Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35341670 | Translational advances of melanocortin drugs: Integrating biology, chemistry and genetics. | 2022 Mar 24 | Melanocortin receptors have emerged as important targets with a very unusual versatility, as their widespread distribution on multiple tissues (e.g. skin, adrenal glands, brain, immune cells, exocrine glands) together with the variety of physiological processes they control (pigmentation, cortisol release, satiety mechanism, inflammation, secretions), place this family of receptors as genuine therapeutic targets for many disorders. This review focuses in the journey of the development of melanocortin receptors as therapeutic targets from the discovery of their existence in the early 1990Â s to the approval of the first few drugs of this class. Two major areas of development characterise the current state of melanocortin drug development: their role in obesity, recently culminated with the approval of setmelanotide, and their potential for the treatment of chronic inflammatory and autoimmune diseases like rheumatoid arthritis, multiple sclerosis or fibrosis. The pro-resolving nature of these drugs offers the advantage of acting by mimicking the way our body naturally resolves inflammation, expecting fewer side effects and a more balanced (i.e. non-immunosuppressive) response from them. Here we also review the approaches followed for the design and development of novel compounds, the importance of the GPCR nature of these receptors in the process of drug development, therapeutic value, current challenges and successes, and the potential for the implementation of precision medicine approaches through the incorporation of genetics advances. | |
| 35192926 | Repurposing of the gold drug auranofin and a review of its derivatives as antibacterial th | 2022 Feb 19 | Multidrug resistance (MDR) is a significant issue associated with the clinical application of antibiotics. It is also challenging to discover and develop new antibiotics with novel scaffolds. Therefore, the repurposing of existing drugs has become a promising strategy for antibiotic drug discovery. Auranofin, an approved gold metallic drug, has been used for the treatment of rheumatoid arthritis (RA) for many years. Recent research revealed that auranofin has strong antibacterial activity against multiple Gram-positive bacteria by inhibiting thioredoxin reductase (TrxR). These results inspired the development of gold complexes as antibacterial agents. Herein, we discuss recent advances in the development of auranofin and other gold complexes as antibacterial agents, providing a new viewpoint for the treatment of bacterial infection. | |
| 35112322 | Meningoencephalitis caused by Fusarium proliferatum: an unusual case. | 2022 Feb 3 | Meningoencephalitis can be a diagnostic dilemma and one of its etiology are infectious causes including fungal agents. Fusarium species have attracted much attention as one of the invasive fungal infections. Major clinical manifestations of infections due to Fusarium spp. are broad such as keratitis, endophthalmitis, sino-pulmonary and central nervous system (CNS) infections. However, CNS fusariosis is rare and often happens due to hematogenous dissemination from other sites. Herein, we describe an unusual case of meningoencephalitis caused by Fusarium proliferatum, in a patient with rheumatoid arthritis. | |
| 35054813 | Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases. | 2022 Jan 6 | Interleukin (IL)-24 belongs to the IL-10 family and signals through two receptor complexes, i.e., IL-20RA/IL-20RB and IL-20RB/IL22RA1. It is a multifunctional cytokine that can regulate immune response, tissue homeostasis, host defense, and oncogenesis. Elevation of IL-24 is associated with chronic inflammation and autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Its pathogenicity has been confirmed by inducing inflammation and immune cell infiltration for tissue damage. However, recent studies also revealed their suppressive functions in regulating immune cells, including T cells, B cells, natural killer (NK) cells, and macrophages. The tolerogenic properties of IL-24 were reported in various animal models of autoimmune diseases, suggesting the complex functions of IL-24 in regulating autoimmunity. In this review, we discuss the immunoregulatory functions of IL-24 and its roles in autoimmune diseases. | |
| 35044659 | Zymography and Reverse Zymography for Testing Proteases and Their Inhibitors. | 2022 | Zymography is a powerful technique for the assay of different hydrolases that act upon any biological macromolecule. In particular, zymography is used to assay the activities of serine proteases, e.g., matrix metalloproteinases (MMPs), and reverse zymography is used for tissue inhibitors of metalloproteinases (TIMPs) in multifarious experimental samples. Zymography is a method of electrophoretic separation of proteases under non-reducing conditions in a polyacrylamide gel containing substrate. The resolved proteins are renatured by exchange of the anionic detergent with a nonionic one, and the gel is incubated in a specific buffer for the specific proteases. After staining the gel by Coomassie blue staining solution, the proteolytic activities are visualized as clear colorless bands against a dark background. In