Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35425183 | Advanced applications of cerium oxide based nanozymes in cancer. | 2022 Jan 5 | Cerium oxide nanozymes have emerged as a new type of bio-antioxidants in recent years. CeO(2) nanozymes possess enzyme mimetic activities with outstanding free radical scavenging activity, facile synthesis conditions, and excellent biocompatibility. Based on these extraordinary properties, use of CeO(2) nanozymes has been demonstrated to be a highly versatile therapeutic method for many diseases, such as for inflammation, rheumatoid arthritis, hepatic ischemia-reperfusion injury and Alzheimer's disease. In addition to that, CeO(2) nanozymes have been widely used in the diagnosis and treatment of cancer. Many examples can be found in the literature, such as magnetic resonance detection, tumour marker detection, chemotherapy, radiotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT). This review systematically summarises the latest applications of CeO(2)-based nanozymes in cancer research and treatment. We believe that this paper will help develop value-added CeO(2) nanozymes, offering great potential in the biotechnology industry and with great significance for the diagnosis and treatment of a wide range of malignancies. | |
| 35355463 | [Advances of using antibody against B cell activating factor for treatment of autoimmune d | 2022 Mar 25 | In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases. | |
| 35232474 | Effects of additional context information in prescription drug information sheets on compr | 2022 Mar 1 | OBJECTIVE: To determine how additional explanatory text (context) about drug side effects in a patient medication information handout affected comprehension and perceptions of risk and efficacy. METHODS: We conducted an online experiment with a national sample of 1,119 U.S. adults with rheumatoid arthritis and related conditions, sampled through random-digit dialing, address-based sampling, and online ads. We randomized participants to receive one of several versions of a patient information handout for a fictitious drug, either with or without additional context, then measured comprehension and other outcomes. RESULTS: Additional qualitative context about warnings and side effects resulted in lower comprehension of side effect information, but not information about uses of the drug or warnings. The effect of additional context on risk perceptions depended on whether the medication handout was delivered online or through the mail. Those who received a hardcopy of the handout with additional context had higher perceived risk of side effects than those who saw the version without additional context. CONCLUSION: More clarifying information is not always better and may lead to cognitive overload, inhibiting comprehension. PRACTICE IMPLICATIONS: Additional research should further explore effects of context in online vs. hard-copy formats before practice implications can be determined. | |
| 35174432 | Applications of Model-Based Meta-Analysis in Drug Development. | 2022 Feb 16 | Model-based meta-analysis (MBMA) is a quantitative approach that leverages published summary data along with internal data and can be applied to inform key drug development decisions, including the benefit-risk assessment of a treatment under investigation. These risk-benefit assessments may involve determining an optimal dose compared against historic external comparators of a particular disease indication. MBMA can provide a flexible framework for interpreting aggregated data from historic reference studies and therefore should be a standard tool for the model-informed drug development (MIDD) framework.In addition to pairwise and network meta-analyses, MBMA provides further contributions in the quantitative approaches with its ability to incorporate longitudinal data and the pharmacologic concept of dose-response relationship, as well as to combine individual- and summary-level data and routinely incorporate covariates in the analysis.A common application of MBMA is the selection of optimal dose and dosing regimen of the internal investigational molecule to evaluate external benchmarking and to support comparator selection. Two case studies provided examples in applications of MBMA in biologics (durvalumab + tremelimumab for safety) and small molecule (fenebrutinib for efficacy) to support drug development decision-making in two different but well-studied disease areas, i.e., oncology and rheumatoid arthritis, respectively.Important to the future directions of MBMA include additional recognition and engagement from drug development stakeholders for the MBMA approach, stronger collaboration between pharmacometrics and statistics, expanded data access, and the use of machine learning for database building. Timely, cost-effective, and successful application of MBMA should be part of providing an integrated view of MIDD. | |
