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Anti-tumor analysis of the RIG-I agonist in vitro and in vivo rig - 1激动剂体内外抗肿瘤分析
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-12 DOI: 10.1016/j.bbrep.2025.102249
Qian Wang , Ziyang Song , Bopei Cui , Chaoqiang An , Fan Gao , Mingchen Liu , Lu Li , Xiao Ma , Xing Wu , Zhenglun Liang
{"title":"Anti-tumor analysis of the RIG-I agonist in vitro and in vivo","authors":"Qian Wang ,&nbsp;Ziyang Song ,&nbsp;Bopei Cui ,&nbsp;Chaoqiang An ,&nbsp;Fan Gao ,&nbsp;Mingchen Liu ,&nbsp;Lu Li ,&nbsp;Xiao Ma ,&nbsp;Xing Wu ,&nbsp;Zhenglun Liang","doi":"10.1016/j.bbrep.2025.102249","DOIUrl":"10.1016/j.bbrep.2025.102249","url":null,"abstract":"<div><div>Retinoic acid-inducible gene I (RIG-I), a key pattern recognition receptor (PRR) detecting cytosolic 5′-triphosphorylated double-stranded RNA (5′-ppp dsRNA), mediated antitumor immunity. Here, we evaluated RIG-I agonists as potential antitumor agents. To analyze the anti-tumor efficacy, we engineered a panel of 5′-PPP-modified stem-loop-structured RNAs leveraging the non-coding sequence of SARS-CoV-2. Through systematic screening, nCoV-L emerged as a potent RIG-I agonist that induced death in hepatocellular carcinomas (HCC), pulmonary carcinomas, and colorectal cancer (CRC) <em>in vitro</em> and suppressed tumor growth <em>in vivo</em>. Mechanistic studies demonstrated that nCoV-L elicited mitochondria-dependent apoptosis, supporting its potential as a broad-spectrum antitumor agent.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102249"},"PeriodicalIF":2.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044740","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
Investigating the cardioprotective effects of Nigella sativa oil on chronic antibiotic use on the myocardium of the left ventricle of male BALB/C mice 研究黑草油对慢性抗生素使用对雄性BALB/C小鼠左心室心肌的保护作用
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-12 DOI: 10.1016/j.bbrep.2025.102259
S. Saka Olusola , A. Komolafe Omobola , A. Enye Linus , A. Saka Alice , S. Ayegbusi Olateju , E. Arayombo Babatunde , Lauretta A. Frederick
{"title":"Investigating the cardioprotective effects of Nigella sativa oil on chronic antibiotic use on the myocardium of the left ventricle of male BALB/C mice","authors":"S. Saka Olusola ,&nbsp;A. Komolafe Omobola ,&nbsp;A. Enye Linus ,&nbsp;A. Saka Alice ,&nbsp;S. Ayegbusi Olateju ,&nbsp;E. Arayombo Babatunde ,&nbsp;Lauretta A. Frederick","doi":"10.1016/j.bbrep.2025.102259","DOIUrl":"10.1016/j.bbrep.2025.102259","url":null,"abstract":"<div><div>The abuse of antibiotics is a significant factor in the emergence of antibiotic resistance and the development of several diseases in the modern world. These were conducted to provide information on the combined impact of chronic antibiotic exposure and <em>Nigella sativa</em> oil (NSO) on the morphology of the left ventricle of the heart of mice.</div><div>40 adult male BALB/c mice weighing about 28–32 kg, divided into 5 groups, were used for this research. Group A was given normal saline, and Group B mice received 1000 mg/kg/of ampicillin. Groups C mice received 2 ml/kg of NSO, Group D were given 1000 mg/kg of ampicillin + 2 ml/kg of NSO, and Group E mice received 1000 mg/kg pre-exposed to ampicillin + 2 ml/kg of NSO. The rats were sacrificed, and the heart tissue was harvested and stored in sample bottles containing 10 % neutral buffer for histological and immunohistochemical studies.</div><div>The results showed that there was a significant difference in superoxide dismutase and catalase activity in group B when compared with the control group (p = 0.0002, p = 0.0047, respectively). The photomicrograph of the control mice showed a regular arrangement with clear striations of myocardial fibres and centrally placed nuclei. There was a distortion of the regular arrangement of the myofibrils and disoriented nuclei in the ampicillin-only group.</div><div>The study concluded that chronic ampicillin exposure induces significant myocardial damage, affecting both the histological integrity and functional capacity of the heart.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102259"},"PeriodicalIF":2.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044755","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
Development and validation of a glycosyltransferase-associated prognostic model for melanoma and characterization of the tumor immune microenvironment using single-cell sequencing data 开发和验证糖基转移酶相关的黑色素瘤预后模型,并利用单细胞测序数据表征肿瘤免疫微环境
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-11 DOI: 10.1016/j.bbrep.2025.102237
Ma Jia-xin , Zhang Yun-bin , Lu Zhong-ting , Guo Zhi-dong
