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ID PMID Title PublicationDate abstract
35536990 Comparison of Web-Based Advertising and a Social Media Platform as Recruitment Tools for U 2022 May 10 OBJECTIVE: Traditional nondigital methods of participant recruitment for clinical research studies in rheumatology can be costly and inefficient, particularly for recruitment of underserved populations. We aimed to address this need by evaluating two methods of online recruitment to an observational cohort of individuals at risk for rheumatoid arthritis, namely web and Facebook advertisements. METHODS: A 3-month countywide web-based recruitment campaign was conducted consisting of text and image-based advertisements. Similar advertisements were subsequently displayed on Facebook, initially in English for 5 months and later in Spanish for an additional 3 months. Individuals who clicked on advertisements were directed to a website landing page containing study information and could contact study personnel to schedule testing for anti-cyclic citrullinated peptide-3 (CCP3). The primary outcome measure for each campaign was the click-through rate. RESULTS: During the web campaign, 413,289 advertisement impressions were displayed, resulting in 428 clicks (click-through rate 0.10%) and only one screened participant. During the English Facebook campaign, 724,815 advertisements were displayed with 6765 clicks (click-through rate 0.93%) and 43 screened participants, significantly greater than the web campaign (P < 0.001). During the Spanish advertisement campaign, 255,730 Spanish advertisements were displayed, resulting in a click-through rate of 2.09% and 24 screened participants, a significantly higher rate than English advertisements. Of participants recruited through social media, 94% were female and 29.8% were Spanish speakers. CONCLUSION: Facebook advertisements were superior to web advertisements for participant recruitment. Spanish Facebook advertisements had a greater click-through rate than English Facebook advertisements. Facebook was an effective recruitment method, particularly for Spanish speakers.
35509787 Epstein-Barr virus-related diffuse large B-cell lymphoma type methotrexate-associated lymp 2022 May INTRODUCTION: Methotrexate-associated lymphoproliferative disorders appear during treatment with methotrexate as an immunosuppressive drug. However, the mechanism and frequency are still unknown, and the treatment is undefined. CASE PRESENTATION: A 76-year-old woman was admitted to the hospital with back pain, and magnetic resonance imaging showed a tumor in the right adrenal region. She had received methotrexate for rheumatoid arthritis. Enhanced computed tomography showed a tumor of 90 mm in diameter on the dorsal side of the liver abutting to the inferior vena cava. The preoperative diagnosis was a hepatic invasion of right adrenocortical carcinoma and right adrenalectomy was performed. The histopathological diagnosis was diffuse large B-cell lymphoma. The final diagnosis was methotrexate-associated lymphoproliferative disorders. CONCLUSION: It is important to consider methotrexate-associated lymphoproliferative disorders before surgery when neoplastic lesions are found in patients taking methotrexate.
35330989 Application of Baricitinib in Dermatology. 2022 There are four JAK subtypes: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Small molecule Janus tyrosine kinase (JAK) inhibitors can inhibit a variety of pro-inflammatory cytokines. Baricitinib is the first generation of JAK1/2 inhibitor targeting the ATPase of JAK, which blocks the intracellular transmission of cytokines through JAK-STATs. Thus far, it has been approved for the treatment of rheumatoid arthritis (RA); however, an increasing number of studies have suggested that baricitinib can be used to treat dermatological diseases, such as atopic dermatitis (AD), psoriasis, vitiligo, and alopecia areata. Baricitinib can be a new choice for the treatment of dermatological diseases, which cannot be treated with conventional drugs. We reviewed the application, efficacy, side effects, precautions, limitations and prospect of baricitinib in atopic dermatitis, psoriasis, vitiligo and alopecia areata (AA) in recent 5 years including clinical trials and case reports. Among them, the application in the field of alopecia areata is the most encouraging, and we reviewed the mechanism in detail.