contrast, reverse zymography is a parallel technique to detect protease inhibitors. In addition to substrate gelatin, proteases (i.e., MMPs) are also incorporated in proper ratio into the polyacrylamide gel. After electrophoresis, during the developing step, the MMPs specifically digest the substrate in regions where TIMPs are absent. Thus, inhibitors/TIMP is represented as dark zones of inhibition against a transparent background after staining. In this chapter, common troubleshoots during sample preparation, running zymography, and data interpretation are discussed. Notes are specified to enhance the sensitivity of the methods. In conclusion, zymography could be crucial for enzyme assay at the nanogram level and for the improvement of new investigative techniques for diseases such as endometriosis, rheumatoid arthritis, osteoarthritis, tumor invasion, and inflammation. | |
| 35016227 | Multifocal Oral Epstein-Barr Virus-Positive Mucocutaneous Ulcers Associated with Dual Meth | 2022 Jan 11 | Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unique clinicopathologic entity of lymphoproliferative disorder, occurring in immunosuppressed patients. Due to its rarity, EBVMCU may be under-recognized by clinicians as well as pathologists. In addition, its clinical and histopathologic features overlap with other benign and malignant conditions, making a diagnosis challenging. This report presents an unusual case of multifocal oral EBVMCUs in a 52-year-old female patient with rheumatoid arthritis, receiving the combination of methotrexate and leflunomide for 5 years. The patient presented with persistent multiple large painful ulcers involving her palate and gingiva for 6 months. The histopathologic examination revealed extensive ulceration with diffuse polymorphic inflammatory infiltrate admixed with scattered atypical lymphoid cells showing occasional Hodgkin and Reed/Sternberg-like cell features. These atypical cells showed immunoreactivity for CD20, CD30 and MUM1/IRF4. EBV-encoded small RNA in situ hybridization was positive, validating the presence of EBV-infected cells. Two months after discontinuation of both immunosuppressive medications, oral lesions gradually regressed. At 9-month follow-up, no evidence of relapsing oral EBVMCU has been observed. The multifocal presentation of EBVMCU is rare and could be resulted from the overwhelming immune suppression by long-term use of dual immunosuppressants. Its diagnosis requires comprehensive correlation of patient history, clinical findings, histopathologic, and immunophenotypic features. The ability of EBVMCU to regress following removal of immunosuppressive causes is in drastic contrast to a variety of its potential clinical and histopathologic mimics. Therefore, accurate diagnosis is crucial to avoid unnecessary patient management and achieve optimal patient outcomes. | |
| 34962287 | B-cell modulation with anti-CD79b antibodies ameliorates experimental autoimmune encephali | 2022 Apr | B cells play a major role in the pathogenesis of many autoimmune diseases like MS, rheumatoid arthritis, or systemic lupus erythematosus. Depletion of B cells with anti-CD20 antibodies is an established therapy for MS. However, total B-cell depletion will also affect regulatory B cells that are known to suppress autoimmune responses. In our studies, we describe an alternative approach based on targeting CD79b that induces only partial B-cell depletion and achieves therapeutic effects by B-cell modulation. Prophylactic and therapeutic treatment with an antibody against CD79b and also a deglycosylated variant of this antibody, lacking effector function like antibody-dependent cellular cytotoxicity or complement activation, significantly reduced the development and progression of EAE in mice. Our data show that modulation of B cells via CD79b is equally effective as almost complete B-cell depletion with anti-CD20 antibodies and may constitute an alternative approach to treat MS. | |
| 34226164 | Chronic inflammatory diseases and coronary heart disease: Insights from cardiovascular CT. | 2022 Jan | Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states. | |
| 31725491 | PSEUDOMONAL CHOROIDAL ABSCESS AFTER ROUTINE PARS PLANA VITRECTOMY IN AN IMMUNOSUPPRESSED P | 2022 Mar 1 | PURPOSE: To describe an unusual case of pseudomonal choroidal abscess which developed after a routine pars plana vitrectomy in an immunosuppressed patient. METHODS: Case report. A 61-year-old woman with a history of rheumatoid arthritis and ulcerative colitis on abatacept underwent pars plana vitrectomy. A few days after the patient's operation, a partially serous choroidal detachment was identified. Her choroidal detachment increased in size despite prednisone therapy, and she was taken to the operating room for repeat vitrectomy and choroidal drainage. Intraoperatively, there was no significant intraocular inflammation, but purulent whitish material was expressed during external choroidal drainage which grew Pseudomonas aeruginosa. RESULTS: The patient was given intravenous antibiotics. Systemic infectious workup was negative for blood and urine cultures. The patient was transitioned to oral antibiotics, but had persistent eye pain after discharge and vision remained at count fingers. A computed tomography orbit scan with contrast showed persistent choroidal abscess, and intravitreal ceftazidime injections were administered. The patient's subjective pain resolved within several days of the first intravitreal injection; repeat ultrasound also showed interval resolution of the choroidal elevation. One year after the resolution of her choroidal abscess, her visual acuity was Snellen 20/250 in the affected eye. CONCLUSION: Isolated choroidal bacterial abscess is a possible, but rare, complication of pars plana vitrectomy. Although visual prognosis is poor, especially for pseudomonal choroidal abscesses, aggressive treatment with timely choroidal drainage, systemic antibiotics, and intravitreal antibiotics may allow recovery of some ambulatory vision. | |