{"title":"Development and validation of a glycosyltransferase-associated prognostic model for melanoma and characterization of the tumor immune microenvironment using single-cell sequencing data","authors":"Ma Jia-xin ,&nbsp;Zhang Yun-bin ,&nbsp;Lu Zhong-ting ,&nbsp;Guo Zhi-dong","doi":"10.1016/j.bbrep.2025.102237","DOIUrl":"10.1016/j.bbrep.2025.102237","url":null,"abstract":"<div><div>This study aimed to develop a predictive model based on glycosyltransferase-related genes (GTs) to forecast the survival time of patients with Skin Cutaneous Melanoma (SKCM) and to explore the pathways and mechanisms through which GTs influence SKCM prognosis. Transcriptomic data of SKCM from The Cancer Genome Atlas (TCGA) were utilized for individualized predictive modeling, and the model's reliability was validated using GEO data. Univariate Cox regression and LASSO-Cox regression analyses were employed to select prognostically relevant biomarkers, and a predictive risk score was constr, ucted using multivariate Cox regression. Functional annotation of the risk score was performed through GO, KEGG, and GSEA analyses. The performance of the nomogram model was evaluated using ROC curves, calibration curves, and the concordance index (C-index). Furthermore, subsequent analyses based on risk grouping were conducted to assess immune infiltration, somatic mutations, and immune responses, and these findings were validated by real-time quantitative PCR (qPCR), Western Blot, and immunohistochemistry (IHC). Our results revealed a significant correlation between the risk score derived from multivariate Cox regression and the overall survival of SKCM patients. Enrichment analysis of the risk score indicated its association with immune functions. The nomogram model, which integrates the risk score with clinical prognostic factors, exhibited robust predictive performance in both training and validation datasets. Further analyses—including immune infiltration, single-cell analysis, somatic mutation analysis, and immune response assessment—demonstrated a strong correlation between the key gene MGAT4A and the infiltration of CD8<sup>+</sup> T cells as well as monocytes/macrophages in tumor tissues. In summary, we have developed an individualized predictive model for forecasting the 1-year, 3-year, 5-year, and 10-year survival rates of SKCM patients. This model holds promise as a potential tool for guiding personalized diagnosis and treatment of SKCM.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102237"},"PeriodicalIF":2.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044742","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 Ongoing Utility of lipoprotein lipase activity in diagnosing familial Chylomicronemia Syndrome 脂蛋白脂肪酶活性在诊断家族性乳糜微粒血症综合征中的持续应用
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-11 DOI: 10.1016/j.bbrep.2025.102245
Gregorio Fariña , Magalí Barchuk , Amira Sleiman , Alejandro Castellanos Pinedo , Johnayro Gutierrez Restrepo , Valeria Zago , Juan Patricio Nogueira , Gabriela Berg
{"title":"The Ongoing Utility of lipoprotein lipase activity in diagnosing familial Chylomicronemia Syndrome","authors":"Gregorio Fariña ,&nbsp;Magalí Barchuk ,&nbsp;Amira Sleiman ,&nbsp;Alejandro Castellanos Pinedo ,&nbsp;Johnayro Gutierrez Restrepo ,&nbsp;Valeria Zago ,&nbsp;Juan Patricio Nogueira ,&nbsp;Gabriela Berg","doi":"10.1016/j.bbrep.2025.102245","DOIUrl":"10.1016/j.bbrep.2025.102245","url":null,"abstract":"<div><h3>Objective</h3><div>Given that lipoprotein lipase (LPL) activity assays are not standardized for clinical use, we aimed to define reference values applicable to our clinical setting and identify a cut-off point to help distinguish Familial Chylomicronemia Syndrome from Multifactorial Chylomicronemia Syndrome, particularly in patients with inconclusive genetic findings.</div></div><div><h3>Methods</h3><div>We evaluated 28 patients with a history of TG levels above 880 mg/dL (10 mmol/L), and assessed their likelihood of FCS using the Moulin score. LPL activity was measured in post-heparin plasma using a radiometric assay. Thirty normotriglyceridemic controls were used to define reference values. Genetic testing for FCS canonical genes and lipid profile was performed in all sHTG patients.</div></div><div><h3>Results</h3><div>The reference value for LPL activity was 33.3 (18.7–70.3) mIU, with a cut-off of 8.42 mIU (25 % of the median of NTG) to distinguish FCS from MCS. Eighteen patients without genetic variants in canonical genes, a Moulin score &lt;9 and LPL activity &gt;25 % of NTG, were classified as MCS. Five genetic diagnosed FCS patients, with a Moulin score&gt;10 presented LPL activity &lt;25 % of NTG. Four patients with inconclusive genetic results and a Moulin score&gt;10 were classified as FCS according to LPL activity.</div></div><div><h3>Conclusion</h3><div>LPL activity in patients with sHTG could be useful for differentiating FCS and MCS, particularly in patients with ambiguous or negative genetic findings, highlighting the need for specialized laboratory support in diagnostics.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102245"},"PeriodicalIF":2.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044754","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