35191669 Molecular Basis for the Interaction of Catalase with d-Penicillamine: Rationalization of S 2022 Mar 21 d-Penicillamine (d-Pen) is a sulfur compound used in the management of rheumatoid arthritis, Wilson's disease (WD), and alcohol dependence. Many side effects are associated with its use, particularly after long-term treatment. However, the molecular basis for such side effects is poorly understood. Based on the well-known oxidase activity of hemoproteins and the participation of catalase in cellular H(2)O(2) redox signaling, we posit that d-Pen could inactivate catalase, thus disturbing H(2)O(2) levels. Herein, we report on the molecular basis that could partly explain the side effects associated with this drug compound, and we demonstrate that it induces the formation of compound II, a temporarily inactive state of the enzyme, through two distinct mechanisms. Initially, d-Pen reacts with native catalase and/or iron metal ions, used to mimic non-heme iron overload observed in long-term treated WD patients, to generate thiyl radicals. These radicals partake in a futile redox cycle, thus producing superoxide radical anions O(2)(•-) and hydrogen peroxide H(2)O(2). Then, either H(2)O(2) unexpectedly reacts with reduced CAT-Fe(II) to produce compound II or both aforementioned reactive oxygen species intervene in compound II generation through compound I formation and then reduction. These findings support the evidence that d-Pen could perturb H(2)O(2) redox homeostasis through transient but recurring catalase inactivation, which may in part rationalize some deleterious effects observed with this therapeutic agent, as discussed.
34936242 LncRNA GAS5 positively regulates IL-10 expression in patients with generalized myasthenia 2022 Jan INTRODUCTION: LncRNA growth arrest-specific transcript 5 (GAS5) has been proven to be involved in autoimmune diseases. Rheumatoid arthritis is a type of autoimmune disease that may affect myasthenia gravis (MG) patients. However, its direct role in MG is unknown. METHODS: Our study included 62 generalized MG patients. GAS5 expression was analyzed with real-time quantitative RT-PCR (qRT-PCR). The interaction between GAS5 and interleukin 10 (IL-10) was explored in overexpressed cells using real time quantitative polymerase chain reactions (RT-qPCRs) and western blot. The correlation of GAS5 and IL-10 was analyzed using Pearson's correlation analysis. The diagnostic value of GAS5 for MG was analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS: GAS5 and IL-10 mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in MG patients than healthy controls. Downregulated GAS5 effectively distinguished MG patients from healthy controls. GAS5 expression was positively correlated with IL-10 expression in both MG patients and healthy controls. GAS5 overexpression significantly upregulated IL-10 expression in PBMCs derived from both MG patients and healthy controls. CONCLUSION: LncRNA GAS5 may improve generalized MG by positively regulating IL-10 expression.
34725722 Complications of occipitocervical fixation: retrospective review of 128 patients with 5-ye 2022 Feb PURPOSE: Occipitocervical fusion is necessary for many pathologies of the craniocervical junction. The anatomy of the region is unique, and fusion can cause significant morbidity. This retrospective review aims to investigate the complication rates and outcomes of occipitocervical fixation. MATERIAL AND METHODS: This is a retrospective review of 128 patients with occipitocervical fixation operated between 1994 and 2020. The average follow-up is 63 months. RESULTS: The indications of occipitocervical fixation were basilar invagination (53 patients; 41.4%), trauma (25 patients; 19.5%), tumor (23 patients; 18%), instability due to rheumatoid arthritis (13 patients; 10.2%), cervical deformity (7 patients; 5.5%) and os odontoideum (7 patients; 5.5%). There were six early postoperative (1st month) deaths. We observed complications in 67 patients (52%). Most common complication was implant-related (32%), followed by wound problems (23.4%), systemic and other complications (11.7%), neurologic complications (6.2%). Implants are removed in 31 patients (24%) for different reasons: deep wound infection (7), local pain and restriction of head movements (21), respiratory distress and swallowing problems (2), screw fracture and local pain (1). CONCLUSIONS: Occipitocervical fixation has quite large number of complications and significantly restricts head movements. With the advent of our biomechanical concepts, indications should be limited, and shorter cervical fixations should be preferred. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
31986916 Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats 2022 Mar Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.
