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ID PMID Title PublicationDate abstract
30035185 Exosomes: mediators of bone diseases, protection, and therapeutics potential. 2018 May Bone remodeling is a continuous lifelong process in the repair of micro-damage to bone architecture and replacement of aging tissue in bone. A failure to such process leads to pathological destructive bone diseases such as osteoporosis, rheumatoid arthritis, and osteoarthritis. However, this active process is regulated by; osteoclasts, which are involved in the bone resorption process; osteoblasts, with involvement in the bone formation process and bone-derived endothelial cells, which promote angiogenesis. In the bone micro-environment, these cellular interactions are mediated by a complex interplay between cell types via direct interaction of cell secreted growth factors, such as cytokines. Recently, the discovery of exosomes (∼ 40-100 nm in size), has attracted more attention in the field of the bone remodeling process. Exosomes and microvesicles are derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, osteoclasts and their precursors. They are also recognized to play pivotal roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. In this review, we especially emphasize the origin and biogenesis of exosomes and bone cell derived exosomes in the regulatory process of bone remodeling. Moreover, this review article also focuses on exosomal secreted proteins and microRNAs and their involvement in the regulation of bone remodeling.
29997500 Molecular Mechanisms of T Cells Activation by Dendritic Cells in Autoimmune Diseases. 2018 The interaction between T cell and dendritic cells (DCs) that leads to T cell activation affects the progression of the immune response including autoimmune diseases. Antigen presentation on immune cell surface, formation of an immunological synapse (IS), and specific identification of complex by T cells including two activating signals are necessary steps that lead to T cell activation. The formation of stimulatory IS involves the inclusion of costimulatory molecules, such as ICAM-1/LFA-1 and CD28/B7-1, and so on. Some fusion proteins and monoclonal antibodies targeting costimulatory molecules have been developed and approved to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (T1D), inflammatory bowel disease (IBD), and psoriasis. These biological agents, including CTLA-4- and LFA-3-Ig, anti-CD3 monoclonal antibody, could prevent the successful engagement of DCs by T cell with significant efficacy and safety profile. In this article, we reviewed the molecular mechanisms of T cell activation during the interaction between T cells and DCs, and summarized some biological agents that target costimulatory molecules involved in the regulation of T cell activation.
29805352 Hemophagocytic Lymphohistiocytosis Secondary to Unknown Underlying Hodgkin Lymphoma Presen 2018 Jan Hemophagocytic lymphohistiocytosis (HLH) is an uncommon disease that often presents with nonspecific findings. A high index of suspicion is necessary to make a prompt diagnosis and prevent fatal disease. A 45-year-old man presented with fever, hypotension, abdominal pain, nausea, and vomiting. Imaging showed hepatosplenomegaly and laboratory tests revealed pancytopenia, increased ferritin, and a cholestatic pattern of injury with elevated alkaline phosphatase and total bilirubin. Due to a history of Crohn disease, systemic lupus erythematous, and rheumatoid arthritis, the patient was on immunosuppressants, including infliximab. After multiple negative cultures, persistent fever, and days of empiric broad spectrum antibiotics, our differential shifted to fever of unknown origin. A liver wedge biopsy revealed areas of sinusoidal dilatation with enlarged, activated macrophages containing erythrocytes and intracytoplasmic iron, consistent with hemophagocytosis due to HLH. The portal tracts showed mixed lymphoplasmacytic inflammation, a prominent bile ductular reaction, periportal fibrosis, and scattered large cells with occasional binucleation and prominent nucleoli. These cells stained positive for Epstein-Barr virus encoding region in situ hybridization, PAX5, CD15, and CD30, and hepatic involvement by classic Hodgkin lymphoma was diagnosed and determined to be the cause of the HLH and cholestatic pattern of injury. Simultaneously, a bone marrow biopsy showed diffuse involvement by Hodgkin lymphoma with a similar staining pattern. Aggressive treatment failed and the patient succumbed to multiorgan failure. HLH is a rare, potentially fatal disease, with nonspecific signs and symptoms, and should be considered in any patient presenting with fever and pancytopenia, especially if they are immune compromised.
