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ID PMID Title PublicationDate abstract
28956500 Clinical trial protocol for TRANSFORM-UK: A therapeutic open-label study of tocilizumab in 2018 Jan Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin-6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One of the most robust observations across multiple cohorts in PAH has been an increase in IL6, both in the lung and systemically. Tocilizumab is an IL-6 receptor antagonist established as safe and effective, primarily in rheumatoid arthritis, and has shown promise in scleroderma. In case reports where the underlying cause of PAH is an inflammatory process such as systemic lupus erythematosus, mixed connective tissue disease (MCTD), and Castleman's disease, there have been case reports of regression of PAH with tocilizumab. TRANSFORM-UK is an open-label study of intravenous (IV) tocilizumab in patients with group 1 PAH. The co-primary outcome measures will be safety and the change in resting pulmonary vascular resistance (PVR). Clinically relevant secondary outcome measurements include 6-minute walk distance, WHO functional class, quality of life score, and N-terminal pro-brain natriuretic peptide (NT-proBNP). If the data support a potentially useful therapeutic effect with an acceptable risk profile, the study will be used to power a Phase III study to properly address efficacy.
29740348 Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overvie 2018 Immune mediated diseases (IMDs) are complex chronic inflammatory diseases involving genetic and environmental factors. Salt intake has been proposed as a diet factor that can influence the immune response. Indeed, experimental data report the influence of sodium chloride on the differentiation of naive CD4(+) T cells into IL-17 secreting T helper (Th) cells (Th17 cells), by a mechanism involving the serum glucocorticoid kinase-1 (SGK1) that promotes the expression of the IL-23 receptor (IL-23R). The IL-23/IL-23R is critical for pathogenic inflammatory Th17 cell differentiation. Experimental data in murine models of arthritis, colitis and encephalomyelitis corroborate these findings. This manuscript reviews the current knowledge on the effects of sodium chloride on innate and adaptive immunity. We also performed a systematic literature review for clinical studies examining the relationships between salt consumption and the development or the activity/severity of the most common IMDs mediated by the IL-23/Th17 pathway, i.e., rheumatoid arthritis (RA), multiple sclerosis (MS), and Crohn's disease (CD). Nine studies were found, 4 in RA, 4 in MS and 1 in CD. An association was found between developments of anti-citrullinated protein antibody (ACPA) positive RA in smokers and salt intake, but these results were not confirmed in another study. For MS, no association was observed in pediatric subjects while in adult patients, a link was found between salt intake and disease activity. However, this result was not confirmed in another study. These conflicting results highlight the fact that further evaluation in human IMDs is required. Moreover, physicians need to develop clinical trials with diet interventions to evaluate the impact of low salt intake on disease activity/severity of IMDs.
29748731 Dioscorea nipponica Makino: a systematic review on its ethnobotany, phytochemical and phar 2018 May 11 Dioscorea nipponica Makino is a perennial twining herbs belonging to the family Dioscoreaceae, which is mainly distributed in the northeastern, northern, eastern and central regions of China. Traditionally, the rhizome of this herb has been commonly used by Miao and Meng ethnic groups of China to treat rheumatoid arthritis, pain in the legs and lumbar area, Kashin Beck disease, bruises, sprains, chronic bronchitis, cough and asthma. Modern pharmacological studies have discovered that this herb possesses anti-tumor, anti-inflammatory, anti-diuretic, analgesic, anti-tussive, panting-calming and phlegm-dispelling activities, along with enhancing immune function and improving cardiovascular health. In recent years, both fat-soluble and water-soluble steroidal saponins were isolated from the rhizomes of D. nipponica using silica gel column chromatography, thin layer chromatography and high performance liquid chromatography methods. Saponin and sapogenins are mainly responsible for most of the pharmacological effects of this plant. Further, the chemical components of the aboveground parts contain more than 10 kinds of phenanthrene derivatives. The present review summarizes the knowledge concerning the geographical distribution, chemical composition, pharmacological effects, toxicology studies and clinical applications of D. nipponica.
