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关键词： Alignement   Alliage dentaire   Arc   Arcade dentaire   Copper Ni-Ti   Essai clinique randomisé   Ni-Ti   Orthodontie  

摘要： Introduction: In the first phase of orthodontic treatment, initial archwires are used to resolve crowding and correct rotations. Light, continuous forces are required to achieve optimal tooth movement. Nickel-titanium (Ni-Ti) archwires are commonly used as initial archwires due to their unique properties. Objective: The objective of this study was to compare the Copper Ni-Ti 35°C and the conventional Ni-Ti in dental alignment and maintaining the mandibular arch form. Material and Methods: A double-blind randomized controlled trial was conducted on adult patients, recruited from the orthodontic department of Saint Joseph University of Beirut and a private orthodontic practice in Beirut. They were randomly allocated into two groups: Copper Ni-Ti 35°C group and conventional Ni-Ti group, where they received both 0.016 inch and 0.018 inch archwires. Out of three available arch forms, each patient received the most suited archwire to their mandibular arch. Digital impressions were taken every three weeks and analyzed on Orthoanalyzer™. The Little Irregurality Index, space analysis and intercanine, interpremolar, intermolar distances were measured. Repeated measures analysis of variance ANOVA was used followed by Bonferroni multiple comparisons tests. Results: Forty patients were randomized in a 1:1 ratio to either Copper Ni-Ti 35°C or Ni-Ti group. No significant difference between the Copper Ni-Ti 35°C and the conventional Ni-Ti was noted in the resolution of dental crowding (p > 0.05). No significant difference in the dimensions of the mandibular arch was found within and between the two groups (p > 0.05). Conclusion: Copper Ni-Ti 35°C doesn't differ from the conventional Ni-Ti regarding the alignment rate and maintaining the mandibular arch form.;Introduction: En début de traitement orthodontique, les arcs initiaux sont insérés pour résoudre l’encombrement dentaire et corriger les rotations. Des forces légères et continues sont nécessaires pour obtenir un mouvement dent

关键词： 牙周炎   辅助性T细胞   细胞因子   转录因子   间充质干细胞   外泌体   免疫调节   微小RNAs  

摘要： 辅助性T细胞（T helper cells,Th细胞）在牙周炎的发病机制中具有重要作用。在牙周炎的发生发展中，Th1细胞与Th17细胞及其分泌的致炎性细胞因子INF-γ、IL-17等水平上升，Th2细胞与调节性T细胞（regulatory T Cells,Tregs）及其产生的抑炎性细胞因子IL-4、TGF-β等水平降低。通过间充质干细胞（mesenchymal stem cells,MSCs）或其外泌体（exosomes,Exos）对牙周炎施加干预时，能够改变辅助性T细胞及相应细胞因子的变化趋势，从而减少牙周炎骨丧失或促进骨再生。间充质干细胞外泌体（mesenchymal stem cell-derived exosomes,MSC-exos）能够通过携带的蛋白分子及微RNAs直接调控辅助性T细胞。当前研究中发现MSC-exos可携带具有免疫抑制作用的蛋白分子：细胞程序性死亡配体1(programmed cell death 1-ligand,PD-L1)与吲哚胺-2,3-双加氧酶分子可调控Th17-Treg平衡；转化生长因子-β(transforming growth factorβ,TGF-β)抑制T淋巴细胞增殖并通过维持叉头框P3(forkhead box protein O3,FOXP3)和Smad的表达促进Tregs分化；CD73则催化单磷酸腺苷分解产生腺苷，与Th1细胞内的腺苷2A受体结合，促使Th1细胞自身凋亡。MiRNA同样具有免疫调控能力：牙周膜干细胞外泌体携带的miRNA-155-5p通过靶向sirtuin-1而降低Th17细胞的分化，其携带的miR-205-5p能够靶向XBP1，进而恢复大鼠牙周炎局部的Th17-Treg平衡。牙髓干细胞外泌体通过miR-1246/Nfat5轴恢复Th17-Treg平衡；骨髓间充质干细胞外泌体携带的miR-1246靶向ACE2，使共培养的CD4阳性T淋巴细胞向Tregs分化。此外，MSC-exos也可以通过抗原呈递细胞或巨噬细胞等其他免疫细胞而间接促进Tregs的分化。本文主要针对辅助性T细胞在牙周炎中的变化及作用，以及间充质干细胞外泌体对辅助性T细胞的调控作用做一综述，希望为牙周炎的免疫治疗提供新思路。

