Yuanjing Zheng , Yue Li , Zhengyang Wei , Yang Wang , Yuanlin Liu , Fengsong Liu , Xue Li , Yi Zhang
{"title":"HUC-MSC-derived exosomal miR-16-5p attenuates inflammation via dual suppression of M1 macrophage polarization and Th1 differentiation","authors":"Yuanjing Zheng , Yue Li , Zhengyang Wei , Yang Wang , Yuanlin Liu , Fengsong Liu , Xue Li , Yi Zhang","doi":"10.1016/j.bbrep.2025.102078","DOIUrl":"10.1016/j.bbrep.2025.102078","url":null,"abstract":"<div><div>Nowadays mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising cell-free therapeutic alternative to MSC-based therapies, demonstrating efficacy in treating degenerative diseases, inflammatory disorders, and autoimmune diseases. MSC-Exos transport bioactive cargoes such as proteins, lipids, mRNAs, and microRNAs (miRNAs) to the recipient cells, mediating intercellular communication to regulate immunomodulation and tissue repair. However, the exosomal miRNA profile varies dynamically based on the culture conditions and tissue sources. Thus, elucidating the specific exosomal miRNA profile and regulatory targets is critical for the precise clinical applications and development of MSC-Exos-based cell-free therapies.</div><div>Here we established an optimized serum-free culture system for human umbilical cord-derived MSCs (hUC-MSCs) and determined the critical 48–72-h harvest window for exosome secretion. High-throughput sequencing identified miR-16-5p as the predominant exosomal miRNA, functioning as a core immunosuppressive effector by suppressing LPS/IFN-γ-induced M1 macrophage polarization and Th1 cell differentiation. Mechanistically, miR-16-5p was found to target key nodes in NF-κB and JAK-STAT pathways, validated via dual-luciferase assays. Additionally, miR-125b-5p and miR-34a-5p enhanced this immunosuppressive effect by co-targeting overlapping pathway components in NF-κB and JAK-STAT pathways, suggesting a multilayered regulatory network. Taken together, our findings highlight the potential of miRNA-engineered exosomes as standardized therapies for inflammatory disorders, emphasizing the importance of optimizing culture conditions and profiling miRNA expression over time in advancing clinical translation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102078"},"PeriodicalIF":2.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240808","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}
{"title":"Combination of AURKA inhibitor and MEK inhibitor strongly enhances G1 arrest and induces synergistic antitumor effect on KRAS or BRAF mutant colon cancer cells","authors":"Masashi Sato , Yoshiyuki Yamamoto , Toshikazu Moriwaki , Kuniaki Fukuda , Kiichiro Tsuchiya","doi":"10.1016/j.bbrep.2025.102073","DOIUrl":"10.1016/j.bbrep.2025.102073","url":null,"abstract":"<div><div>In colorectal cancer, <em>RAS</em> and <em>BRAF</em> are major mutation points in the RAS-MAPK signaling pathway. These gene mutations are known to be important causes of resistance to anti-EGFR antibody therapies. Recently, it has been reported that Aurora kinase A (AURKA), one of the mitotic kinases, interacts with the EGFR-RAS-MAPK signaling pathway. In this study, we examined whether the combination of MK-5108 (AURKA inhibitor) and trametinib (MEK inhibitor) enhanced the antitumor effect for colon cancer cell lines. The combination of MK-5108 and trametinib showed synergistic enhancements of antitumor effect in three colon cancer cell lines harboring <em>KRAS</em> or <em>BRAF</em> mutation. Cell cycle analysis showed induction of G2/M and G1 arrests by MK-5108 and trametinib, respectively, and the potential enhancement of G1 arrest with the two drug combination. The addition of MK-5108 to trametinib enhanced the suppression of <em>p</em>-ERK and other G1/S progression-related proteins expression. In HCT116 cells, harboring wild-type <em>TP53</em>, the combination therapy induced more potent cell proliferation suppression and apoptosis induction than in <em>TP53</em> knockout cells. These were related to potential enhancement of p53 expression and caspase activation. In conclusion, the combination of MK-5108 and trametinib may synergistically inhibit tumor cell division with or without <em>TP53</em> mutation, and with either <em>KRAS</em> or <em>BRAF</em> mutation. Furthermore, the combination therapy could be more effective in wild-type <em>TP53</em> cells.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102073"},"PeriodicalIF":2.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240806","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}
Kylie M. Foster , Ahmed M. El Banayosy , Zheila Azartash-Namin , Phillip Coghill , James W. Long , Edgar O'Rear , Hendra Setiadi