| 35569786 | The crucial mechanism and therapeutic implication of RNA methylation in bone pathophysiolo | 2022 May 13 | Methylation is the most common posttranscriptional modification in cellular RNAs, which has been reported to modulate the alteration of RNA structure for initiating relevant functions such as nuclear translocation and RNA degradation. Recent studies found that RNA methylation especially N6-methyladenosine (m(6)A) regulates the dynamic balance of bone matrix and forms a complicated network in bone metabolism. The modulation disorder of RNA methylation contributes to several pathological bone diseases including osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), and so on. In the review, we will discuss advanced technologies for detecting RNA methylation, summarize RNA methylation-related biological impacts on regulating bone homeostasis and pathological bone diseases. In addition, we focus on the promising roles of RNA methylation in early diagnosis and therapeutic implications for bone-related diseases. Then, we aim to establish a theoretical basis for further investigation in this meaningful field. | |
| 35526815 | Operative Technique for Resection of a Ventral Trans-Dural Retro-Odontoid Pannus: A 2-Dime | 2022 May 5 | Retro-odontoid pseudotumors are rare inflammatory complications of atlantoaxial instability often associated with cervical degenerative disease and rheumatoid arthritis. While propagation of these lesions has been shown to cause spinal cord compression and cervical myelopathy, intradural extension has rarely been reported. In this manuscript and two-dimensional illustrative intra-operative video, we demonstrate cervical decompression, removal of the intradural component, and stabilization with C1-2 instrumentation utilizing a posterior approach. A 71 year old patient presented with progressive cervical myelopathy. Preoperative imaging demonstrated a large retro-odontoid pannus causing severe spinal cord compression and an associated contrast-enhancing intradural lesion, in the absence of obvious C1-2 instability or fractures on CT scan. C1-2 posterior decompression and fusion were performed with maximally safe intradural pannus resection and ventral dural reconstruction. Postoperatively, the patient experienced significant improvement in myelopathic symptoms. Imaging demonstrated good spinal cord decompression with complete intradural pannus resection and debulking of the extradural component. Our outcome in this rare complication suggests a posterior approach may be effective in treating similar patients. | |
| 35343656 | Acacia arabica (Lam.) Willd. On osteoblastogenesis, osteoblast proliferation, osteoclastic | 2022 Mar 29 | BACKGROUND: Since ancient times Acacia arabica (Lam.) Willd. (AA) consumed for the bone and muscle related disorder like the bone fracture, rheumatoid arthritis, and bone loss. OBJECTIVES: To study the effects of the aqueous (AAA) and ethanolic extract (AAE) of AA on osteoblast proliferation and differentiation, osteoclastic activity and bone matrix mineralization using in vitro primary bone-marrow cultures. MATERIAL AND METHODS: : Effect of AAA and AAE was estimated using four in vitro assays. Primary bone marrow cell culture, isolated from rat femur bone, was used for all the assays. Cell growth and viability were assessed by standard colorimetric assays like MTT assay. The differentiation of mesenchymal stem cells into osteoblastic lineage was evaluated by the measuring the levels of the osteoblast-specific marker, alkaline phosphatase. Antiosteoclastic action and matrix mineralization were measured using TRAP assay and Alizarin red-s staining assay, respectively. RESULTS: It indicates that AAA causes more increase in osteoblast differentiation and a reduction in osteoclast activity as compared to AAE. In osteoblast proliferation assay, AAA was found to promote more cell proliferation as compared to AAE. Higher concentrations of AAA significantly increased mineralization of bone-like matrix. CONCLUSIONS: The extracts of AA have a significant positive influence on osteogenesis and they inhibit osteoclastogenesis. Hence, these extracts have the potential to be developed as a therapy for osteoporosis. | |
