Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 34579628 | Therapeutic Potential of Galectin-1 and Galectin-3 in Autoimmune Diseases. | 2022 | Galectins are a highly conserved protein family that binds to β-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. They can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies have indicated that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. This information may provide a novel and promising therapeutic target for autoimmune diseases. | |
| 34499143 | A unique salvage operation strategy: implantation of the ulnar total elbow component to th | 2022 Jan 7 | The elbow joints of patients with rheumatoid arthritis (RA) are often destroyed, and total elbow arthroplasty (TEA) is one treatment for these patients. However, patients with RA tend to develop surgical site infections due to immunosuppression. Once an implant is infected, reoperation may be difficult because of the risk of reinfection. In such patients, the infected site must be debrided thoroughly, although this might reduce the bone scaffold needed for re-TEA. We used a unique method to manage a large ulnar bone defect and an infected implant. The patient with RA had undergone TEA 15 years earlier. Etanercept was initiated to control disease activity; however, this treatment led to infection of the elbow prosthesis. Several surgical debridements were performed to eradicate the bacteria, which improved the symptoms of infection. However, most of the proximal ulna was lost, and it seemed impossible to fix the prosthesis using the remaining small ulna after debridement. Therefore, we planned to implant the ulnar component into the radius as a salvage technique. With this procedure, we provided the patient with elbow mobility and eradicated the infection. This is an alternative method for restoring function in an elbow with a massive bone defect in the ulna. | |
| 35571412 | cGAS/STING signaling in the regulation of rheumatoid synovial aggression. | 2022 Apr | BACKGROUND: Fibroblast-like synoviocytes (FLSs) play a critical role in promoting synovial aggression and joint destruction in rheumatoid arthritis (RA). Cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling plays an important role in controlling a series of cellular biological processes. However, it is still unclear whether cGAS/STING signaling regulates rheumatoid synovial aggression. METHODS: Cell migration and invasion were detected using a Transwell chamber. Gene expression was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and protein expression was detected by western blotting. Reactive oxygen species (ROS) levels were measured by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. F-actin staining and immunofluorescence assays were used to investigate lamellipodia formation and nuclear translocation, respectively. A severe combined immunodeficiency (SCID) mouse model was established to observe the migration and invasion of RA FLSs in vivo. RESULTS: Our results showed that cytosolic double-stranded DNA (dsDNA)-induced cGAS/STING activation promoted the in vitro migration and invasion of RA FLSs. Moreover, RA FLSs treated with cGAS or STING short hairpin RNA (shRNA) exhibited reduced invasion into cartilage in the SCID model. Mechanistically, we determined that cGAS/STING activation leads to increased mitochondrial ROS levels, and thereby increases phosphorylation of mammalian sterile 20-like kinase 1 (MST1), a core component of the Hippo pathway, subsequently promoting activation of forkhead box1 (FOXO1). MST1 and FOXO1 knockdown also diminished the migration and invasion of RA FLSs. CONCLUSIONS: Our findings suggest that cGAS/STING signaling has an important role in regulating rheumatoid synovial aggression and that targeting cGAS/STING may represent a novel potential therapy for RA. | |
