Biochimica et biophysica acta. General subjects最新文献

{"title":"Hybrid virtual screening identifies dipyrazole carboxamide derivatives as novel direct InhA inhibitors with antitubercular activity","authors":"Auradee Punkvang ,&nbsp;Bongkochawan Pakamwong ,&nbsp;Naruedon Phusi ,&nbsp;Paptawan Thongdee ,&nbsp;Kampanart Chayajarus ,&nbsp;Jidapa Sangswan ,&nbsp;Kanjana Pangjit ,&nbsp;Khomson Suttisintong ,&nbsp;Jiraporn Leanpolchareanchai ,&nbsp;Poonpilas Hongmanee ,&nbsp;Pitak Santanirand ,&nbsp;James Spencer ,&nbsp;Adrian J. Mulholland ,&nbsp;Sanya Sureram ,&nbsp;Prasat Kittakoop ,&nbsp;Pornpan Pungpo","doi":"10.1016/j.bbagen.2025.130827","DOIUrl":"10.1016/j.bbagen.2025.130827","url":null,"abstract":"<div><div>Direct inhibitors of <em>M. tuberculosis</em> enoyl-acyl carrier protein reductase (<em>M. tuberculosis</em> InhA) remain effective against variants with mutations associated with isoniazid resistance. In our previous study, structure-based virtual screening was employed to discover such inhibitors. However, most identified hits exhibited limited antimycobacterial activity, with minimum inhibitory concentration (MIC) values of &gt;100 μg/mL. To address this challenge, we refined our virtual screening strategy by integrating ligand- and structure-based virtual screening approaches. The efficacy of this hybrid virtual screening approach was validated through biological assays measuring MIC and half-maximal inhibitory concentration (IC₅₀) for the inhibition of <em>M. tuberculosis</em> growth and InhA activity, respectively. Among 14 identified hits, compounds <strong>3</strong> and <strong>10</strong>, classified as dipyrazole carboxamide derivatives, were validated as promising lead candidates, with MIC values of 25 and 50 μg/mL and IC₅₀ values of 10.60 ± 0.56 and 5.08 ± 0.30 μM, respectively. The relatively low hit-to‑lead conversion rate (14 %) is ascribed to our observation that nine of the identified hits, including compounds <strong>3</strong> and <strong>10</strong>, showed some level of precipitation in the MIC assay medium. Molecular dynamics simulations show that the dipyrazole carboxamide moiety in compounds <strong>3</strong> and <strong>10</strong> forms essential hydrogen bonds with nicotinamide adenine dinucleotide (oxidized form) (NAD⁺) in the InhA binding pocket. Notably, both compounds <strong>3</strong> and <strong>10</strong> exhibit favorable safety profiles, with no toxicity observed in Caco-2 cells at concentrations up to 100 μg/mL. Consequently, we believe that these compounds present promising starting points for further lead optimization and development of novel antitubercular agents.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130827"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of mesenchymal stem cells and their exosomes in radiotherapy: A new opportunity or a potential threat","authors":"Fatemeh Zeinalzadeh ,&nbsp;Seyedeh Nasibeh Mousavikia ,&nbsp;Mohammad Taghi Bahreyni Toossi ,&nbsp;Hosein Azimian","doi":"10.1016/j.bbagen.2025.130823","DOIUrl":"10.1016/j.bbagen.2025.130823","url":null,"abstract":"<div><div>Cancer remains a major global health problem characterized by complex biological mechanisms and diverse clinical manifestations. Radiotherapy is a key element in cancer treatment. However, radioresistance is a major obstacle to achieving optimal results. This resistance is associated with several factors, including genetic and epigenetic changes in tumor cells that allow cancer cells to survive and proliferate despite radiation exposure. In this context, mesenchymal stem cells (MSCs) play an important role in the tumor microenvironment. Due to their unique properties such as self-renewal, migration to tumors <em>via</em> the bloodstream and involvement in paracrine signaling, they are important for understanding cancer biology and treatment responses. MSCs can release exosomes that can promote intercellular communication and influence tumor response to radiotherapy. However, the role of MSCs in cancer is complex and sometimes contradictory. In some contexts they may exhibit tumor suppressive effects, while in others they promote tumor growth and metastasis. This duality raises important questions about their overall impact on cancer therapy, particularly in relation to radiotherapy. This review will first explore the multifaceted role of MSCs and their exosomes as key mediators of cellular communication within the tumor microenvironment, and then assess the implications of these interactions for radiotherapy, focusing on how MSCs may influence treatment efficacy and the potential to harness their properties to improve therapeutic outcomes.