29731776 Potential of iPSC-Derived Mesenchymal Stromal Cells for Treating Periodontal Disease. 2018 Mesenchymal stromal cell-like populations have been derived from mouse-induced pluripotent stem cells (miPSC-MSC) with the capability for tissue regeneration. In this study, murine iPSC underwent differentiation towards an MSC-like immunophenotype. Stable miPSC-MSC cultures expressed the MSC-associated markers, CD73, CD105, and Sca-1, but lacked expression of the pluripotency marker, SSEA1, and hematopoietic markers, CD34 and CD45. Functionally, miPSC-MSC exhibited the potential for trilineage differentiation into osteoblasts, adipocytes, and chondrocytes and the capacity to suppress the proliferation of mitogen-activated splenocytes. The efficacy of miPSC-MSC was assessed in an acute inflammation model following systemic or local delivery into mice with subcutaneous implants containing heat-inactivated P. gingivalis. Histological analysis revealed less inflammatory cellular infiltrate within the sponges in mice treated with miPSC-MSC cells delivered locally rather than systemically. Assessment of proinflammatory cytokines in mouse spleens found that CXCL1 transcripts and protein were reduced in mice treated with miPSC-MSC. In a periodontitis model, mice subjected to oral inoculation with P. gingivalis revealed less bone tissue destruction and inflammation within the jaws when treated with miPSC-MSC compared to PBS alone. Our results demonstrated that miPSC-MSC derived from iPSC have the capacity to control acute and chronic inflammatory responses associated with the destruction of periodontal tissue. Therefore, miPSC-MSC present a promising novel source of stromal cells which could be used in the treatment of periodontal disease and other inflammatory systemic diseases such as rheumatoid arthritis.
29669993 Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspe 2018 Apr 18 Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications, such as the removal of introns and signal peptides, and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing inactive proMPO by the insertion of a heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into the extracellular fluid after oxidative stress and different inflammatory responses. Myeloperoxidase is the only type of peroxidase that uses Hâ‚‚Oâ‚‚ to oxidize several halides and pseudohalides to form different hypohalous acids. So, the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and the pathogenesis of several other major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants. Thus, the enhanced level of MPO activity is one of the best diagnostic tools of inflammatory and oxidative stress biomarkers among these commonly-occurring diseases.
29456634 Limethason reduces airway inflammation in a murine model of ovalbumin-induced chronic asth 2018 Mar Airway inflammation is the major pathological feature of asthma. Thus, the current therapeutic strategy for asthma is to control inflammation. Limethason, an anti-inflammation drug, is widely used in rheumatoid arthritis treatment. The aim of the present study was to detect the anti-inflammatory effect and side effects of limethason on airways that were sensitized with ovalbumin in a murine model of chronic asthma. In the present study, BALB/c mice were sensitized with ovalbumin. Airway hyperresponsiveness was estimated, and hematoxylin and eosin staining, Periodic acid-Schiff staining and bronchoalveolar lavage were used to detect the effect on chronic asthma. Limethason effectively reduced airway hyperresponsiveness, and inhibited inflammatory cell infiltration and mucus secretion. Bronchoalveolar lavage fluid analysis revealed that limethason suppressed levels of airway eosinophils. In the period of treatment, limethason exhibited no influence on morphology of the femoral head, bone mineral content or bone mineral density, which were detected by histological studies and dual-energy X-ray absorptiometry. The index of liver, spleen, kidney, gastrocnemius and brown adipose tissue also demonstrated that limethason had no adverse effects on organs and tissues. The present study revealed that limethason could effectively reduce inflammation in an asthma mouse model without side effects. Therefore, limethason may have therapeutic potential for treating chronic asthma clinically.
