Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
Allograft inflammatory factor-1 in macrophages promotes renal tubular cell epithelial-mesenchymal transition via the NF-κB/IL-1β axis in diabetic kidney disease.
Wu Q, Hou D, Wang X … +5 more , Fu Y, Xing Y, Ji H, Sui M, Hao L
Biochem Biophys Res Commun · 2026 Jun · PMID 42349122 · Publisher ↗
Chronic inflammation and macrophage activation are hallmarks of diabetic kidney disease (DKD). Allograft inflammatory factor-1 (AIF-1), a macrophage-associated inflammatory protein, aggravates high glucose-induced inflam...
Chronic inflammation and macrophage activation are hallmarks of diabetic kidney disease (DKD). Allograft inflammatory factor-1 (AIF-1), a macrophage-associated inflammatory protein, aggravates high glucose-induced inflammation and oxidative stress in glomerular endothelial cells. However, its pathogenic role in macrophages remains unclear. In the present study, knockdown of AIF-1 by adeno-associated virus (AAV) in db/db mice improved renal function and ameliorated renal histopathological changes, with restored E-cadherin expression and reduced α-SMA expression. Double immunofluorescence staining demonstrated that AIF-1 was predominantly localized in infiltrating macrophages in diabetic kidneys. To explore the underlying mechanisms, THP-1-derived macrophages and a macrophage-tubular epithelial cell coculture system were employed. Under high-glucose conditions, AIF-1 knockdown inhibited NF-κB activation and reduced interleukin-1β (IL-1β) secretion in macrophages, whereas AIF-1 overexpression enhanced both responses. In coculture experiments, AIF-1 overexpression in macrophages promoted epithelial-mesenchymal transition (EMT)-related changes in HK-2 cells, as evidenced by decreased E-cadherin expression and increased α-SMA expression. Neutralization of IL-1β with canakinumab partially reversed the EMT changes induced by AIF-1 overexpression, indicating that IL-1β is a key mediator of macrophage-tubular epithelial cell communication. In conclusion, AIF-1 in macrophages promotes EMT of renal tubular epithelial cells through the NF-κB/IL-1β axis and may represent a potential therapeutic target for DKD.
Redirected T-cell cytotoxicity identifies BRD9-PTGES axis as an immune-sensitising vulnerability in ovarian cancer.
Guo S, Shi P, Yang C … +4 more , Qian S, Yang F, Yin X, Sun B
Biochem Biophys Res Commun · 2026 Jun · PMID 42349121 · Publisher ↗
Ovarian cancer shows limited responsiveness to immune checkpoint blockade, suggesting that malignant cells harbor intrinsic programs capable of suppressing T cell-mediated antitumor immunity. To uncover these programs un...
Ovarian cancer shows limited responsiveness to immune checkpoint blockade, suggesting that malignant cells harbor intrinsic programs capable of suppressing T cell-mediated antitumor immunity. To uncover these programs under fixed recognition signal conditions, the research team established and optimized a B7H3×CD3-based, MHC-independent redirected cytotoxicity platform, which generated a reproducible partial-killing window. By screening 1796 bioactive compounds in paired SKOV3 monocultures and SKOV3/PBMC co-cultures, the researchers distinguished immune-sensitizing perturbations from direct cytotoxic agents and identified I-BRD9, a selective BRD9 bromodomain inhibitor, as a top candidate. I-BRD9 enhanced T cell-mediated killing in ovarian cancer models, B7-H3-positive benchmark cell lines, and patient-derived ovarian tumor suspensions, without affecting tumor cell or PBMC viability. Cross-cell line RNA-seq analysis revealed that BRD9 inhibition reshapes a coordinated immune resistance program involving PGE2 biosynthesis, inhibitory ligands, T cell-attracting chemokines, antigen presentation-related transcripts, and extracellular matrix features. Within this program, siRNA-mediated PTGES knockdown functionally recapitulated key effects of I-BRD9 by restoring chemokine/PGE2-axis transcripts, promoting CD8 T-cell proliferation and IFN-γ production, and enhancing T-cell effector-associated gene expression. These findings establish the BRD9-PTGES/PGE2 axis as an actionable tumor-intrinsic pathway that limits ovarian cancer sensitivity to T cell-mediated cytotoxicity.
A three-gene signature (ABCE1, ATAD5, FUT4) for colorectal cancer prognosis: integrative analysis of transcriptomic, single-cell, and machine learning data.
Wang Y, Wang T, He J … +6 more , Zhang T, Jin R, Chen D, Hu Z, Pang Q, Liu H
Biochem Biophys Res Commun · 2026 Jun · PMID 42349120 · Publisher ↗
Colorectal cancer (CRC) remains a leading cause of cancer-related death, highlighting an unmet need for robust, mechanistically grounded prognostic biomarkers. Through an integrative multi-omics approach, we identified a...