| 35104308 | Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joi | 2022 Feb 1 | OBJECTIVE: To explore the spectrum of articular and peri-articular ultrasound (US) findings at metacarpophalangeal (MCP) joints in calcium pyrophosphate (CPP) deposition disease (CPPD). METHODS: Consecutive CPPD patients (chronic CPP crystal inflammatory arthritis or osteoarthritis (OA) with CPPD), and age- and sex-matched controls with rheumatoid arthritis (RA) were prospectively enrolled. Patients underwent bilateral US examination of MCP joints. CPP deposits, synovial inflammation, osteophytes, cartilage damage, and bone erosions were recorded. RESULTS: Sixty CPPD patients (33, 55.0% with osteoarthritis with CPPD and 27, 45.0% with chronic CPP crystal inflammatory arthritis) and 40 RA patients were enrolled. CPP deposits were detected in 24 (40.0%) CPPD patients and in 3 (7.5%) RA patients (p< 0.01). In CPPD patients, different types of CPP deposits were identified at MCP joints: 17 (28.3%) patients had dorsal capsuloligamentous deposits, 14 (23.3%) intra-cartilaginous deposits, 13 (21.7%) lateral capsuloligamentous deposits, 12 (20.0%) intra-articular deposits, 8 (13.3%) double contour sign, and 5 (8.3%) flexor digitorum tendons' deposits.CPPD patients with chronic CPP crystal inflammatory arthritis showed more US findings indicating synovial inflammation and CPP deposits than those with osteoarthritis with CPPD. Conversely, a higher prevalence of US features indicating structural damage was noted in this latter phenotype.CPP deposits and bone erosions were the US findings with the highest value for diagnosing chronic CPP crystal inflammatory arthritis and RA, respectively. CONCLUSION: This study provides pictorial evidence of the broad spectrum of US findings indicating CPP deposits at MCP joints in CPPD. Furthermore, we reported different US patterns in different CPPD phenotypes. | |
| 35238988 | Association of HLA-DRB1 alleles with rheumatoid arthritis in Split-Dalmatia County in sout | 2022 Mar 3 | OBJECTIVE: The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia County (SDC) in Croatia and to determine their relationship with disease severity. METHODS: A total of 74 RA patients and 80 healthy controls from the SR, and 74 RA patients and 80 healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C‑reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index. RESULTS: The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%; P = 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%; P = 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (P = 0.014 and P = 0.004, respectively), higher disease activity (P = 0.043), and worse functional status (P < 0.001), than SE-positive patients from the rest of the SDC. CONCLUSION: The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR. | |
| 33601915 | Revision and 90-day mortality following hip arthroplasty in patients with inflammatory art | 2022 May | AIM: To assess revision rates and postoperative mortality in patients undergoing hip arthroplasty (HA) for inflammatory arthritis compared to hip osteoarthritis (OA). METHODS: The analysis was conducted among cases of HA that were recorded in the National Joint Registry for England and Wales (NJR) between April 2003 and December 2012 and linked to Office for National Statistics mortality records. Procedures were identified where the indication for surgery was listed as seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), other inflammatory arthritis (otherIA), or OA. 5-year revision risk and 90-day postoperative mortality according to indication were compared using Cox regression models adjusted for age, sex, American Society of Anaesthesiologists (ASA) grade, year of operation, implant type, and surgical approach. RESULTS: The cohort included 1457 HA procedures conducted for RA, 615 for AS, 1000 for otherIA, and 183,108 for OA. When compared with OA, there was no increased revision risk for any form of inflammatory arthritis (adjusted HRs: RA: 0.93 (0.64-1.35); AS: 1.14 (0.73-1.79); otherIA: 1.08 (0.73-1.59)). Postoperative 90-day mortality was increased for RA when compared with OA (adjusted HR: 2.86 (1.68-4.88)), but not for AS (adjusted HR: 1.56 (0.59-4.18)) or otherIA (adjusted HR: 0.64 (0.16-2.55)). CONCLUSIONS: The revision risk in HA performed for all types of inflammatory arthritis is similar to that for HA performed for OA. The 3-fold increased risk of 90-day mortality in patients with RA compared with OA highlights the need for active management of associated comorbidities in RA patients during the perioperative period. | |