29451066 Psychometric properties of MDHAQ/RAPID3 in patients with systemic lupus erythematosus. 2018 May BACKGROUND: The Multidimensional Health Assessment Questionnaire (MDHAQ) is a patient-reported outcome (PRO) tool that includes the Routine Assessment of Patient Index Data 3 (RAPID3), an index that can be calculated at the point of care. The objective of this study was to perform psychometric analyses of MDHAQ/RAPID3 to study its measurement properties in systemic lupus erythematosus (SLE). METHODS: The MDHAQ was completed by 161 SLE patients in routine care, along with LupusPRO (a disease-specific PRO). The SLE disease-specific activity index (SELENA-SLEDAI) and damage (SDI) were assessed. Data from 70 patients with rheumatoid arthritis who had completed MDHAQ during their routine medical care were used as controls to compare the results of Physical Function (FN) domain exploratory factor analysis. Internal consistency reliability (ICR) for FN items was calculated using Cronbach's α. Validity of MDHAQ/RAPID3 was evaluated for content validity and construct validity. Responsiveness of the RAPID3 to changes in disease activity anchors was assessed. RESULTS: The ICR of the 10 physical function items on Cronbach's α was 0.88. Exploratory factor analysis revealed cross-loadings of three FN items. RAPID3 showed a strong correlation with LupusPRO health-related quality of life score (rho -0.68 (p < 0.001)), indicating convergent validity. RAPID3 scores did not correlate with disease activity indices or SDI. After adjustment for fibromyalgia status, a weak correlation with the Physician's Global Assessment (PGA) (rho = 0.31, p = 0.008) was noted. RAPID3 could differentiate between SLE patients based on flare status. RAPID3 was not responsive to changes in PGA, SELENA-SLEDAI or SELENA-Flare Index. CONCLUSIONS: MDHAQ/RAPID3 has fair reliability and validity in SLE.
29155234 Survivin and autoimmunity; the ins and outs. 2018 Jan Autoimmunity is a status that immune mechanisms react against self-structure. The immune mechanisms, including cellular and molecular elements have been developed to immune body against foreign invades. Multiple factors such as genetic and epigenetic background, hormonal status, microbiome, and other factors can cause launching the autoreactive responses, in which the immune tolerance breaks and immune mechanisms are against self-antigens. Apoptosis is one of the important mechanisms in maintaining the tolerance and eliminating the autoreactive lymphocyte clones. Due to survivin roles in apoptosis and proliferation, numerous researches have been paying attention to survivin expression and function in autoreactive lymphocytes and tissue cells, playing important roles in the pathogenesis of autoimmune diseases. New line of evidence has been supporting the role of survivin dysfunction or aberrant expression in deriving autoreactive lymphocytes or some important immune tissues, which may underpin the autoimmune conditions such as Lichen planus (LP), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Myasthenia gravis (MG), Multiple sclerosis (MS), Systemic sclerosis (SSc), Psoriasis, and Inflammatory bowel disease (IBD). Hence, the purpose of the current paper was to review the survivin role in the etiology and pathogenesis of abovementioned autoimmune diseases.
30687671 Treatment of Periprosthetic Humeral Shaft Fracture after Total Elbow Arthroplasty in an Os 2018 Jul INTRODUCTION: Periprosthetic humeral shaft fracture after total elbow arthroplasty (TEA) and open reduction and internal fixation at the same side humeral neck fracture in patients with osteoporosis poses a treatment challenge. Herein, we describe our experience with its treatment using the Ilizarov external ring fixator. CASE REPORT: A 74-year-old Japanese woman with rheumatoid arthritis and osteoporosis sustained a periprosthetic humeral shaft fracture. The fracture was externally fixated with the Ilizarov external ring fixator, and five wires (Orthofix, Lewisville, Texas) were inserted just beside the components of the TEA (three wires were beside the humeral component and two wires the ulnar component). 4 months postoperatively, the fracture showed bone union and the fixator was removed. There were minor pin tract infections treated with oral antibiotics and transient ulnar nerve palsy with resolution after 6 months of the fixator removal. During the period of wearing the fixator, the left elbow joint was immobilized, and mainly isometric muscle exercises were performed. At 6 months of follow-up after the fixator removal, the patient was pain free, with good functional results (patient-rated elbow evaluation Japanese version 8.6 and quick- disability of the arm, shoulder, and hand Japanese version 20.5), elbow range of motion 10-°, 80° pronation, and 80° supination. The patient returned successfully to her pre-injury occupational activities. CONCLUSION: We believe that the use of the Ilizarov external fixator is a useful option for managing periprosthetic humeral shaft fractures after TEA in patients with osteoporosis.
