课程文献中心 更多>>

关键词： Small extracellular vesicles   EVT   HLA class I molecules  

摘要： Introduction: Human pregnancy requires acceptance and support for the semi-allogeneic embryo and effective protection of both mother and fetus. A failure to adapt, from either side, may cause abortion. The placentaderived extracellular vesicles (EVs) have a crucial role in human implantation and pregnancy. These are lipid bilayer membrane-delimited, nano-to-micro sized extracellular microvesicles of endosomal origin, containing diverse signaling molecules, and functioning as short and long-distance messengers. We have already shown that first-trimester placenta releases the soluble HLA-C and HLA-G KIR ligands to modulate maternal cytotoxicity via the KIR/HLA axis. This study is to find whether extravillous trophoblast (EVT) secretes these HLA class I molecules via small EVs. Methods: sEVs were isolated by ultrafiltration or precipitation from serum-free conditioned media from primary trophoblast-derived EVT, and non-tumor EVT-like model Sw71 cell line, cultured as monolayer and spheroids. sEVs from cultured placental explants served as a positive control. Combined data from several methods was used for their characterization including BCA, DLS, TEM, IEM, Dot blot, and FACS. Results: Primary trophoblast-derived EVT and Sw71 EVT-like cells produced intact and well-visible CD63+, HLAG- and HLA-C-bearing sEVs, regardless of culture mode and type of isolation. Both methods yielded sEVs sized 30-100 nm. Discussion: We show original data on the HLA-C secretion via sEVs by early pregnancy EVT and confirm the production of HLA-G-positive sEVs. A new asset to the usefulness of the Sw71 spheroid model as an implanting blastocyst surrogate is added as a tool to elucidate the sEV-based signalization in the implantation.

关键词： inflammatory bowel disease   T cell mediated colitis   adoptive transfer   IL-36G   IFNg signaling   Crohn's disease   ulcerative colitis  

摘要： Background Inflammatory bowel disease (IBD) is a multifactorial, chronic disease that affects approximately 1.5 million people in the United States. Several important factors are implicated in the pathogenesis of IBD, one factor being dysregulation of the immune system. This dysregulation results in the accumulation and stimulation of innate and adaptive immune cells, and subsequent release of soluble factors, including pro-inflammatory cytokines. One of these cytokines is a member of the IL-36 cytokine family, IL-36 gamma, which is overexpressed in human IBD and experimental models of colitis. In this study, we explored the role of IL-36 gamma in promoting CD4+ T cell activation and cytokine *** Spleens and lymph nodes were collected from wild-type and IFN gamma-/- mice and were processed into cell suspensions to isolate na & iuml;ve CD4+ T cells. Na & iuml;ve CD4+ T cells were stimulated with IL-36 cytokines. IFN gamma and TNF alpha were evaluated by ELISA using cell culture supernatants, and cell culture pellets were used to isolate RNA for qPCR. Na & iuml;ve CD4+ T cells previously stimulated in the presence or absence of IL-36 gamma, from wild type (WT) or IFN gamma-/- mice were transferred to Rag-/- mice to induce colitis. Fecal pellets were collected from mice during disease to analyze lipocalin (LCN2) levels from fecal supernatants. After euthanasia, colons, spleens, and mesenteric lymph nodes were harvested and processed into cell suspensions for intracellular cytokine *** Our results demonstrate that IL-36 gamma stimulation of naive CD4+ T cells significantly induced IFN gamma expression in vitro and was associated with augmented intestinal inflammation in vivo using the T cell transfer model of colitis. Using IFN gamma-/- naive CD4+ T cells, we observed a dramatic decrease in the ability of these cells to produce TNF alpha. Moreover, the transfer of these cells to Rag-/- mice did not cause robust *** These data no

关键词： 子宫内膜炎   甲羟孕酮   抗生素   炎性因子   子宫内膜受容性   安全性  

摘要： 就给予子宫内膜炎患者甲羟孕酮、抗生素联合干预方案对TNF-α、MMP-9等指标的影响进行分析。方法 随机将本院收治的82例子宫内膜炎患者分为两组。对照组实施常规抗生素治疗,观察组加用甲羟孕酮干预,对比两组干预效果。结果 治疗后观察组临床症状缓解时间、炎性因子指标、子宫内膜受容性指标等均优于对照组。结论 对子宫内膜炎患者实施治疗的时候,在抗生素治疗基础上加用甲羟孕酮可以发挥更好的干预效果,建议推广。