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130823"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-glycosylation of CD4+ T cell changes with the development in Graves' disease and is sensitive to methimazole treatment","authors":"Sara Trzos ,&nbsp;Marta Szewczyk ,&nbsp;Paweł Link-Lenczowski ,&nbsp;Grzegorz Sokołowski ,&nbsp;Małgorzata Trofimiuk-Müldner ,&nbsp;Katarzyna Bocian ,&nbsp;Ewa Pocheć","doi":"10.1016/j.bbagen.2025.130824","DOIUrl":"10.1016/j.bbagen.2025.130824","url":null,"abstract":"<div><div>Graves' disease (GD) is one of the most common autoimmune disorders. Helper T (Th) cells, whose surface receptors are rich in glycans, are involved in the GD pathomechanism. <em>N</em>-glycosylation is altered during autoimmunity and can be modulated by pharmacotherapy. We hypothesized that changes in Th glycosylation accompany GD, and the glycome of these cells is sensitive to methimazole therapy. The study group consisted of patients with Graves' disease before (GD) and after (GD/T) restoring euthyroidism as a result of methimazole therapy. In the control group, healthy donors were recruited. Th cells were isolated from PBMCs and sorted into a subpopulation of CD4⁺CD25⁻ cells and those expressing the CD25 late activation marker (CD4⁺CD25⁺). MALDI-Tof MS was used for analysis of <em>N-</em>linked glycans, and the expression of glycosyltransferases was determined by RT-qPCR. The <em>N</em>-glycosylation profile of CD4⁺ cell subpopulations differed in the ratio of the complex-to-oligomannose <em>N</em>-glycans in GD. Complex <em>N</em>-glycans are partially replaced by oligomannose forms, and their structure is shortened by agalactosylation in CD4⁺CD25⁻ cells from GD. The rearrangement of <em>N</em>-glycans in CD4⁺CD25⁺ cells has the opposite direction, namely the ratio is shifted towards complex structures in GD. The changes in the <em>N</em>-glycan profile were reflected partly in <em>MGAT5</em> and <em>FUT8</em> expression. Methimazole to some extent normalized the glycosyltransferase levels and affected the <em>N</em>-linked glycans profile. Our study shows <em>N</em>-glycosylation changes in CD4⁺ T cells in GD development and methimazole therapy for the first time. Further studies are needed to determine the functional aspect of the identified glycosylation changes in thyroid autoimmunity.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130824"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual generation of stereo- and linear-specific monoclonal antibodies through B-cell receptors by DNA and cell immunization for therapeutic applications","authors":"Chiho Miyamae ,&nbsp;Yushi Isozaki ,&nbsp;Kanta Tsumoto ,&nbsp;Masahiro Tomita","doi":"10.1016/j.bbagen.2025.130822","DOIUrl":"10.1016/j.bbagen.2025.130822","url":null,"abstract":"<div><div>The optimized stereospecific targeting (SST) technique features selective generation of conformation-specific monoclonal antibodies against membranous proteins with high specificity after DNA and cell immunization. This technology consists of two critical steps, which are specific selection of sensitized B lymphocytes by antigen-expressing myeloma cells through B-cell receptors (BCRs) and selective fusion of B cell-myeloma cell complexes by electrical pulses to produce hybridoma cells secreting stereospecific monoclonal antibodies. Here we were able to verify the critical step for the selection of B lymphocytes by intact antigen-expressing