Regulatory interplay of cyclin D1 and INSM1 in suppressing INSL6 expression: Implications for breast cancer biology 细胞周期蛋白D1和INSM1在抑制INSL6表达中的调节相互作用:对乳腺癌生物学的影响
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-10 DOI: 10.1016/j.bbrep.2025.102250
Kozo Homma, Takuya Hasegawa, Shizuka Umezu, Kazumichi Osawa, Hisanori Sato, Koji Sato, Toshiyuki Sakamaki
{"title":"Regulatory interplay of cyclin D1 and INSM1 in suppressing INSL6 expression: Implications for breast cancer biology","authors":"Kozo Homma,&nbsp;Takuya Hasegawa,&nbsp;Shizuka Umezu,&nbsp;Kazumichi Osawa,&nbsp;Hisanori Sato,&nbsp;Koji Sato,&nbsp;Toshiyuki Sakamaki","doi":"10.1016/j.bbrep.2025.102250","DOIUrl":"10.1016/j.bbrep.2025.102250","url":null,"abstract":"<div><div>Cyclin D1, a key regulator of the G1-to-S phase cell cycle transition, is frequently amplified or overexpressed in breast cancer, contributing to tumorigenesis. Beyond its canonical role in cell cycle regulation, Cyclin D1 forms a complex with INSM1, a zinc-finger transcriptional repressor implicated in neuroendocrine differentiation. Here, we identify insulin-like peptide 6 (<em>INSL6</em>) as a novel transcriptional target of the Cyclin D1–INSM1 complex. Chromatin immunoprecipitation assays revealed INSM1 binding near the transcription start site of the <em>INSL6</em> gene, and luciferase reporter assays confirmed Cyclin D1-mediated suppression of <em>INSL6</em> promoter activity. Furthermore, Cyclin D1 overexpression reduced <em>INSL6</em> mRNA levels, while Cyclin D1 knockdown reversed this effect, highlighting its potential regulatory role. Given the observed association of low <em>INSL6</em> expression with shorter relapse-free survival, these findings suggest that the Cyclin D1–INSM1 axis may contribute to tumor progression through <em>INSL6</em> repression. This study provides new insights into the non-canonical functions of Cyclin D1 in breast cancer and identifies potential therapeutic targets within this regulatory pathway.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102250"},"PeriodicalIF":2.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026592","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
Effects of Mg2+ and ATP on YOYO-1 labeling of genomic DNA in single molecule experiments Mg2+和ATP对基因组DNA YOYO-1标记的单分子实验影响
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-10 DOI: 10.1016/j.bbrep.2025.102248
Carl Möller , Dennis Winter , Radhika Nambannor Kunnath, Sriram KK, Fredrik Westerlund
{"title":"Effects of Mg2+ and ATP on YOYO-1 labeling of genomic DNA in single molecule experiments","authors":"Carl Möller ,&nbsp;Dennis Winter ,&nbsp;Radhika Nambannor Kunnath,&nbsp;Sriram KK,&nbsp;Fredrik Westerlund","doi":"10.1016/j.bbrep.2025.102248","DOIUrl":"10.1016/j.bbrep.2025.102248","url":null,"abstract":"<div><div>Nanofluidic channels have emerged as a suitable tool to study DNA-protein interactions. Many DNA-interacting proteins require ATP to fully function and use Mg<sup>2+</sup> as a cofactor. Mg<sup>2+</sup> and ATP are however also known to influence the binding of dyes, such as the commonly used YOYO-1, to DNA. This study investigates the effects of Mg<sup>2+</sup> ions and ATP on YOYO-1 labeled genomic DNA and shows, via single molecule experiments in nanochannels, that Mg<sup>2+</sup> reduces the fluorescence intensity of YOYO-1 labeled DNA, as well as the extension of the DNA, at both low and high dye loadings. When combined, ATP counteracts the loss of fluorescence caused by Mg<sup>2+</sup>, but only at comparable concentrations. Additionally, while increasing the photobleaching rate, Mg<sup>2+</sup> delays dye-mediated photolytic DNA damage, reducing DNA fragmentation in the nanofluidic channels. Determination of the apparent binding constant by bulk measurements corroborates the single molecule observations, suggesting that Mg<sup>2+</sup> causes dissociation of YOYO-1 from DNA. These findings demonstrate that the addition of Mg<sup>2+</sup> and ATP poses challenges in DNA-protein studies using nanofluidics, which can be mitigated by optimizing experimental conditions.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102248"},"PeriodicalIF":2.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026648","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
