Pub Date : 2026-01-31DOI: 10.1016/j.bbrep.2026.102460
Zhaofeng Liang , Yuning Gu , Jiajia Song , Wenhui Yang , Xuezhong Xu
Small RNAs (sRNAs) in plant-derived exosome-like nanoparticles (PELNs) have attracted considerable attention as biologically active substances that play a crucial role in cross-kingdom regulatory processes. However, there is insufficient research dedicated to identifying sRNAs within PELNs. We aimed to analyze the expression profile of sRNAs in onion-derived exosomes-like nanoparticles (OELNs) and explore their potential role in cross-kingdom regulation. In this study, OELNs were extracted, possessing an optimal particle size of approximately 139 nm and a Zeta potential of roughly −20 mV. Subsequently, high-throughput small RNA sequencing was conducted to analyze sRNAs in onion tissues and OELNs. The expression profile of sRNAs in OELNs was elucidated, and it was predicted that highly expressed microRNAs (miRNAs) in OELNs may exert potential regulatory effects on the human genome. By comparing with the reference genome of onion (Allium cepa L.), 11 known miRNAs and 248 novel miRNAs were identified in both onion tissues and OELNs. Target gene prediction analysis of the human genome has revealed that 20 miRNAs highly expressed in OELNs potentially participate in the regulation of human tumor and cardiovascular-related signaling pathways. Furthermore, differential analysis was conducted on small/short interfering RNA (siRNA), small nucleolar RNA (snoRNA), and transfer ribonucleic acid (tRNA) in OELNs. This study laid a theoretical foundation for further exploring the cross-kingdom role of non-coding RNAs in OELNs, and provided new ideas for the development of plant-derived functional components.
{"title":"Identification and analysis of small RNAs in exosome-like nanoparticles derived from onion (Allium cepa L.)","authors":"Zhaofeng Liang , Yuning Gu , Jiajia Song , Wenhui Yang , Xuezhong Xu","doi":"10.1016/j.bbrep.2026.102460","DOIUrl":"10.1016/j.bbrep.2026.102460","url":null,"abstract":"<div><div>Small RNAs (sRNAs) in plant-derived exosome-like nanoparticles (PELNs) have attracted considerable attention as biologically active substances that play a crucial role in cross-kingdom regulatory processes. However, there is insufficient research dedicated to identifying sRNAs within PELNs. We aimed to analyze the expression profile of sRNAs in onion-derived exosomes-like nanoparticles (OELNs) and explore their potential role in cross-kingdom regulation. In this study, OELNs were extracted, possessing an optimal particle size of approximately 139 nm and a Zeta potential of roughly −20 mV. Subsequently, high-throughput small RNA sequencing was conducted to analyze sRNAs in onion tissues and OELNs. The expression profile of sRNAs in OELNs was elucidated, and it was predicted that highly expressed microRNAs (miRNAs) in OELNs may exert potential regulatory effects on the human genome. By comparing with the reference genome of onion (<em>Allium cepa L.</em>), 11 known miRNAs and 248 novel miRNAs were identified in both onion tissues and OELNs. Target gene prediction analysis of the human genome has revealed that 20 miRNAs highly expressed in OELNs potentially participate in the regulation of human tumor and cardiovascular-related signaling pathways. Furthermore, differential analysis was conducted on small/short interfering RNA (siRNA), small nucleolar RNA (snoRNA), and transfer ribonucleic acid (tRNA) in OELNs. This study laid a theoretical foundation for further exploring the cross-kingdom role of non-coding RNAs in OELNs, and provided new ideas for the development of plant-derived functional components.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102460"},"PeriodicalIF":2.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073824","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 : 2026-01-31DOI: 10.1016/j.bbrep.2026.102473
Naoki Fukao , Mito Watanabe , Ryo Takagi , Koki Okumura , Naomi Yoshii , Koma Kawabata , Satoshi Fujita
Essential amino acids (EAA) and resistance exercise (RE) are well-known approaches to activate muscle protein synthesis. Methionine is an EAA that stimulates mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signalling. It is believed that the lack of a single EAA could blunt protein synthesis. However, to our knowledge, no study has investigated the effects of methionine-restricted diet (MR) on RE-induced anabolic and catabolic signalling in skeletal muscle. Therefore, in this study, we aimed to investigate the effects of MR on RE-induced muscle protein synthesis and breakdown-related signalling. Male Sprague–Dawley rats were randomly divided into Control and MR group, and rats in the MR group were fed the experimental diets for 8 weeks. After the dietary intervention, RE was performed. p70S6K phosphorylation exhibited a significant main effect of RE and MR, with higher values observed across both conditions. FoxO3a Ser253 phosphorylation showed a significant main effects of both RE and MR, with lower values observed across conditions, while MuRF-1 protein expression showed a significant main effect of MR, with lower values observed in the MR condition. Furthermore, muscle protein synthesis demonstrated a significant main effect of MR, with higher values observed across MR conditions. These results suggested that the MR for 8 weeks neither attenuate RE-induced muscle anabolic response nor enhance catabolic response in rat skeletal muscle.
