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ID PMID Title PublicationDate abstract
31581859 Off-label studies on tofacitinib in dermatology: a review. 2021 Jun PURPOSE: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. MATERIALS AND METHODS: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. RESULTS: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. CONCLUSION: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.
31521892 Regulation of CP-25 on P-glycoprotein in synoviocytes of rats with adjuvant arthritis. 2019 Nov OBJECTIVE: Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA) and it has been studied in RA resistance recently. P-glycoprotein (P-gp) is one of the important transporters that mediate MTX resistance. This study investigated the effect of Paeoniflorin-6'-O-benzene sulfonate (code: CP-25) in the resistance of P-gp-mediated MTX to RA. METHODS: Adjuvant arthritis (AA) was induced in rats via complete Freund's adjuvant. The experimental groups were divided into normal group; AA model group; monotherapy groups, including CP-25, MTX and dexamethasone; and CP-25 combined with MTX group. The expression of P-gp in synovial tissue was measured by western blot and histochemistry. Besides, P-gp high expression of human hepatoma cell line Bel7402/5-FU and Bel7402 were chose to study in MTX resistance and the function of P-gp was detected by Flow cytometry. RESULTS: CP-25 had a good therapeutic effect on AA rats, significantly improved manifestations and reduced the expression of P-gp in synovial tissue, spleen medulla and small intestinal epithelial cells in the apical tissues of AA rats. In addition, CP-25 significantly inhibited the up-regulation of P-gp induced by TNF-α stimulation in synoviocytes. Furthermore, according to the accumulation and efflux of rhodamine 123 in Bel7402/5-FU resistant cells and Bel7402 sensitive cells, CP-25 could reverse the resistance of MTX in Bel7402/5-FU cells compared with Bel7402 cells, which was reflected by the reduced IC50 values of MTX. Further study indicated that CP-25 could decrease P-gp expression and inhibit P-gp function in Bel7402/5-FU cells. CONCLUSION: CP-25 regulates the expression of P-gp and inhibits the function of P-gp, thereby improving the resistance of MTX.
31211815 Dysbiotic salivary microbiota in dry mouth and primary Sjögren's syndrome patients. 2019 OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by reduced lacrimal and salivary secretion. Sicca symptoms together with fatigue and musculoskeletal pain can significantly reduce the patients' quality of life. Furthermore, low salivary secretion may disrupt the oral microbial homeostasis. The aim of this study was to compare the salivary microbiota from pSS patients with patients with sicca symptoms not fulfilling the classification criteria for pSS (non-SS), and with healthy controls without sicca complaints. METHODS: Pellets from centrifuged chewing-stimulated whole saliva from pSS patients (n = 15), non-SS sicca patients (n = 15) and healthy controls (n = 15) were prepared. DNA was extracted and analyzed by 16S rRNA gene sequencing. The acquired sequencing data were performed using the human oral microbiome database (HOMD). RESULTS: We detected 42, 45, and 34 bacterial genera in saliva samples from pSS patients, non-SS sicca patients, and healthy controls, respectively. The most abundant genera in all samples were Prevotella, Veillonella, Streptococcus, and Haemophilus. At species level Streptococcus intermedius, Prevotella intermedia, Fusobacterium nucleatum subsp. vincentii, Porphyromonas endodontalis, Prevotella nancensis, Tannerella spp., and Treponema spp. were detected in the samples from pSS and non-SS only, while Porphyromonas pasteri was mostly found among the healthy controls. CONCLUSION: Our study indicated dysbiosis in the salivary microbiota from pSS and non-SS patients compared to healthy controls. Additionally, the results showed that the salivary microbiome in the pSS group differed significantly from the non-SS group.
31351032 Applications of RNA interference in the treatment of arthritis. 2019 Dec RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy holds significant promise for the treatment of a wide-range of arthritic diseases. siRNA selectively suppresses the expression of a gene product and can thus achieve the specificity that is lacking in small molecule inhibitors. The potential use of siRNA-based therapy in arthritis, however, has not progressed to clinical trials despite ample evidence for efficacy in preclinical studies. One of the main challenges to clinical translation is the lack of a suitable delivery vehicle to efficiently and safely access diverse pathologies. Moreover, the ideal targets in treatment of arthritides remain elusive given the complexity and heterogeneity of these disease pathogeneses. Herein, we review recent preclinical studies that use RNAi-based drug delivery systems to mitigate inflammation in models of rheumatoid arthritis and osteoarthritis. We discuss a self-assembling peptide-based nanostructure that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.