{"title":"Blood perfusion through ventricular assist devices induces erythrocytes to interact with leukocytes","authors":"Kylie M. Foster , Ahmed M. El Banayosy , Zheila Azartash-Namin , Phillip Coghill , James W. Long , Edgar O'Rear , Hendra Setiadi","doi":"10.1016/j.bbrep.2025.102085","DOIUrl":"10.1016/j.bbrep.2025.102085","url":null,"abstract":"<div><div>Implantations of Ventricular Assist Devices (VADs) have significantly improved quality of life and life expectancy of end-stage heart failure patients. However, despite the advancements in the VAD designs and patient management protocols, the VAD recipients remain at risk of attaining bleeding, infection, pump thrombosis, and stroke. Although blood trauma has been suggested as a critical factor in development of these adverse events, its consequences in inducing interactions between different types of blood cells are largely unknown.</div><div>Following our recent findings on erythrocyte and leukocyte trauma in VAD recipients, we decided to explore interactions between erythrocytes and leukocytes by perfusing human whole blood through two different types of VADs, HeartMate II (HMII) and HeartMate 3 (HM3), concurrently in their respective Blood Circulatory Loop (BCL). By using a flow cytometry assay, we found increasing association between erythrocytes and leukocytes as VADs propelled blood through their BCLs. This time-dependent intercellular association was shown by increasing concomitant events of stained CD235a (specifically expressed on erythrocytes) and stained CD45 (specifically expressed on leukocytes) in the CD235a<sup>+</sup> population. Compared to CentriMag (CM), which served as a control, VADs produced significantly higher concomitant signals. The findings described in this study have opened the need for further studies on a novel path for generation of adverse events that are commonly observed in VAD recipients, notably infection, pump thrombosis, and ischemic stroke.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102085"},"PeriodicalIF":2.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240933","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}
{"title":"Cytoplasmic physicochemical factors drive malignant transformation by adapting bioenergetic settings","authors":"Tattym E. Shaiken","doi":"10.1016/j.bbrep.2025.102079","DOIUrl":"10.1016/j.bbrep.2025.102079","url":null,"abstract":"<div><div>While significant insights have been gained by a study of cancer genetics, the roles of the cytoplasm in regulating chemical processes during the transformation to malignancy are often less appreciated. The cytoplasm functions as a two-phase system consisting of an elastic solid phase (the cytomatrix) and a viscous liquid phase (the cytosol). This finding has led to the development of a tumor progression model based on a two-phase system that connects genetic alterations with the physicochemical processes necessary for sustaining and facilitating malignant growth. Here, we show that the energy required for tumor growth is, in part, required for the cytomatrix activity, which accelerates chemical reactions. The ability to regulate cytomatrix motor proteins provides a mechanism to control whether a genetic mutation is able to induce the energy needed for cancer to develop and offers innovative strategies for cancer treatment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102079"},"PeriodicalIF":2.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240932","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}
{"title":"Engineering bacterial cell morphology for the design of robust cell factories","authors":"Maarten Lubbers, Nova Jaspers, Dennis Claessen","doi":"10.1016/j.bbrep.2025.102076","DOIUrl":"10.1016/j.bbrep.2025.102076","url":null,"abstract":"<div><div>Bacteria come in a wide variety of shapes, ranging from spherical or rod-shaped unicellular cells to complex multicellular structures. These shapes have evolved to benefit the organism in its natural environment. However, industry often takes such organisms from their natural environment to produce useful molecules that favor mankind. Their natural morphology is often far from optimal for use in an industrial setting. Filamentous bacteria, for instance, have a morphology that presents unique challenges for industrial settings. Therefore, various engineering approaches have been developed to optimize their morphology. This review explores a spectrum of successful engineering strategies, offering insights and providing inspiration for future advancements. It holds the potential to lead the way in optimizing morphology in challenging microorganisms and thus improve their exploitability in biotechnology.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102076"},"PeriodicalIF":2.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231061","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}