| 35146055 | Movement Disorders and Musculoskeletal System: A Reciprocal Relationship. | 2022 Feb | The association of movement disorders (MDs) with musculoskeletal (MSK) disorders is observed in two principal scenarios. First, MDs patients may present with MSK issues. This phenomenon is primarily observed in parkinsonian syndromes, but may also be seen in patients with dystonia, Tourette syndrome, and some gene-related MDs. Second, there are MSK disorders that may produce or mimic MDs. Important primary MSK disorders producing MDs are joint hyperlaxity syndrome, non-traumatic craniovertebral junction anomalies, congenital muscular torticollis, and rheumatoid arthritis. Peripheral trauma to the MSK system may also lead to MDs commonly referred to as peripherally induced MDs. The exact pathogenesis of these disorders is not clear, however many patients have associated sensory phenomena such as complex regional pain syndrome. Herein, we provide an overview of disorders that may manifest with a combination of MSK and MDs, as detailed above. The most common MDs are discussed in each section, along with important clinical points, suggested diagnostic workups, and possible differential diagnoses. | |
| 34981437 | Compassionate-use pocapavir and immunoglobulin therapy for treatment of rituximab-associat | 2022 Jan 3 | A 71-year-old woman previously on rituximab treatment for rheumatoid arthritis presented with 2 years of progressive neurologic symptoms. She was found to have persistent hypogammaglobulinemia and B cell depletion despite rituximab discontinuation a year prior. MRI revealed diffuse meningeal enhancement along the entire neuroaxis. LP showed a CSF lymphocytic pleocytosis, elevated protein, and presence of enterovirus by PCR. The patient was hospitalized several times for progressive clinical and radiologic decline, though she had transient improvements following treatment with immunoglobulin therapy. Her CSF remained positive for enterovirus PCR for at least 12 months. Though two brain biopsies were non-diagnostic, pan-Enterovirus was ultimately identified using a high-throughput next-generation sequencing technique. She was treated with compassionate-use pocapavir with clinical stabilization at 4-month follow-up; however, she expired 8 months later from a bacterial pneumonia. | |
| 35647825 | An investigation of the relationship between rheumatological diseases and soluble receptor | 2022 May | OBJECTIVE: Soluble receptor for advanced glycation end products (sRAGE) is one of the forms of RAGE. It is a trap receptor that has a role in inhibiting pro-inflammatory processes that will occur with the combination of RAGE and its ligands. Our study aims to examine the level of sRAGE in rheumatological inflammatory diseases and its relationship with these diseases. PATIENTS AND METHODS: A total of 60 patients with Behçet's disease (BD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and 22 healthy control individuals were included in the study. Comorbidity status, sRAGE levels, disease activity scores, demographic and laboratory data of the patients were recorded. Serum sRAGE levels in these diseases and healthy controls were determined by Enzyme-Linked Immunosorbent Assay (ELISA) kit spectrophotometrically. RESULTS: Serum sRAGE levels in the patient groups were significantly higher when compared to the healthy control group (p < 0.001 for all). On the other hand, when the patient groups were compared with each other in terms of sRAGE levels, there was no significant difference (p > 0.05 for all). The serum sRAGE levels were not correlated with C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and disease activity scores (p > 0.05 for all). CONCLUSIONS: Serum sRAGE levels increased in BD and in other inflammatory rheumatological diseases. However, this increase does not directly correlate with inflammatory markers and disease activity scores. These results suggest that serum sRAGE level may not be used as a biomarker for disease activity in BD and in other rheumatological diseases. | |
| 35562628 | COVID-19 and corticosteroids: a narrative review. | 2022 May 13 | It has been reported that corticosteroid therapy was effective in the management of severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), and recently in coronavirus disease 2019 (COVID-19). Corticosteroids are potent anti-inflammatory drugs that mitigate the risk of acute respiratory distress syndrome (ARDS) in COVID-19 and other viral pneumonia, despite a reduction of viral clearance; corticosteroids inhibit the development of cytokine storm and multi-organ damage. The risk-benefit ratio should be assessed for critical COVID-19 patients. In conclusion, corticosteroid therapy is an effective way in the management of COVID-19, it reduces the risk of complications primarily acute lung injury and the development of ARDS. Besides, corticosteroid therapy mainly dexamethasone and methylprednisolone are effective in reducing the severity of COVID-19 and associated comorbidities such as chronic obstructive pulmonary diseases (COPD), rheumatoid arthritis, and inflammatory bowel disease (IBD). | |
