Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

Quantitative analysis of sialic acids in Chinese conventional foods by HPLC-FLD

Background: Sialic acids are a family of ninecarbon sugar compounds with carboxylic acyl derivatives. It exists in bacteria, fish, mammals and other living organisms, participates in and regulates many important life events, such as cell recognition, membrane flow, endocytosis and so on. Sialic acid is usually located in the outermost layer of the sugar part of the cell membrane and the key positions of secreted glycoconjugates (glycolipids, glycoprotein and lipopolysaccharide). Sialic acid (Sia) is an important material foundation for variety of the structure and founction of glycoconjugates. Sia has been known as nearly 50 members, including N-acetylneuraminic acid (Neu5Ac), N-glycoulylneuraminic acid (Neu5Gc) and deaminoneuraminic acid (KDN) as its core monomer. The rest of the sialic acids are derived from these three monomers. The contents of Sia in Chinese food products are unknown. Objective: To determine the contents of Sia in raw and cooked red meat, seafood, poultry and so on. Design: The following food products were purchased from a Chinese supermarket: pork, beef, lamb, salmon, cod, tuna, cow milk, cheese, butter, duck, chicken and chicken eggs. Human milk was collected from Xiamen Maternity and Child Health Care Hospital (Xiamen, China). All tissues were homogenized and hydrolyzed with 0.05 M, 0.1 M and 0.2 M TFA for 150 min at 80°C in dark, respectively. The concentrations of Neu5Ac, Neu5Gc and KDN were determined by using HPLC with fluorescence detector. Results: The contents of total Sia (μg/g tissue or μg/mL liquid sample) in Chinese raw meat were highest in lamb (269.60), followed by pork (254.88), duck (200.63), chicken (162.86) and beef (88.03). The percentages of Neu5Gc were 36.08%, 26.48%, 0%, 0% and 28.40%, respectively. Cod contained higher levels of Sia (171.63) than salmon (104.43) and tuna (77.98). Only Neu5Ac was 50 found in detected aquatic product. Egg yolk contained the highest level of Sia (682.04), and a higher level of Sia (390.67) was found in the egg white. Also our result showed that human milk contained extremely high level of Sia (602.55). Neu5Ac was the predominant form of Sia in all the deteced samples. KDN was found in cow milk only among the samples, the content was 1.14 μg/g. Conclusion: The highest content of Sia in examined Chinese foods was found in 56 eggs, followed by lamb, pork, duck, cod, chicken, salmon, beef and tuna. Knowledge of the Sia content in conventional foods may help us to better understand possible medical disorders involving the uptake of the “non-human” Neu5Gc from our diet.

Structural Aberrations of Cellular Sialic Acids and Their Functions in Cancer Metastases

Sialic acids (neuraminic acids) are a special series of 9 carbon ring negatively charged carbohydrates, which has been found to be selectively changed in malignant cells from structures (both synthesis and structure modifications) to functions (up and down regulation in cells). Sialic acids, in single forms or conjugates, have been systematically studied both in lab and in clinics by GC, GC MS, NMR, HPTLC, HPLC and other modern analytical means. Sialic acids and related conjugates are predicted to be used in cancer diagnosis, cancer prognostic forecasting, designing of cancer chemotherapy regimens, uncovering carcinogenetic processes and neoplasm metastasis. Tumor cell regulative systems and pathways are correlated with sialic acids, which can be applied to prognostic evaluation of cancer patients, and antimetastatic chemotherapy by sialic acid derivatives and analogues. Searching for new biological characteristics of sialic acids in cells have also been extensively studied these days. In this paper, main stream discoveries and advancements are provided , also discussions of possible mechanisms and hypotheses are invoked.

Application of sialic acid/polysialic acid in the drug delivery systems

The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.

ROLE OF SIALIC ACID RESIDUES IN IRON BINDING BY HUMAN LACTOFERRIN

Lactoferrin(Lf-α)is a major constithent of the secondary granules of neutrophils, and is thought to be involved in bacteriostasis through high affinity binding of plasma Fe required for microbial growth.Lf-αis also the major Fe binding protein in milk. Fe bound to Lf-αis available for metabolic use.but the mechanism of Fe release from Lf-αis unknown.Treatment of human Lf-α with neuraminidase to remove sialic acid residues reduced its ability to bind Fe and caused release of Fe already bound to the protein. Reduction in Fe binding capacity was dependent on time of exposure to and concentration of neuraminidase,and was due to Lf-αloss or degradation. Readdition of sialic arid to desialylated Lf -a using a-2, 6-sialyltransferase restored Fe binding.The results suggest that sialylationdesialylation reactions could play a role in physiologic binding and release of Fe from the very high affinity binding sites of Lf -α.

