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ID PMID Title PublicationDate abstract
35543829 Comparative transcriptome analysis of leaf, stem, and root tissues of Semiliquidambar cath 2022 May 11 BACKGROUND: Semiliquidambar cathayensis is a traditional medicinal plant and endemic species in China. Its roots, branches, leaves, bark, and nectar are known to have therapeutic effects against rheumatoid arthritis, lumbar muscle strain, and several other diseases. However, limited knowledge regarding the molecular properties of S. cathayensis highlights the need for further research in order to elucidate the underlying pathways governing the synthesis of its active ingredients and regulation of its accumulation processes. METHODS: We conducted transcriptome sequencing of the leaf, stem and root epidermises, and stem and root xylems of S. cathayensis with three biological replicates. Moreover, candidate genes involved in terpenoid biosynthesis, such as IDI, FPPS, DXR, SQS, GPPS, and HMGR were selected for quantitative real-time PCR analysis. RESULTS: We identified 88,582 unigenes. Among which, 36,144 unigenes were annotated to the nr protein database, 21,981 to the Gene Ontology database, 11,565 to the Clusters of Orthologous Groups database, 24,209 to the Pfam database, 21,685 to the SWISS-PROT database, and 12,753 to the Kyoto Encyclopedia of Genes and Genomes (KEGG), with 5072 unigenes common to all six databases. Of those annotated using the KEGG database, 187 unigenes were related to the terpenoid metabolism pathway, and expression analysis of the related genes indicated that the mevalonate and methylerythritol 4-phosphate pathways play different roles in terpenoid biosynthesis in different tissues of S. cathayensis. CONCLUSIONS: These findings greatly expand gene resources of S. cathayensis and provide basic data for the study of the biosynthetic pathways and molecular mechanisms of terpenoids.
35466218 Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in P 2022 Mar 30 Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn's disease (CD) in clinical practice. However, differential individual response necessitates a therapeutic response assessment of anti-TNF agents in CD patients for optimizing therapeutic strategy. We aimed to predict anti-TNF therapy response in CD patients using transcriptome analyses. Transcriptome analyses were performed using data from the Gene Expression Omnibus, GeneCards, and Human Protein Atlas databases. The significantly mitigated biological functions associated with anti-TNF therapy resistance in CD patients encompassed immune pathways, including Interleukin-17 (IL-17) signaling, cytokine-cytokine receptor interaction, and rheumatoid arthritis. The scores of immune cell markers, including neutrophils, monocytes, and macrophages/monocytes were also significantly decreased in non-responders compared with that measured in anti-TNF therapy responders. The KAT2B gene, associated with IL-17 cytokine mediated neutrophil mobilization and activation, was significantly under-expressed in both tissue and peripheral blood mononuclear cells (PBMCs) in anti-TNF therapy-resistant CD patients. The reduced expression of several pro-inflammatory cytokines due to down-regulated IL-17 signaling, is suggestive of the primary non-response to anti-TNF agents in CD patients. Furthermore, the PBMC KAT2B gene signature may be a promising pre-treatment prognostic biomarker for anti-TNF drug response in CD patients.
35409152 The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Player 2022 Mar 30 The first description of a new form of neutrophil cell death distinct from that of apoptosis or necrosis was discovered in 2004 and coined neutrophil extracellular traps "(NETs)" or "NETosis". Different stimuli for NET formation, and pathways that drive neutrophils to commit to NETosis have been elucidated in the years that followed. Critical enzymes required for NET formation have been discovered and targeted therapeutically. NET formation is no longer restricted to neutrophils but has been discovered in other innate cells: macrophages/monocytes, mast Cells, basophils, dendritic cells, and eosinophils. Furthermore, extracellular DNA can also be extruded from both B and T cells. It has become clear that although this mechanism is thought to enhance host defense by ensnaring bacteria within large webs of DNA to increase bactericidal killing capacity, it is also injurious to innocent bystander tissue. Proteases and enzymes released from extracellular traps (ETs), injure epithelial and endothelial cells perpetuating inflammation. In the context of autoimmunity, ETs release over 70 well-known autoantigens. ETs are associated with pathology in multiple diseases: lung diseases, vasculitis, autoimmune kidney diseases, atherosclerosis, rheumatoid arthritis, cancer, and psoriasis. Defining these pathways that drive ET release will provide insight into mechanisms of pathological insult and provide potential therapeutic targets.
