miR-183 promotes radioresistance of lung adenocarcinoma H1299 cells via epithelial-mesenchymal transition

Lung adenocarcinomas are usually sensitive to radiation therapy, but some develop resistance. Radiation resistance can lead to poor patient prognosis. Studies have shown that lung adenocarcinoma cells (H1299 cells) can develop radioresistance through epithelial-mesenchymal transition (EMT), and this process is regulated by miRNAs. However, it is unclear which miRNAs are involved in the process of EMT. In our present study, we found that miR-183 expression was increased in a radioresistant lung adenocarcinoma cell line (H1299R cells). We then explored the regulatory mechanism of miR-183 and found that it may be involved in the regulation of zinc finger E-box-binding homeobox 1 (ZEB1) expression and mediate EMT in lung adenocarcinoma cells. qPCR results showed that miR-183, ZEB1, and vimentin were highly expressed in H1299R cells, whereas no difference was observed in E-cadherin expression. Western blot results showed that ZEB1 and vimentin were highly expressed in H1299R cells, while E-cadherin expression was decreased. When miR-183 expression was inhibited in H1299R cells, radiation resistance, proliferation, and cell migration were decreased. The expression of ZEB1 and vimentin in H1299R cells was decreased, while the expression of E-cadherin was increased. Moreover, miR-183 overexpression in H1299 cells enhanced radiation resistance, proliferative capacity, and cell migration ability. The expression of ZEB1 and vimentin in H1299 cells was increased, while that of E-cadherin was decreased. In conclusion, miR-183 may promote EMT and radioresistance in H1299 cells, and targeting the miR-183-ZEB1 signaling pathway may be a promising approach for lung cancer treatment.     

Activity of a subset of vesicular GABA-transporter neurons in the ventral zona incerta anticipates sleep onset

Study ObjectivesSleep and wake are opposing behavioral states controlled by the activity of specific neurons that need to be located and mapped. To better understand how a waking brain falls asleep it is necessary to identify activity of individual phenotype-specific neurons, especially neurons that anticipate sleep onset. In freely behaving mice, we used microendoscopy to monitor calcium (Ca²⁺) fluorescence in individual hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a validated marker of GABA neurons.MethodsvGAT-Cre mice (male = 3; female = 2) transfected with rAAV-FLEX-GCaMP6_M in the lateral hypothalamus were imaged 30 days later during multiple episodes of waking (W), non-rapid-eye movement sleep (NREMS) or REMS (REMS).Results372 vGAT neurons were recorded in the zona incerta. 23.9% of the vGAT neurons showed maximal fluorescence during wake (classified as wake-max), 4% were NREM-max, 56.2% REM-max, 5.9% wake/REM max, while 9.9% were state-indifferent. In the NREM-max group, Ca²⁺ fluorescence began to increase before onset of NREM sleep, remained high throughout NREM sleep, and declined in REM sleep.ConclusionsWe found that 60.2% of the vGAT GABA neurons in the zona incerta had activity that was biased towards sleep (NREM and REMS). A subset of vGAT neurons (NREM-max) became active in advance of sleep onset and may induce sleep by inhibiting the activity of the arousal neurons. Abnormal activation of the NREM-max neurons may drive sleep attacks and hypersomnia.     

Inhibited interleukin 35 expression and interleukin 35–induced regulatory T cells promote type II innate lymphoid cell response in allergic rhinitis

BackgroundInterleukin (IL)-35 and IL-35–producing regulatory T cells (iTr35) have been reported to inhibit T_H2 response in allergic rhinitis (AR). However, its effects on type II innate lymphoid cells (ILC2) are not well characterized.ObjectiveTo investigate the effect of IL-35 on ILC2 in AR.MethodsA total of 25 patients with AR and 20 controls were recruited. The expression and regulation of IL-35 receptor in ILC2 were analyzed by real-time polymerase chain reaction. The effect of IL-35 on ILC2 differentiation and cytokine production was analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, iTr35 were cocultured with ILC2 to explore the effect of iTr35 on ILC2. The AR mice models were also established to confirm the role of IL-35 in vivo.ResultsThe patients with AR had decreased IL-35 expression and iTr35 proportion and increased ILC2 and type II cytokines compared with the controls. Notably, IL-35 inhibited ILC2 differentiation and type II cytokine production by regulating IL-12Rβ2 and gp130. IL-35 promoted the inducible costimulatory molecule expression by iTr35 and the inducible costimulatory molecule ligand expression by ILC2. IL-35–treated mice with AR presented decreased frequency and function of nasal ILC2.ConclusionIL-35 inhibited ILC2 responses directly or through mutual contact between iTr35 and ILC2 in AR, suggesting that IL-35 may be used as a potential treatment target in AR.     

The role of innate immunity in myasthenia gravis

Myasthenia gravis (MG) is a T cell-driven, B cell-mediated and autoantibody-dependent autoimmune disorder against neuromuscular junctions (NMJ). Accumulated evidence has emerged regarding the role of innate immunity in the pathogenesis of MG. In this review, we proposed two hypothesis underlying the pathological mechanism. In the context of gene predisposition, on the one hand, Toll-like receptors (TLRs) pathways were initiated by viral infection in the thymus with MG to generate chemokines and pro-inflammatory cytokines such as Type I interferon (IFN), which facilitate the thymus to function as a tertiary lymphoid organ (TLO). On the another hand, the antibodies against acetylcholine receptors (AChR) generated by thymus then activated the classical pathways on thymus and neuromuscular junction (NMJ). Futher, we also highlight the role of innate immune cells in the pathogenic response. Finally, we provide some future perspectives in developing new therapeutic approaches particularly targeting the innate immunity for MG.     

Atypical and bilateral pigmented villonodular synovitis of wrist in an adolescent patient: case report and literature review

Background: Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disorder of the synovium. It rarely occurs in adolescents, particularly in immature patients with bilateral manifestation. Case presentation: We present a case of atypical and bilateral PVNS of wrist in a 14-year-old boy. Initially, the patient presented with left wrist pain and swelling without the history of trauma. Physical examination revealed an obvious lesion in the dorsal part of left wrist. Radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) showed multiple abnormal signal shadows and arthroedema in the left wrist. Arthroscopy operation was performed, and histologic examination suggested the diagnosis of PVNS. Only 10 months later, the patient presented with the similar symptoms and signs in the right wrist. But MIR and histologic examination were atypical. In this article, we also review and summarize 26 studies on 30 adolescent patients with PVNS. Conclusions: This study provides an example of atypical and bilateral PVNS in adolescents.     

放疗诱发第二原发肿瘤

放射治疗是恶性肿瘤治疗的重要手段之一。放疗与手术、系统治疗联合明显改善了患者预后,部分长期存活患者被诊断为第二原发恶性肿瘤如乳腺癌、食管癌、直肠癌、膀胱癌、肉瘤等。本文主要对放疗诱发第二原发肿瘤的剂量效应关系、潜伏期、影响因素、诊断、治疗、预后等内容进行阐述。