Browse

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

ID PMID Title PublicationDate abstract
33275235 MiR-34a-5p inhibits fibroblast‑like synoviocytes proliferation via XBP1. 2020 Nov OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune, inflammatory disease mainly manifested by joint damage. Its mechanism is not completely clear at present. Previous studies have found that microRNA-34a-5p (miR-34a-5p) is involved in the development of many inflammatory diseases. In this study, we intended to study the role and mechanism of miR-34a-5p in the development of RA. MATERIALS AND METHODS: We predicted that miR-34a-5p could directly inhibit the expression of X-box binding protein 1 (XBP1). We analyzed whether miR-34a-5p could inhibit XBP1 expression by Real-time Quantitative PCR. Cell Counting Kit-8 was used to detect the proliferation of fibroblast‑like synoviocytes (FLS). Tumor Necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) secreted by FLS were measured by Enzyme-Linked Immunosorbent assay. Western blot was used to detect the expression of XBP1 and Luciferase assay was used to verify the interaction between miR-34a-5p and XBP1. RESULTS: We found that miR-34a-5p expression is lower in RA synovial tissue compared to osteoarthritis (OA). Moreover, miR-34a-5p inhibited the proliferation of FLS and inhibited the secretion of TNF-α and IL-6 by FLS. According to the prediction, we found that miR-34a-5p may bind to the 3' untranslated region (3' UTR) of XBP1, thereby inhibiting its expression. Through functional experiments and Luciferase experiments, we showed that miR-34a-5p can directly target XBP1, thereby inhibiting its expression. CONCLUSIONS: In short, miR-34a-5p can directly inhibit the expression of XBP1, ultimately inhibit the proliferation of FLS, and inhibit the secretion of TNF-α and IL-6 by FLS. This study can provide new ideas for the treatment of RA.
33235388 Novel human immunomodulatory T cell receptors and their double-edged potential in autoimmu 2021 Apr In the last decade, approaches based on T cells and their immunomodulatory receptors have emerged as a solid improvement in treatments for various types of cancer. However, the roles of these molecules in the therapeutic context of autoimmune and cardiovascular diseases are still relatively unexplored. Here, we review the best known and most commonly used immunomodulatory T cell receptors in clinical practice (PD-1 and CTLA-4), along with the rest of the receptors with known functions in animal models, which have great potential as modulators in human pathologies in the medium term. Among these other receptors is the receptor CD69, which has recently been described to be expressed in mouse and human T cells in autoimmune and cardiovascular diseases and cancer. However, inhibition of these receptors individually or in combination by drugs or monoclonal antibodies generates a loss of immunological tolerance and can trigger multiple autoimmune disorders in different organs and immune-related adverse effects. In the coming decades, knowledge on the functions of different immunomodulatory receptors will be pivotal for the development of new and better therapies with less harmful side effects. In this review, we discuss the roles of these receptors in the control of immunity from a perspective focused on therapeutic potential in not only cancer but also autoimmune diseases, such as systemic lupus erythematosus, autoimmune diabetes and rheumatoid arthritis, and cardiovascular diseases, such as atherosclerosis, acute myocardial infarction, and myocarditis.
33159500 Unique inflammatory signature in haemophilic arthropathy: miRNA changes due to interaction 2020 Dec In haemophilia, the recurrence of hemarthrosis leads to irreversible arthropathy termed haemophilic arthropathy (HA). However, HA is a unique form of arthropathy in which resident cells, such as fibroblast-like synoviocytes (FLS), come into direct contact with blood. Therefore, we hypothesized that FLS in HA could have a unique inflammatory signature as a consequence of their contact with blood. We demonstrated with ELISA and ELISPOT analyses that HA-FLS expressed a unique profile of cytokine secretion, which differed from that of non-HA-FLS, mainly consisting of cytokines involved in innate immunity. We showed that unstable cytokine mRNAs were involved in this process, especially through miRNA complexes as confirmed by DICER silencing. A miRNOME analysis revealed that 30 miRNAs were expressed differently between HA and non-HA-FLS, with most miRNAs involved in inflammatory control pathways or described in certain inflammatory diseases, such as rheumatoid arthritis or lupus. Analysis of transcriptomic networks, impacted by these miRNAs, revealed that protein processes and inflammatory pathways were particularly targeted in LPS-induced FLS, and in particular vascularization and osteoarticular modulation pathways in steady-state FLS. Our study demonstrates that the presence of blood in contact with FLS may induce durable miRNA changes that likely participate in HA pathophysiology.
