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ID PMID Title PublicationDate abstract
35115945 Anti-Inflammatory and Pro-Autophagy Effects of the Cannabinoid Receptor CB2R: Possibility 2021 Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from loss of insulin-secreting β-cells in islets of Langerhans. The loss of β-cells is initiated when self-tolerance to β-cell-derived contents breaks down, which leads to T cell-mediated β-cell damage and, ultimately, β-cell apoptosis. Many investigations have demonstrated the positive effects of antagonizing cannabinoid receptor 1 (CB1R) in metabolic diseases such as fatty liver disease, obesity, and diabetes mellitus, but the role of cannabinoid receptor 2 (CB2R) in such diseases is relatively unknown. Activation of CB2R is known for its immunosuppressive roles in multiple sclerosis, rheumatoid arthritis, Crohn's, celiac, and lupus diseases, and since autoimmune diseases can share common environmental and genetic factors, we propose CB2R specific agonists may also serve as disease modifiers in diabetes mellitus. The CNR2 gene, which encodes CB2R protein, is the result of a gene duplication of CNR1, which encodes CB1R protein. This ortholog evolved rapidly after transitioning from invertebrates to vertebrate hundreds of million years ago. Human specific CNR2 isoforms are induced by inflammation in pancreatic islets, and a CNR2 nonsynonymous SNP (Q63R) is associated with autoimmune diseases. We collected evidence from the literature and from our own studies demonstrating that CB2R is involved in regulating the inflammasome and especially release of the cytokine interleukin 1B (IL-1β). Furthermore, CB2R activation controls intracellular autophagy and may regulate secretion of extracellular vesicles from adipocytes that participate in recycling of lipid droplets, dysregulation of which induces chronic inflammation and obesity. CB2R activation may play a similar role in islets of Langerhans. Here, we will discuss future strategies to unravel what roles, if any, CB2R modifiers potentially play in T1DM.
35095508 Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of C 2021 Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.
34936242 LncRNA GAS5 positively regulates IL-10 expression in patients with generalized myasthenia 2022 Jan INTRODUCTION: LncRNA growth arrest-specific transcript 5 (GAS5) has been proven to be involved in autoimmune diseases. Rheumatoid arthritis is a type of autoimmune disease that may affect myasthenia gravis (MG) patients. However, its direct role in MG is unknown. METHODS: Our study included 62 generalized MG patients. GAS5 expression was analyzed with real-time quantitative RT-PCR (qRT-PCR). The interaction between GAS5 and interleukin 10 (IL-10) was explored in overexpressed cells using real time quantitative polymerase chain reactions (RT-qPCRs) and western blot. The correlation of GAS5 and IL-10 was analyzed using Pearson's correlation analysis. The diagnostic value of GAS5 for MG was analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS: GAS5 and IL-10 mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in MG patients than healthy controls. Downregulated GAS5 effectively distinguished MG patients from healthy controls. GAS5 expression was positively correlated with IL-10 expression in both MG patients and healthy controls. GAS5 overexpression significantly upregulated IL-10 expression in PBMCs derived from both MG patients and healthy controls. CONCLUSION: LncRNA GAS5 may improve generalized MG by positively regulating IL-10 expression.
34867335 Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbili 2021 Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.
34792872 [RESEARCH OF SCIENTIFIC INTEREST TO THE CHLOROQUINE USE IN CLINICAL MEDICINE IN THE BASIS 2021 Aug Interest in chloroquine, and its analog with a more favorable safety profile - hydroxychloroquine, in 2020 is certainly associated with the outbreak of a new coronavirus infection, SARS-CoV-2. The high pathogenicity and lack of specific immunity in the population caused the rapid spread of infection with an extraordinary increase in the burden on the health systems of many countries. In such conditions, it was necessary to quickly find and implement effective methods of treatment and prevention. One of the most promising candidates for this role was hydroxychloroquine, as a multi-purpose drug with a well-studied safety profile and a rich history of use. The article describes some historical stages of the study of chloroquine and its derivatives starting from the 19th century and ending in 2020. The experience of its use for the treatment of diseases such as malaria, rheumatoid arthritis, diabetes, bronchial asthma, photosensitivity and skin porphyria was reviewed. Separately, some historical aspects of its use for the treatment of viral and oncological diseases were considered. The bibliometric method used in this scientific work clearly demonstrates the dynamics of the changing interest of the scientific community in chloroquine and its derivatives. Chloroquine and its derivatives can definitely be attributed to «pharmaceutical centenarians» with an intense life that continues.
