Cotton (Gossypium hirsutum L.) has experienced extensive breeding in recent decades, leading to a narrowed genetic base that presents challenges for accurate germplasm differentiation and cultivar authentication. This study primarily addresses the lack of reliable, scalable, and interpretable tools for distinguishing closely related Iranian cotton cultivars. To overcome this limitation, the research integrates inter-simple sequence repeat (ISSR) markers with machine learning (ML) algorithms to evaluate genetic diversity and establish diagnostic criteria for cultivar identification. Eighteen commercial cultivars were genotyped using 14 ISSR primers and binary scored data (presence/absence of bands) were used to calculate genetic diversity parameters, including the observed number of alleles (Na), effective number of alleles (Ne), Shannon's information index (I), and expected heterozygosity (He) were calculated. Primers 13, 10, and 26 were identified as the most informative loci, yielding the highest values across diversity parameters. Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering and principal coordinates analysis (PCoA) revealed five cultivar groups, with several accessions (e.g., Jahesh, Fakhr, Sahel) showing marked genetic distinctiveness. To enhance cultivar authentication, ISSR data were analyzed using ML classifiers. A decision tree model generated transparent band-based rules, while Random Forest feature selection highlighted key diagnostic loci (Primer24_525, Primer2_766). The combined framework achieved high classification accuracy and reproducibility, enabling reliable discrimination among closely related cultivars. These findings demonstrate the novelty and practical utility of integrating multilocus ISSR markers with ML for cultivar authentication, seed certification, and genetic resource management, while also highlighting previously underexplored genetic diversity that can inform cotton breeding programs in Iran.
{"title":"Integration of inter-simple sequence repeats with machine learning approach for diversity analysis and authentication of Iranian cotton cultivars","authors":"Rasmieh Hamid , Zahra Ghorbanzadeh , Bahman Panahi","doi":"10.1016/j.bbrep.2025.102435","DOIUrl":"10.1016/j.bbrep.2025.102435","url":null,"abstract":"<div><div>Cotton (<em>Gossypium hirsutum</em> L.) has experienced extensive breeding in recent decades, leading to a narrowed genetic base that presents challenges for accurate germplasm differentiation and cultivar authentication. This study primarily addresses the lack of reliable, scalable, and interpretable tools for distinguishing closely related Iranian cotton cultivars. To overcome this limitation, the research integrates inter-simple sequence repeat (ISSR) markers with machine learning (ML) algorithms to evaluate genetic diversity and establish diagnostic criteria for cultivar identification. Eighteen commercial cultivars were genotyped using 14 ISSR primers and binary scored data (presence/absence of bands) were used to calculate genetic diversity parameters, including the observed number of alleles (Na), effective number of alleles (Ne), Shannon's information index (I), and expected heterozygosity (He) were calculated. Primers 13, 10, and 26 were identified as the most informative loci, yielding the highest values across diversity parameters. Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering and principal coordinates analysis (PCoA) revealed five cultivar groups, with several accessions (e.g., Jahesh, Fakhr, Sahel) showing marked genetic distinctiveness. To enhance cultivar authentication, ISSR data were analyzed using ML classifiers. A decision tree model generated transparent band-based rules, while Random Forest feature selection highlighted key diagnostic loci (Primer24_525, Primer2_766). The combined framework achieved high classification accuracy and reproducibility, enabling reliable discrimination among closely related cultivars. These findings demonstrate the novelty and practical utility of integrating multilocus ISSR markers with ML for cultivar authentication, seed certification, and genetic resource management, while also highlighting previously underexplored genetic diversity that can inform cotton breeding programs in Iran.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102435"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938385","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102436
Lingling Wang , Huihao Ao , Cheng Huang , Deling Wu , Yan Hong , Yanquan Han
Background
The thermal processing of Xanthii Fructus is known to attenuate its hepatotoxicity. Carboxyatractyloside (CATR) and atractyloside (ATR), the primary toxic constituents, exhibit differential toxicity, with CATR being more potent. While the conversion of CATR to the less toxic ATR during processing is believed to underlie this toxicity reduction, the precise conversion dynamics and associated molecular mechanisms remain to be fully elucidated.
Purpose
This study aimed to elucidate the mechanisms responsible for the reduced hepatotoxicity of Xanthii Fructus following sand-frying. We employed an integrated approach combining ultra-high-performance liquid chromatography (UHPLC), metabolomics, and network pharmacology to investigate the differences in chemical composition and toxicological pathways between the crude and processed herb.
Methods
The UHPLC method was used to establish fingerprint of Xanthii Fructus from different origins before and after processing, and the contents of CATR and ATR were determined. The thermal conversion and comparative toxicity of these compounds were subsequently evaluated. Cellular metabolomics was performed to identify differential metabolites and perturbed pathways, while network pharmacology and molecular docking were used to predict and validate primary protein targets and their binding affinities.