| 35471670 | Metabolic syndrome may be more frequent in treatment-naive sarcoidosis patients. | 2022 Apr 26 | INTRODUCTION: Sarcoidosis is a chronic granulomatous multisystem inflammatory disease. An association between sarcoidosis and subclinical atherosclerosis has recently been demonstrated. However, there are limited publications on metabolic syndrome (MetS) and its metabolic changes in sarcoidosis. In this study, we evaluated our hypothesis that the frequency of MetS may also be increased in treatment-naive, newly diagnosed sarcoidosis patients. METHODS: We included 133 newly diagnosed sarcoidosis patients, 133 age- and sex-matched controls, and 51 untreated rheumatoid arthritis (RA) patients as diseased controls. We then compared the frequency of MetS and MetS-related items in the three groups. The criteria defined for metabolic syndrome in the National Cholesterol Education Program (NCEP) Adult Treatment Panel III report (ATP III) were used to diagnose MetS. RESULTS: MetS was more common in sarcoidosis than controls (odds ratio, OR: 5.3; 95% confidence interval, CI 95%: 2.4-11.5; p < 0.001) and was similar to RA. In addition, triglyceride and glucose levels, diastolic blood pressure measurements, and waist circumference of female sarcoidosis patients were significantly higher than in controls. CONCLUSION: We show that MetS is a frequent feature of sarcoidosis even before treatment is started. Therefore, clinicians should be aware of MetS both during treatment and during the course of the disease to reduce the risk of cardiovascular events. | |
| 35612587 | How Do Mexican Patients With Rheumatoid Arthritis Define Sexual and Reproductive Health? A | 2022 May 25 | BACKGROUND: A patient-centered approach is essential for promoting sexual health (SH) and reproductive health (RH) in rheumatoid arthritis patients. The study aimed to describe and interpret Mexican rheumatoid arthritis outpatients' testimonies of their SH and RH definitions. METHODS: Qualitative and quantitative content analysis was conducted on free-text comments from 219 and 223 descriptions of patients' SH and RH definitions, respectively. A comprehensive system of major themes, categories, and subcategories was structured for each definition. The representational foundations of these categories and the context of their production were analyzed. Integration of quantitative and qualitative content analysis was used to comprehend patients' definitions of SH and RH. Internal review board approved the study. RESULTS: Ten major themes emerged for each definition, and their assigned frequencies differed between SH and RH definitions, and between groups of patients integrated according to age, education level, and sex. Both definitions had similar contents, expressed in the shared major themes and categories, and in managing at the same time SH- and RH-related contents within each definition. The "overall prevention-patient oriented care" major theme defined a common core for both definitions' contents. Meanwhile, a diversity of meanings was also evident particularly at the subcategory level. CONCLUSIONS: In our population, SH content was distinguished by related diseases and their consequences, individual actions directed to prevention, and couple mentions. Meanwhile, RH was distinguished by a primarily biological perspective of the reproductive function, which was required at a particular life stage to concrete a family project. | |
| 35594728 | Age-associated B cells indicate disease activity in rheumatoid arthritis. | 2022 May 6 | Age-associated B cells (ABCs) are characterized by CD11c and T-bet expression. ABCs are elevated in several autoimmune diseases and may be associated with RA. This study aimed to investigate ABCs' role in RA and identify potential factors affecting ABCs in RA patients. Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected from 75 RA patients and 27 sex- and age-matched healthy controls. Proportions of ABCs (CD19(+)CD11c(+)T-bet(+)), plasmablasts (CD19(+)CD27(+)CD38(hi)), Bregs (CD19(+)IL-10(+)), and T follicular helper (Tfh) cells (CD4(+)CXCR5(+)PD-1(hi)) in PBMCs were detected using flow cytometry. Plasma IL-21, IFN-γ, and IL-10 levels were detected by ELISA. Plasma miRNAs (miR-34a, -122, -133a, -142, -146a, -208a, and -155) were detected by RT-PCR. Naïve B cells transfected with different miRNA mimics were deteced after 3 days culture under stimulation of anti-IgM and anti-CD40 or IL-21, IFN-γ, anti-IgM and anti-CD40. ABC proportions in PBMCs were increased in RA patients with higher disease activity and decreased in those with good treatment responses. Additionally, ABC proportions in PBMCs in RA patients were positively correlated with DAS28 scores. Plasma levels of IL-21, miR-142, and miR-146a and proportions of Tfh cells were positively correlated with ABC percentages in PBMCs. Herein, ABCs were identified as potential biological indicators for disease activity and treatment responses. Moreover, miR-142 and miR-146a could induce the differentiation of ABCs in naïve B cells in conjunction with IL-21 and IFN-γ. | |