{"title":"Eight-week dietary methionine restriction does not impair resistance exercise-induced mTORC1 signalling activation in rats","authors":"Naoki Fukao , Mito Watanabe , Ryo Takagi , Koki Okumura , Naomi Yoshii , Koma Kawabata , Satoshi Fujita","doi":"10.1016/j.bbrep.2026.102473","DOIUrl":"10.1016/j.bbrep.2026.102473","url":null,"abstract":"<div><div>Essential amino acids (EAA) and resistance exercise (RE) are well-known approaches to activate muscle protein synthesis. Methionine is an EAA that stimulates mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signalling. It is believed that the lack of a single EAA could blunt protein synthesis. However, to our knowledge, no study has investigated the effects of methionine-restricted diet (MR) on RE-induced anabolic and catabolic signalling in skeletal muscle. Therefore, in this study, we aimed to investigate the effects of MR on RE-induced muscle protein synthesis and breakdown-related signalling. Male Sprague–Dawley rats were randomly divided into Control and MR group, and rats in the MR group were fed the experimental diets for 8 weeks. After the dietary intervention, RE was performed. p70S6K phosphorylation exhibited a significant main effect of RE and MR, with higher values observed across both conditions. FoxO3a Ser253 phosphorylation showed a significant main effects of both RE and MR, with lower values observed across conditions, while MuRF-1 protein expression showed a significant main effect of MR, with lower values observed in the MR condition. Furthermore, muscle protein synthesis demonstrated a significant main effect of MR, with higher values observed across MR conditions. These results suggested that the MR for 8 weeks neither attenuate RE-induced muscle anabolic response nor enhance catabolic response in rat skeletal muscle.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102473"},"PeriodicalIF":2.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073825","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 : 2026-01-30DOI: 10.1016/j.bbrep.2026.102471
Lijun Zhang, Meiyan Liu, Haiyang Chen
<div><h3>Objective</h3><div>To further explore the underlying mechanism by which the traditional Mongolian medicine Anshen Buxin Liuwei Pills (ABLP) alleviates cardiac dysfunction and depressive behaviors in a model of myocardial infarction (MI) combined with depression.</div></div><div><h3>Method</h3><div>Eighteen eight-week-old C57BL/6JNifdc male mice were divided into sham group (n = 6), MI + NS group (n = 6), MI + ABLP group (n = 6). Mice in the MI + ABLP group were treated with ABLP for 4 weeks. Seventeen eight-week-old wide-type (SERT<sup>+/+</sup>) mice and reduced SERT expression (SERT<sup>+/−</sup>) mice were allocated into SERT<sup>+/+</sup> NS group (n = 5), SERT<sup>+/+</sup> ABLP group (n = 4), SERT<sup>+/−</sup> NS group (n = 4), and SERT<sup>+/−</sup> ABLP group (n = 4). Mice in the SERT<sup>+/+</sup> ABLP and SERT<sup>+/−</sup> ABLP group were treated with ABLP for 1 week. Open field test (OFT) and sucrose preference test (SPT) were conducted for assessing depressive behaviors. The echocardiographic measurements were taken for the left ventricle fractional shortening (LVFS), and left ventricle ejection fraction (LVEF). Masson's trichrome staining was carried out to assess pathological alterations in the mice myocardium. Spleen samples were collected for detecting macrophages (M), M1, M2 by flow cytometry. ELISA was performed on serum, cardiac, and cortical tissues to quantify levels of TNF-α, TNFR1, TNFR2, P65, IKB-α, 5-HT, and hs-TNI. RT-qPCR was implemented to quantify TNFR1 mRNA expression in cardiac, cortical, and hippocampal tissues. SPSS version 24.0 software was applied for statistic analysis.</div></div><div><h3>Results</h3><div>MI mice exhibited lower level of LVEF and LVFS than the sham mice, which were elevated by ABLP treatment. MI mice displayed depressive behaviors, as evidenced by a shorter total distance, slower speed, longer immobility time, shorter activity time, reduced center distance, shorter center time, decreased center entry times, shorter peripheral distance, decreased peripheral entry times, decreased sucrose water consumption and sucrose preference than the sham group (all P < 0.05); these behavioral deficits were rescued by ABLP administration. MI mice presented elevated levels of M1 cells, cardiac TNFR1, TNF-α, IKB-α and P65 proteins and TNFR1 mRNA expression, along with reduced TNFR2 proteins, relative to the sham group. ABLP significantly decreased the concentration of M1 cells, IKB-α, P65 (P < 0.05). Both the MI + NS and MI + ABLP groups had significantly higher level of cortex TNFR1, TNF-α, IKB-α, P65 proteins and TNFR1 mRNA expression, as well as lower level of cortex TNFR2 than the sham group (P < 0.05). There were no significant differences in serum hs-TNI, LVFS, LVEF, and SPT results among SERT<sup>+/+</sup> NS, SERT<sup>+/+</sup> ABLP, SERT<sup>+/−</sup> NS, and SERT<sup>+/−</sup>ABLP groups (all P > 0.05). SERT<sup>+/−</sup> NS group had longer activity time, peripheral time, shor