34791103 Positioning filgotinib in the treatment algorithm of moderate to severe ulcerative colitis 2021 Nov 16 BACKGROUND AND AIMS: Filgotinib is a small molecule that selectively inhibits Janus kinase (JAK) type 1. It is already approved for the treatment of rheumatoid arthritis and is being evaluated for the management of patients with moderate to severe ulcerative colitis (UC). The purpose of this review is to provide an overview of the currently available data on filgotinib and to define how to position this new drug in the treatment algorithm of patients with ulcerative colitis. METHODS: Pubmed, Embase, and Scopus databases were searched up to June 25, 2021 in order to identify studies reporting efficacy and safety data of filgotinib in patients with UC. RESULTS: Data from a phase III study enrolling UC patients with moderate to severe disease show that filgotinib is effective with a reassuring safety profile. Filgotinib treatment is not associated with a greater risk of thrombosis and herpes zoster infections compared to other JAK inhibitors. However, animal studies reported impaired spermatogenesis and histopathological effects on male reproductive organs, making it necessary to deepen this aspect in dedicated human studies. CONCLUSIONS: Filgotinib is an effective and safe drug for treatment of both biologic-naive and biologic experienced patients with moderate to severe UC and may soon be available.
34725722 Complications of occipitocervical fixation: retrospective review of 128 patients with 5-ye 2022 Feb PURPOSE: Occipitocervical fusion is necessary for many pathologies of the craniocervical junction. The anatomy of the region is unique, and fusion can cause significant morbidity. This retrospective review aims to investigate the complication rates and outcomes of occipitocervical fixation. MATERIAL AND METHODS: This is a retrospective review of 128 patients with occipitocervical fixation operated between 1994 and 2020. The average follow-up is 63 months. RESULTS: The indications of occipitocervical fixation were basilar invagination (53 patients; 41.4%), trauma (25 patients; 19.5%), tumor (23 patients; 18%), instability due to rheumatoid arthritis (13 patients; 10.2%), cervical deformity (7 patients; 5.5%) and os odontoideum (7 patients; 5.5%). There were six early postoperative (1st month) deaths. We observed complications in 67 patients (52%). Most common complication was implant-related (32%), followed by wound problems (23.4%), systemic and other complications (11.7%), neurologic complications (6.2%). Implants are removed in 31 patients (24%) for different reasons: deep wound infection (7), local pain and restriction of head movements (21), respiratory distress and swallowing problems (2), screw fracture and local pain (1). CONCLUSIONS: Occipitocervical fixation has quite large number of complications and significantly restricts head movements. With the advent of our biomechanical concepts, indications should be limited, and shorter cervical fixations should be preferred. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
34689554 Rational Synthesis of Imine-Linked Fluorescent Covalent Organic Frameworks with Different 2021 Nov 3 Precise modulation of pH in living cells plays a vital role in the study of many diseases, such as cancer and rheumatoid arthritis. Here, a series of imine-linked covalent organic frameworks (COFs) were rationally designed and developed for pH sensing in tumor cells and zebrafish. Four monomers were chosen to synthesize COFs (COF(1)-COF(4)) with different pK(a) by a simple orthogonal combination through condensation reaction. The as-obtained COFs exhibited a sensitive pH-dependent fluorescence response compared to their building blocks. Among them, COF(2) possessed a high crystallinity, excellent fluorescence, and suitable pK(a) for biosensing. For bioimaging applications, COF(2) was modified with poly-d-lysine (PDL) to improve its biocompatibility and endocytosis efficiency. After that, PDL-modified COF(2) (PDL@COF(2)) was used as a novel fluorescence probe with a superior linear pH response over the range from 5.0 to 8.0 due to its fully reversible protonation and deprotonation. The fluorescent PDL@COF(2) was further employed as a good candidate for pH imaging in tumor cells and zebrafish. The as-constructed environment-sensitive fluorescent COFs have greatly expanded the applications of COFs in the biological area.
