Yanqin Xu , Yalu Wu , Hao Zheng , Jiliang Zhao , Jingru Chen , Sijia Liu , Minghui Han , Fan Li , Feilong Zhou , Xiaoqi Zhang , Youjia Cao , Hongkai Zhang , Cuizhu Zhang
{"title":"CRISPR-based metabolic screening identifies PLCE1 as a pivotal regulator of oncolytic viral antitumor immunity via tumor immune microenvironment remodeling","authors":"Yanqin Xu , Yalu Wu , Hao Zheng , Jiliang Zhao , Jingru Chen , Sijia Liu , Minghui Han , Fan Li , Feilong Zhou , Xiaoqi Zhang , Youjia Cao , Hongkai Zhang , Cuizhu Zhang","doi":"10.1016/j.bbrc.2026.153505","DOIUrl":"10.1016/j.bbrc.2026.153505","url":null,"abstract":"<div><div>As a promising cancer immunotherapeutic agent, oncolytic viruses (OV) can specifically kill tumor cells and elicit systemic antitumor immune responses. However, the intrinsic resistance of tumors to oncolytic virotherapy severely limits its therapeutic efficacy. This study identified phospholipase C epsilon 1 (PLCE1) as a key negative regulator of OV antitumor effects via CRISPR-Cas9 metabolic gene screening in MC38 colorectal cancer model. PLCE1 inhibitor U-73122 enhanced OV infection efficiency and immunogenic cell death <em>in vitro</em>. <em>In vivo</em>, U-73122 combined with OV synergistically reduced tumor volume and prolonged survival. The combination therapy has been shown to remodel the tumor immune microenvironment, leading to an increase in CD45<sup>+</sup> immune cells and CD8<sup>+</sup> T cells, including naïve subsets, and a decrease in FOXP3<sup>+</sup> Treg cells. This shift promotes T cell activation by modulating relevant genes and signaling pathways. This study provides a novel target for optimizing OV immunotherapy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153505"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Zhao , Ronak Ansaripour , Deepti Singh , Guoxin Rong , Michael J. Young , Rebecca L. Carrier
{"title":"Novel explant model for human retinal progenitor cell transplantation","authors":"Peng Zhao , Ronak Ansaripour , Deepti Singh , Guoxin Rong , Michael J. Young , Rebecca L. Carrier","doi":"10.1016/j.bbrc.2026.153432","DOIUrl":"10.1016/j.bbrc.2026.153432","url":null,"abstract":"<div><div>Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, have led to vision loss for millions worldwide. While stem/progenitor cell transplantation shows promise, its clinical application is limited by poor survival, efflux, and low integration of transplanted cells. Biopolymer scaffolds have been explored to improve viability and differentiation, but most <em>in vitro</em> assessments rely on simplified or endpoint analyses that fail to capture dynamic behaviors. Retinal explant models, which preserve tissue architecture and neuronal connections, provide a more physiologically relevant platform. However, conventional explant models are often limited to endpoint analyses and lack real-time monitoring capabilities. Here, we developed a novel explant model for human retinal progenitor cell (hRPC) transplantation using porcine retinal tissue slice, agarose hydrogel, and confocal microscope with an incubation cage. Retinal tissue slices exhibited comparable viability before and after imaging. Alginate-based hydrogels containing hRPCs were injected adjacent to photoreceptor or ganglion cell layer of cross-sectional retinal tissue slices, enabling visualization of the cells’ position relative to retinal tissue slice over time. Real-time confocal imaging tracked key cellular behaviors, including migration, attachment, invasion, viability, and apoptosis. Injected hRPCs displayed random movement within the bulk alginate hydrogel and localized attachment or invasion at the hydrogel–tissue interface. Notably, laminin-incorporated alginate hydrogels promoted cell clustering and facilitated deeper invasion into retinal tissue compared with single cells.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153432"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MK-3903 alleviates myocardial ischemia/reperfusion injury and mitochondrial dysfunction associated with AMKP-PGC-1α signaling","authors":"Pang-Bo Li, Jing Gao, Hui-Hua Li, Wen-Xi Jiang","doi":"10.1016/j.bbrc.2026.153387","DOIUrl":"10.1016/j.bbrc.2026.153387","url":null,"abstract":"<div><div>Myocardial ischemia/reperfusion (I/R) injury frequently occurs in acute coronary artery disease after timely reperfusion to rescue the ischemic heart. AMP-activated protein kinase (AMPK) is a key sensor that regulates metabolic metabolism and mitochondrial function and protects against myocardial I/R injury. Thus, pharmacologically activating AMPK modulation of AMPK has been suggested as a potential approach for attenuating myocardial I/R injury. MK-3903 is a potent and selective activator of AMPK, but its importance and mechanism of action in modulating this disease remain unclear. I/R