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摘要： Background:Patients living with Human Immunodeficiency Virus (PLWH) develop accelerated liver fibrosis, but the exact mechanism remains unknown. Hepatic stellate cell (HSC) activation is the cornerstone for liver fibrosis and influenced by multiple factors, such as viral infection, hepatocellular injury, chronic immune activation, gut mucosal barrier dysfunction, and microbial translocation. Unlike gram-negative bacterial products, the impact of gram-positive microbial products in Human Immunodeficiency Virus 1 (HIV-1) associated liver inflammation and fibrosis remains poorly understood. In this study, we investigated the effect of lipoteichoic acid (LTA), a major gram-positive bacterial component, on HSCs in the context of HIV-1 infection. Methods:Human HSCs were isolated from the livers of both non-HIV and HIV-infected patients undergoing hepatic resection. The inflammatory responses of HSCs to LTA stimulation were measured by ELISA before or after HIV-1BaL ex vivo expision. Western blotting, ChIP-qPCR and RNA-seq were used to reveal the mechanisms contributing to the IL-8 response to LTA stimulation and HIV-1BaL exposure in HSCs. Results:While LTA stimulation modestly increased IL-8 production in HSCs, this effect was significantly amplified in HIV-1-infected HSCs. Elevated IL-8 levels were detected in HIV-1+ liver sections, and IL-8 treatment of cultured HSCs significantly increased α-SMA and COL1A1 expression, supporting IL-8 as a key inflammatory driver of liver fibrosis in HIV-1 individuals. Transcriptomic analyses implicated histone acetylation as a regulator of the enhanced IL-8 response of HSCs to LTA in HIV-1 infection. Consistent with this, treatment with Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, further increased the IL-8 response in HIV-1-infected HSCs. ChIP-qPCR confirmed that histone H4K5 acetylation facilitated IL-8 promoter transactivation, rendering HIV-1-infected cells more responsive to LTA. Conclusions:HIV-1 infection sensi

关键词： 嗜酸细胞性食管炎   度普利尤单克隆抗体   皮炎   特应性   进食梗阻  

摘要： 嗜酸细胞性食管炎(EoE)是一种由过敏原诱发、免疫反应介导的慢性食管炎症，以食管功能障碍及食管黏膜嗜酸性粒细胞浸润为主要特征。成人EoE患者的典型表现为吞咽困难、进食梗阻，以及胃食管反流病样症状，且常合并食物过敏史和一种或多种特应性疾病。既往我国EoE的药物治疗主要包括质子泵抑制剂和口服糖皮质激素，本文报道1例因合并特应性皮炎而应用度普利尤单克隆抗体治疗的EoE病例，并结合文献对国内外EoE疾病诊治的相关进展进行探讨。

摘要： 前不久,湖南怀化向女士的6岁儿子在跟家里的狗玩耍时,不小心被咬伤了手臂,伤口虽不大,但有明显出血. 她不敢耽搁,赶紧带儿子去附近医院的犬伤门诊处理伤口,接种狂犬疫苗. 但医生还建议,要给儿子打一针"单抗",一支600多元. 按照体重计算,儿子需要打两针,得花掉一千多元,是一笔不小的开支.