Colorectal cancer (CRC) remains a leading cause of cancer-related death, highlighting an unmet need for robust, mechanistically grounded prognostic biomarkers. Through an integrative multi-omics approach, we identified and validated a novel three-gene signature for CRC. Utilizing paired tumor and adjacent tissues from 15 patients, public datasets (TCGA, GSE231559), and machine learning (LASSO, SVM-RFE), we derived a signature comprising ABCE1, ATAD5, and FUT4. These genes were consistently upregulated in tumors, as confirmed by qPCR, and are functionally linked to core oncogenic pathways: ABCE1 (protein synthesis/immune modulation), ATAD5 (DNA replication stress response), and FUT4 (cell adhesion/immune evasion). The signature demonstrated high diagnostic accuracy (AUC 0.85) and significant prognostic value, stratifying patients into distinct risk groups with divergent survival outcomes. Single-cell RNA-seq analysis localized expression to specific cellular compartments, while immune deconvolution revealed a correlated macrophage-dominated microenvironment. A clinically interpretable nomogram was developed with excellent calibration. This study establishes a compact, biologically coherent three-gene signature as a promising tissue-based molecular classifier for CRC, offering novel insights into the intertwined mechanisms of metabolism, genomic instability, and immune suppression, and presenting potential targets for therapeutic development.
Circadian dysregulation of voltage-gated ion channels orchestrates cross-organ electrophysiological remodeling and therapeutic timing.
Mohammadiaria M
Biochem Biophys Res Commun · 2026 Jun · PMID 42349119 · Publisher ↗
Disruption of intrinsic circadian rhythms alters cellular electrophysiology, promoting disease across multiple organ systems. We show that dysregulation of core clock genes (BMAL1, CLOCK, PER, CRY) remodels voltage-gated...
Disruption of intrinsic circadian rhythms alters cellular electrophysiology, promoting disease across multiple organ systems. We show that dysregulation of core clock genes (BMAL1, CLOCK, PER, CRY) remodels voltage-gated ion-channel (VGIC) expression, leading to sustained depolarization, impaired repolarization, and oxidative stress, unifying malignant and degenerative phenotypes. Integrative transcriptomic analysis across multi-organ datasets (GSE130408, GSE62944, TCGA-BRCA, TCGA-LAML, GSE56473) revealed consistent signatures: upregulation of sodium channels (SCN family), suppression of potassium channels (KCNQ, KCNH), and membrane potential drift toward -45 mV. In neuronal simulations, Vm shifted from -63 to -50 mV with a 2.3-fold ROS increase and firing rates rising from 2.5 to 6.7 Hz, reproducing seizure-like hyperexcitability. Retinal photoreceptors (rd10) depolarized from -65 to -47 mV, with a doubled burst index, indicating stress. In cardiac models and MEA-validated human iPSC-cardiomyocytes, SCN5A upregulation and KCNQ1/KCNH2 suppression prolonged action-potential duration by ∼35% and generated circadian oscillations in beat rate and field-potential duration, accurately predicted by a phase-aware LSTM network (r = 0.86 for BPM, r = 0.79 for FPD). In hematologic tissue, Gardos-channel impairment and TF/PAI-1 overexpression disrupted ROS-ATP coupling, accelerating leukemogenic and prothrombotic signaling. The LSTM model, trained on circadian multi-omic trajectories, predicted VGIC remodeling and cell-cycle transitions with >85% accuracy. Validation against published datasets via reanalysis in synchronized cell systems (MCF-10A → MDA-MB-231, U2OS, OCI-AML3) showed that NaV blockers (tetrodotoxin, lidocaine) or K openers (retigabine) restored rhythmicity, reduced ROS by ∼40%, and lowered proliferation by ∼35%. This integrative circadian-electrophysiological framework highlights tissue-specific trends in VGIC remodeling and suggests potential circadian-informed therapeutic strategies. While phase-dependent effects are supported in neuronal, retinal, and cardiac models, predictions for other organs remain inferred from transcriptomic data and require further experimental validation.
Functional characterization of PIK3CA E545A mutation in MCF-7 breast cancer cells reveals enhanced proliferation and resistance to Alpelisib.
Le HT, Nghi NB, My VD … +5 more , Vu HA, Thanh MC, Tri BM, Niem VVT, Phuong HA
Biochem Biophys Res Commun · 2026 Jun · PMID 42341421 · Publisher ↗
PIK3CA mutations are central oncogenic drivers in hormone receptor-positive, HER2-negative breast cancer; however, the functional and therapeutic relevance of noncanonical variants remains incompletely defined. The E545A...