{"title":"Treating myocardial infarction combined with depression via regulating M1/TNF-α/TNFR1/NF-κB","authors":"Lijun Zhang, Meiyan Liu, Haiyang Chen","doi":"10.1016/j.bbrep.2026.102471","DOIUrl":"10.1016/j.bbrep.2026.102471","url":null,"abstract":"<div><h3>Objective</h3><div>To further explore the underlying mechanism by which the traditional Mongolian medicine Anshen Buxin Liuwei Pills (ABLP) alleviates cardiac dysfunction and depressive behaviors in a model of myocardial infarction (MI) combined with depression.</div></div><div><h3>Method</h3><div>Eighteen eight-week-old C57BL/6JNifdc male mice were divided into sham group (n = 6), MI + NS group (n = 6), MI + ABLP group (n = 6). Mice in the MI + ABLP group were treated with ABLP for 4 weeks. Seventeen eight-week-old wide-type (SERT<sup>+/+</sup>) mice and reduced SERT expression (SERT<sup>+/−</sup>) mice were allocated into SERT<sup>+/+</sup> NS group (n = 5), SERT<sup>+/+</sup> ABLP group (n = 4), SERT<sup>+/−</sup> NS group (n = 4), and SERT<sup>+/−</sup> ABLP group (n = 4). Mice in the SERT<sup>+/+</sup> ABLP and SERT<sup>+/−</sup> ABLP group were treated with ABLP for 1 week. Open field test (OFT) and sucrose preference test (SPT) were conducted for assessing depressive behaviors. The echocardiographic measurements were taken for the left ventricle fractional shortening (LVFS), and left ventricle ejection fraction (LVEF). Masson's trichrome staining was carried out to assess pathological alterations in the mice myocardium. Spleen samples were collected for detecting macrophages (M), M1, M2 by flow cytometry. ELISA was performed on serum, cardiac, and cortical tissues to quantify levels of TNF-α, TNFR1, TNFR2, P65, IKB-α, 5-HT, and hs-TNI. RT-qPCR was implemented to quantify TNFR1 mRNA expression in cardiac, cortical, and hippocampal tissues. SPSS version 24.0 software was applied for statistic analysis.</div></div><div><h3>Results</h3><div>MI mice exhibited lower level of LVEF and LVFS than the sham mice, which were elevated by ABLP treatment. MI mice displayed depressive behaviors, as evidenced by a shorter total distance, slower speed, longer immobility time, shorter activity time, reduced center distance, shorter center time, decreased center entry times, shorter peripheral distance, decreased peripheral entry times, decreased sucrose water consumption and sucrose preference than the sham group (all P < 0.05); these behavioral deficits were rescued by ABLP administration. MI mice presented elevated levels of M1 cells, cardiac TNFR1, TNF-α, IKB-α and P65 proteins and TNFR1 mRNA expression, along with reduced TNFR2 proteins, relative to the sham group. ABLP significantly decreased the concentration of M1 cells, IKB-α, P65 (P < 0.05). Both the MI + NS and MI + ABLP groups had significantly higher level of cortex TNFR1, TNF-α, IKB-α, P65 proteins and TNFR1 mRNA expression, as well as lower level of cortex TNFR2 than the sham group (P < 0.05). There were no significant differences in serum hs-TNI, LVFS, LVEF, and SPT results among SERT<sup>+/+</sup> NS, SERT<sup>+/+</sup> ABLP, SERT<sup>+/−</sup> NS, and SERT<sup>+/−</sup>ABLP groups (all P > 0.05). SERT<sup>+/−</sup> NS group had longer activity time, peripheral time, shor","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102471"},"PeriodicalIF":2.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073823","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}
This study aims to investigate the potential interplay between circ_WHSC1 and miR-145-5p in breast cancer pathogenesis using in silico tools, assess their clinical relevance, and evaluate the diagnostic utility of circ_WHSC1 in clinical samples as a biomarker for breast cancer.
Materials and methods
This multi-component study employed a combination of bioinformatic analyses and laboratory validation. First, in silico tools were used to investigate miR-145-5p and circ_WHSC1 using public databases. Subsequently, their expression, correlation, and clinical relevance were experimentally assessed in a cohort of breast cancer patients.