Results
The attenuated hepatotoxicity was primarily attributed to the thermal conversion of CATR to ATR. Metabolomic analysis revealed that CATR significantly impacted alanine, aspartate, and glutamate metabolism and the TCA cycle, whereas ATR predominantly affected pyrimidine, arginine, and proline metabolism. Glutathione metabolism was a common pathway for both. Molecular docking simulations showed that CATR exhibited a stronger binding affinity than ATR towards key protein targets (DSS, DESG2, and ENTPD1), which is consistent with its greater toxicity.
{"title":"Study on the processing transformation law of CATR and ATR in Xanthii Fructus and the metabolomics mechanism of their transformation products in LO2 cells","authors":"Lingling Wang , Huihao Ao , Cheng Huang , Deling Wu , Yan Hong , Yanquan Han","doi":"10.1016/j.bbrep.2025.102436","DOIUrl":"10.1016/j.bbrep.2025.102436","url":null,"abstract":"<div><h3>Background</h3><div>The thermal processing of Xanthii Fructus is known to attenuate its hepatotoxicity. Carboxyatractyloside (CATR) and atractyloside (ATR), the primary toxic constituents, exhibit differential toxicity, with CATR being more potent. While the conversion of CATR to the less toxic ATR during processing is believed to underlie this toxicity reduction, the precise conversion dynamics and associated molecular mechanisms remain to be fully elucidated.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the mechanisms responsible for the reduced hepatotoxicity of Xanthii Fructus following sand-frying. We employed an integrated approach combining ultra-high-performance liquid chromatography (UHPLC), metabolomics, and network pharmacology to investigate the differences in chemical composition and toxicological pathways between the crude and processed herb.</div></div><div><h3>Methods</h3><div>The UHPLC method was used to establish fingerprint of Xanthii Fructus from different origins before and after processing, and the contents of CATR and ATR were determined. The thermal conversion and comparative toxicity of these compounds were subsequently evaluated. Cellular metabolomics was performed to identify differential metabolites and perturbed pathways, while network pharmacology and molecular docking were used to predict and validate primary protein targets and their binding affinities.</div></div><div><h3>Results</h3><div>The attenuated hepatotoxicity was primarily attributed to the thermal conversion of CATR to ATR. Metabolomic analysis revealed that CATR significantly impacted alanine, aspartate, and glutamate metabolism and the TCA cycle, whereas ATR predominantly affected pyrimidine, arginine, and proline metabolism. Glutathione metabolism was a common pathway for both. Molecular docking simulations showed that CATR exhibited a stronger binding affinity than ATR towards key protein targets (DSS, DESG2, and ENTPD1), which is consistent with its greater toxicity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102436"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938387","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102423
Nadège Emégam Kouémou , Louis Aimé Sepi , Mireille Sylviane Nguepi Dongmo , Ndzweng Linda Tamanji , Franklin Savo Mbeboh , Stephanie Jacqueline Kameni Ndjapdounke , Paul Aimé Noubissi , Bernard Tiencheu , Elisabeth Ngo Bum
Background
Alcohol withdrawal syndrome (AWS) happens following a sudden interruption of chronic alcohol intake. AWS is a severe condition, often leading to anxiety and seizures. Current treatments against AWS do not target all the features of the disease. This study aimed to evaluate Hibiscus sabdariffa aqueous extract on AWS in mice.
Methods
Thirty-five male mice were grouped into seven sets of 5 animals. Each set (except the sham control) received alcohol (5 %) as drinking water and, in addition, alcohol at increasing concentrations (5 %–35 %, 0.4 g/kg to 2.8 g/kg) once every 24 h for 28 days. After alcohol weaning on day 29, anxiety was evaluated (days 29–31). Following behavioural recording, animals were euthanised. Brain and liver homogenates were used for biochemical evaluation of oxidative stress parameters. Alanine aminotransferase and Aspartate aminotransferase were assessed in the serum.
Results
Alcohol withdrawal led to a significant (P < 0.001) decrease in open arm activities in the elevated plus maze. Hibiscus sabdariffa administration reversed the ethanol effect and increased open arms stay and exploration. Hibiscus sabdariffa also significantly (P < 0.05) increased center exploration of the open field, which was reduced by alcohol withdrawal. A treatment with Hibiscus sabdariffa significantly (P < 0.01) reduced the increase of brain and liver oxidation induced by alcohol withdrawal. Serum Alanine aminotransferase level was also significantly (P < 0.001) decreased by Hibiscus sabdariffa extract.
Conclusion
This study's results justify the traditional utilisation of the drinks prepared from Hibiscus sabdariffa cayxes in treating patients suffering from AWS.