33130388 Computational engineering the binding affinity of Adalimumab monoclonal antibody for desig 2021 Jan Amongst the anti-TNF-α therapy for rheumatoid arthritis and other autoimmune diseases, Adalimumab mAb is one of the best candidates. However, several risk factors are found to be associated with higher doses. Improvement of the binding properties will therefore significantly increase its therapeutic efficacy, reduce the dosage requirements, and ultimately the associated toxicity and treatment cost. Here, we proposed a systematic in silico approach of finding newer mAb variants with improved binding properties. Using various bioinformatics tools, we have identified the significant amino acid residues on Adalimumab mAb. Next, we searched for the suitability of the other residues for mutating the significant residues and from the combinations of suitable mutations, variants were designed. To find the most significant ones, binding properties of the variants were compared with the wild type Adalimumab mAb using molecular docking scrutiny and molecular dynamics simulation. Finally, structural properties between the variant and wild type were analyzed. We have identified the six most significant residues on Adalimumab mAb involved in the antigen-antibody interactions. Using the suitable mutations replacing each of these residues, we have modeled 143 variants. From several docking analyses, we have found five significant variants and after molecular dynamics simulation, one most significant variant with improved binding affinity was identified whose structural properties are similar to the wild type Adalimumab mAb. Designed variant from this study, may provide newer insights on the structure-based affinity improvements of monoclonal antibodies and likewise modifications of the Fc region will also improve the therapeutic effector functions of antibodies too.
32903395 Novel Muscle Imaging in Inflammatory Rheumatic Diseases-A Focus on Ultrasound Shear Wave E 2020 In recent years, imaging has played an increasing role in the clinical management of patients with rheumatic diseases with respect to aiding diagnosis, guiding therapy and monitoring disease progression. These roles have been underpinned by research which has enhanced our understanding of disease pathogenesis and pathophysiology of rheumatology conditions, in addition to their key role in outcome measurement in clinical trials. However, compared to joints, imaging research of muscles is less established, despite the fact that muscle symptoms are very common and debilitating in many rheumatic diseases. Recently, it has been shown that even though patients with rheumatoid arthritis may achieve clinical remission, defined by asymptomatic joints, many remain affected by lingering constitutional systemic symptoms like fatigue, tiredness, weakness and myalgia, which may be attributed to changes in the muscles. Recent improvements in imaging technology, coupled with an increasing clinical interest, has started to ignite new interest in the area. This perspective discusses the rationale for using imaging, particularly ultrasound and MRI, for investigating muscle pathology involved in common inflammatory rheumatic diseases. The muscles associated with rheumatic diseases can be affected in many ways, including myositis-an inflammatory muscle condition, and myopathy secondary to medications, such as glucocorticoids. In addition to non-invasive visual assessment of muscles in these conditions, novel imaging techniques like shear wave elastography and quantitative MRI can provide further useful information regarding the physiological and biomechanical status of the muscle.
32734810 Hydroxychloroquine Alternatives for Chronic Disease: Response to a Growing Shortage Amid t 2022 Feb With the emergence of a novel severe acute respiratory syndrome coronavirus, investigators worldwide are scrambling to identify appropriate treatment modalities, develop accurate testing, and produce a vaccine. To date, effective treatment remains elusive. Chloroquine phosphate and hydroxychloroquine sulfate (HCQ), well-known antimalarial drugs effective in the treatment of systemic lupus erythematosus, rheumatoid arthritis, porphyria cutanea tarda, and chronic Q fever, are currently under investigation. The United States Food and Drug Administration recently issued an Emergency Use Authorization for CQ and HCQ use in the treatment of coronavirus disease 2019 (COVID-19). With spikes in HCQ use and demand, ethical considerations encompassing appropriate use, patient autonomy, nonmaleficence, and distributive justice abound. As drug experts, pharmacists are uniquely positioned to advocate for patients with chronic conditions necessitating HCQ use, assist in the appropriate prescribing of HCQ for COVID-19, and ensure patients and health care professionals are continually educated during this public health crisis. This review highlights the worldwide pandemic, describes appropriate HCQ use for chronic conditions, highlights available alternatives, and deliberates evolving ethical questions. With assistance from colleagues, state boards of pharmacy, and national organizations, pharmacists ensure the just distribution of valuable pharmaceuticals to patients having COVID-19 while supporting the needs of patients requiring HCQ for chronic conditions.