myeloma cells by a double-label immunofluorescence analysis. Interestingly, the cell complex was a single attachment. Furthermore, we newly found the new progress that the optimized SST technique offered dual production of anti-intact and anti-linear specific monoclonal antibodies against a human ephrin type-A receptor 2 (hEphA2). The optimized SST technique may be useful for producing not only stereospecific monoclonal antibodies, but also primary-specific monoclonal antibodies based on the selection of sensitized B lymphocytes by the target intact antigen through BCRs. It would elicit more advanced medical applications by generating dual monoclonal antibodies against the intact antigen.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130822"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mastering the plant growth symphony: The interplay between calcium sensing machinery and phytohormone signaling during abiotic stress","authors":"Tanashvi Seth,&nbsp;Shruti Saxena,&nbsp;Barkha Ravi,&nbsp;Girdhar K. Pandey","doi":"10.1016/j.bbagen.2025.130820","DOIUrl":"10.1016/j.bbagen.2025.130820","url":null,"abstract":"<div><div>Climate change introduces a multitude of abiotic stressors, affecting plants' ability to thrive and produce. Abiotic stresses significantly impair plant growth, development, and production, jeopardizing food security. Despite extensive research on individual stress adaptation mechanisms, a critical gap remains in understanding the synergistic role of calcium (Ca²⁺) signaling and phytohormonal regulation in plant stress responses. Ca²⁺, a ubiquitous second messenger, plays a pivotal role in stress perception and signal transduction, while phytohormones regulate adaptive physiological and molecular responses. This review aims to bridge the knowledge gap by synthesizing recent advancements in Ca²⁺-phytohormone interactions and their combined role in enhancing plant resilience to abiotic stress. Hence, understanding these interconnected signaling cascades would pave the path for the development of innovative strategies for enhancing crop stress tolerance, thereby promoting sustainable agriculture in the face of climate change.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130820"},"PeriodicalIF":2.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLAMF9 aggravates myocardial ischemia reperfusion injury through activating the hippo-yap pathway","authors":"Tingting Liu ,&nbsp;Xiuli Guo ,&nbsp;Yanhua Fu ,&nbsp;Weili Zhang","doi":"10.1016/j.bbagen.2025.130821","DOIUrl":"10.1016/j.bbagen.2025.130821","url":null,"abstract":"<div><h3>Background</h3><div>The objective was to investigate the impact of signaling lymphocyte activation molecule family member 9 (SLAMF9) on myocardial infarction (MI) and its mechanisms.</div></div><div><h3>Methods</h3><div>SLAMF9 expression in MI rats was firstly measured. SLAMF9 effect on cardiac functions, myocardial fibrosis, cardiomyocyte hypertrophy, cardiomyocyte apoptosis and inflammation in MI rats was explored using echocardiography, HE staining, masson staining, wheat germ agglutinin staining, western blot, TUNEL staining and qRT-PCR. Meanwhile, SLAMF9 effect on the viability, apoptosis, and inflammation in H9C2 cells was investigated by CCK-8 assay, TUNEL staining and western blot. Moreover, the potential mechanisms of SLAMF9 were investigated using western blot, ELISA and TUNEL staining after different treatment.</div></div><div><h3>Results</h3><div>SLAMF9 expression was upregulated in MI rats. SLAMF9 knockdown ameliorated heart damage, cardiomyocyte apoptosis and inflammatory response in MI rats. Similarly, SLAMF9 silencing in macrophages attenuated the apoptosis and inflammatory response in H/R-induced H9C2 cells. Moreover, SLAMF9 knockdown inhibited Hippo-Yap pathway in MI in vitro and in vivo. Besides, SLAMF9 knockdown in macrophages suppressed the activation of Hippo-Yap pathway in H9C2 cells by inhibiting TNF-α release. Additionally, LATS1 overexpression in H9C2 cells reversed the effect of SLAMF9 silencing on the apoptosis and inflammatory response in H/R-induced H9C2 cells. Meanwhile, PY-60 treatment in H9C2 cells reversed the effect of SLAMF9 overexpression on the apoptosis and inflammatory response in H/R-induced H9C2 cells.