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Integrative metabolome and transcriptome analyses provide insights into PHGDH in colon cancer organoids. 代谢组和转录组的综合分析为了解结肠癌有机体中的 PHGDH 提供了线索。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2025-01-28 DOI: 10.1042/BSR20240842
Lin Chen, Zhihui Dai, Yanfei Zhang, Huichao Sheng, Bin Hu, Jinlin Du, Jie Chang, Wenxia Xu, Yuqing Hu
{"title":"Integrative metabolome and transcriptome analyses provide insights into PHGDH in colon cancer organoids.","authors":"Lin Chen, Zhihui Dai, Yanfei Zhang, Huichao Sheng, Bin Hu, Jinlin Du, Jie Chang, Wenxia Xu, Yuqing Hu","doi":"10.1042/BSR20240842","DOIUrl":"10.1042/BSR20240842","url":null,"abstract":"<p><p>As a rate-limiting enzyme in the endogenous serine de novo synthesis pathway, 3-Phosphoglycerate dehydrogenase (PHGDH) has been widely concerned about its role in a variety of tumors including colon cancer and the development of inhibitors. In our previous study, we studied PHGDH in colon cancer cell lines. However, with the development of personalized therapy, we realized that in scientific research, two-dimensional cell lines lost a lot of original characteristic information during long-term culture, and the results obtained may not be enough to support the conclusion. Patient-derived tumor organoids maintain genomic stability and make up for information missing from cell lines due to monoclonal growth. Therefore, in our study, a colon cancer organoid with high PHGDH expression was selected and analyzed for transcriptomic and metabolomic changes through targeted inhibition of PHGDH. The results showed that inhibition of PHGDH significantly inhibited the proliferation of colon cancer organoids. The transcriptome, metabolome, and combined omics analysis showed that the changes in colon cancer organoids after inhibition of PHGDH were mainly involved in PRSS1 and PRSS56, steroid hormone biosynthesis, phenylalanine metabolism, ascorbate and aldarate metabolism, and tyrosine metabolism. In our study, the role of PHGDH in serine metabolism in colon cancer organoids was clarified by multi-omics analysis to provide new knowledge for an in-depth understanding of serine metabolism and PHGDH function in colon cancer.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817038","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}
引用次数: 0
Exploration of Vitamin D Hydroxy Metabolites C3 Epimers in Patients with Cardiovascular Disease: an observational study.
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2025-01-27 DOI: 10.1042/BSR20241558
Mohamed Abouzid, Łukasz Kruszyna, Julia Kerner, Leonid Kagan, Aniceta Mikulska-Sauermann, Dorota Filipowicz, Matylda Resztak, Franciszek Krzysztof Główka, Marta Karaźniewicz-Łada
{"title":"Exploration of Vitamin D Hydroxy Metabolites C3 Epimers in Patients with Cardiovascular Disease: an observational study.","authors":"Mohamed Abouzid, Łukasz Kruszyna, Julia Kerner, Leonid Kagan, Aniceta Mikulska-Sauermann, Dorota Filipowicz, Matylda Resztak, Franciszek Krzysztof Główka, Marta Karaźniewicz-Łada","doi":"10.1042/BSR20241558","DOIUrl":"https://doi.org/10.1042/BSR20241558","url":null,"abstract":"<p><p>Roughly 90% of the Polish population experiences vitamin D deficiency. The 3-epi-25(OH)D2 and 3-epi-25(OH)D3 are stereoisomers of 25(OH)D2 and 25(OH)D3, and they can inadvertently be included in measurements of 25(OH)D levels, potentially leading to its overestimating. We aimed to measure 25(OH)D2 and 25(OH)D3, their epimers 3-epi-25(OH)D2 and 3-epi-25(OH)D3, and biologically active 1,25(OH)2D3 in patients with cardiovascular disease and healthy volunteers. We enrolled 27 adult patients with cardiovascular disease (64 ±15 years) and 35 healthy volunteers (36.37±12.29 years). We used a validated UPLC-MS/MS method to measure 25(OH)D2/3 concentrations and their epimers. Plasma concentrations of 1α,25(OH)2D3 were determined by sensitive and quantitative enzyme immunoassay following intra- and inter-day validation. Vitamin D insufficiency was observed in approximately 52% of the patients and 37% of healthy volunteers. Comparable levels of 25(OH)D3 and 25(OH)D2 were seen in both groups. The observed levels of the epimeric form 3-epi-25(OH)D3 appeared about 1.7 times higher in healthy volunteers, accounting for 9% misclassified according to vitamin D status. Also, patients had lower concentrations of 1,25(OH)2D3, and their 3-epi-25(OH)D2 levels were below the detection limit (2 ng/mL). In all studied subjects, 25(OH)D3 was negatively correlated with % 3-epi-25(OH)D3 (R=-0.758; p<0.001), and 3-epi-25(OH)D2 was negatively correlated with % 3-epi-25(OH)D2 (R = -0.842; p=0.002). While the mechanism of how vitamin D epimeric forms influence diseases remains unclear, we recommend maintaining 25(OH)D3 levels above 20 ng/mL.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051025","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}
引用次数: 0
Carbonyl Reductase 1: a novel regulator of blood pressure in Down Syndrome.
