Acute myeloid leukemia (AML) is maintained by a rare subpopulation of leukemic initiating cells, which drive disease progression, therapy resistance, and relapse. Transcription factor AP-2α, known for its role in tumor regulation, has an unclear function in leukemic initiating cells. Here, we found that low AP-2α expression correlated with poor AML prognosis, while high expression suppressed disease progression and improved survival. Functionally, AP-2α limited leukemic stem/initiating cell self-renewal and AML maintenance but was dispensable for normal hematopoiesis, as demonstrated using a Tfap2a conditional knockout model in hematopoietic stem cells. Moreover, loss of Tfap2a accelerated MLL-AF9 (MA9)-driven leukemogenesis in vivo, with knockout bone marrow exhibiting an expansion of leukemic granulocyte–monocyte progenitors, reflecting enhanced leukemia stem cell activity. Mechanistically, RNA-sequencing of Tfap2a-deficient cells revealed activation of inflammatory and stemness-related pathways, including JAK–STAT and TLR4 signaling. We further identified AP-2α as a direct transcriptional repressor of TLR4 by binding to its promoter, thereby exerting tumor-suppressive effects in AML-5 cells. Notably, the JAK2 inhibitor Fedratinib elevated AP-2α protein levels by attenuating STAT3 binding at the AP-2α promoter, positioning AP-2α as a downstream target of STAT3. Combining AP-2α overexpression with Fedratinib treatment or STAT3 knockdown synergistically inhibited AML-5 cell proliferation and leukemic stem cell self-renewal. These findings define a novel STAT3–AP-2α–TLR4 regulatory axis in AML and highlight AP-2α as a tumor suppressor that restrains leukemic stemness and disease progression. Therapeutic strategies that restore AP-2α expression or enhance its function—particularly in combination with JAK2 inhibition—may effectively target leukemic initiating cells in specific AML subtypes.

BACKGROUND:The absence of known inhibitors for TNFAIP1, a TNF-α-induced protein, has limited its exploration as a therapeutic target for ulcerative colitis (UC). This study aimed to validate TNFAIP1's pathogenic role in UC and to identify the first direct TNFAIP1-targeting compound from natural compounds. METHODS:We integrated bioinformatics analysis, DSS-induced colitis models in Tnfaip1-knockout mice, and virtual screening to identify Salidroside as a potential TNFAIP1-targeting compound. Cellular thermal shift and ubiquitination assays confirmed its direct interaction with TNFAIP1 and its effect on protein stability. Oral administration of Salidroside ameliorated colitis in wild-type mice, phenocopying the protective effect of Tnfaip1 deficiency. RESULTS:TNFAIP1 was significantly upregulated in UC patients and colitic mice. Tnfaip1-knockout conferred profound resistance to colitis, mechanistically linked to the suppression of the IKK/IκB/NF-κB pathway, modulation of CREB signaling, and restoration of a beneficial gut microbiota. Based on this target validation, virtual screening identified Salidroside as a top candidate. Crucially, Salidroside administration in wild-type mice phenocopied the protective effects of genetic knockout, alleviating disease severity and downregulating the TNFAIP1-driven inflammatory network. CETSA confirmed a direct physical interaction between Salidroside and TNFAIP1. CONCLUSION:This study validates TNFAIP1 as a key pathogenic driver of UC and identifies Salidroside as a first-in-class direct TNFAIP1-targeting compound with therapeutic potential.