PIK3CA mutations are central oncogenic drivers in hormone receptor-positive, HER2-negative breast cancer; however, the functional and therapeutic relevance of noncanonical variants remains incompletely defined. The E545A mutation, increasingly reported in specific patient populations, has not been systematically investigated. We generated an isogenic MCF-7 cell model harboring the PIK3CA E545A mutation using CRISPR/Cas9-mediated homology-directed repair to delineate its phenotypic and pharmacological consequences. E545A induced a robust gain-of-function phenotype, characterized by a mesenchymal-like morphological transition with reduced circularity and decreased cell size. This structural shift was accompanied by enhanced tumor cell fitness, including accelerated proliferation kinetics, increased metabolic activity, and significantly elevated clonogenic capacity compared with wild-type controls. Notably, growth trajectories showed sustained divergence between mutant and control cells across all time points, indicating a stable proliferative advantage. Importantly, E545A conferred diminished sensitivity to the PI3Kα inhibitor Alpelisib. Mutant cells retained migratory capacity under treatment and exhibited a pronounced, time-dependent increase in IC, consistent with adaptive resistance. Collectively, these findings identify E545A as a functionally active and therapeutically consequential PIK3CA variant. Our study expands the current understanding of PIK3CA-driven oncogenic diversity beyond canonical hotspot mutations and underscores the need for variant-resolved stratification to improve the efficacy of PI3K-targeted therapies.
Imeglimin enhances GLUT4-mediated glucose uptake and is more effective than metformin in 3T3-L1 adipocytes.
Takahashi N, Kimura AP, Yoshizaki T … +1 more , Ohmura K
Biochem Biophys Res Commun · 2026 Jun · PMID 42341420 · Publisher ↗
Imeglimin, a novel oral antidiabetic agent derived from metformin, improves insulin secretion and sensitivity in patients with type 2 diabetes. Recent clinical clamp studies have identified adipose tissue as a potential...
Imeglimin, a novel oral antidiabetic agent derived from metformin, improves insulin secretion and sensitivity in patients with type 2 diabetes. Recent clinical clamp studies have identified adipose tissue as a potential target of imeglimin; however, its direct effects on adipocytes are unclear. In this study, differentiated 3T3-L1 adipocytes were treated with imeglimin or metformin. We then examined glucose concentration in the culture medium, glucose uptake, plasma membrane glucose transporter expression, and the effects of signaling inhibitors. Imeglimin enhanced glucose uptake in a dose-dependent manner and reduced glucose concentration in the culture medium. Imeglimin was more effective than metformin at equivalent concentrations. Imeglimin also exerted an additive effect in the presence of insulin. Plasma membrane fractionation and immunoblotting revealed that imeglimin increased cell-surface glucose transporter (GLUT) 4 expression selectively, without altering total GLUT4 protein or plasma membrane GLUT1 levels. This suggests that increased GLUT4 translocation contributes to enhanced glucose uptake. Further, pharmacological inhibition studies demonstrated that imeglimin-induced glucose uptake was unaffected by AMPK inhibition but attenuated by inhibition of phosphoinositide 3-kinase, Akt, or protein kinase C. Additionally, the PI3K inhibitor Ly294002 suppressed imeglimin-induced GLUT4 accumulation at the plasma membrane. These findings identify adipocytes as a relevant cellular target of imeglimin and support, at least in part, the involvement of PI3K-dependent GLUT4 regulation in facilitating glucose transport, which may contribute to favorable effects of imeglimin on adipose tissue glucose metabolism in vivo.
The D-enantiomer of the antimicrobial peptide KLKLLLLLKLK-NH preferentially binds to lipopolysaccharide assemblies stabilized by divalent cations.
Sato S, Kawasaki K
Biochem Biophys Res Commun · 2026 Jun · PMID 42341419 · Publisher ↗
The all-D-enantiomer of the α-helical antimicrobial peptide KLKLLLLLKLK-NH (DL5), which is based on Sapecin B derived from the flesh fly Sarcophaga peregrina, exhibits superior antimicrobial activity compared to its L-fo...
The all-D-enantiomer of the α-helical antimicrobial peptide KLKLLLLLKLK-NH (DL5), which is based on Sapecin B derived from the flesh fly Sarcophaga peregrina, exhibits superior antimicrobial activity compared to its L-form counterpart (L5). While the enhanced efficacy of D-form peptides is conventionally attributed to their intrinsic resistance to proteolytic degradation, emerging evidence suggests stereoselective interactions with bacterial surface components may independently contribute to their biological activity. To elucidate this mechanism, we investigated the binding properties of these enantiomers to lipopolysaccharide (LPS), the primary structural component of the Gram-negative bacterial outer membrane, utilizing surface plasmon resonance (SPR). DL5 displayed a significantly higher affinity for LPS micelles, exhibiting an approximately 2.52-fold lower apparent dissociation constant than L5. Kinetic analysis further revealed that DL5 dissociated more slowly from LPS, indicating the formation of a highly stable peptide-LPS complex that may prolong interactions at the bacterial surface. Importantly, this enantiomeric divergence in binding affinity was accentuated under physiologically relevant conditions where divalent cations (Mg or Ca) bridge and stabilize the LPS assemblies, regardless of whether they adopt a micellar or a bilayer-like supramolecular morphology. Conversely, disrupting this structural stabilization by chelating endogenous cations with EDTA significantly reduced the affinity difference between the enantiomers. These findings demonstrate that DL5 preferentially recognizes the rigidified, cation-stabilized architecture of LPS aggregates. This specific stereochemical interaction provides a novel structural and mechanistic rationale for the enhanced efficacy of D-form antimicrobial peptides against Gram-negative pathogens.
