or idiopathic subglottic stenosis (SGS) were included. Patients with a history of prolonged intubation or other causes of iatrogenic stenosis were excluded. PGS was confirmed on videostrobolaryngoscopy recordings by a fellowship-trained laryngologist. PGS type (1-4) was also recorded. Demographic information was recorded, and if applicable, autoimmune disease type was specified. Time until PGS was recorded along with the number of interventions. Chi-squared analysis was used to compare PGS in autoimmune and idiopathic SGS. RESULTS: A total of 77 patients were identified with autoimmune (32 patients) or idiopathic (45 patients) subglottic stenosis. Autoimmune pathologies included systemic lupus erythematosus, granulomatosis with polyangiitis (GPA), rheumatoid arthritis, relapsing polychondritis, and sarcoidosis, with GPA the most common (14/32). Patients with autoimmune SGS had a higher rate of PGS (10 of 32) compared to idiopathic subglottic stenosis (1 of 45) for an odds ratio of 20 (95% CI: 2.4-166.4, P = .006). Patients with idiopathic SGS were more likely to be female (all 45 compared to 29/32 autoimmune, P = .07) and older (mean 53 (range 29-75) compared to 46 (20-82), P = .02). CONCLUSIONS: In this large patient cohort, autoimmune SGS patients were found to have a higher likelihood of developing PGS compared to their idiopathic counterparts, suggesting that counseling for this progression may be warranted. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1816-1820, 2021.
32880072 Estimating the relative contribution of comorbidities in predicting health-related quality 2021 Feb BACKGROUND: Little is known about the relative contribution of comorbidities in predicting the health-related quality of life (HRQoL) of people with Multiple Sclerosis (PwMS). OBJECTIVE: To determine the associations between the number of and individual comorbidities and HRQoL and estimate the relative contribution of different comorbidities on HRQoL. METHODS: Cross-sectional analysis of data on self-reported presence of 30 comorbidities and HRQoL from the Australian MS Longitudinal Study (AMSLS) participants (n = 902). HRQoL was measured using the Assessment of Quality of Life-8 Dimensions (AQoL-8D). Linear regression and general dominance analysis were used. RESULTS: Higher number of comorbidities was associated with lower HRQoL (p trend p < 0.01). Comorbidities accounted for 18.1% of the variance in HRQoL. Mental health and musculoskeletal disorders were the strongest contributors to lower HRQoL. Of individual comorbidities, systemic lupus erythematosus (SLE) [β = - 0.16 (- 0.27, - 0.05)] and depression [β = - 0.15(- 0.18, - 0.13)] were most strongly associated with overall HRQoL, depression [β = - 0.14(- 0.16, - 0.11)] and anxiety [β = - 0.10 (- 0.13, - 0.07)] with psychosocial HRQoL, and SLE [β = - 0.18 (- 0.29, - 0.07)], rheumatoid arthritis [β = - 0.11 (- 0.19, - 0.02)] and hyperthyroidism [β = - 0.11 (- 0.19, - 0.03)) with physical HRQoL. CONCLUSION: Comorbidities potentially make important contributions to HRQoL in PwMS. Our findings highlight groups of and individual comorbidities that could provide the largest benefits for the HRQoL of PwMS if they were targeted for prevention, early detection, and optimal treatment.
35295464 Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therap 2021 The persistence of increased excitability and spontaneous activity in injured peripheral neurons is imperative for the development and persistence of many forms of neuropathic pain. This aberrant activity involves increased activity and/or expression of voltage-gated Na(+) and Ca(2+) channels and hyperpolarization activated cyclic nucleotide gated (HCN) channels as well as decreased function of K(+) channels. Because they display limited central side effects, peripherally restricted Na(+) and Ca(2+) channel blockers and K(+) channel activators offer potential therapeutic approaches to pain management. This review outlines the current status and future therapeutic promise of peripherally acting channel modulators. Selective blockers of Na(v)1.3, Na(v)1.7, Na(v)1.8, Ca(v)3.2, and HCN2 and activators of K(v)7.2 abrogate signs of neuropathic pain in animal models. Unfortunately, their performance in the clinic has been disappointing; some substances fail to meet therapeutic end points whereas others produce dose-limiting side effects. Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K(+) channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na(+) channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca(2+) channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing "pain" as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a histone methyltransferase inhibitor used in the management of T-cell lymphoma, or cercosporamide a MNK 1/2 inhibitor used in treatment of rheumatoid arthritis; (vi) combination therapy using drugs that are selective for different channel types or regulatory processes; (vii) directing preclinical validation work toward the use of human or human-derived tissue samples; and (viii) application of molecular biological approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) technology.
34438028 Kirenol: A promising bioactive metabolite from siegesbeckia species: A detailed review. 2021 Dec 5 ETHNOPHARMACOLOGICAL RELEVANCE: Kirenol (Kr) is an ent-pimarane type diterpenoid that has been reported from Siegesbeckiaorientalis, S. pubescens, and S. glabrescens (family Asteraceae). These plants have been used traditionally for treating various ailments such as hypertension, neurasthenia, rheumatoid arthritis, asthma, snakebites, allergic disorders, paralysis, soreness, cutaneous disorders, rubella, menstrual disorders, numbness of limbs, dizziness, headache, and malaria. Importantly, in recent years, Kr has received great attention due to its diversified pharmacological activities. AIM OF THE STUDY: The current work aims to give an overview on the reported pharmacological activities of Kr. Furthermore, the findings regarding its methods for extraction, quantitative analysis, purification, pharmacokinetics, pharmaceutical and food preparations, biosynthesis, identification, semisynthetic analogues, and toxicity are highlighted to provide a reference and perspective for its further investigation. METHODS: Electronic databases including ScienceDirect, Web of Knowledge, SCOPUS, Wiley Online Library, Taylor & Francis, PubMed, Springer, JACS, and Google Scholar were searched up to the beginning of 2021 to identify the reported studies. RESULTS: A total of 93 articles have been reviewed. The reported data suggested that Kr possessed various bioactivities including cytotoxic, apoptotic, anticancer, anti-inflammatory, cardio-protective, anti-photo-aging, anti-adipogenic, antimicrobial, muscle function improvement, fracture and wound healing, and anti-arthritic. In addition, studies revealed that the antioxidative and anti-inflammatory activities of Kr may mediate many of its therapeutic potentials as confirmed by several in-vitro and in-vivo studies. CONCLUSION: This review provides an updated summary of the recent studies on Kr, including methods for extraction, quantitative analysis, purification, pharmacokinetics, pharmaceutical and food preparations, biosynthesis, and identification, as well as semisynthetic analogues, pharmacological activities, and toxicity. Thus, this work can provide useful considerations for planning and design future research on Kr.