IntroductionHepatocellular carcinoma (HCC) is the most prevalent liver cancer and a leading cause of cancer-related deaths worldwide. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays a critical role in RNA metabolism, including alternative splicing, which is linked to cancer progression. Our study investigated the role of hnRNPA1 in HCC and its potential as a therapeutic target.MethodsWe analyzed hnRNPA1 expression in HCC tissues compared to non-tumor tissues using RNA-seq and immunohistochemistry. hnRNPA1 was knocked down in Hep G2 cells to assess its impact on cell proliferation, migration, and apoptosis using scratch assays, flow cytometry, qPCR, and Western blot. We also explored the interaction between hnRNPA1 and ZNF207, as well as its splicing effects and downstream signaling pathways by RIP assay, bioinformatics, qPCR and Western blot.ResultshnRNPA1 was significantly upregulated in HCC tissues compared to normal tissues, correlating with poor patient survival. hnRNPA1 knockdown reduced Hep G2 cell proliferation and migration while increasing apoptosis. We identified that hnRNPA1 bound to ZNF207 and regulated its exon 9 skipping, influencing ZNF207 splicing and the PI3K/Akt/mTOR pathway, key regulators of cell growth and survival.ConclusionOur findings demonstrate that hnRNPA1 promotes HCC progression by regulating ZNF207 splicing and the PI3K/Akt/mTOR pathway. hnRNPA1-ZNF207 interaction represents a potential therapeutic target for HCC, providing insights into the molecular mechanisms underlying HCC progression.

Background: Tumor necrosis factor-alpha (TNF-α) serves as a central mediator of inflammation and represents key therapeutic target in inflammatory bowel disease (IBD). This study investigates the protective effects of salidroside (Sal) against inflammation and explores its underlying molecular mechanisms. Methods: We employed network pharmacology to identify potential targets of Sal. The anti-inflammatory effects of Sal were evaluated in LPS-Induced cellular models using NCM460 colonic epithelial cells and RAW264.7 macrophages, as well as in a murine model of acute colonic inflammation. Direct target engagement was confirmed through cellular thermal shift assay (CETSA) and co-immunoprecipitation (Co-IP). The mechanism was further elucidated via site-directed mutagenesis and analysis of the IKK/NF-κB signaling pathway. Results: Network pharmacology predicted TNF-α as a key target. Sal significantly attenuated LPS-Induced inflammation in vitro and ameliorated colitis symptoms in vivo. Notably, CETSA and Co-IP assays confirmed direct interaction between Sal and TNF-α. Mutagenesis studies identified Arg179, Lys188, and Tyr191 as critical residues for this binding. Mechanistically, Sal inhibited TNF-α-mediated activation of the IKK/NF-κB pathway and the subsequent production of pro-inflammatory cytokines. Conclusion: Our findings demonstrate that Sal alleviates inflammation by directly binding to TNF-α and suppressing the downstream NF-κB signaling cascade, thereby positioning it as a promising therapeutic candidate for TNF-α-driven inflammatory diseases.

Treatment options for advanced or recurrent cervical cancer (CC) remain limited, highlighting the urgent need for effective molecular biomarkers and therapeutic strategies. This study investigates nuclear-cytoplasmic consistent genes (NCCGs) in CC and other epithelial-derived malignancies, exploring their potential in molecular subtyping, prognosis evaluation, and therapeutic response prediction. NCCGs were identified using single-cell sequencing and single-nucleus RNA sequencing data. Through Cox regression and single-sample gene set enrichment analysis, TCGA-CESC cohort were stratified into high-risk (HRG) and low-risk (LRG) groups. Pan-cancer analysis of 14 TCGA epithelial-derived malignancies, including BLCA and BRCA, validated the classification capability and prognostic relevance of NCCGs. Clinical utility in predicting chemotherapy and immunotherapy responses was assessed using GSE168009 and IMvigor210CoreBiologies cohorts. NCCGs effectively stratified CC cohort into HRG and LRG. LRG demonstrated significantly better survival (HR = 3.24, 95% CI 1.57–6.7) and higher immune scores, including elevated CD8 + T and memory CD4 + T cell levels. Pan-cancer analysis confirmed NCCGs’ ability to differentiate HRG and LRG and associate with overall survival. LRG also showed greater sensitivity to PD-1/CTLA4 inhibitors and chemotherapeutic agents (e.g., Panobinostat and Doxorubicin). The NCCG-based risk score showed robust accuracy in predicting chemotherapy and immunotherapy efficacy. This study reveals the molecular mechanisms and clinical significance of NCCGs in CC and epithelial-origin cancers. NCCGs hold value in molecular classification, prognostic assessment, and predicting therapeutic responses, offering new markers and targets for precision medicine.