Solubilized lignin promotes the growth of Akkermansia muciniphila and improves insulin sensitivity.
Kurakawa T, Fukushima S, Ami Y … +7 more , Chudan S, Arai Y, Tabuchi Y, Nagai Y, Kurihara S, Ikushiro S, Furusawa Y
Biochem Biophys Res Commun · 2026 Jun · PMID 42341418 · Publisher ↗
Solubilized lignin (SL) is a water-soluble derivative of lignin, which is typically classified as an insoluble dietary fiber and is predicted to possess structural and physicochemical properties that are distinct from th...
Solubilized lignin (SL) is a water-soluble derivative of lignin, which is typically classified as an insoluble dietary fiber and is predicted to possess structural and physicochemical properties that are distinct from those of conventional dietary fibers. In this study, we evaluated the effects of SL intake on gut microbial composition, intestinal barrier function, and insulin sensitivity in mice. SL supplementation significantly increased the abundance of Akkermansia muciniphila in both lean and diet-induced obese (DIO) mice. In vitro, SL supported the growth of A. muciniphila, suggesting a unique substrate-utilization mechanism. In DIO mice, SL intake improved insulin sensitivity, as evidenced by reduced blood glucose levels during insulin tolerance tests. Mechanistically, SL-induced increases in A. muciniphila were accompanied by modest improvements in intestinal barrier function and reduced expression of intestinal inflammatory markers, which may be associated with improved insulin sensitivity. In addition, predicted microbial pathway analysis indicated that SL-induced alterations in fecal carbohydrate metabolism may also be linked to improved glucose homeostasis. Collectively, these findings indicate that SL acts as a prebiotic for A. muciniphila and may ameliorate insulin sensitivity through the microbiota-mediated modulation of gut barrier integrity and metabolic function. Thus, SL intake may represent a novel dietary strategy for targeting specific gut microbes and mitigating metabolic disorders.
Modulating the magnetic properties of CoO nanostructures through Sr doping for spintronics applications and biosensing through antibacterial activity.
Rosy SJ, Murugesan P, Raj MSM
Biochem Biophys Res Commun · 2026 Jun · PMID 42341417 · Publisher ↗
The development of new magnetic materials with tunable properties has been the focus of significant research because of the quick development of spintronics, which utilizes the intrinsic spin of electrons in addition to...
The development of new magnetic materials with tunable properties has been the focus of significant research because of the quick development of spintronics, which utilizes the intrinsic spin of electrons in addition to their charge. Although CoO is a promising material for high-end spintronic devices because of its well-defined magnetic hysteresis, its weak ferromagnetic nature results in low saturation magnetization. In this work, a simple sol-gel approach was employed to synthesize Sr-doped CoO nanorods, which were successfully obtained with varying Sr dopant concentrations (1%, 2%, and 3%). With the incorporation of XRD, Raman Spectra, TEM, XPS, UV-Vis spectroscopy, and VSM, the structural, morphological, chemical, optical, and magnetic properties have all been examined. For both pure and doped samples, the XRD data validate the spinel cubic phase CoO crystalline structure with the space group Fd3m. The diameter and length of a typical individual nanorod, displayed in TEM images of 3% Sr-doped CoO, are 14 and 99 nm, respectively, with an aspect ratio of 7.1 nm. The Sr-doped CoO NPs' X-ray photoelectron spectroscopy (XPS) shows evidence of dopant incorporation. As the Sr content rises, the band gap falls from 1.50 eV to 1.31 eV, according to UV-Vis spectra. A weak ferromagnetism is established due to the doping, as evidenced by the notable 3% Sr-doped CoO nanorods with a robust ferromagnetic characteristic, which exhibit a maximum saturation magnetization of 0.59 emu/g at room temperature, higher than that of pristine CoO nanostructures. Additionally, this material contributes to a coercivity of 293.8 Oe and a remanence of 0.05 emu/g. 2% Sr-doped CoO exhibited the highest zone of inhibition against S. aureus (18 ± 0.32 mm at 1 mg/ml) among the studied samples, but pristine CoO was the most effective against E. coli (15 ± 0.24 mm at 1 mg/ml). Thus, Sr-doped CoO nanorods' potential as a promising bioactive material with antimicrobial applications is highlighted by their antibacterial activity. These findings denote the significance and enormous potential of Sr-doped CoO in the development of high-performance spintronic devices and antimicrobial applications.