{"title":"Hibiscus sabdariffa calyx aqueous extract mitigates alcohol withdrawal-induced anxiety and oxidative stress in mice","authors":"Nadège Emégam Kouémou , Louis Aimé Sepi , Mireille Sylviane Nguepi Dongmo , Ndzweng Linda Tamanji , Franklin Savo Mbeboh , Stephanie Jacqueline Kameni Ndjapdounke , Paul Aimé Noubissi , Bernard Tiencheu , Elisabeth Ngo Bum","doi":"10.1016/j.bbrep.2025.102423","DOIUrl":"10.1016/j.bbrep.2025.102423","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol withdrawal syndrome (AWS) happens following a sudden interruption of chronic alcohol intake. AWS is a severe condition, often leading to anxiety and seizures. Current treatments against AWS do not target all the features of the disease. This study aimed to evaluate <em>Hibiscus sabdariffa</em> aqueous extract on AWS in mice.</div></div><div><h3>Methods</h3><div>Thirty-five male mice were grouped into seven sets of 5 animals. Each set (except the sham control) received alcohol (5 %) as drinking water and, in addition, alcohol at increasing concentrations (5 %–35 %, 0.4 g/kg to 2.8 g/kg) once every 24 h for 28 days. After alcohol weaning on day 29, anxiety was evaluated (days 29–31). Following behavioural recording, animals were euthanised. Brain and liver homogenates were used for biochemical evaluation of oxidative stress parameters. Alanine aminotransferase and Aspartate aminotransferase were assessed in the serum.</div></div><div><h3>Results</h3><div>Alcohol withdrawal led to a significant (P < 0.001) decrease in open arm activities in the elevated plus maze. <em>Hibiscus sabdariffa</em> administration reversed the ethanol effect and increased open arms stay and exploration. <em>Hibiscus sabdariffa</em> also significantly (P < 0.05) increased center exploration of the open field, which was reduced by alcohol withdrawal. A treatment with <em>Hibiscus sabdariffa</em> significantly (P < 0.01) reduced the increase of brain and liver oxidation induced by alcohol withdrawal. Serum Alanine aminotransferase level was also significantly (P < 0.001) decreased by <em>Hibiscus sabdariffa</em> extract.</div></div><div><h3>Conclusion</h3><div>This study's results justify the traditional utilisation of the drinks prepared from <em>Hibiscus sabdariffa</em> cayxes in treating patients suffering from AWS.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102423"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938986","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102426
Laura A.E. Brunmaier, Travis W. Walker
Epidemiological studies have indicated that strong causal evidence exists to link the inhalation of particulate matter to the exacerbation of pathology in the cardiovascular system, ranging from myocardial infarction and atherosclerosis to direct cytotoxicity and inflammation. Ultrafine particles are ubiquitous in ambient air, in industrial sites, and in air pollution. When particles are inhaled, deposition can occur in the lungs, and the mechanisms of pathology have been well-studied. However, ultrafine particulate matter can translocate from the lungs into the bloodstream to circulate throughout the body (Choi et al. 2010).Contradictory evidence exists of inflammation and cytotoxicity that is caused from nanoparticle exposure to the endothelium.
When endothelial cells (ECs) are adversely stimulated, they have been shown to secrete cytokines that mediate an inflammatory response. Currently, studies that quantitatively evaluated the secretion of pro-inflammatory cytokines from ECs upon nanoparticle exposure are not accounting for the aggregation that can occur between particles over time and, therefore, are likely exposing cells to a wider range of aggregated sizes. This study evaluates the inflammatory response from ECs after particle exposure, with acute attention devoted to controlling particle aggregation. Specifically, we introduce a protocol that exposes ECs to the particles in a transwell system, where we take advantage of the effects of gravitational settling to expose the ECs only to the smallest fraction of the particles that are in suspension. After 72 h in the transwell assay, we found that the inflammatory response between varying concentrations of particles mirrored the inflammatory response of the positive control of lipopolysaccharide (LPS). These results indicate that the inflammatory response may have a stronger relationship to the particle size than to the concentration of the particles in mass per volume.
流行病学研究表明,有强有力的因果证据表明,颗粒物质的吸入与心血管系统的病理恶化有关,从心肌梗死和动脉粥样硬化到直接的细胞毒性和炎症。超细颗粒在环境空气、工业场所和空气污染中无处不在。当颗粒被吸入,沉积可发生在肺部,病理机制已被充分研究。然而,超细颗粒物可以从肺部转移到血液中,在全身循环(Choi et al. 2010)。存在相互矛盾的证据表明,炎症和细胞毒性是由纳米颗粒暴露于内皮细胞引起的。当内皮细胞(ECs)受到不良刺激时,它们已被证明会分泌介导炎症反应的细胞因子。目前,定量评估纳米颗粒暴露后内皮细胞促炎细胞因子分泌的研究并没有考虑颗粒之间随着时间的推移可能发生的聚集,因此,可能会使细胞暴露于更大范围的聚集大小。本研究评估颗粒暴露后ECs的炎症反应,重点关注控制颗粒聚集。具体来说,我们引入了一种将ec暴露于transwell系统中的粒子的协议,在该协议中,我们利用重力沉降的影响,使ec仅暴露于悬浮粒子的最小部分。在transwell实验72小时后,我们发现不同浓度颗粒之间的炎症反应反映了脂多糖(LPS)阳性对照的炎症反应。这些结果表明,炎症反应可能与颗粒大小的关系比与每体积颗粒的质量浓度的关系更强。