关键词： Vasorin(VASN)   树鼩   单克隆抗体  

摘要： 目的 通过表达和纯化树鼩Vasorin（VASN）重组蛋白，免疫小鼠制备抗树鼩VASN单克隆抗体并探讨抗体的应用。方法 用反转录PCR（Reverse Transcription-Polymerase Chain Reaction，RT-PCR）法体外扩增树鼩Vasn基因全长序列，将树鼩Vasn基因插入pET30a载体中，构建树鼩pET30a-VASN重组载体，对重组质粒用BamHI酶和SalI酶进行双酶切和测序鉴定；将测序正确的重组载体转化至大肠杆菌BL21（DE3），异丙基-β-D-硫代半乳糖苷（Isopropyl β-D-thiogalactoside，IPTG）诱导表达树鼩VASN重组蛋白；通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳（Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis，SDS-PAGE）电泳分离蛋白，氯化钾（Potassium chloride，KCl）切胶纯化树鼩VASN重组蛋白；将纯化的树鼩VASN重组蛋白对BALB/c小鼠进行4次免疫，酶联免疫吸附实验（Enzyme Linked Immunosorbent Assay，ELISA）检测小鼠血清效价；取效价达到1:10 000以上的小鼠脾脏细胞进行细胞融合，通过含黄嘌呤、氨基蝶呤及胸腺嘧啶核苷（Hypoxanthine-Aminopterin-Thymidine，HAT）的培养基筛选杂交瘤细胞，ELISA法筛选出能够分泌特异性抗体的阳性杂交瘤细胞株，并通过有限稀释法获得单克隆细胞株；通过腹水诱生法大量制备VASN单克隆抗体并利用rProtein G纯化抗体，ELISA、实时定量反转录PCR （Real-Time Quantitative Reverse Transcription PCR，qRT-PCR）、Western blotting检测单克隆抗体的亲和力和特异性，以及树鼩永生化成纤维细胞和树鼩组织中VASN的表达情况。结果 成功扩增出树鼩Vasn基因全长序列并构建了树鼩pET30a-VASN重组质粒载体，重组质粒载体经测序得到的序列与树鼩Vasn目的基因序列一致；重组载体表达后的蛋白主要以包涵体的形式存在，重组树鼩VASN蛋白纯化后的纯度达到90%，符合后续免疫实验的要求；利用重组树鼩VASN蛋白4次免疫小鼠后，小鼠血清抗体效价达1:729 000；利用杂交瘤技术及有限稀释法获得单克隆阳性杂交瘤细胞株，通过腹水诱生法及纯化后得到的单克隆抗体，ELISA法测定单克隆抗体的亲和力常数值达2.59×107mol/L；Western blotting检测单克隆抗体特异性，结果显示，树鼩VASN单克隆抗体能与树鼩VASN重组蛋白结合，而与猪视黄醇结合蛋白4（Retinol-Binding Protein 4，RBP4）重组蛋白、人源VASN-富含亮氨酸重复序列（Leucine Rich Repeat，LRR）重组蛋白以及牛血清白蛋白（Bovine Serum Albumin，BSA）标准蛋白均无结合反应；Western blotting检测树鼩各主要组织VASN表达，结果显示抗树鼩VASN单抗能与树鼩的主要器官组织（心脏、肝脏、脾脏、肺脏、肾脏、肌肉）在相对分子量约70 000位置出现特异性的条带且背景清晰；qRT-PCR检测结果显示树鼩脾脏组织和肺脏组织Vasn的mRNA表达水平相对较高，利用树鼩VASN单克隆抗体进行免疫组化检测，发现该基因mRNA水平表达较高的树鼩脾脏组织、肺脏组织、树鼩永生化成纤维细胞中免疫组化呈现阳性结果，在相对低表达的组织中呈现阴性结果。结论 成功制备了抗树鼩VASN的单克隆抗体，该抗体可用于树鼩永生化成纤维细胞、树鼩脾脏组织和肺脏组织免疫组化检测，研究结果为进一步探索VASN在树鼩模型中功能研究提供了重要的工具。

摘要： Highlights•We experienced Surfer's myelopathy (SM) occurred during exercise unrelated to surfing. •Spine MRI showed T2 hyperintensity with “pencil-like” long-axis lesion, typical for SM. •Significant elevation of IL-6 levels were seen in the CSF. •The nerve conduction tests indicated motor dominant neuropathy in the lower limbs. •The flaccid paralysis and sensory loss only slightly improved after steroid pulse therapies.

关键词： Acne vulgaris   Interleukin-19   Global acne grading system (GAGS)   Case-control  

摘要： Acne vulgaris (AV) has a multifactorial pathogenesis, with inflammation being a key factor. The pro-inflammatory role of interleukin (IL)-19 has been explored in several systemic and some dermatological conditions. This study aimed to analyse serum levels of IL-19 in cases as well as healthy controls and to assess its correlation with the disease severity. A cross sectional, observational, analytical study was performed over a time period of 18 months at a tertiary care hospital. The study included 37 clinically diagnosed cases of acne aged between 16 to 30 years and 37 age and sex matched controls. Severity of the lesions was calculated using the Global Acne Grading System (GAGS). IL-19 levels of all the participants were measured with the help of quantitative Enzyme Linked Immunosorbent Assay (ELISA). The Spearman's rank correlation coefficient was used to evaluate the relationship between serum levels of IL-19 and the severity of AV, and a p-value of less than 0.05 was considered statistically significant. In this study, serum IL-19 levels showed a positive correlation with both the patients' age and the duration of their symptoms, with p values of 0.04 for each. The median serum IL-19 levels were observed to be higher in the cases (80.89 ng//L) as compared to controls (44.82 ng/L), although this difference was not statistically significant (p = 0.095). Additionally, no significant correlation was found between IL-19 levels and the severity of acne (p = 0.45). Unlike prior work, our study found no link between IL-19 and severity of AV. Thus, we conclude that IL-19 may not be a reliable marker of the disease severity as previously stated and further research, preferably in larger sample size is warranted to confirm the same.

