Chemico-Biological Interactions最新文献

{"title":"CNIH4 governs cervical cancer progression through reducing ferroptosis","authors":"Jun-Yuan Yang ,&nbsp;Dong Ke ,&nbsp;Yanli Li ,&nbsp;Jie Shi ,&nbsp;Shi-Meng Wan ,&nbsp;An-Jin Wang ,&nbsp;Meng-Na Zhao ,&nbsp;Han Gao","doi":"10.1016/j.cbi.2023.110712","DOIUrl":"10.1016/j.cbi.2023.110712","url":null,"abstract":"<div><p><span><span>Cervical cancer<span><span><span> is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family </span>AMPA receptor<span> auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors<span> to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. </span></span></span>Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and </span></span>disease free survival<span> rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated </span></span>cystine<span> import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110712"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10272438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cu(II)-acylhydrazone complex, a potent and selective antitumor agent against human osteosarcoma: Mechanism of action studies over in vitro and in vivo models","authors":"Lucia M. Balsa ,&nbsp;Luisina M. Solernó ,&nbsp;Maria R. Rodriguez ,&nbsp;Beatriz S. Parajón-Costa ,&nbsp;Ana C. Gonzalez-Baró ,&nbsp;Daniel F. Alonso ,&nbsp;Juan Garona ,&nbsp;Ignacio E. León","doi":"10.1016/j.cbi.2023.110685","DOIUrl":"10.1016/j.cbi.2023.110685","url":null,"abstract":"<div><p><span>Osteosarcoma<span> (OS) is a frequent bone cancer, affecting largely children and young adults. Cisplatin (CDDP) has been efficacious in the treatment of different cancer such us OS but the development of chemoresistance and important side effects leading to therapeutic failure. Novel therapies including copper compounds have shown to be potentially effective as </span></span>anticancer drugs<span> and one alternative to usually employed platinum compounds.</span></p><p>The goal of this work is the evaluation of the <em>in vitro</em> and <em>in vivo</em><span> antitumoral activity and dilucidate the molecular target of a Cu(II) cationic complex containing a tridentate hydrazone ligand, CuHL for short, H</span>₂L=N'-'-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide, against human OS MG-63 cells.</p><p><span>Anticancer activity on MG-63 cell line was evaluated in OS monolayer and spheroids. CuHL significantly impaired cell viability in both models (IC</span>₅₀<span> 2D: 2.1 ± 0.3 μM; 3D: 9.1 ± 1.0 μM) (p &lt; 0.001). Additional cell studies demonstrated the copper compound inhibits cell proliferation<span><span> and conveys cells to apoptosis, determined by flow cytometry. CuHL showed a great genotoxicity, evaluated by </span>comet assay<span>. Proteomic analysis by Orbitrap Mass Spectometry identified 27 differentially expressed proteins: 17 proteins were found overexpressed and 10 underexpressed in MG-63 cells after the CuHL treatment. The response to unfolded protein was the most affected biological process.</span></span></span></p><p>In addition, <em>in vivo</em><span><span><span> antitumor effects of the compound were evaluated on human OS tumors xenografted in nude mice. CuHL treatment, at a dose of 2 mg/kg i.p., given three times/week for one month, significantly inhibited the progression of OS xenografts and was associated to a reduction in mitotic index and to an increment of </span>tumor necrosis (p &lt; 0.01). Administration of standard-of-care </span>cytotoxic agent CDDP, following the same treatment schedule as CuHL, failed to impair OS growth and progression.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110685"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis contributes to cyclophosphamide-induced hemorrhagic cystitis","authors":"Zhimin Mao,&nbsp;Kun Zhong,&nbsp;Xiaojun Liu,&nbsp;Xuhui Zeng","doi":"10.1016/j.cbi.2023.110701","DOIUrl":"10.1016/j.cbi.2023.110701","url":null,"abstract":"<div><p>Cyclophosphamide<span><span><span> (CYP) is extensively used in tumor therapy, but its clinical application is limited by its toxic effects on the bladder. Since CYP-induced cystitis is believed to be mediated by acrolein (ACR), a product of lipid peroxidation that triggers </span>ferroptosis, we hypothesized that ferroptosis might be an essential molecular mechanism underlying CYP-induced cystitis. The purpose of this study was to test this hypothesis. </span>Intraperitoneal injection<span><span> of CYP led to bladder hemorrhage and edema, along with increased oxidation, inflammation, and cell injury. Further analysis revealed these changes were associated with altered ferroptosis markers in the bladder, such as FPN1, ACSL4, SLC7A11, and GPX4, indicating the existence of ferroptosis. Administration of ferroptosis inhibitor </span>dexrazoxane (DXZ) improved ferroptosis and prevented CYP-induced pathological changes in the bladder. Collectively, our study revealed that ferroptosis is an important mechanism underlying CYP-induced cystitis, and therapeutic approaches targeting ferroptosis could be developed to treat CYP-induced cystitis.