Cell Biochemistry and Biophysics最新文献

{"title":"Cellular Stress Responses and Associated Diseases: A Focus on Heat Shock Proteins.","authors":"Bandana Kumari","doi":"10.1007/s12013-025-01724-3","DOIUrl":"https://doi.org/10.1007/s12013-025-01724-3","url":null,"abstract":"<p><p>Cellular stress response is the response of the cell at molecular level in order to combat various environmental stressors / viral infections. These stressors can be either intra or extracellular. In the beginning of the insult cell tries to recoup from these adverse events by various mechanism like heat shock protein response, unfolded protein response, mitochondrial stress signaling, DNA damage response etc. However, if these stressors exceed the cellular capacity to coup with it, it leads to programmed cell death and senescence. Also, chronic stress and cortisol released in response to cellular stress decreases telomerase activity which is needed to replenish telomeres which are protective casing at the end of a strand of DNA. Too low telomeres lead to cell death or cell become pro-inflammatory leading to aging process and other health associated risks like cardiovascular diseases neurodegenerative diseases, autoimmune diseases, cancers etc.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isogarcinol Reduces MARS Levels and Deactivates the PI3K/AKT Pathway to Suppress the Malignant Properties of Breast Cancer Cells.","authors":"Dechao Zhang, Yunhai Chu, Meng Li, Lin Du","doi":"10.1007/s12013-025-01727-0","DOIUrl":"https://doi.org/10.1007/s12013-025-01727-0","url":null,"abstract":"<p><p>Natural products and their extracts are increasingly considered valuable sources for small-molecule anti-cancer drugs. This study investigates the biological impacts of isogarcinol (ISO) on breast cancer (BC) cells and delves into the underlying mechanisms. In vitro, treatment of ISO at 13 μM substantially reduced the viability, proliferation, and mobility of BC. In vivo, ISO treatment at 5, 10, and 15 mg/kg reduced the tumorigenic activity of MDA-MB-231 cells and decreased the levels of Ki-67 and CD31. ISO exerted tumor suppressive effects by reducing the protein level of methionyl-tRNA synthetase (MARS), as the MARS restoration reversed the trends induced by ISO. Phosphorylation levels of phosphatidyl inositol 3 (PI3K) and protein kinase B (AKT) in BC cells were reduced by ISO but restored by MARS. In the presence of MARS upregulation, further treatment of Alpelisib, a suppressor of the PI3K/AKT pathway, suppressed the malignant properties of BC cells. Collectively, these results demonstrate that ISO curbs the malignant behavior of BC cells by reducing the MARS protein level and deactivating the PI3K/AKT pathway. ISO may be considered a promising regimen for the management of BC.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effect of Rosuvastatin Calcium Combined with Hyperbaric Oxygen Mediated p38MAPK Pathway in Rats with Leukoaraiosis.","authors":"Yafeng Shi, Gemin Zhu, Jun Yan, Linxin Zhang, Yongku Du, Zhuoqiong Bian, Jing Fan","doi":"10.1007/s12013-025-01702-9","DOIUrl":"https://doi.org/10.1007/s12013-025-01702-9","url":null,"abstract":"<p><p>This study explored the neuroprotective mechanism of rosuvastatin calcium (RSC) combined with hyperbaric oxygen (HBO) in rats with leukoaraiosis (LA), and its impact on the p38MAPK signaling pathway (SPW). Clean-grade male SD rats were used as subjects, which were assigned into Sham group (SG), LA group (LAG), RSC group (RSCG), HBO group (HBOG), and RSC + HBO group (combination group, CG), 20 rats in each. At 14 d post-modeling, the effects of RSC, HBO, and RSC + HBO treatment on the cognitive function, brain neuronal cell apoptosis, brain tissue matrix metalloproteinases (MMPs) family gene expression, and the status of the p38MAPK SPW in LA rats were analyzed. As against the LAG, the escape latency (EL) was shortened, the count of platform crossings was augmented, the number of brain neuronal cell apoptosis decreased, the relative expression (RE) of brain TIMP-1, MMP-2, MMP-3, and MMP-9 mRNA were reduced (P < 0.05), and the RE of brain cleaved caspase (Cas)-3 and p-p38MAPK proteins were reduced in the RSCG, HBOG, and CG (P < 0.05); As against the RSCG and HBOG, the CG showed more visible improvements in all indicators (P < 0.05). The combination of RSC and HBO can inhibit brain neuronal cell apoptosis and the expression of the MMPs family genes in rats with LA by suppressing the overactivation of the p38MAPK SPW, which is beneficial for the recovery of the rats' cognitive function.