Colorectal cancer is a highly prevalent malignant tumor of the digestive tract worldwide. Immunotherapy has emerged as a critical therapeutic approach for CRC patients. We observed that KCTD10 expression is significantly downregulated in colorectal cancer tissues compared to normal tissues, and patients with higher KCTD10 expression exhibited prolonged survival. To investigate its functional role, we established stable KCTD10-overexpressing CT26 and SW480 colorectal cancer cell lines. Both in vitro and in vivo experiments demonstrated that KCTD10 overexpression suppresses colorectal cancer progression and inhibits the EMT process. Notably, KCTD10 overexpression upregulated PD-L1 expression and synergistically enhanced the therapeutic efficacy of anti-PD-1 treatment. Our findings reveal that KCTD10 functions as a tumor suppressor in colorectal cancer pathogenesis. Mechanistically, KCTD10 potentiates the antitumor efficacy of anti-PD-1 immunotherapy by upregulating PD-L1 expression, thereby proposing a novel therapeutic target and suggesting a promising combination strategy for CRC treatment. Insight box KCTD10 can inhibit the development of colorectal cancer and the EMT process. And the over-expression of KCTD10 increased the expression of PD-L1, improved the efficacy of PD-1 treatment.

Lung cancer remains a critical global health concern, characterized by the highest incidence and mortality rates among all cancers. Due to its heterogeneity and complexity, the molecular mechanism underlying lung cancer occurrence and progression needs to be further investigated. KCTD10 has been implicated in malignant phenotypes of several tumors, but the role of KCTD10 in lung cancer remains largely unexplored. In this study, we found that KCTD10 expression is significantly reduced in lung cancer tissues, and overexpression of KCTD10 could inhibit lung cancer progression both in vitro and in vivo. Immunoprecipitation-mass spectrometry (IP-MS), co-immunoprecipitation (Co-IP), and ubiquitination assays revealed that the BTB domain of KCTD10 interacts with Armadillo repeat domains 1–9 of β-catenin and facilitates ubiquitin-dependent degradation of β-catenin via the K48-linked ubiquitin chains, followed by the downregulation of the β-catenin downstream target gene PD-L1. Notably, the combined treatment of KCTD10 overexpression with anti-PD-1 antibodies exhibited a synergistic effect in suppressing lung cancer progression and brain metastatic colonization in mice. In addition, vascular endothelial cell-specific knockout of Kctd10 (Kctd10flox/floxCDH5CreERT2/+) promoted lung cancer metastasis and tumor angiogenesis through β-catenin signaling. Finally, we identified METTL14- mediated N6-methyladenosine (m6A) modification within the coding sequence (CDS) region of KCTD10, which enhanced KCTD10 mRNA stability in a YTHDF2-dependent manner. These findings highlight KCTD10 as a critical regulator of lung cancer progression and the tumor microenvironment, suggesting its potential as a promising therapeutic target for lung cancer.