32600150 Patient-related risk factors associated with less favourable outcomes following hip arthro 2020 Jul AIMS: This paper aims to review the evidence for patient-related factors associated with less favourable outcomes following hip arthroscopy. METHODS: Literature reporting on preoperative patient-related risk factors and outcomes following hip arthroscopy were systematically identified from a computer-assisted literature search of Pubmed (Medline), Embase, and Cochrane Library using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a scoping review. RESULTS: Assessment of these texts yielded 101 final articles involving 90,315 hips for qualitative analysis. The most frequently reported risk factor related to a less favourable outcome after hip arthroscopy was older age and preoperative osteoarthritis of the hip. This was followed by female sex and patients who have low preoperative clinical scores, severe hip dysplasia, altered hip morphology (excess acetabular retroversion or excess femoral anteversion or retroversion), or a large cam deformity. Patients receiving workers' compensation or with rheumatoid arthritis were also more likely to have a less favourable outcome after hip arthroscopy. There is evidence that obesity, smoking, drinking alcohol, and a history of mental illness may be associated with marginally less favourable outcomes after hip arthroscopy. Athletes (except for ice hockey players) enjoy a more rapid recovery after hip arthroscopy than non-athletes. Finally, patients who have a favourable response to local anaesthetic are more likely to have a favourable outcome after hip arthroscopy. CONCLUSION: Certain patient-related risk factors are associated with less favourable outcomes following hip arthroscopy. Understanding these risk factors will allow the appropriate surgical indications for hip arthroscopy to be further refined and help patients to comprehend their individual risk profile. Cite this article: Bone Joint J 2020;102-B(7):822-831.
32522746 Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therap 2020 Jun 17 The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
32458614 [Relationship between parasitic infections and hygiene hypothesis: a review]. 2020 Apr 26 Recently, the incidence of infectious diseases continues to decline in many developed countries; however, the incidence of autoimmune diseases and allergic asthma appears a tendency towards a rise over years. "Hygiene hypothesis" provides new insights into the treatment of autoimmune disorders and allergic diseases based on parasitic infections. Increasing evidence shows that parasitic infections may effectively inhibit the development of diabetes, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis and allergic asthma. There are complex mechanisms underlying the relationship between parasitic infections and "hygiene hypothesis", among which regulatory T (Treg) cells and Th17 cells are becoming a hot topic of research. This paper reviews the progresses in the research on the relationship between parasitic infections and "hygiene hypothesis", and summarizes the roles of Treg cells and Th17 cells in the interplay between parasitic infections and "hygiene hypothesis".
32428860 Type I Interferons Ameliorate Zinc Intoxication of Candida glabrata by Macrophages and Pro 2020 May 22 Host and fungal pathogens compete for metal ion acquisition during infectious processes, but molecular mechanisms remain largely unknown. Here, we show that type I interferons (IFNs-I) dysregulate zinc homeostasis in macrophages, which employ metallothionein-mediated zinc intoxication of pathogens as fungicidal response. However, Candida glabrata can escape immune surveillance by sequestering zinc into vacuoles. Interestingly, zinc-loading is inhibited by IFNs-I, because a Janus kinase 1 (JAK1)-dependent suppression of zinc homeostasis affects zinc distribution in macrophages as well as generation of reactive oxygen species (ROS). In addition, systemic fungal infections elicit IFN-I responses that suppress splenic zinc homeostasis, thereby altering macrophage zinc pools that otherwise exert fungicidal actions. Thus, IFN-I signaling inadvertently increases fungal fitness both in vitro and in vivo during fungal infections. Our data reveal an as yet unrecognized role for zinc intoxication in antifungal immunity and suggest that interfering with host zinc homeostasis may offer therapeutic options to treat invasive fungal infections.