</div></div><div><h3>Conclusion</h3><div>The absence of SLAMF9 led to a reduction in TNF-α secretion in macrophages, consequently repressing Hippo-Yap pathway in cardiomyocytes, and ultimately ameliorating myocardial damage, cardiomyocyte apoptosis and inflammation in MI.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130821"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the calcium signal: Structural insights into CBL-CIPK pathway in plants","authors":"Subhash Chandra Bihani ,&nbsp;Tarushi ,&nbsp;Ashish Kumar Srivastava","doi":"10.1016/j.bbagen.2025.130819","DOIUrl":"10.1016/j.bbagen.2025.130819","url":null,"abstract":"<div><div>Calcium (Ca²⁺) signaling in plants is a major pathway in transducing diverse environmental stimuli. Calcineurin B-like proteins (CBLs) are one of the unique groups of Ca²⁺ sensors that transduce the Ca²⁺ signals by interacting with plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). In recent years, structure-function studies have provided key insights into the molecular basis of CBL-CIPK signaling and their interactions with the target proteins. The crystal structures of CBL2 and CBL4 have elucidated the architecture of non-canonical EF hands and provided the rationale for Ca²⁺ binding by CBLs. The molecular basis of interaction of the regulatory domain of CIPKs with CBLs has been established, providing rationale for CBL-mediated activation of CIPKs. The molecular mechanism of fine regulation of CIPK activity under non-stressed conditions and full activation under stressed conditions has been established using crystal structures of CIPK23 and CIPK24. Recently, high-resolution CryoEM structures of Arabidopsis and rice SOS1 led to a comprehensive understanding of its regulation and ion transport mechanism. In this review, major advances in understanding the structural basis of Ca²⁺ sensing by CBLs, molecular determinants of CIPK activation, and subsequent phosphorylation of target proteins are discussed. Remaining questions that need to be answered for a holistic understanding of the CBL-CIPK network are also discussed.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130819"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyanobacterial KdpD modulates in vivo and in vitro activities of a membrane-anchored histidine kinase","authors":"Anand Ballal ,&nbsp;Shree Kumar Apte","doi":"10.1016/j.bbagen.2025.130817","DOIUrl":"10.1016/j.bbagen.2025.130817","url":null,"abstract":"<div><div>The prokaryotic KdpATPAse complex, encoded by the <em>kdpABC</em> operon, is an inducible, high-affinity K⁺ transporter. In <em>E. coli</em>, the operon is transcriptionally regulated by a two-component sensor-kinase response-regulator system, constituted by the KdpD and KdpE proteins. In contrast, cyanobacteria exhibit a truncated <em>kdpD</em> gene that encodes a KdpD homolog that is similar to the N-terminal domain (NTD) of <em>E. coli</em> KdpD, but lacks the transmitter, histidine kinase-containing, C-terminal domain (CTD). Here we show that the cyanobacterium <em>Anabaena</em> sp. strain L-31 constitutively transcribes the short <em>kdpD</em> gene, but synthesizes KdpATPase only during potassium starvation. However, unlike <em>E. coli</em>., expression of the <em>kdpD</em> gene remains unaffected by K⁺ limitation in <em>Anabaena</em>. To gain insight into the possible role of <em>Anabaena</em> KdpD, the chimeric Anacoli KdpD protein, wherein the NTD of <em>E. coli</em> KdpD was replaced with <em>Anabaena</em> KdpD, was functionally analyzed. Detailed investigation has revealed that the Anacoli KdpD (a) responds to a much lower threshold of external K⁺ than the <em>E. coli</em> KdpD (b) exhibits much reduced ability to induce <em>kdp</em> in response to ionic osmolytes than <em>E. coli</em> KdpD, and is therefore unable to sustain optimal growth in the presence of these osmolytes and (c) displays higher in vitro phosphatase activity than the wild type <em>E. coli</em> KdpD. Thus, <em>Anabaena</em> KdpD modulates properties of <em>E. coli</em> KdpD-CTD in a manner that is quite distinct from the <em>E. coli</em> KdpD-NTD. Based on these evidences, a model for <em>kdp</em> regulation by the short KdpD is proposed.