It is a great challenge to obtain an ideal hydrogel for the clinical treatment of intrauterine adhesion (IUA) disease. Here, a novel injectable chitosan-lignin/poloxamer hydrogel loaded with platelet-rich plasma (CL-PF127@PRP) was prepared by self-assembly at room temperature. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), rheological analysis, and injectable writing were used to characterize the structure of the hydrogel. The results confirmed that the amino group of chitosan and the sulfonic group of sodium lignosulfonate were ionic-crosslinked by electrostatic attraction, which stabilized the three-dimensional structure of the PF127 hydrogel loaded with PRP, and PRP made the porous structure gradually become tight. Moreover, the CL-PF127@PRP hydrogel displayed good injectability and a solid state. The soaking experiment showed that the CL-PF127@PRP hydrogel had suitable degradation at pH = 7 and a good PRP release rate (PRP release 70% at 96 h). Cell experiments in vitro demonstrated that the CL-PF127@PRP hydrogel possessed good biocompatibility, an anti-inflammatory function, and pro-angiogenic activity. Furthermore, an animal experiment of skin wound and IUA confirmed that the skin wound closure rate of the CL-PF127@PRP hydrogel was over 50% on the seventh day. PRP improved the thickness of the endometrium and uterus receptivity, suggesting that the CL-PF127@PRP hydrogel offers great promise for the clinical treatment of IUA.

AIMS:The incidence of recurrent gliomas is high, exerting low survival rates and poor prognoses. Transcription factor AP-2α has been reported to regulate the progression of primary glioblastoma (GBM). However, the function of AP-2α in recurrent gliomas is largely unclear. METHODS:The expression of AP-2α and O6-methylguanine DNA-methyltransferase (MGMT) was detected in recurrent glioma tissues and cell lines by Western blots, the regulation mechanisms between AP-2α/MGMT promoter and RA/AP-2α promoter were studied by luciferase reporter assays, EMSA, and chIP assays. The effects of AP-2α and TMZ/RA treatment on cell viability in vitro and in vivo were investigated by MTT assays, γH2AX staining, comet assays and intracranial injection. KEY FINDINGS:AP-2α expression negatively correlates with the expression of MGMT in glioma samples. AP-2α could directly bind with the promoter of the MGMT gene, suppresses transcriptional levels of MGMT and downregulate MGMT expression in TMZ-resistant U87MG-R and T98G cells, but TMZ treatment decreases AP-2α expression and increases MGMT expression. The extended TMZ treatment and increased TMZ concentrations reversed these effects. Moreover, AP-2α overexpression combines with TMZ to decrease cell viability, concurrently with improved DNA damage marker γH2AX. Furthermore, retinoic acid (RA) activates RAR/RXR heterodimers, which bind to RA-responsive elements (RAREs) of the AP-2α promoter, and activates AP-2α expression in recurrent glioma cells. Finally, in intracranial relapsed glioma mouse model, both RA and TMZ could retard tumor development and prolong the mouse survival. SIGNIFICANCE:AP-2α activation by gene overexpression or RA treatment reveals the suppressive effects on glioma relapse, providing a novel therapeutic strategy against malignant refractory gliomas.

Programmed death-ligand 1 (PD-L1) ensures that tumor cells escape T-cell-mediated tumor immune surveillance. However, gliomas are characteristic of the low immune response and high-resistance therapy, it is necessary to understand molecular regulatory mechanisms in glioblastoma, especially the limited regulation of PD-L1 expression. Herein, we show that low expression of AP-2α is correlated with high expression of PD-L1 in high-grade glioma tissues. AP-2α binds directly to the promoter of the CD274 gene, not only inhibits the transcriptional activity of PD-L1 but enhances endocytosis and degradation of PD-L1 proteins. Overexpression of AP-2α in gliomas enhances CD8+ T cell-mediated proliferation, effector cytokine secretion, and cytotoxicity in vitro. Tfap2a could increase the cytotoxic effect of Cd8+ T cells in CT26, B16F10, and GL261 tumor-immune models, improve anti-tumor immunity, and promote the efficacy of anti-PD-1 therapy. Finally, the EZH2/H3K27Me3/DNMT1 complex mediates the methylation modification of AP-2α gene and maintains low expression of AP-2α in gliomas. 5-Aza-dC (Decitabine) treatment combines with anti-PD-1 immunotherapy to efficiently suppress the progression of GL261 gliomas. Overall, these data support a mechanism of epigenetic modification of AP-2α that contributes to tumor immune evasion, and reactivation of AP-2α synergizes with anti-PD-1 antibodies to increase antitumor efficacy, which may be a broadly applicable strategy in solid tumors.

