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ID PMID Title PublicationDate abstract
32220799 The αC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases. 2020 Jul Despite being crucial for combating microbes, paradoxical Toll-like receptors (TLRs) signaling have been associated with the aggravation of multiple immune disorders such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, and nonalcoholic steatohepatitis. The stoichiometry and precise arrangement of the interaction of adapters (via their Toll/interleukin-1 receptor [TIR] domains) are indispensable for the activation of TLRs and of downstream signaling cascades. Among adapters, plasma membrane-anchored MyD88 adaptor-like (MAL) has the potential for BB-loop-mediated self-oligomerization and interacts with other TIR domain-containing adaptors through αC and αD helices. Here, we used information on the MAL-αC interface to exploit its pharmacophores and to design a decoy peptide (MIP2) with broad-range TLR-inhibitory abilities. MIP2 abrogated MyD88- and TRIF-dependent lipopolysaccharide (LPS)-induced TLR4 signaling in murine and human cell lines and manifested a therapeutic potential in models of psoriasis, systemic lupus erythematosus, nonalcoholic steatohepatitis, and sepsis. Levels of hallmark serological and histological biomarkers were significantly restored and the disease symptoms were substantially ameliorated by MIP2 treatment of the animals. Collectively, our biophysical, in vitro, and in vivo findings suggest that MIP2 has broad specificity for TLRs and may be effective in modulating autoimmune complications caused by microbial or environmental factors.
32118763 Hematological indices as indicators of silent inflammation in achalasia patients: A cross- 2020 Feb Complete blood count (CBC)-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte (ELR) ratio, and platelet-to-lymphocyte ratio (PLR) are sensitive markers of occult inflammation and disease activity for systemic lupus erythematosus, rheumatoid arthritis, psoriasis, esophageal cancer, etc. We assessed NLR, PLR, MLR, and ELR as indicators of inflammation in achalasia patients.This cross-sectional study included 103 achalasia patients and 500 healthy blood donor volunteers (HD). Demographic, clinical and laboratory information was collected. NLR, MLR, ELR and PLR were calculated. Peripheral Th22, Th17, Th2 and Th1 subsets were determined by flow cytometry. Correlation between hematologic indices and clinical questionnaires scores, HRM parameters and CD4+ T-cells were assessed. Hematologic parameters associated with the different achalasia subtypes were evaluated by logistic regression analysis.Hemoglobin, leukocytes, lymphocytes, monocytes, and platelets counts were significantly lower in achalasia patients vs controls. NLR (P = .006) and ELR (P < .05) were higher in achalasia patients vs controls. NLR was significantly associated with achalasia in multivariate analysis (P < .001). Compared to HD, the achalasia group was 1.804 times more likely to have higher NLR (95% CI 1.287-2.59; P < .001). GERD-HRQL score had statistically significant correlations with PLR (Pearson's rho:0.318, P = .003), and ELR (Pearson's rho:0.216; P = .044). No correlation between CD4+ T-cells and hematologic indices were determined. NLR with a cut-off value of ≥2.20 and area under the curve of 0.581 yielded a specificity of 80% and sensitivity of 40%, for the diagnosis of achalasia.NLR is increased in achalasia patients vs HD. Sensitivity and specificity achieved by NLR may contribute to a clinical and manometric evaluation. We suggest these indices as potential indicators of silent inflammation and disease activity.
33241941 Mindfulness-Based Cognitive Therapy for Treating Chronic Pain A Systematic Review and Meta 2021 Mar Chronic pain is a significant public health problem with emotional and disabling factors, which may not completely respond to current medical treatments such as opioids. The systematic review and meta-analysis aimed to examine the effectiveness and safety of MBCT for patients with chronic pain. Database searches of PubMed, Medline, EMBASE, the Cochrane Library, PsycINFO, Web of Science, Scopus and CINAHL up to 15 October 2019. Included studies assessed with the Cochrane risk-of-bias tool. Eight RCTs involved 433 patients, including chronic low back pain, fibromyalgia, migraine, rheumatoid arthritis and mix etiology. MBCT intervention demonstrated a short-term improvement on depression mood [standardized mean difference -0.72; 95% confidence interval = -1.22 to -0.22, p = 0.005] compared with usual care and was associated with short-term improvement in mindfulness compared with non-MBCT [SMD 0.51; 95% CI = 0.01 to 1.01, p = 0.04]. Between-group differences in pain intensity, pain inference and pain acceptance were not significant at short- or long-term follow-up. Compared to active treatments, MBCT intervention not found significant differences in either short- or long-term outcomes. MBCT showed short-term efficacious on depressed mood and mindfulness of chronic pain patients. Longer follow-ups, large sample and rigorous RCTs that can be best understand remaining uncertainties needed.
