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ID PMID Title PublicationDate abstract
34393784 Pharmacological Properties, Therapeutic Potential and Molecular Mechanisms of JWH133, a CB 2021 The endocannabinoid system has attracted attention as a pharmacological target for several pathological conditions. Cannabinoid (CB2)-selective agonists have been the focus of pharmacological studies because modulation of the CB2 receptor (CB2R) can be useful in the treatment of pain, inflammation, arthritis, addiction, and cancer among other possible therapeutic applications while circumventing CNS-related adverse effects. Increasing number of evidences from different independent preclinical studies have suggested new perspectives on the involvement of CB2R signaling in inflammation, infection and immunity, thus play important role in cancer, cardiovascular, renal, hepatic and metabolic diseases. JWH133 is a synthetic agonist with high CB2R selectivity and showed to exert CB2R mediated antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, and immunomodulatory activities. Cumulative evidences suggest that JWH133 protects against hepatic injury, renal injury, cardiotoxicity, fibrosis, rheumatoid arthritis, and cancer as well as against oxidative damage and inflammation, inhibits fibrosis and apoptosis, and acts as an immunosuppressant. This review provides a comprehensive overview of the polypharmacological properties and therapeutic potential of JWH133. This review also presents molecular mechanism and signaling pathways of JWH133 under various pathological conditions except neurological diseases. Based on the available data, this review proposes the possibilities of developing JWH133 as a promising therapeutic agent; however, further safety and toxicity studies in preclinical studies and clinical trials in humans are warranted.
34341698 Premature Senescence of T-cells Favors Bone Loss During Osteolytic Diseases. A New Concern 2021 Aug Cellular senescence is a biological process triggered in response to time-accumulated DNA damage, which prioritizes cell survival over cell function. Particularly, senescent T lymphocytes can be generated prematurely during chronic inflammatory diseases regardless of chronological aging. These senescent T lymphocytes are characterized by the loss of CD28 expression, a co-stimulatory receptor that mediates antigen presentation and effective T-cell activation. An increased number of premature senescent CD4(+)CD28(-) T lymphocytes has been frequently observed in osteolytic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, osteopenia, osteoporosis, and osteomyelitis. Indeed, CD4(+)CD28(-) T lymphocytes produce higher levels of osteoclastogenic molecular mediators directly related to pathologic bone loss, such as tumor necrosis factor (TNF)-α, interleukin (IL)-17A, and receptor-activator of nuclear factor κB ligand (RANKL), as compared with regular CD4(+)CD28(+) T lymphocytes. In addition, premature senescent CD8(+)CD28(-) T lymphocytes have been negatively associated with bone healing and regeneration by inhibiting osteoblast differentiation and mesenchymal stromal cell survival. Therefore, accumulated evidence supports the role of senescent T lymphocytes in osteoimmunology. Moreover, premature senescence of T-cells seems to be associated with the functional imbalance between the osteolytic T-helper type-17 (Th17) and bone protective T regulatory (Treg) lymphocytes, as well as the phenotypic instability of Treg lymphocytes responsible for its trans-differentiation into RANKL-producing exFoxp3Th17 cells, a key cellular phenomenon directly related to bone loss. Herein, we present a framework for the understanding of the pathogenic characteristics of T lymphocytes with a premature senescent phenotype; and particularly, we revise and discuss their role in the osteoimmunology of osteolytic diseases.