31844478 Inappropriate sinus tachycardia or…something else? 2019 Dec We report the case of a 45-year old female patient with a past medical history of rheumatoid arthritis who presented to our cardiology department with a suspicion of inappropriate sinus tachycardia. Echocardiography showed a nondilated left ventricle with a preserved ejection fraction. A careful reinterpretation of her 12-lead ECG reoriented the diagnosis toward an incessant atrial tachycardia. The diagnosis was confirmed by an electrophysiologic study performed with an electro-anatomic mapping system, which identified the origin of the tachycardia at the level of the right atrial appendage. Radiofrequency ablation of the ectopic focus eliminated the tachycardia and improved the patient's symptoms.
30957966 Generation and Analysis of Human and Murine Osteoclasts. 2019 Jun Osteoclasts are the only bone-resorbing cells in the body. Together with bone-forming osteoblasts, they are responsible for bone homeostasis and constant bone remodeling. Aberrant activation of osteoclasts leads to bone loss, as seen in postmenopausal osteoporosis or in autoimmune diseases like rheumatoid arthritis. Although much research has been performed to understand and prevent osteoclast-mediated bone loss, the mechanisms of osteoclast hyperactivation are not completely understood. This unit describes several protocols for ex vivo generation of murine and human osteoclasts, allowing study of the effects of specific cells, cytokines, or chemical substances on osteoclast formation and activity without the need for expensive and time-consuming animal experiments. In addition, we provide protocols for specific staining of osteoclasts and for analysis of resorption activity using calcium phosphate-coated surfaces or bone slices. © 2019 by John Wiley & Sons, Inc.
30051737 Biologic and small-molecule medications in the management of pyoderma gangrenosum. 2019 May Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disorder characterized by neutrophil dysfunction. There are currently no FDA-approved drugs for the treatment of this disease, and treatment has typically relied on traditional immunosuppressive medications such as prednisone or cyclosporine. The efficacy of biologics in the treatment of other pro-inflammatory conditions such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease is well-documented in the literature. Therefore, the use of biologic medications for the treatment of rarer inflammatory skin conditions, such as PG, is a compelling topic for investigation. Biologic and small-molecule therapies allow physicians to target specific pro-inflammatory mediators that underlie PG pathogenesis. This review provides an update on the use of biologic and small-molecule medications for the treatment of PG and summarizes the latest data on the clinical efficacy and pharmacology of these treatments.
31497027 Macrophage Rewiring by Nutrient Associated PI3K Dependent Pathways. 2019 Class 1 Phosphoinositide-3-Kinases (PI3Ks) have been widely studied and mediate essential roles in cellular proliferation, chemotaxis, insulin sensitivity, and immunity. Here, we provide a comprehensive overview of how macrophage expressed PI3Ks and their downstream pathways orchestrate responses to metabolic stimuli and nutrients, polarizing macrophages, shaping their cellular identity and function. Particular emphasis will be given to adipose tissue macrophages, crucial players of insulin resistance and chronic metabolically triggered inflammation during obesity. An understanding of PI3K dependent wiring of macrophage responses is important as this is involved in various diseases ranging from obesity, type 2 diabetes to chronic inflammatory disease.
30568149 A Rare Presentation of Hypermagnesemia Associated with Acute Kidney Injury due to Hypercal 2019 Apr 15 A 79-year-old Japanese woman presented with consciousness disturbance, hypercalcemia, and hypermagnesemia. She had rheumatoid arthritis and osteoporosis. Three months before admission, she was treated with oral calcitriol for osteoporosis. Two months before admission, she was treated with magnesium oxide for constipation. One month before admission, she underwent articular femoral bone replacement. Two weeks postoperatively, consciousness disturbance and elevated serum calcium levels were observed, and she was transferred to our hospital. On admission, her laboratory data showed elevated serum magnesium and creatinine levels. This is a rare case of coexistent hypercalcemia and hypermagnesemia associated with consciousness disturbance and acute kidney injury.