33182024 Gut microbiome and multiple sclerosis: New insights and perspective. 2020 Nov The human gastrointestinal microbiota, also known as the gut microbiota living in the human gastrointestinal tract, has been shown to have a significant impact on several human disorders including rheumatoid arthritis, diabetes, obesity, and multiple sclerosis (MS). MS is an inflammatory disease characterized by the destruction of the spinal cord and nerve cells in the brain due to an attack of immune cells, causing a wide range of harmful symptoms related to inflammation in the central nervous system (CNS). Despite extensive studies on MS that have shown that many external and genetic factors are involved in its pathogenesis, the exact role of external factors in the pathophysiology of MS is still unclear. Recent studies on MS and experimental autoimmune encephalomyelitis (EAE), an animal model of encephalitis, have shown that intestinal microbiota may play a key role in the pathogenesis of MS. Therefore, modification of the intestinal microbiome could be a promising strategy for the future treatment of MS. In this study, the characteristics of intestinal microbiota, the relationship between intestine and brain despite the blood-brain barrier, various factors involved in intestinal microbiota modification, changes in intestinal microbial composition in MS, intestinal microbiome modification strategies, and possible use of intestinal microbiome and factors affecting it have been discussed.
33154498 Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20  2020 Nov 5 Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment.
33039995 Healthcare experiences of patients with chronic heart failure in Germany: a scoping review 2020 Oct 10 OBJECTIVES: To review systematically the past 10 years of research activity into the healthcare experiences (HCX) of patients with chronic heart failure (CHF) in Germany, in order to identify research foci and gaps and make recommendations for future research. DESIGN: In this scoping review, six databases and grey literature sources were systematically searched for articles reporting HCX of patients with CHF in Germany that were published between 2008 and 2018. Extracted results were summarised using quantitative and qualitative descriptive analysis. RESULTS: Of the 18 studies (100%) that met the inclusion criteria, most were observational studies (60%) that evaluated findings quantitatively (60%). HCX were often concerned with patient information, global satisfaction as well as relationships and communication between patients and providers and generally covered ambulatory care, hospital care and rehabilitation services. Overall, the considerable heterogeneity of the included studies' outcomes only permitted relatively trivial levels of synthesis. CONCLUSION: In Germany, research on HCX of patients with CHF is characterised by missing, inadequate and insufficient information. Future research would benefit from qualitative analyses, evidence syntheses, longitudinal analyses that investigate HCX throughout the disease trajectory, and better reporting of sociodemographic data. Furthermore, research should include studies that are based on digital data, reports of experiences gained in under-investigated yet patient-relevant healthcare settings and include more female subjects.
32632386 Trends and outcomes of fungal infections in hospitalized patients of inflammatory bowel di 2020 BACKGROUND: Immunosuppressive therapy is being increasingly used in the management of inflammatory bowel disease (IBD) which comprises of ulcerative colitis (UC) and Crohn's disease (CD). Patients on immunosuppressive therapy are at increased risk of developing opportunistic fungal infections. We conducted this analysis to describe the epidemiology of opportunistic fungal infections in this cohort. METHODS: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of IBD (UC and Crohn's disease) & Fungal infections (Histoplasmosis, Pneumocystosis, Cryptococcosis, Aspergillosis, Blastomycosis, candidiasis, Coccidioidomycosis) as primary or secondary diagnosis via ICD 9 codes during the period from 2002-2014. RESULTS: In UC, the incidence of all fungal infections was more in age above 50 (except for pneumoconiosis) male gender (except Candidiasis) and in Caucasians. In CD, the incidence was more in age above 50 (except Pneumocystosis, Blastomycosis & Coccidioidomycosis), female gender (except Histoplasmosis, Pneumocystosis & Cryptococcosis) and in Caucasians. Histoplasmosis and Blastomycosis were more prevalent in Midwest, Cryptococcosis and Candidiasis in South, Coccidioidomycosis in west in both UC and CD. Age above 50, south region, HIV, Congestive heart failure, underlying malignancies, diabetes mellitus with complications, chronic pulmonary disease, anemia, rheumatoid arthritis, collagen vascular disease, pulmonary circulation disorders, weight loss were significant predictors of fungal infections in IBD. The yearly trend showed a consistent small rise in incidence, and the mortality dropped till 2006 to peak again in 2008 with a subsequent decline. CONCLUSIONS: Our study is the first one to describe the basic demographics features and characteristics of opportunistic fungal infections in hospitalized patients with IBD. The yearly incidence of fungal infections did not show a significant rise. The mortality increased between 2006-2008 and a significant difference remains between IBD patients with and without fungal infections. One explanation of rise in mortality but a consistent incidence could be due to the use of biologics that did not increase but compromised the ability of IBD patients to fight opportunistic fungal infections.
