课程文献中心 更多>>

关键词： Coccidiosis   Major histocompatibility complex   Alloantigen system   Disease resistance   Chicken  

摘要： Coccidiosis, a major poultry protozoal disease caused by several Eimeria species, compromises gut health causing significant losses. This study assessed the association of haplotypes of the major histocompatibility complex (MHC) and other blood alloantigens found in commercial egg production chickens with resistance to coccidiosis. Pedigreed White Leghorn offspring segregating for the MHC-B region, plus four additional alloantigen systems A (C4BPM), D (CD99), E (FCAMR), and I (RHCE) were tested for differential resistance to coccidiosis in five 26-day (d) trials (n= 235 birds in total). On d 19, all birds were inoculated with a cocktail of E. acervulina, E. maxima, and E. tenella oocysts and allocated to individual cages. Phenotypes evaluated included body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), gross and microscopic lesion scores (GLS and MLS), and oocyst shedding (oocysts per gram, OPG). Haplotypes of the five blood systems were determined by SNP genotyping. A positive and negative association means an increase and decrease in a phenotypic trait, respectively, with each additional copy (0, 1 or 2) of a given haplotype. Results were considered statistically significant at P <= 0.05. The CD99-H01 haplotype association was positive with BWG but negative with FCR. Genotype B21B21 had the highest GLS in the jejunum establishing a positive association between MHC B21 and jejunal GLS. Further, the B12B15 genotype had a lower E. maxima OPG compared with the B12B21 genotype. The I system I-H01 haplotype had a negative association with jejunal and cecal GLS. Duodenal GLS was lower in E-H02/H02 compared to the E-H07/H07 genotype of the E system. Haplotypes B21, blood systems D-H01, E-H02, and I-H01 were associated with improved resistance to coccidiosis. The association of specific haplotypes of the MHC-B and other alloantigen systems D, E, and I with resistance and susceptibility traits during mixed Eimeria infection underscores the need for furthe

关键词： T2D   EIAS   Glycemic Variability   Insulin Antibodies   HLA   Proteomics  

摘要： Aims: Insulin antibodies (IAs) are prevalent in insulin-treated patients with diabetes and may cause immunological dysglycemia, known as exogenous insulin antibody syndrome (EIAS). This study aims to elucidate the clinical, genetic, and proteomic characteristics of patients with concurrent type 2 diabetes (T2D) and EIAS. Methods: This was a case-control study with 177 IA-positive and 177 IA-negative T2D patients receiving insulin therapy. Among the IA-positive group, 46 patients with hypoglycemia and aberrantly elevated molar ratio of insulin to C-peptide (ICPR > 1) were identified as EIAS cases, followed with human leukocyte antigen (HLA) genotyping and plasma proteomic analysis by Olink platform. Results: Patients with EIAS exhibited greater glycemic variability than patients in other groups (IA-positive ICPR <= 1 or IA-negative). Higher ICPR was associated with increased glycemic variability in the IA-positive group. DRB1*0405-DQA1*03-DQB1*0401, DRB1*0803-DQA1*0103-DQB1*0601, and DRB1*1501-DQA1*0102-DQB1*0502 are the susceptible HLA haplotypes for EIAS. Additionally, nine differentially expressed proteins were identified in EIAS patients, with GALNT3, IL10, and CCL28 showing promising diagnostic performance. Conclusions: IA-positive patients with remarkably elevated ICPR are prone to glycemic variability and should be evaluated for the diagnosis of EIAS. In this pilot study with limited sample size, EIAS is associated with unique HLA-DR-DQ risk haplotypes and enhanced immunoinflammatory response.

关键词： Lipopolymersome   Pep-1L peptide   IL13RA2 receptor   Glioblastoma   Low dosage  

摘要： Glioblastoma is the most aggressive form of primary malignant brain cancer. The blood-brain barrier limits the penetration of therapeutic agents and often contributes to a poor prognosis. Targeted therapy, an emerging strategy, shows promise for improving glioblastoma treatment outcomes by reducing drug dosages and mitigating drug resistance. Interleukin-13 receptor alpha 2, which is overexpressed in glioblastoma, serves as a potential target for such therapy. In this study, we investigated Pep-1L-modified, temozolomide-loaded lipopolymersomes for targeted delivery to interleukin-13 receptor alpha 2-positive glioblastoma. These nanoparticles exhibited a uniform size of approximately 100 nm and remained stable for up to 96 h under physiological conditions (pH 7.4). Temozolomide was released in a controlled manner, reaching nearly 100 % release over 96 h. The Pep-1L peptide demonstrated specificity for interleukin-13 receptor alpha 2-positive glioblastoma and enhanced cellular internalization via receptor-mediated endocytosis. Additionally, the IC50 was reduced by approximately 9.5-fold in interleukin-13 receptor alpha 2-positive U-251 MG cells, highlighting the potential of Pep-1L-modified, temozolomide-loaded lipopolymersomes as an effective targeted therapy for glioblastoma. This approach suggests a pathway toward more personalized and effective treatments for glioblastoma patients.