| 35242406 | Chronic atlantoaxial rotatory fixation with neurofibromatosis type I: A case report. | 2022 | BACKGROUND: Atlantoaxial rotatory fixation (AARF) can be caused by infection, rheumatoid arthritis, surgery of head and neck, and congenital diseases. Type 1 neurofibromatosis (NF-1) is often associated with various musculoskeletal diseases, but few reports have described AARF with NF-1. Here, we report the success of a closed reduction and halo fixation utilized to treat chronic AARF with NF-1 in a 7-year-old female. CASE DESCRIPTION: A 7-year-old female with NF-1 presented with a 2-month history of torticollis and neck pain. C2 facet deformity had previously been identified on computed tomography (CT) before the onset of neck pain. Cervical radiography and CT showed AARF classified Fielding's Type I and Ishii's Grade II. Following 2 weeks of cervical traction, a closed reduction was followed by halo fixation that was utilized for 2 months. The patient fully recovered cervical range of motion following halo vest removal 4 months later. Further, the follow-up CT documented a normal atlantoaxial joint despite residual C2 facet deformity. In addition, no recurrence was evident 2 years later. CONCLUSION: Halo fixation for chronic AARF with NF-1 proved effective. C2 facet deformity associated with NF-1 might have contributed to the onset of AARF. | |
| 35228033 | An overview of immune checkpoint therapy in autoimmune diseases. | 2022 Jun | Immune checkpoint receptors are critical regulators of initiation and termination of effective immune responses as well as maintain self-tolerance. Since the successful use of immune checkpoint inhibitors in cancer immunotherapy, they gained huge interest to be used in autoimmune diseases treatment. Indeed, abatacept (CTLA4-Ig), as immune checkpoint inhibitors has made major advancement in the treatment of rheumatoid arthritis patients who have failed to respond to csDMARDs or TNF-α inhibitor. Over the past decade, an increasing number of new immune checkpoints have been detected and lots of investigations are in progress to address their potential as possible targets of effective novel immunotherapy. Here we focus on the biological functions and structures of these immune checkpoints, their pharmacological mechanisms, pathogenesis, therapeutic effects, and their related adverse events. We also discuss the application of agonistic or antagonistic agents targeting co-inhibitory or co-stimulatory checkpoints for the treatment of autoimmune diseases. Furthermore, we summarize previous and recent clinical trials utilizing these immune checkpoints in autoimmune diseases. Obviously, the characterization of such processes might help to develop more effective therapeutic agents in the future. | |
| 33539089 | Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections. | 2022 Jan 27 | Kinases are a group of therapeutic targets involved in the progression of numerous diseases, including cancer, rheumatoid arthritis, Alzheimer's disease, and viral infections. The majority of approved antiviral agents are inhibitors of virus-specific targets that are encoded by individual viruses. These inhibitors are narrow-spectrum agents that can cause resistance development. Viruses are dependent on host cellular proteins, including kinases, for progression of their life-cycle. Thus, targeting kinases is an important therapeutic approach to discovering broad-spectrum antiviral agents. As there are a large number of FDA approved kinase inhibitors for various indications, their repurposing for viral infections is an attractive and time-sparing strategy. Many kinase inhibitors, including baricitinib, ruxolitinib, imatinib, tofacitinib, pacritinib, zanubrutinib, and ibrutinib, are under clinical investigation for COVID-19. Herein, we discuss FDA approved kinase inhibitors, along with a repertoire of clinical/preclinical stage kinase inhibitors that possess antiviral activity or are useful in the management of viral infections. | |
| 35636449 | Tranexamic Acid and Its Potential Anti-Inflammatory Effect: A Systematic Review. | 2022 May 30 | Tranexamic acid (TXA) is an antifibrinolytic drug primarily used for reducing blood loss in patients with major bleedings. Animal and cell studies have shown that TXA might modulate the inflammatory response by either enhancing or inhibiting cytokine levels. Furthermore, recent human studies have found altered inflammatory biomarkers in patients receiving TXA when compared with patients who did not receive TXA. In this systematic review we investigated the effect of TXA on inflammatory biomarkers in different patient groups. A systematic literature search was conducted on the databases PubMed and Embase to identify all original articles that investigated inflammatory biomarkers in patients receiving TXA and compared them to a relevant control group. The review was performed according to the PRISMA guidelines, and the literature search was performed on November 29, 2021. Thirty-three studies were included, among which 14 studies compared patients receiving TXA with patients getting no medication, another 14 studies investigated different dosing regimens of TXA, and finally five studies examined the administration form of TXA. The present review suggests that TXA has an anti-inflammatory effect in patients undergoing orthopaedic surgery illustrated by decreased levels of C-reactive protein and interleukin-6 in patients receiving TXA compared with patients receiving no or lower doses of TXA. However, the anti-inflammatory effect was not found in patients undergoing cardiac surgery, pediatric craniosynostosis patients, or in rheumatoid arthritis patients. The inflammatory response was not affected by administration form of TXA (oral, intravenous, or topical). In conclusion, an anti-inflammatory effect of TXA was consistently found among orthopaedic patients only. | |