34012432 Increased Concentrations of Circulating Soluble MHC Class I-Related Chain A (sMICA) and sM 2021 Systemic lupus erythematosus (SLE) is a severe autoimmune disease of unknown etiology. The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are stress-inducible cell surface molecules. MICA and MICB label malfunctioning cells for their recognition by cytotoxic lymphocytes such as natural killer (NK) cells. Alterations in this recognition have been found in SLE. MICA/MICB can be shed from the cell surface, subsequently acting either as a soluble decoy receptor (sMICA/sMICB) or in CD4(+) T-cell expansion. Conversely, NK cells are frequently defective in SLE and lower NK cell numbers have been reported in patients with active SLE. However, these cells are also thought to exert regulatory functions and to prevent autoimmunity. We therefore investigated whether, and how, plasma membrane and soluble MICA/B are modulated in SLE and whether they influence NK cell activity, in order to better understand how MICA/B may participate in disease development. We report significantly elevated concentrations of circulating sMICA/B in SLE patients compared with healthy individuals or a control patient group. In SLE patients, sMICA concentrations were significantly higher in patients positive for anti-SSB and anti-RNP autoantibodies. In order to study the mechanism and the potential source of sMICA, we analyzed circulating sMICA concentration in Behcet patients before and after interferon (IFN)-α therapy: no modulation was observed, suggesting that IFN-α is not intrinsically crucial for sMICA release in vivo. We also show that monocytes and neutrophils stimulated in vitro with cytokines or extracellular chromatin up-regulate plasma membrane MICA expression, without releasing sMICA. Importantly, in peripheral blood mononuclear cells from healthy individuals stimulated in vitro by cell-free chromatin, NK cells up-regulate CD69 and CD107 in a monocyte-dependent manner and at least partly via MICA-NKG2D interaction, whereas NK cells were exhausted in SLE patients. In conclusion, sMICA concentrations are elevated in SLE patients, whereas plasma membrane MICA is up-regulated in response to some lupus stimuli and triggers NK cell activation. Those results suggest the requirement for a tight control in vivo and highlight the complex role of the MICA/sMICA system in SLE.
33762234 R(x)IALTA: evaluating the effect of a pharmacist-led intervention on CV risk in patients w 2021 Mar 24 Patients with inflammatory conditions are at high risk for cardiovascular (CV) disease. Despite such elevated risk, their CV risk factors are suboptimally managed. OBJECTIVE: To evaluate the effect of a pharmacist-led intervention on CV risk in patients with inflammatory conditions. METHODS: DESIGN: Prospective pre-postintervention. SETTING: 17 community pharmacies across Alberta. POPULATION: Adults with inflammatory conditions (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, systemic lupus erythematosus, psoriasis vulgaris) who had at least one uncontrolled risk factor (A1C, blood pressure, LDL-cholesterol or current tobacco users). INTERVENTION: All patients enrolled in the study received: physical and laboratory assessment, individualised CV risk assessment and education regarding this risk, treatment recommendations, prescription adaptation and prescribing where necessary to meet treatment targets, regular communication with the patient's treating physician(s) and regular follow-up with all patients every month for 6 months. OUTCOMES: Primary: change in estimated CV risk (risk of a major CV event in the next 10 years) after 6 months. Secondary: change in individual risk factors (blood pressure, LDL-cholesterol, A1C and tobacco cessation) over a 6-month period. RESULTS: We enrolled 99 patients. The median age was 66.41 years (IQR 57.64-72.79), More than half of them (61%) were female and more than three-quarters (86%) were Caucasians. After adjusting for age, sex and ethnicity and centre effect, there was a reduction of 24.5% in CV risk (p<0.001); including a reduction of 0.3 mmol/L in LDL-c (p<0.001), 10.7 mm Hg in systolic blood pressure (p<0.001), 1.25% in A1C (p<0.001). There was a non-significant trend towards tobacco cessation. CONCLUSION: This is the first study on CV risk reduction in patients with inflammatory conditions in a community pharmacy setting. R(x)IALTA provides evidence for the benefit of pharmacist care on global cardiovascular risk reduction as well as the individual cardiovascular risk factors in patients with inflammatory conditions. TRIAL REGISTRATION NUMBER: NCT03152396.