35314796 Challenges in the management of older patients with inflammatory rheumatic diseases. 2022 Jun The rise in the number of people aged 65 years and older living with inflammatory rheumatic diseases such as rheumatoid arthritis is causing considerable challenges for clinicians. As patients get older, they are at an increased risk of multiple chronic diseases, a situation termed multimorbidity. Multimorbidity inevitably drives polypharmacy, where by a patient requires treatment with multiple medications. In addition, advancing age, multimorbidity and polypharmacy all place a patient at an increased risk of developing geriatric syndromes, which are clinical conditions in older people that do not fit into disease categories and include malnutrition, sarcopenia and frailty. Geriatric syndromes further increase the risk of adverse outcomes, including the accrual of additional morbidity, nursing home admission and mortality. Patients with inflammatory rheumatic diseases are especially prone to developing geriatric syndromes. Some predisposing risk factors for geriatric syndromes, such as joint swelling and functional limitations, are also inherent to rheumatic inflammatory disease itself. The frequent coexistence of multimorbidity, polypharmacy and geriatric syndromes in this patient group requires individually tailored interventions to preserve patient independence and overall functioning. To prepare for the changing demography, rheumatologists should gain more insight into the implications of multimorbidity, polypharmacy and geriatric syndromes for the management of older patients with inflammatory rheumatic diseases.
35196176 Case 303. 2022 Mar History A 54-year-old man was found by paramedics in his home face-down at his computer desk with a substantially reduced level of consciousness. He had not contacted his family for more than 50 hours. The patient lived alone and was a heavy smoker with a history of alcohol abuse. His medical history was otherwise unremarkable, and there was no history of cancer, psoriasis, or rheumatoid arthritis, nor was there a history of methotrexate administration. On presentation to the emergency department, he was mildly hypotensive and was experiencing hypercapnic respiratory failure and acute renal failure with rhabdomyolysis. His toxicology screen was mildly positive for opiates. He received naloxone (Narcan; Emergent) with minimal effect. An unenhanced CT scan of the head was obtained (Fig 1A). Of note, this patient's presentation predated the COVID-19 pandemic. He was admitted to the intensive care unit for decreased level of consciousness and respiratory failure. The decreased level of consciousness was thought to be secondary to seizure, as he developed seizurelike movements prior to intubation, probably in the context of intoxication or alcohol withdrawal. Electroencephalography revealed moderate bilateral cerebral dysfunction and encephalopathy, with no evidence of nonconvulsive seizures. He had a short course of intermittent hemodialysis and was discharged home 8 days later with an appointment for neurology follow-up. At discharge, he was at his cognitive and functional baseline. Approximately 3 weeks later, the patient was brought back to the emergency department for progressive confusion and decrease in balance. He became apathetic with reduced psychomotor activity and was no longer able to perform basic daily activities, such as cooking or bathing. He displayed bizarre behavior, such as staring at a wall for hours, and was somnolent, irritable, and inattentive. He eventually became incontinent of urine and stool. Results of a neurologic examination of the cranial nerves, motor function, sensation, and reflexes were normal. The results of blood work-up were grossly normal, and the results of an extensive toxicology work-up were negative. Repeat head CT was performed (Fig 1B). MRI was ordered to further investigate the patient's encephalopathic presentation (Figs 2-3).
35093687 Co-existence of type 1 diabetes and other autoimmune ailments in subjects with autoimmune 2022 Feb BACKGROUND AND AIMS: Autoimmune thyroid dysfunction (AITD) is a significant autoimmune disorder affecting the population across age groups. The clustering of autoimmune diseases tends to occur within the same patients and families. Thus, this study aimed to determine the association of Type 1 diabetes and other autoimmune ailments in patients with autoimmune thyroid disorders. METHODS: We performed a cross-sectional study, evaluating 500 subjects with a diagnosis of AITD (130 with Graves' disease; 370 with Hashimoto's thyroiditis) on presentation to our tertiary care centre to ascertain the prevalence of associated autoimmune disorders. RESULTS: The frequency of Type 1 diabetes and other autoimmune disorders was 18.5% in Graves' disease and 27.8% in Hashimoto's thyroiditis patients. Coeliac disease (8.8%) (found in 6.9% of Graves' disease and 9.5% of Hashimoto's thyroiditis patients) and type 1 diabetes (7.8%) (found in 3.1% of Graves' disease and 9.5% of Hashimoto's thyroiditis patients) were the most common coexisting autoimmune disorders. Rheumatoid arthritis was the most common non-endocrine autoimmunity (2.8%). Female sex and duration of AITD more than five years were associated with increased odds of associated autoimmune disorders. CONCLUSION: A high prevalence of associated autoimmune disorders was observed in subjects with autoimmune thyroid dysfunction. We suggest the patients who remain symptomatic and those who develop other symptoms even with appropriate treatment undergo screening for associated autoimmune disorders, thus preventing a delay in diagnosis.