关键词： HLA matching   deep sequencing   next-generation sequencing   multilocus sequence typing   HLA alleles  

摘要： Introduction Accurate human leukocyte antigen (HLA) genotyping is critical for organ transplantation to ensure donor-recipient compatibility. Conventional methods, such as sequence-based typing (SBT), often face challenges in resolving allelic ambiguities, particularly in highly polymorphic regions of HLA loci. Therefore, this study aimed to develop 6 locus multiplex primers combined with Next-generation sequencing NGS for high-resolution of long sequenceshigh-resolution sequencing, focusing on improving sequencing depth and reducing *** Multiplex PCR primers targeting HLA-A, -B, -C, -DPB1, -DQB1, -DRB1 loci were designed using high-frequency alleles from public databases. PThe primers were optimized using as reference the sequencing depth across loci. The method was validated using SBT and probe capture-based targeted next-generation sequencing to evaluate its approach accuracy. Moreover, 770 samples from Chinese population were further studied to verify the allele frequency adding information about HLA types of this *** The optimized multiplex PCR-NGS sequencing showed depths within athe target range of 100-1000 with high accuracy determined in the 2ndtwo-digit ,and 4thfour-digit and six-digit HLA typing, with a reliability of >= 98%, >= 95% and >= 95% respectively in both *** Allele digits in the HLA-class I and II loci. However, in the 6th digit of HLA-C, -DQB1, and -DRB1 the accuracy was 94.74%. The developed multiplex PCR-NGS method offers a reliable, cost-effective approach for high-resolution HLA genotyping, and may be particularly suitable for clinical studies, especially in donor-recipient matching during organ transplantation.

摘要： Neuroblastoma (NB) is a highly aggressive childhood solid tumor with poor outcomes. Chimeric antigen receptor (CAR) T cells have shown limited efficacy in NB, with the best outcomes reported in patients with a low tumor burden, highlighting the need for further CAR optimization. One approach to addressing the high tumor burden involves engineering CAR T cells to release or express transgenic cytokines. However, its systemic toxicity remains an important therapeutic challenge. Here, we evaluated the efficacy of interleukin (IL)-15- and IL-21-enhanced glypican-2 (GPC2)-targeted CAR T cells (GPC2-CAR T cells) in targeting high-burden NB. Three strategies for expressing the cytokines were evaluated: constitutive secretion (GPC2-CAR+***21), constitutive membrane-tethered expression (GPC2-CAR+***21), and NFAT-inducible membrane-tethered expression (GPC2-CAR+***21). Engineered GPC2-CAR T cells were tested in vitro and in vivo using high NB-burden xenograft models. Additionally, single-cell RNA sequencing was used to profile the effector cells in the tumor microenvironment. All three versions of GPC2-CAR T cells significantly enhanced killing against a high NB burden, both in vitro and in vivo, relative to control GPC2-CAR T cells. Mice treated with GPC2-CAR+***21 exhibited significantly lower anorexia-associated morbidity/mortality. Supporting these data, tumor-infiltrating GPC2-CAR+***21 developed an immunosuppressive transcriptional profile upon tumor regression, leading to prolonged survival in treated mice. In contrast, GPC2-CAR+***21 maintained a pro-inflammatory transcriptional signature despite near tumor clearance, resulting in hypercytokinemia and death. NFAT-inducible co-expression of tethered IL-15/IL-21 enhanced GPC2-CAR T-cell function against a high NB burden with acceptable tolerability in mice. Further studies are required to validate these findings.