Results
Circ_WHSC1 level was significantly higher in breast tumor compared with patient-matched adjacent normal tissues (4.17-fold change, p-value <0.01). Additionally, significant reduction of miR-145-5p (9.11-fold downregulation, p-value <0.01) level was detected in breast tumors compared with neighboring non-tumor tissues. A weak negative correlation was detected between levels of circ_WHSC1 and miR-145-5p (r = −0.314, p-value <0.05). Circ_WHSC1 may serve as a weak biomarker for breast cancer (AUC = 0.683; p-value <0.01) with 71 % specificity and 70 % sensitivity. Up-regulation of circ_WHSC1 in breast tumor was linked with lymph node invasion (p-value = 0.005), HER2 negativity (p-value = 0.031) and positive family history (p-value = 0.012).
Conclusion
Cumulatively, circ_WHSC1/miR-145-5p can be suggested as a potential molecular axis contributing to the pathogenesis of breast cancer. However, further functional assays are needed to validate this hypothesis.
{"title":"Potential role of circ_WHSC1 and miR-145-5p in breast cancer promotion","authors":"Maryam Abtin , Asghar Hosseinzadeh , Nahid Nafisi , Ramesh Omranipour , Leyla Sahebi , Mohsen Ahmadi , Soudeh Ghafouri-Fard , Abbas Shakoori","doi":"10.1016/j.bbrep.2026.102472","DOIUrl":"10.1016/j.bbrep.2026.102472","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to investigate the potential interplay between <em>circ_WHSC1</em> and <em>miR-145-5p</em> in breast cancer pathogenesis using <em>in silico</em> tools, assess their clinical relevance, and evaluate the diagnostic utility of <em>circ_WHSC1</em> in clinical samples as a biomarker for breast cancer.</div></div><div><h3>Materials and methods</h3><div>This multi-component study employed a combination of bioinformatic analyses and laboratory validation. First, <em>in silico</em> tools were used to investigate <em>miR-145-5p</em> and <em>circ_WHSC1</em> using public databases. Subsequently, their expression, correlation, and clinical relevance were experimentally assessed in a cohort of breast cancer patients.</div></div><div><h3>Results</h3><div><em>Circ_WHSC1</em> level was significantly higher in breast tumor compared with patient-matched adjacent normal tissues (4.17-fold change, p-value <0.01). Additionally, significant reduction of <em>miR-145-5p</em> (9.11-fold downregulation, p-value <0.01) level was detected in breast tumors compared with neighboring non-tumor tissues. A weak negative correlation was detected between levels of <em>circ_WHSC1</em> and <em>miR-145-5p</em> (r = −0.314, p-value <0.05). <em>Circ_WHSC1</em> may serve as a weak biomarker for breast cancer (AUC = 0.683; p-value <0.01) with 71 % specificity and 70 % sensitivity. Up-regulation of <em>circ_WHSC1</em> in breast tumor was linked with lymph node invasion (p-value = 0.005), HER2 negativity (p-value = 0.031) and positive family history (p-value = 0.012).</div></div><div><h3>Conclusion</h3><div>Cumulatively, <em>circ_WHSC1/miR-145-5p</em> can be suggested as a potential molecular axis contributing to the pathogenesis of breast cancer. However, further functional assays are needed to validate this hypothesis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102472"},"PeriodicalIF":2.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073715","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 : 2026-01-29DOI: 10.1016/j.bbrep.2026.102470
Lara Gentemann , Fabian Röpken , Philipp Joel Mroch , Nils Noltemeyer , Sören Donath , Anna Elisabeth Seidler , Christopher Werlein , Patrick Zardo , Lavinia Neubert , Danny Jonigk , Hans-Gerd Fieguth , Alexander Heisterkamp , Katherina Sewald , Stefan Kalies
Precision-cut lung slices (PCLS) are a complex three-dimensional ex vivo model system comprised of all resident cell types of the lung, thus closely mimicking the in vivo situation in regards to structural composition and function. The herein described application of a precise airway epithelial lesion via femtosecond laser-based nanosurgery and subsequent longitudinal imaging via two-photon or confocal microscopy enables the examination of the tissue's repair responses on a single-cell level. Allowing for live observation of intercellular cross-talk, this study demonstrates an endogenous repair program is induced in human PCLS upon damage induction. As early reaction to a small epithelial lesion, physiological stress responses, including transient airway constriction and increased mucus secretion, occur, followed by epithelial restitution within 24 h. Automated cell detection and subsequent cell track analysis reveal a more linearly confined cellular movement in the course of repair. Further, non-stationary, motile cells directly interact with cell debris, thereby contributing to final resolution of the lesion. Together, these findings emphasize the suitability of PCLS, combined with localized laser-based damage induction and state-of-the-art microscopy techniques, as a model system to study complex intercellular interactions in the course of endogenous repair processes.