{"title":"Investigating the inflammatory response to exposure of ultrafine TiO2 particulate matter to HUVECs","authors":"Laura A.E. Brunmaier, Travis W. Walker","doi":"10.1016/j.bbrep.2025.102426","DOIUrl":"10.1016/j.bbrep.2025.102426","url":null,"abstract":"<div><div>Epidemiological studies have indicated that strong causal evidence exists to link the inhalation of particulate matter to the exacerbation of pathology in the cardiovascular system, ranging from myocardial infarction and atherosclerosis to direct cytotoxicity and inflammation. Ultrafine particles are ubiquitous in ambient air, in industrial sites, and in air pollution. When particles are inhaled, deposition can occur in the lungs, and the mechanisms of pathology have been well-studied. However, ultrafine particulate matter can translocate from the lungs into the bloodstream to circulate throughout the body (Choi et al. 2010).Contradictory evidence exists of inflammation and cytotoxicity that is caused from nanoparticle exposure to the endothelium.</div><div>When endothelial cells (ECs) are adversely stimulated, they have been shown to secrete cytokines that mediate an inflammatory response. Currently, studies that quantitatively evaluated the secretion of pro-inflammatory cytokines from ECs upon nanoparticle exposure are not accounting for the aggregation that can occur between particles over time and, therefore, are likely exposing cells to a wider range of aggregated sizes. This study evaluates the inflammatory response from ECs after particle exposure, with acute attention devoted to controlling particle aggregation. Specifically, we introduce a protocol that exposes ECs to the particles in a transwell system, where we take advantage of the effects of gravitational settling to expose the ECs only to the smallest fraction of the particles that are in suspension. After 72<!--> <!-->h in the transwell assay, we found that the inflammatory response between varying concentrations of particles mirrored the inflammatory response of the positive control of lipopolysaccharide (LPS). These results indicate that the inflammatory response may have a stronger relationship to the particle size than to the concentration of the particles in mass per volume.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102426"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938985","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102418
Fereshteh Moheb Afzali , Masoumeh Heshmati , Ali Salimi , Somayeh Kalanaky , Saideh Fakharzadeh , Maryam Hafizi , Mohammad Esmail Akbari , Mohammad Hassan Nazaran , Mehrdad Hashemi
Background
Breast cancer (BC) ranks as the most prevalent cancer type among women globally. Nanoparticle technology, a promising approach, plays a crucial role in effective cancer diagnosis and treatment. In this context, researchers investigated the efficacy of BCc1 nanomedicine, which utilizes nanochelating technology and possesses anti-neoplastic properties, in mice with breast tumors. Notably, this study represents the first global exploration of BCc1 nanomedicine's potential to induce autophagy, a process mediated by autophagy-related genes (Beclin-1, ATG-4B, ATG-7, and mTOR), while evaluating tumor cell death.
Methods
In this study, female BALB/c mice bearing 4T1 mammary tumors received daily treatments with BCc1 nanomedicine for 24 consecutive days via two administration routes: intraperitoneal (i.p.) injection and oral administration by gavage. The research investigated the impact of BCc1 nanomedicine on autophagy induction. Importantly, BCc1 nanomedicine played a role in mitigating tumor cell death severity by activating essential genes. Real-time PCR facilitated detailed gene expression analysis during the 24-day treatment period.
Results
Cyclophosphamide and BCc1 nanomedicine exhibited distinct regulatory effects on autophagy-associated genes. Beclin-1 expression was significantly upregulated in both cyclophosphamide-treated and BCc1-administered groups compared to controls. In BCc1-treated mice, ATG-4B and ATG-7—genes essential for autophagosome formation and maturation—were markedly downregulated across all dosing regimens. Concurrently, BCc1 induced a significant reduction in mTOR expression, consistent with the removal of a major inhibitory checkpoint in autophagy initiation. Taken together, these findings suggest that BCc1 exerts a stage-specific influence on autophagy, potentially enhancing its initiation phase while attenuating subsequent maturation steps.
Conclusion
In summary, BCc1 nanomedicine demonstrates therapeutic potential in BC, in part through the modulation of autophagy pathways. The observed gene expression profile—characterized by mTOR suppression and Beclin-1 upregulation alongside reduced ATG-4B and ATG-7 expression—indicates a selective enhancement of autophagy initiation, coupled with alterations in autophagosome maturation. This nuanced modulation of autophagy may contribute to BCc1's anti-tumor activity and warrants further investigation into its stage-specific mechanistic effects in cancer therapy.