| 35264540 | [A case of methotrexate-associated diffuse large B-cell lymphoma with splenial lesions of | 2022 | An 86-year-old woman in a wheelchair was accompanied by her husband and son as she visited our outpatient clinic due to disturbed consciousness and fever. Twenty-seven years earlier, she had been diagnosed with rheumatoid arthritis and had been treated with methotrexate (MTX) and low-dose prednisolone (PSL). She stopped taking MTX four years previously when she was diagnosed with diffuse large B cell lymphoma of the paranasal sinus. Her lymphoma went into remission after six cycles of systemic immunochemotherapy. MRI after hospitalization revealed a lesion in the splenium of the corpus callosum that was hyperintense on diffusion-weighted imaging and which had low apparent diffusion coefficient values. An analysis of the cerebrospinal fluid revealed no atypical cells. The MRI findings were atypical, but her consciousness disturbance improved, leading to the diagnosis of mild encephalitis/encephalopathy with a reversible splenial lesion, which would be associated with a transient consciousness disturbance with a good course. However, her consciousness worsened over the next 3 weeks. One month later, a contrast-enhanced MRI showed an enlarged lesion in the callosum as well as new lesions, and the diagnosis of secondary CNS lymphoma was made. Brain biopsy is often not feasible. Less invasive and highly accurate diagnostic methods are needed, such as the identification of a spinal fluid tumor marker. | |
| 35115766 | Evaluation of Newly Designed Blister Packs for Easier Handling to Prevent Pill Dropping. | 2022 | BACKGROUND: Blister packs with paperboard backing, which is useful for displaying instructions and information, are the most popular type of packaging for osteoporosis drugs in Japan. However, the main users of drugs are the aged, who often find blister packs difficult to open or drop their pills during opening. In this study, we compared different types of blister packs in terms of usability and handling. METHODS: We conducted a subjective and objective study to compare commonly used blister packs with newly designed ones that have a jagged notch designed to hold a pill temporarily and a perforated line that enables the pack to be held easily in one hand. Regarding subjective data, packaging and sensory tests were performed. The participants in the sensory test were healthy older adults and patients with rheumatoid arthritis (RA). We also measured the pinch power of all participants. RESULTS: A comparison of several items, including opening status, prevention of pill dropping, and understanding of the instructions, using a numerical rating scale revealed no significant differences between ordinary (type A) and newly designed (type B) packaging. However, the scores for type B were the same or better than those for type A for every evaluation item. In addition, more than 85% of the participants reported preferring to use type B. More than 80% of the participants in both groups reported dropping pills using type A, which seemed to be related to their preference for type B. In the evaluation by the examiner (objective study), all participants could successfully remove their pills without dropping using type B, including those in the RA group who had difficulty handling packages. CONCLUSION: These findings suggest that the new type of blister pack assessed in this study (type B) is preferable among older and shows promise for a universal design. | |
| 35156634 | Undetectable mannose binding lectin confers increased risk for serious infection in rheuma | 2022 Feb 14 | Physical activity and psychosomatic status in patients with Behçet's disease during coronavirus disease pandemic. | |