{"title":"Live imaging of human airway epithelial repair in precision-cut lung slices after targeted cell damage","authors":"Lara Gentemann , Fabian Röpken , Philipp Joel Mroch , Nils Noltemeyer , Sören Donath , Anna Elisabeth Seidler , Christopher Werlein , Patrick Zardo , Lavinia Neubert , Danny Jonigk , Hans-Gerd Fieguth , Alexander Heisterkamp , Katherina Sewald , Stefan Kalies","doi":"10.1016/j.bbrep.2026.102470","DOIUrl":"10.1016/j.bbrep.2026.102470","url":null,"abstract":"<div><div>Precision-cut lung slices (PCLS) are a complex three-dimensional <em>ex vivo</em> model system comprised of all resident cell types of the lung, thus closely mimicking the <em>in vivo</em> situation in regards to structural composition and function. The herein described application of a precise airway epithelial lesion via femtosecond laser-based nanosurgery and subsequent longitudinal imaging via two-photon or confocal microscopy enables the examination of the tissue's repair responses on a single-cell level. Allowing for live observation of intercellular cross-talk, this study demonstrates an endogenous repair program is induced in human PCLS upon damage induction. As early reaction to a small epithelial lesion, physiological stress responses, including transient airway constriction and increased mucus secretion, occur, followed by epithelial restitution within 24 h. Automated cell detection and subsequent cell track analysis reveal a more linearly confined cellular movement in the course of repair. Further, non-stationary, motile cells directly interact with cell debris, thereby contributing to final resolution of the lesion. Together, these findings emphasize the suitability of PCLS, combined with localized laser-based damage induction and state-of-the-art microscopy techniques, as a model system to study complex intercellular interactions in the course of endogenous repair processes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102470"},"PeriodicalIF":2.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073716","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 : 2026-01-29DOI: 10.1016/j.bbrep.2026.102449
Houda Haddad , Reyadh R. AL-Rashidi , Ahmed Loghmari , Wissal Sahtout , Raja Boukadida , Rihem Dahmene , Emeny Ettouil , Houcemeddine Othman , Ines Ouahchi , Amira Zaϊri
The emergence of infections caused by multi-drug resistant bacteria (MDR) to antibiotic treatments poses a significant challenge in the healthcare field. Indeed, the resistance of MDR such as: Klebsiella pneumonia and Staphyloccus epidermidis to antibiotics has become an increasingly concerning issue, especially in hospital settings, necessitating the development of new therapies and more potent antimicrobial agents. Although numerous conventional antibiotic agents have been developed in recent years, but many of them still present toxicity to eukaryotic cells, despite their significant efficacy against multi-resistant microorganisms. Therefore, antimicrobial peptides (AMPs), particularly, dermaseptins (DRSs), are considered promising candidates against MDR, mainly due to their low toxicity and their different mode of action compared to conventional antibiotics. Indeed, these peptides are generally less likely to lead to the resistance phenomena observed for traditional antibiotics. The objectives of this study were to examine the physicochemical and structural properties of peptide derivatives of dermaseptin S4 and B2, and to ascertain their antibacterial potency against Staphylococcus epidermis and Klebsiella pneumoniae. The dermaseptin peptide derivatives used in this study were K4K20S4, K4S4(1–16), B2 and K3K4B2. In this research, we describe the synthesis and the bioactivity of DRSs and their derivatives against Staphylococcus epidermis and Klebsiella pneumoniae. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. The cytotoxicity of DRSs was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 6.25 to 25 μg/ml and Minimum Bactericidal Concentrations (MBCs) ranging from 12.5 to 50 μg/ml. In summary, these findings indicate that dermaseptins could serve as promising lead compounds for the development of potent antibacterial agents targeting infections caused by Klebsiella pneumoniae and Staphylococcus epidermidis.