关键词： Lymphocyte biology  

摘要： Unconventional T cells, including mucosal-associated invariant T (MAIT), natural killer T (NKT), and gamma-delta T (gamma delta T) cells, comprise distinct T-bet+, IFN-gamma+ and ROR gamma t+, IL-17+ subsets which play differential roles in health and disease. NKT1 cells are susceptible to ARTC2-mediated P2X7 receptor (P2RX7) activation, but the effects on other unconventional T-cell types are unknown. Here, we show that MAIT, gamma delta T, and NKT cells express P2RX7 and are sensitive to P2RX7-mediated cell death. Mouse peripheral T-bet+ MAIT1, gamma delta T1, and NKT1 cells, especially in liver, co-express ARTC2 and P2RX7. These markers could be further upregulated upon exposure to retinoic acid. Blocking ARTC2 or inhibiting P2RX7 protected MAIT1, gamma delta T1, and NKT1 cells from cell death, enhanced their survival in vivo, and increased the number of IFN-gamma-secreting cells without affecting IL-17 production. Importantly, this revealed the existence of IFN-gamma and IL-4 co-producing unconventional T-cell populations normally lost upon isolation due to ARTC2/P2RX7-induced death. Administering extracellular NAD in vivo activated this pathway, depleting P2RX7-sensitive unconventional T cells. Our study reveals ARTC2/P2RX7 as a common regulatory axis modulating the unconventional T-cell compartment, affecting the viability of IFN-gamma- and IL-4-producing T cells, offering important insights to facilitate future studies into how these cells can be regulated in health and disease.

关键词： 塞内加谷病毒   VP1蛋白   细胞因子   荧光定量  

摘要： 为了研究塞内加谷病毒（SVV）VP1蛋白对细胞因子的影响，本研究通过RT-PCR、双酶切和连接实验构建表达VP1蛋白真核质粒，免疫印迹试验鉴定VP1是否正确表达，荧光定量实验检测VP1过表达对细胞因子IL-1α、IL-1β、CCL-2、CCL-5和TNF-α的影响。双酶切结果显示VP1真核质粒构建成功，遂被命名为pEGFP-C1-VP1。免疫印迹试验显示蛋白能够正确表达。荧光定量试验结果显示VP1蛋白在转染后第24小时显著促进IL-1α的转录，在第12小时和第36小时分别显著促进和抑制IL-1β的转录，在第12小时和第24 小时显著促进CCL-2的转录，在第12、24 、36小时显著促进CCL-5的转录，在第12小时和第24 小时显著促进TNF-α的转录。结果表明，SVV VP1蛋白能够诱导IL1α、CCL-2、CCL-5、TNF-α的转录；对于IL-1β，SVV VP1蛋白早期促进IL-1β的转录，后期抑制IL-1β的转录。

关键词： virology   interferons   innate immunity   proteasome   HMPV   human metapneumovirus   Pneumoviridae  

摘要： Human metapneumovirus (HMPV) is a leading cause of respiratory infections in children, older adults, and those with underlying conditions (K. M. Edwards et al., N Engl J Med 368:633-643, 2013, https://***/10.1056/NEJMoa1204630;A. R. Falsey et al., J Infect Dis 187:785-790, 2003, https://***/10.1086/367901;J. S. Kahn, Clin Microbiol Rev 19:546-557, 2006, https://***/10.1128/CMR.00014-06;N. Shafagati and J. Williams, F1000Res 7:135, 2018, https://***/10.12688/f1000research.12625.1). HMPV must evade immune defenses to replicate successfully;however, the viral proteins used to accomplish this are poorly characterized. The HMPV small hydrophobic (SH) protein has been reported to inhibit signaling through type I and type II interferon (IFN) receptors in vitro in part by preventing STAT1 phosphorylation (A. K. Hastings et al., Virology (Auckl) 494:248-256, 2016, https://***/10.1016/***.2016.04.022). HMPV infection also inhibits IL-6 signaling. However, the mechanisms by which SH inhibits signaling and its involvement in IL-6 signaling inhibition are unknown. Here, we used transfection of SH expression plasmids and SH-deleted virus (Delta SH) to show that SH is the viral factor responsible for the inhibition of IL-6 signaling during HMPV infection. Transfection of SH-expression vectors or infection with wild-type, but not Delta SH virus, blocked IL-6-mediated STAT3 activation. Furthermore, JAK1 protein (but not RNA) was significantly reduced in cells infected with wild-type, but not Delta SH virus. The SH-mediated reduction of JAK1 was partially restored by the addition of proteasome inhibitors, suggesting proteasomal degradation of JAK1. Confocal microscopy indicated that infection relocalized JAK1 to viral replication factories. Co-immunoprecipitation showed that SH interacts with JAK1 and ubiquitin, further linking SH to proteasomal degradation machinery. These data indicate that SH inhibits IL-6 and IFN signaling in infected cells in part by prom

关键词： IL-37   Multiple sclerosis   IL-10   Inflammation   Experimental autoimmune encephalomyelitis (EAE)  

摘要： BackgroundInterleukin-37 (IL-37) has anti-inflammatory properties in innate and adaptive immunity. Patients with multiple sclerosis (MS), an autoimmune inflammatory demyelinating disease of the central nervous system (CNS), have increased serum levels of IL-37. However, it is unknown whether IL-37 has an inhibitory effect on ongoing autoimmune neuroinflammation, thus offering a potential MS ***, we examined the effect of IL-37 in an experimental autoimmune encephalomyelitis (EAE) model after disease onset to determine if it was ***-37-treated mice developed a less severe disease than control mice, with reduced demyelination as determined by increased expression of myelin basic protein. IL-37 suppressed inflammation by decreasing infiltration of CD4 + T cells into the CNS and increasing the frequency of regulatory T cells, while IL-10 expression by CD4 + T cells decreased over time in the *** findings confirm the immunomodulatory role of IL-37 in CNS inflammation during ongoing disease, thus indicating the potential of IL-37 as an inhibitory reagent for MS therapy.