TNFAIP1 regulates cellular biological functions, including DNA replication, DNA repair, and cell cycle, by binding to target proteins. Identification of Tnfaip1-interacting proteins contributes to the understanding of the molecular regulatory mechanisms of their biological functions. In this study, 48 hpf, 72 hpf, and 96 hpf wild-type zebrafish embryo mRNAs were used to construct yeast cDNA library. The library titer was 1.12 × 107 CFU/mL, the recombination rate was 100%, and the average length of the inserted fragments was greater than 1000 bp. A total of 43 potential interacting proteins of Tnfaip1 were identified using zebrafish Tnfaip1 as a bait protein. Utilizing GO functional annotation and KEGG signaling pathway analysis, we found that these interacting proteins are mainly involved in translation, protein catabolic process, ribosome assembly, cytoskeleton formation, amino acid metabolism, and PPAR signaling pathway. Further yeast spotting analyses identified four interacting proteins of Tnfaip1, namely, Ubxn7, Tubb4b, Rpl10, and Ybx1. The Tnfaip1-interacting proteins, screened from zebrafish embryo cDNA in this study, increased our understanding of the network of Tnfaip1-interacting proteins during the earliest embryo development and provided a molecular foundation for the future exploration of tnfaip1’s biological functions.

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used in various products, such as plastic packaging in food industries. As an environmental endocrine disruptor, it induces adverse effects on brain development and function. However, the molecular mechanisms by which DEHP induces learning and memory impairment remain poorly understood. Herein, we found that DEHP impaired learning and memory in pubertal C57BL/6 mice, decreased the number of neurons, downregulated miR-93 and the β subunit of casein kinase 2 (CK2β), upregulated tumor necrosis factor-induced protein 1 (TNFAIP1), and inhibited Akt/CREB pathway in mouse hippocampi. Co-immunoprecipitation and western blotting assays revealed that TNFAIP1 interacted with CK2β and promoted its degradation by ubiquitination. Bioinformatics analysis showed a miR-93 binding site in the 3'-untranslated region of Tnfaip1. A dual-luciferase reporter assay revealed that miR-93 targeted TNFAIP1 and negatively regulated its expression. MiR-93 overexpression prevented DEHP-induced neurotoxicity by downregulating TNFAIP1 and then activating CK2/Akt/CREB pathway. These data indicate that DEHP upregulates TNFAIP1 expression by downregulating miR-93, thus promoting ubiquitin-mediated degradation of CK2β, subsequently inhibiting Akt/CREB pathway, and finally inducing learning and memory impairment. Therefore, miR-93 can relieve DEHP-induced neurotoxicity and may be used as a potential molecular target for prevention and treatment of related neurological disorders.

Di-(2-ethylhexyl) phthalate (DEHP) plasticizer, a well-known environmental and food pollutant, has neurotoxicity. However, it is unknown whether DEHP leads to learning and memory impairment through gut-brain axis and whether Clostridium butyricum can alleviate this impairment. Here, C57BL/6 mice were exposed to DEHP and treated with C. butyricum. Learning and memory abilities were evaluated through the Morris water maze. The levels of synaptic proteins, inflammatory cytokines, and 5-hydroxytryptamine (5-HT) were detected by immunohistochemistry or ELISA. Gut microbiota were analyzed through 16S rRNA sequencing. C. butyricum alleviated DEHP-induced learning and memory impairment and restored synaptic proteins. It significantly relieved DEHP-induced inflammation and recovered 5-HT levels. C. butyricum recovered the richness of the gut microbiota decreased by DEHP, with the Bifidobacterium genus increasing the most. Overall, C. butyricum alleviated DEHP-induced learning and memory impairment due to reduced inflammation and increased 5-HT secretion, which was partly attributed to the recovery of gut microbiota.