</span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110701"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The selective activator protein-1 inhibitor T-5224 regulates the IRF4/MYC axis and exerts cooperative antimyeloma activity with bortezomib","authors":"Sishi Tang ,&nbsp;Fangrong Zhang ,&nbsp;Jian Li ,&nbsp;Hang Dong ,&nbsp;Qin Yang ,&nbsp;Jing Liu ,&nbsp;Yunfeng Fu","doi":"10.1016/j.cbi.2023.110687","DOIUrl":"10.1016/j.cbi.2023.110687","url":null,"abstract":"<div><p><span>The activating protein-1 (AP-1) transcription factors (TFs) have been associated with many different cancer types and are promising therapeutic targets in logical malignancies. However, the mechanisms of their role in multiple myeloma (MM) remain elusive. The present study determined and compared the mRNA and protein expression levels of the AP-1 family member JunB in CD138</span>⁺<span><span> mononuclear cells from MM patients and healthy donors. Herein, we investigated the effect of T-5224, an inhibitor of JUN/AP-1, on MM. We found that the cytotoxicity of T-5224 toward myeloma<span> is due to its ability to induce cell apoptosis, inhibit proliferation, and induce cell cycle arrest by increasing the levels of cleaved caspase3/7 and concomitantly inhibiting the IRF4/MYC axis. We also noticed that siJunB-mediated deletion of JunB/AP-1 enhanced MM cell apoptosis and affected cell proliferation<span>. The software PROMO was used in the present study to predict the AP-1 TF that may bind the promoter region of IRF4. We confirmed the correlation between JunB/AP-1 and IRF4. Given that </span></span></span>bortezomib (BTZ) facilitates IRF4 degradation in MM cells, we applied combination treatment of BTZ with T-5224. T-5224 and BTZ exerted synergistic effects, and T-5224 reversed the effect of BTZ on CD138</span>⁺ primary resistance in MM cells, in part due to suppression of the IRF4/MYC axis. Our results suggest that targeting AP-1 TFs is a promising therapeutic strategy for MM. Additionally, targeting both AP-1 and IRF4 with T-5224 may be a synergistic therapeutic strategy for this clinically challenging subset of MM.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110687"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10128647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rottlerin impairs early and late steps of Toxoplasma gondii infection in human trophoblast cells and villous explants","authors":"Samuel Cota Teixeira ,&nbsp;Marina Paschoalino ,&nbsp;Guilherme de Souza ,&nbsp;Alessandra Monteiro Rosini ,&nbsp;Joed Pires de Lima Junior ,&nbsp;Luana Carvalho Luz ,&nbsp;Aryani Felixa Fajardo Martínez ,&nbsp;Rosiane Nascimento Alves ,&nbsp;Marcos Paulo Oliveira Almeida ,&nbsp;Jaqueline Lopes Damasceno ,&nbsp;Marcelo José Barbosa Silva ,&nbsp;Francesca Ietta ,&nbsp;Bellisa Freitas Barbosa ,&nbsp;Eloisa Amália Vieira Ferro ,&nbsp;Carlos Henrique Gomes Martins","doi":"10.1016/j.cbi.2023.110716","DOIUrl":"10.1016/j.cbi.2023.110716","url":null,"abstract":"<div><p><span>Congenital toxoplasmosis, caused by the opportunistic protozoan parasite </span><em>T. gondii</em><span><span>, can cause stillbirths, miscarriages and </span>fetal abnormalities<span><span>, as well as encephalitis and chorioretinitis in newborns. Available treatment options rely on </span>antiparasitic drugs<span> that have been linked to serious side effects, high toxicity and the development of drug-resistant parasites. The search for alternative therapeutics to treat this disease without acute toxicity for the mother and child is essential for the advancement of current therapeutic procedures. The present study aimed to unravel the mode of the anti-</span></span></span><em>T. gondii</em><span><span> action of Rottlerin, a natural polyphenol with multiple pharmacological properties described. Herein, we further assessed the </span>antiparasitic activity of Rottlerin against </span><em>T. gondii</em><span> infection on the human trophoblastic cells (BeWo cells) and, for the first time, on human villous explants. We found that non-cytotoxic doses of Rottlerin impaired early and late steps of parasite infection<span> with an irreversible manner in BeWo cells. Rottlerin caused parasite cell cycle arrest in G1 phase and compromised the ability of tachyzoites<span> to infect new cells, thus highlighting the possible direct action on parasites. An additional and non-exclusive mechanism of action of Rottlerin involves the modulation of host cell components, by affecting lipid droplet formation, mitochondrial function and upregulation of the IL-6 and MIF levels in BeWo cells. Supporting our findings, Rottlerin also controlled </span></span></span><em>T. gondii</em> proliferation in villous explants with low toxicity and reduced the IL-10 levels, a cytokine associated with parasite susceptibility. Collectively, our results highlighted the potential use of Rottlerin as a promising tool to prevent and/or treat congenital toxoplasmosis.