摘要： OBJECTIVE:Cutaneous polyarteritis nodosa (cPAN) is a rare necrotizing vasculitis that primarily affects small-to-medium-sized arteries in subcutaneous tissue. cPAN is often characterized by a chronic and relapsing disease that presents with skin ulcers, livedo, and painful erythema. In this study, we evaluated the efficacy of anti-TNF-α inhibitor treatment for cPAN-associated refractory leg ulcers. METHODS:This retrospective study was conducted between 2016 and 2023 at three medical institutions in Japan and targeted patients with cPAN presenting with refractory leg ulcers who were treated with anti-TNF-α inhibitors. The diagnosis of cPAN was histologically confirmed, and patients with secondary PAN were excluded. Data on the clinical background, treatments, ulcer status, and glucocorticoid dosages were collected, and the therapeutic efficacy of the treatment was evaluated. RESULTS:Ten patients were included, with a mean age of 51 years, and nine were female. All patients presented with recurrent leg ulcers. Anti-TNF-α inhibitors included adalimumab (five cases), etanercept (four cases), and infliximab (one case). Complete epithelialization of the leg ulcers was achieved in all patients, and the average glucocorticoid dose was successfully reduced from 20 mg/day to 3.5 mg/day. Additionally, five patients achieved a glucocorticoid-free status. No serious adverse events were observed in any of the patients. CONCLUSION:Anti-TNF-α inhibitors suggested therapeutic efficacy for cPAN-associated refractory leg ulcers and enabled ulcer epithelialization and significant glucocorticoid dose reduction. These findings support the utility of anti-TNF-α inhibitors in the management of refractory leg ulcers in cPAN, highlighting the need for further large-scale studies to validate the results.

摘要： Purpose: Developing T-cell or vaccine therapies for pancreatic ductal adenocarcinoma (PDAC) has been challenging because of a lack of knowledge regarding immunodominant, cancer-specific antigens as PDAC are characterized by a scarcity of genomic mutation-associated neoepitopes, and effective approaches to discover them are *** Design: An advanced mass spectrometry approach was employed to compare the immunopeptidome of PDAC tissues and matched normal tissues from the same ***: This study identified HLA class I-binding variant peptides derived from canonical proteins, which had single amino-acid substitutions not attributed to genetic mutations or RNA editing. These amino-acid substitutions appeared to result from translational errors. The variant peptides were predominantly found in tumor tissues, with certain peptides common among multiple patients. Importantly, several of these variant peptides were more immunogenic than their wild-type ***: The shared noncanonical neoepitopes identified in this study offer promising candidates for vaccine and T-cell therapy development, potentially providing new avenues for immunotherapy in PDAC. See related commentary by Yuan et al., p. 1821Conclusions: The shared noncanonical neoepitopes identified in this study offer promising candidates for vaccine and T-cell therapy development, potentially providing new avenues for immunotherapy in PDAC. See related commentary by Yuan et al., p. 1821

关键词： Cellular immune response   Dermatology   Immunology   Infectious disease   Molecular pathology   Parasitology  

摘要： Human cutaneous leishmaniasis (CL) is characterized by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome, but the cellular and molecular niches that facilitate IC molecule expression during leishmaniasis are ill defined. In Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) were enriched in skin lesions, and reduced PD-L1 expression early after treatment initiation was predictive of a cure rate following antimonial therapy. Here, we used spatial cell interaction mapping to identify IL-32-expressing CD8+ memory T cells and Tregs as key components of the IDO1/PD-L1 niche in Sri Lankan patients with CL and in patients with distinct forms of dermal leishmaniasis in Brazil and India. Furthermore, the abundance of IL-32+ cells and IL-32+CD8+ T cells at treatment initiation was negatively correlated with the rate of cure in Sri Lankan patients. This study provides insights into the spatial mechanisms underpinning IC expression during CL and offers a strategy for identifying additional biomarkers of treatment response.