34616297 Nanostructured Lipid Carrier-Mediated Transdermal Delivery of Aceclofenac Hydrogel Present 2021 Aceclofenac (ACE), a cyclooxygenase-2 inhibitor, is the derivative of the diclofenac group that has been in use for the symptomatic treatment of systemic inflammatory autoimmune disease, rheumatoid arthritis (RA). Partial solubility, high lipophilic nature, and stability challenge its use in developing topical formulations. Hence, we developed and characterized nanostructured lipid carrier (NLC)-based ACE (ACE-NLC) hydrogel for an efficient transdermal delivery. NLC microemulsion was prepared using different lipids by various methods and was characterized with respect to particle size, zeta potential, surface morphology, and drug encapsulation efficiency. The optimized NLC formulation was incorporated into Carbopol(®) 940 gel, and this arrangement was characterized and compared with the existing marketed gel (Mkt-gel) formulation to assess in vitro drug release, rheology, texture profile, in vivo skin retention and permeation, and stability. Furthermore, prepared and characterized ACE-loaded NLC formulation was evaluated for skin integrity and fitted in a dermatokinetic model. The results of this study confirmed the spherical shape; smooth morphology and nanometric size attested by Zetasizer and scanning and transmission electron microcopy; and stability of the ACE-NLC formulation. The ACE-NLC-gel formulation showed good rheological and texture characteristics, and better skin distribution in the epidermis and dermis. Moreover, ACE-NLC permeated deeper in the skin layers and kept the skin integrity intact. Overall, NLC-based gel formulation of ACE might be a promising nanoscale lipid carrier for topical application when compared with the conventional Mkt-gel formulation.
34601486 Group B Streptococcus Meningitis Associated with Acute Otitis Media in an Adult Patient. 2021 Oct 3 BACKGROUND We present a case of Group B Streptococcus (Streptococcus agalactiae or GBS) meningitis in a non-pregnant woman that likely originated from acute otitis media. Although invasive Group B Streptococcal infections are increasing in the United States, GBS meningitis is still rare in non-pregnant adults. At the end, we discuss risk factors for this disease and data that suggest that invasive GBS infection is increasing in the adult and elderly populations of the United States. CASE REPORT Our patient was a 55-year-old woman with a history of juvenile rheumatoid arthritis who presented with altered mental status after failure of outpatient treatment of otitis media with oral doxycycline and steroids. Upon admission, she was initially afebrile and hemodynamically stable, but she had a rapid decline and required emergent intubation. Blood cultures grew GBS. CSF PCR analysis performed by BioFire® FilmArray® Meningitis/Encephalitis Panel revealed GBS. Middle-ear fluid and CSF cultures drawn after 1 day of antibiotic therapy did not grow any organisms. Treatment was achieved with high-dose intravenous ceftriaxone for 14 days, and tympanoplasty. At the end of 14 days of antibiotic therapy, the patient had full neurological recovery, without any residual neurological deficits. CONCLUSIONS GBS meningitis is classically associated with neonatal disease, but invasive GBS infection is fairly common in adults and appears to be increasing in incidence secondary to increasing populations living with diabetes, immunosuppressed conditions, and advanced age. Central nervous system infection with this organism is still rare. In this case report we describe a non-pregnant woman who presented with GBS meningitis.
34562225 Low Urine Secretion of Semaphorin3A in Lupus Patients with Proteinuria. 2022 Apr Immune semaphorins are important in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to correlate with SLE disease activity. The aim was to assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Urine levels of sema3A were analyzed in 38 SLE patients, 13 with renal involvement, and were compared to 10 healthy volunteers and 8 RA patients (disease control group). The excretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy volunteers and RA patients (4.9 ± 3.9 ng/ml, 8.5 ± 2.7 ng/ml, 9.85 ± 1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0 ± 3.4 ng/ml vs. 6.5 ± 3.8 ng/ml, p = 0.03). Urine sema3A inversely correlated with proteinuria and SLE disease activity. Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.