SERUM LIPID-BOUND SIALIC ACID IN LUNG CANCER PATIENTS

Serum lipid-bound sialic acid (LSA) assay was evaluated for differential diagnosis between benign and malignant pulmonary disease.Mean serum LSA for normal controls was 13.7±3.7 mg/dl and the upper limit of the normal value was set at 19.8 mg/dl (95% confidence limit,one side).The specificity was 97.l% (95% confidence interval was 93.8%, 100.0%).The mean for benign pulmonary disease was 1 7.l±5.l mg/dl,the specificity was 89.l% (95% confidence interval was 80.9%,97.3%), and the sensitivity was 10.9%.The mean for malignant pulmonary disease was 27.l±7.9 mg/dl, and the sensitivity was 93.3%(95% confidence interval was 88.5%, 98.1%).The serum LSA levels for different malignant pulmonary diseases were different between small cell carcinoma and adenocarcinoma. The results indicate that serum LSA assay might be used as tumor marker to differentiate lung cancer from normal subjects or benign lung disease.

APOPTOSIS OF EPIDIDYMIS EPITHELIUM AND CONTENT OF EPIDIDYMIS SIALIC ACID FOLLOWING TORSED/DETORSED TESTES IN RAT

Objective To investigate the apoptosis of epididyrnis epithelium and the change of epididymissialic acid following torsed/detorsed testes. Methods Twenty four adult male Sprague-Dawley rats were subjected to unilateral 720 testicular torsion with the duration of 2h and 4h, then repaired. The ischemic epididymis were collected for detecting the content of sialic acid by using spectrophotometry and the apoptosis with TUNEL technique. Results There were no statistically significant difference in the apoptosis of epididymis epithelium [(9.51± 2.78)% vs (6.34±1. 98)%] and the content of epididymis sialic acid(23, 3851 ± 9. 2199mg/mgprot vs 19. 3661 6. 3373mg/mgprot) at 24h between following 2h-torsed/detorsed testes and those of sham group. There were statistically significant difference in the apopotosis of epididymis epithelium[ (46. 81 ±3. 55)% vs (6. 34±1. 98) % ] and the content of epididymis sialic acid (13. 7249±7. 8006mg/mgprot vs 19. 3661±6. 3373mg/mgprot) at 24h between following 4h-torsed/detorsed testes and those of sham group(P <0. 05). Conclusion The results suggest that the sialic acid-secreting-function of epididymis remain normal at 24h following 2h-torsed/detorsed testes, while the apoptosis index of epididymis epithelium do not increase. The epididymis would be injured at 24h following 4h-torsed/detorsed testes, while the apoptosis index increased.

Blockade of neutrophil recruitment to tumor sites based on sialic acid-modified nanoplatforms enhances the efficacy of checkpoint blockade immunotherapy

Checkpoint inhibitors are designed to rejuvenate depleted or suppressed T cells in the tumor microenvironment,relying on the immune system to control and kill tumors.However,accumulating evidence indicates that tumor-infiltrating neutrophils impede the proliferation and activation of T cells and determine the resistance to checkpoint blockade and chemotherapy.In this study,sialic acid ligand-modified colchicine derivative phospholipid complexes specifically targeted tumor-associated neutrophils in the peripheral blood,blocked neutrophil accumulation in tumors,and attenuated the inhibitory effect of infiltrating neutrophils on T cells.Neutrophil blocking therapy enhanced the immunotherapy effect of the PD-L1 antibody in S180 advanced tumors and 4T1 breast cancer.Our study found that PD-L1 antibody monotherapy increased the tumor infiltration of immunosuppressive neutrophils.Combination therapy with neutrophil blocking can greatly reduce tumor-infiltrating neutrophils and increase the proliferation of cytotoxic CD8^(+) T lymphocytes in the tumor.The combination therapy significantly improved the survival rate of mice with advanced S180 tumors and increased the sensitivity of immune checkpoint inhibitors to 4T1 cold tumors.