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Analysis of Plasmodium falciparum DNA Damage Inducible Protein 1 (PfDdi1): Insights into Binding of Artemisinin and its Derivatives and Implications for Antimalarial Drug Design.","authors":"Ernest Oduro-Kwateng, Ibrahim Oluwatobi Kehinde, Musab Ali, Kabange Kasumbwe, Vuyisa Mzozoyana, Narasimham L Parinandi, Mahmoud E S Soliman","doi":"10.1007/s12013-025-01709-2","DOIUrl":"https://doi.org/10.1007/s12013-025-01709-2","url":null,"abstract":"<p><p>Human malaria remains a global health challenge, with Plasmodium falciparum responsible for the most severe cases. Despite global efforts, eradicating malaria has proven difficult, mainly because of the rise in drug resistance, particularly against artemisinin and its derivatives. One possible cause of this resistance is the activation of the unfolded protein response (UPR), which helps maintain cellular balance under stress. In P. falciparum, the UPR operates through the ubiquitin-proteasome system (UPS), which involves proteins such as Dsk2, Rad23, and Ddi1. Among these, Plasmodium falciparum DNA-damage-inducible protein 1 (PfDdi1) plays a crucial role in DNA repair and is present throughout the parasite life cycle, making it an attractive drug target. However, there is limited research on PfDdi1 as a therapeutic target. Recent in vitro studies have indicated that artemisinin (ART) and dihydroartemisinin (DHA) inhibit PfDdi1 activity. Building on this, we investigated whether ART and its derivatives could serve as inhibitors of PfDdi1 using computational modeling. Our study included clinically relevant ART derivatives such as artemether (ARM), arteether (AET), artemiside (AMD), and artesunate (ATS). All these compounds showed strong binding to PfDdi1, with free binding energies ranging from -20.75 kcal/mol for AET to -34.24 kcal/mol for ATS. ARM increased PfDdi1's structural rigidity and hydrophobic stability, whereas AMD improved its kinetic stability, resulting in the least residue motion. Unlike AET and AMD, the other ligands destabilize the PfDdi1 structure. Importantly, three key binding regions-Loop 1 (GLN 266 - ILE 269), Loop 2 (ILE 323 - TYR 326), and Loop 3 (ALA 292 - GLY 294)-were identified as potential targets for new antimalarial drugs against PfDdi1. This study highlights the potential of ART derivatives as PfDdi1 inhibitors, paving the way for further experimental validation.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the NLRP3 by Natural Compounds: Therapeutic Strategies to Mitigate Doxorubicin-Induced Cardiotoxicity.","authors":"Dareuosh Shackebaei, Kheirollah Yari, Nader Rahimi, Sara Gorgani, Fatemeh Yarmohammadi","doi":"10.1007/s12013-025-01723-4","DOIUrl":"https://doi.org/10.1007/s12013-025-01723-4","url":null,"abstract":"<p><p>Doxorubicin (DOX), a widely utilized anthracycline chemotherapy agent, is known for its potent anticancer efficacy across various malignancies. However, its clinical use is considerably restricted due to the risk of dose-dependent cardiotoxicity, which can lead to long-term heart dysfunction. The underlying mechanism of DOX-induced cardiotoxicity has been associated with the formation of reactive oxygen species (ROS) and disrupting cellular signaling pathways. This is particularly relevant to the activation of the NLRP3 inflammasome, which triggers inflammation and pyroptosis in cardiac cells. In recent years, there has been growing interest in natural compounds that exhibit potential cardioprotective effects against the adverse cardiac effects of DOX. The present study showed that specific natural compounds, such as honokiol, resveratrol, cynaroside, and curcumin, can confer significant protection against DOX-induced cardiotoxicity through the modulation of NLRP3 inflammasome signaling pathways. In summary, incorporating natural compounds into treatment plans could be a practical approach to improve the safety profile of DOX, thereby protecting cardiac health through the regulation of the NLRP3 pathway.