关键词： MSCs   Extracellular vesicles (EVs)   Zika virus (ZIKV)   IFN-beta   miR-431-5p   CD95  

摘要： BackgroundZika virus (ZIKV) primarily spreads through mosquito bites and can lead to microcephaly in infants and Guillain-Barre syndrome in adults. It is noteworthy that ZIKV can persist in the semen of infected males for extended periods and can be sexually transmitted. Infection with ZIKV has severe pathological manifestations on the testicular tissues of male mice, resulting in reduced sperm motility and fertility. However, there are no approved prophylactic vaccines or therapeutics available to treat Zika virus *** a male type I and II interferon receptor-deficient (ifnar1(-/-) ifngr1(-/-)) C57BL/6 (AG6) mouse model infected with ZIKV as a representative model, we evaluated the degree of testicular damage and viral replication in various organs in mice treated with EVs derived from MSC-stimulated with IFN-beta (IFN beta-EVs) and treated with controls. We measured testicle size, detected viral load in various organs, and analyzed gene expression to assess treatment *** findings demonstrated that intravenous administration of IFN beta-EVs effectively suppressed ZIKV replication in the testes. Investigation with in-depth RNA sequencing analysis found that IFN-beta treatment changed the cargo miRNA of EVs. Notably, miR-431-5p was identified to be significantly enriched in IFN beta-EVs and exhibited potent antiviral activity in vitro. We showed that CD95 was a direct downstream target for miR-431-5p and played a role in facilitating ZIKV replication. miR-431-5p effectively downregulated the expression of CD95 protein, consequently promoted the phosphorylation and nuclear localization of NF-kB, which resulted in the activation of anti-viral status, leading to the suppression of viral *** study demonstrated that the EVs produced by IFN beta-treated MSCs could effectively convey antiviral activity.

关键词： coronavirus   PEDV   MHC-I   NLRC5   NSP1  

摘要： Major histocompatibility complex class I (MHC-I) plays crucial roles against viral infections not only by initiating CD8(+) T cell immunity but also by modulating natural killer (NK) cell cytotoxicity. Understanding how viruses precisely regulate MHC-I to optimize their infection is important;however, the manipulation of MHC-I molecules by porcine epidemic diarrhea virus (PEDV) remains unclear. In this study, we demonstrate that PEDV infection promotes the transcription of NLRC5, a key transactivator of MHC-I, in several porcine cell lines and in vivo. Paradoxically, no increase in MHC-I expression is observed after PEDV infection both in vitro and in vivo. Mechanistic studies revealed that PEDV infection inhibits the translation of PEDV-elicited NLRC5 mRNA and the expression of downstream MHC-I proteins, without affecting the expression of physiological NLRC5 and MHC-I proteins. Through viral protein screening, we identified PEDV nonstructural protein 1 (nsp1) as the critical antagonist that inhibits NLRC5-mediated upregulation of MHC-I, and the nsp1's inhibitory effect on MHC-I requires the motif of 15 amino acids at its C-terminus. Notably, our results revealed that the cytotoxic ability of NK cells against PEDV-infected cells is similar to that against healthy cells. Collectively, our findings uncover an immune evasion mechanism by which PEDV-infected cells masquerade as healthy cells to evade NK and T cell immunity. This is achieved by targeting NLRC5, a key MHC-I transcriptional regulator, via nsp1.

关键词： Cancer   Cytokines   Immunology   Immunotherapy   Oncology  

摘要： The cytokine interleukin-18 (IL-18) has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18's anti-cancer efficacy. A "decoy-resistant" form of IL-18 (DR-18), that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential, has recently been developed. Here, we investigated the therapeutic potential of DR-18 in renal cell carcinoma (RCC). Using pan-tumor transcriptomic data, we found that clear cell RCC had among the highest expression of IL-18 receptor subunits and IL18BP of tumor types in the database. In samples from RCC patients treated with immune checkpoint inhibitors, IL-18BP protein expression increased in the tumor microenvironment and circulating in plasma in non-responding patients and decreased in the majority of responding patients. We used immunocompetent RCC murine models to assess the efficacy of DR-18 in combination with single- and dual-agent anti-PD-1 and anti-CTLA-4. In contrast to preclinical models of other tumor types, in RCC models DR-18 enhanced the activity of anti-CTLA-4 but not anti-PD-1 treatment. This activity correlated with intra-tumoral enrichment and clonal expansion of effector CD8+ T cells, decreased regulatory T cell levels, and enrichment of pro-inflammatory, anti-tumor myeloid cell populations. Our findings support further clinical investigation of the combination of DR-18 and anti-CTLA-4 in RCC.