32553602 Surgical Treatment for Central Sleep Apnea due to Occipitocervical Compression Myelopathy 2020 Sep BACKGROUND: Central sleep apnea (CSA) due to occipitocervical compression myelopathy is an extremely rare condition. Here we report a case of surgical treatment for CSA due to occipitocervical compression myelopathy in a patient with Klippel-Feil syndrome. CASE DESCRIPTION: A 60-year-old man had become aware of a gradually progressive clumsiness and gait disturbance without any cause of injury 5 years before. He had complicated respiratory discomfort during sleep for the previous month and visited our hospital. Neurologic examination revealed severe myelopathy. Polysomnography showed CSA and Cheyne-Stokes respiration. Imaging findings showed C2-3 vertebral fusion and severe spinal cord compression caused by hypoplasia of the C1 posterior arch complicated by an anomaly of the vertebral artery. We diagnosed the patient with CSA due to occipitocervical compression myelopathy complicated by Klippel-Feil syndrome. After a simulation using a full-scale 3-dimensional model, resection of the C1 posterior arch and C4-5 laminoplasty was performed. After surgery, both clumsiness and gait disturbance gradually improved. Polysomnography 1 month after surgery showed that the CSA and the Cheyne-Stokes respiration disappeared. CONCLUSIONS: Although a recent report has indicated the cause of sleep apnea in patients with rheumatoid arthritis and occipitocervical disorders as obstructive sleep apnea, a significant improvement of CSA was observed with decompression surgery in this case. Appropriate surgical planning resulted in a favorable outcome.
32487775 Increased risk of endocrine autoimmunity in first-degree relatives of patients with autoim 2020 Jul OBJECTIVE: Autoimmune conditions tend to cluster in subjects with Addison's disease (AD) and probably also among their relatives. The aim of the study was to estimate the frequency of the endocrine gland-specific autoantibodies in first-degree relatives of patients with AD. METHODS: Autoantibodies were investigated in 113 family members using RIA and ELISA assays. The control group comprised 143 age-matched volunteers. RESULTS: Autoimmune diseases were diagnosed in 38.1% relatives. Hashimoto's thyroiditis was found in 20.3%, Graves' disease in 8.0%, vitiligo and type 1 diabetes in 3.5%, whereas AD, rheumatoid arthritis and atrophic gastritis with pernicious anaemia in 2.7% each. All studied antibodies except for islet antigen-2 (P = 0.085) were significantly more frequent in AD relatives than in controls (P < 0.05). Antibodies to 21-hydroxylase were detected in 6.2% relatives, thyroid peroxidase in 28.3%, thyroglobulin in 19.5%, glutamic acid decarboxylase in 8.0%, and zinc transporter-8 in 7.1%. Two and more autoantibodies were detected in 18.6% subjects. Significant gender difference was revealed only for aTPO, more common in female relatives (P = 0.014; OR: 3.16; 95% CI: 1.23-8.12). Circulating autoantibodies were found more frequently in the relatives of affected males (P = 0.008; OR: 3.31; 95% CI: 1.33-8.23), and in family members of patients with polyendocrine autoimmunity (P = 0.009; OR: 3.55; 95% CI: 1.31-9.57). CONCLUSIONS: This study provides evidence of increased susceptibility for the endocrine autoimmunity, especially thyroid disease, in close relatives of patients with AD. Relatives of the male AD patients and of those with autoimmune polyendocrine syndrome are at particular risk and should undergo periodic screening for autoimmune endocrine disorders.