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2025-01-27 DOI: 10.1042/BSR20241636
Alexandra Malbon, Alicja Czopek, Andrew Beekman, Zoë Goddard, Aileen Boyle, Jessica Ivy, Kevin Stewart, Scott G Denham, Joanna Simpson, Natalie Z M Homer, Brian Walker, Neeraj Dhaun, Matthew Bailey, Ruth Morgan
{"title":"Carbonyl Reductase 1: a novel regulator of blood pressure in Down Syndrome.","authors":"Alexandra Malbon, Alicja Czopek, Andrew Beekman, Zoë Goddard, Aileen Boyle, Jessica Ivy, Kevin Stewart, Scott G Denham, Joanna Simpson, Natalie Z M Homer, Brian Walker, Neeraj Dhaun, Matthew Bailey, Ruth Morgan","doi":"10.1042/BSR20241636","DOIUrl":"https://doi.org/10.1042/BSR20241636","url":null,"abstract":"<p><p>Approximately one in every 800 children is born with the severe aneuploid condition of Down Syndrome, a trisomy of chromosome 21. Low blood pressure (hypotension) is a common condition associated with DS and can have a significant impact on exercise tolerance and quality of life. Little is known about the factors driving this hypotensive phenotype and therefore therapeutic interventions are limited. Carbonyl reductase 1 (CBR1) is an enzyme contributing to the metabolism of prostaglandins, glucocorticoids, reactive oxygen species and neurotransmitters, encoded by a gene (CBR1) positioned on chromosome 21 with the potential to impact blood pressure. Utilising telemetric blood pressure measurement of genetically modified mice, we tested the hypothesis that CBR1 influences blood pressure and that its overexpression contributes to hypotension in Down Syndrome by evaluating possible contributing mechanisms in vitro. In a mouse model of Down Syndrome (Ts65Dn), which exhibits hypotension, CBR1 activity was increased and pharmacological inhibition of CBR1 increased blood pressure. Mice heterozygous null for Cbr1 had reduced CBR1 enzyme activity and elevated blood pressure. Further experiments indicate that the underlying mechanisms include alterations in sympathetic tone and prostaglandin metabolism. We conclude that CBR1 activity contributes to blood pressure homeostasis and inhibition of CBR1 may present a novel therapeutic opportunity to correct symptomatic hypotension in Down Syndrome.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051517","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}
引用次数: 0
The fluoroquinolone compounds potentiate the antifungal activity of the echinocandins against Aspergillus fumigatus. 氟喹诺酮类化合物增强了棘白菌素对烟曲霉的抗真菌活性。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2025-01-20 DOI: 10.1042/BSR20250001
Jin-Ju Choi, Suzie Kang, Yoonseo Lee, Dong-Hyun Lee, Yuju Jang, Ja-Il Goo, Yongseok Choi, Dongho Lee, Cheol-Won Yun
{"title":"The fluoroquinolone compounds potentiate the antifungal activity of the echinocandins against Aspergillus fumigatus.","authors":"Jin-Ju Choi, Suzie Kang, Yoonseo Lee, Dong-Hyun Lee, Yuju Jang, Ja-Il Goo, Yongseok Choi, Dongho Lee, Cheol-Won Yun","doi":"10.1042/BSR20250001","DOIUrl":"https://doi.org/10.1042/BSR20250001","url":null,"abstract":"<p><p>The antifungal drugs of the echinocandin family show high efficacy against Aspergillus fumigatus. However, their paradoxical effect, which restores fungal growth at high drug concentrations, and the emergence of resistant strains necessitate improvements. We identified 13 fluoroquinolone compounds from a chemical library containing 10,000 compounds that potentiate the antifungal activity of caspofungin. Among them, NE-E07 significantly enhanced the efficacy of echinocandins against A. fumigatus, including resistant strains, without potentiating other antifungal families like voriconazole or amphotericin B. Specifically, NE-E07 demonstrated a unique ability to potentiate caspofungin's activity against the echinocandin-resistant strain USHM-M0051 isolated from patients. Our experiments revealed that NE-E07, in combination with caspofungin, affected ergosterol biosynthesis in a manner consistent with azole drugs. Docking tests suggest NE-E07 has a high binding affinity with CYP51, which affects ergosterol biosynthesis similarly to azole drugs. Interestingly, known fluoroquinolones like ciprofloxacin, nalidixic acid, and norfloxacin did not show this potentiating effect, suggesting that NE-E07's unique structure is critical for its activity. Moreover, NE-E07 did not enhance echinocandin activity against Candida albicans or Cryptococcus neoformans, highlighting its specific action against A. fumigatus. In vivo studies demonstrated that co-treatment with NE-E07 and caspofungin increased the survival rate of mice infected with A. fumigatus. This significant improvement in survival underscores the potential clinical relevance of NE-E07 as a co-administered drug with echinocandins for treating fungal infections, particularly those resistant to echinocandins.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999523","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}