32199591 [Synovial fluid cytodiagnosis]. 2020 Apr Synovial fluid samples represent only a very small percentage of routine work in a cytology laboratory. However, its microscopic examination allows us to observe different types of cells, particles and structures that, due to their morphological characteristics, may provide relevant data for cytodiagnosis. We present certain aspects related to arthrocentesis, the relationship between the gross appearance of synovial fluid and certain pathological processes, as well as the different techniques for processing and staining the smears. Furthermore, we describe the main cytological findings in various pathological conditions of the synovial joints, such as infections (bacterial and fungal), non-infectious inflammatory type (osteoarthrosis, rheumatoid arthritis, connective tissue diseases) and tumoral, distinguishing between primary and metastatic, both solid and haematological neoplasms.
31948600 The body's integrated repair kit: Studying mesenchymal stem cells for better ligament repa 2019 Dec In this issue of the Biomedical Journal, we learn that the sport injury-prone knee ligaments might harbour their own repair kit in the form of mesenchymal stem cells, and that TERT transformation helps to keep these cells longer in culture for more extensive studies. In addition, we get a demonstration that diffusion tensor imaging can reliably show the activity of specific neural circuits, that rheumatoid arthritis patients are more prone to insulin resistance, and that platelet-enriched plasma gels significantly improve wound healing after pilonidal sinus surgery. Furthermore, two procreation-related articles inform us that growth hormone treatment improves endometrial receptivity in older women, and that elevated maternal liver enzymes do not impact on the outcome of laser therapy for twin-twin transfusion syndrome. Finally, our attention is brought to the importance of subjective well-being evaluation for orthodontic correction needs, as well as the possibility that exercise could maybe increase sperm telomere length.
31422395 Trimethoprim-sulfamethoxazole Induced Hyponatremia and Hyperkalemia, The Necessity of Elec 2019 Jul Trimethoprim-sulfamethoxazole (TMP/SMX) is a bactericidalantibiotic. The most common adverse effect of TMP/SMX is skinrashes and gastrointestinal symptoms. Although hyperkalemia canoccur with TMP/SMX component but hyponatremia is uncommon. A55- year old woman, known case of rheumatoid arthritis, presentedwith fever and mild dyspnea. According to diagnostic work upthe infection with pneumocystis jirovecii was confirmed. TMP/SMX was started but after 10 days the patient acutely representedwith nausea and became lethargic. The laboratory studies showedmoderate hyperkalemia and severe hyponatremia. TMP/SMX wasstopped and alternative treatment started. Upon discontinuation ofthe drug, serum sodium and potassium levels were both changed tonormal. Hyponatremia as a life threatening adverse effect appearsto be rare with TMP-SMX therapy, but clinicians should be awareof electrolyte disturbances developed with this drug and electrolytemonitoring should always be considered.
31341228 A combined experimental and theoretical study of radon solubility in fat and water. 2019 Jul 24 Radon is a radioactive noble gas that can enter the human body, thus increasing the risk of lung cancer. But it is also used for treatment of various ailments, most notably rheumatoid arthritis. The accumulation of radon differs between tissues, with particularly high concentrations in fat tissue. To understand the underlying mechanisms, a combination of γ-spectroscopy and molecular dynamics simulations were performed, to study the accumulation of radon gas in contact with several liquids (water, fatty acids). The solubilities, specific for a defined radon activity concentration, are in good agreement and differ by two orders of magnitude between water and fat, caused by radon disrupting the hydrogen bond network of water. In contrast, the energy cost of introducing radon atoms into fat is low due to the dispersive interaction between radon and fat, which is a non-polar solvent. This correlation was also explicitly demonstrated in our simulations by changing the polarization of the solvent.
31205394 Facial tumor as a presenting complaint in a patient with primary Sjögren's syndrome. 2019 Jan Sjögren's syndrome is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. Up to one-half of affected individuals also develop extraglandular involvement in organs distinct from the salivary and lacrimal glands, including the joints, skin, lung, gastrointestinal tract, nervous system, and kidneys. The disease also occurs in conjunction with other autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis. We report a case of a 76-year-old woman who presented to our department with a swelling on the left cheek. Investigations revealed Sjögren's syndrome as the underlying cause of the facial tumor.
