Biochimie Pub Date : 2024-10-09 DOI: 10.1016/j.biochi.2024.10.007

Michaela Dobrovolná, Jean-Louis Mergny, Václav Brázda

{"title":"Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y.","authors":"Michaela Dobrovolná, Jean-Louis Mergny, Václav Brázda","doi":"10.1016/j.biochi.2024.10.007","DOIUrl":"10.1016/j.biochi.2024.10.007","url":null,"abstract":"Recent advancements have finally delivered a complete human genome assembly, including the elusive Y chromosome. This accomplishment closes a significant knowledge gap. Prior efforts were hampered by challenges in sequencing repetitive DNA structures such as direct and inverted repeats. We used the G4Hunter algorithm to analyze the presence of G-quadruplex forming sequences (G4s) within the current human reference genome (GRCh38) and the new telomere-to-telomere (T2T) Y chromosome assemblies. This analysis served a dual purpose: identifying the location of potential G4s within the genomes and exploring their association with functionally annotated sequences. Compared to GRCh38, the T2T assembly exhibited a significantly higher prevalence of G-quadruplex forming sequences. Notably, these repeats were abundantly located around precursor RNA, exons, genes, and within protein binding sites. This remarkable co-occurrence of G4-forming sequences with these critical regulatory regions suggests their role in fundamental DNA regulation processes. Our findings indicate that the current human reference genome significantly underestimated the number of G4s, potentially overlooking their functional importance.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone. 极性溶解物埃克托因和羟基埃克托因对热诱导蛋白质聚集的影响：以生长激素为例

Biochimie Pub Date : 2024-10-09 DOI: 10.1016/j.biochi.2024.10.006

Rūta Gruškienė, Jolanta Sereikaitė

{"title":"The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone.","authors":"Rūta Gruškienė, Jolanta Sereikaitė","doi":"10.1016/j.biochi.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.10.006","url":null,"abstract":"The extremolytes ectoine and hydroxyectoine are osmolytes found in extremophilic microorganisms. They are stabilisers of proteins and other macromolecules, including DNA and lipids. The aim of the study was to investigate the effect of the additives on the heat-induced aggregation of mink growth hormone as a model protein. The first-order rate constants of protein aggregation were determined at 60 °C depending on the additive concentration and pH of the solution. The onset temperature of aggregation was also recorded using a circular dichroism spectropolarimeter. The study showed that the effect of the additives depended on the pH of the solution. The first-order rate constants of aggregation were lower when the protein molecule had a negative charge. The effect also depended on the structure of the extremolyte itself. When the protein molecule was positively charged, hydroxyectoine destabilised the mink growth hormone molecule and promoted the aggregation. The different effects of the additives were determined by the different interactions with the protein molecules, as shown by circular dichroism measurements and previously by fluorescence spectroscopy. Therefore, when using ectoine or hydroxyectoine for protein formulation, the effect of the additive should be carefully analysed for each protein individually.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration. 细胞外基质结构介导的分子信号在伤口修复和组织再生中的作用。

Biochimie Pub Date : 2024-10-05 DOI: 10.1016/j.biochi.2024.10.003

Sousan Cheong, Yujie Peng, Feng Lu, Yunfan He

{"title":"Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration.","authors":"Sousan Cheong, Yujie Peng, Feng Lu, Yunfan He","doi":"10.1016/j.biochi.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.10.003","url":null,"abstract":"The extracellular matrix (ECM) is a complex, non-cellular network of molecules that offers structural support for cells and tissues. The ECM is composed of various structural components, including collagen, fibronectin, laminin, perlecan, nidogen, tenascin, and fibulin, which are capable of binding to each other and to cell-to-adhesion receptors, endowing the ECM with unique physical and biochemical properties that are essential for its function in maintaining health and managing disease. Over the past three decades, extensive research has shown that the core of the ECM can significantly impact cellular events at the molecular level. Structural modifications have also been strongly associated with tissue repair. Through interactions with cells, matrix proteins regulate critical processes such as cell proliferation and differentiation, migration, and apoptosis, essential for maintaining tissue homeostasis, formation, and regeneration. This review emphasizes the interlocking networks of ECM macromolecules and their primary roles in tissue regeneration and wound repair. Through studying ECM dynamics, researchers have discovered molecular signaling pathways that demonstrate how the ECM influences protein patterns and open up more possibilities for developing therapeutics that target the ECM to enhance wound repair and tissue regeneration.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. 槲皮素对由卡波西肉瘤相关疱疹病毒 G 蛋白偶联受体转化的内皮细胞具有抗肿瘤活性的体外和体内证据。

Biochimie Pub Date : 2024-10-05 DOI: 10.1016/j.biochi.2024.10.004

Gabriel Principe, Virginia Lezcano, Silvina Tiburzi, Alicia B Miravalles, Betina N García, Fernanda Gumilar, Verónica González-Pardo