35393919 A case of adult-onset Grisel's syndrome. 2022 Apr 8 Aim: Grisel's syndrome is a non-traumatic subluxation of the atlanto-axial joint that occurs after infection or inflammation in the otolaryngological area, primarily in children.Method: This report describes the clinical characteristics of an extremely rare case of adult-onset Grisel's syndrome.Result: A 77-year-old woman presented with neck and bilateral shoulder pain and stiffness. Her temperature was 37.6 °C. Blood testing revealed a mildly elevated inflammatory response, although blood cultures were negative. Computed tomography (CT) showed atlanto-axial subluxation and joint destruction. T2-weighted magnetic resonance imaging (MRI) displayed high signals in the soft tissues in the anterior space of the atlas and axis, posterior wall of the pharynx, and interspinous ligament, indicating spinal cord compression at the C1 level. Differential diagnoses of inflammation and diseases causing atlanto-axial subluxation included rheumatoid arthritis, amyloidosis, pyogenic spondylitis due to posterior pharyngeal abscess, and crowned dens syndrome. After the systematic elimination of each condition, we considered Grisel's syndrome and began non-surgical treatment with intravenous antibiotics and a Philadelphia neck collar. Her inflammatory response and neck pain gradually decreased. Six months later, there was no progression of instability. She was able to walk unaided and live normally with the use of a neck collar as needed.Conclusion: Grisel's syndrome occurs predominantly in children, but can also afflict adults. Since early diagnosis and treatment can improve symptoms in some cases and prevent progressive atlanto-axial instability, prompt evaluation of the atlanto-axial joint using CT or MRI is advised in patients with neck pain and limited range of motion.
35115945 Anti-Inflammatory and Pro-Autophagy Effects of the Cannabinoid Receptor CB2R: Possibility 2021 Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from loss of insulin-secreting β-cells in islets of Langerhans. The loss of β-cells is initiated when self-tolerance to β-cell-derived contents breaks down, which leads to T cell-mediated β-cell damage and, ultimately, β-cell apoptosis. Many investigations have demonstrated the positive effects of antagonizing cannabinoid receptor 1 (CB1R) in metabolic diseases such as fatty liver disease, obesity, and diabetes mellitus, but the role of cannabinoid receptor 2 (CB2R) in such diseases is relatively unknown. Activation of CB2R is known for its immunosuppressive roles in multiple sclerosis, rheumatoid arthritis, Crohn's, celiac, and lupus diseases, and since autoimmune diseases can share common environmental and genetic factors, we propose CB2R specific agonists may also serve as disease modifiers in diabetes mellitus. The CNR2 gene, which encodes CB2R protein, is the result of a gene duplication of CNR1, which encodes CB1R protein. This ortholog evolved rapidly after transitioning from invertebrates to vertebrate hundreds of million years ago. Human specific CNR2 isoforms are induced by inflammation in pancreatic islets, and a CNR2 nonsynonymous SNP (Q63R) is associated with autoimmune diseases. We collected evidence from the literature and from our own studies demonstrating that CB2R is involved in regulating the inflammasome and especially release of the cytokine interleukin 1B (IL-1β). Furthermore, CB2R activation controls intracellular autophagy and may regulate secretion of extracellular vesicles from adipocytes that participate in recycling of lipid droplets, dysregulation of which induces chronic inflammation and obesity. CB2R activation may play a similar role in islets of Langerhans. Here, we will discuss future strategies to unravel what roles, if any, CB2R modifiers potentially play in T1DM.
35095508 Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of C 2021 Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.