33074636 2020 Apr 13 Chronic pain is generally defined as pain lasting for three months or longer, or persisting beyond the time needed for normal tissue healing. It can impact the individual’s quality of life and productivity, and is associated with substantial health care costs.(,) Chronic pain is a global problem. It is estimated that one in five Canadians suffer from chronic pain. It is generally more common among older adults, females, Indigenous people, Veterans, and people encountering inequalities and discrimination. According to one report, in Canada during the period 2007 to 2008, the prevalence rates for chronic pain in the age groups 26 years to 35 years, 46 years to 55 years, 56 years to 65 years, and 66 years and older were respectively 17.4%, 23.4%, 28.6% and 31.5% in females and 15.3%, 22.8%, 22.0%, and 22.2% in males. There are a variety of chronic pain conditions such as chronic back pain, chronic neck pain, chronic tension headache, and chronic arthritic pain.(,) Chronic pain can affect various parts of the body such as the lower back, upper back, knee, leg, feet, shoulder, neck, and hip. Lower back pain appears to be the most predominant type, accounting for more than one-third of those suffering from chronic pain. There are several non-pharmacological treatment options available for chronic pain such as exercise, multidisciplinary rehabilitation, psychological therapies, and physical modalities. Foot orthotics are one example of a non-pharmacological treatment option for chronic pain, and include custom-made shoe inserts or prefabricated shoe inserts (with a treatment intent). These inserts are intended to support or align foot structures or to prevent or correct foot deformaties, and can be of various types such as soft, semi-rigid, and rigid.(,) These inserts are sometimes referred to as insoles; however, these are specialized insoles with a treatment intent. It is thought that foot function can affect the kinematics of the knee, hip, pelvis, and the thorax. Foot orthotics have been used for the management of chronic pain, in individuals with various conditions such as rheumatoid arthritis and low back pain.(,) However, there appears to be some uncertainty with respect to its effectiveness in improving pain and disability. This report is an upgrade from a recent (published in 2020) CADTH Reference List report and with additional restrictions with respect to inclusion criteria. The purpose of the current report is summarize and critically appraise the relevant evidence identified in the previous report regarding the clinical effectiveness of customized foot orthotics or prefabricated shoe inserts (with a therapeutic intent) for chronic non-cancer pain.
32236928 [Interstitial lung disease in rheumatic diseases - new therapeutic approaches]. 2020 Apr Pulmonary involvement is an important aspect in the management of rheumatic diseases. Connective tissue disease-associated interstitial lung diseases (CTD-ILD) are of particular importance, as their occurrence is often decisive for patient outcome. We use corticosteroids, immunosuppressants and eventually also biologicals in the therapy of CTD-ILD.Except for the "Scleroderma Lung Study" (SLS) I and II, which confirm the effectiveness of the immunosuppressive drugs cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in pulmonary involvement of scleroderma (SSc-ILD), there is little data on the treatment of other CTD-ILD. Within the group of biologicals the use of Rituximab (RTX) increases in importance. The currently expected study results compare the efficacy of immunosuppressive drugs (in particular MMF and CYC) with RTX. Other investigated biologicals include Tocilizumab in SSc-ILD and Abatacept in pulmonary involvement in rheumatoid arthritis (RA-ILD). Autologous stem cell transplantation is a potent but potentially risky therapy for severe scleroderma.For the group of pulmonary interstitial diseases of different dignity, including CTD-ILD, with a increasingly fibrosing course despite adequate therapy, (e. g. chronic hypersensitivity pneumonitis, sarcoidosis) the term and concept of "fibrosing interstitial lung diseases with progressive phenotype" (PF-ILD) is being established. In the last months studies were published, which show a positive effect of antifibrotic drugs (Nintedanib, Pirfenidon) in such constellations. Currently a number of other studies regarding the effectiveness of antifibrotics in CTD-ILD are expected to be published. The studies in this field bring new aspects in the understanding of interstitial diseases and have the potential of expanding treatment options in CTD-ILD.The topic of CTD-ILD is a difficult, but at the same time exciting field.
32228113 An updated patent review of p38 MAP kinase inhibitors (2014-2019). 2020 Jun Introduction: During the first half of the last decade the p38 MAP kinase family was a very popular target in academic as well as industrial research programs. Many attempts to achieve marketing authorization for a p38 MAPK inhibitor for the treatment of pro-inflammatory diseases, like rheumatoid arthritis (RA), failed at the state of clinical trials, mostly due to selectivity and/or toxicity issues.Areas covered: Herein, the patents and corresponding publications of international companies, universities and other research institutions, which focus on the development, identification and optimization of new selective p38 inhibitors and their fields of use are summarized.Expert opinion: p38 MAP kinase inhibitors are a mature field with many pre-clinically validated structural classes, more than 20 candidates in clinical trials but still (except the weak and unselective p38 inhibitor pirfenidone) no approved drug. Big Pharma hasn't contributed much to the patents of the last five years but remarkable contribution have come from academic environment or small biotech companies. Three general punchlines of innovation have shown up. Tailor-made molecules with properties for local application, mainly type-II (Urea-type) inhibitors for lung- or skin diseases, isoform p38γ,δ-selective inhibitors for the treatment of cutaneous t-cell lymphoma (CTCL) and substrate-specific inhibitors (e.g. p38/MK2).