30636600 Pattern Recognition Receptors and Control of Innate Immunity: Role of Nucleic Acids. 2018 The innate immune system protects against infectious microbes by the recognition of pathogen- associated molecular patterns, which serve to detect pathogens on the host cell surface or in endosomes by pattern recognition receptors such as Toll-like receptors, nucleotide-binding oligomerization domain-containing protein-1-like receptors, mannose-receptor, or retinoic acid-inducible gene-1- like receptors that initiate proper host defense mechanisms. In addition to pathogen-associated molecular patterns, a series of endogenous danger-associated molecular patterns, such as nucleic acids, are recognized by pattern recognition receptors, which serve as body´s own alarm signals under sterile conditions, such as ischemic injuries, trauma, tumors, tissue transplants, or autoimmune diseases. Thus, exogenous as well as endogenous nucleic acids can function as "alarmins" to alert the body about danger or disease by triggering inflammation, dendritic cell maturation, and stimulate the immune response resulting in the release of cytokines, which in turn can augment the local inflammatory environment. Moreover, danger-associated molecular patterns such as nucleic acids can act as cofactor in the activation of pattern recognition receptors in situations of cellular stress or upon infection leading to a massive amplification of the inflammatory response. As a consequence, acute and also chronic inflammatory diseases such as rheumatoid arthritis, cancer, or atherosclerosis may depend on such perpetuated proinflammatory responses involving activities of nucleic acids. As antagonists, RNase1 or DNase administration or nucleic acid complexing agents may result in a significant blockade of the outcome of particular pathological situations and in considerable tissue protection.
30296970 Use of contrast-enhanced magnetic resonance imaging of the pelvis to describe changes at d 2018 Sep OBJECTIVES: To identify inflammatory pelvic structures of patients with polymyalgia rheumatica (PMR) by magnetic resonance imaging (MRI) in detail, searching for a disease-specific pattern. METHODS: A total of 40 contrast-enhanced pelvic MRIs of patients with a clinical diagnosis of PMR was reviewed by an experienced musculoskeletal radiologist who assessed all abnormalities semi-quantitatively, based on a predefined scoring system. RESULTS: The median (25th/75th percentiles) age of patients was 67 (55/73) years, median symptom duration 13 (6/22) weeks, 55% female, median CRP 1.9 (0.7/4) mg/dl, median ESR 30/1h (17/43). Ten patients were diagnosed with rheumatoid arthritis (25%), in addition to their leading polymyalgic symptom. Multi-locular, mostly bilateral, peritendinous enhancement of pelvic girdle tendons was found to be the hallmark of PMR in all patients. Low-grade hip synovitis was also detected frequently. In all cases, ≥4 extracapsular tendinous sites were bilaterally affected. Besides involvement of the common ischiocrural tendon and the glutaeus medius and minimus tendon (present in all cases), an enhancement of the proximal rectus femoris origin was observed in 100% and of the adductor muscles at the inferior medial pubic bone in 90% of cases. The observed MRI pattern patho-anatomically suggests inflammation of the external peritendineum. CONCLUSIONS: The uniformity of the observed pelvic inflammatory pattern detected by contrast-enhanced MRI in PMR patients suggests that it may become relevant for diagnostic purposes. The bilateral involvement of at least 4 extracapsular sites (including the origins of proximal rectus femoris or adductorial muscles) appears to be characteristic of PMR.