| 29489227 | Leukocytoclastic Vasculitis. | 2022 Jan | Vasculitis refers to inflammation of the blood vessels leading to tissue destruction with or without organ damage. Vasculitis is classified as small vessel, medium vessel or large vessel vasculitis and maybe either idiopathic or associated with an underlying pathology/disease. Small vessel vasculitis can be seen secondary to systemic vasculitides such as Anti-neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (Microscopic polyangiitis, Granulomatosis with polyangiitis or Eosinophilic granulomatosis with polyangiitis), Behçet’s disease, and Cogan’s syndrome. Immune complex-mediated small vessel vasculitis can be seen in rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, Henoch-Schönlein purpura, cryoglobulinemic vasculitis, Hypocomplementemic urticarial vasculitis, Erythema elevatum diutinum, and cutaneous leukocytoclastic angiitis, formerly known as hypersensitivity vasculitis. Other causes of small vessel vasculitis or leukocytoclastic vasculitis include drug-induced vasculitis, paraneoplastic vasculitis, and infection associated vasculitis (hepatitis B, hepatitis C, syphilis). Leukocytoclastic vasculitis is a small vessel vasculitis characterized histopathologically by immune complex-mediated vasculitis of the dermal capillaries and venules. Cutaneous leukocytoclastic vasculitis is usually confined to skin with rare extracutaneous manifestations in less than 30% of the cases. Key clinical features of cutaneous leukocytoclastic angiitis include palpable purpura, lower extremity location, small vessel involvement. If leukocytoclastic vasculitis is suspected, a punch biopsy should be performed with direct immunofluorescence studies. If no systemic symptoms are present, laboratory testing including C-reactive protein, complete blood count (CBC), basic metabolic panel, liver function tests, and urinalysis should be done as well. If there is a concern for systemic involvement, a more extensive workup needs to be performed. Most cases of idiopathic cutaneous small-vessel vasculitis cases are self-limited with 90% resolving in weeks to months of onset. In persistent vasculitis, treatment depends on the severity of disease and can range from oral corticosteroids to various steroid-sparing agents. | |
| 35113362 | A Patient with Symmetrical Polyarthritis. The Value of Conventional Radiography for a Corr | 2022 Apr | PURPOSE OF REVIEW: Among the imaging modalities for the investigation of articular damage of patients with peripheral inflammatory arthropathies, conventional radiography (CR) is the mostly used. Other imaging modalities such as the musculoskeletal ultrasonography, magnetic resonance imaging, and dual-energy computed tomography scans are often used depending on a patient's clinical needs. RECENT FINDINGS: With the publication of new classification criteria for rheumatoid arthritis (RA), spondyloarthropathies, polymyalgia rheumatica, and others, many physicians are not using any of the above imaging techniques because they believe that by relying only on the classification criteria of a disease the diagnosis can be an easy task. We present a patient with peripheral symmetrical polyarthritis involving the small joints of the hands, diagnosed and treated as RA and we discuss the role of imaging, especially the use of CR as an initial screening tool for the evaluation of the articular manifestations and joint damage, and its further usefulness in order to reach a definitive correct diagnosis. | |
| 32936748 | Treatment innovation for patients: a collaborative network in the Benelux and an inside vi | 2022 Feb | A better understanding of disease pathology, improvements in relevant disease outcomes, better treatment strategies and the development of novel therapies all contribute to improving healthcare and treatment options. However, the global drug development model today is under increasing pressure, with very high drug development costs. Collaborative research is critical for bringing together different capabilities and expertise to increase the success of drug development, and large-scale collaborations with multiple partners are becoming increasingly common. Research clusters supported by local governments play an important role in bringing together academic centres, hospitals, scientists, and pharmaceutical and biotechnology industries. The 'triple helix' model, with academia, industry and governments working together, has been an important factor in the successful development of novel therapies. During the past 20Â years, Galapagos has worked closely with academic centres, hospitals, governments and pharmaceutical companies to conduct innovative research and to develop a novel therapy for rheumatoid arthritis. These collaborations have brought unique knowledge, expertise and skills together, as well as crucial funding at various stages. Local governments in the Benelux have operated in this triple helix model to provide the necessary environment and to stimulate companies to achieve innovation through collaboration. Although the triple helix has already proved successful, evolution to a quadruple helix that includes patients and patient representatives could be the next step to ensure innovation remains transformational. | |