TNF α-induced protein 1 (TNFAIP1) was first identified in human umbilical vein endothelial cells and can be induced by tumor necrosis factor α (TNFα). Early studies have found that TNFAIP1 is involved in the development of many tumors and is closely associated with the neurological disorder Alzheimer's disease. However, little is known about the expression pattern of TNFAIP1 under physiological conditions and its function during embryonic development. In this study, we used zebrafish as a model to illustrate the early developmental expression pattern of tnfaip1 and its role in early development. First, we examined the expression pattern of tnfaip1 during early zebrafish development using quantitative real-time PCR and whole mount in situ hybridization and found that tnfaip1 was highly expressed in early embryonic development and, subsequently, expression became localized to anterior embryonic structures. To investigate the function of tnfaip1 during early development, we constructed a model of a stably inherited tnfaip1 mutant using the CRISPR/Cas9 system. Tnfaip1 mutant embryos showed significant developmental delays as well as microcephaly and microphthalmia. At the same time, we found decreased expression of the neuronal marker genes tuba1b, neurod1, and ccnd1 in tnfaip1 mutants. Analysis of transcriptome sequencing data revealed altered expression of the embryonic development related genes dhx40, hspa13, tnfrsf19, nppa, lrp2b, hspb9, clul1, zbtb47a, cryba1a, and adgrg4a in the tnfaip1 mutants. These findings suggest an important role for tnfaip1 in the early development of zebrafish.

The chemical and physical structure of cationic liposomes pays an important effect on their gene transfection efficiency. Investigation on the structure-function relationship of cationic liposomes will guide the design of novel cationic liposomes with high transfection efficiency and biosafety. In this paper, two novel series of lipids based on the backbone of pentaerythritol and trimethylolpropane were discovered, and their gene transfection efficiencies were assayed in vitro. The four lipids 8c, 9c, 14b, and 15b, exhibited much better transfection efficiency in the HEK293 cell lines compared with Lipo2000, lipid 9c also showed good transfection efficiency in the SW480 cell lines. And the structure-efficiency relationship revealed that a hydroxyethyl polar head group boosted transfer potency in trimethylolpropane-type lipids, but reduced in pentaerythritol-type lipids.

Gene co-expression network analysis has been widely used in gene function annotation, especially for long noncoding RNAs (lncRNAs). However, there is a lack of effective cross-platform analysis tools. For biologists to easily build a gene co-expression network and to predict gene function, we developed GCEN, a cross-platform command-line toolkit developed with C++. It is an efficient and easy-to-use solution that will allow everyone to perform gene co-expression network analysis without the requirement of sophisticated programming skills, especially in cases of RNA-Seq research and lncRNAs function annotation. Because of its modular design, GCEN can be easily integrated into other pipelines.

Oxidative stress-induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element-binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (H2O2) in vitro. PD inhibited the H2O2-induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated H2O2-induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against H2O2. The results indicated that PD protected neuronal cells from H2O2 by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.