{"title":"Nanochelate-based BCc1 delivery and its impact on key regulatory pathways in BALB/c breast cancer: An analysis of Beclin-1, ATG-4B, ATG-7, and mTOR expression","authors":"Fereshteh Moheb Afzali , Masoumeh Heshmati , Ali Salimi , Somayeh Kalanaky , Saideh Fakharzadeh , Maryam Hafizi , Mohammad Esmail Akbari , Mohammad Hassan Nazaran , Mehrdad Hashemi","doi":"10.1016/j.bbrep.2025.102418","DOIUrl":"10.1016/j.bbrep.2025.102418","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) ranks as the most prevalent cancer type among women globally. Nanoparticle technology, a promising approach, plays a crucial role in effective cancer diagnosis and treatment. In this context, researchers investigated the efficacy of BCc1 nanomedicine, which utilizes nanochelating technology and possesses anti-neoplastic properties, in mice with breast tumors. Notably, this study represents the first global exploration of BCc1 nanomedicine's potential to induce autophagy, a process mediated by autophagy-related genes (<em>Beclin-1</em>, <em>ATG-4B</em>, <em>ATG-7</em>, and <em>mTOR</em>), while evaluating tumor cell death.</div></div><div><h3>Methods</h3><div>In this study, female BALB/c mice bearing 4T1 mammary tumors received daily treatments with BCc1 nanomedicine for 24 consecutive days via two administration routes: intraperitoneal (i.p.) injection and oral administration by gavage. The research investigated the impact of BCc1 nanomedicine on autophagy induction. Importantly, BCc1 nanomedicine played a role in mitigating tumor cell death severity by activating essential genes. Real-time PCR facilitated detailed gene expression analysis during the 24-day treatment period.</div></div><div><h3>Results</h3><div>Cyclophosphamide and BCc1 nanomedicine exhibited distinct regulatory effects on autophagy-associated genes. <em>Beclin-1</em> expression was significantly upregulated in both cyclophosphamide-treated and BCc1-administered groups compared to controls. In BCc1-treated mice, <em>ATG-4B</em> and <em>ATG-7</em>—genes essential for autophagosome formation and maturation—were markedly downregulated across all dosing regimens. Concurrently, BCc1 induced a significant reduction in <em>mTOR</em> expression, consistent with the removal of a major inhibitory checkpoint in autophagy initiation. Taken together, these findings suggest that BCc1 exerts a stage-specific influence on autophagy, potentially enhancing its initiation phase while attenuating subsequent maturation steps.</div></div><div><h3>Conclusion</h3><div>In summary, BCc1 nanomedicine demonstrates therapeutic potential in BC, in part through the modulation of autophagy pathways. The observed gene expression profile—characterized by <em>mTOR</em> suppression and <em>Beclin-1</em> upregulation alongside reduced <em>ATG-4B</em> and <em>ATG-7</em> expression—indicates a selective enhancement of autophagy initiation, coupled with alterations in autophagosome maturation. This nuanced modulation of autophagy may contribute to BCc1's anti-tumor activity and warrants further investigation into its stage-specific mechanistic effects in cancer therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102418"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938390","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102427
Dimitri Vanauberg, Céline Schulz, Guillaume Brysbaert, Nessim Raouraoua, Peggy Mistarz-Gruau, Marc F. Lensink, Anne-Sophie Vercoutter-Edouart, Tony Lefebvre
Fatty Acid Synthase (FASN) is a central enzyme in the de novo lipogenesis pathway. By producing fatty acids, FASN is implicated in numerous crucial cellular processes, but it is also frequently overexpressed in cancer. O-GlcNAc Transferase (OGT) governs the addition of N-acetylglucosamine residues onto cytosolic, nuclear and mitochondrial proteins. Like FASN, OGT actively participates in carcinogenesis. We previously showed that OGT regulates FASN in different ex vivo and in vivo models. Reciprocally, FASN promotes OGT expression and activity. The two enzymes physically interact together and contribute to cancer cell survival. It is therefore fundamental to define the respective interaction region of each enzyme to explore new therapeutic solutions for patients suffering from cancer. By using the hepatocarcinoma cell line Hep3B, we show thanks to two series of deletion mutants that both enzymes preferentially interact via their respective N-terminal regions. Analysis of the O-GlcNAc status of the various FASN deletion mutants shows that stronger interaction with OGT correlates with higher glycosylation, suggesting that OGT catalyzes the transfer of GlcNAc with limited substrate specificity.
{"title":"Mammalian fatty acid synthase and O-GlcNAc transferase preferentially interact via their respective N-terminal regions","authors":"Dimitri Vanauberg, Céline Schulz, Guillaume Brysbaert, Nessim Raouraoua, Peggy Mistarz-Gruau, Marc F. Lensink, Anne-Sophie Vercoutter-Edouart, Tony Lefebvre","doi":"10.1016/j.bbrep.2025.102427","DOIUrl":"10.1016/j.bbrep.2025.102427","url":null,"abstract":"<div><div>Fatty Acid Synthase (FASN) is a central enzyme in the <em>de novo</em> lipogenesis pathway. By producing fatty acids, FASN is implicated in numerous crucial cellular processes, but it is also frequently overexpressed in cancer. <em>O</em>-GlcNAc Transferase (OGT) governs the addition of N-acetylglucosamine residues onto cytosolic, nuclear and mitochondrial proteins. Like FASN, OGT actively participates in carcinogenesis. We previously showed that OGT regulates FASN in different <em>ex vivo</em> and <em>in vivo</em> models. Reciprocally, FASN promotes OGT expression and activity. The two enzymes physically interact together and contribute to cancer cell survival. It is therefore fundamental to define the respective interaction region of each enzyme to explore new therapeutic solutions for patients suffering from cancer. By using the hepatocarcinoma cell line Hep3B, we show thanks to two series of deletion mutants that both enzymes preferentially interact <em>via</em> their respective N-terminal regions. Analysis of the <em>O</em>-GlcNAc status of the various FASN deletion mutants shows that stronger interaction with OGT correlates with higher glycosylation, suggesting that OGT catalyzes the transfer of GlcNAc with limited substrate specificity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102427"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938486","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102421
Therése Cedervall , Baptiste Jude , Ferdinand von Walden , Lilly Velentza , Johanna T. Lanner , Thomas Sejersen , Farasat Zaman , Lars Sävendahl
Duchenne muscular dystrophy (DMD) is a progressive muscle disease for which glucocorticoid (GC) treatment is standard therapy. Patients typically suffer from short stature and osteoporosis, caused by the underlying disease and adverse effects of GCs. We investigated whether the mitochondrial peptide humanin (HNG) could prevent GC-induced growth retardation and osteoporosis in mouse models of DMD.