28722873 C Reactive Protein. 2022 Jan C-reactive protein (CRP) was discovered by Tillett and Francis in 1930. The name CRP arose because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the "c" carbohydrate antibody of the capsule of pneumococcus. CRP is a pentameric protein synthesized by the liver, whose level rises in response to inflammation. CRP is an acute-phase reactant protein that is primarily induced by the IL-6 action on the gene responsible for the transcription of CRP during the acute phase of an inflammatory/infectious process. There is some question of whether dysregulation of the role of CRP in the clearance of apoptotic cells and cellular debris plays a role in the pathogenesis of systemic lupus erythematosus (SLE), but this has not been definitively demonstrated. It has been demonstrated to have some protective properties in animal studies on lung tissue in alveolitis by reducing neutrophil-mediated damage to the alveoli and protein leakage into the lung. CRP has both proinflammatory and anti-inflammatory properties. It plays a role in the recognition and clearance of foreign pathogens and damaged cells by binding to phosphocholine, phospholipids, histone, chromatin, and fibronectin. It can activate the classic complement pathway and also activate phagocytic cells via Fc receptors to expedite the removal of cellular debris and damaged or apoptotic cells and foreign pathogens. This can become pathologic, however, when it is activated by autoantibodies displaying the phosphocholine arm in auto-immune processes, such as idiopathic thrombocytopenic purpura (ITP). It can also worsen tissue damage in certain cases by activation of the complement system and thus inflammatory cytokines. As compared to the erythrocyte sedimentation rate, which is an indirect test for inflammation, the levels of CRP rise and fall rapidly with the onset and removal of the inflammatory stimulus respectively. Persistently elevated CRP levels can be seen in chronic inflammatory conditions such as chronic infections or inflammatory arthritides such as rheumatoid arthritis. There are numerous causes of an elevated C-reactive protein.  These include acute and chronic conditions, and these can be infectious or non-infectious in etiology. However, markedly elevated levels of CRP are most often associated with an infectious cause (an example of pathogen-associated molecular pattern recognition).  Trauma can also cause elevations in CRP (alarmin response). More modest elevations tend to be associated with a broader spectrum of etiologies, ranging from sleep disturbances to periodontal disease.
34562225 Low Urine Secretion of Semaphorin3A in Lupus Patients with Proteinuria. 2022 Apr Immune semaphorins are important in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to correlate with SLE disease activity. The aim was to assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Urine levels of sema3A were analyzed in 38 SLE patients, 13 with renal involvement, and were compared to 10 healthy volunteers and 8 RA patients (disease control group). The excretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy volunteers and RA patients (4.9 ± 3.9 ng/ml, 8.5 ± 2.7 ng/ml, 9.85 ± 1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0 ± 3.4 ng/ml vs. 6.5 ± 3.8 ng/ml, p = 0.03). Urine sema3A inversely correlated with proteinuria and SLE disease activity. Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.
34515214 Use of Systemic Corticosteroids for Reasons Other than Asthma in Subjects with Asthma. 2022 BACKGROUNDS: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. OBJECTIVES: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. METHOD: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. RESULTS: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. CONCLUSIONS: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.
35377276 The suitability of treating atopic dermatitis with Janus kinase inhibitors. 2022 May INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant morbidity and reduced quality of life, especially in patients with moderate-severe AD. Recently, topical and oral Janus kinase (JAK)-inhibitors were investigated as treatments for mild-moderate and moderate-severe AD. However, rare serious adverse-events observed with JAK-inhibitor therapy in AD, rheumatoid arthritis, and other immune-mediated disorders warrant careful consideration. AREAS COVERED: This review examines the efficacy and safety of topical and oral JAK-inhibitors for treatments in AD, and reviews potential applications in AD. EXPERT OPINION: JAK-inhibitors have rapid-onset and robust and durable efficacy, which give them considerable versatility for treating the gamut of AD patients. While the U.S. Food and Drug Administration has only approved upadacitinib and abrocitinib to treat moderate-severe AD refractory to treatment with other systemic medications including biologics, or when use of those therapies is not recommended, oral JAK-inhibitors have the potential to be used both as first-line or second-line systemic therapies in moderate-severe AD. However, oral JAK-inhibitors can lead to laboratory anomalies and rare serious adverse events. All of these important characteristics should be addressed in shared-decision-making conversations, patient counseling, choosing appropriate therapies for patients, and monitoring patients in clinical practice.