29559215 Casticin from Vitex species: a short review on its anticancer and anti-inflammatory proper 2018 May This short review provides an update of the anticancer and anti-inflammatory properties of casticin from Vitex species. Casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups and four methoxyl groups. Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia, aerial parts and seeds of V. agnus-castus and leaves of V. negundo. Studies have reported the antiproliferative and apoptotic activities of casticin from Vitex species. The compound is effective against many cancer cell lines via different molecular mechanisms. Studies have also affirmed the anti-inflammatory properties of casticin, with several molecular mechanisms identified. Other pharmacological properties include anti-asthmatic, tracheospasmolytic, analgesic, antihyperprolactinemia, immunomodulatory, opioidergic, oestrogenic, anti-angiogenic, antiglioma, lung injury protection, rheumatoid arthritis amelioration and liver fibrosis attenuation activities. Clinical trials and commercial use of the casticin-rich fruit extract of V. agnus-castus among women with premenstrual syndrome were briefly discussed.
29558225 Bioactivity and pharmacological properties of α-mangostin from the mangosteen fruit: a re 2018 May INTRODUCTION: α-Mangostin (α-MG) is the most representative xanthone isolated from the pericarp of mangosteen, possessing extensive biological activities and pharmacological properties, considered as an antineoplastic agent, antioxidant, anti-proliferation and induces apoptosis. AREAS COVERED: The bioactivity and pharmacological properties of α-MG are being actively investigated by various industrial and academic institutions. The bioactivities of α-MG have been summarized in several previous reviews, which were worthy of high compliment. However, recently, many new literatures about the bioactivities of α-MG have been further reported from 2016 to 2017. Herein, the activities of α-MG are supplemented and summarized in this text. EXPERT OPINION: As previously said, α-MG possesses good bioactivities pharmacological properties. More recently, it found that α-MG has the effect of maintaining cardiovascular system and gastrointestinal health and controlling free radical oxidation. Furthermore, α-MG has more applications in cosmetics, with the effects of anti-aging, anti-wrinkle, acne treatment, maintenance of skin lubrication. The application of α-MG in treating rheumatoid arthritis has been disclosed and the MG-loaded self-micro emulsion (MG-SME) was designed to improve its pharmacokinetic deficiencies. As mentioned above, α-MG can be a promising drug, also worthy of developing, and further research is crucial for the future application of α-MG.
29453041 MicroRNA signature of regulatory T cells in health and autoimmunity. 2018 Apr MicroRNAs (miRNAs) are small RNA molecules with regulatory functions on the expression of genes through binding directly to target messenger RNA (mRNA) transcripts, eventuating in gene expression suppression via translational hindrance and/or target mRNA cleavage. These molecules have been established to participate in numerous critical cellular settings, including differentiation, development, and function of immune cells. As an important suppressor cell of immune system, regulatory T cells (Tregs) are important in modulating the immune homeostasis as well as tolerance to self-antigens. Despite identification of numerous transcription factors, cytokines, and other mediators regulate the biology of Tregs, investigations have demonstrated that noncoding RNAs are involved in several mechanisms of the regulation of Treg cells. On the other side, dysregulation of expression of several miRNAs has been reported in Tregs, implicating to the impaired function of these regulatory cells, resulting in autoimmune and other immune-based disorders. In this review, we aim to go through the overall microRNA network and specific miRNAs that are involved in the development, differentiation, and function of Tregs. Moreover, an overview was provided with respect to the role of aberrant expression of miRNAs in Tregs of autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, diabetes, and psoriasis.
