Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Extracellular vesicles (EVs) are crucial for facilitating intercellular communication, promoting cell migration, and orchestrating the immune response. Recently, EVs can diagnose and treat tumors. EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy. Furthermore, EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs. Herein, we review the molecular composition, biogenesis, and separation methods of EVs. We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy. Finally, we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.

OBJECTIVES: To analyze MYO1B expression in gastric cancer, its association with long-term prognosis and its role in regulating biological behaviors of gastric cancer cells. METHODS: We analyzed MYO1B expression in gastric cancer and its correlation with tumor grade, tumor stage, and patient survival using the Cancer Public Database. We also examined MYO1B expression with immunohistochemistry in gastric cancer and paired adjacent tissues from 105 patients receiving radical surgery and analyzed its correlation with cancer progression and postoperative 5-year survival of the patients. GO and KEGG enrichment analyses were used to explore the biological functions of MYO1B and the key pathways. In cultured gastric cancer cells, we examined the changes in cell proliferation, migration and invasion following MYO1B overexpression and knockdown. RESULTS: Data from the Cancer Public Database showed that MYO1B expression was significantly higher in gastric cancer tissues than in normal tissues with strong correlations with tumor grade, stage and patient prognosis (P<0.05). In the clinical tissue samples, MYO1B was significantly overexpressed in gastric cancer tissues in positive correlation with Ki67 expression (r=0.689, P<0.05) and the parameters indicative of gastric cancer progression (CEA ≥5 μg/L, CA19-9 ≥37 kU/L, G3-4, T3-4, and N2-3) (P<0.05). Kaplan-Meier analysis and multivariate Cox regression analysis suggested that high MYO1B expression was associated with decreased postoperative 5-year survival and was an independent risk factor (HR: 3.522, 95%CI: 1.783-6.985, P<0.05). MYO1B expression level was a strong predictor of postoperative survival (cut-off value: 3.11, AUC: 0.753, P<0.05). GO and KEGG analyses suggested that MYO1B may regulate cell migration and the mTOR signaling pathway. In cultured gastric cancer cells, MYO1B overexpression significantly enhanced cell proliferation, migration, and invasion and promoted the phosphorylation of Akt and mTOR. CONCLUSIONS High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is correlated with poor patient prognosis.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Prognosis ; Cell Movement ; Myosin Type I/genetics* ; Neoplasm Invasiveness ; Cell Line, Tumor ; Female ; Male

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Objective:To investigate whether continued low-dose aspirin (LDA) intervention affects the incidence of pre-eclampsia (PE) and adverse pregnancy outcomes in pregnant women with high-risk PE screening in the first trimester and reassessed as low risk at 28 weeks of gestation.Methods:This study was a prospective observational cohort study. From April 2022 to April 2024, a total of 106 pregnant women who underwent prenatal examination in the Affiliated Jiangyin Hospital of Nantong University were enrolled. They were assessed as high risk of PE by multiple indicators combined screening at 11-13 +6 weeks of gestation, received LDA intervention, and were reassessed as low risk of PE at 28 weeks of gestation. The patients were divided into withdrawal group (49 cases) and continuation group (57 cases). The incidence of PE and adverse pregnancy outcomes were compared between the two groups. Results:(1) There were no statistically significant differences in general conditions and the incidence of pregnancy complications between the two groups (all P>0.05). During the PE risk screening at 11-13 +6 weeks of gestation, there were no statistically significant differences in mean arterial pressure (MAP) and ultrasound uterine artery pulsation index (UtPI) between the two groups (all P>0.05), but the placental growth factor (PlGF) level in the withdrawal group was significantly lower than that in the continuation group ( P=0.023). There was no significant difference in the proportion of pregnant women with high risk of PE before 32 weeks and 34 weeks of pregnancy between the two groups (all P>0.05). (2) There were 7 cases (14%, 7/49) of PE in the withdrawal group, including 1 case (2%, 1/49) of early-onset PE and 3 cases (6%, 3/49) of PE before 37 weeks of pregnancy. There were 11 cases (19%, 11/57) of PE in the continuation group, including 2 cases (4%, 2/57) of early-onset PE and 4 cases (7%, 4/57) of PE before 37 weeks of pregnancy. There were no significant differences in the incidence of PE (including early-onset PE and PE before 37 weeks of pregnancy), gestational hypertension, severe PE, chronic hypertension complicated with PE and chronic hypertension complicated with pregnancy between the two groups (all P>0.05). (3) There were no significant differences in cesarean section rate, preterm birth rate, placental abruption, postpartum hemorrhage, fetal growth restriction, fetal distress rate, neonatal birth weight, neonatal asphyxia, and 1-minute and 5-minute Apgar scores between the two groups (all P>0.05). No stillbirth occurred in the two groups. Conclusion:For pregnant women with high risk of PE screening in the first trimester and taking LDA intervention, there is no difference in the incidence of PE and adverse pregnancy outcomes whether to continue LDA or not after being reassessed as low risk at 28 weeks of gestation.

AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

Apolipoprotein D(APOD)is a protein that is widely present in animal tissues and is in-volved in the reproductive regulation of the body.In order to investigate the expression regularity of APOD in bactrian camel epididymis and its regulation effect on sperm maturation,this study took the epididymis of bactrian camel during estrus and anestrus as materials,and first cloned the complete sequence of APOD coding sequence(CDS)region.The physicochemical properties of AP-OD were analyzed by ProParam,SOPMA,SWISS-MODEL and MEGA7.0 software.Meanwhile,the expression and distribution of APOD in epididymis were detected by qRT-PCR,Western blot and IHC.The cloning results showed that:the length of the CDS region of APOD gene was 624 bp,encoding 207 amino acids.The APOD sequence of Bactrian camel was highly conserved with the nucleotide and amino acid sequence of alpaca,and the homology of APOD sequence with elk was the lowest.The results of qRT-PCR showed that the mRNA levels of APOD in the head,body and tail of epididymis in estrus were significantly higher than those in estrus(P＜0.01).Western blot results showed that the APOD protein expression and mRNA expression trend was similar in the head and body of the epididymis during anestrus,but the APOD expression level in the tail of the epididymis during anestrus was opposite to the mRNA expression level(P＜0.05).The results of H&E and IHC showed that there were significant differences in epididymal tissue between estrus and anestrus.In addition,APOD showed positive reactions in epididymal epithelial cells,smooth muscle cells,sperm and connective tissue to varying degrees,suggesting that APOD may be in-volved in the maturation of sperm during estrus and anestrus,providing evidence for further explo-ring the regulatory mechanism of APOD's involvement in seasonal estrus.

Objective To investigate the mechanisms through which Qinggan Yipi formula(QgYp)may alleviate liver fibrosis by integrating network pharmacology with experiments.Methods The active ingredients and gene targets of QgYp,associated with liver fibrosis,were sourced from several databases,including the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),various professional chemical databases,the HERB database,the GeneCards database,and the Online Mendelian Inheritance in Man(OMIM)database.Protein-protein interaction(PPI)networks were developed using the STRING database and visualized through Cytoscape software.Furthermore,GO enrichment analysis and KEGG pathway analysis were conducted with the Metascape database,alongside molecular docking studies using the CB-DOCK 2 platform.HSC-T6 cells were used as the research model,and the MTT assay along with Western blotting were applied to evaluate cell proliferation and protein expression levels,and the expression of related proteins was also detected in the animal experiment.Results A total of 22 bioactive components and 124 gene targets were identified within the formula.Enrichment analyses revealed 896 GO entries and 123 signaling pathways,notably including the IL-7,TNF,Toll-like receptor,and NF-kappa B pathways.Molecular docking indicated that the key components of the formula exhibited a strong binding affinity with proteins involved in the TLR4/NF-κB signaling pathway.Additionally,experiments confirmed that QgYp effectively inhibited the proliferation of HSC-T6 cells induced by LPS,and the expression of α-SMA,COL-1,TLR4,IκB-α,and NF-κB p65 proteins in both HSC-T6 cells and rats with liver fibrosis decreased.Conclusion QgYp can effectively inhibit the TLR4/NF-κB signaling pathway and has a suppressive effect on the fibrosis process in hepatic stellate cells,offering a theoretical basis for its clinical application in treating liver fibrosis.

Post-translational modification of protein is a key mechanism for regulating cancer development and immune re-sponses,and has become an important target for cancer diagnosis and treatment.Among them,lactylation modification provides a new perspective for the precise prevention and control of tumors by affecting metabolism and epigenetics.Lactylation modification precisely regulates the functions of histone and non-histone,affecting tumor cell characteristics,microenvironment acidification,and immune cell functions,becoming a key hub connecting metabolic reprogramming and malignant phenotypes.This article reviews the regulatory roles of lactylation modification in tumor development,immune escape,clinical translation,and explores the potential of targeted inhi-bition of lactylation modification and its related pathways,as well as the inhibition of key enzyme activity.