1.Next-generation clinically relevant antibody detection: Unlocking electrochemical biosensors for critical disease management.
Zheng ZHAO ; Zhiwei CHEN ; Jacques CROMMEN ; Shengfeng HUANG ; Qiqin WANG ; Zhengjin JIANG
Acta Pharmaceutica Sinica B 2025;15(11):5632-5662
Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.
2.Effects of vesicular stomatitis virus on anti-tumour immunity, growth of xenografts, and lung metastasis in mouse mammary carcinoma 4T1 cells tumor-bearing mice
LI Yuqian1a ; XU Qingsheng1a ; WEI Hong1b ; WANG Hao2 ; WANG Shuoshi3 ; JIANG Lina1a ; YUAN Xinyi1c
Chinese Journal of Cancer Biotherapy 2024;31(5):452-461
[摘 要] 目的:探究野生型水疱性口炎病毒印第安纳株(VSV-IN)对小鼠三阴性乳腺癌4T1细胞移植模型小鼠的免疫调节及肿瘤转移的影响。方法:VSV以MOI=1、MOI=10、MOI=100感染4T1细胞12、24、48 h后,CCK-8法检测4T1细胞死亡率,划痕愈合实验检测细胞迁移能力,qPCR检测细胞中E-cadherin、MMP-2、MMP-9 mRNA的表达。于雌性BALB/c小鼠脂肪垫接种1×106个/mL的4T1细胞0.1 mL,构建4T1细胞荷瘤小鼠模型,待小鼠肿瘤体积达200 mm3,分别向移植瘤内注射PBS、紫杉醇(TAX)(15 mg/kg)、VSV-IN(1×106 pfu/只),每周1次。给药4次后,处死小鼠、剥离完整移植瘤组织,测量肿瘤体积及质量,肺组织病理切片经H-E染色后观察肿瘤肺部转移结节,流式细胞术检测脾组织中T细胞亚群比例,ELISA法检测小鼠血清IL-6及TNF-α水平,利用GEPIA在线分析乳腺肿中迁移相关蛋白mRNA的表达,免疫组化法检测肿瘤中MMP-2、MMP-9与E-cadherin的表达,利用蛋白-蛋白对接技术预测VSV-IN的G蛋白、M蛋白与ERK2、E-cadherin的亲和力。结果:经MOI=10、100的VSV-IN处理48 h后,4T1细胞死亡率显著高于对照组(均P<0.01);与对照组相比,VSV-IN组(MOI=10)细胞迁移率明显降低(P<0.01),MMP-9 mRNA的相对表达量明显降低(P<0.05);与对照组小鼠相比,VSV-IN组移植瘤生长较对照组减缓且终点体积显著减小(P<0.05),VSV-IN组小鼠肺转移结节数量显著减少[(12.86±1.86) vs (24±3.67)个,P<0.01],脾内CD4+ T、CD8+ T细胞比例显著升高(均P<0.05),血清TNF-α、IL-6含量显著升高(均P<0.01);GEPIA分析发现在乳腺癌中E-cadherin、MMP-9表达水平均高于癌旁组织(P<0.05);VSV-IN组小鼠肿瘤细胞内MMP-9表达明显低于对照组(P<0.05);VSV-IN的G、M蛋白与ERK2的结合自由能分别为–11.7 kcal/mol、–6.4 kcal/mol。结论:野生型VSV-IN可抑制4T1细胞荷瘤小鼠的移植瘤生长及转移,这可能与其促进抗肿瘤免疫及调控迁移相关蛋白表达有关。
3.1, 25-dihydroxyvitamin D3 promotes apoptosis in human breast cancer MCF-7 cells by glycolysis pathway
ZHANG Lia ; LI Qinga ; JIANG Shana ; GAN Yindia ; LI Huijuana ; CHEN Xinyuana ; LIU Miaob
Chinese Journal of Cancer Biotherapy 2023;30(9):784-788
[摘 要] 目的:探讨1, 25-二羟维生素D3(VD3)对人乳腺癌MCF-7细胞凋亡的影响及其作用机制。方法:取体外培养的人乳腺癌MCF-7细胞,随机分为6组:对照组、2-脱氧葡萄糖(2-DG,葡萄糖抑制剂)组、1 µmol/L VD3组、10 µmol/L VD3组、2-DG+1 µmol/L VD3组和2-DG+10 µmol/L VD3组。药物干预6组细胞48 h后,以葡萄糖摄取测定试剂盒检测细胞的葡萄糖摄取量、ATP试剂盒检测细胞中ATP含量和乳酸试剂盒检测细胞的乳酸水平,WB法检测MCF-7细胞中细胞色素C(Cyt c)和凋亡相关蛋白(Bcl-2、BAX、PARP1、caspase9和caspase3)的表达水平。结果:与对照组比较,VD3干预后,MCF-7细胞的凋亡率明显增加(P<0.05或P<0.01),同时细胞的葡萄糖摄取量、ATP含量及乳酸水平均明显降低(P<0.05或P<0.01),Cyt c、BAX、PARP1、caspase9及caspase3蛋白表达量明显升高(均P<0.05),Bcl-2蛋白表达量降低(P<0.05或P<0.01);VD3联合2-DG干预后,各组细胞检测指标的变化更为明显(P<0.05或P<0.01)。结论:VD3可通过抑制人乳腺癌MCF-7细胞的糖酵解过程并以线粒体的Cyt c途径促进细胞凋亡。
5.Role of intestinal flora and 5-HT in depression- and anxiety-like behaviors in mice exposed to PM2.5
Jiajie TANG ; Jiaxue ZHENG ; Qian SONG ; Huiwen KANG ; Yaqi CUI ; Xuemei ZHANG ; Xuan SHANG ; Shoufang JIANG
Journal of Environmental and Occupational Medicine 2022;39(12):1343-1349
<b>Backgroundb> Some studies have shown that PM2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM2.5-induced depression- and anxiety-like behaviors in mice. <b>Objectiveb> To observe the effects of PM2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM2.5. <b>Methodsb> Eight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. <b>Resultsb> The percentage of open-arm entry [M(P25, P75)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P<0.05). The total travelled distance and the time spent in central area (
6.Features in digitorum muscular tension and shear-wave elastography in hemiplegic patients with stroke before and after manual digitorum sensory stimulation