引用次数: 0
Structural analysis of genetic variants of the human tumor suppressor Palb2 coiled-coil domain. 人类肿瘤抑制因子Palb2螺旋结构域遗传变异的结构分析。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2025-01-02 DOI: 10.1042/BSR20241173
Pothula Purushotham Reddy, Apurva Phale, Ranabir Das
{"title":"Structural analysis of genetic variants of the human tumor suppressor Palb2 coiled-coil domain.","authors":"Pothula Purushotham Reddy, Apurva Phale, Ranabir Das","doi":"10.1042/BSR20241173","DOIUrl":"https://doi.org/10.1042/BSR20241173","url":null,"abstract":"<p><p>The tumor suppressor PALB2 is a key player in the Homologous Recombination (HR) pathway, functionally connecting BRCA proteins at the DNA damage site. PALB2 forms homodimers via its coiled-coil domain, and during HR, it forms a heterodimeric complex with BRCA1 using the same domain. However, the structural details of the human PALB2 coiled-coil domain are unknown. Several missense variants have been reported in the coiled-coil domain. The structure-function relationship of these variants is poorly understood, posing a challenge to genetic counseling. In this study, we present the solution structure of the human PALB2 coiled-coil domain, which forms an antiparallel homodimer. We then use this structure to investigate the impact of a few well-characterized missense mutations on the fold and interactions of the PALB2 coiled-coil domain. Our findings reveal a strong correlation between the structural impact of mutations and their efficiency in homologous recombination, suggesting that our approach can be applied to study other genetic variations in PALB2. These findings hold promise for improving genetic counseling and advancing cancer research.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913812","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}
引用次数: 0
Electron transfer in multicentre redox proteins: from fundamentals to extracellular electron transfer. 多中心氧化还原蛋白中的电子转移:从基本原理到细胞外电子转移。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2024-12-23 DOI: 10.1042/BSR20240576
Busra Bayar, Ricardo Soares, Haris Nalakath, Alexandra S Alves, Catarina M Paquete, Ricardo O Louro
{"title":"Electron transfer in multicentre redox proteins: from fundamentals to extracellular electron transfer.","authors":"Busra Bayar, Ricardo Soares, Haris Nalakath, Alexandra S Alves, Catarina M Paquete, Ricardo O Louro","doi":"10.1042/BSR20240576","DOIUrl":"https://doi.org/10.1042/BSR20240576","url":null,"abstract":"<p><p>Multicentre redox proteins participate in diverse metabolic processes, such as redox shuttling, multielectron catalysis, or long-distance electron conduction. The detail in which these processes can be analysed depends on the capacity of experimental methods to discriminate the multiple microstates that can be populated while the protein changes from the fully reduced to the fully oxidized state. The population of each state depends on the redox potential of the individual centres and on the magnitude of the interactions between the individual redox centres with their neighbours. It also depends on the interactions with binding sites for other ligands such as protons giving origin to the redox-Bohr effect. Modelling strategies that match the capacity of experimental methods to discriminate the contributions of individual centres are presented. These models provide thermodynamic and kinetic characterization of multicentre redox proteins. The current state of the art in the characterization of multicentre redox proteins is illustrated using the case of multiheme cytochromes involved in the process of extracellular electron transfer. In this new frontier of biological electron transfer, which can extend for distances that exceed the size of the individual multicentre redox proteins by orders of magnitude, current experimental data is still unable, in most cases, to provide discrimination between incoherent conduction by heme orbitals from coherent band conduction.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876057","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}