Male mdx mice (B10.mdx and D2.mdx) were treated with GCs, with/without HNG, from 5 to 9 weeks of age using two different treatment regimens. Tibial growth was monitored by weekly X-ray imaging; growth plates analyzed with immunohistochemistry and histomorphometry; and bone structure examined using peripheral quantitative computed tomography. Effects on skeletal muscle were evaluated by immunohistochemistry, qPCR, and ex vivo force measurements.
D2.mdx, but not B10.mdx, showed decreased bone growth and impaired bone structure compared with wild type (WT). D2.mdx also displayed increased growth plate height with lower endogenous humanin expression than D2.WT. GC treatment caused growth retardation and reductions in cortical bone area, thickness, and mineral content. Co-administration with HNG prevented bone growth impairment at one week of treatment and mitigated GC adverse effects on cortical bone in B10.mdx mice. Adding HNG to GCs did not exacerbate skeletal muscle pathology; in fact, HNG had a mild enlarging effect on muscle fibers.
These data suggest that HNG is a potential candidate for improving bone health in DMD during GC therapy. Further in vivo studies are needed to determine optimal HNG dosing and to assess the effects of long-term treatment on skeletal muscle function.
{"title":"Humanin improves bone health in a glucocorticoid-treated mouse model of Duchenne muscular dystrophy","authors":"Therése Cedervall , Baptiste Jude , Ferdinand von Walden , Lilly Velentza , Johanna T. Lanner , Thomas Sejersen , Farasat Zaman , Lars Sävendahl","doi":"10.1016/j.bbrep.2025.102421","DOIUrl":"10.1016/j.bbrep.2025.102421","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a progressive muscle disease for which glucocorticoid (GC) treatment is standard therapy. Patients typically suffer from short stature and osteoporosis, caused by the underlying disease and adverse effects of GCs. We investigated whether the mitochondrial peptide humanin (HNG) could prevent GC-induced growth retardation and osteoporosis in mouse models of DMD.</div><div>Male mdx mice (B10.mdx and D2.mdx) were treated with GCs, with/without HNG, from 5 to 9 weeks of age using two different treatment regimens. Tibial growth was monitored by weekly X-ray imaging; growth plates analyzed with immunohistochemistry and histomorphometry; and bone structure examined using peripheral quantitative computed tomography. Effects on skeletal muscle were evaluated by immunohistochemistry, qPCR, and <em>ex vivo</em> force measurements.</div><div>D2.mdx, but not B10.mdx, showed decreased bone growth and impaired bone structure compared with wild type (WT). D2.mdx also displayed increased growth plate height with lower endogenous humanin expression than D2.WT. GC treatment caused growth retardation and reductions in cortical bone area, thickness, and mineral content. Co-administration with HNG prevented bone growth impairment at one week of treatment and mitigated GC adverse effects on cortical bone in B10.mdx mice. Adding HNG to GCs did not exacerbate skeletal muscle pathology; in fact, HNG had a mild enlarging effect on muscle fibers.</div><div>These data suggest that HNG is a potential candidate for improving bone health in DMD during GC therapy. Further <em>in vivo</em> studies are needed to determine optimal HNG dosing and to assess the effects of long-term treatment on skeletal muscle function.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102421"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938488","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102433
Ningning Li , Xianghua Liu , Wei Liu , Saifei Li , Yanfei Lei , Baoying Wang
Drug-related factors represent a primary cause of acute kidney injury. Gentamicin (GM), while being one of the most effective and commonly used clinical agents against Gram-negative bacteria, frequently induces nephrotoxicity and triggers acute kidney injury during treatment. Melatonin, a natural antioxidant produced by the pineal gland, has been shown in recent studies to mitigate drug-induced nephrotoxicity. This study aimed to delineate the dose-dependent effects and underlying mechanisms of GM-induced acute kidney injury, along with the protective role of melatonin. Results demonstrated that GM administration elicited dose-dependent nephrotoxicity in rats, significantly elevating urinary biomarkers of tubular injury (KIM-1 and NGAL) and serum markers of renal dysfunction (BUN and SCr) at doses ≥50 mg/kg. Histopathological analysis revealed progressive renal damage including brush border loss, epithelial necrosis, basement membrane disruption, and interstitial inflammation. GM further exacerbated renal oxidative stress, depleting SOD and GSH while elevating MDA levels. Mechanistically, GM dose-dependently upregulated Keap1 and downregulated NRF2 expressions, consequently suppressing downstream antioxidants (GPX1, NQO1, HO-1). However, melatonin treatment significantly ameliorated high-dose GM-induced acute kidney injury by normalizing biochemical markers of renal impairment, attenuating histopathological damage, restoring antioxidant capacity, and reactivating the KEAP1/NRF2 pathway through suppression of Keap1 while enhancing NRF2 and its target proteins (GPX1/NQO1/HO-1) to nearly double of GM-H group levels, confirming its renoprotective role against GM-induced oxidative injury.