Biological properties of copper: Antibacterial, osteogenesis of biomaterials 铜的生物学特性:抗菌、成骨的生物材料
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-10 DOI: 10.1016/j.bbrep.2025.102251
Mohammad Javad Salek Rahimi , Abbas Kianvash , Mohmmad Rezvani , Mohammad Yousef Memar
{"title":"Biological properties of copper: Antibacterial, osteogenesis of biomaterials","authors":"Mohammad Javad Salek Rahimi ,&nbsp;Abbas Kianvash ,&nbsp;Mohmmad Rezvani ,&nbsp;Mohammad Yousef Memar","doi":"10.1016/j.bbrep.2025.102251","DOIUrl":"10.1016/j.bbrep.2025.102251","url":null,"abstract":"<div><div>Copper (Cu) has gained significant attention from the researchers on biomaterials due to its important biological roles in the body. Researchers have found that Cu has biological properties, especially in orthopedic applications as an additive element in alloys or bio-compatible coatings. Additionally, Cu has anti-bacterial, angiogenic, and osteogenic properties. The antibacterial properties of Cu provide an alternative to antibiotics and prevent the development of antibiotic resistance. Furthermore, Cu contributes to bone and blood vessel formation and improves the performance of biological materials. This study examines the potential of Cu-containing implant materials in anti-bacterial and bone and blood vessel regeneration.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102251"},"PeriodicalIF":2.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044741","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
Circadian and photoperiodic control of melatonin in Drosophila ananassae 果蝇褪黑素的昼夜节律和光周期控制
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-10 DOI: 10.1016/j.bbrep.2025.102255
Hannah K. Dollish , Justin M. Snider , Hannah Doskicz , Michael A. Grandner , Fabian-Xosé Fernandez
{"title":"Circadian and photoperiodic control of melatonin in Drosophila ananassae","authors":"Hannah K. Dollish ,&nbsp;Justin M. Snider ,&nbsp;Hannah Doskicz ,&nbsp;Michael A. Grandner ,&nbsp;Fabian-Xosé Fernandez","doi":"10.1016/j.bbrep.2025.102255","DOIUrl":"10.1016/j.bbrep.2025.102255","url":null,"abstract":"<div><div>Melatonin is a widely conserved indoleamine with well-established roles in circadian timekeeping, sleep regulation, and physiological coordination across taxa. In <em>Drosophila melanogaster</em>, early studies reported daily melatonin rhythms, but little is known about melatonin dynamics in other <em>Drosophila</em> species. Here, we measured melatonin secretion in &gt;14,000 <em>Drosophila ananassae</em> across 12 circadian timepoints under four simulated photoperiods: LD 8:16 (short day), LD 12:12 (equatorial), LD 16:8 (long day), and LD 20:4 (arctic summer). Using LC-MS/MS detection in pooled whole-fly samples, we identified robust, bimodal melatonin rhythms across all conditions, with conserved peaks at approximately ZT7 and ZT13 irrespective of daylength. Melatonin levels were significantly elevated under the short-day photoperiod compared to all others (<em>p</em> &lt; 0.0005), indicating photoperiod-sensitive amplitude modulation. These findings confirm the presence of circadian melatonin rhythms in <em>Drosophila</em>, replicate a previously reported early-day peak observed in <em>D. melanogaster</em>, and reveal a second rhythm component not described in earlier studies. The data suggest that melatonin secretion in <em>Drosophila</em> is governed by an endogenous clock and phase-locked to lights-on, even in the absence of nighttime darkness. This work refines our understanding of melatonin rhythmicity in insects and underscores its potential role as a conserved circadian output across species.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102255"},"PeriodicalIF":2.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044806","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 multifaceted impact of a high-salt environment on the immune system and its contribution to salt-sensitive hypertension 高盐环境对免疫系统的多方面影响及其对盐敏感性高血压的贡献
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-09 DOI: 10.1016/j.bbrep.2025.102244
Li Wang , Jihong Hu , Kailun Ren