关键词： Psoriasis   Euphorbia humifusa willd   Keratinocyte   Inflammation   IL-17 signaling pathway  

摘要： Ethnopharmacological relevance: Psoriasis is a chronic immune-mediated skin disease characterized by the infiltration of multiple inflammatory cells and abnormal differentiation of keratinocytes in the skin. The treatment of psoriasis is primarily based on immunosuppressive drugs;however, their long-term use can lead to various adverse effects. Euphorbia humifusa Willd. (EuH) is used in traditional Chinese medicine for its anti-inflammatory properties and effects on skin diseases such as psoriasis. Aim of the study: This study aimed to evaluate the anti-psoriasis effects of EuH extract, and explore its underlying mechanisms. Methods and materials: The main components of EuH extract were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology. Then, we administered EuH extract to imiquimod-induced psoriasis mice for 6 consecutive days, and evaluated the effects according to the psoriasis area and severity index (PASI), spleen index, histological analysis, immunohistochemical and immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qRTPCR), and flow cytometry analysis. The potential mechanism was revealed using RNA sequencing (RNA-seq) and validated by target prediction, ELISA, qRT-PCR and Western blot (WB) analysis. Results: The UPLC-QTOF-MS/MS analysis showed that phenolics were the essential components in the water extracts of EuH, including flavonoids, phenolic acids, and gallotannins. Treatment with EuH alleviated psoriatic symptoms including skin condition, high PASI scores (erythema, scaling, and thickness), and spleen index values in imiquimod-induced mice. EuH treatment also inhibited keratinocyte hyperproliferation, reduced epidermal thickness, reduced inflammatory cell infiltration into skin lesions, decreased the mRNA levels of inflammatory factors, and restored T and Treg cellular balance in the spleen. RNA-seq, ELISA, qRT-PCR and WB analyses indi

关键词： IL-35 blockade   MR imaging   radioimmunotherapy   theranostics   tumor microenvironment  

摘要： The cGAS-STING signaling pathway has emerged as a promising target for cancer immunotherapy. However, STING agonists have a dual-edged nature. Although they enhance antitumor T cell activity, STING agonists also elicit protumorigenic effects by promoting IL-35-producing B regulatory (Breg) cells, suppressing natural killer (NK) cell density, and fostering immune suppression. To address these challenges, this work develops a tumor microenvironment-responsive hollow mesoporous nanosystem that degrades under high glutathione conditions, thereby releasing the STING agonist MSA-2 and Mn ions. This nanosystem facilitates magnetic resonance imaging-guided chemodynamic therapy and radiosensitization, efficiently activating the cGAS-STING pathway by disrupting mitochondrial and nuclear DNA. Notably, by integrating this nanosystem with an anti-IL-35 blockade, this work successfully mitigates the Breg cell-mediated suppression of NK cells, restores innate immune responses, and enhances antitumor efficacy. This study highlights the pivotal role of anti-IL-35 in reversing immunosuppression, enhancing innate immunity, and establishing a synergistic theranostic platform for molecular imaging-guided cancer radioimmunotherapy.

关键词： Hepatitis B infection   functional cure   sterilizing cure   cccDNA   HBV DNA integration   viral persistence   ASO   Antisense Oligonucleotides   Cas9   CRISPR-associated Protein 9   cccDNA   Covalently Closed Circular DNA   CHB   Chronic Hepatitis B Infection   CpG   Cytosine Phosphoguanine   CRISPR   Clustered Regularly Interspaced Short Palindromic Repeats   ddPCR   Droplet-Digital Polymerase Chain Reaction   DDB1   Damaged DNA Binding Protein 1   DR1   Direct Repeat 1   dslDNA   Double-Stranded Linear DNA   H3K27ac   Histone H3 Lysine 27 Acetylation   H3K4me2   Histone H3 Lysine 4 Dimethylation   H3K4me3   Histone H3 Lysine 4 Trimethylation   HBcAg   Hepatitis B Core Antigen   HBsAg   Hepatitis B Surface Antigen   HBV   Hepatitis B Virus   HBx   Hepatitis B X Protein   HBeAg   Hepatitis B e Antigen   HCC   Hepatocellular Carcinoma   HDAC   Histone Deacetylase   HSPG   Heparin Sulfate Proteoglycans   IFIT1   Interferon-Induced Protein with Tetratricopeptide Repeats 1   IFN   Interferon   LINE   Long Interspersed Nuclear Element   NA   Nucleos(t)ide Analogues   NGS   Next-Generation Sequencing   NHEJ   Non-Homologous End-Joining (DNA repair pathway)   NTCP   Sodium-Taurocholate-Cotransporting Polypeptide   PARP1   Poly-ADP Ribose Polymerase 1   PAS   Polyadenylation Signal   pDCs   Plasmacytoid Dendritic Cells   PD-1   Programmed Cell Death Protein 1   PD-L1   Programmed Death-Ligand 1   pgRNA   Pre-genomic RNA   qPCR   Quantitative Polymerase Chain Reaction   rcDNA   Relaxed Circular DNA   RNAi   RNA Interference   SAHA   Suberoylanilide Hydroxamic Acid   siRNA   Small Interfering RNA   SINE   Short Interspersed Nuclear Element   TLR   Toll-like Receptor   WGS   Whole Genome Sequencing   XRCC4   X-ray Repair Cross-Complementing Protein 4  