{"title":"Antibacterial activity of peptide derivatives of dermaseptins against multidrug-resistant Klebsiella pneumoniae and Staphylococcus epidermis","authors":"Houda Haddad , Reyadh R. AL-Rashidi , Ahmed Loghmari , Wissal Sahtout , Raja Boukadida , Rihem Dahmene , Emeny Ettouil , Houcemeddine Othman , Ines Ouahchi , Amira Zaϊri","doi":"10.1016/j.bbrep.2026.102449","DOIUrl":"10.1016/j.bbrep.2026.102449","url":null,"abstract":"<div><div>The emergence of infections caused by multi-drug resistant bacteria (MDR) to antibiotic treatments poses a significant challenge in the healthcare field. Indeed, the resistance of MDR such as: <em>Klebsiella pneumonia</em> and <em>Staphyloccus epidermidis</em> to antibiotics has become an increasingly concerning issue, especially in hospital settings, necessitating the development of new therapies and more potent antimicrobial agents. Although numerous conventional antibiotic agents have been developed in recent years, but many of them still present toxicity to eukaryotic cells, despite their significant efficacy against multi-resistant microorganisms. Therefore, antimicrobial peptides (AMPs), particularly, dermaseptins (DRSs), are considered promising candidates against MDR, mainly due to their low toxicity and their different mode of action compared to conventional antibiotics. Indeed, these peptides are generally less likely to lead to the resistance phenomena observed for traditional antibiotics. The objectives of this study were to examine the physicochemical and structural properties of peptide derivatives of dermaseptin S4 and B2, and to ascertain their antibacterial potency against <em>Staphylococcus epidermis</em> and <em>Klebsiella pneumoniae.</em> The dermaseptin peptide derivatives used in this study were K<sub>4</sub>K<sub>20</sub>S4, K<sub>4</sub>S4(1–16), B2 and K<sub>3</sub>K<sub>4</sub>B2. In this research, we describe the synthesis and the bioactivity of DRSs and their derivatives against <em>Staphylococcus epidermis</em> and <em>Klebsiella pneumoniae</em>. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. The cytotoxicity of DRSs was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 6.25 to 25 μg/ml and Minimum Bactericidal Concentrations (MBCs) ranging from 12.5 to 50 μg/ml. In summary, these findings indicate that dermaseptins could serve as promising lead compounds for the development of potent antibacterial agents targeting infections caused by <em>Klebsiella pneumoniae</em> and <em>Staphylococcus epidermidis</em>.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102449"},"PeriodicalIF":2.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073826","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 : 2026-01-29DOI: 10.1016/j.bbrep.2026.102463
Fuminori Kawabata , Yuko Kawabata
Cattle frequently consume acidic feeds such as silage and are continuously exposed to acidic substances originating from ruminal fermentation during rumination. These acids are presumed to be detected via sour taste receptors expressed in taste buds; however, the functional properties of bovine sour taste receptors remain poorly understood. In this study, we focused on the bovine sour taste receptor candidate Otopetrin 1 (OTOP1) and characterized its functional responses to physiologically relevant dietary and ruminal acids, as well as its modulation by zinc ions. Bovine OTOP1 was heterologously expressed in HEK293T cells, and its acid responsiveness was evaluated using whole-cell patch clamp and membrane potential assays. Cells expressing bovine OTOP1 exhibited pH-dependent inward currents in response to HCl. In addition, bovine OTOP1 was activated by a range of organic acids present in cattle feed and the rumen, including formic, citric, malic, tartaric, lactic, acetic, butyric, and propionic acids. Furthermore, acid-induced OTOP1 currents were inhibited by zinc ions in a concentration-dependent manner. These findings demonstrate that bovine OTOP1 can function as a sour taste receptor responsive to multiple physiologically relevant acidic compounds.
{"title":"Functional characterization of the bovine sour taste receptor Otopetrin 1 (OTOP1) in response to dietary and ruminal acids","authors":"Fuminori Kawabata , Yuko Kawabata","doi":"10.1016/j.bbrep.2026.102463","DOIUrl":"10.1016/j.bbrep.2026.102463","url":null,"abstract":"<div><div>Cattle frequently consume acidic feeds such as silage and are continuously exposed to acidic substances originating from ruminal fermentation during rumination. These acids are presumed to be detected <em>via</em> sour taste receptors expressed in taste buds; however, the functional properties of bovine sour taste receptors remain poorly understood. In this study, we focused on the bovine sour taste receptor candidate Otopetrin 1 (OTOP1) and characterized its functional responses to physiologically relevant dietary and ruminal acids, as well as its modulation by zinc ions. Bovine OTOP1 was heterologously expressed in HEK293T cells, and its acid responsiveness was evaluated using whole-cell patch clamp and membrane potential assays. Cells expressing bovine OTOP1 exhibited pH-dependent inward currents in response to HCl. In addition, bovine OTOP1 was activated by a range of organic acids present in cattle feed and the rumen, including formic, citric, malic, tartaric, lactic, acetic, butyric, and propionic acids. Furthermore, acid-induced OTOP1 currents were inhibited by zinc ions in a concentration-dependent manner. These findings demonstrate that bovine OTOP1 can function as a sour taste receptor responsive to multiple physiologically relevant acidic compounds.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102463"},"PeriodicalIF":2.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073831","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 : 2026-01-29DOI: 10.1016/j.bbrep.2026.102465
Vikas Chandnani , Sanjay Tiwari , Manoj Bob , S.G. Vasantharaju , Gundawar Ravi , A. Supraja , Amol Pawar , Suhas Khandave , Sandeep Jagtap , Muddukrishna Badamane Sathyanarayana
Bevacizumab (BVZ) is an anti-vascular Endothelial Growth Factor-A monoclonal antibody (mAb) widely used in oncology and ophthalmology indications globally. Accurate quantification of mAbs in biological fluids is an essential prerequisite for determining pharmacokinetic (PK) parameters to assess the relationship between drug exposure and response. We developed and evaluated PK assays for BVZ in human serum using enzyme-linked immunosorbent assays (ELISA) and Meso Scale Discovery (MSD) immunoassay platforms to assess sensitivity and performance. The ELISA method, employing a Streptavidin-Biotin detection system with anti-idiotypic antibodies, demonstrated five times greater sensitivity than the conventional horseradish peroxidase-based ELISA format. The validated PK bridging ELISA achieved a quantification range of 10–220 ng/mL, extendable to 5000 ng/mL via dilution. In contrast, the MSD assay utilized electrochemiluminescence detection with Sulfo Tag labeling, offering a 20-fold higher sensitivity and detecting BVZ at concentrations as low as 500 pg/mL. This parallel evaluation concluded that ELISA is suitable for routine PK analysis due to its robustness and cost-efficiency. At the same time, MSD is advantageous for detecting BVZ at low concentrations in early-phase clinical trials and ophthalmic applications where serum levels are minimal.