{"title":"The multifaceted impact of a high-salt environment on the immune system and its contribution to salt-sensitive hypertension","authors":"Li Wang ,&nbsp;Jihong Hu ,&nbsp;Kailun Ren","doi":"10.1016/j.bbrep.2025.102244","DOIUrl":"10.1016/j.bbrep.2025.102244","url":null,"abstract":"<div><div>Salt-sensitive hypertension (SSBP) is a common form of hypertension which responds strongly to dietary sodium intake. It is also associated with a significantly higher risk of cardiovascular events and target organ damage. Traditional research has focused on how the vascular, renal and neuroendocrine systems regulate SSBP. However, this study explores the profound effects of a high-salt environment on the immune system and its central role in SSBP pathogenesis, revealing key innovative findings in this field. High salt intake activates multiple key signalling pathways (NF-κB, JAK/STAT, MAPK and the NLRP3 inflammasome) in immune cells, such as antigen-presenting cells, macrophages and Th17 cells, triggering significant oxidative stress and inflammatory cascades. Specific mechanisms include high salt inducing immune cells to perceive sodium ions through the ENaC channel and NCX1, activating the SGK1/FOXO1 axis and NFAT5 to drive Th17/Treg imbalance and the release of pro-inflammatory factors such as IL-6, IL-17A, TNF-α and IL-1β.), excessive ROS production and the resulting protein modifications create new antigens (e.g. IsoLG), and gut microbiota dysbiosis (e.g. reduced Lactobacillus and elevated TMAO) amplifies systemic inflammation by reducing short-chain fatty acids (SCFAs) and increasing endotoxin release, thereby activating TLR4/NF-κB and other pathways. This study emphasises the novel mechanisms by which these signalling pathways NF-κB as the core hub of inflammation; JAK2 in CD11c<sup>+</sup> APC cells; and p38 MAPK in endothelial dysfunction and their interactions drive SSBP. These inflammatory processes impair vascular endothelial function, affect renal sodium excretion and promote renal fibrosis. They also form a vicious cycle with sympathetic nervous system activation, which collectively drives the onset and progression of SSBP. Understanding these immune-mediated inflammatory mechanisms provides an important theoretical basis for developing novel anti-inflammatory therapeutic strategies for SSBP, such as targeting specific signalling pathways or regulating intestinal microbiota.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102244"},"PeriodicalIF":2.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026594","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
Selective real-time disulfide reduction with simultaneous fluorescent labeling of a humanized anti-cocaine mAb 选择性实时二硫还原与同时荧光标记的人源抗可卡因单抗
IF 2.2
Biochemistry and Biophysics Reports Pub Date : 2025-09-09 DOI: 10.1016/j.bbrep.2025.102243
Terence L. Kirley, Andrew B. Norman
{"title":"Selective real-time disulfide reduction with simultaneous fluorescent labeling of a humanized anti-cocaine mAb","authors":"Terence L. Kirley,&nbsp;Andrew B. Norman","doi":"10.1016/j.bbrep.2025.102243","DOIUrl":"10.1016/j.bbrep.2025.102243","url":null,"abstract":"<div><div>A procedure for rapid screening and development of facile and limited partial reduction, with simultaneous fluorescent labeling, of a humanized anti-cocaine mAb was devised and characterized. This employed a standard soluble protein reductant, tris (2-carboxyethyl) phosphine (TCEP), paired with an alkylating agent that can be used without removal of the reductant, yielding a fluorescent adduct of the generated cysteine. This reaction can also be monitored by absorbance in a nanophotometer, allowing for rapid, simple screening of reduction and alkylation conditions using small mAb amounts and volumes. The degree of reduction is readily controllable, and yields results similar to limited reductions followed by separate labeling reactions, as recently reported using immobilized TCEP, and a less reactive phosphine reductant, triphenylphosphine-3,3′,3″-trisulfonic acid (TPPTS). The overall structure of the mAb is not perturbed, and the thermal stability of the Fab portion of the mAb, where most selective disulfide reductions occur, is only minimally decreased. The antigen (cocaine) binding and binding thermodynamics are not changed, as demonstrated by isothermal titration calorimetry. However, differential scanning fluorimetry demonstrated that the thermal stabilization of the Fab domain by cocaine binding is dramatically decreased after reductive labeling to a level of 5.44 modified cys/mAb, suggesting the importance of light-heavy chain disulfide bonds for the cocaine-induced thermal stabilization of the mAb Fab. Methods described in this work should aid in the selective reduction and labeling of disulfides in mAbs and other proteins, assisting the assignment of structural and functional importance to specific protein disulfide bonds.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102243"},"PeriodicalIF":2.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026593","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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