29334503 Family history of autoimmune diseases and risk of gastric cancer: a national cohort study. 2018 May A personal history of autoimmune diseases is associated with an increased incidence of gastric cancer, but whether they share familial susceptibility is still unknown. The contribution of shared environmental or genetic factors toward the observed familial aggregation has not been determined. We used a few Swedish registers, including the Swedish Multigeneration Register and the Cancer Register, to examine the familial risk of gastric cancer among individuals with a family history of a set of autoimmune diseases. Standardized incidence ratios were used to calculate the relative risk. The overall risk of gastric cancer was 1.22 (95% confidence interval: 1.14-1.30) among individuals with a sibling affected with any of the 33 autoimmune diseases. For specific disease, siblings of individuals with Crohn's diseases, diabetes type 1, Graves'/hyperthyroidism, myasthenia gravis, psoriasis, rheumatoid arthritis, sarcoidosis, and uncreative colitis showed an association with an increased incidence of gastric cancer, with a standardized incidence ratio ranging between 1.17 and 1.64. Familial aggregation was found only for corpus cancer. No association was observed between spouses. Gastric cancer, mainly corpus cancer, shares familial susceptibility with a few autoimmune diseases, suggesting that shared genetic polymorphisms may contribute toward both Helicobacter pylori infection and autoimmune diseases.
28669338 MicroRNA Key to Angiogenesis Regulation: MiRNA Biology and Therapy. 2018 Angiogenesis is involved in maintaining normal physiological processes like embryonic development, wound healing, inflammation and reproduction. Pathogenesis of various diseases like diabetic retinopathy, rheumatoid arthritis and cancer are associated with imbalanced angiogenesis. Angiogenic stimulators and inhibitors act together for keeping angiogenic switch in balance. Recently, miRNAs have been found to regulate various stages of angiogenesis. miRNAs are 21-23 nucleotides long, single stranded, noncoding RNA molecules generated endogenously. miRNA's ability to target multiple genes within a signaling pathway makes them promising target for the development of second generation anti-angiogenesis drugs. This review was conceived with the notion of availability of specific and comprehensive knowledge about AngiomiRs at one place. This will facilitate the research in basic understanding and in the development of new drugs. In this review, we have summarized the biology and therapeutic potential of the miRNAs, which are involved in controlling angiogenesis process. In miRNA biology, we have provided the updated summary of miRNAs in the regulation of endothelial cells, showed role of miRNAs in the signaling pathways of angiogenesis and, discussed the gaps in complete knowledge of mechanism. We have also provided exclusive insights regarding therapeutic potential of these miRNAs, in angiogenesis related disorders. Additionally, we have discussed the challenges in miRNA based drug delivery and updated the current efforts in the development of miRNA delivery methods. Though much research is needed to discover the complete miRNA network regulating angiogenesis but once it is done, targeting miRNA may be considered as a potential candidate for therapeutic invention against angiogenesis related disorders.
30670225 Hot sand baths (psammotherapy): A systematic review. 2019 Feb INTRODUCTION: Psammotherapy is a traditional practice in which hot sand baths are employed for therapeutic purposes. This systematic review aims to investigate the potential efficacy of psammotherapy in the treatment of any disease. METHODS: Medline via PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar were searched for articles describing studies on the efficacy of psammotherapy in patients with different health conditions. Articles were screened by the two author independently and, in case of disagreements, items were discussed until consensus was reached. All relevant clinical outcomes (symptom and pain relief, modifications in any functional and laboratory parameter, changes in drug consumption, variations of quality of life) were extracted from included studies. RESULTS: After article screening and selection, three studies were included in the review. One study involved patients with chronic obstructive pulmonary disease, while in the other two studies patients with rheumatoid arthritis were recruited. Included trials indicate that psammotherapy might be useful for the management of studied diseases. DISCUSSION: Based on available data, no conclusions can be driven on the clinical efficacy of psammotherapy. However, very limited evidence suggests that hot sand baths might be useful in improving symptoms and functionality of patients with some rheumatic and respiratory chronic illnesses. Further studies are encouraged to better assess the clinical efficacy of hot sand baths.