30229667 The effectiveness of backward walking as a treatment for people with gait impairments: a s 2019 Feb OBJECTIVE: To investigate the effectiveness of backward walking in the treatment of people with gait impairments related to neurological and musculoskeletal disorders. DESIGN: Systematic review and meta-analysis of randomized and quasi-randomized control studies. DATA SOURCES: Searched from the date of inception to March 2018, and included PubMed, Scopus, Cochrane Library, PEDro, CINAHL, and the MEDLINE databases. METHODS: Investigating the effects of backward walking on pain, functional disability, muscle strength, gait parameters, balance, stability, and plantar pressure in people with gait impairments. The PEDro scale was used to assess the quality. Similar outcomes were pooled by calculating the standardized mean difference. RESULTS: Of the 21 studies (neurological 11 and musculoskeletal 10), 635 participants were included. The average PEDro score was 5.4/10. The meta-analysis demonstrated significant standardized mean difference values in favour of backward walking, with conventional physiotherapy treatment for two to four weeks to reduce pain (-0.87) and functional disability (-1.19) and to improve quadriceps strength (1.22) in patients suffering from knee osteoarthritis. The balance and stability in cases of juvenile rheumatoid arthritis, and gait parameters and muscle strength in anterior cruciate ligament injury improved significantly when backward walking was included as an exercise. There was no significant evidence in favour of backward walking in any of the other conditions. CONCLUSION: The systematic review and meta-analysis suggests that backward walking with conventional physiotherapy treatment is effective and clinically worthwhile in patients with knee osteoarthritis. Insufficient evidence was available for the remaining gait impairment conditions and no conclusions could be drawn.
32789227 Association of Pain Quality with Pain Catastrophizing and Self-efficacy in People with Kne 2018 OBJECTIVE: Patients with chronic pain often have symptoms similar to neuropathic pain (NeP). Such symptoms are also frequently observed in people with knee osteoarthritis (OA). However, pain quality may be related to psychological problems such as high pain catastrophizing and/or low self-efficacy. The objective of the current study was to investigate whether pain quality is associated with pain catastrophizing and self-efficacy in individuals with symptomatic knee OA. METHODS: This was a cross-sectional study in which 50 subjects with symptomatic knee OA were enrolled. NeP scores were evaluated using the painDETECT questionnaire (PDQ), the pain catastrophizing scores were evaluated using the coping strategy questionnaire, and the self-efficacy scores were evaluated using the self-efficacy scale for rheumatoid arthritis (SERA). Participants were classified as members of the unlikely NeP group (PDQ score ≤12) or the uncertain/likely NeP group (PDQ score >12). The pain catastrophizing scores and the self-efficacy scores were compared between the two groups. RESULTS: Of the 50 participants, 17 (34%) were classified in the uncertain/likely NeP group. The pain catastrophizing score was higher for the uncertain/likely NeP group (6.2 ± 3.3) than for the unlikely NeP group (4.5 ± 2.8; P=0.03). On the SERA scale, the self-efficacy for pain score was lower for the uncertain/likely NeP group (21.9 ± 3.1) than for the unlikely NeP group (24.2 ± 3.1; P=0.03). CONCLUSION: High pain catastrophizing and low self-efficacy for pain control are significantly associated with the existence of an NeP component on PDQ in people with symptomatic knee OA.
30863521 Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children. 2018 BACKGROUND: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce. OBJECTIVE: To assess the effect of leflunomide on BKvirus in kidney-transplanted children. METHODS: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded. RESULTS: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis. CONCLUSION: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30-40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.
