Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis

Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factors suppress IL-10 activity at the level of signal transduction. Out of many factors tested, only ligation of Fc receptors by immune complexes inhibited IL-10 activation of the Jak-Stat signaling pathway. IL-10 signaling was suppressed in rheumatoid arthritis joint macrophages that are exposed to immune complexes in vivo. Activation of macrophages with interferon-γ was required for Fc receptor–mediated suppression of IL-10 signaling, which resulted in diminished activation of IL-10–inducible genes and reversal of IL-10–dependent suppression of cytokine production. The mechanism of inhibition involved decreased cell surface IL-10 receptor expression and Jak1 activation and was dependent on protein kinase C delta. These results establish that IL-10 signaling is regulated during inflammation and identify Fc receptors and interferon-γ as important regulators of IL-10 activity. Generation of macrophages refractory to IL-10 can contribute to pathogenesis of inflammatory and infectious diseases characterized by production of interferon-γ and immune complexes

A New Onset of Systemic Lupus Erythematosus Developed After Bee Venom Therapy

Lupus is a systemic autoimmune disease of an unknown origin, and systemic lupus erythematosus (SLE) can be triggered by numerous stimuli. Bee venom therapy is an alternative therapy that is believed to be effective for various kinds of arthritis. We present here a case of a 49-year-old female who experienced a new onset lupus after undergoing bee venom therapy, and this looked like a case of angioedema. The patient was successfully treated with high dose steroids and antimalarial drugs. We discuss the possibility of bee venom contributing to the development of SLE, and we suggest that such treatment should be avoided in patients with lupus

Aminooxy acetic acid suppresses Th17-mediated psoriasis-like skin inflammation by inhibiting serine metabolism

Background: Psoriasis is a common chronic inflammatory skin disease characterized by an external red rash that is caused by abnormal proliferation and differentiation of keratinocytes and immune T cells. This study aimed to elucidate the role of aminooxy acetic acid (AOA) in alleviating psoriasis from the perspective of immunology and metabolomics. Therefore, contributing to the development of new drugs as candidates for psoriasis treatment.Methods: To investigate the symptom-alleviating effects and the related mechanisms of AOA on the treatment of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin mouse model and interleukin (IL)-17-stimulated human keratinocytes.Results: The results showed that AOA ameliorated psoriasis-related symptoms and decreased inflammation-associated antimicrobial peptides and T-helper 17 (Th17)-associated cytokines in a mouse model of psoriasis. Furthermore, AOA inhibited the activation of mechanistic target of rapamycin (mTOR) by suppressing serine metabolism-related genes. Importantly, mTOR inhibition ameliorated psoriatic disease by affecting the differentiation of various T cells and normalizing the Th17/regulatory T (Treg) cell balance. In addition, IL-17-stimulated human keratinocytes showed the same results as in the in vivo experiments.Conclusion: Taken together, these results suggest that targeting the serine metabolism pathway in the treatment of psoriasis is a novel strategy, and that AOA could be utilized as a novel biologic to treat psoriasis

Flexible room-temperature NO2 gas sensors based on carbon nanotubes/reduced graphene hybrid films

We present a flexible room temperature NO2 gas sensor consisting of vertical carbon nanotubes (CNTs)/reduced graphene hybrid film supported by a polyimide substrate. The reduced graphene film alone showed a negligible sensor response, exhibiting abnormal N-P transitions during the initial NO2 injection. A hybrid film, formed by the growth of a vertically aligned CNT array (with CNTs 20 ??m in length) on the reduced graphene film surface, exhibited remarkably enhanced sensitivities with weak N-P transitions. The increase in sensitivity was mainly attributed to the high sensitivity of the CNT arrays. The outstanding flexibility of the reduced graphene films ensured stable sensing performances in devices submitted to extreme bending stress.open786

Comparison of Posterior Lumbar Interbody Fusion and Posterolateral Lumbar Fusion in Monosegmental Vacuum Phenomenon within an Intervertebral Disc