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130817"},"PeriodicalIF":2.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"There is more to scanning than meets the eye: Raster Image Correlation Spectroscopy","authors":"Irene Gialdini ,&nbsp;Jelle Hendrix ,&nbsp;Don C. Lamb","doi":"10.1016/j.bbagen.2025.130818","DOIUrl":"10.1016/j.bbagen.2025.130818","url":null,"abstract":"<div><div>Raster Image Correlation Spectroscopy (RICS) is a confocal image analysis method that can measure the diffusion and interactions of fluorescently labeled molecules in real time in solution and in living cells. RICS is easy to implement on commercial confocal microscopes and allows detailed investigations of complex biological systems and pathways. The method is especially robust for measurements in living cells using commonly used labels such as fluorescent proteins. Moreover, since its invention in 2005, the robustness and applicability of RICS has been significantly increased to allow, e.g., straightforward kinetic analyses, advanced image segmentation, parameter mapping, and multi-species analysis. In this review, we describe the methodological principles of RICS in a manner that is accessible to a broad readership, position RICS in relation to other fluorescence fluctuation techniques, highlight recent methodological advances and present exemplary applications of the method. With this review, we hope to facilitate the implementation of this powerful method into the everyday repertoire of confocal imaging approaches.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130818"},"PeriodicalIF":2.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LACTB promotes cell differentiation and inhibits cell proliferation in colorectal cancer","authors":"Lili Ma ,&nbsp;Guan Huang ,&nbsp;Chun Lin ,&nbsp;Xiaoqing Li ,&nbsp;Chao Liu ,&nbsp;Weiye Huang ,&nbsp;Qingling Zhang ,&nbsp;Yang Luo","doi":"10.1016/j.bbagen.2025.130816","DOIUrl":"10.1016/j.bbagen.2025.130816","url":null,"abstract":"<div><div>This study aims at exploring the role of LACTB on colorectal cancer (CRC) cell differentiation. In this study, 143 colorectal cancer tissue samples were collected for analyzing the correlation between LACTB level and clinical information. Another 24 recent cases and adjacent tissues underwent qPCR, Western blot, and immunohistochemistry (IHC) to detect LACTB expression. The differentiation and proliferation of CRC cells were evaluated by AKP levels, E-cadherin expression, cell viability, colony formation, EdU assay, and cell cycle. Subcutaneous models explored LACTB's pro-differentiation effects. The glandular-like structures of tumor were observed by HE staining, immunofluorescence detection of microvilli proteins, and transmission electron microscopy. Our results showed that LACTB expression in colorectal cancer tissues was lower than that in adjacent normal tissues. Higher LACTB expression was correlated with slower tumor progression, better prognosis and higher differentiation degree. Overexpressing LACTB in CRC cells enhanced differentiation markers level (AKP and E-cadherin), while inhibited cell proliferation and colony formation, induced cell cycle arrest. Conversely, LACTB knockdown had an opposite effect. Subcutaneous xenograft tumor model suggested that LACTB overexpression inhibited tumor growth, induced tissue differentiation and glandular-like structures formation. Collectively, our results show that LACTB overexpression promotes cell differentiation and inhibits cell proliferation in CRC cells, which may serve as a therapy target for CRC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130816"},"PeriodicalIF":2.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}