Rapid screening approaches to identify and confirm lysosomotropic agents among ECCS class 2 basic drugs.
Enogieru OJ, Nguyen M, Zou L … +9 more , Abbasi A, Rodgers J, Bryniarski MA, Ko EC, Humphreys S, Li CY, Wahlstrom J, Bhamidipati RK, Chien HC
Biochem Biophys Res Commun · 2026 Jun · PMID 42341416 · Publisher ↗
Lysosomes are acidic organelles that function as the digestive system of the cell. Weak basic small molecule compounds can diffuse into lysosomes and become protonated and trapped in a phenomenon known as lysosomal seque...
Lysosomes are acidic organelles that function as the digestive system of the cell. Weak basic small molecule compounds can diffuse into lysosomes and become protonated and trapped in a phenomenon known as lysosomal sequestration or trapping. Lysosomal trapping can influence unbound drug concentrations at the site of action, and consequently, drug responses. Drug accumulation in lysosomes may also impair phospholipid metabolism, leading to a severe side effect called drug-induced phospholipidosis. Current methods used to evaluate lysosomotropism are either indirect (high-throughput, but low sensitivity) or direct (sensitive but time- and labor-intensive). Moreover, no validated in-silico lysosomotropism prediction tools are publicly available. In this study, we developed a rapid fluorescence-based platform to screen for lysosomotropism and quantify lysosomal trapping propensity (IC50) of compounds in a standardized way. We also apply this method to various compound libraries including BBB (Blood-Brain Barrier) and protein degrader/PROTAC (Proteolysis-Targeting Chimera) compounds. This platform confirmed basic ECCS (Extended Clearance Classification System) class 2 compounds as lysosomotropic, and other ECCS class compounds as non-lysosomotropic. Collectively, this study provides measurable and efficient tools (in-silico & in-vitro) to identify and measure lysosomotropism, which can be applied by preclinical programs to decipher causes of intracellular accumulation.
Impact of alcohol cessation on hepatic metabolic signaling during cancer cachexia.
Tice AL, Murphy RD, Laudato JA … +4 more , Tangen AR, Lima MJ, Gordon BS, Steiner JL
Biochem Biophys Res Commun · 2026 Jun · PMID 42341415 · Publisher ↗
UNLABELLED: The liver is central to macronutrient metabolism, with cancer and alcohol both impacting its function. The objective was to investigate the effects of alcohol use and its cessation, on hepatic gene expression...
UNLABELLED: The liver is central to macronutrient metabolism, with cancer and alcohol both impacting its function. The objective was to investigate the effects of alcohol use and its cessation, on hepatic gene expression for lipid metabolism and mitochondrial proteins during cachexia inducing distal site cancer. METHODS: Male CD2F1 mice were randomized to Control no cancer, Control-Cancer, prior alcohol (PE), PE-cancer, EtOH, or EtOH-cancer groups. Mice consumed control or alcohol (20% kcals from ethanol) liquid diet for 6 weeks, after which PE groups were weaned off alcohol. C26 colon carcinoma cells were implanted and 2 weeks later, livers were collected for RNA, cDNA, RT-PCR and Western blotting. RESULTS: Cancer lowered body weight and epidydimal adipose tissue weight, led to higher liver weight and greater percent weight loss. Alcohol also increased liver weight and reduced fat mass, while cessation attenuated body weight loss with cancer. Cancer increased genes related to lipid uptake and cholesterol synthesis, while genes for de novo lipogenesis and lipolysis were suppressed in the liver. Distal site cancer led to decrements in hepatic mitochondrial respiratory chain protein content and the mitophagy related proteins, DRP-1 and BNIP3. Alcohol also lowered DRP-1 and BNIP3 content. In non-cancer mice, the cessation of alcohol led to lower expression of cholesterol synthesis genes and higher levels of vATP5A (complex V) of the mitochondrial respiratory chain. CONCLUSION: Cessation of alcohol attenuates body weight loss due to cancer but has fewer effects on mitochondrial proteins, and genes regulating lipid balance in the liver.
SaPosin-like protein SPP-10 promotes apoptotic cell degradation in Caenorhabditis elegans.
Yuan L, Li P, Li C … +5 more , Xi Y, Liu F, Zheng Q, Wang H, Xiao H
Biochem Biophys Res Commun · 2026 Jun · PMID 42341414 · Publisher ↗
Apoptotic cell clearance is essential for maintaining tissue homeostasis and preventing inflammation. While the involvement of certain lysosomal proteins in apoptotic cell clearance has been established, the roles of oth...