was modeled in wild-type mice pretreated with MK-3903 (30 mg/kg). In addition, hypoxia/reoxygenation (H/R) was modeled using neonatal rat cardiomyocytes (NRCMs), and these cells were treated with MK-3903 and SR-18292 (a PGC-1α inhibitor). Our results revealed that in I/R model mice, the administration of MK-3903 dramatically alleviated myocardial dysfunction; reduced the infarct size, myocyte apoptosis, oxidative stress and inflammation; along with increased AMPK-PGC-1α signaling, improved imitochondrial biogenesis and the balance of mitochondrial dynamics. Conversely, the treatment of NRCMs with SR-18292 markedly diminished the cardioprotective effects of MK-3903 following H/R <em>in vitro</em>. In conclusion, these data demonstrate that MK-3903 may attenuate myocardial I/R injury and mitochondrial dysfunction possibly by activating AMPK-PGC-1α signaling and highlight its potential as a candidate for further investigation in ischemic heart injury.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153387"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response surface methodology based Box-Behnken Design for statistical optimization of Curcuma caesia mediated copper oxide nanoparticles synthesis","authors":"Sakshi Sharma , Saurabh Srivastava , Abhishek Chaudhary","doi":"10.1016/j.bbrc.2026.153414","DOIUrl":"10.1016/j.bbrc.2026.153414","url":null,"abstract":"<div><div><em>Curcuma caesia</em>, a lesser known therapeutically potential herb, rich in bioactive compounds but still limitedly used for pharmaceutical applications due to poor solubility, stability and bioavailability of active constituents. To overcome these limitations, the present study aims to synthesis unipot copper oxide nanoparticles through eco-friendly green synthesis approach using <em>Curcuma caesia</em> extract as stabilizing and reducing agent. The synthesised nanoparticles were initially optimized using one variable at a time approach followed by statistical validation through Response Surface Methodology framework based on Box-Behnken Design. Synthesised nanoparticles were further characterized using UV-Vis spectroscopy, FTIR, SEM, TEM and XRD which confirmed the crystalline spherical nanoparticles of 50-70 nm size with distinct Surface Plasmon Resonance peak at 430 nm. FTIR analysis revealed the synthesis mechanism including reduction and capping of nanoparticles with bioactive compound. Further, biological assays demonstrated that synthesised nanoparticles exhibited strong antioxidant activity with IC<sub>50</sub> value of 13.037 nM through DPPH assay followed by strong antibacterial activity, membrane lipid peroxidation (75.2-16.4%), anti-inflammatory (62-72%) and anti-diabetic activity (36.62-59.79%). These findings highlight the potential of <em>Curcuma caesia</em> mediated copper oxide nanoparticles as strong therapeutic agent and directing it towards biomedical applications.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153414"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"bucky ball mRNA is responsive to the total RNA content in the fertilized zebrafish oocyte","authors":"Divya Chaubey , Dheeraj Chandra Joshi , Sanovar Dayal , Shweta Verma , Chetana Sachidanandan , Beena Pillai","doi":"10.1016/j.bbrc.2026.153328","DOIUrl":"10.1016/j.bbrc.2026.153328","url":null,"abstract":"<div><div>The DNA to cytoplasm ratio in the early stages of development is long held theoretically to be the determinant by which zygotic genome activation is synchronized with cell number. Through rapid cell divisions, the DNA increases, while the cytoplasm remains constant, causing a steady increase in the DNA: cytoplasm ratio until eventually transcription of the zygotic genome is initiated. However, the mechanism by which the embryo computes the DNA to cytoplasm ratio is not known. Here, we show that the mRNA for the gene <em>bucky ball</em> increases when the RNA pool in the oocyte is artificially increased at the single-cell stage. <em>bucky ball</em> mRNA is inherited in the unfertilized oocyte, rapidly degraded during the first few cell divisions, and never expressed again. Ectopic injection of multiple zebrafish lncRNAs, translation competent mRNA, irrespective of its capping status, and even a human lncRNA would all lead to the persistence of <em>bucky ball</em> mRNA at 11 hpf, well beyond its normal period of expression. We propose that degradation dynamics of <em>bucky ball</em> mRNA should be added to the growing list of factors including transcription factors, histones, and chromatin modifications that tightly regulate the timing of the maternal to zygotic transition in response to DNA: cytoplasm ratio.