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-218 Exhibits Anti-Leukemia Effects by Targeting CTNND2 in Primary Acute Erythroid Leukemia HEL Cells.","authors":"Ming-Qiang Chu, Ting-Juan Zhang, Zi-Qi Liu, Qian Yang, Ting-Ting Du, Min-Jie Zhang, Ye Jin, Yong-Jie Cao, Xiang-Mei Wen, Zi-Jun Xu, Yang-Jing Zhao, Jiang Lin, Jun Qian, Jing-Dong Zhou","doi":"10.1007/s12013-025-01722-5","DOIUrl":"https://doi.org/10.1007/s12013-025-01722-5","url":null,"abstract":"<p><p>Acute erythroid leukemia (AEL) is a rare acute myeloid leukemia (AML) subtype that is highly aggressive and is associated with a poor prognosis. Notably, the blockage of erythroid differentiation represents a significant factor in the pathogenesis of erythroleukemia. Prior studies indicated that miR-218 inhibited the erythroid differentiation in a chronic myeloid leukemia (CML)-derived erythroleukemia cell line K562. However, functions of miR-218 in primary AEL remains to be elucidated. To address this gap, functions of miR-218 in HEL cells were evaluated through cell differentiation, cell proliferation, colony formation, cell cycle and cell apoptosis experiments. Subsequently, the targeted downstream genes of miR-218 were identified by the transcriptome sequencing and bioinformatic research, of which demonstrated by the dual-luciferase reporter experiment. Finally, the underlying mechanism of miR-218 in leukemogenesis was identified by enrichment analysis and was validated by western blot (WB) assays. Intriguingly, enhanced miR-218 showed no effect on the erythroid differentiation in HEL cells by determination of the expression of erythroid markers including GATA1, KLF1, TFRC and GYPA. However, miR-218 overexpression in HEL cells presented a markedly anti-proliferative and pro-apoptotic effects, inhibited colony formation and G0/G1 arrest. Transcriptome sequencing and bioinformatics analysis revealed that CTNND2 as the candidate gene of miR-218 within its 3'-untranslated region (3'-UTR) could be bonded by it. Reduced expression level of CTNND2 was further demonstrated by quantitative-PCR and WB after miR-218 overexpression in HEL cells. Furthermore, the luciferase report assay revealed that the CTNND2 production was reduced with its 3'-UTR region was bonded by miR-218. In addition, MAPK signaling pathway was identified and validated as the potential functional pathway involved in leukemogenesis caused by miR-218 overexpression in HEL cells. In summary, miR-218 exhibits anti-proliferative and pro-apoptotic functions by targeting CTNND2 and modulating MAPK signaling in HEL cells, yet it has no impact on the erythroid differentiation process.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Development of Allosteric Peptide Inhibitors Targeting LIM Kinases as a Novel Therapeutic Intervention.","authors":"Nagarajan Hemavathy, Sampathkumar Ranganathan, Vetrivel Umashankar, Jeyaraman Jeyakanthan","doi":"10.1007/s12013-025-01718-1","DOIUrl":"https://doi.org/10.1007/s12013-025-01718-1","url":null,"abstract":"<p><p>LIM Kinases (LIMKs) have emerged as critical therapeutic targets in cancer research due to their central role in regulating cytoskeletal dynamics and cell motility via cofilin phosphorylation. Allosteric inhibitors, which bind outside the ATP-binding pocket, offer distinct advantages over ATP-competitive inhibitors, such as increased specificity, reduced off-target effects, and the ability to overcome resistance. This study investigates a series of novel tetrapeptides mimicking the binding mode of TH470, an allosteric LIMK inhibitor, using in silico docking and molecular dynamics simulations to identify potential lead compounds with high specificity, binding affinity, and favorable pharmacokinetic properties. Structural analyses revealed critical interactions between TH470 and LIMKs, particularly with conserved residues such as Thr405 (gatekeeper residue), Ile408 (hinge region), and Asp469 (XDFG motif), which are essential for stabilizing inhibitor binding. Molecular dynamics simulations confirmed the stability of TH470-LIMK1 and TH470-LIMK2 complexes, with lower RMS deviations and robust interaction patterns enhancing binding affinity. From the set of tetrapeptides mimicking TH470 binding mode, only YFYW, WPHW, and YWFP for LIMK1, and PYWG, FYWV, and WFVW for LIMK2 demonstrated high binding affinities, non-toxic profiles, and promising anti-cancer, anti-angiogenic, and anti-inflammatory properties. Among the studied peptides, LIMK1-YFYW and LIMK2-WFVW exhibited the most substantial binding affinities, supported by high hydrogen bond occupancy with key residues such as Ile416 and Thr405. The findings highlight the therapeutic potential of allosteric peptide inhibitors targeting LIMK-mediated pathways in cancer progression. The study underscores the importance of specific interactions with conserved LIMK residues, providing a foundation for further developing selective inhibitors to modulate actin dynamics and combat cancer-related processes.