{"title":"Bioanalytical methods for quantification of Bevacizumab in human serum: ELISA versus MSD","authors":"Vikas Chandnani , Sanjay Tiwari , Manoj Bob , S.G. Vasantharaju , Gundawar Ravi , A. Supraja , Amol Pawar , Suhas Khandave , Sandeep Jagtap , Muddukrishna Badamane Sathyanarayana","doi":"10.1016/j.bbrep.2026.102465","DOIUrl":"10.1016/j.bbrep.2026.102465","url":null,"abstract":"<div><div>Bevacizumab (BVZ) is an anti-vascular Endothelial Growth Factor-A monoclonal antibody (mAb) widely used in oncology and ophthalmology indications globally. Accurate quantification of mAbs in biological fluids is an essential prerequisite for determining pharmacokinetic (PK) parameters to assess the relationship between drug exposure and response. We developed and evaluated PK assays for BVZ in human serum using enzyme-linked immunosorbent assays (ELISA) and Meso Scale Discovery (MSD) immunoassay platforms to assess sensitivity and performance. The ELISA method, employing a Streptavidin-Biotin detection system with anti-idiotypic antibodies, demonstrated five times greater sensitivity than the conventional horseradish peroxidase-based ELISA format. The validated PK bridging ELISA achieved a quantification range of 10–220 ng/mL, extendable to 5000 ng/mL via dilution. In contrast, the MSD assay utilized electrochemiluminescence detection with Sulfo Tag labeling, offering a 20-fold higher sensitivity and detecting BVZ at concentrations as low as 500 pg/mL. This parallel evaluation concluded that ELISA is suitable for routine PK analysis due to its robustness and cost-efficiency. At the same time, MSD is advantageous for detecting BVZ at low concentrations in early-phase clinical trials and ophthalmic applications where serum levels are minimal.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102465"},"PeriodicalIF":2.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073713","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 : 2026-01-28DOI: 10.1016/j.bbrep.2026.102452
Mohammadreza Rahimian , Mohammad Aghazadeh-Soltan-Ahmadi , Bahman Panahi
The unique and underexplored aquatic ecosystems of Iran represent a significant reservoir of microbial diversity. This study presents the first comprehensive genomic survey of 38 native Iranian bacterial strains from hypersaline lakes and wetlands, integrating in silico analyses of their secondary metabolome, bacteriocin potential, resident prophages, and genomic architecture. Our genome mining revealed a prolific capacity for secondary metabolite production, identifying dozens of biosynthetic gene clusters (BGCs). Ectoine biosynthesis was ubiquitous, underscoring its role as a key osmoprotectant, while diverse BGCs for terpenes, polyketides, and hybrid metabolites were also prevalent. Concurrently, we identified a wide array of ribosomally synthesized and post-translationally modified peptides (RiPPs), including known bacteriocins. Furthermore, we characterized eight high-quality prophages integrated within these genomes, encoding auxiliary genes such as carbohydrate-active enzymes (CAZymes) and putative anti-CRISPR (ACR) proteins. The bacterial hosts themselves were equipped with robust defense systems, with CRISPR-Cas loci, predominantly Type I, detected in most strains. Crucially, we identified multi-functional genomic islands that physically link BGCs with defense systems (e.g., CRISPR-Cas, restriction-modification) and prophage regions. We propose the “Fortress Hypothesis” to explain this architecture, wherein the co-localization of metabolite production and defense machinery protects metabolic investment against phage predation and genetic loss. This integrative genomic arrangement highlights a sophisticated co-evolutionary strategy for survival in extreme environments. Our findings position these indigenous bacteria as a promising genetic repository for discovering novel bioactive compounds, enzymes, and biotechnological tools, with implications for antibiotic discovery, CRISPR modulation, and understanding adaptive microbial genomics in extreme niches.