34515214 Use of Systemic Corticosteroids for Reasons Other than Asthma in Subjects with Asthma. 2022 BACKGROUNDS: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. OBJECTIVES: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. METHOD: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. RESULTS: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. CONCLUSIONS: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.
34440354 Host Genetics and Gut Microbiome: Perspectives for Multiple Sclerosis. 2021 Jul 29 As a complex disease, Multiple Sclerosis (MS)'s etiology is determined by both genetic and environmental factors. In the last decade, the gut microbiome has emerged as an important environmental factor, but its interaction with host genetics is still unknown. In this review, we focus on these dual aspects of MS pathogenesis: we describe the current knowledge on genetic factors related to MS, based on genome-wide association studies, and then illustrate the interactions between the immune system, gut microbiome and central nervous system in MS, summarizing the evidence available from Experimental Autoimmune Encephalomyelitis mouse models and studies in patients. Finally, as the understanding of influence of host genetics on the gut microbiome composition in MS is in its infancy, we explore this issue based on the evidence currently available from other autoimmune diseases that share with MS the interplay of genetic with environmental factors (Inflammatory Bowel Disease, Rheumatoid Arthritis and Systemic Lupus Erythematosus), and discuss avenues for future research.
34227446 Periodontal and dental health in inflammatory bowel diseases: a systematic review. 2021 Jul 19 Introduction: An increased risk of dental caries and periodontal diseases has been reported for inflammatory bowel disease (IBD) patients and are challenging conditions to manage.Areas covered: The authors searched international databases to find all studies assessing dental/periodontal outcomes in patients with IBD and other immune-mediated inflammatory disease (IMID), as well as the association between IMID medications and dental/periodontal status.Expert opinion: IBD are associated with a higher risk of both periodontitis and caries. Some evidence from rheumatoid arthritis suggests that periodontitis may be associated with a lower response to anti-TNF. There is no reliable evidence that IBD patients may be at greater risk of complications during routine dental care. On the basis of current data, guidelines can be proposed for the dental management focusing on the detection and eradication of infectious foci prior to the implementation of immunosuppressants/biologics and modified dental treatment protocol for invasive dental procedures that includes antibiotic prophylaxis.
34121894 Relationship between high CRP and cytokines in Saudi old people with dental caries in alkh 2021 Jun OBJECTIVE: Dental caries is one of the most common problems of the oral cavity which is frequently observed in older people. The aim of this study is to evaluate serum C-reactive proteins (CRP) levels and to identify the correlation between dental caries and CRP levels. METHODOLOGY: The study included 12 aged patients with an average age of 65-years; the patients were diagnosed with dental caries and did not have clinical history of heart diseases, rheumatoid arthritis or any other infection. The control group consisted of 10 healthy donors with an average age of 60-years. The CRP level of positive samples was measured by using CRP Enzyme-linked immunosorbent assay-ELISA Kit. RESULTS: The currents study showed that only 5 out of 12 patients were CRP positive. CONCLUSIONS: Because of study limitations, it is early to conclude of close relationship between serum CRP and dental caries from the findings of this study; however, this study will give a clearer picture to understand the relationship between serum CRP, inflammatory cytokines and dental caries.
34092180 Safety and tolerability of nabiximols oromucosal spray: a review of more than 15 years" ac 2021 Jul Introduction: Nabiximols, a cannabinoid-based oromucosal spray, is indicated as add-on therapy for symptomatic relief of spasticity in persons with multiple sclerosis (MS). This review compiles tolerability and safety data from clinical trials that investigated nabiximols for spasticity and/or chronic pain.Areas covered: Systematic searches identified 38 placebo-controlled randomized controlled trials (RCTs) or post-RCT open-label studies reporting safety data: 15 in spasticity; 16 in neuropathic pain; six in chronic cancer pain; and one in rheumatoid arthritis pain. In RCTs, discontinuation rates due to adverse events (AEs) for nabiximols and placebo were lower in spasticity studies (5.4% and 2.8%) than in neuropathic pain (12.9% and 5.3%) or cancer pain (19.5% and 16.6%) studies. The most consistently identified AEs were dizziness, nausea and fatigue in spasticity or neuropathic pain studies; and dizziness, nausea, vomiting and somnolence in cancer pain studies. Serious AE (SAE) rates for nabiximols and placebo were higher in cancer pain (21.8% and 16.9%) than in MS spasticity (4.7% vs. 0.8%) and neuropathic pain (4.1% vs. 3.1%) studies despite similar dose ranges. Treatment-related SAEs showed no particular pattern.Expert opinion: More than 15 years of investigation of nabiximols oromucosal spray in spasticity and chronic pain conditions indicates an acceptable overall safety profile.