Apoptotic cell clearance is essential for maintaining tissue homeostasis and preventing inflammation. While the involvement of certain lysosomal proteins in apoptotic cell clearance has been established, the roles of other lysosome-associated proteins remain unclear. Using genome-wide RNAi screening of lysosomal genes in Caenorhabditis elegans and tissue-specific analysis, we identified 14 lysosome-associated proteins crucial for apoptotic cell clearance, with the SaPosin-like protein SPP-10 being a key factor. The present study demonstrated that spp-10 defects significantly prolonged apoptotic cell persistence. Further investigations revealed that loss of spp-10 causes excessive accumulation of LAAT-1 and NUC-1 on phagolysosomes and sustained phagosomal acidification, which in turn impairs phagosomal degradation. The mammalian homolog of PSAP, whose knockdown reduces efferocytosis in mammalian cells, demonstrates that its function is evolutionarily conserved. Our findings reveal the essential role of spp-10 in apoptotic cell clearance and suggest that targeting lysosomal pathways may be a potential therapeutic strategy for diseases characterized by defective efferocytosis.
CIRBP maintains skeletal muscle mitochondrial energy homeostasis via mt-ATP6 to ameliorate sarcopenia.
Wang Z, Guo Y, Hu Z … +2 more , Zhang H, Liu Q
Biochem Biophys Res Commun · 2026 Jun · PMID 42335659 · Publisher ↗
Sarcopenia, characterized by progressive loss of skeletal muscle mass and function, represents a major public health challenge in aging societies; its underlying molecular mechanisms remain incompletely understood, and n...
Sarcopenia, characterized by progressive loss of skeletal muscle mass and function, represents a major public health challenge in aging societies; its underlying molecular mechanisms remain incompletely understood, and no approved disease-specific pharmacotherapy exists. Here, we demonstrate that CIRBP is essential for skeletal muscle homeostatic maintenance during aging. Eighteen-month-old Cirbp mice exhibited a canonical sarcopenic phenotype-reduced compound muscle action potential amplitude, decreased grip strength, accelerated fatigue, and prominent myofiber atrophy-accompanied by coordinate upregulation of the ubiquitin-proteasome effectors Atrogin-1, MuRF1, and Myostatin. Whole-transcriptome RNA sequencing identified 814 differentially expressed genes, predominantly downregulated, among which mt-Atp6-encoding mitochondrial ATP synthase subunit 6-exhibited the most pronounced reduction in absolute expression. CIRBP deficiency led to coordinate downregulation of Atp6 mRNA and ATP6 protein, accompanied by severe mitochondrial cristae disruption and oxidative phosphorylation dysfunction, collectively producing chronic energy insufficiency that drove protein degradation pathway activation and progressive myofiber atrophy. Conversely, AAV-mediated CIRBP overexpression simultaneously upregulated ATP6 expression, suppressed protein degradation pathway activation, and substantially improved skeletal muscle function in aged mice at both electrophysiological and mechanical levels. This study establishes the CIRBP-Atp6 mRNA-mitochondrial energy metabolism regulatory axis as a central node in skeletal muscle aging homeostasis, providing a new mechanistic framework and potential therapeutic targets for sarcopenia intervention.
Optimizing phage elution for biopanning of plastic materials.
Lyngsø NM, Otzen DE
Biochem Biophys Res Commun · 2026 Jun · PMID 42335658 · Publisher ↗
Biopanning of phage-displayed peptides is a useful method for peptide probe discovery and has been applied to multiple plastic targets. The most widely used elution method on plastic targets, acidic glycine buffer, is we...
Biopanning of phage-displayed peptides is a useful method for peptide probe discovery and has been applied to multiple plastic targets. The most widely used elution method on plastic targets, acidic glycine buffer, is well-established as a general binding disrupter for protein targets, but a comparative study of elution buffers for plastic targets has never been published. Here we demonstrate how elution from plastics with mild surfactant C12E8 or ethanol increases phage yield up to 1000-fold compared to the commonly used acidic elution while also yielding more diverse phage populations. This implies that the classical acidic elution method fails to recover a substantial fraction of plastic binding phage clones. The alternative elution methods described here should therefore be considered when applying biopanning to non-protein targets, where acidic elution is unlikely to disrupt binding through pH-induced conformational changes.
E-InfertilityTest: Implementing an explainable AI framework for male infertility assessment.
Das G, Ghosh B, Ghosh Z
Biochem Biophys Res Commun · 2026 Jun · PMID 42335657 · Publisher ↗
Male infertility has emerged as a significant concern in modern society, with genetic defects as one of the major underlying cause behind it. This impairment negatively impacts sperm motility and morphology, leading to c...