{"title":"In silico exploration of the genomic repertoire of Iranian aquatic bacteria: Prophage carriage, bioactive compound potential, CRISPR-Cas immunity, and integrated defensive-metabolic islands","authors":"Mohammadreza Rahimian , Mohammad Aghazadeh-Soltan-Ahmadi , Bahman Panahi","doi":"10.1016/j.bbrep.2026.102452","DOIUrl":"10.1016/j.bbrep.2026.102452","url":null,"abstract":"<div><div>The unique and underexplored aquatic ecosystems of Iran represent a significant reservoir of microbial diversity. This study presents the first comprehensive genomic survey of 38 native Iranian bacterial strains from hypersaline lakes and wetlands, integrating in silico analyses of their secondary metabolome, bacteriocin potential, resident prophages, and genomic architecture. Our genome mining revealed a prolific capacity for secondary metabolite production, identifying dozens of biosynthetic gene clusters (BGCs). Ectoine biosynthesis was ubiquitous, underscoring its role as a key osmoprotectant, while diverse BGCs for terpenes, polyketides, and hybrid metabolites were also prevalent. Concurrently, we identified a wide array of ribosomally synthesized and post-translationally modified peptides (RiPPs), including known bacteriocins. Furthermore, we characterized eight high-quality prophages integrated within these genomes, encoding auxiliary genes such as carbohydrate-active enzymes (CAZymes) and putative <em>anti</em>-CRISPR (ACR) proteins. The bacterial hosts themselves were equipped with robust defense systems, with CRISPR-Cas loci, predominantly Type I, detected in most strains. Crucially, we identified multi-functional genomic islands that physically link BGCs with defense systems (e.g., CRISPR-Cas, restriction-modification) and prophage regions. We propose the “Fortress Hypothesis” to explain this architecture, wherein the co-localization of metabolite production and defense machinery protects metabolic investment against phage predation and genetic loss. This integrative genomic arrangement highlights a sophisticated co-evolutionary strategy for survival in extreme environments. Our findings position these indigenous bacteria as a promising genetic repository for discovering novel bioactive compounds, enzymes, and biotechnological tools, with implications for antibiotic discovery, CRISPR modulation, and understanding adaptive microbial genomics in extreme niches.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102452"},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073832","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 : 2026-01-28DOI: 10.1016/j.bbrep.2026.102467
Maria Rita Assenza , Federica Barbagallo , Fabiola Moretti
Quiescence is a reversible, tightly regulated state in which cells exit the cell cycle while retaining the potential to re-enter proliferation upon an appropriate stimulus. In solid tumors, quiescent cancer cells are thought to contribute to therapy resistance and disease relapse, especially in poorly vascularized regions. Detecting these dormant cells could be key to predicting therapeutic outcomes and personalizing treatment. To assess the metabolic state of individual cells, we developed a fluorescence-based method using acridine orange (AO) staining, paired with algorithm-driven quantification. By measuring AO-RNA and AO-DNA signals, we distinguished metabolic differences in 3D non-small cell lung cancer spheroids. The RNA/DNA staining ratio correlated with transcriptional activity, validating this approach as a reliable readout of cell state. This method provides a powerful tool to uncover hidden pockets of drug-resistant, quiescent cancer cells in 3D culture.
{"title":"A workflow for quantifying cell quiescence in 3D spheroids","authors":"Maria Rita Assenza , Federica Barbagallo , Fabiola Moretti","doi":"10.1016/j.bbrep.2026.102467","DOIUrl":"10.1016/j.bbrep.2026.102467","url":null,"abstract":"<div><div>Quiescence is a reversible, tightly regulated state in which cells exit the cell cycle while retaining the potential to re-enter proliferation upon an appropriate stimulus. In solid tumors, quiescent cancer cells are thought to contribute to therapy resistance and disease relapse, especially in poorly vascularized regions. Detecting these dormant cells could be key to predicting therapeutic outcomes and personalizing treatment. To assess the metabolic state of individual cells, we developed a fluorescence-based method using acridine orange (AO) staining, paired with algorithm-driven quantification. By measuring AO-RNA and AO-DNA signals, we distinguished metabolic differences in 3D non-small cell lung cancer spheroids. The RNA/DNA staining ratio correlated with transcriptional activity, validating this approach as a reliable readout of cell state. This method provides a powerful tool to uncover hidden pockets of drug-resistant, quiescent cancer cells in 3D culture.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102467"},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073639","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}
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