30083550 Altered Fc galactosylation in IgG(4) is a potential serum marker for chronic lung disease. 2018 Jul Characterising chronic lung diseases is challenging. New, less invasive diagnostics are needed to decipher disease pathologies and subphenotypes. Fc galactosylation is known to affect IgG function, and is altered in autoimmune disorders and under other pathological conditions. We tested how well Fc glycans in IgG from bronchoalveolar lavage fluid (BALF) and serum correlated, and if the Fc glycan profile could reveal pulmonary inflammation. A shotgun proteomics approach was used to profile Fc glycans in serum and BALF of controls (n=12) and sarcoidosis phenotypes (Löfgren's syndrome (LS), n=11; and non-LS, n=12). Results were further validated in severe asthma (SA) (n=20) and published rheumatoid arthritis (RA) patient data (n=13) including clinical information. Intra-individually, Fc-galactosylation status of IgG(1) (R(2)=0.87) and IgG(4) (R(2)=0.95) correlated well between matrixes. Following GlycoAge-index correction, the ratio between agalactosylated and digalactosylated Fc glycans of IgG(4) could distinguish sarcoidosis and SA from healthy and RA subjects with a mean±se area under the curve (AUC) of 78±6%. The AUC increased to 83±6% using the more chronic lung disease types (non-LS and SA) and most strikingly, to 87±6% for the SA subgroup. The results indicate that the Fc galactosylation status of IgG(4) is a potential blood test marker for chronic lung inflammation.
30077735 Subcutaneous delivery of monoclonal antibodies: How do we get there? 2018 Sep 28 The convenience of subcutaneous (SC) administration and the increasing interest in monoclonal antibody (mAb)-based therapies for chronic diseases, hint their potential for SC delivery in a near future. In addition, there is a common interest among patients, clinicians and pharmaceutical industry in moving from intravenous to SC administration of mAbs due to benefits of improved patient compliance and reduced costs to the healthcare system. Despite the wide use of this route of administration in diseases like diabetes and rheumatoid arthritis, SC bioavailability of mAbs has been shown to be incomplete and variable in most preclinical and clinical studies. This evidences a gap in the understanding of SC absorption process of mAbs and in their drug development process. Likewise, challenges present in drug formulation, such as high viscosity and aggregation, and the inherent immunogenicity of mAbs have also been hampering the successful translation to clinical settings. This review provides a characterization of the subcutaneously delivered mAbs that have entered the market in the last 10 years as well as a snapshot of the landscape of currently undergoing clinical trials. Moreover, there is an overview of the factors influencing SC absorption of mAbs and the preclinical models in use to study SC pharmacokinetics. Considerations about drug formulation and immunogenicity of mAbs are also explored.
32232080 Is-there a place for vagus nerve stimulation in inflammatory bowel diseases? 2018 The vagus nerve (VN), the longest nerve of the organism that innervates the gastrointestinal tract, is a mixed nerve composed of 80% of afferent and 20% of efferent fibers. The VN has anti-inflammatory properties, in particular an anti-TNFα effect through the cholinergic anti-inflammatory pathway. The VN is a key component of the autonomic nervous system, i.e. the parasympathetic nervous system. An imbalance of the autonomic nervous system, as represented by a low vagal tone, is described in many diseases and has a pro-inflammatory role. Inflammatory bowel diseases (IBD) are chronic disorders of the gastro-intestinal tract where TNFα is a key cytokine. VN stimulation (VNS), classically used for the treatment of drug resistant epilepsy and depression, would be of interest in the treatment of IBD. We have recently reported in a 6 month follow-up pilot study that VNS improves active Crohn's disease. Preliminary data of another pilot study confirm this interest. Similarly, VNS has recently been reported to improve rheumatoid arthritis, another TNFα mediated disease. Bioelectronic Medicine, as represented by VNS, opens new therapeutic avenues in the treatment of such chronic inflammatory disorders. In the present manuscript, we will focus on the interest of VNS in IBD.