| 35466746 | Unusual Presentations of Mycobacterium Tuberculosis in HIV-Positive Patients: A Case Serie | 2022 Apr 24 | Necrotizing and non-necrotizing epithelioid granulomatous chronic inflammation is the usual recognizable histopathologic presentation of mycobacterial infections. In immunosuppressed patients, atypical histomorphologic patterns may occur. Rare and diagnostically challenging manifestations of nontubercular mycobacterial infections in transplant and Human Immunodeficiency Virus (HIV)-infected patients include mycobacterial spindle cell pseudotumor and suppurative lesions. Lesions composed of nodular spindle cell proliferation mimicking inflammatory, histiocytoid and spindle cell tumors, and similarly suppurative lesions simulating abscesses have been mostly reported in association with nontuberculous mycobacterial infections mainly in nodal and various extranodal sites. Similar lesions related to Mycobacterium tuberculosis that involve serosal membranes are unusual and diagnostically challenging. Our aim is to report mycobacterial spindle cell pseudotumor-associated pericarditis, suppurative abscess-forming pleuritis, and cholesterol pleuritis due to tuberculosis in three HIV-infected young adult males. Initially, we confused the mycobacterial spindle cell pseudotumor for Kaposi sarcoma, the suppurative pleuritis for bacterial and fungal empyema, and the cholesterol pleuritis with rheumatoid arthritis. A prior knowledge of the immune status of our patients helped us confirm our final correct diagnosis of mycobacterial infection by performing Ziehl-Neelsen special stain. Polymerase chain reaction detected Mycobacterium tuberculosis in respiratory samples. Utilization of acid-fast special stains in all HIV-patients regardless of the histopathologic appearances, and the application of an appropriate panel of immunomarkers should help pathologists reach the correct diagnosis and avoid pitfalls. Without prior clinical knowledge, pathologists should raise this possibility in young patients with such unusual manifestations, because correct pathologic recognition is clinically important for the appropriate management of these vulnerable patients. | |
| 35432355 | Perspectives of JAK Inhibitors for Large Vessel Vasculitis. | 2022 | Vasculitis is an inflammation of the blood vessels caused by autoimmunity and/or autoinflammation, and recent advances in research have led to a better understanding of its pathogenesis. Glucocorticoids and cyclophosphamide have long been the standard of care. However, B-cell depletion therapy with rituximab has become available for treating antineutrophil cytoplasmic antibody-associated vasculitis (AAV). More recently, avacopan, an inhibitor of the complement 5a receptor, was shown to have high efficacy in remission induction against AAV. Thus, treatment options for AAV have been expanded. In contrast, in large vessel vasculitis (LVV), including giant cell arteritis and Takayasu arteritis, tocilizumab, an IL-6 receptor antagonist, was shown to be effective in suppressing relapse and has steroid-sparing effects. However, the relapse rate remains high, and other therapeutic options have long been awaited. In the last decade, Janus kinase (JAK) inhibitors have emerged as therapeutic options for rheumatoid arthritis (RA). Their efficacy has been proven in multiple studies; thus, JAK inhibitors are expected to be promising agents for treating other rheumatic diseases, including LVV. This mini-review briefly introduces the mechanism of action of JAK inhibitors and their efficacy in patients with RA. Then, the pathophysiology of LVV is updated, and a rationale for treating LVV with JAK inhibitors is provided with a brief introduction of our preliminary results using a mouse model. Finally, we discuss the newly raised safety concerns regarding JAK inhibitors and future perspectives for treating LVV. | |
| 35431170 | Current perspective of progressive-fibrosing interstitial lung disease. | 2022 Apr 14 | Interstitial lung disease (ILD) is a parenchymal lung disease and restrictive disorder that presents as diffuse infiltrative shadows. The initial diagnosis of ILD is important because management strategies depend on the disease pathogenesis. Connective-tissue disease (CTD)-associated ILD including rheumatoid arthritis (RA), systemic sclerosis (SSc) requires a thorough evaluation of chronic respiratory symptoms such as non-productive cough and exertional dyspnea, as well as physical findings. Moreover, myeloperoxidase-positive anti-neutrophilic cytoplasmic antibody (MPO-ANCA)-associated vasculitis with ILD also shows disease progression. In CTD-associated ILD, the first-line treatment is anti-inflammatory drugs such as prednisolone or immunosuppressants. In hypersensitivity pneumonitis (HP), detailed environmental history-taking is crucial. Therefore, systematic standardized questionnaires are needed. However, the causative antigens are often not identified in daily clinical practice. When an antigen is identified or suspected, the first action is avoidance. If antigen avoidance does not contribute to clinical improvement, anti-inflammatory drugs such as prednisolone