Study DesignRetrospective.PurposeTo compare the clinical and radiological outcomes of posterolateral lumbar interbody fusion (PLIF) and posterolateral lumbar fusion (PLF) in monosegmental vacuum phenomenon within an intervertebral disc.Overview of LiteratureThe vacuum phenomenon within an intervertebral disc is a serious form of degenerative disease that destabilizes the intervertebral body. Outcomes of PLIF and PLF in monosegmental vacuum phenomenon are unclear.MethodsMonosegmental instrumented PLIF and PLF was performed on 84 degenerative lumbar disease patients with monosegmental vacuum phenomenon (PLIF, n=38; PLF, n=46). Minimum follow-up was 24 months. Clinical outcomes of leg and back pain were assessed using visual analogue scales for leg pain (LVAS) and back pain (BVAS), and the Oswestry disability index (ODI). The radiographic outcome was the estimated bony union rate.ResultsLVAS, BVAS, and ODI improved in both groups. There was no significant difference in the degree of these improvements between PLIF and PLF patients (p>0.05). Radiological union rate was 91.1% in PLIF group and 89.4% in PLF group at postoperative 24 months (p>0.05).ConclusionsNo significant differences in clinical results and union rates were found between PLIF and PLF patients. Selection of the operation technique will reflect the surgeon's preferences and patient condition

A clinical review of acute myocarditis in children

Purpose The aims of this study are to document our single-center experience with pediatric acute myocarditis and to investigate its clinical features and outcomes. Methods We performed a retrospective chart review of all children aged 12 months (55%) of age. The overall incidence of upper respiratory tract infection symptoms was 69%; general symptoms, 66%; cardiac symptoms, 24%; gastrointestinal symptoms, 17%; and neurologic symptoms, 10%. Twelve patients (41%) had cardiomegaly. Ten patients had electrocardiographic abnormalities (tachycardia, ST changes, T wave changes, and low voltage). Echocardiographic abnormalities were pericardial effusion or impaired contractility. Severe group consisted of 13 patients who were either transferred or died and contained more patients with cardiomegaly and electrocardiogram abnormalities, but this was statistically irrelevant. Most patients had elevated concentrations of cardiac biomarkers, but the median concentrations were not statistically different between the 2 groups. Main treatment modalities included antibiotics (90%), inotropics (59%), and intravenous immunoglobulin (76%). Conclusion Definite diagnostic criteria for acute myocarditis do not exist, so misdiagnosis can occur. Extracorporeal membrane oxygenation therapy for severe cases is available only in some hospitals, so proper treatment can be delayed. Further evaluation of the current situation regarding acute myocarditis will contribute towards proper treatment

B7-H3 regulates osteoclast differentiation via type I interferon-dependent IDO induction

While their function, as immune checkpoint molecules, is well known, B7-family proteins also function as regulatory molecules in bone remodeling. B7-H3 is a receptor ligand of the B7 family that functions primarily as a negative immune checkpoint. While the regulatory function of B7-H3 in osteoblast differentiation has been established, its role in osteoclast differentiation remains unclear. Here we show that B7-H3 is highly expressed in mature osteoclasts and that B7-H3 deficiency leads to the inhibition of osteoclastogenesis in human osteoclast precursors (OCPs). High-throughput transcriptomic analyses reveal that B7-H3 inhibition upregulates IFN signaling as well as IFN-inducible genes, including IDO. Pharmacological inhibition of type-I IFN and IDO knockdown leads to reversal of B7-H3-deficiency-mediated osteoclastogenesis suppression. Although synovial-fluid macrophages from rheumatoid-arthritis patients express B7-H3, inhibition of B7-H3 does not affect their osteoclastogenesis. Thus, our findings highlight B7-H3 as a physiologic positive regulator of osteoclast differentiation and implicate type-I IFN-IDO signaling as its downstream mechanism

Temporary bilateral sensorineural hearing loss following cardiopulmonary bypass -A case report-

Sudden sensorineural hearing loss has been reported to occur following anesthesia and various non-otologic surgeries, mostly after procedures involving cardiopulmonary bypass. Unilateral sensorineural hearing loss resulting from microembolism is an infrequent complication of cardiopulmonary bypass surgery that has long been acknowledged. Moreover, there are few reports on the occurrence of bilateral sensorineural hearing loss without other neurologic deficits and its etiology has also not been determined. We describe here a rare case of bilateral hearing loss without other neurologic deficits in an otherwise healthy 27-year-old woman who underwent cardiopulmonary bypass surgery for repair of severe mitral valve stenosis. The patient suffered from profound sensorineural hearing loss in both ears that was recognized immediately upon extubation, and audiometry tests confirmed the diagnosis. Without any treatment, her hearing recovered almost completely by the time of her discharge one week after surgery