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153328"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An effective tumor-inhibiting siRNA delivery platform","authors":"Qixin Leng, A. James Mixson","doi":"10.1016/j.bbrc.2026.153430","DOIUrl":"10.1016/j.bbrc.2026.153430","url":null,"abstract":"<div><div>We recently found that combining two histidine-lysine (HK) peptides effectively delivered siRNA and silenced their tumor targets. One HK peptide stabilized the siRNA within the polyplex, while the other primarily targeted the NRP-1 receptor. This receptor is often overexpressed in tumors, particularly aggressive ones. In this study, we investigated the antitumor efficacy of this delivery system against the triple-negative breast cancer cell line MDA-MB-231. These cells express high levels of NRP-1, making them a suitable model for this approach. Two tumor-promoting oncogenes, Raf-1 or PD-L1, were targeted with the systemically delivered HK peptide polyplex in an athymic mouse model. The siRaf-1 and siPD-L1 polyplexes reduced tumor size by 75% and 82%, respectively, compared with the siControl polyplex. The size reduction of these tumors, achieved through siRNA therapy, was confirmed by decreased levels of Raf-1 and PD-L1 proteins. We observed no weight differences between the therapeutic and untreated groups. These promising results should encourage further development of siRNA therapy with this carrier platform.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153430"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transient replication of bovine mitochondrial DNA and subsequent placental development in mouse embryos","authors":"Masaya Komatsu , Hanako Bai , Masashi Takahashi , Manabu Kawahara","doi":"10.1016/j.bbrc.2026.153431","DOIUrl":"10.1016/j.bbrc.2026.153431","url":null,"abstract":"<div><div>Mitochondrial DNA (mtDNA) replication during early development is believed to depend on species-specific coordination between the mitochondrial and nuclear genomes. Here, we examined the fate and developmental consequences of bovine mtDNA introduced into mouse embryos using an interspecies mitochondrial transplantation model. Bovine mtDNA exhibited transient amplification during mouse preimplantation development, but declined at the blastocyst stage. Nevertheless, bovine mtDNA persisted in both embryonic and extraembryonic tissues after implantation. Using tetraploid complementation, we further demonstrated that mtB–M embryos developed enlarged placentas with expansion of the spongiotrophoblast layer, accompanied by upregulation of the <em>Sfmbt2</em>–<em>miR-466 m</em> axis. These findings highlight partial engagement of host replication machinery by heterologous mtDNA and species-specific constraints on mtDNA replication in shaping placental development <em>in vivo</em>.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153431"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristin Luer , Christian Marinus Huber , Pascal-Raphael Blersch , Diego Pallarola , Stefan Lyer
{"title":"Micro-/nanorobots in nanomedicine - Guidance, imaging and the integration of AI and robotics","authors":"Kristin Luer , Christian Marinus Huber , Pascal-Raphael Blersch , Diego Pallarola , Stefan Lyer","doi":"10.1016/j.bbrc.2026.153390","DOIUrl":"10.1016/j.bbrc.2026.153390","url":null,"abstract":"<div><div>The integration of robotics and artificial intelligence (AI) into nanomedicine represents a significant advancement in developing targeted therapeutic and diagnostic platforms. This field focuses on engineering micro- and nanoscale agents, such as magnetic nanoparticles (MNPs), microbots, and nanobots, for tasks like targeted therapies, sensing, and manipulation at diseased sites. MNPs are typically composed of iron oxides and serve as foundational components due to their biocompatibility, tunable surface chemistry, and responsiveness to external magnetic fields. They are used in targeted drug delivery, magnetic hyperthermia for tumor ablation, and as contrast agents in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI).</div><div>Microbots and nanobots, which often incorporate MNPs for propulsion, can be actively guided using external magnetic fields to navigate complex biological environments, perform micromanipulation, and enable triggered drug release. The precise control of these magnetic agents relies on electromagnetic or permanent magnet-based guidance systems, which balance magnetic force strength, workspace volume, and clinical integration. Other classes like biohybrid microbots or DNA nanobots, utilize magnetic field independent mechanisms for molecular sensing and cargo delivery.</div><div>AI and machine learning enhance these systems by optimizing material and bot design through in silico modeling, facilitating real-time navigation via medical imaging feedback, and enabling adaptive pathfinding. AI can also support swarm control and data analysis for diagnostic improvement. However, clinical translation faces challenges, including ensuring long-term biocompatibility and biodistribution, achieving scalable Good Manufacturing Practice (GMP) production, demonstrating therapeutic advantage in preclinical models, navigating evolving regulatory frameworks, and securing sufficient funding.