| 35071503 | Changes in rheumatoid arthritis under ultrasound before and after sinomenine injection. | 2022 Jan 7 | BACKGROUND: Rheumatoid arthritis (RA) is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate. In recent years, the application of traditional Chinese medicine in RA has received widespread attention; it promotes blood circulation, strengthens the immune system, and eliminates evil. The sinomenine preparation of Zhingqeng Fengtongning is studied as a possible treatment for patients with RA. AIM: To explore the value of sinomenine injection into the articular cavity for the treatment of RA. METHODS: A total of 94 patients with RA treated from January 2019 to January 2021 were selected and divided into the study and control groups with 47 patients each using a simple random number table method. Both groups received conventional treatment with diclofenac sodium and methotrexate tablets. The control group received diproxone and lidocaine by intra-articular administration while the study group received an intra-articular administration of the sinomenine preparation of Zhengqing Fengning and lidocaine. χ (2) test was used to evaluate the therapeutic effect and synovial thickness, degree of pain through the visual analog scale (VAS), blood flow grade, arthroinflammatory indexes [rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)] before and after treatment in the two groups. RESULTS: The total effective rate of the study group (93.62%) was higher than that of the control group (78.72%) (P < 0.05). Before treatment, there were no significant differences between the two groups in terms of synovial thickness, VAS score, blood flow grading, levels of RF, and ESR (P > 0.05). After treatment, the synovial thickness and VAS score were significantly lower (P < 0.05) in the study group than in the control group (2.05 ± 0.59 mm vs 2.87 ± 0.64 mm and 2.11 ± 0.62 vs 2.90 ± 0.79 scores, respectively). The rate of blood flow at grade 0 in the study group (76.60%) was higher than that in the control group (57.45%), and the rate of blood flow at grade I (10.64%) was lower than that in the control group (31.91%) (P < 0.05). Furthermore, the levels of RF (55.61 ± 6.13 U/mL), CRP (11.43 ± 3.59 mg/L), and ESR (29.60 ± 5.56 mm/h) in the study group were lower than those in the control group (73.04 ± 9.23 U/mL, 15.07 ± 4.06 mg/L, 36.64 ± 6.10 mm/h, respectively) (P < 0.05). CONCLUSION: Sinomenine administration of Zhengqing Fengtongning in the articular cavity with conventional treatment of RA can improve ultrasonographic blood flow and synovial thickness, reduce pain, regulate inflammation, and enhance therapeutic effect. | |
| 35088674 | Interleukin 6 Concentration in Synovial Fluid of Patients with Inflammatory and Degenerati | 2022 Jan 28 | AIM: The present study aims to compare interleukin 6 (IL-6) concentration in synovial fluid in patients with known types of arthritis. BACKGROUND: Persistent synovitis without known markers such as Rheumatoid Factor (RF), Anti-Citrullinated Protein Antibodies (ACPA), and genetic markers as HLA-B27 is not uncommon. It is valuable to determine the presence of chronic inflammation and put it in correlation with age-related changes, which are especially relevant for middle-aged patients with mono- or oligoarthritis, when the dilemma to start disease-modifying drugs for inflammatory disease often is present. INTERLEUKIN 6 (IL-6) plays a significant role in chronic inflammation. OBJECTIVES: IL-6 concentration in synovial fluid reflects the presence and activity of joint inflammation. METHODS: Synovial fluid was obtained from 101 patients with chronic synovitis. IL-6 concentration was determined by the immunochemical luminescence method. RESULTS: The median IL-6 concentration in synovial fluid in patients with osteoarthritis (OA) was 138.0 pg/ml (interquartile range [IQR] 43.4 to 296.0); in patients with rheumatoid arthritis was 2516.5 pg/ml, (IQR 1136.0 to 25058.0); in reactive arthritis 2281.0 pg/ml (IQR 1392.0 to 8652.0); psoriatic arthritis 1964.0 pg/ml (IQR 754.0 to 7300.0); ankylosing spondylitis 2776.0 pg/ml (IQR 514.7, 3944.0); in a group with negative RF, ACPA and HLA-B27 inflammatory arthritis 2163.0 pg/ml (IQR 822.0 to 7875.0). There is statistically significant difference of IL-6 concentration comparing OA and each inflammatory arthritis group, p<0.0001. CONCLUSION: IL-6 detection in the synovial fluid is helpful in arthritis evaluation. The results show that an IL-6 level over 1000 pg/ml suggests the diagnosis of inflammatory arthritis. | |