Male infertility has emerged as a significant concern in modern society, with genetic defects as one of the major underlying cause behind it. This impairment negatively impacts sperm motility and morphology, leading to conditions such as Asthenozoospermia (reduced sperm motility), Teratozoospermia (abnormal sperm morphology) and sometimes Asthenoteratozoospermia (both motility and morphology defects). Assisted reproductive technologies (ART), such as in-vitro fertilization (IVF), offer a potential solution for such cases but with a low success rate. Classical semen analysis provides only a phenotypic snapshot without revealing the fertilizing potential of the sperms. Hence, in order to screen the functional sperm population as well as to get a deeper insight into the reasons underlying the aberrant sperm population, it is important to study their genetic profile. In this work, we have performed a meta analysis of the transcriptomic data of infertile sperms from Asthenozoospermia and Teratozoospermia patients with that from fertile sperms of normal individuals. Thereafter we have screened a signature gene set which has been used to develop a prediction model named Explainable Infertility Test (E-InfertilityTest) to classify between fertile versus infertile sperm at the preliminary level. For each prediction, it will also provide the set of genes which are playing a dominant role towards such prediction. Thus, it will provide patient specific dominant gene expression profile responsible for the aberration. Overall, this AI based framework will serve as a proof-of-concept towards predicting the genetic basis associated with male infertility. User can access the tool named E-InfertilityTest as a standalone version on GitHub. Github Link: https://github.com/zglabDIB/einfertility.git.
Tetrastigma hemsleyanum ELN-derived miR-396b suppresses pancreatic cancer cell proliferation by targeting IL33.
Lv M, Ding W, Zhou M … +2 more , Xiang T, Zhang D
Biochem Biophys Res Commun · 2026 Jun · PMID 42335656 · Publisher ↗
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and remains largely refractory to current therapeutic strategies. Plant-derived exosome-like nanovesicles (ELNs) have recentl...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and remains largely refractory to current therapeutic strategies. Plant-derived exosome-like nanovesicles (ELNs) have recently emerged as promising natural nanocarriers capable of delivering bioactive molecules across kingdoms; however, their functional cargos and molecular mechanisms in PDAC remain poorly understood. METHODS: ELNs were isolated from Tetrastigma hemsleyanum and characterized by nanoparticle tracking analysis and zeta potential measurement. Cellular uptake was evaluated using PKH67 fluorescence labeling. Small RNA sequencing and RT-qPCR were performed to identify abundant ELN-associated miRNAs. The biological effects of ELNs and miR-396b were assessed by CCK-8 and colony formation assays. Transcriptomic profiling was conducted to identify downstream targets, and IL33 was validated by RT-qPCR, immunoblotting, bioinformatic prediction, and dual-luciferase reporter assays. Rescue experiments were further performed to investigate the functional involvement of the miR-396b/IL33 axis. RESULTS: T. hemsleyanum-derived ELNs were efficiently internalized by pancreatic cancer cells and inhibited cell proliferation in a dose-dependent manner. Small RNA sequencing identified miR-396b as a highly enriched ELN cargo. Both ELN treatment and miR-396b overexpression significantly reduced IL33 expression. Mechanistically, miR-396b directly bound the IL33 3' untranslated region and suppressed reporter activity, whereas mutation of the predicted binding site abolished this inhibitory effect. Functional rescue experiments demonstrated that inhibition of miR-396b attenuated ELN-mediated growth suppression, while IL33 re-expression partially reversed the anti-proliferative effects induced by miR-396b overexpression, indicating that the miR-396b/IL33 axis contributes substantially to the biological activity of ELNs. CONCLUSIONS: This study identifies miR-396b as a major functional cargo of T. hemsleyanum-derived ELNs and demonstrates that ELN-delivered miR-396b suppresses pancreatic cancer cell proliferation, at least in part, through direct repression of IL33. These findings provide mechanistic insight into a cross-kingdom ELN-miRNA-IL33 regulatory pathway and support the potential of plant-derived ELNs as a bioactive nanoplatform for PDAC intervention. Nevertheless, additional ELN cargos and in vivo validation warrant further investigation.
Developmental stage-dependent cellular plasticity governs β-cell reprogramming efficiency in human fibroblasts.
Raj N, Panneerselvam DS, Thummer RP
Biochem Biophys Res Commun · 2026 Jun · PMID 42335655 · Publisher ↗
Direct reprogramming of somatic cells into alternative lineages, bypassing a pluripotent intermediate state, represents a promising strategy to reduce the risks of tumorigenesis and genomic instability associated with in...