32141499 Loss of core fucosylation in both ST6GAL1 and its substrate enhances glycoprotein sialylat 2020 Mar 27 Fucosyltransferase 8 (FUT8) and β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) are glycosyltransferases that catalyze α1,6-fucosylation and α2,6-sialylation, respectively, in the mammalian N-glycosylation pathway. They are aberrantly expressed in various human diseases. FUT8 is non-glycosylated but is responsible for the fucosylation of ST6GAL1. However, the mechanism for the interaction between these two enzymes is unknown. In this study, we show that serum levels of α2,6-sialylated N-glycans are increased in Fut8-/- mice, whereas the mRNA and protein levels of ST6GAL1 are unchanged in mouse live tissues. The level of α2,6-sialylation on IgG was also enhanced in Fut8-/- mice along with ST6GAL1 catalytic activity increase in both serum and liver. Moreover, it was observed that ST6GAL1 prefers non-fucosylated substrates. Interestingly, increased core fucosylation accompanied by a reduction in α2,6-sialylation, was detected in rheumatoid arthritis patient serum. These findings provide new insight into the interactions between FUT8 and ST6GAL1.
31960044 Placement of C1 Lateral Mass Screw-Alternative Technique: 2-Dimensional Operative Video. 2020 Sep 1 This operative video demonstrates a C1 lateral mass instrumentation technique that is an alternative to the traditional Goel and Harms techniques.1,2 The advantages of the alternative technique include minimized blood loss from the rich venous plexus surrounding the C2 dorsal root ganglia (DRG), avoidance and preservation of the C2 DRG, and placement of a robust fully threaded screw without risking neuralgia. These are discussed in detail and presented through a case of atlantoaxial instability. Patient's consent was obtained for creating this surgical video. The patient is a 50-yr-old woman with a 17-yr history of rheumatoid arthritis. She presented with 1 yr of neck pain that failed conservative measures. Flexion-extension radiographs demonstrated an atlantodental index (ADI) that reduced from 7 mm on flexion to 0 mm on extension. The patient underwent a C1-C2 posterior instrumented fusion using the alternative technique of C1 lateral mass instrumentation.2 The steps of this technique are explained in great detail through a microsurgical video. The patient's postoperative course was uneventful. Postoperative radiographs and computed tomography (CT) scan demonstrated reduction of ADI and well-placed instrumentation and fusion construct. Her neck pain was completely resolved by 3 mo following surgical stabilization. In the senior author's experience with placing over 120 C1 lateral mass screws with this alternative technique, there have been no instances of vascular injury, sacrifice of C2 DRG, or instrumentation failure. The alternative technique for placement of C1 lateral mass screw is safe, efficient, and holds certain advantages in comparison to the traditionally described method.  Images within the video have been reproduced from AOSpine section of the AO Surgery Reference, www.aosurgery.org, with permission from AO Surgery. Copyright by AOSpine International, Switzerland; and reprinted from World Neurosurgery, 78(1-2), Kang MM et al, C2 Nerve Root Sectioning in Posterior C1-2 Instrumented Fusions, 170-177, Copyright 2012, with permission from Elsevier.
31845043 The role of melatonin in Multiple Sclerosis. 2020 Apr Melatonin is a neurohormone mainly produced by the pineal gland following a circadian rhythm. It is characterized as a pleiotropic factor because it not only regulates the wake-sleep rhythm but also exerts antinociceptive, antidepressant, anxiolytic, and immunomodulating properties. Recent studies suggest that dysregulation of melatonin secretion is associated with the pathogenesis of various autoimmune diseases, such as, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS). MS is an autoimmune disorder characterized by an abnormal immune response directed against the myelin sheath in the central nervous system, demyelination, oligodendrocyte death, and axonal degeneration. Recent evidence reveals that melatonin secretion is dysregulated in MS patients, suggesting that melatonin could be a potential target for therapeutic intervention. Here, we summarize the available literature regarding the role of melatonin in immune processes relevant for experimental autoimmune encephalomyelitis (EAE), MS, and the current clinical trials of melatonin supplementation in MS patients.