| 35428307 | Transformation of lymphoid interstitial pneumonia (LIP) into malignant lymphoma in patient | 2022 Apr 15 | BACKGROUND: Lymphoid interstitial pneumonia (LIP) is a very rare disease and its malignant transformation is even more rare. LIP is easily misdiagnosed by clinicians and radiologists. CASE PRESENTATION: The medical record of a 64-year-old female with Sjogren's syndrome was reviewed. The clinical and pathological data along with chest CT images were obtained. The literature related to the transformation was reviewed. There were no specific clinical manifestations of LIP and its transformation into malignant lymphoma in the patient. The chest CT mainly displayed multiple cystic foci, with multiple nodules and ground-glass shadows in both lungs. CONCLUSIONS: Malignant transformation to lymphoma is suspected with findings of large nodules (> 11 mm) or their sizes doubly increased, pleural effusion and alveolar consolidation. | |
| 32951458 | When EGFR inhibitor meets autoimmune disease: Severe corneal complications in a patient wi | 2022 Jan | INTRODUCTION: To report the first case of severe corneal complications in a patient with Sjögren syndrome after receiving erlotinib treatment. CASE DESCRIPTION: A 51-year-old woman with Sjögren syndrome presented with persistent corneal epithelial defects, which did not respond to conservative therapies. She had been diagnosed with lung cancer and was being treated with erlotinib, a kind of epidermal growth factor receptor (EGFR) inhibitor, for over 2 years. Cornea stromal melting and perforation were not avoided and a total of four penetrating keratoplasties were performed. Stable corneal surface was achieved after the erlotinib treatment was paused. CONCLUSION: This report, to the best of our knowledge, is the first description of severe ocular complications present in a patient with Sjögren syndrome after receiving the EGFR inhibitor. The underlying ocular or system diseases that were thought to be irrelevant upon receiving the EGFR inhibitors might negatively influence the tumor patients planning to take these kinds of targeted medication. Therefore, it is important to have eye examinations before and during the EGFR inhibitors treatment and supplement the relative contraindications (such as Sjögren syndrome) to EGFR inhibitor treatments as necessary. | |
| 35610634 | Acute fibrinous and organizing pneumonia in a patient with Sjögren's syndrome and Legione | 2022 May 24 | BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare clinicopathological condition. Studies in the literature have reported that AFOP may be associated with respiratory infections, such as respiratory syncytial virus, influenza virus, Pneumocystis jirovecii, Penicillium citrinum, and Chlamydia infections. However, AFOP associated with Legionella infection has not been reported previously. Here, we report a case of a patient with AFOP secondary to Sjögren's syndrome and Legionella infection. CASE PRESENTATION: A 47-year-old man was admitted to the hospital because of fever, expectoration, and shortness of breath. Lung imaging showed irregular patchy consolidation. A diagnosis of Legionella pneumonia was initially considered on the basis of the patient's history of exposure to soil before disease onset, signs of extrapulmonary involvement, and a positive Legionella urine antigen test result. However, the patient's symptoms and lung imaging did not improve after treatment with levofloxacin, moxifloxacin, and tigecycline for Legionella infection. In addition, Sjögren's syndrome was diagnosed on the basis of clinical manifestations and immunological indicators. Pathological changes associated with AFOP were confirmed from the results of ultrasound-guided percutaneous lung biopsy. The patient's clinical symptoms improved rapidly after a short course of low-dose corticosteroid therapy, and lung imaging showed significant improvement. CONCLUSIONS: The possibility of secondary AFOP should be considered when Legionella pneumonia does not improve after standard antibiotic therapy. Lung biopsy and histopathological examination are important for the adjustment of treatment strategy. Our case also highlights the importance of screening for autoimmune diseases in patients with AFOP. | |