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110716"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10656854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel self-assembled nanoplatform based on retrofitting poloxamer 188 for triple-negative breast cancer targeting treatment","authors":"Xueyan Hou ,&nbsp;Yalin Guan ,&nbsp;Sisi He ,&nbsp;Zeqing Wu ,&nbsp;Jintao Bai ,&nbsp;Jingjing Xu ,&nbsp;Jingwen Wang ,&nbsp;Suyue Xu ,&nbsp;Huiqing Zhu ,&nbsp;Yanyan Yin ,&nbsp;Xue Yang ,&nbsp;Yongli Shi","doi":"10.1016/j.cbi.2023.110710","DOIUrl":"10.1016/j.cbi.2023.110710","url":null,"abstract":"<div><p><span>Poloxamer 188<span> is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs<span>, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (&lt; 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, </span></span></span>docetaxel<span> (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity<span> of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.</span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110710"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10272010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrine disrupts Nrf2/GPX4 antioxidant system and promotes hepatocyte ferroptosis","authors":"Xi Wang,&nbsp;Wenjing Zhu,&nbsp;Miao Xing,&nbsp;Haiyan Zhu,&nbsp;Enqing Chen,&nbsp;Jie Zhou","doi":"10.1016/j.cbi.2023.110713","DOIUrl":"10.1016/j.cbi.2023.110713","url":null,"abstract":"<div><p><span>Matrine (MT) is an alkaloid isolated from </span><span><em>Sophora flavescens</em></span><span><span><span><span> with various bioactivities and is widely used clinically. However, the broader its clinical use, the greater its toxicity concerns. We investigate the role of </span>ferroptosis<span> in MT-induced liver injury caused by an imbalance in the antioxidant pathway. Our results showed that MT could cause pathological changes in liver tissues and lead to a significant reduction in L02 cell viability<span>. MT also reduced superoxide dismutase (SOD) and </span></span></span>glutathione<span> (GSH), increased malondialdehyde<span><span> (MDA), reactive oxygen species (ROS), and lipid peroxidation levels, and disrupted iron </span>homeostasis<span>, leading to ferroptosis. In addition, MT decreased the protein levels of FTH, Nrf2, xCT, GPX4, HO-1 and ferroptosis suppressor </span></span></span></span>protein 1<span> (FSP1) and increased the protein levels of TRF1 and DMT1, characteristic indicators of ferroptosis. Interestingly, the cytotoxic effects of MT were alleviated by ferroptosis inhibitor, Nrf2 agonist, or selenium supplementation. These results revealed that MT triggers hepatocyte ferroptosis by inhibiting the Nrf2/GPX4 antioxidant system.</span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110713"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-Acetyldeoxynivalenol induces apoptosis, barrier dysfunction and endoplasmic reticulum stress by inhibiting mTORC1-dependent autophagy in porcine enterocytes","authors":"Tongkun Zhang ,&nbsp;Jun Bai ,&nbsp;Guangye Chen ,&nbsp;Zhaohui Chen ,&nbsp;Shenming Zeng ,&nbsp;Ying Yang ,&nbsp;Zhenlong Wu","doi":"10.1016/j.cbi.2023.110695","DOIUrl":"10.1016/j.cbi.2023.110695","url":null,"abstract":"<div><p><span>3-Acetyldeoxynivalenol (3-Ac-DON), an acetylated form of deoxynivalenol<span>, is widely present in mycotoxin-contaminated food, feed as well as in other natural sources. Ingestion of 3-Ac-DON may result in intestinal dysfunction, leading to gut diseases<span> in humans and animals. Nevertheless, the molecular mechanism of 3-Ac-DON in intestinal epithelial cytotoxicity remains unclear. In this study, intestinal porcine epithelial cell line 1 (IPEC-1) cells were treated with different concentrations of 3-Ac-DON for 12 h or 24 h, respectively. The results showed that 3-Ac-DON caused decreased cell viability<span>, cell cycle arrest in G1 phase and depolarization of mitochondrial membrane potential. Western blotting<span><span> analysis showed that 3-Ac-DON significantly decreased the expression of tight junction proteins, inhibited autophagy and activated </span>endoplasmic reticulum (ER) stress in IPEC-1 cells (</span></span></span></span></span><em>P</em><span><span> &lt; 0.05). Further investigation demonstrated that 3-Ac-DON caused apoptosis, ER stress and barrier dysfunction were reversed after co-treatment with the autophagy activator rapamycin (100 nM), indicating that autophagy plays a key role in the process of 3-Ac-DON-induced cell damage. In addition, we demonstrated that 3-Ac-DON inhibits the occurrence of autophagy mediated by mTORC1 protein. In conclusion, our research indicated that the mTORC1 protein and autophagy played a key role in the 3-Ac-DON-induced cytotoxic in IPEC-1 cells, which would provide new therapeutic targets and ideas for 3-Ac-DON-mediated </span>intestinal injury</span><strong>.