Direct reprogramming of somatic cells into alternative lineages, bypassing a pluripotent intermediate state, represents a promising strategy to reduce the risks of tumorigenesis and genomic instability associated with induced pluripotent stem cell-based approaches. Although β-cell-like cells have been efficiently generated from developmentally related endodermal sources such as acinar cells, ductal cells and α-cells, their derivation from phylogenetically distant cell types, such as fibroblasts, remains challenging. In this study, we employed lentiviral-mediated reprogramming using a polycistronic construct encoding the pancreatic transcription factors Neurog3, Pdx1 and MafA to enable β-cell-like formation from human fibroblasts. To assess the influence of developmental stage on reprogramming efficiency, fibroblasts derived from neonatal, juvenile and adult stages were analyzed comparatively. Transgene delivery, expression and functional effects were validated by reporter gene analysis, microscopy, flow cytometry, RT-qPCR and immunoblotting. Reprogrammed cells derived from neonatal fibroblasts exhibited the highest reprogramming efficiency, as demonstrated by robust induction of INS and MAFA expression, along with concurrent downregulation of fibroblast marker PRRX1. In contrast, reprogrammed cells derived from adult fibroblasts displayed markedly reduced responsiveness. Flow cytometry analysis revealed that approximately 38% of reprogrammed cells derived from neonatal fibroblasts acquired an INS-positive phenotype. Notably, reprogrammed cells derived from juvenile fibroblasts exhibited a higher proportion of GCG-expressing cells compared to those derived from neonatal fibroblasts, indicating a more pronounced heterogeneous endocrine-like state characteristic of intermediate stages of pancreatic differentiation in the former compared to the latter. Collectively, these findings demonstrate that the developmental stage significantly influences reprogramming competence, with neonatal fibroblasts representing a more permissive cell source for β-cell-like conversion. These results highlight developmental stage-dependent cellular plasticity as a key determinant of reprogramming efficiency and reveal the optimal cell sources for β-cell generation.
Circadian and sympathetic regulation of intestinal eosinophil abundance in mice.
Le HPT, Uchida Y, Nakamura Y … +1 more , Nakao A
Biochem Biophys Res Commun · 2026 Jun · PMID 42335654 · Publisher ↗
Eosinophils are abundant residents of the mouse small intestine under steady-state conditions. Their survival depends on the local cytokine milieu, including GM-CSF, and these cells contribute to the generation of IgA pl...
Eosinophils are abundant residents of the mouse small intestine under steady-state conditions. Their survival depends on the local cytokine milieu, including GM-CSF, and these cells contribute to the generation of IgA plasma cells. Here, we demonstrate that the abundance of small-intestinal eosinophils exhibits time-of-day variation accompanied by rhythmic GM-CSF expression. These oscillations were abolished in Clock-mutant mice, under disrupted light/dark cycles, and following pharmacological blockade of sympathetic nerve activity. Fecal IgA levels displayed similar temporal variation, which was likewise lost under these conditions. Together, these findings suggest that the circadian clock, potentially through sympathetic regulation of GM-CSF, helps coordinate eosinophil homeostasis and IgA production in the mouse small intestine.
Corrigendum to "Neutralizing serum amyloid a protects against sinusoidal endothelial cell damage and platelet aggregation during acetaminophen-induced liver injury" [Biochem. Biophys. Res. Commun. 639 (2023) Pages 20-28].
You K, Wang Y, Chen X … +11 more , Yang Z, Chen Y, Tan S, Tao J, Getachew A, Pan T, Xu Y, Zhuang Y, Yang F, Lin X, Li Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42331637 · Publisher ↗
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Formulation and characterization of 15d-PGJ2 loaded PLGA nanoparticles and in vitro evaluation of small intestinal submucosa integrated with nanoparticles for diabetic wound.
Koolabadi Z, Taghipour N, Rouhani M … +5 more , Soleimani M, Keshel SH, Rahimi A, Pourjabbar B, Saeedi Landi F
Biochem Biophys Res Commun · 2026 Jun · PMID 42330890 · Publisher ↗
Diabetic foot ulcers represent chronic and often non-healing wounds. Their treatment is particularly challenging due to persistent inflammation and infection, necessitating the exploration of innovative strategies for mo...
Diabetic foot ulcers represent chronic and often non-healing wounds. Their treatment is particularly challenging due to persistent inflammation and infection, necessitating the exploration of innovative strategies for more effective therapeutic approaches. This study aimed to develop a biodegradable extracellular matrix-mimicking wound dressing with anti-inflammatory properties designed to control inflammation and support cell proliferation and migration in the wound area. The anti-inflammatory drug prostaglandin J2 (15d-PGJ2) was encapsulated in PLGA nanoparticles (NPs). The average hydrodynamic size and zeta potential of 15d-PGJ2-loaded NPs were 261.6 nm and -14.3 mV, respectively, with a polydispersity index below 0.2. The entrapment efficiency and drug loading were 96.7% and 18.5%, respectively, with 50% of the drug released within 240 min. Cellular studies, including MTT assays and scratch tests, were performed to evaluate drug toxicity and determine the safe dose of NPs. Porcine small intestinal submucosa (SIS) sheets were cross-linked with EDC/NHS and integrated with NPs. The modified scaffolds were subjected to in vitro characterization, including FTIR analysis, enzymatic degradation, swelling behavior, contact angle measurements, mechanical evaluation, and cell adhesion studies. They demonstrated a hydrophilic surface with suitable water adsorption capacity, a low degradation rate, enhanced mechanical strength, and effective interaction with fibroblast cells. The EDC-crosslinked SIS scaffold carrying anti-inflammatory NPs exhibited promising characteristics based on its physicochemical and biological properties. Thus, it can be considered a suitable option for diabetic wound healing.
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