Ziyan HE ; Xiaoxiao TANG ; Yaxing TIAN ; Fan JIANG ; Xiuli KAN ; Xianshan SHEN ; Jing MAO ; Jun XU ; Xue LIU ; Jianxian WU ; Tingting WU ; Yongfeng HONG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(2):204-211
Objective To demonstrate the changes in flexor digitorum and extensor digitorum tension in the affected hands with shear-wave elastography (SWE) before and after manual digitorum sensory stimulation (MDSS) in hemiplegic patients with stroke. Methods A total of 51 hemiplegic post-stroke inpatients in the Department of Rehabilitation Medicine in Second Hospital of Anhui Medical University from April to June, 2020, underwent MDSS completed by a researcher who used a bare thumb and index finger to squeeze each nail bed as well as the sides of each fingertip in the affected hand. The stimulation intensity was the minimum that could cause finger extension without obvious pain, and the interval between two stimulations was five to ten seconds. Muscular tension of the flexor digitorum superficialis, flexor digitorum profundus, flexor pollicis longus and extensor digitorum were assessed with modified Ashworth Scale (MAS) and shear-wave velocity (SWV) of SWE on the affected side before and immediately after MDSS. MAS score was -1 as low muscular tension. Results The MAS scores of all the muscles significantly reduced after MDSS (|Z| > 2.843, P < 0.001); while the changes of SWV were not significantly in all the muscles with initially MAS score of 0 or -1 (t < 1.052, P > 0.05), and it reduced in those muscles with initial MAS scores of one to three (t > 2.672, P < 0.05). The SWV were positively correlated with the MAS scores both before and after MDSS (r > 0.334, P < 0.05). Conclusion MDSS can effectively, immediately, and safely relieves muscle spasms of the flexor digitorum and facilitate active finger extension in the affected hand for hemiplegic patients with stroke. SWE is useful for quantitatively and objectively evaluating muscular tension in the affected hand for hemiplegic patients with stroke.
7.circ_0000615 regulates proliferation, migration and invasion of cholangiocarcinoma cells by targeting miR-432-5p
GUAN Canghaia,b ; WANG Haicuna ; YU Shaoboa ; GAO Xina ; JIANG Xingminga ; SUN Dongshenga
Chinese Journal of Cancer Biotherapy 2022;29(6):527-533
[摘 要] 目的:探讨circ_0000615在胆管癌细胞中的表达及其对胆管癌细胞增殖、迁移和侵袭能力的影响和可能的调控机制。方法:通过qPCR检测circ_0000615在正常胆管上皮HIBEC细胞和胆管癌CCLP-1、QBC939、TFK-1和RBE细胞中的表达水平。双荧光素酶报告基因实验验证circ_0000615与miR-432-5p的靶向关系。将si-NC、si-circ_0000615(si-circ-1、si-circ-2)、inhibitor-NC和inhibitor-miR-432-5p转染至CCLP-1和QBC939细胞,转染细胞分为si-NC组、si-circ-1组、si-circ-2组、si-NC+inh-NC组、si-NC+inh-miR-432-5p组和si-circ-1+inh-miR-432-5p组,通过CCK-8、EdU和Transwell实验检测各转染组胆管癌细胞的增殖、迁移和侵袭能力。结果:在胆管癌细胞中circ_0000615呈高表达而miR-432-5p呈低表达(P<0.05或P<0.01);双荧光素酶报告基因实验证实circ_0000615与miR-432-5p之间存在靶向关系(P<0.01);敲减circ_0000615可明显抑制CCLP-1、QBC939细胞的增殖、侵袭和迁移能力(P<0.05或P<0.01);下调miR-432-5p可部分逆转敲减circ_0000615对胆管癌CCLP-1和QBC939细胞增殖、迁移和侵袭的抑制作用(P<0.05或P<0.01)。结论:circ_0000615通过靶向miR-432-5p调控胆管癌细胞的增殖、侵袭和迁移。
9.miR-125a-5p regulates migration and invasion of gastric cancer cells by down-regulating BAG4 expression
JIANG Le ; CHEN Yan ; WANG Jun ; MIN Guangtao ; CHEN Wei ; WANG Hongpeng ; WANG Xiangwen ; YAO Nan
Chinese Journal of Cancer Biotherapy 2021;28(6):558-566