35210147 Distribution and Correlates of Hip-Knee-Ankle Angle in Early Osteoarthritis and Preoperati 2022 Jun BACKGROUND: Several studies have investigated the distribution of hip-knee-ankle (HKA) angle in healthy populations; however, few have evaluated this metric in patients undergoing total knee arthroplasty (TKA). The purpose of this study is to compare HKA angle distribution in early and advanced knee osteoarthritis (OA) patients. METHODS: Full limb radiographs were used to measure HKA angle for 983 subjects from the Osteoarthritis Initiative (OAI) cohort and 4,901 pre-TKA patients from an institutional cohort. Measurements were made using a previously validated deep learning algorithm. Linear regression models were used to determine the association of HKA alignment angle with patient characteristics. RESULTS: The mean ± standard deviation HKA angle was -1.3° ± 3.2° in the OAI cohort and -4.1° ± 6.1° in the pre-TKA cohort. In the OAI cohort, normal alignment (64%) was the most common knee alignment followed by varus (29%), and valgus (7%). In pre-TKA patients, the most common alignment was varus (62%), followed by normal (27%) and valgus (11%). In pre-TKA patients, mean HKA angle in primary knee OA, post-traumatic knee OA, and rheumatoid arthritis patients were -4.3° ± 6.1°, -3.2° ± 6.4°, and -2.9° ± 6.1°, respectively. HKA angle was strongly associated (P < .001) with gender and body mass index. CONCLUSION: TKA patients have a wider alignment distribution and more severe varus and valgus alignment than individuals "at risk" for knee OA from the OAI cohort. These epidemiologic findings improve our understanding of HKA angle distribution and its correlation with demographic characteristics in early and late-stage arthritis.
35160295 The Link between Fibromyalgia Syndrome and Anger: A Systematic Review Revealing Research G 2022 Feb 5 Anger has been associated with increased pain perception, but its specific connection with Fibromyalgia Syndrome (FMS) has not yet been established in an integrated approach. Therefore, the present systematic review focuses on exploring this connection, and based on this connection, delimiting possible gaps in the research, altogether aimed at improving FMS clinical intervention and guiding future research lines. Anger is considered a basic negative emotion that can be divided into two dimensions: anger-in (the tendency to repress anger when it is experienced) and anger-out (the leaning to express anger through verbal or physical means). The current systematic review was performed based on the guidelines of the PRISMA and Cochrane Collaborations. The Prospective Register of Systematic Reviews (PROSPERO) international database was forehand used to register the review protocol. The quality of chosen articles was assessed and the main limitations and research gaps resulting from each scientific article were discussed. The search included PubMed, Scopus, and Web of Science databases. The literature search identified 13 studies eligible for the systematic review. Levels of anger-in have been shown to be higher in FMS patients compared to healthy participants, as well as patients suffering from other pain conditions (e.g., rheumatoid arthritis). FMS patients had also showed higher levels of state and trait anxiety, worry and angry rumination than other chronic pain patients. Anger seems to amplify pain especially in women regardless FMS condition but with a particularly greater health-related quality of life´s impact in FMS patients. In spite of the relevance of emotions in the treatment of chronic pain, including FMS, only two studies have proposed intervention programs focus on anger treatment. These two studies have observed a positive reduction in anger levels through mindfulness and a strength training program. In conclusion, anger might be a meaningful therapeutic target in the attenuation of pain sensitivity, and the improvement of the general treatment effects and health-related quality of life in FMS patients. More intervention programs directed to reduce anger and contribute to improve well-being in FMS patients are needed.