关键词： GBM   TMZ   ADAM12   TNF-alpha   DNA damage response  

摘要： Development of temozolomide (TMZ) resistance is a critical factor contributing to a poor prognosis in glioma patients. TMZ resistance is also closely associated with the phosphorylation level of NF-kappa B, yet targeted inhibition of NF-kappa B activity in glioma can be leveraged to overcome TMZ resistance. ADAM12, a protein significantly overexpressed in glioma cells, is implicated in the pathogenesis and progression of glioma, yet its role in the development of TMZ resistance is completely understood. We found that knockdown of ADAM12 was shown to arrest the glioma cell cycle, enhance apoptosis, inhibit DNA damage repair mechanisms, and sensitize glioma cells to TMZ. Targeting ADAM12 in vivo was found to increase the sensitivity of glioma cells to TMZ. Survival analysis indicated that ADAM12 serves as a prognostic marker for TMZ treatment. Using ELISA and protein interaction predictions via docking simulation, we identified the TNF-alpha shedding function of ADAM12 as a critical regulator of glioma progression. Furthermore, in glioma cell lines with unmethylated MGMT, the knockdown of ADAM12 enhanced sensitivity to TMZ by inhibiting the TNF-alpha/NF-kappa B pathway and reducing MGMT expression. In all, these results demonstrated that ADAM12 aids in shedding of membrane-bound TNF-a to drive TMZ resistance in glioma.

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： 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

摘要： Herpes simplex keratitis (HSK) is a leading cause of corneal blindness globally, primarily resulting from herpes simplex virus type 1 (HSV-1) infection. HSK can cause pervasive and irreversible corneal nerve damage, leading to decreased corneal sensitivity and vision loss. Interleukin (IL)-33, a multifunctional cytokine, plays an important role in immune and inflammatory responses. However, the effects of IL-33 on nerve damage associated with HSK and the underlying mechanisms remain poorly understood. In this study, we first evaluated the effects of IL-33 on the severity of HSK and corneal nerve damage in a mouse model of HSK. The mechanisms of IL-33 on the production of neuroprotective factors by corneal epithelial cells (HCE-Ts) were investigated in an HSV-1 infection model in vitro. Additionally, the role and mechanism of IL-33 in regulating macrophage polarization for neuroprotection were investigated through in vitro co-culture experiments. The results indicated that IL-33 reduced the severity of HSK and protected corneal nerves in HSK mouse model. Mechanistically, IL-33 promoted the production of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) via activation of the GSK3 beta/beta-catenin signaling pathway in corneal epithelial cells. Furthermore, IL-33 promoted M2 macrophage polarization through activation of the JAK2/STAT6 pathway, which in turn attenuated inflammatory responses and reduced neuronal apoptosis. These findings reveal the neuroprotective mechanisms of IL-33 in HSK and offer new insights for further research and treatment of HSK.

关键词： 复发性流产   寿胎丸   血管内皮生长因子   可溶性血管内皮生长因子受体-1   白细胞介素17  

摘要： 目的：研究寿胎丸加味辅助治疗复发性流产患者效果及对血清血管内皮生长因子（vascular endothelial growth factor，VEGF）、可溶性血管内皮生长因子受体-1（soluble fms-like tyrosine kianse-1，sFLT-1）、白细胞介素17(interleukin-17， IL-17)的影响。方法：选取2023年1月～2024年3月医院治疗的复发性流产患者96例，按照随机数字表法均分为两组，各48例患者。对照组采用常规西药治疗，观察组在对照组基础上增加寿胎丸加味辅助治疗，用药至孕12周。比较两组患者的疗效，中医证候积分变化，血清VEGF、sFLT-1、IL-17水平，不良反应发生情况。结果：观察组治愈率87.50%、对照组70.83%，观察组高于对照组（P＜0.05）。治疗后，两组患者神疲肢软、肢体寒冷、头晕耳鸣、夜尿频繁积分均显著降低，观察组低于对照组（P＜0.05）。治疗后，两组患者血清VEGF水平明显降低，sFLT-1、IL-17水平明显升高，观察组患者血清VEGF水平高于对照组，sFLT-1、IL-17水平低于对照组，差异有统计学意义（P＜0.05）。两组均无严重不良反应发生。结论：寿胎丸加味辅助治疗复发性流产患者效果满意，能够有效调控血清内炎症因子与血管内皮相关因子，促进患者的症状缓解，保证妊娠安全。

关键词： Treatment   Immune response   Biotechnology  

摘要： Psoriasis is an inflammatory skin disease with aberrant epidermal differentiation and chronic inflammation. Plant-derived exosome-like nanovesicles (PDNVs) are exosome-mimetic structures isolated from plants with enhanced bioavailability and solubility. Herein, we investigated the therapeutic efficacy of PDNVs for psoriasis treatment. In our initial phenotype-driven screen, PDNVs from apple, garlic, and shallot displayed both pro-differentiation and anti-inflammatory activity in vitro. In imiquimod (IMQ)-induced psoriasis-like murine model, topical application of either shallot or garlic PDNV hydrogels led to complete recovery of normal skin phenotype. In porcine skin ex vivo assay, both shallot and garlic PDNVs displayed percutaneous penetration up to the suprabasal epidermis. Using next generation sequencing and quantitative mRNA profiling in keratinocytes and murine skin, we elucidated a suppressive effect of shallot and garlic PDNVs on IL-17 signaling via modulation of upstream nuclear factor erythroid-2-related factor 2 (NRF2) pathway. Since PDNVs are economical to produce, shallot and garlic PDNVs could be natural and cost-effective topical alternative for psoriasis.