32279516 The mysteries of rapidly destructive arthrosis of the hip joint: a systemic literature rev 2020 May Rapidly destructive arthrosis (RDA) is considered a rare and poorly diagnosed disease but is now seen more frequently in practice due to ageing populations. The most typical radiological features are flat femoral heads, absence of articular cartilage, subchondral bone destruction and signs of joint effusion. These features could be found on X-ray or magnetic resonance imaging (MRI). Surgeons should consider the presence of RDA when patients show rapid femoral head destruction. The purpose of this study is to review the distinct clinical features and successful treatments which may lead to the diagnosis and early handling of RDA. A comprehensive review of the literature was undertaken using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with no language restrictions. Overall 23 publications with 17 detailed cases of RDA met the inclusion criteria. We found that the only prevalent factors associated with RDA were: (I) age greater than 60 years; (II) female gender; (III) presence of underlying systemic diseases such as rheumatoid arthritis, diabetes mellitus or systemic lupus erythematosus. Further studies should be conducted to clarify the histopathology and define the diagnosis as well as the treatment.
32199306 Design and characterization of a novel structural class of Kv1.3 inhibitors. 2020 May The voltage-gated potassium channel K(v)1.3 is involved in multiple autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, diabetes mellitus type 1 and psoriasis. In many auto-immune diseases better treatment options are desired as existing therapies are often ineffective or become less effective over time, for which K(v)1.3 inhibitors arise as promising candidates. In this study, five compounds were selected based on a 3D similarity searching methodology and subsequently screened ex vivo on the K(v)1.3 channel. The screening resulted in two compounds inhibiting the K(v)1.3 channel, of which TVS-12 was the most potent compound, while TVS-06 -although less potent- showed an excellent selectivity for K(v)1.3. For both compounds the mechanism of action was investigated by an electrophysiological characterization on the K(v)1.3 channel and three K(v)1.3 mutants, designed to resemble the pore region of K(v)1.2 channels. Structurally, the presence of a benzene ring and/or an oxane ring seems to cause a better interaction with the K(v)1.3 channel, resulting in a 20-fold higher potency for TVS-12.
32013856 miR-18a-3p Encourages Apoptosis of Chondrocyte in Osteoarthritis via HOXA1 Pathway. 2020 BACKGROUND: Osteoarthritis is a disorder of joints featuring inflammation and degeneration of articular cartilage. Recently, miRs have been found to be associated in the regulation of chondrocytes and their apoptosis. miR-18a-3p has been found to be associated in the pathogenesis of rheumatoid arthritis, however, its role in articular cartilage tissues remains unclear. METHODS: C57BL/6 strain of mice and human cartilage tissue were used for the study. Histological analysis was done on isolated cartilage samples followed by TUNEL assay and immunohistochemical analysis. The chondrocytes were isolated from mouse and human cartilage tissues, RNA was isolated and subjected for qRT-PCR analysis. The chondrocytes were transfected with miR-18a-3p agomir, antagomir and siHOXA-1. Luciferase assay was done in 293T cells. Flow cytometry analysis was done and western blot analysis for studying the expression of proteins. RESULTS: The expression of miR-18a-3p was upregulated in chondrocytes after exposing them to interlukin- 1β (IL-1β) in vitro. The transfection of miR-18a-3p antagomir halted the IL-1β mediated apoptosis. The luciferase assay suggested that miR-18a-3p targets the 3'UTR region of HOXA1 gene thus blocking its expression. The treatment of HOXA1 siRNA demonstrated the rescuing effect of miR- 18a-3p antagomir on the apoptosis of chondrocytes. Treatment of miR-18a-3p antagomir attenuated the surface of cartilage in osteoarthritis mice and the agomir worsened it. TUNEL assay suggested decreased apoptosis and over-expression of HOAX1 in osteoarthritis mice post miR-18a-3p knockdown. CONCLUSION: The findings confirmed the involvement of miR-18a-3p/HOXA1 pathway as a potential mechanism in the regulation of Osteoarthritis.