34699634 Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial c 2022 Feb BACKGROUND: Patients with chronic inflammatory diseases (e.g. psoriasis and rheumatoid arthritis) are at increased risk for the development of atherosclerosis and cardiovascular diseases (CVD). Previous studies have suggested that phosphodiesterase 4 (PDE4) inhibitors possess anti-inflammatory properties. OBJECTIVES: Here we examined the effect of the PDE4 inhibitor apremilast, a well-established anti-psoriatic drug, on pro-inflammatory responses in TNFα-activated endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor-α (TNFα) in the presence or absence of apremilast. Expression levels of pro-inflammatory cytokines, chemokines and adhesion molecules were assessed by ELISA, western blot and RT-PCR. Effects of apremilast on adhesion and transendothelial migration (TEM) of THP-1 monocytic cells were analysed in transwell assays. RESULTS: Apremilast suppressed TNFα-induced expression and secretion of important endothelial and monocytic pro-inflammatory factors, including granulocyte-macrophage colony-stimulating factor (GM-CSF), C-X-C motif chemokine ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and matrix metalloproteinase-9 (MMP9). Functionally, apremilast reduced adhesion of THP-1 cells to activated HUVECs and TEM in response to TNFα. Mechanistically, apremilast suppressed activation of nuclear factor κB (NFκB) and mitogen-activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C-Jun-N-terminale Kinase (JNK) and NFκB in activated HUVECs decreased expression of GM-CSF, VCAM-1 and E-selectin. Additionally, apremilast decreased IL-17A-induced secretion of IL-6 and CCL2. CONCLUSIONS: We demonstrate that apremilast has distinct anti-inflammatory effects in activated HUVECs, indicating that apremilast could have the therapeutic potential to prevent higher risk for CVD in patients with chronic inflammatory diseases.
35331875 Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemis 2022 Jun 28 ETHNOPHARMACOLOGICAL RELEVANCE: Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy. AIM OF THE STUDY: This review aims to document and summarize critical and comprehensive information about traditional uses, phytochemistry, pharmacology, toxicology and processing methods of Tiebangchui. Perspectives for possible future investigations have been discussed. MATERIALS AND METHODS: Relevant information about Tiebangchui (A. pendulum and A. flavum) was collected from internationally recognized electronic scientific databases, such as Web of Science, PubMed, Science Direct, Springer Link, ACS, and CNKI. Then, classic Tibetan medical books, such as Four Medical Tantra, and Jing Zhu Materia Medica, and official drug standards were reviewed. RESULTS: A total of 95 chemical constituents have been isolated and identified from Tiebangchui, and most of them were diterpenoid alkaloids. These phytochemicals showed a wide range of pharmacological properties, such as anti-inflammation, anti-rheumatoid arthritis, analgesic, local anesthetic, anti-cancer and anti-bacterial activities. Hence, Tiebangchui is broadly used in hundreds of preparations to treat fever, arthritis, rheumatic arthralgia, traumatic injury, furuncle and swelling. Cardiotoxicity, neurotoxicity and gastrointestinal toxicity are the main toxic effects caused by the Aconitum alkaloids of Tiebangchui. Various processing methods, including steaming, decocting and sand-frying, and traditional Tibetan medicine processing methods, such as processing with Hezi decoction, Qingke wine and Zanba, are effective in attenuating toxicity while retaining efficacy. CONCLUSIONS: The present review provides primary information of Tiebangchui, particularly for its traditional uses, botanical characteristics, phytochemicals, outstanding bioactivities and processing methods. However, studies that explored the in vivo pharmacokinetics and mechanism of Tiebangchui, as well as its quality markers, qualitative and quantitative analysis are still insufficient. Processing methods that attenuate toxicities, evaluations of efficacy, in vivo processes and biological effects, the mechanisms of processed products should be further explored.
34913284 Catalpol Inhibits Tregs-to-Th17 Cell Transdifferentiation by Up-Regulating Let-7g-5p to Re 2022 Jan PURPOSE: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, and Th17 cells are key factors in the pathogenesis of human inflammatory conditions, such as RA. Catalpol (CAT), a component in Rehmanniae Radix (RR), has been found to regulate human immunity. However, the effects of CAT on Th17 cell differentiation and improvement of RA are not clear. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were constructed to detect the effects of CAT on arthritis and Th17 cells. The effect of CAT on Th17 differentiation was evaluated with let-7g-5p transfection experiments. Flow cytometry was used to detect the proportion of Th17 cells after CAT treatment. Levels of interleukin-17 and RORγt were assessed by qRT-PCR and enzyme-linked immunosorbent assay. The expression of signal transducer and activator of transcription 3 (STAT3) was determined by qRT-PCR and Western blot. RESULTS: We found that the proportion of Th17 cells was negatively associated with let-7g-5p expression in CIA mice. In in vitro experiments, CAT suppressed traditional differentiation of Th17 cells. Simultaneously, CAT significantly decreased Tregs-to-Th17 cells transdifferentiation. Our results demonstrated that CAT inhibited Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p and that the suppressive effect of CAT on traditional differentiation of Th17 cells is not related with let-7-5p. CONCLUSION: Our data indicate that CAT may be a potential modulator of Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p to reduce the expression of STAT3. These results provide new directions for research into RA treatment.