30613282 Rho-Associated Coiled-Coil Kinase (ROCK) in Molecular Regulation of Angiogenesis. 2018 Identified as a major downstream effector of the small GTPase RhoA, Rho-associated coiled-coil kinase (ROCK) is a versatile regulator of multiple cellular processes. Angiogenesis, the process of generating new capillaries from the pre-existing ones, is required for the development of various diseases such as cancer, diabetes and rheumatoid arthritis. Recently, ROCK has attracted attention for its crucial role in angiogenesis, making it a promising target for new therapeutic approaches. In this review, we summarize recent advances in understanding the role of ROCK signaling in regulating the permeability, migration, proliferation and tubulogenesis of endothelial cells (ECs), as well as its functions in non-ECs which constitute the pro-angiogenic microenvironment. The therapeutic potential of ROCK inhibitors in angiogenesis-related diseases is also discussed.
30499081 Recombinant Antibody Production in CHO and NS0 Cells: Differences and Similarities. 2018 Dec The commercial production of monoclonal antibodies (mAbs) has revolutionized the treatment of many diseases, including cancer, multiple sclerosis, and rheumatoid arthritis. These biotherapeutics have the potential to generate a global annual revenue of more than US$150 billion. Two cell hosts are predominantly utilized to produce these mAbs: Chinese hamster ovary (CHO) cells and murine myeloma cells (NS0). By 2017, nearly one-quarter of all approved mAbs in the market were produced using the NS0 host cell line, and around two-thirds were produced in CHO cells. Several different expression platforms are available: CHO-GS (glutamine synthetase), CHO-DHFR (dihydrofolate reductase), NS0, and GS-NS0, which have been characterized with respect to cell line and process development. Even though the major components of the cell culture media are common for both CHO and NS0 cells, specific growth media have been modified based on individual cellular requirements, such as cholesterol for NS0 cells. Additionally, understanding genomic and metabolic differences between the two cell hosts from an 'omics perspective has created a reference for media composition and antibody quality improvements.
30416069 Modeling specialty medicine access: Understanding key health system processes and players. 2019 Jan OBJECTIVES: To map the specialty medicine process from prescription writing to the patient obtaining medication, identify perceived barriers to access, and highlight potential opportunities for improved efficiency as understood from the perspective of 3 key stakeholder groups: specialty disease clinicians, staff members, and specialty pharmacists. DESIGN: Qualitative research study using semi-structured individual interviews. SETTING AND PARTICIPANTS: Interviews were conducted at a single large tertiary care center targeting clinicians and staff in the hepatitis C, oncology, cystic fibrosis, multiple sclerosis, and rheumatoid arthritis clinics. The second set of participants was pharmacists and technicians at specialty community pharmacies within one large retail chain that was not directly affiliated with the health system. RESULTS: Four conceptual models of specialty medicine access were described by participants. These models varied by disease state, available human resources, and medication. Clinics and specialty pharmacies were not fully aware of the others' systems and contributions to the specialty medicine access process. Perceptions of inefficient communication resulted in frustration and higher perceived work burden. CONCLUSION: There is not a single streamlined pathway for clinics and patients to access specialty medicines in health systems that do not own their own specialty pharmacies. The current system architecture can lead to duplicative work, challenges in communication, and other inefficiencies. Future interventions should focus on streamlining communications between specialty pharmacies, clinics, manufacturers, and payors to create the most efficient access to specialty medicines.
30315972 Retro-Odontoid Pseudotumor without Radiologic Atlantoaxial Instability: A Systematic Revie 2019 Jan BACKGROUND: Retro-odontoid pseudotumor (RP) can be caused by several diseases, especially rheumatoid arthritis, and is usually associated with the presence of atlantoaxial instability. On the other hand, a different group of patients have been identified in whom RP is observed without radiologic findings of atlantoaxial instability. The pathophysiology, clinical characteristics, and prognosis of this latter group of patients are not well described in the literature. METHODS: A PubMed and Scopus search adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed to include studies reporting patients with RP without radiologic instability (RPWRI). The data gathered from this review were analyzed to characterize RPWRI. RESULTS: The search yielded 36 articles with a total of 62 patients. All studies were case reports and small case series. Different characteristics of RPWRI are described, including causes, pathophysiology, and treatment. CONCLUSIONS: The results of this review show that RPWRI has different causes such as hypermobility, deposition of substances, and perhaps disc herniation. Depending on the cause of RPWRI, the pathophysiologic mechanism is different. Treatment should be tailored based on the primary cause of RP and the degree of compression of the cervicomedullary junction. Different degrees of improvement are usually observed after surgical treatment in these patients regardless of the treatment used, but a higher rate of mass regression was observed in those patients in whom the atlantoaxial joint was stabilized.