32008212 Characteristics and Symptom Severity of Patients Reporting Systemic Lupus Erythematosus in 2020 Mar INTRODUCTION: Online health communities and research networks such as PatientsLikeMe (PLM) capture patient perspectives of diseases, including systemic lupus erythematosus (SLE). We performed a retrospective observational study of data provided by patients in the PLM SLE community to characterize demographics, clinical characteristics, patient experience, and symptom impact. METHODS: Adults who registered with PLM in 2011-2017 and reported SLE diagnosis and treatment with one or more SLE-related drug (antimalarials, immunosuppressives, corticosteroids, calcineurin inhibitors, or biologics) were included in the analysis. Information reported within 30 days from PLM registration was used to assess patient eligibility; demographics and clinical characteristics; and primary outcome measures of SLE treatments, symptoms, primary lupus manifestations, and comorbidities. RESULTS: Among 21,101 PLM members included in this analysis, median ages at registration, onset of SLE symptoms, and SLE diagnosis were 46 years (interquartile range [IQR] 38-53, n = 21,101), 30 years (IQR 21-39; n = 6489), and 36 years (IQR 27-44; n = 6936), respectively. Most patients were female (96.8%, n = 20,370). Country of residence was reported by 19,502 patients (92.4%), of whom 18,491 (94.8%) were US residents. Race was recorded by 17,994 patients (85.3%), of whom 67.8% were white and 22.4% were black/African American. Patients reported a mean of 2.2 SLE-related medications, including antimalarials (83.8%), corticosteroids (78.8%), immunosuppressives (32.3%), and biologics (9.4%). Fatigue, pain, and joint pain were rated as moderate or severe by at least 80% of patients who reported these symptoms. Reported primary lupus manifestations and comorbidities included fibromyalgia (7.9%), discoid lupus (6.8%), lupus nephritis (6.3%), rheumatoid arthritis (4.8%), subacute cutaneous lupus (4.7%), central nervous system lupus (3.9%), Sjögren's syndrome (3.9%), and lupus pneumonitis (3.1%). CONCLUSIONS: Age, sex, and race of patients in the PLM SLE community are broadly consistent with characteristics of the general SLE population in the United States. The PLM SLE population may provide valuable data on self-reported patient experience. Plain language summary available for this article.
31977675 Spontaneous Incidence of Vertebral Body Infection Following Osteoporotic Vertebral Fractur 2020 Jun 15 STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to examine the spontaneous incidence rate and features of pyogenic vertebral osteomyelitis in osteoporotic vertebral fracture (OVF). SUMMARY OF BACKGROUND DATA: Pyogenic vertebral osteomyelitis is a rare complication of OVF. We experienced some cases of vertebral body infection after OVF. METHODS: In this retrospective, single-center study, clinical data were collected by chart review. We examined the number of cases of pyogenic vertebral osteomyelitis following OVF between April 2014 and August 2018. Further, we examined the mechanism of injury, age, sex, duration from the diagnosis of OVF to the diagnosis of vertebral body infection, C-reactive protein level at the time of diagnosis of OVF, medical history, primary infection site, and serious events. RESULTS: The spontaneous incidence rate of complications was 0.7% (4/554). In all cases (two males and two females), fall history was present and vertebral body infection was not suspected to be present at the point of injury. The average age was 81.8 (range, 75-89, SD, 5.7) years. The average duration from the diagnosis of OVF to the diagnosis of vertebral body infection was 55.0 (range, 16-132, SD, 52.4) days. The average C-reactive protein level at the time of diagnosis of OVF was 11.5 (range, 0.5-29.7, SD, 12.7) mg/L. Medical history included rheumatoid arthritis (n = 1), diabetes mellitus (n = 1), malignant tumor (stage IV) (n = 1), and brain infarction (n = 2). The primary sources of infection were pneumonia (n = 3), and urinary tract infection (n = 1), and all patients experienced bacillemia at/after the diagnosis of fracture. All patients died due to septic shock. CONCLUSION: The spontaneous incidence rate of vertebral body infection among OVF patients was 0.7%; however, the occurrence of this complication led to serious events. Clinicians should pay attention to the possibility of bacillemia in elderly or immunocompromised OVF patients. LEVEL OF EVIDENCE: 4.
31899346 Possible involvement of elastase in enhanced osteoclast differentiation by neutrophils thr 2020 Mar Neutrophils are one of the most abundant leukocytes in the sites of lesion of inflammatory diseases such as periodontitis and rheumatoid arthritis. These diseases are accompanied by bone loss, which worsens the quality of life of the patients. However, the role of neutrophils in the inflammatory bone loss has not been fully investigated. In the present study, we found that human neutrophils enhanced osteoclast differentiation from mouse bone marrow cells co-cultured with mouse osteoblasts in the presence of active vitamin D(3). The enhanced osteoclast differentiation was significantly suppressed by elastatinal, a synthetic inhibitor of neutrophil elastase. Also, we found that human neutrophils degraded human recombinant osteoprotegerin (OPG), a decoy receptor for nuclear factor κB (RANK) ligand (RANKL), the essential osteoclast differentiation-inducing factor, expressed by osteoblasts. Degradation of OPG by neutrophils was suppressed by human α(1)-protease inhibitor, the major endogenous inhibitor of neutrophil elastase. Recombinant human neutrophil elastase degraded human OPG in its death domain-like region. These results indicated that the degradation of OPG by elastase contributed at least in part to the enhanced osteoclast differentiation by neutrophils. There is a possibility that neutrophils play an important role in inflammatory bone loss.