might be introduced. Regarding sarcoidosis, while most patients do not require treatment for lung involvement, some need anti-inflammatory drugs or immunosuppressants. Additionally, steroid treatment should be considered for the critical status of extrapulmonary sarcoidosis including cardiac, neurogenic and ocular sarcoidosis. Once starting treatment for ILD, multi-dimensional approaches are applied, including symptom tracking, chest imaging, pulmonary function test (PFT), and 6-min walking test. Recently, the concept of progressive-fibrosing interstitial lung disease (PF-ILD) has been proposed as a new disease entity. The definition of PF-ILD includes symptom progression, PFT decline, and extension of chest high-resolution computed tomography (HRCT) findings. This mini-review describes the background, definition, clinical characteristics, management, and challenges of PF-ILD. | |
| 35199874 | Circulating inflammatory cell profiling and periodontitis: A systematic review and meta-an | 2022 May | Inflammation is a key driver of common noncommunicable diseases. Among common triggers of inflammation, chronic gingival inflammation (periodontitis) triggers a consistent humoral host inflammatory response, but little is known on its impact on circulating inflammatory cell profiles. We aimed to systematically appraise all the evidence linking periodontitis and its treatment to circulating inflammatory cell profiles. From 6 databases, 157 studies were eligible for qualitative synthesis and 29 studies for meta-analysis. Our meta-analysis showed that participants with periodontitis exhibited a significant mean increase in circulating CD4(+) , CD4(+) CD45RO(+) , IFNγ-expressing CD4(+) and CD8(+) T cells, CD19(+) CD27(+) and CD5(+) B cells, CD14(+) CD16(+) monocytes, and CD16(+) neutrophils but decrease in CD8(+) T and CD14(++) CD16(-) monocytes. Our qualitative synthesis revealed that peripheral blood neutrophils of patients with periodontitis consistently showed elevated production of reactive oxygen species (ROS) when compared with those of healthy controls. Some evidence suggested that the treatment of periodontitis reversed the exaggerated ROS production, but limited and inconclusive data were found on several circulating inflammatory cell profiling. We conclude that periodontitis and its treatment are associated with minor but consistent alterations in circulating inflammatory cell profiles. These changes could represent key mechanisms explaining the association of periodontitis with other comorbidities such as cardiovascular disease, diabetes, and rheumatoid arthritis. | |
| 35084317 | Histopathological changes of synovial tissue in rheumatoid arthritis patients treated with | 2022 Jan 25 | OBJECTIVES: To investigate the cell types that undergo apoptosis in TNF-α inhibitor (TNFI)- and IL-6 inhibitor (IL-6I)-treated synovia of RA patients, and to observe and compare histological changes in them. METHODS: Synovial tissue was collected during total knee arthroplasty from 20 RA patients who were divided into three groups based on RA treatment received: conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs, control group), TNFI, or IL-6I. Tissue samples were subjected to haematoxylin and eosin staining, terminal deoxynucleotidyl transferase fluorescein-deoxyuridine triphosphate nick end labelling (TUNEL), immuno-histochemistry (IHC) and immunofluorescence staining for, respectively, histopathological assessment, apoptosis detection and IHC evaluation and scoring. RESULTS: TUNEL-positive cells were detected surrounding the discoid fibrosis unique to the TNFI group, while those in the IL-6I group were distributed widely, especially surrounding the blood vessels. IHC revealed that in TNFI-treated tissue, CD86- and CD80-positive cells were detected only in the lining and sublining layer, while CD163- and CD206-positive cells were detected more broadly; in the IL-6I-treated tissue, all four were detected widely but their levels were lower than in the control group. Immunofluorescence also revealed macrophages mainly were the apoptotic cells in the lining and sublining layers of TNFI group. TUNEL Expression levels of CD20- and CD3-positive cells were remarkably lower in the IL-6I group, compared with the control and TNFI groups. CONCLUSIONS: TNFIs and IL-6Is target different action sites and synovial cell types, resulting in histopathological features of synovium distinct from one another. | |