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution.","authors":"Nidhi N Shah, Bhavarth P Dave, Kashvi C Shah, Disha D Shah, Kunal G Maheshwari, Mehul R Chorawala","doi":"10.1007/s12013-025-01715-4","DOIUrl":"10.1007/s12013-025-01715-4","url":null,"abstract":"","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLC2: Physiological Functions and Potential Roles in Tumorigenesis.","authors":"Jiaxue Lu, Nan Li, Wenling Zhang","doi":"10.1007/s12013-025-01721-6","DOIUrl":"https://doi.org/10.1007/s12013-025-01721-6","url":null,"abstract":"<p><p>The myosin regulatory light chain 2 (MLC2) is a crucial regulator of myosin activity. Its phosphorylation, mediated by various kinases, plays a vital role in maintaining normal physiological functions in skeletal muscle, myocardium, smooth muscle, and nonmuscle cells. Moreover, MLC2 has been implicated in the development of many cancers through its phosphorylation. An increasing number of studies have shown that MLC2 may influence tumor progression by modulating cancer cell growth, migration, invasion, apoptosis, and autophagy. In this paper, we provide a concise overview of the phosphorylation regulatory mechanisms of MLC2 and its roles in both physiology and tumorigenesis. Furthermore, this study proposes potential directions for future research.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of Programmed Obesity and Postnatal High Fat Diet but Not (-)-Epicatechin Treatment Modifies Muscle Atrophy Proteins Levels in Male Wistar Rats.","authors":"Ana Luisa Alvarez-Chávez, Sergio De Los Santos, Ramón Mauricio Coral-Vázquez, Luis Antonio Reyes-Castro, Elena Zambrano, Patricia Canto","doi":"10.1007/s12013-025-01690-w","DOIUrl":"https://doi.org/10.1007/s12013-025-01690-w","url":null,"abstract":"<p><p>We determine whether the offspring of obese mothers and a postnatal high-fat diet (HFD) modify protein levels related to muscle synthesis (p70S6K-alpha) or atrophy (Murf and MAFbx), and if the administration of (-)-epicatechin (Epi) can modify these alterations. We hypothesized that the ubiquitin ligases Murf and MAFbx would be increased in the obesogenic context, either by in utero obesogenic environment or by a postnatal high-fat diet, while the p70S6K-alpha kinase and its activation might be decreased. Eight groups of six male Wistar offspring formed eight experimental groups: control (C), control fed with HFD (CHFD), maternal obesity (MO), maternal obesity fed with HFD (MOHFD), and the groups with Epi intervention: C+Epi long, CHFD+Epi long, MO+Epi long and MOHFD+Epi long. By Western blot, we evaluated the Epi effect on the Murf, MAFbx, and p70S6K-alpha proteins in gastrocnemius and soleus tissues. The Murf level increased 2.59-fold in CHFD vs C group and 2.62-fold for MOHFD vs C group (p = 0.049 and p = 0.048, respectively) in gastrocnemius tissue. In soleus tissue, we observed an increase of MAFbx (1.52-fold) for the MOHFD group versus the C group (p = 0.049). Epi treatment did not modify any protein expression. In conclusion, we found an increase in the Murf1 protein levels in gastrocnemius tissue of the direct model of obesity; as well, we observed an increase of the Murf1 in gastrocnemius and of the MAFbx in soleus muscles in the group of rats obese by programming and fed postnatally with a high-fat diet (doble stimulus). In addition, since obesity could cause muscle atrophy, which results in impaired muscle function, it would be relevant in future research to evaluate these signaling pathways in animals of different ages in order to search for markers of the progression of diseases such as sarcopenia obesity.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}