{"title":"Novel and efficient synthesis of 5-chloro-6-methoxy-3-(2-((1-(aryl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)benzo[d]isoxazole derivatives as new α-glucosidase inhibitors","authors":"Ram Reddy Mudireddy , Rambabu Gundla , Chandra Prakash Koraboina , Vani Madhuri Velavalapalli , Venkata Veernjaneya Sarma Dhulipalla , Gowri Sankararao Burle , Sreekantha B. Jonnalagadda , Naresh Kumar Katari","doi":"10.1016/j.bbrep.2025.102074","DOIUrl":"10.1016/j.bbrep.2025.102074","url":null,"abstract":"<div><div>A new series of benzisoxazole derivatives (<strong>9a-o</strong>) were designed by using molecular hybridization approach and synthesized <em>via</em> click-chemistry. All the synthesized compounds were evaluated for their α-glucosidase enzyme inhibition and antibacterial activity. All tested compounds (<strong>9a-o</strong>) exhibited a promising α-glucosidase inhibitory activity with IC<sub>50</sub> range of 14.69–38.71 nmol in comparison with the positive drug <strong>Acarbose</strong> (IC<sub>50</sub> 35.91 nmol). Additionally, these compounds have found to be active against <em>B. cereus</em> and <em>E. coli</em>. The <em>in vitro</em> inhibition results supported to <em>in silico</em>. Additionally, the compounds were subjected to computational drug-likeness/ADME testing, which revealed that this all the compounds had good ADME profiles in addition to exhibiting drug-like qualities. SAR indicates that analysis revealed that electron-withdrawing substituents such as Br and CF<sub>3</sub> at specific positions significantly enhanced α-glucosidase inhibition, while unsubstituted and ortho-methoxy phenyl derivatives also showed potent activity, highlighting the benzo[d]isoxazole–triazole scaffold as a promising pharmacophore for developing novel anti-diabetic agents.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102074"},"PeriodicalIF":2.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220857","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}
{"title":"Isolation, biochemical characterization, and primary structure and active site determination of Dioscorea opposita (‘Nagaimo’) oligopeptidase B","authors":"Sayaka Miyazaki-Katamura , Mami Chosei , Sota Tate , Tomohisa Sakaue , Takuya Yamane , Junko Suzuki , Shigeki Higashiyama , Iwao Ohkubo","doi":"10.1016/j.bbrep.2025.102071","DOIUrl":"10.1016/j.bbrep.2025.102071","url":null,"abstract":"<div><div>A protease was purified to homogeneity from <em>Dioscorea opposita “</em>Nagaimo” using ion exchange, hydrophobic and gel filtration columns, and its biochemical characterization including molecular weight, substrate specificity and kinetic parameters were determined. Protease activity was strongly inhibited by AEBSF, DCI and TLCK. The enzyme moderately inhibited by NEM and HgCl<sub>2</sub>. The enzyme activity inhibited by NEM and HgCl<sub>2</sub> was restored with the addition of β-ME. These findings suggest that the enzyme is a trypsin-like serine protease, which is regulated by SH compounds. The N-terminal amino acid of this protease is blocked in an unknown manner. We determined the structure of the cDNA and deduced amino acid sequence of the protease from <em>D. opposita</em>. The cDNA was composed of 2420 nucleotides and encoded 751 amino acids in the coding region. The results indicated that this enzyme is an oligopeptidase B (OPB), consisting of a N-terminal region (M<sup>1</sup> ∼ T4<sup>7</sup>), a N-terminal β-propeller domain (A<sup>48</sup>∼ L<sup>465</sup>), a connecting domain (K<sup>466</sup> ∼ D<sup>527</sup>), a peptidase_S9 domain (P<sup>528</sup> ∼ D<sup>744</sup>) and C-terminal region (R<sup>745</sup> ∼ S<sup>751</sup>). The overall homology of amino acid sequences of <em>D. opposita</em> to <em>D. alata</em> and <em>D. rotundata</em> was 99.07 % and 97.07 %, respectively. The catalytically active amino acid sites [S<sup>599</sup>, D<sup>684</sup>, and H<sup>719</sup>] among these yam species were found to be highly conserved. Site-directed mutagenesis confirmed that these three the active center.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102071"},"PeriodicalIF":2.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204346","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}
Kei-ichi Sugiyama , Petr Grúz , Kaoru Sato , Masamitsu Honma