31870154 Modeling Tryptophan/Indoleamine 2,3-Dioxygenase with Heme Superoxide Mimics: Is Ferryl the 2020 Jan 29 Tryptophan oxidation in biology has been recently implicated in a vast array of paramount pathogenic conditions in humans, including multiple sclerosis, rheumatoid arthritis, type-I diabetes, and cancer. This 2,3-dioxygenative cleavage of the indole ring of tryptophan with dioxygen is mediated by two heme enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), during its conversion to N-formylkynurenine in the first and rate-limiting step of kynurenine pathway. Despite the pivotal significance of this enzymatic transformation, a vivid viewpoint of the precise mechanistic events is far from complete. A heme superoxide adduct is thought to be the active oxidant in both TDO and IDO, which, following O-O bond cleavage, presumably generates a key ferryl (Fe(IV)=O) reaction intermediate. This study, for the first time in model chemistry, demonstrates the potential of synthetic heme superoxide adducts to mimic the bioinorganic chemistry of indole dioxygenation by TDO and IDO, challenging the widely accepted categorization of these metal adducts as weak oxidants. Herein, an electronically divergent series of ferric heme superoxo oxidants mediates the facile conversion of an array of indole substrates into their corresponding 2,3-dioxygenated products, while shedding light on an unequivocally occurring, putative ferryl intermediate. The oxygenated indole products have been isolated in ∼31% yield, and characterized by LC-MS, (1)H and (13)C NMR, and FT-IR methodologies, as well as by (18)O(2(g)) labeling experiments. Distinctly, the most electron-deficient superoxo adduct is observed to react the fastest, specifically with the most electron-rich indole substrate, underscoring the cruciality of electrophilicity of the heme superoxide moiety in facilitating the initial indole activation step. Comprehensive understanding of such mechanistic subtleties will benefit future attempts in the rational design of salient therapeutic agents, including next generation anticancer drug targets with amplified effectivity.
31868961 Poor diet predicts periodontal disease development in 11-year follow-up study. 2020 Apr OBJECTIVE: To study whether diets based on the Nordic food culture and dietary recommendations are related to periodontal disease development. METHODS: The data were based on the Health 2000 and 2011 Surveys (BRIF8901). The participants were aged 30-49 in 2000, periodontally healthy, without diabetes or rheumatoid arthritis. Analyses were made in the total study population (n = 240) and among nonsmokers (n = 193) in 2011. Periodontal condition was determined in a clinical examination, and the number of teeth with deepened (≥4 mm) periodontal pockets in 2011 was used as an outcome. The diet was measured using a validated food frequency questionnaire and the quality of the diet using the Baltic Sea Diet Score (BSDS) and the Recommended Finnish Diet Score (RFDS) in 2000. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using Poisson regression models. RESULTS: Low scores (indicating poor diet) in both the BSDS and the RFDS were associated with the development of deepened periodontal pockets. Among nonsmokers, the associations between low dietary scores and the number of teeth with deepened periodontal pockets were stronger than among the whole study population. CONCLUSIONS: Among middle-aged adults, poor-quality diet appears to be associated with the development of periodontal disease.
31751538 Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption b 2020 Jan Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects. However, its effects on osteoclast formation and function remain unknown. In the present study, we showed that catalpol inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, as well as the expression of osteoclast-related marker genes. The investigation of molecular mechanisms showed that catalpol upregulated phosphatase and tensin homolog (PTEN) activity by reducing its ubiquitination and degradation, subsequently suppressing RANKL-induced NF-κB and AKT signaling pathways, leading to an inhibition on NFATc1 induction. Furthermore, catalpol protected mice against inflammation- and ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo. These results suggest that catalpol might be developed as a promising candidate for treating osteoclast-related bone diseases.
30796524 Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of 2020 Mar BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.
33124565 Efficacy and safety of certolizumab pegol in pregnant women with uveitis. Recommendations 2021 Jan OBJECTIVES: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP. METHODS: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed. RESULTS: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications. CONCLUSIONS: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.