{"title":"Melatonin alleviates gentamicin-induced acute kidney injury through the Keap1/Nrf2/HO-1 signaling pathway","authors":"Ningning Li , Xianghua Liu , Wei Liu , Saifei Li , Yanfei Lei , Baoying Wang","doi":"10.1016/j.bbrep.2025.102433","DOIUrl":"10.1016/j.bbrep.2025.102433","url":null,"abstract":"<div><div>Drug-related factors represent a primary cause of acute kidney injury. Gentamicin (GM), while being one of the most effective and commonly used clinical agents against Gram-negative bacteria, frequently induces nephrotoxicity and triggers acute kidney injury during treatment. Melatonin, a natural antioxidant produced by the pineal gland, has been shown in recent studies to mitigate drug-induced nephrotoxicity. This study aimed to delineate the dose-dependent effects and underlying mechanisms of GM-induced acute kidney injury, along with the protective role of melatonin. Results demonstrated that GM administration elicited dose-dependent nephrotoxicity in rats, significantly elevating urinary biomarkers of tubular injury (KIM-1 and NGAL) and serum markers of renal dysfunction (BUN and SCr) at doses ≥50 mg/kg. Histopathological analysis revealed progressive renal damage including brush border loss, epithelial necrosis, basement membrane disruption, and interstitial inflammation. GM further exacerbated renal oxidative stress, depleting SOD and GSH while elevating MDA levels. Mechanistically, GM dose-dependently upregulated Keap1 and downregulated NRF2 expressions, consequently suppressing downstream antioxidants (GPX1, NQO1, HO-1). However, melatonin treatment significantly ameliorated high-dose GM-induced acute kidney injury by normalizing biochemical markers of renal impairment, attenuating histopathological damage, restoring antioxidant capacity, and reactivating the KEAP1/NRF2 pathway through suppression of Keap1 while enhancing NRF2 and its target proteins (GPX1/NQO1/HO-1) to nearly double of GM-H group levels, confirming its renoprotective role against GM-induced oxidative injury.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102433"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938391","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}
Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102406
Zeling Zhang , Meihong Hu , Di Yan, Yuanqi Zhao, Wen Tao, Shengyuan Chen, Meijie Qi, Lei Luo, Xiaohua Jiang, Bo Xu, Shun Bai
Spmip8, also known as Tepp, is a protein-coding gene which highly conserved in the mammals. Although SPMIP8 has been reported to be highly expressed in the testis, the function of SPMIP8 in spermatogenesis and male fertility remain unknown. In this study, we used CRISPR/cas9-mediated genome editing system to generate Spmip8-deficient mice. The phenotype of Spmip8 knockout (KO) male mice was performed by fertility tests, histology, and immunofluorescence. SPMIP8 is localization to the flagella of elongating spermatids in testis. Spmip8 KO male mice exhibited normal fertility. No significant differences were found in sperm count, motility, morphology and kinematic parameters between WT and Spmip8 KO mice. Furthermore, no detectable defects in spermatogenesis were found in KO mice. The transcription level of several Spmip genes (Spmip1, Spmip2, Spmip3, Spmip7 and Spmip11) was elevated in the testes of Spmip8 knockout mice, suggesting that Spmip8 gene in male fertility could be compensated by other Spmip family members. Overall, the findings of this study suggest that Spmip8 is not an essential gene for male fertility in mice. Our study helps researchers avoid duplication and repetitive work and explore genes that are integral to spermatogenesis and male fertility.