{"title":"In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor.","authors":"Gabriel Principe, Virginia Lezcano, Silvina Tiburzi, Alicia B Miravalles, Betina N García, Fernanda Gumilar, Verónica González-Pardo","doi":"10.1016/j.biochi.2024.10.004","DOIUrl":"10.1016/j.biochi.2024.10.004","url":null,"abstract":"Quercetin (QUE) is a natural flavonoid with well-known anticancer capabilities, although its effect on viral-induced cancers is less studied. Kaposi's sarcoma (KS) is a viral cancer caused by the human herpesvirus-8, which, during its lytic phase, expresses a constitutively activated viral G protein-coupled receptor (vGPCR) able to induce oncogenic modifications that lead to tumor development. The aim of this work was to investigate the potential effect of QUE on in vitro and in vivo models of Kaposi's sarcoma, developed by transforming endothelial cells with the vGPCR of Kaposi's sarcoma-associated herpesvirus. Initially, the antiproliferative effect of QUE was determined in endothelial cells stably expressing the vGPCR (vGPCR cells), with an IC50 of 30 μM. Additionally, QUE provoked a decrease in vGPCR cell viability, interfered with the cell cycle progression, and induced apoptosis, as revealed by annexin V/PI analysis and caspase-3 activity. The presence of apoptotic bodies and disorganized actin filaments was observed by SEM and phalloidin staining. Furthermore, tumors from vGPCR cells were induced in nude mice, which were treated with QUE (50 or 100 mg/kg/d) resulting in retarded tumor progression and reduced tumor weight. Notably, neither kidney nor liver damage was observed, as indicated by biochemical parameters in serum. In conclusion, this study suggests for the first time that QUE exhibits antineoplastic activity in both in vitro and in vivo models of KS, marking a starting point for further investigations and protocols for therapeutic purpose.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A yummy blend of homeostasis and proteolytic mechanisms. 平衡与蛋白质分解机制的完美融合。

Biochimie Pub Date : 2024-10-05 DOI: 10.1016/j.biochi.2024.10.005

Chahrazade El Amri, Carmela Giglione, Gilles Lalmanach

引用次数: 0

Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer. 电阻素与乳腺癌预后、细胞迁移以及 p38 和 ERK1/2 激活之间的关系分析。

Biochimie Pub Date : 2024-10-04 DOI: 10.1016/j.biochi.2024.10.001

Reyna L Cuachirria-Espinoza, Alin García-Miranda, Rafael Hernández-Barragán, Dania A Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito

{"title":"Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer.","authors":"Reyna L Cuachirria-Espinoza, Alin García-Miranda, Rafael Hernández-Barragán, Dania A Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito","doi":"10.1016/j.biochi.2024.10.001","DOIUrl":"10.1016/j.biochi.2024.10.001","url":null,"abstract":"Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect in vitro of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between RETN and MAPK3 expression in basal triple-negative breast cancer. Importantly, we found amplifications of the RETN gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Evaluation of Water-Soluble Antioxidants Derived from L-carnosine and Syringaldehyde (or Vanillin). 合成和评估由左旋肉碱和丁香醛（或香兰素）衍生的水溶性抗氧化剂。

Biochimie Pub Date : 2024-10-04 DOI: 10.1016/j.biochi.2024.10.002

Collins Antwi-Boasiako, Blessed Agbemade, Jacqueline H Ko, Veronica Barone, Rebecca Uzarski, Choon Young Lee

{"title":"Synthesis and Evaluation of Water-Soluble Antioxidants Derived from L-carnosine and Syringaldehyde (or Vanillin).","authors":"Collins Antwi-Boasiako, Blessed Agbemade, Jacqueline H Ko, Veronica Barone, Rebecca Uzarski, Choon Young Lee","doi":"10.1016/j.biochi.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.10.002","url":null,"abstract":"Polyphenols are well known for their health-related benefits, including antioxidant activities, but most of them are hydrophobic, decreasing their bioavailability. This study reports water-soluble trimeric antioxidants synthesized with L-carnosine and the hydrophobic ortho-methoxy-substituted phenolic unit, syringaldehyde or vanillin. In the DPPH assay, carnosine-syringaldehyde (7.5 μM) and carnosine-vanillin (19 μM) derivatives showed much lower IC50 values than ascorbic acid (27.5 μM) and sodium ascorbate (30.5 μM) standards. According to the AAPH assay, carnosine-syringaldehyde and carnosine-vanillin protect DNA at concentrations as low as 6.5 μM and 26 μM, respectively, while both sodium ascorbate and ascorbic acid protected until 52 μM. Another notable property of these antioxidants is they can protect DNA well against hydroxyl radicals, produced via the Fenton reaction: carnosine-syringaldehyde showed DNA protection at all tested concentrations (833-1.6 μM), but the protection was slightly weaker between 26-1.6 μM. Carnosine-vanillin showed strong protection in the 833-104 μM range and some protection between 52-3.2 μM. Conversely, both sodium ascorbate and ascorbic acid did not protect DNA at any test concentration. In the pro-oxidant potential assessments, the synthesized antioxidants did not show any pro-oxidant effects at all concentrations, whereas sodium ascorbate showed severe pro-oxidant effects between 833-13 μM and ascorbic acid, 833-52 μM. Our study stresses the importance of ortho-methoxy group(s) for antioxidants as its electron-donating nature contributes to enhancing antioxidant activities, while steric bulk eliminates pro-oxidant effects by preventing the effective binding of transition metal ions to the phenolic hydroxyl group. The hydrophobicity of hindered phenols can be overcome if attached to a water-soluble scaffold.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of immunostimulatory RNA on the fibrosis development in Bleomycin- or LPS-induced mouse models. 免疫刺激 RNA 对博莱霉素或 LPS 诱导的小鼠模型纤维化发展的影响