31757417 Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by 2020 Jan 29 Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH-HIF-1α axis may facilitate host modulation therapy of chronic periodontitis.
31712033 Effect of stopping hydroxychloroquine therapy on the multifocal electroretinogram in patie 2020 Feb OBJECTIVE: To report the effect of hydroxychloroquine therapy cessation on the multifocal electroretinogram (mfERG) in a case series of patients with rheumatic disease suspected to have retinopathy. METHODS: Comprehensive data were retrospectively reviewed on 14 patients from a total of 50 cases who discontinued hydroxychloroquine due to suspected toxicity. Patients were followed for 4 years after the cessation of therapy. mfERG testing had been part of original screening for hydroxychloroquine retinopathy and was continued after therapy cessation at 6-month intervals. Descriptive statistics, independent sample t test, and one-way analysis of variance with repeated measures and post hoc analysis were conducted to determine patients' clinical characteristics and changes in the mfERG after therapy cessation, respectively. RESULTS: All 14 patients were female; 12 were treated for rheumatoid arthritis and 2 for systemic lupus erythematosus. Three groups were identified: (i) 9 patients in whom the responses of the mfERG recovered to within normative values after cessation of hydroxychloroquine therapy, (ii) 3 who experienced limited recoveries, and (iii) 1 patient whose mfERG response was unchanged. There was no significant difference (p > 0.05) in the clinical characteristics of these patients. However, the proportional reduction of mfERG ring 1, 2, and 3 amplitudes from age normal responses at the time of discontinuation of drug use for the first and second groups of patients was significantly different, with more reduction in group 2 (p < 0.05). CONCLUSION: Early detection of hydroxychloroquine retinopathy through screening and subsequent therapy discontinuation could result in recovery of the mfERG ring amplitude response and preservation of visual function.
31702518 Phospholipase Cγ Signaling in Bone Marrow Stem Cell and Relevant Natural Compounds Therap 2020 Excessive bone resorption has been recognized play a major role in the development of bone-related diseases such as osteoporosis, rheumatoid arthritis, Paget's disease of bone, and cancer. Phospholipase Cγ (PLCγ) family members PLCγ1 and PLCγ2 are critical regulators of signaling pathways downstream of growth factor receptors, integrins, and immune complexes and play a crucial role in osteoclast. Ca2+ signaling has been recognized as an essential pathway to the differentiation of osteoclasts. With growing attention and research about natural occurring compounds, the therapeutic use of natural active plant-derived products has been widely recognized in recent years. In this review, we summarized the recent research on PLCγ signaling in bone marrow stem cells and the use of several natural compounds that were proven to inhibit RANKL-mediated osteoclastogenesis via modulating PLCγ signaling pathways.
31412748 Decreased Expression of Semaphorin 3A and Semaphorin 7A Levels and Its Association with Sy 2020 Feb A growing body of data suggests that semaphorins are involved in both normal and pathological immune responses, as well as autoimmune pathologies. To investigate the plasma semaphorin 3A (Sema3A) and semaphorin 7A (Sema7A) levels in systemic lupus erythematosus (SLE) patients and their correlation with clinical manifestations and laboratory indexes, a two-step method was applied. First, 80 SLE patients and 80 healthy controls were recruited for comparing serum Sema3A and Sema7A concentrations. Second, 40 rheumatoid arthritis (RA) patients and 40 sjögren's syndrome (SS) patients were then included as disease controls. Plasma Sema3A and Sema7A concentrations were detected by ELISA. There were significant differences in Sema3A and Sema7A among four groups. When compared to healthy controls, both Sema3A and Sema7A levels were decreased in SLE and increased in RA; increased Sema3A level and decreased Sema7A level were found in SS. There were significant differences in Sema3A concentration between SLE and RA, SLE and SS. Moreover, there were significant differences in Sema7A level between SLE and RA, SS and RA. However, no significant differences in Sema3A between SS and RA and no significant differences in Sema7A between SS and SLE were observed. Both plasma Sema3A and Sema7A levels were correlated with anti-SSA and IgM. Area under curve (AUC) of the receiver operating characteristic (ROC) curve for Sema3A and Sema7A were 0.535 (0.455-0.613) and 0.671 (0.594-0.742), respectively. Aberrant Sema3A and Sema7A expression and their clinical associations in SLE suggest their important role in this disease.