35021057 Inflammation in obesity, diabetes, and related disorders. 2022 Jan 11 Obesity leads to chronic, systemic inflammation and can lead to insulin resistance (IR), β-cell dysfunction, and ultimately type 2 diabetes (T2D). This chronic inflammatory state contributes to long-term complications of diabetes, including non-alcoholic fatty liver disease (NAFLD), retinopathy, cardiovascular disease, and nephropathy, and may underlie the association of type 2 diabetes with other conditions such as Alzheimer's disease, polycystic ovarian syndrome, gout, and rheumatoid arthritis. Here, we review the current understanding of the mechanisms underlying inflammation in obesity, T2D, and related disorders. We discuss how chronic tissue inflammation results in IR, impaired insulin secretion, glucose intolerance, and T2D and review the effect of inflammation on diabetic complications and on the relationship between T2D and other pathologies. In this context, we discuss current therapeutic options for the treatment of metabolic disease, advances in the clinic and the potential of immune-modulatory approaches.
34893889 Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome re 2022 Jan 11 Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB plays a critical role in orchestrating the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype.
32734810 Hydroxychloroquine Alternatives for Chronic Disease: Response to a Growing Shortage Amid t 2022 Feb With the emergence of a novel severe acute respiratory syndrome coronavirus, investigators worldwide are scrambling to identify appropriate treatment modalities, develop accurate testing, and produce a vaccine. To date, effective treatment remains elusive. Chloroquine phosphate and hydroxychloroquine sulfate (HCQ), well-known antimalarial drugs effective in the treatment of systemic lupus erythematosus, rheumatoid arthritis, porphyria cutanea tarda, and chronic Q fever, are currently under investigation. The United States Food and Drug Administration recently issued an Emergency Use Authorization for CQ and HCQ use in the treatment of coronavirus disease 2019 (COVID-19). With spikes in HCQ use and demand, ethical considerations encompassing appropriate use, patient autonomy, nonmaleficence, and distributive justice abound. As drug experts, pharmacists are uniquely positioned to advocate for patients with chronic conditions necessitating HCQ use, assist in the appropriate prescribing of HCQ for COVID-19, and ensure patients and health care professionals are continually educated during this public health crisis. This review highlights the worldwide pandemic, describes appropriate HCQ use for chronic conditions, highlights available alternatives, and deliberates evolving ethical questions. With assistance from colleagues, state boards of pharmacy, and national organizations, pharmacists ensure the just distribution of valuable pharmaceuticals to patients having COVID-19 while supporting the needs of patients requiring HCQ for chronic conditions.
35388531 Gut microbiome and prostate cancer. 2022 Apr 6 The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country. Lifestyle, especially diet, plays an important role in the development and progression of prostate cancer. Recent studies have revealed a connection between the gut microbiome and prostate cancer. A high-fat diet causes gut dysbiosis and gut bacterial metabolites, such as short-chain fatty acids and phospholipids that enter systemic circulation result in promoting prostate cancer growth. Additionally, the gut microbiota can serve as a source of testosterone, which affects prostate cancer progression. Men with castration-resistant prostate cancer have an increased abundance of gut bacteria with androgenic functions. Men with high-risk prostate cancer share a specific gut microbial profile and profiling gut microbiota could be a potentially effective tool to screen men with high-risk prostate cancer. Lifestyle modifications can improve the gut microbiome. Furthermore, altering the gut microbiome using prebiotic or probiotic interventions may prevent or delay prostate cancer development. Further study into the "Gut-Prostate Axis" would help in the discovery of new strategies for the prevention, screening, and treatment of prostate cancer.