</strong></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110695"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effect of the quercetin on cardiovascular remodeling and atherosclerosis in rodents fed a high-fat diet: A systematic review","authors":"Djane A. Espírito-Santo ,&nbsp;Gabriele S. Cordeiro ,&nbsp;Lucimeire S. Santos ,&nbsp;Rafael T. Silva ,&nbsp;Márcia U. Pereira ,&nbsp;Rhowena Jane B. Matos ,&nbsp;Gilson T. Boaventura ,&nbsp;Jairza Maria Barreto-Medeiros","doi":"10.1016/j.cbi.2023.110700","DOIUrl":"10.1016/j.cbi.2023.110700","url":null,"abstract":"<div><p><span><span>Cardiovascular diseases (CVD) are the leading cause of death globally, estimated at 17.9 million premature deaths. Several risk factors contribute to the development of CVD, including unhealthy diet rich in saturated fat. </span>Quercetin<span> (Q) is a important natural flavonoid<span><span><span> with cardioprotective effect. However, it is crucial to understand and clarify which dosages and intervention times quercetin promotes better cardioprotective effects when exposed to a High-Fat Diet (HFD). We aim was to carry out a review to identify and compare experimental studies that investigated the quercetin effect on cardiac parameters in rodents fed a HFD. This literature search was performed through the specialized databases PubMed, Embase, Web of Science and Lilacs in May 2022. The following information was collected and assessed: Species of animals, dietary fat content, intervention protocol (quercetin), and main results of alterations associated with cardiac change. A total of 116 articles were selected from the database and 30 articles were included in this study. The administration form of quercetin was used in the diet supplemented in 73.4% (n = 22) of the studies. The dosage ranged between 10 and 100 mg/kg, 0.01%–0.36%, and 4–8 g/kg diet. The treatment time ranged between 14 and 63 days in 48.4% studies and most of the selected studies observed changes in the: Serum concentrations of lipids (60%, n = 18) mainly decrease in TC and TG, left ventricle (LV) (16.13%, n = 5) includes attenuation of the </span>cardiac hypertrophy; inhibition of atherosclerotic progression (32%, n = 10) with decrease in lesions and plaque formation; improvement in the expression of gene and protein associated with cardiac functionality and </span>oxidative stress (51.6%; n = 16). </span></span></span><em>Q</em><span>uercetin supplementation at different concentrations/doses promotes important cardioprotective effects in experimental models exposed to a HFD. The supplemented diet was shown to be the better administration option. The methodological variation presented in the articles selected in this review proves that the most appropriate intervention protocol, as well as the most effective route of administration, promotes these effects.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110700"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10649415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells","authors":"Yewei Wang ,&nbsp;Zeljka Popovic ,&nbsp;Georgia Charkoftaki ,&nbsp;Rolando Garcia-Milian ,&nbsp;TuKiet T. Lam ,&nbsp;David C. Thompson ,&nbsp;Ying Chen ,&nbsp;Vasilis Vasiliou","doi":"10.1016/j.cbi.2023.110714","DOIUrl":"10.1016/j.cbi.2023.110714","url":null,"abstract":"<div><p><span>Colon cancer<span><span> is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human </span>colon adenocarcinoma cell line (SW480) in which the </span></span><em>ALDH1B1</em><span> protein expression has been knocked down by 80% via shRNA<span>. Through multi-omics (transcriptomics, proteomics, and untargeted metabolomics) analysis, we identified the impact of </span></span><em>ALDH1B1</em> knocking down (KD) on molecular signatures in colon cancer cells. Suppression of ALDH1B1 expression resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs) and 891 differentially altered metabolites (DAMs). Functional annotation and enrichment analyses revealed that: (1) DEGs were enriched in integrin-linked kinase (ILK) signaling and growth and development pathways; (2) DEPs were mainly involved in apoptosis signaling and cellular stress response pathways; and (3) DAMs were associated with biosynthesis, intercellular and second messenger signaling. Collectively, the present study provides new molecular information associated with the cellular functions of ALDH1B1, which helps to direct future investigation of colon cancer.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"384 ","pages":"Article 110714"},"PeriodicalIF":5.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10284948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}