{"title":"Effects of carminic acid on gene expressions under epigenetic regulation","authors":"Kei-ichi Sugiyama , Petr Grúz , Kaoru Sato , Masamitsu Honma","doi":"10.1016/j.bbrep.2025.102070","DOIUrl":"10.1016/j.bbrep.2025.102070","url":null,"abstract":"<div><div>Carminic acid, which is an anthracene derivative, is a dye used as a food additive. Although anthracene is considered not to be epigenetic modifier, some anthracene derivatives affect yeast flocculation that is under the epigenetic regulation. FLO assay can detect the expression of <em>Saccharomyces cerevisiae FLO1</em> gene that mediates the flocculation phenotype influenced by epigenetic regulation. FLO reporter assays showed that 5–20 μM carminic acid induced the <em>FLO1</em> promoter in wild type yeast as well as in the yeast transformed with human DNA methyltransferase genes, in the absence of rat liver homogenates. Furthermore, in mouse embryonic stem cell line EB3, carminic acid decreased the expression of <em>Oct3/4,</em> which is also under epigenetic regulation, and induced slight morphological changes. These results suggest that carminic acid, but not its metabolites, has the potential to alter the epigenetic state of the genome.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102070"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204345","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}
Himanshu , Gunjan , Ramendera Pati Pandey , Riya Mukherjee , Chung-Ming Chang
{"title":"Meta-analysis study of the therapeutic impact of Mesenchymal stem cells derived exosomes for chronic kidney diseases","authors":"Himanshu , Gunjan , Ramendera Pati Pandey , Riya Mukherjee , Chung-Ming Chang","doi":"10.1016/j.bbrep.2025.102072","DOIUrl":"10.1016/j.bbrep.2025.102072","url":null,"abstract":"<div><div>Mesenchymal stem cell-derived exosomes (EXOs) represent a promising avenue for treating chronic kidney diseases (CKD), though their precise impact remains somewhat elusive. To address this gap, we conducted a systematic analysis, scouring databases and clinical trial repositories for relevant studies from 2019 to 2023. Seventeen papers were meticulously selected for their focus on mesenchymal stem cell-derived exosomes (MSC-EXOs) and their potential in CKD treatment. Our comprehensive meta-analysis, incorporating 15 preclinical and 6 clinical studies, underscores the efficacy of MSC-EXOs in improving renal function while attenuating tubular injury, inflammation, apoptosis, collagen deposition, and renal fibrosis. Notably, post-treatment with MSC-EXOs exhibited significant associations with various CKD markers, with pooled proportions indicating a considerable impact on blood urea nitrogen (BUN) and serum creatinine (SCR) levels. Subgroup analyses based on animal models further elucidated heterogeneity within the studies. In conclusion, MSC-EXOs demonstrate promise in enhancing renal function and reducing CKD risk, as evidenced by both preclinical and clinical data. Their efficacy in lowering SCR and BUN levels while enhancing filtration rate suggests MSC-EXOs as a viable and secure alternative to cell-based therapies, thereby providing valuable insights for personalized CKD treatments despite inherent limitations.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102072"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204344","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}
{"title":"Fundamental mechanisms of cell death for polycystic ovary syndrome","authors":"Ying-ying Li, Yi-qiu Peng, Yu-xi Yang, Ning Xu, Ting-juan Shi, Rui-xia Liu, Ying-yi Luan, Cheng-hong Yin","doi":"10.1016/j.bbrep.2025.102043","DOIUrl":"10.1016/j.bbrep.2025.102043","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age with complex symptoms and multiple hormone imbalances. Patients usually present with irregular menstruation, ovarian cysts, and metabolic abnormalities. Current research has been found that multiple cell death programs may be involved in the occurrence of the disease. This article focuses on the mechanism between PCOS and six cell death processes including apoptosis, autophagy, ferroptosis, pyroptosis, NETosis and necroptosis. Ovarian granulosa cell apoptosis, autophagy, and ferroptosis play key roles in PCOS. In addition, pyroptosis and NETosis may also be involved, but the specific mechanism needs further study. In general, a deeper understanding of these cell death mechanisms will help develop innovative treatments for PCOS.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102043"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195628","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}