33243033 Costs of medication use among patients with juvenile idiopathic arthritis in the Dutch hea 2021 Oct Background: This study aims to quantify medication costs in juvenile idiopathic arthritis (JIA), based on subtype.Research design and methods: This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients, aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, subtype) and medication use were extracted. Medication use and costs were reported as: 1) mean total annual costs; 2) between-patient heterogeneity in these costs; 3) duration of medication use; and, 4) costs over the treatment course.Results: The analysis included 691 patients. Mean total medication costs were €2,103/patient/year, including €1,930/patient/year (91.8%) spent on biologicals. Costs varied considerably between subtypes, with polyarticular rheumatoid-factor positive and systemic JIA patients having the highest mean costs (€5,020/patient/year and €4,790/patient/year, respectively). Mean annual medication costs over the patient's treatment course ranged from <€1,000/year (71.1% of patients) to >€11,000/year (2.5% of patients). Etanercept and adalimumab were the most commonly used biologicals. Cost fluctuations over the treatment course were primarily attributable to biological use.Conclusions: Polyarticular rheumatoid-factor positive and systemic JIA patients had the highest mean total annual medication costs, primarily attributable to biologicals. Costs varied considerably between subtypes, individuals, and over the treatment course.
34413853 The Transcriptomic Profile of Monocytes from Patients With Sjögren's Syndrome Is Associat 2021 Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of the exocrine glands and prominent B cell hyperactivity. Considering the key role of monocytes in promoting B cell hyperactivity, we performed RNA-sequencing analysis of CD14(+) monocytes from patients with pSS, non-Sjögren's sicca (nSS), and healthy controls (HC). We demonstrated that the transcriptomic profile of pSS patients is enriched in intermediate and non-classical monocyte profiles, and confirmed the increased frequency of non-classical monocytes in pSS patients by flow-cytometry analysis. Weighted gene co-expression network analysis identified four molecular signatures in monocytes from pSS patients, functionally annotated for processes related with translation, IFN-signaling, and toll-like receptor signaling. Systemic and local inflammatory features significantly correlated with the expression of these signatures. Furthermore, genes highly associated with clinical features in pSS were identified as hub-genes for each signature. Unsupervised hierarchical cluster analysis of the hub-genes identified four clusters of nSS and pSS patients, each with distinct inflammatory and transcriptomic profiles. One cluster showed a significantly higher percentage of pSS patients with higher prevalence of anti-SSA autoantibodies, interferon-score, and erythrocyte sedimentation rate compared to the other clusters. Finally, we showed that the identified transcriptomic differences in pSS monocytes were induced in monocytes of healthy controls by exposure to serum of pSS patients. Representative hub-genes of all four signatures were partially inhibited by interferon-α/β receptor blockade, indicating that the circulating inflammatory mediators, including type I interferons have a significant contribution to the altered transcriptional profile of pSS-monocytes. Our study suggests that targeting key circulating inflammatory mediators, such as type I interferons, could offer new insights into the important pathways and mechanisms driving pSS, and holds promise for halting immunopathology in Sjögren's Syndrome.
34385474 Psoriatic arthritis. 2021 Aug 12 Psoriatic arthritis (PsA) is a complex inflammatory disease with heterogeneous clinical features, which complicates psoriasis in 30% of patients. There are no diagnostic criteria or tests available. Diagnosis is most commonly made by identifying inflammatory musculoskeletal features in joints, entheses or the spine in the presence of skin and/or nail psoriasis and in the usual absence of rheumatoid factor and anti-cyclic citrullinated peptide. The evolution of psoriasis to PsA may occur in stages, although the mechanisms are unclear. In many patients, there may be little or no relationship between severity of musculoskeletal inflammation and severity of skin or nail psoriasis. The reason for this disease heterogeneity may be explained by differences in genotype, especially in the HLA region. New targeted therapies for PsA have been approved with additional therapies in development. These developments have substantially improved both short-term and long-term outcomes including a reduction in musculoskeletal and skin manifestations and in radiographic damage. With efforts underway aimed at improving our understanding of the molecular basis for the heterogeneity of PsA, a personalized approach to treating PsA may become possible.