Bitter Melon (Momordica Charantia) Reduces Serum Sialic Acid in Type2 Diabetics: Evidence to Delay the Process of Atherosclerosis

More than 1000 herbal products have been used by diverse cultures of the world to treat hyperglycemia and among them bitter melon (Momordica charantia) is one of the most popular herbal resource. The beneficial effects of bitter melon is not limited to hypoglycaemia only, but it also ameliorates diet induced obesity, insulin resistance and exhibit cardioprotective effects. The present study attempts to investigate the effect of bitter melon fruit juice on a newly investigated risk factor, sialic acid in type2 diabetics. A total of 40 type2 diabetic patients, divided into group A (n = 20) and group B (n = 20) were investigated during the present study. The patients of group A were following bitter melon fruit juice treatment along with diet control, whereas the patients of group B were on diet control only. Serum sialic acid (SSA) decreased in group A from 66.20 ± 2.30 mg/dl to 63.50 ± 2.10 mg/dl (<0.11) but, increased in group B from 66.50 ± 1.70 mg/dl to 68.20 ± 2.50 mg/dl (<0.12), compared to baseline. Post-treatment between group comparison revealed a significant difference (<0.05). The beneficial effects on fasting plasma glucose (FPG) and glycohemoglobin (HbA1-c) were also greater in group A compared to group B as was the case with blood lipids, weight and blood pressure. The study provides another mechanism for the cardioprotective effect of bitter melon and further strengthens its value in the management of type2 diabetes.

New Extracellular Bacillus subtilis Lectins with Sialic Acid-Specificity

The purpose of this work is to perform a detailed study of carbohydrate specificity of the new extracellular bacilli lectins which is considered to determine mechanisms of the lectins action. Sources of lectins were bacterial strains from Ukrainian collection of microorganisms. The optimized protocol of bacilli lectins isolation and purification included precipitation with ammonium sulfate with subsequent gel filtration chromatography on Sepharose CL-6B. Hemagglutinating activity of bacilli lectins and their fine carbohydrate specificity to sialic acids and their derivatives as well as sialic asid-containing and asialic glycoconjugates were studied. The ability of extracellular bacilli lectins to discriminate a- and 13-conformation of carbohydrate molecule and the type of connection between the monomers was determined. Studied lectins showed the most affinity to glycoconjugates containing both types of sialic acids （N-acetylneuraminic acid （Neu5Ac） and N-glycolylneuraminic acid （NeuGc）） and it is supposed to be a basis of their diagnostic and analytical potential.

Correlation of Cerebrospinal Fluid Sialic Acid with Various Enzymes in Patients with Meningitis

Meningitis is often associated with cerebral compromise which may be responsible for neurological squeal in nearly half of the survivors. Little is known about the mechanisms of Central Nervous System （CNS） involvement in bacterial meningitis. The present study was undertaken to assess the changes in biochemical parameters including glucose, protein, Sialic Acid （SA） and various enzymes like Aspartate Aminotransferase （AST）, Alanine Aminotransferase （ALT）, Creatine Kinase （CK）, Gamma Glutamyltranspeptidase 7 （GGTP） and Lactate Dehydrogenase （LDH） have been determined in the Cerebrospinal Fluid （CSF） of the meningitis patients （n = 26） and compared with control subjects （n = 26）. Total Protein, CK, SA （P 〈 0.02）, AST （P 〈 0.001） and ALT （P 〈 0.0001） of meningitis patients were significantly higher, whereas, glucose （P 〈 0.05） and Gamma Glutamyltranspeptidase （GGT） （P 〈 0.01 and P 〈 0.05, respectively） were significantly lower than those of the controls. This study suggests that loss of integrity of brain-CSF barriers, sialic acid and enzyme profiles may contribute to the severity and neurological complications of meningitis.

离子交换树脂法规模化生产乳源酪蛋白糖巨肽及其对流感病毒的血凝抑制活性

目的:优化规模化生产乳源酪蛋白糖巨肽(CGMP)的工艺条件,并探讨其对流感病毒的血凝抑制能力。方法:以阴离子交换树脂为分离介质,唾液酸含量为产品的活性检测指标,分别从上样体积、上样流量、洗脱液浓度、洗脱液体积和树脂使用周期5个工艺条件,在前期小试和中试的基础上,考察从乳清粉中规模化生产CGMP;同时利用血球凝集抑制试验验证产品CGMP对流感病毒的抑制活性。结果:优化的CGMP产品技术路线为上样体积3BV、上样流量0.8 L/min、洗脱体积1BV、洗脱液浓度0.6 mol/L、树脂适宜使用周期4次。该工艺条件下处理乳清粉溶液体积为108 L(2160 g)、树脂36 L,得到CGMP产品21.183 g,得率为0.981 g/100 g,产品纯度为89.032%,回收率为51.972%,唾液酸含量为21.503 g/100 g,蛋白CGMP产品对流感病毒A(H1N1)和流感病毒B的最低抑制质量浓度分别为1.0000,1.2500 mg/mL。结论:利用优化的技术路线生产获得CGMP产品的纯度和唾液酸含量均优于市售商品CGMP,且对流感病毒有明显的抑制作用。