35319515 Persistent Shoulder Pain After Vaccine Administration Is Associated with Common Incidental 2022 Mar 23 BACKGROUND: Claims of shoulder injury now account for half of all claims to the Vaccine Injury Compensation Program. Reports from databases of claims or potential adverse events note a relatively high mean age and high prevalences of rotator cuff tendinopathy and adhesive capsulitis-common shoulder problems that might be incidental to vaccination. Published case reports provide much more detail about individual patients than is available in databases. A review of published cases provides an opportunity for more detailed review of symptoms, diagnoses, pathology, treatment, and prognosis. Such a review can better assess the relative likelihood that pathologies associated with new persistent shoulder symptoms after vaccination are coincidental or unique to and caused by vaccine. QUESTIONS/PURPOSES: Regarding published case reports addressing persistent shoulder pain after vaccination: (1) In what proportion of patients was a specific diagnosis made? (2) What diagnoses were most common? (3) Among patients treated nonsurgically, what proportion resolved, and over what time span did they resolve? METHODS: In August 2020, we searched PubMed and Embase between 2006 and 2020 using the following search strategy: Search 1: (shoulder dysfunction OR shoulder pain OR shoulder bursitis OR rotator cuff tendonitis OR adhesive capsulitis OR glenohumeral arthritis AND [vaccine OR vaccination OR immunization]); Search 2: (shoulder injury related to vaccine administration or SIRVA). The search was supplemented by reviewing reference lists of identified studies. Inclusion criteria were any detailed report of three or fewer cases involving shoulder pain after vaccine administration. Twenty published reports of 29 patients were identified and assessed by two reviewers independently. One reported glenohumeral joint infection was excluded because the relationship between this type of relatively uncommon, discrete diagnosis and vaccination raises different considerations. We assumed a high risk of bias, although we are not aware of bias assessment tool for case reports. We recorded and summarized patient demographics, symptoms, examination and imaging findings, surgery findings, diagnoses, treatments, and outcomes. Seventy-five percent (21 of 28) of patients were women, with a mean age of 54 ± 19 years. In search of an underlying pathology, at least one diagnostic study was performed in 82% (23 of 28) of patients including radiographs in seven, ultrasound in seven, and MRI in 16 patients (some patients underwent more than one type of imaging). We distinguished specific pathophysiological diagnosis from shoulder pain and stiffness, counted the most common diagnoses among patients a specific diagnosis, and tracked symptom resolution among patients treated nonoperatively. RESULTS: A specific diagnosis was made in 57% (16 of 28) of patients. Twelve patients had pain and limitation of motion due to pain but no specific pathological diagnosis. The most common specific diagnoses were rotator cuff tendinopathy (9 of 16) and adhesive capsulitis (4 of 16). Less common specific diagnoses included rotator cuff arthropathy (and rheumatoid arthritis) and suspected septic arthritis with nonspecific synovitis on arthroscopy. One patient had transient MRI signal change in the humeral head, which was interpreted as osteonecrosis that resolved in a manner not typical for that diagnosis. Of the 17 patients treated nonsurgically, 15 reported resolution, and two had incomplete symptom resolution with the mean 6-month evaluation period. CONCLUSION: The observation that persistent shoulder pain after vaccination overlaps with common shoulder pathology-both in large databases as well as in more detailed reports of specific patients as analyzed in this review-establishes a high probability of a coincidental rather than a causal association. In the absence of high-quality experimental evidence of vaccine-specific shoulder pathology, in our opinion, it seems safest and healthiest to assume that perceived shoulder injury related to vaccine administration (SIRVA) is due to misinterpretation of new symptoms from established pathology rather than a new, vaccine-specific pathology. LEVEL OF EVIDENCE: Level IV, therapeutic study.