32857280 Early-onset subclinical cardiovascular damage assessed by non-invasive methods in children 2021 Feb Chronic inflammation starting early in life and continuing into adulthood may predispose children with Juvenile Idiopathic Arthritis (JIA) to cardiovascular (CV) complications. To compare non-invasive CV risk markers- left ventricular mass index (LVMi), brachial artery flow mediated dilatation (FMD) and carotid artery intima-media thickness (CIMT) between patients with JIA and healthy controls. Measurements of LVMi, CIMT and FMD and lipid profile were compared between 4 and 18 year old 81 patients with JIA and 78 age and sex matched healthy controls. Among 81, 20 had systemic onset, 19 enthesitis related arthritis, 9 polyarticular rheumatoid factor (RF) + ve, 19 polyarticular RF -ve, 11 oligo-articular, and 3 un-differentiated JIA. FMD was significantly lower (p < 0.001), CIMT and LVMi significantly higher in patients (p ≤  0.001). CIMT showed positive correlation with blood pressure (p = 0.001), disease duration (p  ≤  0.001) and negative correlation with high density lipoprotein (HDL) (p ≤  0.001). FMD correlated positively with HDL (p = 0.006) and negatively with disease duration (p ≤  0.001). CIMT (p = 0.017) and FMD (p = 0.04) were significantly worse in active than inactive disease. Children with JIA have worse lipid profile, increased LVMi, CIMT, and reduced brachial artery FMD, suggestive of early cardiovascular dysfunction.
34224660 Magnetic Resonance Imaging-Assessed Subchondral Cysts and Incident Knee Pain and Knee Oste 2022 Jan OBJECTIVE: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. METHODS: We used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes. RESULTS: Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit. CONCLUSION: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease.
33919084 Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An 2021 Apr 21 The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract's ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.
34769250 Autoimmune Epithelitis and Chronic Inflammation in Sjögren's Syndrome-Related Dry Eye Dis 2021 Oct 30 Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren's syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.
33883324 SELL and IFI44 as potential biomarkers of Sjögren's syndrome and their correlation with i 2021 Jul 14 The onset of Sjögren's syndrome (SS) is hidden, early diagnosis is difficult, and the disorder seriously endangers the physical and mental health of affected people. This study aims to identify potential biomarkers of SS and to investigate the characteristics of immune cell infiltration. We used four SS gene expression profile data series from the Gene Expression Omnibus database, and applied bioinformatics analysis and machine learning algorithms to screen two biomarkers, SELL (L-selectin) and IFI44 (interferon-induced protein 44), from 101 differentially expressed genes. The two-gene model comprising SELL and IFI44 showed good diagnostic ability for SS in the training set (AUC = 0.992) and verification set (AUC = 0.917). Analysis of infiltrating immune cells in SS identified naive B cells, resting CD4 memory T cells, activated CD4 memory T cells, gamma delta T cells, M0 macrophages, M1 macrophages, plasma cells, CD8 T cells, activated NK cells and monocytes as candidate participants in the SS process. Furthermore, SELL was associated with M2 macrophages, activated CD4 memory T cells, gamma delta T cells, resting NK cells and plasma cells, while IFI44 was associated with activated mast cells, resting NK cells, resting mast cells and CD8 T cells. This study demonstrates that SELL and IFI44 can serve as good diagnostic markers for SS and may also be new diagnostic and therapeutic targets for SS.
33168359 The amino acid variants in HLA II molecules explain the major association with adult-onset 2021 Jan Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10(-14)) and Asn in HLA-DRβ1 position 37 (p = 5.12 × 10(-11)) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10(-14)), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10(-13)), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10(-9)). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.