30283799 Recurrent carpal tunnel syndrome: Evaluation and treatment of the possible causes. 2018 Sep 26 AIM: To investigate the causes of the recurrent carpal tunnel syndrome (CTS) and implemented surgical interventions. METHODS: Four hundred and eighty-seven patients, who were diagnosed with CTS and underwent surgical intervention between October 2016 and September 2007, were evaluated in this retrospective study. The age, gender, physical evaluation findings, electrophysiological examination reports and implemented surgical treatment methods were analyzed. RESULTS: Thirty-nine of the cases were operated due to recurrent CTS. Further examination of the patients with recurrent CTS revealed that ten cases had diabetic polyneuropathy, three cases had hypothyroidism, two cases had rheumatoid arthritis and one case had systemic amyloidosis. Postoperative electromyography confirmed the neuropathy was due to systemic diseases. The remaining 23 patients with recurrent CTS did not have any systemic disease and all of them had applied previously to another health center. CONCLUSION: We concluded that the recurrence rates in CTS might be decreased with exploration and incision of the entire transverse ligament. Damage to the motor and sensory branches of the median nerve could be avoided with an incision on the ulnar side.
30233590 Regulatory Mechanisms of IL-33-ST2-Mediated Allergic Inflammation. 2018 Interleukin-33 (IL-33) plays multiple roles in tissue homeostasis, prevention of parasitic infection, and induction of allergic inflammation. Especially, IL-33-ST2 (IL-1RL1) axis has been regarded as the villain in allergic diseases such as asthma and atopic dermatitis and in autoimmune diseases such as rheumatoid arthritis. Indeed, a number of studies have indicated that IL-33 produced by endothelial cells and epithelial cells plays a critical role in the activation and expansion of group 2 innate lymphoid cells (ILC2s) which cause allergic inflammation by producing large amounts of IL-5 and IL-13. However, mechanisms that antagonize IL-33-ST2-mediated allergic responses remain largely unknown. Recently, several groups including our group have demonstrated cellular and molecular mechanisms that could suppress excessive activation of ILC2s by the IL-33-ST2 axis. In this review, we summarize recent progress in the regulatory mechanisms of IL-33-ST2-mediated allergic responses. Selective targeting of the IL-33-ST2 axis would be a promising strategy in the treatment of allergic diseases.
30211384 Rapid Complete Acetabular Destruction in Metal-on-Metal Total Hip Arthroplasty. 2018 Apr Adverse local tissue reaction, osteolysis, and subsequent increased incidence of failure have been associated with metal-on-metal (MoM) total hip arthroplasty (THA). We present the case of a 68-year-old woman with rheumatoid arthritis who has undergone left THA with a MoM bearing. Seven years postoperatively, she presented with 6 weeks of severe left hip pain. Sequential radiographs and advanced imaging demonstrated a rapid onset of extensive acetabular osteolysis with pelvic discontinuity and pseudotumor formation. She underwent revision THA using a cup-cage construct with a satisfactory outcome. In this article, we review current evidence-based management options for pelvic discontinuity, as well as other complications related to MoM THA.