{"title":"Normal spermatogenesis and fertility in Spmip8 deficiency male mice","authors":"Zeling Zhang , Meihong Hu , Di Yan, Yuanqi Zhao, Wen Tao, Shengyuan Chen, Meijie Qi, Lei Luo, Xiaohua Jiang, Bo Xu, Shun Bai","doi":"10.1016/j.bbrep.2025.102406","DOIUrl":"10.1016/j.bbrep.2025.102406","url":null,"abstract":"<div><div>Spmip8, also known as Tepp, is a protein-coding gene which highly conserved in the mammals. Although SPMIP8 has been reported to be highly expressed in the testis, the function of SPMIP8 in spermatogenesis and male fertility remain unknown. In this study, we used CRISPR/cas9-mediated genome editing system to generate <em>Spmip8</em>-deficient mice. The phenotype of <em>Spmip8</em> knockout (KO) male mice was performed by fertility tests, histology, and immunofluorescence. SPMIP8 is localization to the flagella of elongating spermatids in testis. <em>Spmip8</em> KO male mice exhibited normal fertility. No significant differences were found in sperm count, motility, morphology and kinematic parameters between WT and <em>Spmip8</em> KO mice. Furthermore, no detectable defects in spermatogenesis were found in KO mice. The transcription level of several <em>Spmip</em> genes (<em>Spmip1</em>, <em>Spmip2</em>, <em>Spmip3</em>, <em>Spmip7</em> and <em>Spmip11</em>) was elevated in the testes of <em>Spmip8</em> knockout mice, suggesting that <em>Spmip8</em> gene in male fertility could be compensated by other <em>Spmip</em> family members. Overall, the findings of this study suggest that <em>Spmip8</em> is not an essential gene for male fertility in mice. Our study helps researchers avoid duplication and repetitive work and explore genes that are integral to spermatogenesis and male fertility.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102406"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938392","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}
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by serum ANCA and systemic small-vessel vasculitis. Neutrophils are primed to express ANCA antigens on the plasma membrane. ANCA binding to the antigens can transduce signals into neutrophils, releasing reactive oxygen species (ROS) and contributing to AAV development. ANCA-mediated signals are transduced via two pathways: ANCA antigens crosslinked by ANCA, and Fcγ receptor (FcγR), to which the Fc portion of ANCA binds. This study aimed to demonstrate the association of ANCA-mediated neutrophil activation pathways with clinical manifestations of AAV, including renal dysfunction and kidney survival at 6 months after treatment. For this purpose, IgG was extracted from the serum of AAV patients before treatment (n = 112), and ROS production from neutrophils exposed to IgG and its suppression by FcγR inhibitors (FcX) were assessed. IgG exhibiting higher ROS production than control IgG was classified as ROS-inducing ANCA and the others as ROS-noninducing ANCA. The former was subclassified into antigen-driven ANCA and FcγR-driven ANCA according to whether the ROS production suppression rate by FcX was <50 % or ≧50 %, respectively. As a result, ANCA was classified into ROS-inducing antigen-driven ANCA (n = 74), ROS-inducing FcγR-driven ANCA (n = 22), and ROS-noninducing ANCA (n = 16). Serum levels of blood urea nitrogen and creatinine were significantly higher in patients with ROS-inducing FcγR-driven ANCA than in those with ROS-noninducing ANCA. Patients with ROS-inducing FcγR-driven ANCA had a significantly lower kidney survival rate 6 months after treatment than other patients. The collective findings suggest that ROS-inducing FcγR-driven ANCA may predict poor kidney prognosis in AAV.
{"title":"Functional classification of antineutrophil cytoplasmic antibody (ANCA) and its relation with clinical parameters of ANCA-associated vasculitis","authors":"Mai Taniguchi , China Washio , Momo Uchizawa , Naho Ogawa , Riku Manabe , Suishin Arai , Hodaka Ogawa , Yuka Nishibata , Sakiko Masuda , Daigo Nakazawa , Utano Tomaru , Yoshihiro Arimura , Koichi Amano , Yukio Yuzawa , Ken-Ei Sada , Tatsuya Atsumi , Hiroaki Dobashi , Masayoshi Harigai , Seiichi Matsuo , Hirofumi Makino , Akihiro Ishizu","doi":"10.1016/j.bbrep.2025.102428","DOIUrl":"10.1016/j.bbrep.2025.102428","url":null,"abstract":"<div><div>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by serum ANCA and systemic small-vessel vasculitis. Neutrophils are primed to express ANCA antigens on the plasma membrane. ANCA binding to the antigens can transduce signals into neutrophils, releasing reactive oxygen species (ROS) and contributing to AAV development. ANCA-mediated signals are transduced via two pathways: ANCA antigens crosslinked by ANCA, and Fcγ receptor (FcγR), to which the Fc portion of ANCA binds. This study aimed to demonstrate the association of ANCA-mediated neutrophil activation pathways with clinical manifestations of AAV, including renal dysfunction and kidney survival at 6 months after treatment. For this purpose, IgG was extracted from the serum of AAV patients before treatment (n = 112), and ROS production from neutrophils exposed to IgG and its suppression by FcγR inhibitors (FcX) were assessed. IgG exhibiting higher ROS production than control IgG was classified as ROS-inducing ANCA and the others as ROS-noninducing ANCA. The former was subclassified into antigen-driven ANCA and FcγR-driven ANCA according to whether the ROS production suppression rate by FcX was <50 % or ≧50 %, respectively. As a result, ANCA was classified into ROS-inducing antigen-driven ANCA (n = 74), ROS-inducing FcγR-driven ANCA (n = 22), and ROS-noninducing ANCA (n = 16). Serum levels of blood urea nitrogen and creatinine were significantly higher in patients with ROS-inducing FcγR-driven ANCA than in those with ROS-noninducing ANCA. Patients with ROS-inducing FcγR-driven ANCA had a significantly lower kidney survival rate 6 months after treatment than other patients. The collective findings suggest that ROS-inducing FcγR-driven ANCA may predict poor kidney prognosis in AAV.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102428"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938992","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}