唾液酸结合免疫球蛋白样凝集素-15在食管鳞癌组织中的表达及意义

目的探讨免疫检查点唾液酸结合免疫球蛋白样凝集素-15(Siglec-15)在食管鳞癌中的表达及意义。方法免疫组化检测食管鳞癌组织、癌旁正常食管组织中Siglec-15表达情况,并比较分析其与食管鳞癌患者临床病理特征的关系。结果Siglec-15在食管鳞癌组织中表达阳性率为60.0%(48/80),高于癌旁正常食管组织中的23.75%(19/80)(χ^(2)=21.595,P<0.001)。食管鳞癌组织中Siglec-15蛋白表达与患者肿瘤直径、T分期、TNM分期、N分期及分化程度有关(χ^(2)=7.500,P=0.006;χ^(2)=10.342,P=0.001;χ^(2)=22.547,P=0.016;χ^(2)=20.508,P<0.001;χ^(2)=12.586,P=0.002)。结论Siglec-15在食管鳞癌组织中高表达,与患者的疾病进展显著相关。

食用燕窝对促进认知影响的定性研究

目的:系统评价燕窝对认知的影响。方法:在中国知网、万方、中国生物医学文献数据库、PubMed和Embase数据库中检索自2012年9月1日—2022年9月1日国内外发表的相关研究文献,并根据纳入排除标准对文献进行筛选。参照SYRCLE动物实验风险评估工具,对相关文献进行综合评价。结果:共纳入5项研究,均为动物模型实验。无论燕窝的来源、给药途径、治疗时间、治疗目的(营养、治疗或预防)是否一致,综述结果都表明,燕窝可以改善实验动物的认知功能,用于诱导性认知功能障碍的治疗,作为子代的认知营养增强剂,对动物暴露于脑毒性物质后续产生的认知损伤具有预防保护作用,且呈现出剂量依赖效应。并且,燕窝的促进认知作用可能与燕窝或其有效成分可以增强抗氧化能力,降低神经炎症和氧化应激反应有关。结论:动物实验表明,燕窝具有促进认知的潜在功效,但因缺乏人群实验,尙无法确定燕窝对人群认知的影响。

食物中唾液酸含量分布研究进展

目的:唾液酸广泛存在于多种生物组织中,有50多种存在形式,其中,N-乙酰神经氨酸(Neu5Ac)和N-羟乙酰神经氨酸(Neu5Gc)是最主要的2种存在形式。唾液酸具有抗炎、抗病毒和抗肿瘤等多种生物活性,并能有效促进婴儿的认知发育、增强学习和记忆能力。目前中国食物成分表中无唾液酸含量数据,本研究旨在总结和分析各类食物中唾液酸分布及含量,并推测每日膳食中可能的唾液酸摄入量。方法:在PubMed、Embase、Web of Science、中国知网、万方数据库、维普检索自建库至2022年6月国内外公开发表的相关研究文献。纳入测定食物中唾液酸分布与含量的定性与定量研究,包括一手研究数据、综述、系统综述等非一手研究数据,语言限定为中英文、意大利语;排除与主题无关、重复、数据不完整、无法获得全文的文章。结果:共检索出文献11187篇,本文共纳入35篇文献作为本综述的主要证据,其中,奶及奶制品、动物性食物、蔬菜类、水果类、谷薯类、其他食物文献各15、9、3、2、4、4篇。研究显示,燕窝中唾液酸含量最高,可高达116.2 mg/g。其次是动物性食物、奶及奶制品。动物性食物中唾液酸含量在0~4574.298μg/g、奶及奶制品中唾液酸含量在28~1596 mg/L。谷类、蔬菜类、水果类食物中含有微量或不含唾液酸,油、薯类中不含唾液酸。总结:动物性食物、奶及奶制品含有唾液酸,大豆及坚果类、蔬菜类、水果类、谷类中含有微量或不含唾液酸。