30045390 Preventing or Eradicating Factor VIII Antibody Formation in Patients with Hemophilia A: Wh 2018 Sep Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in this narrative review of antidrug antibody prevention or eradication strategies that have been used in disorders beyond hemophilia A, with the aim of analyzing what we can learn from these strategies for hemophilia A. Prevention of antidrug antibody formation using rituximab, methotrexate, and intravenous immunoglobulins in patients with Pompe's disease seems effective but carries a high risk of adverse events. Based on studies in patients with rheumatoid arthritis and inflammatory bowel disease, it seems likely that treatment with methotrexate alone would also be able to prevent inhibitor formation in hemophilia A patients. Besides side effects, it is unclear whether immune tolerance to FVIII would persist after cessation of immunomodulatory therapy with methotrexate. A combination of cyclophosphamide and corticosteroids, used to treat antibody-mediated pure red cell aplasia, could be further investigated to eradicate inhibitors in hemophilia A patients who are refractory to ITI. In summary, insights gained from research on antidrug antibody formation in other diseases could be helpful in devising alternative treatment strategies for inhibitor development.
30023945 Discovery of Retinoic Acid-Related Orphan Receptor γt Inverse Agonists via Docking and Ne 2018 Jun 30 Retinoic acid-related orphan receptor γt (RORγt) has a vital role in the differentiation of T-helper 17 (TH17) cells. Potent and specific RORγt inverse agonists are sought for treating TH17-related diseases such as psoriasis, rheumatoid arthritis, and type 1 diabetes. Here, the aim was to discover novel RORγt ligands using both standard molecular docking and negative image-based screening. Interestingly, both of these in silico techniques put forward mostly the same compounds for experimental testing. In total, 11 of the 34 molecules purchased for testing were verified as RORγt inverse agonists, thus making the effective hit rate 32%. The pIC(50) values for the compounds varied from 4.9 (11 μM) to 6.2 (590 nM). Importantly, the fact that the verified hits represent four different cores highlights the structural diversity of the RORγt inverse agonism and the ability of the applied screening methodologies to facilitate much-desired scaffold hopping for drug design.
29773891 Assessing the Feasibility of Neutralizing Osteopontin with Various Therapeutic Antibody Mo 2018 May 17 Osteopontin is a secreted glycophosphoprotein that is highly implicated in many physiological and pathological processes such as biomineralization, cell-mediated immunity, inflammation, fibrosis, cell survival, tumorigenesis and metastasis. Antibodies against osteopontin have been actively pursued as potential therapeutics for various diseases by pharmaceutical companies and academic laboratories. Many studies have demonstrated the efficacy of osteopontin inhibition in a variety of preclinical models of diseases such as rheumatoid arthritis, cancer, nonalcoholic steatohepatitis, but clinical utility has not yet been demonstrated. To evaluate the feasibility of osteopontin neutralization with antibodies in a clinical setting, we measured its physiological turnover rate in humans, a sensitive parameter required for mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Results from a stable isotope-labelled amino acid pulse-chase study in healthy human subjects followed by mass spectrometry showed that osteopontin undergoes very rapid turnover. PK/PD modeling and simulation of different theoretical scenarios reveal that achieving sufficient target coverage using antibodies can be very challenging mostly due to osteopontin's fast turnover, as well as its relatively high plasma concentrations in human. Therapeutic antibodies against osteopontin would need to be engineered to have much extended PK than conventional antibodies, and be administered at high doses and with short dosing intervals.
29729941 Biologics and chronic obstructive pulmonary disease. 2018 Jun The presence of airway inflammation in patients with chronic obstructive pulmonary disease (COPD) provides a rationale for biological agents targeting specific inflammatory pathways. This approach has been strikingly effective in patients with other chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and asthma. However, there are important and unresolved challenges in COPD, including our incomplete understanding of heterogeneity of the lower airway inflammatory response and how these contribute to the clinical expression of disease. As a result, progress has been slow, and there have been many failures. One notable exception is the targeting of eosinophilic airway inflammation with anti-IL-5, which has an acknowledged and important role in the treatment of severe eosinophilic asthma. Recent phase III studies have shown a reduction in exacerbations of around 20% in patients with COPD and clear evidence of a blood eosinophil count-dependent beneficial effect. The demonstration of clinical efficacy linked to a clinically accessible biomarker raises the possibility of precision biomarker-directed use of biological agents in patients with COPD. The hope is that this will be an exemplar for the future development of biological agents in patients with COPD.