| 35122384 | Inhibition of Rgs10 aggravates periodontitis with collagen-induced arthritis via the nucle | 2022 Feb 4 | OBJECTIVE: To explore the role of the Rgs10-associated nuclear factor (NF)-κB signalling pathway in periodontitis with rheumatoid arthritis. METHODS: Porphyromonas gingivalis and collagen were locally applied to mice to establish in vivo periodontitis and rheumatoid arthritis models, respectively. Both agents were administered together to establish the comorbid group. All models were treated with adeno-associated virus-green fluorescent protein (AAV-GFP) or adeno-associated virus small hairpin Rgs10 (AAV-sh-Rgs10). In vivo expression of Rgs10 and inflammatory cytokines was analysed, along with exploration of the NF-κB signalling pathway in lipopolysaccharide-stimulated mouse-derived RAW264.7 cells, with and without treatment of small interfering RNA (siRNA; Rgs10-Mus-MSS245072). RESULTS: In the comorbidity mouse group (mice with both periodontitis and rheumatoid arthritis), inhibition of Rgs10 exacerbated periodontitis, along with upregulation of phospho-RelA (pP65), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression in the NF-κB signalling pathway. Similarly, treatment of LPS-stimulated RAW264.7 cells with siRNA resulted in the inhibition of Rgs10, along with upregulation of pP65, TNF-α and IL-6 expression in vitro. CONCLUSION: Inhibition of Rgs10 in mice with periodontitis and rheumatoid arthritis can promote the progression of periodontitis, indicating the potential therapeutic role of Rgs10 in this condition. | |
| 35309364 | Tear miRNAs Identified in a Murine Model of Sjögren's Syndrome as Potential Diagnostic Bi | 2022 | OBJECTIVE: The tear miRNAome of the male NOD mouse, a model of ocular symptoms of Sjögren's syndrome (SS), was analyzed to identify unique miRNAs. METHODS: Male NOD mice, aged 12-14 weeks, were used to identify tear miRNAs associated with development of autoimmune dacryoadenitis. Age- and sex-matched male BALB/c mice served as healthy controls while age-matched female NOD mice that do not develop the autoimmune dacryoadenitis characteristic of SS were used as additional controls. Total RNA was isolated from stimulated tears pooled from 5 mice per sample and tear miRNAs were sequenced and analyzed. Putative miRNA hits were validated in additional mouse cohorts as well as in tears of SS patients versus patients with another form of dry eye disease, meibomian gland disease (MGD) using qRT-PCR. The pathways influenced by the validated hits were identified using Ingenuity Pathway Analysis. RESULTS: In comparison to tears from both healthy (male BALB/c) and additional control (female NOD) mice, initial analy1sis identified 7 upregulated and 7 downregulated miRNAs in male NOD mouse tears. Of these, 8 were validated by RT-qPCR in tears from additional mouse cohorts. miRNAs previously implicated in SS pathology included mmu-miR-146a/b-5p, which were significantly downregulated, as well as mmu-miR-150-5p and mmu-miR-181a-5p, which were upregulated in male NOD mouse tears. All other validated hits including the upregulated miR-181b-5p and mmu-miR-203-3p, as well as the downregulated mmu-miR-322-5p and mmu-miR-503-5p, represent novel putative indicators of autoimmune dacryoadenitis in SS. When compared to tears from patients with MGD, miRNAs hsa-miR-203a-3p, hsa-miR-181a-5p and hsa-miR-181b-5p were also significantly increased in tears of SS patients. CONCLUSIONS: A panel of differentially expressed miRNAs were identified in tears of male NOD mice, with some preliminary validation in SS patients, including some never previously linked to SS. These may have potential utility as indicators of ocular symptoms of SS; evaluation of the pathways influenced by these dysregulated miRNAs may also provide further insights into SS pathogenesis. | |
| 35212163 | 2-Deoxy-d-glucose induces deglycosylation of proinflammatory cytokine receptors and strong | 2022 Apr | Anti-proinflammatory cytokine therapies against interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. Such therapies are mainly performed by injection of antibodies against cytokines or cytokine receptors. We initially found that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG), a simple monosaccharide, attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. Aglycoforms of gp130 did not bind to IL-6 or activate downstream intracellular signals that included Janus kinases. 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin-induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. These diseases have been shown to be partially dependent on IL-6. We also found that 2-DG inhibited signals for other proinflammatory cytokines such as TNF-α, IL-1β, and interferon -γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. Furthermore, 2-DG prevented LPS shock, a model for a cytokine storm, and LPS-induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID-19). These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. |