30894374 Citrullination in Cancer. 2019 Apr 1 Posttranslational modifications of proteins have been implicated in pathogenesis of numerous diseases. Arginine deimination (also known as citrullination) has a principal role in progression of rheumatoid arthritis through generation of autoantibodies and exacerbation of the inflammatory response. Recently, multiple research groups provided solid evidence of citrullination being in control of cancer progression; however, there is no comprehensive overview of these findings. This article summarizes and critically reviews the influence of citrullination on different aspects of tumor biology, including (i) regulation of apoptosis and differentiation, (ii) promoting EMT and metastasis, and (iii) potential use of citrullinated antigens for immunotherapy. In addition, (iv) the role of citrullination as a cancer biomarker and (v) implication of neutrophil extracellular traps in tumorigenesis are discussed. In summary, current findings testify to the significance of arginine deimination in tumor biology and thus more basic and translational studies are needed to further explore this topic.
30710284 The Multifaceted S100A4 Protein in Cancer and Inflammation. 2019 The metastasis-promoting S100A4 protein, a member of the S100 family, has recently been discovered as a potent factor implicated in various inflammation-associated diseases. S100A4 is involved in a range of biological functions such as angiogenesis, cell differentiation, apoptosis, motility, and invasion. Moreover, S100A4 is also a potent trigger of inflammatory processes and induces the release of cytokines and growth factors under different pathological conditions.Indeed, the release of S100A4 upon stress and mainly its pro-inflammatory role emerges as the most decisive activity in disease development, such as rheumatoid arthritis (RA), systemic sclerosis (SSc) allergy, psoriasis, and cancer. In the scope of this review, we will focus on the role of S100A4 as a mediator of pro-inflammatory pathways and its associated biological processes involved in the pathogenesis of various human noncommunicable diseases (NCDs) including cancer.
32029347 HPLC-MS/MS method for the determination and pharmacokinetic study of six compounds against 2020 Mar 20 Caulophyllum robustum Maxim (CRM) is a well-known traditional Chinese medicine (TCM) mainly present in the northeast, northwest and southwest regions of China, which is belong to the family Berberidaceae. The roots and rhizomes of CRM have been used as a famous TCM for the treatment of rheumatoid arthritis (RA). The selective, sensitive and accurate high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination and pharmacokinetic study cauloside H, leonticin D, cauloside G, cauloside D, cauloside C and magnoflorine in rat plasma was developed and validated in this paper. Chromatographic separation was achieved by using a Waters ACQUITY UPLC HSS T3 (100 mm × 2.1 mm, 1.7 μm) with gradient elution using a mobile phase consisting of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed in multiple reaction monitoring (MRM) mode and electrospray ionization (ESI) in positive and negative modes. The linearity, precision, accuracy, extraction recovery, matrix effects and stability were assessed to validate the current high-performance liquid chromatography/mass spectrometry (HPLC-MS) assay. Good linearity was achieved for each analyte with a correlation coefficient (r(2)) > 0.99). All the precision (RSD) data were less than 12.20 %, the accuracies ranged from -12.39 % to 10.55 %, the recovery rates from the rat plasma ranged from 85.48%-98.69 %, and the matrix effects ranged from 80.96 % to 91.35 %. The validated approach was successfully applied to study the pharmacokinetic characteristics of saponins and alkaloids in plasma after administering CRME to rats, and this assay provides a platform for studying the active components of multicomponent traditional Chinese medicines and provides useful information for further clinical studies.