唾液酸结合免疫球蛋白样凝集素在细菌感染性疾病中的研究进展

唾液酸结合免疫球蛋白样凝集素(sialic acid-binding immunoglobulin-like lectins,Siglecs)在大多数白细胞上表达,并且在免疫细胞信号传导中起关键作用。最近的研究表明,许多细菌通过唾液酸(sialic acid,Sia)与Siglecs的相互作用来调控宿主免疫应答,影响疾病的发生发展。深入了解细菌致病机制对于破译潜在的有效治疗靶点和帮助人类管理细菌感染性疾病十分重要。本文就Siglecs的结构、生物学功能以及其在细菌感染性疾病中的研究进展作简要综述。

食用燕窝和唾液酸对抗氧化影响的定性研究

背景:燕窝的食用历史悠久,具有食药两用的特征,被人们尊崇为珍馐佳肴和滋补圣品。尽管有研究表明燕窝或其有效成分唾液酸具有抗氧化的功效,目前还缺乏系统分析燕窝的抗氧化作用的相关研究。目的:系统评价燕窝和唾液酸对抗氧化的作用及其潜在机制。方法:采用关键词“燕窝”或“唾液酸”以及“抗氧化”,针对2012—2022年间相关学术文献进行全面检索,包括PubMed、Embase、中国知网、万方和中国生物医学文献数据库。严格按照纳排标准筛选所检索的相关文章。文献风险评估采用SYRCLE动物实验风险评估工具。结果:6项动物模型实验研究被最终纳入。综述结果表明:燕窝和唾液酸有促进动物机体抗氧化能力的潜在功效,并存在剂量效应。燕窝和唾液酸可能通过增加抗氧化物质来提升抗氧化能力,同时减少炎症和氧化应激水平。结论:动物模型实验结果表明燕窝和唾液酸有助于提高抗氧化能力,并且效果与摄入量成正比。然而,由于目前缺乏相关的临床实验数据,因此尚无法确定燕窝对人体抗氧能力的影响。

半乳糖上调内皮细胞Siglec-9聚糖配体水平抑制巨噬细胞活性

目的探究半乳糖对人原代肺动脉内皮细胞上唾液酸特异性Ig样凝集素-9(sialic-acid-binding immunoglobulin-like lectin 9,Siglec-9)聚糖配体表达的影响及作用机制。方法采用流式细胞术确定内皮细胞表面Siglec-9聚糖配体的表达并鉴定该聚糖配体末端糖苷键类型;分别用左旋葡萄糖、葡萄糖、N-乙酰基葡萄糖、甘露糖、N-乙酰基甘露糖、半乳糖、唾液酸、蔗糖处理内皮细胞48 h,采用流式细胞术检测内皮细胞Siglec-9聚糖配体的表达;将内皮细胞分为对照组和半乳糖组(n=3),Western blot、流式细胞术、免疫荧光分析半乳糖对内皮细胞Siglec-9聚糖配体表达的影响;α2-3,6,8唾液酸酶处理内皮细胞后,Western blot检测半乳糖对内皮细胞Siglec-9聚糖配体恢复时间的影响;半乳糖处理内皮细胞后,Western blot检测分析细胞内唾液酸合成关键酶(GNE、NANS、NANP、CMAS、NPL以及ST3Gals)表达水平,并用RT-qPCR验证相关蛋白的mRNA表达;siRNA敲低NANP、CMAS及ST3Gal-Ⅲ,Western blot检测内皮细胞Siglec-9聚糖配体水平变化;巨噬细胞与内皮细胞共培养实验分析Siglec-9聚糖配体的增加对巨噬细胞的凋亡与吞噬能力的影响。结果内皮细胞上表达有Siglec-9聚糖配体且该配体为末端结构为α2-3连接的唾液酸糖蛋白;与对照组比较,半乳糖组内皮细胞上该聚糖配体表达水平显著增加(P<0.01),但半乳糖的添加对该配体的自我恢复时间无影响;与对照组比较,半乳糖处理的内皮细胞中NANP、CMAS、ST3Gal-Ⅲ表达水平升高(P<0.05,P<0.01),且RT-qPCR验证结果与其一致;抑制内皮细胞中NANP、CMAS、ST3Gal-Ⅲ的表达后,内皮细胞Siglec-9聚糖配体水平下降(P<0.01)。共培养实验中,与未处理组比较,半乳糖处理的内皮细胞促进巨噬细胞凋亡增加(P<0.01),并导致其吞噬能力减弱(P<0.05)。结论半乳糖通过NANP-CMAS-ST3Gal-Ⅲ通路上调内皮细胞上Siglec-9聚糖配体水平,从而抑制巨噬细胞活性。