Biochimie Pub Date : 2024-10-01 DOI: 10.1016/j.biochi.2024.09.016

Aleksandra V Sen'kova, Ali Bishani, Innokenty A Savin, Marina A Zenkova, Elena L Chernolovskaya

引用次数: 0

Systemic and joint adipose tissue lipids and their role in osteoarthritis. 全身和关节脂肪组织脂质及其在骨关节炎中的作用。

Biochimie Pub Date : 2024-09-27 DOI: 10.1016/j.biochi.2024.09.015

Natalia Zapata-Linares, Léa Loisay, Diego de Haro, Francis Berenbaum, Thomas Hügle, Jeroen Geurts, Xavier Houard

{"title":"Systemic and joint adipose tissue lipids and their role in osteoarthritis.","authors":"Natalia Zapata-Linares, Léa Loisay, Diego de Haro, Francis Berenbaum, Thomas Hügle, Jeroen Geurts, Xavier Houard","doi":"10.1016/j.biochi.2024.09.015","DOIUrl":"10.1016/j.biochi.2024.09.015","url":null,"abstract":"Osteoarthritis (OA) is a major disease whose prevalence increases with aging, sedentary lifestyles, and obesity. The association between obesity and OA has been well documented, but the precise mechanisms underlying this heightened risk remain unclear. While obesity imposes greater forces on joints, systemic fat-derived factors such as lipids or adipokine may potentially act on the pathophysiology of OA, but the exact role of these factors in weight-bearing and non-weight-bearing joints remains elusive. Intra-articular adipose tissues (IAAT) have gained significant attention for actively participating in OA pathogenesis by interacting with various joint tissues. Lipid content has been proposed as a diagnostic target for early OA detection and a potential source of biomarkers. Moreover, targeting a specific IAAT called infrapatellar fat pad (IFP) and its lipids hold promise for attenuating OA-associated inflammation. Conversely, bone marrow adipose tissue (BMAT), which was long thought to be an inert filling tissue, is now increasingly considered a dynamic tissue whose volume and lipid content regulate bone remodeling in pathological conditions. Given OA's ability to alter adipose tissues, particularly those within the joint (IFP and BMAT), and the influence of adipose tissues on OA pathogenesis, this review examines the lipids produced by OA-associated adipose tissues, shedding light on their potential role in OA pathophysiology and highlighting them as potential therapeutic targets.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality. 纳豆激酶的定点突变：揭示结构-功能关系以增强功能

Biochimie Pub Date : 2024-09-26 DOI: 10.1016/j.biochi.2024.09.014

Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur

{"title":"Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality.","authors":"Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur","doi":"10.1016/j.biochi.2024.09.014","DOIUrl":"10.1016/j.biochi.2024.09.014","url":null,"abstract":"Site-directed mutagenesis was employed to investigate the structure-function relationship of nattokinase (NK) and its effect on the enzymatic activity, thermostability, pH tolerance, and fibrinolytic properties of NK. Specific mutations (T270S, V271I, E262D, and A259T) were introduced within the nk gene, targeting regions predicted to be involved in substrate binding. The NK(E262D) mutant exhibited a significant increase in enzymatic activity (2-fold) and catalytic efficiency (2.2-fold) as assessed by N-Succinyl-Ala-Ala-Pro-Phe p-nitroanilide (Suc-AAPF-pNA) hydrolysis, compared to the wild type. In silico analysis supported these findings, demonstrating lower binding energy for the NK(E262D) mutant, suggesting stronger fibrin affinity. Thermostability assays revealed that NK(E262D) and NK(A259T) displayed exceptional stability, retaining enzyme activity at 60 °C. All mutants exhibited a broader pH tolerance range (pH 5.0-10.0) compared to the wild-type NK. The fibrinolytic activity assay revealed that the E262D mutant possessed the highest fibrinolytic activity (2414 U/mg), surpassing the wild-type. This study reported an NK variant with improved enzymatic activity, thermostability, and fibrinolytic properties.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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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