引用次数: 0
Palmitoylation and regulation of potassium dependent sodium/calcium exchangers (NCKX). 棕榈酰化和钾依赖性钠/钙交换剂(NCKX)的调控。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2024-12-18 DOI: 10.1042/BSR20241051
Ran Tao, Alan D Robertson, William Fuller, Caglar Gök
{"title":"Palmitoylation and regulation of potassium dependent sodium/calcium exchangers (NCKX).","authors":"Ran Tao, Alan D Robertson, William Fuller, Caglar Gök","doi":"10.1042/BSR20241051","DOIUrl":"https://doi.org/10.1042/BSR20241051","url":null,"abstract":"<p><p>Cellular Ca2+ homeostasis is critical for normal cell physiology and is regulated by several mechanisms. Two major players in intracellular Ca2+ homeostasis in multiple tissues belong to SLC8 (Na+/Ca2+ exchangers (NCXs); NCX1-3) and SLC24 (K+ dependent Na+/Ca2+ exchangers (NCKXs); NCKX1-5) families. It has been established that NCXs and NCKX4 are palmitoylated, and that palmitoylation promotes NCX1 inactivation. However, there is still little known about NCKXs' palmitoylation. We found that (1) NCKX3 and NCKX5 but not NCKX1 are palmitoylated, (2) Cys to Ala mutation at position 467 for NCXK3 and 325 for NCKX5 notably diminished palmitoylation and (3) reduced palmitoylation enhanced NCKX3 activity. Our findings bring novel insights on NCKX1, NCKX3 and NCKX5 palmitoylation, and establish palmitoylation as endogenous regulator of NCKX3 activity, paving the way for investigations evaluating the role of palmitoylation in NCKX3 function in health and disease.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852233","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}
引用次数: 0
Transcriptional profiling reveals the role of Candida albicans Rap1 in oxidative stress response. 转录谱分析揭示了白色念珠菌 Rap1 在氧化应激反应中的作用。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2024-12-17 DOI: 10.1042/BSR20240689
Wen-Han Wang, Hsuan-Yu Chen, Sheng-Yuan Chen, Chung-Yu Lan
{"title":"Transcriptional profiling reveals the role of Candida albicans Rap1 in oxidative stress response.","authors":"Wen-Han Wang, Hsuan-Yu Chen, Sheng-Yuan Chen, Chung-Yu Lan","doi":"10.1042/BSR20240689","DOIUrl":"10.1042/BSR20240689","url":null,"abstract":"<p><p>Candida albicans is a member of the human commensal microbiota but can also cause opportunistic infections, including life-threatening invasive candidiasis, particularly in immunocompromised patients. One of the important features of C. albicans commensalism and virulence is its ability to adapt to diverse environmental stress conditions within the host. Rap1 is a DNA-binding protein identified in yeasts, protozoa, and mammalian cells, and it plays multiple functions, including telomere regulation. Intriguingly, our previous study showed that Rap1 is also involved in cell wall integrity, biofilm formation, and virulence in C. albicans. In this work, using RNA-seq analysis and other approaches, the role of C. albicans Rap1 in oxidative stress response was further revealed. The RAP1-deletion mutant exhibited greater resistance to the superoxide generator menadione, a lower level of intracellular reactive oxygen species (ROS) upon menadione treatment, and higher expression levels of superoxide dismutase genes, all in response to oxidative stress. Moreover, the association between Rap1-mediated oxidative stress response and the mitogen-activated protein kinase (MAPK) Hog1, the transcription factor Cap1 and the TOR signalling was also determined. Together, these findings expand our understanding of the complex signalling and transcriptional mechanisms regulating stress responses in C. albicans.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The physiological anti-hypertensive peptide catestatin and its common human variant Gly364Ser: differential cardiovascular effects in a rat model of hypertension. 生理性抗高血压肽 catestatin 及其常见人类变体 Gly364Ser:在高血压大鼠模型中的不同心血管效应。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2024-12-17 DOI: 10.1042/BSR20241433