[摘 要] 目的:探讨miR-125a-5p通过调控Bcl-2相关永生基因4(Bcl-2-associated athanogene 4,BAG4)的表达抑制胃癌细胞迁移和侵袭的分子机制。方法:选用2014年1月至2015年12月兰州大学第一医院手术切除的82例胃癌组织标本及配对的癌旁组织以及人胃癌细胞系MGC803、BGC823、SGC7901、HGC27及人胃黏膜上皮细胞(GES-1),qPCR法检测胃癌组织、癌旁组织及胃癌细胞系中miR-125a-5p的表达水平。分别将miR-125a-5p mimic、miR-125a-5p inhibitor、(si-BAG4)siRNA-BAG4及阴性对照质粒转染至胃癌细胞,划痕愈合实验和Transwell侵袭实验分别检测miR-125a-5p/BAG4信号轴对胃癌细胞迁移和侵袭能力的影响。WB检测胃癌细胞中BAG4蛋白的表达。荧光素酶报告基因实验验证miR-125a-5p和BAG4之间的靶向调控关系。结果:miR-125a-5p在胃癌组织和细胞系中均低表达(均P<0.01)。miR-125a-5p的表达与患者的性别(P=0.953)、年龄(P=0.772)、肿瘤部位(P=0.867)、组织学分级(P=0.745)和肿瘤大小(P=0.088)无相关性,与胃癌患者的T分期(P=0.003)、N分期(P=0.001)、M分期(P=0.027)和TNM分期(P=0.035)显著相关,差异有统计学意义。miR-125a-5p低表达是胃癌患者总生存时间的独立危险因素。过表达miR-125a-5p显著抑制胃癌细胞的迁移和侵袭能力(均P<0.01)。敲降BAG4可逆转miR-125a-5p inhibitor对胃癌细胞迁移和侵袭能力的抑制作用。荧光素酶报告基因实验证实miR-125a-5p可与BAG4 3'非翻译区(untranslated regions,UTR)结合抑制其表达。结论:miR-125a-5p通过靶向下调BAG4的表达水平进而抑制胃癌细胞的迁移和侵袭。
10.Correlation between the expression of PD-L1 and dMMR related proteins in follicular thyroid carcinoma tissues and its clinical significance
QIU Yanrua ; DAI Yijuna ; JIANG Zhenjiana ; LIN Jianguanga, ; ZENG Yidanb, ; XU Tianwena
Chinese Journal of Cancer Biotherapy 2021;28(3):269-274
[Abstract] Objective: To investigate the correlation between PD-L1 expression and dMMR related proteins in follicular thyroid carcinoma tissues and its clinical significance. Methods: The postoperative paraffin-embedded tissue samples from 60 patients with thyroid follicular carcinoma were collected from the Second Affiliated Hospital of Fujian Medical University during January 2015 and June 2020. The collected samples were re-confirmed as thyroid follicular carcinoma tissues by Hematoxylin-eosin staining. The expression of PD-L1 and four homologous proteins encoded by four genes (MLH1, MSH2, MSH6, PMS2) in MMR system were detected by immunohistochemistry in the cancer and paracancerous tissues. The relationship between the expression of PD-L1 and depletion of MMR related proteins in thyroid follicular carcinoma tissues and its clinical significance were analyzed. Results: The positive expression rate of PD-L1 was significantly higher in the follicular thyroid carcinoma tissues than that in paracancerous tissues [63.3%(38/60) vs 11.7%(7/60), P<0.05]. The expression of PD-L1 was significantly correlated with tumor diameter, extrathyroidal infiltration, vascular invasion and recurrence (all P<0.05). In the cancer tissue specimens from 60 patients, 24 (40.0%) had expression of four MMR related proteins, which were pMMR tumors, and 36 (60.0%) had depletion of one or more MMR related proteins, which were dMMR tumors. The dMMR-type thyroid follicular carcinoma was significantly correlated with the status of lymph node metastasis and tumor staging (all P<0.05). PD-L1 was positively correlated with the incidence of dMMR, and PD-L1 was an independent risk factor for disease recurrence, while dMMR was associated with a better prognosis. Patients with PD-L1+/pMMR type were associated with higher tumor malignancy, while patients with PD-L1+/dMMR type were not associated with tumor pathological features but may easily benefit from immunotherapy. Conclusion: Positive PD-L1 expression and dMMR highly occur in follicular thyroid carcinoma. PD-L1 is associated with the increased tumor invasion and is an independent risk factor for disease recurrence, while dMMR is an early molecular event in the development of thyroid follicular carcinoma and is associated with better prognosis of patients.

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