新型免疫检查点SIGLEC9在宫颈癌中的表达及临床相关性分析

目的:探讨新型免疫检查点SIGLEC9及SIGLEC9^(+)T细胞在宫颈癌中的表达情况及SIGLEC9与临床相关性分析。方法:前瞻性收集2022年5月至2023年10月,于新疆医科大学第一附属医院行手术治疗或病理活检的宫颈癌患者的宫颈组织石蜡标本132例作为宫颈癌组,选取同期收治的良性子宫肌瘤行子宫全切患者的正常宫颈组织石蜡标本58例作为正常对照组;同时收集行手术治疗或病理活检的宫颈癌患者的外周血108例为宫颈癌组,选取同期健康人群的外周血86例为正常对照组。使用生物信息学技术和免疫组织化学染色、流式细胞术及双重免疫荧光染色检测SIGLEC9及SIGLEC9^(+)T细胞在宫颈癌中的表达情况,并与临床指标进行相关性分析。结果:免疫组织化学染色及双重免疫荧光染色结果显示SIGLEC9及SIGLEC9^(+)T细胞在宫颈癌组织中高表达(P<0.05);流式细胞术结果显示SIGLEC9^(+)CD4^(+)T和SIGLEC9^(+)CD8^(+)T细胞在宫颈癌外周血中表达增高(P<0.05)。SIGLEC9高表达与肿瘤直径、FIGO分期、淋巴结转移、HPV感染情况相关(P<0.05)。结论:新型免疫检查点SIGLEC9在宫颈癌组织中高表达,且在宫颈癌组织中SIGLEC9^(+)T细胞浸润较多。SIGLEC9为宫颈癌的免疫逃逸机制提供新的研究方向,并为宫颈癌的免疫治疗提供新的治疗靶点。

唾液酸灌胃干预肠道微生态预防小鼠更年期抑郁症的机制

目的探讨唾液酸(SA)灌胃干预肠道微生态预防小鼠更年期抑郁症的机制。方法将60只小鼠按照随机数字表法分为Sham组、模型组、SA低剂量组、SA中剂量组、SA高剂量组及盐酸氟西汀组,各10只。除Sham组外其他五组制备更年期抑郁症模型。造模成功后1~2 d,SA低、中、高剂量组分别给予16、32、64 mg/kg的SA灌胃,盐酸氟西汀组给予2 mg盐酸氟西汀灌胃,Sham组及模型组给予等体积生理盐水灌胃,每天1次,连续灌胃14 d。末次灌胃后进行强迫游泳实验(FST)、小鼠悬尾实验(TST),统计4 min内不动时间;用激光多普勒血流灌注成像仪检测肠壁血流灌注(血流灌注单位)、血流速度;16s rRNA基因测序法分析肠道菌群;Western blotting法检测肠组织糖酸结合免疫球蛋白样受体11(Siglecs)、骨钙素(OC)、组织紧密连接带蛋白1(ZO-1)、紧密连接蛋白4(claudin4)及海马组织色氨酸羟化酶2(TPH2)、酪氨酸羟化酶(TH)、吲哚胺2,3-双加氧酶(IDO)、脑源性神经营养因子(BDNF)蛋白。结果与Sham组比较,模型组TST、FST的4 min内不动时间长,血流灌注单位、血流速度、小杆菌属和小杆菌属丰度、Siglecs、OC、ZO-1、claudin4、TPH2、TH、BDNF蛋白表达低,Shannon指数、拟杆菌门和变形杆菌门丰度、IDO蛋白表达高(P均<0.05);与模型组比较,SA低、中、高剂量组及盐酸氟西汀组TST、FST短,肠壁血流灌注单位、血流速度、小杆菌属和小杆菌属丰度、Siglecs、OC、ZO-1、claudin4、TPH2、TH及BDNF蛋白表达高,Shannon指数、拟杆菌门和变形杆菌门丰度、IDO蛋白表达低(P均<0.05);SA高剂量组以上指标变化较SA低、中剂量组显著;与盐酸氟西汀组比较,SA高剂量组血流灌注单位、血流速度高(P均<0.05),两组其他指标比较差异无统计学意义(P均>0.05)。结论SA灌胃治疗小鼠更年期抑郁症的机制可能与促进小鼠肠道Siglecs高表达、降低拟杆菌门及变形杆菌丰度、促进BDNF分泌有关。