Acta biochimica et biophysica Sinica最新文献

{"title":"Lung metastases formed by disseminated tumor cells exhibit different proliferation states.","authors":"Jiajun Liu, Shihui Liu, Jianhui Tian, Jiaxuan Li, Minghua Li, Zujun Que","doi":"10.3724/abbs.2024118","DOIUrl":"https://doi.org/10.3724/abbs.2024118","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Emerin in regulating fibroblast differentiation and migration at the substrate of stiffness coupled topology.","authors":"Tiantian Yang, Li Wang, Haiyang Ma, Kailun Li, Yajing Wang, Wenjie Tang, Zichen Wang, Meiwen An, Xiang Gao, Ludan Xu, Yunyun Guo, Jiqiang Guo, Yong Liu, Hugen Wang, Yang Liu, Quanyou Zhang","doi":"10.3724/abbs.2024094","DOIUrl":"10.3724/abbs.2024094","url":null,"abstract":"<p><p>In hypertrophic scars, the differentiation and migration of fibroblasts are influenced by the extracellular matrix microenvironment, which includes factors such as stiffness, restraint, and tensile force. These mechanical stresses incite alterations in cell behavior, accompanied by cytoskeletal protein reorganization. However, the role of nucleo-skeletal proteins in this context remains underexplored. In this study, we use a polyacrylamide hydrogel (PAA) to simulate the mechanical stress experienced by cells in scar tissue and investigate the impact of Emerin on cell behavior. We utilize atomic force microscopy (AFM) and RNA interference technology to analyze cell differentiation, migration, and stiffness. Our findings reveal that rigid substrates and cellular restriction elevate Emerin expression and diminish differentiation. Conversely, reducing Emerin expression leads to attenuated cell differentiation, where stiffness and constraining factors exert no notable influence. Furthermore, a softening of cells and an enhanced migration rate are also markedly observed. These observations indicate that variations in nuclear skeletal proteins, prompted by diverse matrix microenvironments, play a pivotal role in the pathogenesis of hypertrophic scars (HSs). This research offers novel insights and a reference point for understanding scar fibrosis formation mechanisms and preventing fibrosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1387-1400"},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma.","authors":"Changshuai Zhou, Huanhuan Cui, Yuechao Yang, Lei Chen, Mingtao Feng, Yang Gao, Deheng Li, Liangdong Li, Xin Chen, Xiaoqiu Li, Yiqun Cao","doi":"10.3724/abbs.2024109","DOIUrl":"10.3724/abbs.2024109","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that <i>SEC61G</i> knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant downregulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1748-1760"},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism of <i>Panax notoginseng</i> saponin in inhibiting the inflammatory response of microglia in cerebral ischemia based on network pharmacology.","authors":"Zhaoda Duan, Wenji Jia, Jianxiang Wang, Dongyao Xu, Yujia Yang, Zhi Qi, Li Yang, Chunyun Wu","doi":"10.3724/abbs.2024114","DOIUrl":"10.3724/abbs.2024114","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1566-1570"},"PeriodicalIF":3.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway.","authors":"Yunlian Diao, Shibo Huang, Fangpeng Liu, Shu Liao, Chenxi Guan, Xiaojian Xiong, Ping Zhang, Junyao Li, Wei Zhang, Ying Ying","doi":"10.3724/abbs.2024106","DOIUrl":"10.3724/abbs.2024106","url":null,"abstract":"<p><p>Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or <i>CCL2</i> knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by <i>CCL2</i> knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1549-1560"},"PeriodicalIF":3.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glyco-signatures in patients with advanced lung cancer during anti-PD-1/PD-L1 immunotherapy.","authors":"Xinyi Cao, Zhihuang Hu, Xiangying Sheng, Zhenyu Sun, Lijun Yang, Hong Shu, Xiaojing Liu, Guoquan Yan, Lei Zhang, Chao Liu, Ying Zhang, Huijie Wang, Haojie Lu","doi":"10.3724/abbs.2024110","DOIUrl":"10.3724/abbs.2024110","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN ¹⁷⁷STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, <i>P</i>=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, <i>P</i>=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN ¹⁷⁷STYR (H3N4) of IgG4, EEQYN ²²⁷STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1099-1107"},"PeriodicalIF":3.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-373-3p promotes aerobic glycolysis in colon cancer cells by targeting MFN2.","authors":"Yu Wang, Jie Lun, Yuying Zhang, Mengchao Yu, Xingqian Liu, Jing Guo, Hongwei Zhang, Wensheng Qiu, Jing Fang","doi":"10.3724/abbs.2024090","DOIUrl":"10.3724/abbs.2024090","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of <i>MFN2</i>, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts <i>in vivo</i> tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of <i>MFN2</i> mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of <i>MFN2</i> mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1498-1508"},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circIARS: a potential plasma biomarker for diagnosing non-small cell lung cancer.","authors":"Qi Zhang, Xinfeng Fan, Xinyu Zhang, Shaoqing Ju","doi":"10.3724/abbs.2024043","DOIUrl":"10.3724/abbs.2024043","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers in the world, and early diagnosis can effectively improve patient survival. Here, differentially expressed circIARS genes are screened from the sequencing results, and their molecular characteristics are examined by Sanger sequencing, RNase R assay, agarose gel electrophoresis (AGE), and fluorescence <i>in situ</i> hybridization (FISH). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) is performed to detect the expression level of circIARS. The diagnostic value of the signature is analyzed using a subject operating characteristic (ROC) curve. Moreover, plasma is collected from postsurgical, chemotherapy, and relapse patients to investigate the prognostic value of circIARS in NSCLC. The expression of circIARS is greater in both the plasma and tissues of NSCLC patients than in those of healthy individuals, and could be used to distinguish NSCLC patients from patients with benign pulmonary disease (BPD), small cell lung cancer (SCLC) patients, and healthy individuals. The expression level of circIARS relatively decreases after antitumor therapy, such as chemotherapy, and relatively increases after recurrence. ROC analysis reveals that circIARS has better detection efficiency than traditional markers. In addition, circIARS expression level is strongly correlated with several clinicopathological parameters. Finally, we tentatively predict the downstream miRNAs or RBP that might bind to circIARS. Plasma circIARS is significantly greater in NSCLC patients and has good stability and specificity as a diagnostic marker, which could aid in the adjuvant diagnosis and dynamic monitoring of NSCLC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"927-936"},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling a novel <i>GJB2</i> dominant K22T mutation in a Chinese family with hearing loss.","authors":"Haiting Ji, Yilai Shu, Huawei Li","doi":"10.3724/abbs.2024064","DOIUrl":"10.3724/abbs.2024064","url":null,"abstract":"<p><p>Hearing loss constitutes one of the most prevalent conditions within the field of otolaryngology. Recent investigations have revealed that mutations in deafness-associated genes, including point mutations and variations in DNA sequences, can cause hearing impairments. With the ethology of deafness remaining unclear for a substantial portion of the affected population, further screenings for pathogenic mutations are imperative to unveil the underlying mechanisms. On this study, by using next-generation sequencing, we examine 129 commonly implicated deafness-related genes in a Chinese family with hearing loss, revealing a novel heterozygous dominant mutation in the <i>GJB2</i> gene (GJB2: c.65T>G: p. Lys22Thr). This mutation consistently occurs in affected family members but is not detected in unaffected individuals, strongly suggesting its causative role in hearing loss. Structural analysis indicates potential disruption to the Cx26 gap junction channel's hydrogen bond and electrostatic interactions, aligning with predictions from the PolyPhen and SIFT algorithms. In conclusion, our study provides conclusive evidence that the identified heterozygous <i>GJB2</i> mutation (GJB2: c.65T>G: p. Lys22Thr), specifically the K22T alteration, is the primary determinant of the family's deafness. This contribution enhances our understanding of the interplay between common deafness-associated genes and hearing loss, offering valuable insights for diagnostic guidance and the formulation of therapeutic strategies for this condition.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"945-951"},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A subunit vaccine based on <i>Brucella</i> rBP26 induces Th1 immune responses and M1 macrophage activation.","authors":"Jia Wen, Zihua Li, Yongxue Lv, Shuqin Ding, Yazhou Zhu, Jihui Yang, Jing Tang, Mingxing Zhu, Yinqi Zhao, Wei Zhao","doi":"10.3724/abbs.2024023","DOIUrl":"10.3724/abbs.2024023","url":null,"abstract":"<p><p>Brucellosis is a global zoonotic infection caused by <i>Brucella</i> bacteria, which poses a significant burden on society. While transmission prevention is currently the most effective method, the absence of a licenced vaccine for humans necessitates the urgent development of a safe and effective vaccine. Recombinant protein-based subunit vaccines are considered promising options, and in this study, the <i>Brucella</i> BP26 protein is expressed using prokaryotic expression systems. The immune responses are evaluated using the well-established adjuvant CpG-ODN. The results demonstrate that rBP26 supplemented with a CpG adjuvant induces M1 macrophage polarization and stimulates cellular immune responses mediated by Th1 cells and CD8 ⁺ T cells. Additionally, it generates high levels of rBP26-specific antibodies in immunized mice. Furthermore, rBP26 immunization activates, proliferates, and produces cytokines in T lymphocytes while also maintaining immune memory for an extended period of time. These findings shed light on the potential biological function of rBP26, which is crucial for understanding brucellosis pathogenesis. Moreover, rBP26 holds promise as an effective subunit vaccine candidate for use in endemic areas.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"879-891"},"PeriodicalIF":3.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}