35647269 Impact of COVID-19 Pandemic on Patients with Rheumatic and Musculoskeletal Diseases: Disru 2022 The COVID-19 pandemic presented a challenge to the care of patients with rheumatic and musculoskeletal diseases (RMDs). The objective of this study was to evaluate the impact of the pandemic on the care of RMDs patients and their health and well-being. This cross-sectional study involved 120 RMDs patients at the rheumatology department at Suez Canal University Hospital in Ismailia, Egypt, in July 2020. Patients were interviewed for sociodemographic and disease-related history. Further assessments were performed using Kessler 6-items, fears of COVID-19, and COV19-impact on quality of life scales. Rheumatoid arthritis and systemic lupus erythematosus represented the majority of our sample of RMDs patients (72.5% and 19.2%, respectively). About 50% of patients reported experiencing limitations in the access to rheumatologic care, and a similar percentage had changed or discontinued their medications. Disease-modifying antirheumatic drugs shortage and concerns about the increased risk of COVID-19 infection due to immunosuppressive drugs were the most frequently reported reasons for nonadherence. The percentage of patients with uncontrolled disease had significantly increased from 8.3% prior to the COVID-19 pandemic to 20% during the pandemic. About 60% of patients reported a high level of psychological distress. In conclusion, the pandemic negatively influenced mental health, quality of life, adherence to medications, access to rheumatology care, and the degree of disease control of RMDs patients.
35441682 Iron plays a role in sulfasalazine-induced ferroptosis with autophagic flux blockage in K7 2022 May 27 Osteosarcoma is the most common primary bone malignancy in children and young adults, with a very poor prognosis. It is of great importance to develop targeted therapeutic strategies for osteosarcoma. Sulfasalazine (SAS) is an FDA-approved drug for the treatment of Crohn's disease, rheumatoid arthritis, and inflammatory bowel disease. It acts as an inhibitor of cystine/glutamate system, which is important for cellular glutathione synthesis and maintenance of GPx4 activity. Nowadays, SAS has been repurposed as an antitumor drug for inducing ferroptosis in cancers. This study aimed to uncover the role of iron in SAS-induced ferroptotic cell death in K7M2 osteosarcoma cells. Herein, SAS led to an iron-dependent cell death mode in K7M2 cells, accompanied with decreased antioxidant defense and increased production of cytosolic and lipid reactive oxygen species. Results also showed that iron supplement with ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS) exacerbated the declined cell viability of SAS-treated K7M2 cells, while in the case of iron depletion, it weakened such suppression. Furthermore, iron promoted SAS-induced alterations on cell cycle, cytoskeleton, mitochondria morphology and function, and redox system. Iron also induced the dysfunction of autophagic activity in SAS-treated K7M2 cells. In conclusion, our study uncovered the essential role of iron in SAS's effects on K7M2 cells and provided the potential combined therapy of inhibition on antioxidant defense and an increase in oxidative potential, which further disturbed the redox status in tumor cells.
35443244 GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemi 2022 Apr 20 Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15-/- C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.
35364743 [Rheumatologic inpatient treatment-more than a complex treatment : Data reflecting service 2022 Apr 1 To review and be prepared for upcoming reforms, data from the InEK (Institut für das Entgeltsystem im Krankenhaus, institute for remuneration in hospitals) data browser and the structured quality reports for inpatient rheumatologic treatment were evaluated. Rheumatologic treatment is very diversified, both in terms of diagnoses and structures. Different specializations can be identified. Rheumatologic complex treatment (RCT) is just one of these and is performed on average in just over 10% of cases. In 2020, cases for selected rheumatological diagnoses decreased by more than 20% compared to 2019. For RCT, the decline was even more pronounced with more than 30%. Evidence of higher disease severity could not be found in the available data. It remains to be seen whether the pre-Corona caseload will be regained in the coming years. In all, 146 organizational departments with more than 20 principal diagnoses of rheumatoid arthritis (RA) were identified in 2019. Forty-seven (32%) of these coded RCT more than ten times, and 29 (20%) more than one hundred times. All 23 departments with more than 300 principle diagnoses of RA are members of the Association of Rheumatological Acute Care Hospitals (Verband rheumatologischer Akutkliniken, VRA), 15 of which participated in the KOBRA quality project and carry the VRA seal of approval. Of the 116 internal medicine departments, only 55 (47%) use a specific specialty code for a rheumatology department according to Article 301 SGB V (social insurance code). Information on specialist staffing was partly contradictory. How many cases with inflammatory rheumatic diseases are treated in specialized departments cannot be answered with the available data. Nevertheless, the available data can be used for specialist, structural, and organizational developments in acute inpatient rheumatology.