34149728 Type I Interferon Dependent hsa-miR-145-5p Downregulation Modulates MUC1 and TLR4 Overexpr 2021 Sjögren's syndrome (SS) is an autoimmune disease that mainly affects salivary glands (SG) and is characterized by overactivation of the type I interferon (IFN) pathway. Type I IFNs can decrease the levels of hsa-miR-145-5p, a miRNA with anti-inflammatory roles that is downregulated in SG from SS-patients. Two relevant targets of hsa-miR-145-5p, mucin 1 (MUC1) and toll-like receptor 4 (TLR4) are overexpressed in SS-patients and contribute to SG inflammation and dysfunction. This study aimed to evaluate if hsa-miR-145-5p modulates MUC1 and TLR4 overexpression in SG from SS-patients in a type I IFN dependent manner. Labial SG (LSG) biopsies from 9 SS-patients and 6 controls were analyzed. We determined hsa-miR-145-5p levels by TaqMan assays and the mRNA levels of MUC1, TLR4, IFN-α, IFN-β, and IFN-stimulated genes (MX1, IFIT1, IFI44, and IFI44L) by real time-PCR. We also performed in vitro assays using type I IFNs and chemically synthesized hsa-miR-145-5p mimics and inhibitors. We validated the decreased hsa-miR-145-5p levels in LSG from SS-patients, which inversely correlated with the type I IFN score, mRNA levels of IFN-β, MUC1, TLR4, and clinical parameters of SS-patients (Ro/La autoantibodies and focus score). IFN-α or IFN-β stimulation downregulated hsa-miR-145-5p and increased MUC1 and TLR4 mRNA levels. Hsa-miR-145-5p overexpression decreased MUC1 and TLR4 mRNA levels, while transfection with a hsa-miR-145-5p inhibitor increased mRNA levels. Our findings show that type I IFNs decrease hsa-miR-145-5p expression leading to upregulation of MUC1 and TLR4. Together, this suggests that type I interferon-dependent hsa-miR-145-5p downregulation contributes to the perpetuation of inflammation in LSG from SS-patients.
35281989 Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogene 2021 Aging is characterized, amongst other features, by a complex process of cellular senescence involving both innate and adaptive immunity, called immunosenescence and associated to inflammaging, a low-grade chronic inflammation. Both processes fuel each other and partially explain increasing incidence of cancers, infections, age-related autoimmunity, and vascular disease as well as a reduced response to vaccination. Multiple sclerosis (MS) is a lifelong disease, for which considerable progress in disease-modifying therapies (DMTs) and management has improved long-term survival. However, disability progression, increasing with age and disease duration, remains. Neurologists are now involved in caring for elderly MS patients, with increasing comorbidities. Aging of the immune system therefore has relevant implications for MS pathogenesis, response to DMTs and the risks mediated by these treatments. We propose to review current evidence regarding markers and molecular mechanisms of immunosenescence and their relevance to understanding MS pathogenesis. We will focus on age-related changes in the innate and adaptive immune system in MS and other auto-immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. The consequences of these immune changes on MS pathology, in interaction with the intrinsic aging process of central nervous system resident cells will be discussed. Finally, the impact of immunosenescence on disease evolution and on the safety and efficacy of current DMTs will be presented.
35227350 Access to chloroquine in patients with rheumatic and musculoskeletal diseases attending rh 2021 Jun 8 Herbal medicines made from the bark of the Cinchona tree, and later quinine, have been widely used for centuries to treat medical conditions such as tropical malaria. More recently, chloroquine (CQ) and its synthetic derivatives have been used as antimalarials and to treat systemic lupus erythematosus, rheumatoid arthritis, and in the past 14 months or so, COVID-19 pneumonia. Anecdotal evidence and the erratic covering through social media of its potential efficacy in the treatment of COVID-19 pneumonia have resulted in the widespread off-label use of CQ in South Africa and worldwide. This study aimed to show that access to CQ as a chronic medication for rheumatic and musculoskeletal diseases was limited during the COVID-19 pandemic, and that this resulted in an increased incidence of flares in these patients, affecting their morbidity and potentially leading to mortality.