| 35566283 | Procyanidins and Their Therapeutic Potential against Oral Diseases. | 2022 May 4 | Procyanidins, as a kind of dietary flavonoid, have excellent pharmacological properties, such as antioxidant, antibacterial, anti-inflammatory and anti-tumor properties, and so they can be used to treat various diseases, including Alzheimer's disease, diabetes, rheumatoid arthritis, tumors, and obesity. Given the low bioavailability of procyanidins, great efforts have been made in drug delivery systems to address their limited use. Nowadays, the heavy burden of oral diseases such as dental caries, periodontitis, endodontic infections, etc., and their consequences on the patients' quality of life indicate a strong need for developing effective therapies. Recent years, plenty of efforts are being made to develop more effective treatments. Therefore, this review summarized the latest researches on versatile effects and enhanced bioavailability of procyanidins resulting from innovative drug delivery systems, particularly focused on its potential against oral diseases. | |
| 35217873 | Tofacitinib Treatment in Primary Herpes Simplex Encephalitis Interferes With Antiviral Res | 2022 May 4 | Tofacitinib, a Janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis. Herpes simplex virus type 1 (HSV-1) may cause encephalitis during primary infection or following reactivation from a latent state. Long-term tofacitinib treatment may increase the risk of this life-threatening condition. The aim of this study was to investigate the effect of tofacitinib on HSV-1 primary infection using a mouse model. Mice pretreated with tofacitinib were intranasally infected with a clinical strain of HSV-1 and monitored for infection severity and antiviral response. Tofacitinib treatment of HSV-1 primary infection resulted in increased viral loads and worsened clinical outcome. Furthermore, tofacitinib promoted M2 anti-inflammatory phenotype of microglia and infiltrating monocytes, as well as inhibited production of inflammatory and antiviral cytokines by macrophages in vitro. Our findings show that treatment with tofacitinib increases severity of herpes simplex encephalitis in mice, by impairing antiviral response induced by monocytes and microglia. | |
| 35146402 | Pharmacological blockade of KV1.3 channel as a promising treatment in autoimmune diseases. | 2022 | There are more than 100 autoimmune diseases (AD), which have a high prevalence that ranges between 5% and 8% of the general population. Type I diabetes mellitus, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis remain the health problem of highest concern among people worldwide due to its high morbidity and mortality. The development of new treatment strategies has become a research hotspot. In recent years, the study of the ion channels presents in the cells of the immune system, regarding their functional role, the consequences of mutations in their genes and the different ways of blocking them are the subject of intense research. Pharmacological blockade of KV1.3 channel inhibits Ca2+ signaling, T cell proliferation, and pro-inflammatory interleukins production in human CD4(+) effector memory T cells. These cells mediated most of the AD and their inhibition is a promising therapeutic target. In this review, we will highlight the biological function of KV1.3 channel in T cells, consequence of the pharmacological inhibition (through anemone and scorpion toxins, synthetic peptides, nanoparticles, or monoclonal antibodies) as well as the possible therapeutical application in AD. | |
| 35145499 | "Osteomicrobiology": The Nexus Between Bone and Bugs. | 2021 | A growing body of scientific evidence supports the notion that gut microbiota plays a key role in the regulation of various physiological and pathological processes related to human health. Recent findings have now established that gut microbiota also contributes to the regulation of bone homeostasis. Studies on animal models have unraveled various underlying mechanisms responsible for gut microbiota-mediated bone regulation. Normal gut microbiota is thus required for the maintenance of bone homeostasis. However, dysbiosis of gut microbiota communities is reported to be associated with several bone-related ailments such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Dietary interventions in the form of probiotics, prebiotics, synbiotics, and postbiotics have been reported in restoring the dysbiotic gut microbiota composition and thus could provide various health benefits to the host including bone health. These dietary interventions prevent bone loss through several mechanisms and thus could act as potential therapies for the treatment of bone pathologies. In the present review, we summarize the current knowledge of how gut microbiota and its derived microbial compounds are associated with bone metabolism and their roles in ameliorating bone health. In addition to this, we also highlight the role of various dietary supplements like probiotics, prebiotics, synbiotics, and postbiotics as promising microbiota targeted interventions with the clinical application for leveraging treatment modalities in various inflammatory bone pathologies. |