34863286 Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells 2021 Dec 4 BACKGROUND: Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. METHODS: Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. RESULTS: Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. CONCLUSIONS: Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties.
34706401 Methotrexate related cutaneous adverse drug reactions: a systematic literature review. 2021 Oct 27 OBJECTIVES: Recently, there is an increased number of reports being published on Methotrexate (MTX) related cutaneous manifestations. We aimed to identify and critically appraise descriptive studies describing the MTX related skin manifestations, treatment approach, and their outcomes. METHODOLOGY: An extensive literature search was performed in the PubMed, Embase, and Scopus databases from inception to April 2021 without any restrictions along with the bibliographic search of included studies, grey literature search, and a snowball search was performed in Google and Google Scholar to identify the relevant literature. Descriptive studies reporting MTX related cutaneous manifestations were considered for the review. The study selection, data extraction, and quality assessment were conducted by two independent reviewers and any disagreements were settled by consensus with the third reviewer. RESULTS: 31 out of 8,365 descriptive studies including 38 patients (22 females and 16 males) aged between 12 and 78 years prescribed for the management of rheumatoid arthritis, ankylosing spondylitis, and psoriasis were included in this review. Toxic epidermal necrolysis (TEN), papular eruption, vasculitis, erosions of psoriasis, ulcerated psoriatic plaques, local reactions, keratinocyte dystrophy, erythema multiforme, drug rash with eosinophilia and systemic symptoms, Steven Johnson syndrome and photosensitive dermatitis were the majority of MTX induced cutaneous reactions. Immediate withdrawal of MTX, providing appropriate care with anti-inflammatory, topical steroids, and supplementation with folic acid were reported to be effective for the management of the MTX related cutaneous manifestations. CONCLUSIONS: Clinicians and healthcare professionals should be aware of possible acute cutaneous drug reactions induced by MTX to avoid further consequences and fatal conditions. Immediate withdrawal of MTX and supportive care were reported as an efficacious therapeutic management of acute cutaneous drug reactions. PROSPERO REGISTRATION NUMBER: CRD42020220038.
34646331 Exploring the Mechanism of Resveratrol in Reducing the Soft Tissue Damage of Osteoarthriti 2021 AIM: To explore the mechanism of resveratrol in reducing the soft tissue damage of osteoarthritis (OA) based on network pharmacology. METHODS: Pharmmapper was used to predict the target of resveratrol, OMIM and Genecards were used to collect OA-related disease genes, and David ver 6.8 was used for enrichment analysis. Then, animal experiments were carried out for verification. The rat OA model was established and the rats were randomly divided into 4 groups: model group, resveratrol low-dose group, resveratrol high-dose group, and blank control group for follow-up experiments. Hematoxylin-eosin (HE) staining was used to detect the degree of pathological damage of rat bones and joints. Enzyme-linked immunosorbent assay (ELISA) was used for the content of inflammatory factors. Western blot was used to detect the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), nuclear factor kappa B protein (NF-κB), cysteine protease-9 (CASP-9), Bcl-2 protein, and Bax protein. RESULTS: Through network pharmacological analysis, this study found that resveratrol may regulate the TLR4 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Osteoclast differentiation, Rheumatoid arthritis, etc. Animal experiments showed that compared with the model group, the pathological damage of bone and joint in the resveratrol low-dose and high-dose groups was significantly improved. Compared with the model group, the serum levels of IL-1beta, IL-6, IL-17, TNF-α, and MCP-1 in the resveratrol low-dose and high-dose groups were significantly reduced (P < 0.05); protein levels of TLR-4, MyD88, and NF-κB p65 were significantly reduced (P < 0.05); caspase-9 and Bax protein levels were significantly reduced (P < 0.05), and Bcl-2 was significantly increased (P < 0.05). CONCLUSION: Resveratrol may inhibit the activation of the TLR4-mediated NF-κB signaling pathway and has a repairing effect on soft tissue damage in OA.
34284112 Tyrosine kinases regulate chondrocyte hypertrophy: promising drug targets for Osteoarthrit 2021 Oct Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which leads to cartilage damage, aggravating the disease. Therefore, a therapeutic agent inhibiting hypertrophy would be a promising disease-modifying drug. The therapeutic use of tyrosine kinase inhibitors has been mainly focused on oncology, but the Food and Drug Administration (FDA) approval of the Janus kinase inhibitor Tofacitinib in Rheumatoid Arthritis has broadened the applicability of these compounds to other diseases. Interestingly, tyrosine kinases have been associated with chondrocyte hypertrophy. In this review, we discuss the experimental evidence that implicates specific tyrosine kinases in signaling pathways promoting chondrocyte hypertrophy, highlighting their potential as therapeutic targets for OA.