35302698 Effect of A. polygama APEE (Actinidia polygama ethanol extract) or APWE (Actinidia polygam 2022 Mar 18 BACKGROUND: Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging. OBJECTIVE: To evaluate the anti-photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB-irradiated hairless mice. METHODS: SKH-1 hairless mice were exposed to UVB irradiation (30~60 mJ /cm(2) ), following orally APEE or APWE oral administration for 10 weeks. We examined the effect on winkle improvement by a measuring Fullscope, PRIMOS, Craniometer and Cutometer. Furthermore, we analyzed histological changes in mouse dorsal skin through hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. The expression of matrix metalloproteinase (1, 3, and 9) expression was analyzed by immunoblotting. RESULTS: Oral administration of APEE or APWE at 100 or 200 mg/kg in UVB-irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression. CONCLUSION: Based on results for our study, APEE or APWE could protect the UVB-mediated skin wrinkle and is new target for the developing anti-wrinkle cosmetics.
34998312 [Autoimmunity in chronic urticaria. A historical and current perspective]. 2022 Chronic spontaneous urticaria is a condition that persists for more than six weeks, it occurs in the absence of an identifiable triggering factor and from the pathogenic activation of mast cells and basophils. The possibility of autoimmune etiology in up to 40 % of patients is presented, followed by subclinical infections and psychological factors. Two main mechanisms of the pathogenesis of chronic urticaria have been proposed: the former is the dysregulation of intracellular signaling pathways within mast cells and basophils, which leads to defects in the traffic or function of these cells. The latter is the development of autoantibodies against FcεRIα or IgE, in both mast cells and basophils. Numerous autoimmune diseases such as systemic lupus erythematosus, polymyositis, dermatomyositis, and rheumatoid arthritis have been associated with chronic urticaria; however, autoimmune thyroid disease deserves a special mention. A higher prevalence of antithyroid antibodies has been found, regardless of thyroid function (euthyroidism, hypo and hyperthyroidism) in patients with chronic spontaneous urticaria. Several infections have been linked to chronic urticaria. The best evidence is for Helicobacter pylori infection. Finally, stress is associated with the onset of the disease through the activation of the sympathetic and adrenomedullary system and the hypothalamic-pituitary- adrenal axis. Diagnosis may vary in different regions of the world, but the common feature is the completion of a thorough medical history.
34881658 DNA methyltransferase inhibitors increase NOD-like receptor activity and expression in a m 2022 Feb Background: The intracellular NOD-like receptor (NLR) family of pathogen recognition receptors (PRRa) is involved in initiating the innate immune response of which NOD1 and NOD2 are the best-characterized members. Aberrant expression of NOD1 and NOD2 has been uncovered in a number of chronic inflammatory diseases, such as inflammatory bowel disease and rheumatoid arthritis. However, the mechanism underlying NOD1/NOD2 gene expression regulation is still in its infancy. Epigenetic modifications such as DNA methylation and histone acetylation regulate the expression of genes and alterations in their patterns have been linked to many inflammatory diseases. This study investigated whether epigenetic modifying drugs affect the regulation of NOD1/NOD2 activity and expression. DNA methyltransferase inhibitors have recently been used in the treatment of myelodysplastic syndrome and as combination therapy in cancer but the full extent of their effects has not been quantified.Methods: Pharmacological inhibition of epigenetic enzymes in a human monocytic THP-1 cell line was carried out and NOD1/NOD2 expression and pro-inflammatory responses were quantified.Results: Cells primed with a DNA methyltransferase inhibitor (but not a histone deacetylase [HDAC] inhibitor) were found to be consistently more responsive to NOD1/NOD2 stimulation and had increased basal expression.Conclusion: The novel experimentation carried out here suggests for the first time that NOD1/NOD2 receptor activity and expression in monocytes are possibly regulated directly by DNA methylation.