30142584 Developments of nano-TiO(2) incorporated hydroxyapatite/PEEK composite strut for cervical 2018 Oct The technique of anterior cervical corpectomy and fusion (ACCF) for strut grafting has become a widespread and actively applied for many cervical complaints including cervical degeneration of the intervertebral disks, cervical trauma, cancer, rheumatoid arthritis and multilevel cervical spondylotic diseases. To avoid the complications of the old techniques, the construct stability and long anterior screw-plate designs of the bone strut have been improved by using effective biomaterials. The nanostructured hydroxyapatite (HAp) incorporated with biocompatible polymer matrixes is an effective biomedical material and creating a functional properties applied for different tissue replacements such as dental, hips, knees, tendon and ligaments and tissue repair for maxillofacial reconstruction, stabilization of the jaw bone and spinal fusion. In the present investigation, we have successfully designed cylindrical nano titanium dioxide (n-TiO(2)) interbody fusion with anterior plate fixation. The n-TiO(2) incorporated HAp/ Polyetheretherketone (PEEK) nanocomposite strut has a superior mechanical properties and larger contact area with high fusion rates as compared with the HAp/PEEK strut in the absence of n-TiO(2) nanoparticles. It is highly able to provide appropriate strength and biological activity similar to the conventional titanium cage and also mainly it has been minimizes subsidence value. The synthesized novel material of n-TiO2 incorporated HAp/PEEK nanocomposite strut is scientifically given effective outcomes for fusion and reconstruction of the ACCF.
29924943 Peptidylarginine deiminase 4: a nuclear button triggering neutrophil extracellular traps i 2018 Jun 20 Peptidylarginine deiminase 4 (PAD4) is a nuclear citrullinating enzyme that is critically involved in the release of decondensed chromatin from neutrophils as neutrophil extracellular traps (NETs). NETs, together with fibrin, are implicated in host defense against pathogens; however, the formation of NETs (NETosis) has injurious effects that may outweigh their protective role. For example, PAD4 activity produces citrullinated neoantigens that promote autoimmune diseases, such as rheumatoid arthritis, to which PAD4 is genetically linked and where NETosis is prominent. NETs are also generated in basic sterile inflammatory responses that are induced by many inflammatory stimuli, including cytokines, hypoxia, and activated platelets. Mice that lack PAD4-deficient in NETosis-serve as an excellent tool with which to study the importance of NETs in disease models. In recent years, animal and human studies have demonstrated that NETs contribute to the etiology and propagation of many common noninfectious diseases, the focus of our review. We will discuss the role of NETs in thrombotic and cardiovascular disease, the induction of NETs by cancers and its implications for cancer progression and cancer-associated thrombosis, and elevated NETosis in diabetes and its negative impact on wound healing, and will propose a link between PAD4/NETs and age-related organ fibrosis. We identify unresolved issues and new research directions.-Wong, S. L., Wagner, D. D. Peptidylarginine deiminase 4: a nuclear button triggering neutrophil extracellular traps in inflammatory diseases and aging.
29659479 Oral Dysbiotic Communities and Their Implications in Systemic Diseases. 2018 Apr 16 The human body supports the growth of a wide array of microbial communities in various niches such as the oral cavity, gastro-intestinal and urogenital tracts, and on the surface of the skin. These host associated microbial communities include yet-un-cultivable bacteria and are influenced by various factors. Together, these communities of bacteria are referred to as the human microbiome. Human oral microbiome consists of both symbionts and pathobionts. Deviation from symbiosis among the bacterial community leads to “dysbiosis”, a state of community disturbance. Dysbiosis occurs due to many confounding factors that predispose a shift in the composition and relative abundance of microbial communities. Dysbiotic communities have been a major cause for many microbiome related systemic infections. Such dysbiosis is directed by certain important pathogens called the “keystone pathogens”, which can modulate community microbiome variations. One such persistent infection is oral infection, mainly periodontitis, where a wide array of causal organisms have been implied to systemic infections such as cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease. The keystone pathogens co-occur with many yet-cultivable bacteria and their interactions lead to dysbiosis. This has been the focus of recent research. While immune evasion is one of the major modes that leads to dysbiosis, new processes and new virulence factors of bacteria have been shown to be involved in this important process that determines a disease or health state. This review focuses on such dysbiotic communities, their interactions, and their virulence factors that predispose the host to other systemic implications.