摘要： HBV persists within the hepatocyte due to the presence of intranuclear covalently closed circular DNA (cccDNA) and double-stranded linear DNA (dslDNA) integration. These bodies pose formidable challenges for achieving HBV functional and sterilizing cure. In this virology-focused review we provide an overview of HBV persistence with consideration of the negative implications for chronic infection. We also discuss advancements in HBV therapies that aim to disrupt these targets.

关键词： recurrent aphthous stomatitis   macrophage   IL-17a   IFN-gamma   mucosa immunity   CD4+T cell   anti-Ly6G  

摘要： Recurrent aphthous stomatitis (RAS) is a common chronic oral disease with unclear pathogenesis. Chronic inflammation associated with RAS has been linked to the dysregulation of local immune responses. We used a murine model of acetic acid-induced chemical stomatitis (CS) to assess changes in the systemic and local immune environments of CS mice relative to healthy mice. Flow cytometry revealed a significant increase in neutrophil infiltration and elevated proportions of Th1 (CD4+IFN-gamma+) and Th17 (CD4+IL-17a+) cells in the lingual mucosa of CS mice 7 d after CS induction, indicating an active inflammatory response in the CS immune microenvironment. Given that Th17 cells indirectly recruit neutrophils, we used Rorc-/- mice to evaluate the effects of Th17 cell depletion. Neutrophil infiltration was markedly reduced, and decreased tissue damage was observed in the lingual mucosa of Rorc-/- mice, as confirmed by hematoxylin and eosin staining. To further investigate the mechanism underlying Th17 cell generation in stomatitis, we induced CS in Il6ra-/- mice, which exhibited significantly reduced inflammatory cell infiltration and ulcer severity in the lingual mucosa. Treatment with an anti-Ly6G antibody treatment, which can directly target and deplete neutrophils, also significantly reduced local inflammation in the CS mouse immune microenvironment and diminished Th1 and Th17 cell infiltration, indicating a positive feedback loop between Th17 cells and neutrophils in stomatitis. In conclusion, the IL-6-Th17-neutrophil axis plays a critical role in stomatitis pathogenesis, suggesting that targeting this axis could present a novel immunotherapeutic strategy for alleviating mucosal damage in patients with RAS.

关键词： 法莫替丁   急性肠胃炎   血清IL-6   hs-CRP  

摘要： 针对急性肠胃炎患者实施法莫替丁辅助治疗,探究其对PCT、hs-CRP、TNF-α、IL-6的影响。方法 样本研究对象:2022.12-2024.12期间参与诊治的86例急性肠胃炎患者,以不同治疗方法实施组别划分,43例/组,参照组为患者开展甲氧氯普胺治疗,试验组予以法莫替丁辅助治疗,分析两组评价效果。结果 与参照组比较分析,试验组上腹疼痛消失时间、腹泻消失时间、恶心呕吐消失时间及其消化不良消失时间更短,P<0.05;试验组PCT、hs-CRP、TNF-α、IL-6、胃泌素、胃动素均低于参照组,有效率较比参照组更高,P<0.05;两组不良反应对比无差异,P>0.05。结论 将法莫替丁辅助治疗用于急性肠胃炎患者中可显著降低炎性因子水平和胃泌素、胃动素水平,缩短症状改善时间,且不会显著增加不良反应,具有一定用药安全性。