Journal Article Adjuvant transarterial chemoembolization for intermediate-stage hepatocellular carcinoma with microvascular invasion Get access Xiao-Hui Wang, Xiao-Hui Wang Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China https://orcid.org/0000-0003-0544-2599 Search for other works by this author on: Oxford Academic Google Scholar Qun-Fang Zhou, Qun-Fang Zhou Department of Minimally Invasive Interventional Radiology, and Department of Radiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Search for other works by this author on: Oxford Academic Google Scholar Chen-Meng Wang, Chen-Meng Wang Department of Minimally Invasive Interventional Radiology, and Department of Radiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Search for other works by this author on: Oxford Academic Google Scholar Cai-Ling Xiang, Cai-Ling Xiang Department II of General Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China Search for other works by this author on: Oxford Academic Google Scholar Ying-Hui Song, Ying-Hui Song Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China Search for other works by this author on: Oxford Academic Google Scholar Shao-Qiang Li, Shao-Qiang Li Department of Liver Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China https://orcid.org/0000-0002-7108-2520 Search for other works by this author on: Oxford Academic Google Scholar Min-Shan Chen, Min-Shan Chen Department of Liver Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, China Search for other works by this author on: Oxford Academic Google Scholar Shuang-Lin Xiang, Shuang-Lin Xiang State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, China Correspondence to: Xian-Hai Mao, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China (e-mail: mxhaiszy@yahoo.com); Chang-Jun Liu, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China (e-mail: liuchangjun712@163.com); Shuang-Lin Xiang, State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, 36 Lushan Road, Yuelu, Changsha, Hunan 410081, China (e-mail: xshlin@hunnu.edu.cn) Search for other works by this author on: Oxford Academic Google Scholar Chang-Jun Liu, Chang-Jun Liu Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China Correspondence to: Xian-Hai Mao, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China (e-mail: mxhaiszy@yahoo.com); Chang-Jun Liu, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China (e-mail: liuchangjun712@163.com); Shuang-Lin Xiang, State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, 36 Lushan Road, Yuelu, Changsha, Hunan 410081, China (e-mail: xshlin@hunnu.edu.cn) Search for other works by this author on: Oxford Academic Google Scholar Xian-Hai Mao Xian-Hai Mao Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, China Correspondence to: Xian-Hai Mao, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China (e-mail: mxhaiszy@yahoo.com); Chang-Jun Liu, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan, China (e-mail: liuchangjun712@163.com); Shuang-Lin Xiang, State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, 36 Lushan Road, Yuelu, Changsha, Hunan 410081, China (e-mail: xshlin@hunnu.edu.cn) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 110, Issue 8, August 2023, Pages 913–916, https://doi.org/10.1093/bjs/znac376 Published: 17 November 2022 Article history Received: 07 May 2022 Revision received: 22 September 2022 Accepted: 20 October 2022 Published: 17 November 2022

Activity-dependent neuroprotective protein (ADNP) is vital for embryonic development and brain formation. Besides, the upregulated expression of ADNP enhances tumorigenesis in some human tumors like bladder cancer (BC). However, the potential roles of ADNP in drug resistance and the related mechanisms in BC is unknown. We performed this study to elucidate the influence of ADNP in the chemoresistance of BC and tried to explore the underlying molecular mechanism. The expressions of ADNP in BC from progression and non-progression patient specimens were measured by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). In vitro experiments including colony formation, cell counting kit-8 (CCK-8), wound healing, and in vivo tumorigenesis assay were performed to explore the effects of ADNP on chemoresistance of BC. The impacts of ADNP on TGF-β/Smad signaling pathways were explored by western blot. Our results showed that the expression of ADNP mRNA and protein were significantly upregulated in BC tissues of the patients who suffered tumor-progression via RT-PCR and western blot. Cox regression survival analysis revealed that patients with high ADNP expression closely linked to shorter tumor-free survival. ADNP downregulation in BC showed more sensitive to cisplatin in vivo, while ADNP overexpression showed the opposite results. Additionally, we confirmed that ADNP promoted cell migration and EMT, thereby inducing cisplatin resistance, which may be related to TGF-β / Smad signaling pathway.

We report a series of 20 cases of heterotopic cesarean scar pregnancy in this study. The results show that transvaginal sonography offers highly accurate diagnoses of heterotopic cesarean scar pregnancy during the first trimester. Careful exclusion of cesarean scar pregnancy is of great clinical importance for patients with a history of cesarean section after in vitro fertilization-embryo transfer, even when an intrauterine pregnancy has been detected. We recommend single embryo transfer for patients with a history of cesarean section. Expectant management may provide the opportunity for a live cesarean scar pregnancy to develop, albeit at high risks of placenta accreta and hemorrhage, and this needs further verification in the future.