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153390"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Imeglimin protects against acute kidney injury caused by transient ischemia","authors":"Hiroki Muramatsu , Naoto Yoshida , Kaori Suzuki , Kohei Ueda , Wakako Kawarazaki , Takeshi Marumo","doi":"10.1016/j.bbrc.2026.153437","DOIUrl":"10.1016/j.bbrc.2026.153437","url":null,"abstract":"<div><div>Imeglimin is a first-in-class oral antidiabetic that enhances glucose-induced insulin secretion and improves insulin resistance. Although imeglimin has been shown to exert protective effects on β-cells and hepatocytes partly by reducing the production of reactive oxygen species, its renoprotective effects remain largely unknown. In this study, we evaluated the effects of imeglimin on the kidneys using a mouse model of acute kidney injury induced by ischemia-reperfusion injury. Imeglimin significantly attenuated the increase in serum creatinine and blood urea nitrogen levels, as well as histological kidney injury. Gene ontology analysis of differentially expressed genes identified by RNA-sequencing of kidney tissues revealed that pathways related to inflammation were enriched in genes downregulated by imeglimin, whereas lipid metabolism and regulation of sodium ion transport were among the top enriched categories for genes upregulated by imeglimin. Moreover, ischemia-induced increase in the number of γH2AX-positive nuclei in proximal tubules was significantly suppressed by imeglimin. In addition, imeglimin inhibited increase in reactive oxygen species levels in human proximal tubule cells induced by transient hypoxia. These results indicate that imeglimin protects the kidney from ischemia-reperfusion injury by attenuating inflammatory responses and DNA damage, thereby maintaining gene expression associated with renal function. This protective effect may be partly mediated by a reduction in reactive oxygen species production. The potential of imeglimin to provide clinically meaningful protection against kidney complications warrants further investigation, considering the protective effects observed in ischemia-reperfusion injury.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153437"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William A. Kronert, Girish C. Melkani , Anju Melkani, Sanford I. Bernstein
{"title":"Drosophila myosin function and muscle structure are modulated by isoform-specific amino acid residues of the relay domain","authors":"William A. Kronert, Girish C. Melkani , Anju Melkani, Sanford I. Bernstein","doi":"10.1016/j.bbrc.2026.153439","DOIUrl":"10.1016/j.bbrc.2026.153439","url":null,"abstract":"<div><div>The relay domain of the myosin molecular motor communicates with the nucleotide binding site of the molecule, the actin-binding region, and the converter domain. Interactions between the relay and converter domains are critical for the converter to elicit movement of the lever arm, which yields the molecule's power stroke. An invariant tryptophan relay residue at the converter interface is flanked by two poorly conserved amino acids. Here we utilize mutant versions of the <em>Drosophila melanogaster</em> muscle myosin heavy chain to probe the function of these variable relay residues, residues 509 and 511. We replaced either or both poorly-conserved residues within an embryonic myosin isoform with those of the indirect flight muscle isoform. All such replacements eliminate <em>in vitro</em> actin motility, suggesting abnormal communication between the relay and converter domains that disables the power stroke. Interestingly, we found that the variations at residues 509 and 511 differentially disrupt both myosin ATPase activity and indirect flight muscle ultrastructure, with the double mutant showing the most severe effect upon ATPase activity and the least severe effect on emergent adult ultrastructure. Isoform-specific interactions may be implicated in these differential effects, as our molecular modeling at two stages of the mechanochemical cycle defined differences in contacts between the embryonic, flight muscle and chimeric 509 and 511 relay residues with a key residue in the converter domain. Overall, our studies show that two poorly conserved amino acid residues at the relay-converter interface are important to isoform-specific function of myosin and to the structural integrity of muscle.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"807 ","pages":"Article 153439"},"PeriodicalIF":2.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}