| 34859718 | Effects and mechanisms of natural plant active compounds for the treatment of osteoclast-m | 2022 Apr | Bone-destructive diseases, caused by overdifferentiation of osteoclasts, reduce bone mass and quality, and disrupt bone microstructure, thereby causes osteoporosis, Paget's disease, osteolytic bone metastases, and rheumatoid arthritis. Osteoclasts, the only multinucleated cells with bone resorption function, are derived from haematopoietic progenitors of the monocyte/macrophage lineage. The regulation of osteoclast differentiation is considered an effective target for the treatment of bone-destructive diseases. Natural plant-derived products have received increasing attention in recent years due to their good safety profile, the preference of natural compounds over synthetic drugs, and their potential therapeutic and preventive activity against osteoclast-mediated bone-destructive diseases. In this study, we reviewed the research progress of the potential antiosteoclast active compounds extracted from medicinal plants and their molecular mechanisms. Active compounds from natural plants that inhibit osteoclast differentiation and functions include flavonoids, terpenoids, quinones, glucosides, polyphenols, alkaloids, coumarins, lignans, and limonoids. They inhibit bone destruction by downregulating the expression of osteoclast-specific marker genes (CTSK, MMP-9, TRAP, OSCAR, DC-STAMP, V-ATPase d2, and integrin av3) and transcription factors (c-Fos, NFATc1, and c-Src), prevent the effects of local factors (ROS, LPS, and NO), and suppress the activation of various signalling pathways (MAPK, NF-κB, Akt, and Ca(2+)). Therefore, osteoclast-targeting natural products are of great value in the prevention and treatment of bone destructive diseases. | |
| 34850406 | Upgrade of an old drug: Auranofin in innovative cancer therapies to overcome drug resistan | 2022 May | Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthritis. Currently, Auranofin is under investigation for oncological application within a drug repurposing plan due to the relevant antineoplastic activity observed both in vitro and in vivo tumor models. In this review, we analysed studies in which Auranofin was used as a single drug or in combination with other molecules to enhance their anticancer activity or to overcome chemoresistance. The analysis of different targets/pathways affected by this drug in different cancer types has allowed us to highlight several interesting targets and effects of Auranofin besides the already well-known inhibition of thioredoxin reductase. Among these targets, inhibitory-κB kinase, deubiquitinates, protein kinase C iota have been frequently suggested. To rationalize the effects of Auranofin by a system biology-like approach, we exploited transcriptomic data obtained from a wide range of cell models, extrapolating the data deposited in the Connectivity Maps website and we attempted to provide a general conclusion and discussed the major points that need further investigation. | |
| 34229081 | TNF-α: The shape of small molecules to come? | 2022 Jan | In 2020, the anti-tumor necrosis factor (TNF) monoclonal antibody Humira® generated US$165.8 billion in cumulative sales and snatched the crown for the industry's most successful drug from Lipitor (atorvastatin). TNF-α is a major component in beneficial and disease-related inflammation and TNF-α-inhibitor biologics have gained widespread use in autoimmune diseases, such as rheumatoid arthritis (RA). Many more diseases could benefit from TNF-α inhibitors, such as Alzheimer's disease (AD) or major depression. However, the nature of TNF-α-inhibitor biologics prohibits central nervous system (CNS) applications. Moreover, high drug production costs and pricing, together with antidrug immune reactions and insufficient patient coverage, argue for the development of small-molecule drugs. Recently, drug-like orally available small molecules were described with high activity in animal disease models with activities comparable to those of antibodies. | |
| 34847389 | Specialized pro-resolving receptors are expressed in salivary glands with Sjögren's syndr | 2022 Feb | Our previous studies demonstrated that resolvin D1 (RvD1) and its aspirin-trigged (AT) form AT-RvD1, are effective in decreasing inflammation while restoring saliva flow rates in a Sjögren's syndrome (SS)-like mouse model before and after disease onset. Resolvins are specialized pro-resolving mediators (SPM) that actively regulate inflammation. However, we only have extensive data within the salivary glands for RvD1 and AT-RvD1, both of which bind to the receptor ALX/FPR2. As such, the presence of other SPM receptors is unknown within salivary glands. Therefore, the goal of this study was to determine the expression of SPM receptors in non-SS and SS patients. For this purpose, six human minor salivary glands from female subjects were analyzed by H&E using the Chisholm and Mason classification to determine the degree of lymphocytic infiltration. Next, confocal immunofluorescence analysis was performed to determine the presence and distribution of different SPM receptors in mucous acini and striated ducts. We observed diffuse presence of lymphocytic infiltration and clinical data were consistent with SS diagnosis in three patients. Moreover, confocal immunofluorescence analysis indicated the presence of the receptors ALX/FPR2, BLT1 and CMKLR1 in the mucous acini and striated ducts of both non-SS and SS patients. GPR32 was absent in SS and non-SS minor salivary glands. In summary, our results showed that various SPM receptors are expressed in non-SS and SS minor salivary glands, all of which may pose as potential targets for promoting pro-epithelial and anti-inflammatory/pro-resolution signaling on SS patients. |