Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.

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ASIC1a activation in endplate chondrocytes may trigger Ca(2+)-dependent proteases activity and signaling, which leads to apoptosis of endplate chondrocytes in IVDs.

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

Tumor immune escape mechanism mediated by CD41CD251regulatory T cells (Tregs) is a key factor in the pathogenesis of acute myeloid leukemia (AML). IL-35, as a novel inhibitory cytokine, is produced by Tregs specially and regulates functions of Tregs in murine. However, IL-35 expression of Tregs in human is still disputed, and its role in AML is yet to be elucidated. In this study, we found that IL-35 was expressed highly in peripheral blood plasma of adult patients with AML and significantly correlated with the clinical stages of malignancy. Tregs-derived from adult AML patients produced IL-35 in a stimulationdependent manner. IL-35 promoted AML blasts immune escape by expanding Tregs and inhibiting CD41CD25-effector T cells (Teffs). Furthermore, IL-35 directly promoted the proliferation of AML blasts and reduced the apoptosis of AML blasts. Together, our study demonstrates that IL-35-derived from Tregs promotes the growth of adult AML blasts, suggesting that IL-35 has an important role in the pathogenesis of AML.Acute myeloid leukemia (AML) accounts for about 90% of acute leukemia in adults, and its incidence increases with age. Although some clinic advances including new moleculetargeting agents and hematopoietic stem cell transplantation (HSCT) have been applied over the past three decades, the five-year survival of adult AML still ranges from 30 to 40% in total patients and is even lower than 15% in the refractory and relapsed ones. 1 The pathogenesis of leukemia is complicated and has not been fully clarified. Recent studies have demonstrated that tumor immune escape mechanism governed by CD4 1 CD25 1 regulatory T cells (Tregs) is a key factor in the tumorigenesis of AML. 2-4 Especially, inhibitory cytokines TGF-b and IL-10 have been implicated as an important mediator contributing to immunosuppressive functions of Tregs, and are involved in the pathophysiological process of AML. 2,5 However, blocking TGF-b and IL-10 does not absolutely abrogate the suppressive activity of Tregs,6 suggesting some other mechanisms may be responsible for Tregs-mediating suppression.IL-35, composed of an IL-12 subunit p35 and an IL-27 subunit Epstein-Barr virus induced gene 3 (EBI3), is a newly identified heterodimeric cytokine and belongs to IL-12 cytokines family. 7,8 In mice, IL-35 is specifically produced by Tregs and required for their suppressive activity. IL-35 has been demonstrated to be involved in murine infectious tolerance, tumorigenesis and tumor progression. 7,9 However, IL-35 expression in human Tregs is still disputed 10-13 and its impact on AML is yet to be elucidated. In this study, we examined IL-35 in following three aspects: first, the expression of IL-35 in the occurrence and development of adult AML; second, the source of IL-35 in adult AML; and third, the exact role of IL-35 in adult AML. We found that Tregsderived IL-35 promoted the growth of adult AML blasts through direct and indirect effects, suggesting that IL-35 can be a potential target for the treatment of adult AML. Material and Methods Patient...

Background The immunosuppressive tumour microenvironment is a critical factor in the initiation and progression of glioblastoma (GBM), which is characterized by an abundance of tumour-associated macrophages (TAMs) but a paucity of infiltrating T cells. In this research, we studied whether epithelial membrane protein 3 (EMP3) plays a crucial role in immune modulation in GBM. Methods TCGA and CGGA transcriptomic profiles of wild-type IDH1 GBM were used for bioinformatic analysis. The role of EMP3 in GBM was validated through in vivo and in vitro experiments. Human GBM specimens were collected and evaluated using immunofluorescence analysis. Results EMP3 was associated with immunosuppression in GBM. Elevated EMP3 in GBM areas was accompanied by high expression of PD-L1 and abundant M2 TAM recruitment but a lake of T cell infiltration. We found that EMP3 was a potent protein in M2 TAM polarization and recruitment that impaired the ability of GBM cells to secrete CCL2 and TGF-β1. Furthermore, EMP3 suppressed T cell infiltration into GBM tumours by inhibiting the secretion of CXCL9 and CXCL10 by macrophages and led to an effective response to anti-PD1 therapy. Conclusions EMP3 is thus a critical immunosuppressive factor for recruiting TAMs in GBM and suppressing intratumoural T cell infiltration to facilitate tumour progression and is a potential therapeutic target.

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-Epidemiological studies have confirmed that ambient fine particulate matter (PM 2.5 ) exposure is associated with cardiovascular disease (CVD). However, the underlying mechanisms in PM 2.5 exposure-induced heart injury are largely unknown. It has been acknowledged that NADPH oxidase (Nox) 4 plays a critical role in CVD development. To investigate the acute effects of PM 2.5 on the mouse heart and the role of Nox4 in PM 2.5 exposure-induced cardiac injury, C57BL/6J mice were instilled with saline or 1.5, 3.0, 6.0 mg/kg BW PM 2.5 suspension for two weeks (five days per week). The levels of malondialdehyde (MDA), super oxide dismutase (SOD), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in heart supernatants were determined using related kits. The expression of Nox4, p67 phox , p47 phox and p22 phox in heart tissue was evaluated by immunofluorescence staining or Western blotting, respectively. Protein levels of p53, Bax, Bcl-2 and Caspase-3 in the heart were examined using immunohistochemical staining and Western blotting. TUNEL assay was used to measure myocardial apoptosis. PM 2.5 exposure leads to obvious cardiac injury. PM 2.5 exposure increases MDA level and iNOS activity, and decreases activity of SOD in heart supernatants of mice. High levels of TNF-α and IL-1β in heart supernatants of mice with PM 2.5 instillation were determined. Nox4 and Noxassociated subunits such as p67 phox , p47 phox and p22 phox expression levels were increased in heart tissue of mice after PM 2.5 exposure. Additionally, PM 2.5 exposure causes myocardial apoptosis in the mouse heart. This study suggested that Nox4 is involved in PM 2.5 exposure-induced cardiac injury in mice.