34703373 Autoinjector - A smart device for emergency cum personal therapy. 2021 Oct Autoinjectors are self-injectable devices; they are important class of medical devices which can deliver drugs through subcutaneous or intramuscular route. They enclose prefilled syringes or cartridges which are driven by a spring system. The major benefits of this device are easy self-administration, improved patient compliance, reduced anxiety, and dosage accuracy. Immediate treatment during emergency conditions such as anaphylaxis, migraine, and status epilepticus or for chronic conditions like psoriasis, diabetes, multiple sclerosis, and rheumatoid arthritis, Reformulation of first-generation biologics, technical advancements, innovative designs, patient compliance, overwhelming interest for self-administration all these made entry of more and more autoinjectors into use. In this review, intensive efforts have been made for exploring the different types of currently available autoinjectors for the management of emergency and chronic diseases.
34495537 Glycosylation in Autoimmune Diseases. 2021 Autoimmune diseases are accompanied by changes in protein glycosylation, in both the immune system and target tissues. The best-studied alteration in autoimmunity is agalactosylation of immunoglobulin G (IgG), characterized primarily in rheumatoid arthritis (RA), and then detected also in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and multiple sclerosis (MS). The rebuilding of IgG N-glycans in RA correlates with the relapses and remissions of the disease, is associated with physiological states such as pregnancy but also depends on applied anti-inflammatory therapy. In turn, a decreased core fucosylation of the whole pool of IgG N-glycans is a serum glycomarker in autoimmune thyroid diseases (AITD) encompassing Hashimoto's thyroiditis (HT) and Grave's disease (GD). However, fucosylation of anti-thyroglobulin IgG (an immunological marker of HT) was elevated in HT serum. Core fucosylation of IgG oligosaccharides was also lowered in MS and SLE. In AITD and IBD, chronic inflammation T lymphocytes showed the reduced expression of MGAT5 gene encoding β1,6-N-acetylglucosaminyltransferase V (GnT-V) responsible for β1,6-branching of N-glycans, which is important for T cell receptor activation. Structural changes of glycans have a profound effect on the pro-inflammatory activity of immune cells and serum immune proteins, including IgG in autoimmunity.
34401281 Cavitated pulmonary nodules in a female patient with breast cancer: Keep in mind Serratia 2021 Serratia species are gram-negative bacteria, which could be isolated from soil, water, plants, animals and air. They are responsible for a heterogeneous spectrum of diseases, affecting the central nervous system, the urinary tract, the respiratory tract and the bloodstream. Pulmonary involvement is rare and typically occurs in immunocompromised patients; radiological appearances include haemorrhagic bronchopneumonia, even with the development of pulmonary abscesses and cavitated parenchymal lesions, or diffuse alveolar damage. Concerning pulmonary cavities, the differential diagnosis should include metastatic lung nodules, rheumatoid arthritis, Langerhans cell histiocytosis, mycotic infections and septic emboli. The knowledge of these radiological features, in association with clinical history and laboratory findings, is mandatory to make the correct diagnosis, suggesting the right treatment and the adequate follow-up. We described a challenging case of a Serratia marcescens' pulmonary infection, which occurred in a patient with breast cancer: clinical features and main imaging findings have been discussed - in order to help clinicians and radiologists in the management of the disease.
34393789 Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for 2021 The onset of the 2019 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated the identification of approved drugs to treat the disease, before the development, approval and widespread administration of suitable vaccines. To identify such a drug, we used a visual analytics workflow where computational tools applied over an AI-enhanced biomedical knowledge graph were combined with human expertise. The workflow comprised rapid augmentation of knowledge graph information from recent literature using machine learning (ML) based extraction, with human-guided iterative queries of the graph. Using this workflow, we identified the rheumatoid arthritis drug baricitinib as both an antiviral and anti-inflammatory therapy. The effectiveness of baricitinib was substantiated by the recent publication of the data from the ACTT-2 randomised Phase 3 trial, followed by emergency approval for use by the FDA, and a report from the CoV-BARRIER trial confirming significant reductions in mortality with baricitinib compared to standard of care. Such methods that iteratively combine computational tools with human expertise hold promise for the identification of treatments for rare and neglected diseases and, beyond drug repurposing, in areas of biological research where relevant data may be lacking or hidden in the mass of available biomedical literature.