34027788 Long-term experience with rituximab therapy for treatment-resistant moderate-to-severe pem 2021 Jun 8 BACKGROUND: Rituximab appears to be effective for treating pemphigus, although there are limited long-term data. METHODS: This retrospective single-center study evaluated patients with conventional treatment-resistant pemphigus who received rituximab during September 2010-December 2019. The first rituximab cycle was based on the rheumatoid arthritis protocol in all patients except one patient, and additional single doses (500 mg or 1000 mg) were administered after clinical and/or serological relapse. The consensus definitions were used for complete remission off therapy, complete remission on minimal therapy, and clinical relapse. Serological relapse was defined as a progressive ≥2-fold increase in anti-desmoglein titers (vs. previous the measurement). RESULTS: The study included 52 patients with pemphigus vulgaris and 1 patient with pemphigus foliaceus. The mean number of infusions was 5 and the average follow-up after the first infusion was 56 months. The average time to clinical and/or serological relapse was 12 months. Complete remission was achieved in 84.9% of patients, including after the first rituximab cycle in 25 patients (47.1%). Two patients died during the follow-up period. CONCLUSION: Additional rituximab cycles may help achieve and prolong remission in patients with moderate-to-severe pemphigus resistant to conventional therapies. However, prospective trials are needed to identify the optimal dosing protocol.
33797765 Potential application of immunotherapy for modulation of pulp inflammation: opportunities 2021 Aug Caries results in the demineralization and destruction of enamel and dentine, and as the disease progresses, irreversible pulpitis can occur. Vital pulp therapy (VPT) is directed towards pulp preservation and the prevention of the progression of inflammation. The outcomes of VPT are not always predictable, and there is often a poor correlation between clinical signs and symptoms, and the events occurring at a molecular level. The inflamed pulp expresses increased levels of cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23, which recruit and drive a complex cellular immune response. Chronic inflammation and sustained cytokine release can result in irreversible pulp damage and a decreased capacity for tissue healing. Other chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis, are also characterized by an dysregulated immune response composed of relatively high cytokine levels and increased numbers of immune cells along with microbial and hard-soft tissue destructive pathologies. Whilst anti-cytokine therapies have been successfully applied in the treatment of these diseases, this approach is yet to be attempted in cases of pulp inflammation. This review therefore focuses on the similarities in the aetiology between chronic inflammatory diseases and pulpitis, and explores how anti-cytokine therapies could be applied to manage an inflamed pulp and facilitate healing. Further proof-of-concept studies and clinical trials are justified to determine the effectiveness of these treatments to enable more predictable outcomes in VPT.
33569065 Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases. 2020 The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.
33502796 Trans-ventricular catheter device-based closure of postmyocardial infarction ventricular s 2021 Apr A 66-year-old woman with a history of hypertension, ischemic stroke, and rheumatoid arthritis presented to the hospital with severe angina pectoris and dyspnea and was diagnosed with myocardial infarction (MI). Coronary angiography revealed multisystem coronary artery occlusive disease. Due to refractory myocardial ischemia/evolving MI, emergency coronary artery bypass grafting (CABG) was undertaken. Intraoperative transesophageal echocardiography additionally revealed an apical muscular ventricular septal defect (VSD). Concomitant VSD repair was deferred due to the absence of surface evidence of transmural MI for left ventriculotomy, in the setting of pre-existing severe left ventricular dysfunction. An initial totally percutaneous attempt to close the VSD postoperatively failed. A hybrid surgical/catheter-based VSD closure was performed on postoperative day 4, with a successful outcome. The patient did well postoperatively and currently is alive in good condition. To the best of our knowledge, this is the first report of a staged (post-CABG) and hybrid surgical/catheter-based technique without the utilization of cardiopulmonary bypass.