35478968 Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mech 2022 Monocytes and macrophages are innate immune cells with diverse functions ranging from phagocytosis of microorganisms to forming a bridge with the adaptive immune system. A lesser-known attribute of macrophages is their ability to fuse with each other to form multinucleated giant cells. Based on their morphology and functional characteristics, there are in general three types of multinucleated giant cells including osteoclasts, foreign body giant cells and Langhans giant cells. Osteoclasts are bone resorbing cells and under physiological conditions they participate in bone remodeling. However, under pathological conditions such as rheumatoid arthritis and osteoporosis, osteoclasts are responsible for bone destruction and bone loss. Foreign body giant cells and Langhans giant cells appear only under pathological conditions. While foreign body giant cells are found in immune reactions against foreign material, including implants, Langhans giant cells are associated with granulomas in infectious and non-infectious diseases. The functionality and fusion mechanism of osteoclasts are being elucidated, however, our knowledge on the functions of foreign body giant cells and Langhans giant cells is limited. In this review, we describe and compare the phenotypic aspects, biological and functional activities of the three types of multinucleated giant cells. Furthermore, we provide an overview of the multinucleation process and highlight key molecules in the different phases of macrophage fusion.
35257683 Prevalence of Apical Periodontitis in Patients with Autoimmune Diseases under Immunomodula 2022 Jun INTRODUCTION: The aim of this retrospective cohort study was to investigate the prevalence of apical periodontitis (AP) in patients affected by autoimmune diseases (ADs) taking biologic medications (BMs). METHODS: Ninety-nine patients (2440 teeth) with ADs referred to the university clinic for dental evaluation were investigated. The controls included 99 patients (2655 teeth) with no systemic diseases and taking no medications. The patients underwent a complete oral, dental, and radiographic examination for the presence of AP. The periapical index and the status of endodontic and restorative treatments were obtained. Statistics were based on descriptive analysis and continuous variables for the total sample and by subgroups. Adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: The prevalence of AP was 65.7% in the autoimmune diseases group (AI) and 46.5% in the controls (P ≤ .05). The association between smoking and AP was significant (P ≤ .05). Among the AI subgroups, rheumatoid arthritis patients at the tooth level had a lower probability of developing AP than patients with inflammatory bowel disease (P ≤ .05). Furthermore, each additional year of age implied a +1% risk of AP; women had a lower periapical index than men in both groups (P ≤ .05), and tocilizumab was associated with a reduced risk of AP compared with infliximab (P ≤ .05). CONCLUSIONS: Patients with ADs taking BMs had a higher prevalence of AP. These results indicate that the status of the patients' immune system may have an effect on the development and prevalence of AP.
34923952 Impact of smoking on the incidence and post-operative complications of total knee arthropl 2022 Jun 1 Osteoarthritis and rheumatoid arthritis are the most ubiquitous joint disorders which cause tremendous loss of life quality and impose an economic burden on society. At present, the treatment options for these two diseases comprise non-operative and surgical treatments, amongst those total knee arthroplasties (TKA). Various studies have recognized smoking as a significant risk factor for postoperative complications. Therefore, the purpose of this study was to examine the impact of smoking on the incidence and postoperative complications after a total knee arthroplasty by a systematic review and meta-analysis. The research was performed using PUBMED, Cochrane Library and EMBASE, extracting data from thirteen suitable studies and incorporating 2,109,482 patients. Cohort studies evaluating the impact of smoking on TKA with sufficient data were included for the study, and cohort studies without a proper control group and complete data were excluded. A fixed-effects or random-effects model was used to measure the pooled risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI). Compared to non-smokers, smokers had a significantly lower incidence of TKA (p<0.01). However, smokers had a higher incidence of total complications (p=0.01), surgical complications (p<0.01), pneumonia (p<0.01) and revision surgery (p=0.01). No significant difference in the risk of blood transfusion (p=0.42), deep vein thrombosis (p=0.31), pulmonary embolism (p=0.34), urinary tract infection (p=0.46) or mortality (p=0.39) was found between smokers and non-smokers. In conclusion, the study indicated that tobacco has two diametrically opposite effects on TKA patients: 1. Tobacco increases the incidence of surgical complications, pneumonia and revision after TKA; 2. It decreases the overall risk of being a candidate for TKA.