31665206 A cross-sectional study assessing agreement between self-reported and general practice-rec 2019 Dec 1 BACKGROUND: self-reported data regarding health conditions are utilised in both clinical practice and research, but their agreement with general practice records is variable. The extent of this variability is poorly studied amongst older adults, particularly amongst those with multiple health conditions, cognitive impairment or frailty. This study investigates the agreement between self-reported and general practice-recorded data amongst such patients and the impact of participant factors on this agreement. METHODS: data on health conditions was collected from participants in the Community Ageing Research 75+ (CARE75+) study (n = 964) by self-report during face-to-face assessment and interrogation of the participants' general practice electronic health records. Agreement between self-report and practice records was assessed using Kappa statistics and the effect of participant demographics using logistic regression. RESULTS: agreement ranged from K = 0.25 to 1.00. The presence of ≥2 health conditions modified agreement for cancer (odds ratio, OR:0.62, 95%confidence interval, CI:0.42-0.94), diabetes (OR:0.55, 95%CI:0.38-0.80), dementia (OR:2.82, 95%CI:1.31-6.13) and visual impairment (OR:3.85, 95%CI:1.71-8.62). Frailty reduced agreement for cerebrovascular disease (OR:0.45, 95%CI:0.23-0.89), heart failure (OR:0.40, 95%CI:0.19-0.84) and rheumatoid arthritis (OR:0.41, 95%CI:0.23-0.75). Cognitive impairment reduced agreement for dementia (OR:0.36, 95%CI:0.21-0.62), diabetes (OR:0.47, 95%CI:0.33-0.67), heart failure (OR:0.53, 95%CI:0.35-0.80), visual impairment (OR:0.42, 95%CI:0.25-0.69) and rheumatoid arthritis (OR:0.53, 95%CI:0.37-0.76). CONCLUSIONS: significant variability exists for agreement between self-reported and general practice-recorded comorbidities. This is further affected by an individual's health conditions. This study is the first to assess frailty as a factor modifying agreement and highlights the importance of utilising the general practice records as the gold standard for data collection from older adults.
31365340 Serum hepcidin level and rheumatoid arthritis disease activity. 2019 Apr OBJECTIVE: The present study aimed to determine the relationship between the serum hepcidin level and disease activity in patients with rheumatoid arthritis (RA). METHODS: This study was conducted on 80 patients with RA (36 cases with anemia of chronic disease [ACD] and 44 patients without ACD). Disease activity was measured by the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). According to the DAS28-ESR score, 52 and 28 cases were categorized as inactive to moderately active RA (DAS28-ESR≤5.1) and highly active RA (DAS28-ESR>5.1), respectively. In addition, the serum hepcidin level was evaluated in all patients to determine its correlation with the DAS28-ESR score. RESULTS: There was no significant difference between the RA with ACD and RA without ACD groups in terms of the median (interquartile range) hepcidin level (1207 [985.2] vs. 923.8 [677.3] ng/mL; P=0.57). Likewise, no significant difference was observed between the active RA and inactive to moderately active RA groups in this regard (1131.8 [991.3] vs. 1090.9 [631.4] ng/mL; P=0.53). CONCLUSION: Hepcidin has no association with disease activity in RA. Therefore, it is not necessary to measure hepcidin to determine the RA activity.
31345729 Potential role of melatonin in autoimmune diseases. 2019 Aug Autoimmune diseases are a broad spectrum of disorders involved in the imbalance of T-cell subsets, in which interplay or interaction of Th1, Th17 and Tregs are most important, resulting in prolonged inflammation and subsequent tissue damage. Pathogenic Th1 and Th17 cells can secrete signature proinflammatory cytokines, including interferon (IFN)-γ and IL-17, however Tregs can suppress effector cells and dampen a wide spectrum of immune responses. Melatonin (MLT) can regulate the humoral and cellular immune responses, as well as cell proliferation and immune mediators. Treatment with MLT directly interferes with T cell differentiation, controls the balance between pathogenic and regulatory T cells and regulates inflammatory cytokine release. MLT can promote the differentiation of type 1 regulatory T cells via extracellular signal regulated kinase 1/2 (Erk1/2) and retinoic acid-related orphan receptor-α (ROR-α) and suppress the differentiation of Th17 cells via the inhibition of ROR-γt and ROR-α expression through NFIL3. Moreover, MLT inhibits NF-κB signaling pathway to reduce TNF-α and IL-1β expression, promotes Nrf2 gene and protein expression to reduce oxidative and inflammatory states and regulates Bax and Bcl-2 to reduce apoptosis; all of which alleviate the development of autoimmune diseases. Thus, MLT can serve as a potential new therapeutic target, creating opportunities for the treatment of autoimmune diseases. This review aims to highlight recent advances in the role of MLT in several autoimmune diseases with particular focus given to novel signaling pathways involved in Th17 and Tregs as well as cell proliferation and apoptosis.