Jitesh Singh Rathee, Dhanya R Iyer, Malapaka Kiranmayi, Samarasimha Reddy, V V Sureshbabu, Nitish R Mahapatra
{"title":"The physiological anti-hypertensive peptide catestatin and its common human variant Gly364Ser: differential cardiovascular effects in a rat model of hypertension.","authors":"Jitesh Singh Rathee, Dhanya R Iyer, Malapaka Kiranmayi, Samarasimha Reddy, V V Sureshbabu, Nitish R Mahapatra","doi":"10.1042/BSR20241433","DOIUrl":"10.1042/BSR20241433","url":null,"abstract":"<p><p>Catestatin (CST), a 21-amino acids physiological peptide, has emerged as a key modulator of cardiovascular functions due to its anti-hypertensive and cardioprotective properties. However, the ramifications of the most common human variant of CST (viz., Gly364Ser) on cardiovascular pathophysiology remain partially understood. In this study, hypertension was induced in uninephrectomized rats by treatment with deoxycorticosterone-acetate and sodium chloride (DOCA-salt). The DOCA-salt-induced hypertensive (DSHR) animals were then intraperitoneally administered with either CST wild-type (CST-WT) or 364Ser variant (CST-Ser) peptide. CST-Ser was profoundly less effective than CST-WT in rescuing the elevated systolic blood pressure [from ∼211 mmHg to ∼176 mmHg, p < 0.0001 (CST-Ser) versus ∼116 mmHg, p < 0.0001 (CST-WT)] and heart rate [from ∼356 bpm to ∼314 bpm, p = 0.66 (CST-Ser) versus ∼276 bpm, p = 0.02 (CST-WT)]. CST-Ser also showed diminished effects in lowering diastolic blood pressure and mean arterial pressure in the DSHR animals. Furthermore, CST-Ser was inefficient/markedly less potent in rescuing the impaired contractile and diastolic function in DSHR animals [improvements in the contractility index by ∼22 s-1 (CST-Ser), p = 0.15 versus by ∼84 s-1 (CST-WT), p < 0.0001 and decrease in end-diastolic pressure by ∼4 mmHg (CST-Ser), p = 0.015 versus by ∼14 mmHg (CST-WT), p < 0.0001]. Moreover, CST-Ser exerted less potent anti-inflammatory effects on the DSHR hearts than CST-WT. These findings are in concordance with the elevated systolic/diastolic blood pressure observed in Ser variant carriers from various human populations. This study provides compelling evidence for the diminished anti-hypertensive and cardioprotective effects of the CST-Gly364Ser variant.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recycle, Repair, Recover: The Role of Autophagy in Modulating Skeletal Muscle Repair and Post-Exercise Recovery. 循环、修复、恢复:自噬在调节骨骼肌修复和运动后恢复中的作用。
IF 3.8 3区 生物学
Bioscience Reports Pub Date : 2024-12-13 DOI: 10.1042/BSR20240137
Jordan Acheson, Sophie Joanisse, Craig Sale, Nathan Hodson
{"title":"Recycle, Repair, Recover: The Role of Autophagy in Modulating Skeletal Muscle Repair and Post-Exercise Recovery.","authors":"Jordan Acheson, Sophie Joanisse, Craig Sale, Nathan Hodson","doi":"10.1042/BSR20240137","DOIUrl":"https://doi.org/10.1042/BSR20240137","url":null,"abstract":"<p><p>Skeletal muscle is a highly plastic tissue which can adapt relatively rapidly to a range of stimuli. In response to novel mechanical loading, e.g. unaccustomed resistance exercise, myofibers are disrupted and undergo a period of ultrastructural remodelling to regain full physiological function, normally within 7 days. The mechanisms which underpin this remodelling are believed to be a combination of cellular processes including UPS/Calpain-mediated degradation, immune cell infiltration and satellite cell proliferation/differentiation. A relatively understudied cellular system which has the potential to be a significant contributing mechanism to repair and recovery is autophagolysosomal system, a cellular process which degrades damaged and dysfunctional cellular components to provide constituent components for the resynthesis of new organelles and cellular structures. This review summarises our current understanding of the autophagolysosomal system in the context of skeletal muscle repair and recovery. In addition, we also provide hypothetical models of how this system may interact with other processes involved in skeletal muscle remodelling and provide avenues for future research to improve our understanding of autophagy in human skeletal muscle.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817040","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}
引用次数: 0
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