Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
GPAT3 is associated with lipid deposition and AMPK signaling in skeletal muscle.
Wang M, Gu W, Sheng Z … +2 more , Fan G, Yang X
Biochem Biophys Res Commun · 2026 Jun · PMID 42330889 · Publisher ↗
As metabolic disorders associated with excessive lipid deposition in skeletal muscle rise, strategies to alleviate this accumulation have emerged as a major focus in metabolic research. Glycerol-3-phosphate acyltransfera...
As metabolic disorders associated with excessive lipid deposition in skeletal muscle rise, strategies to alleviate this accumulation have emerged as a major focus in metabolic research. Glycerol-3-phosphate acyltransferase 3 (GPAT3) is a key enzyme in triglyceride biosynthesis; however, its role in muscle lipid metabolism remains unclear. In this study, we overexpressed or knocked down GPAT3 in C2C12 myoblasts to evaluate its effects on muscle lipid metabolism and then validated the findings in GPAT3 knockout (KO) mice. GPAT3 deficiency significantly reduced lipid deposition in muscle cells. In C2C12 cells, changes in GPAT3 expression were accompanied by alterations in AMPK signaling activity. These results demonstrate that GPAT3 promotes lipid deposition in skeletal muscle. Our in vitro data reveal a correlation between GPAT3 and AMPK signaling; further in vivo validation and functional assays are required to clarify the role of AMPK in this process. This study highlights GPAT3 as a potential therapeutic target for metabolic diseases characterized by excessive intramuscular lipids.
Functional expression of calcium homeostasis modulator 2 (CALHM2) regulates the bioenergetic transition of BV2 microglial cells.
Choi SW, Kim J, Yu J … +5 more , Park KS, Chung EDS, Kim G, Shin HM, Kim SJ
Biochem Biophys Res Commun · 2026 Jun · PMID 42330888 · Publisher ↗
Microglia play pivotal roles in neuroinflammation and central nervous system disorders. The Calcium Homeostasis Modulator (CALHM) family forms large-pore ion channels implicated in ATP release and mitochondrial function....
Microglia play pivotal roles in neuroinflammation and central nervous system disorders. The Calcium Homeostasis Modulator (CALHM) family forms large-pore ion channels implicated in ATP release and mitochondrial function. Here, we identified the functional expression of CALHM in BV2 microglial cells. Whole-cell patch-clamp recordings revealed a thermosensitive, voltage-gated slow outward current, consistent with the cloned CALHM channel current (I). RT-PCR confirmed that CALHM2 is the predominantly expressed isoform in BV2. CRISPR/Cas9-mediated knockout of Calhm2 (CALHM2) abolished the I in BV2. While ATP release and Ca influx rate was not affected, Seahorse XF analysis revealed an impaired metabolic flexibility in CALHM2. Specifically, the LPS-induced increase in the oxygen consumption rate (OCR) was abolished, and the extracellular acidification rate (ECAR) was reduced in the LPS-treated CALHM2 cells. These results demonstrate that CALHM2 in microglia might be essential for the metabolic shift required during inflammatory activation.
Inhibition of AGR2 triggers secretion of GRP78 and sensitizes gastroesophageal junction adenocarcinoma cells to ER stress.
Bourgery Q, Martin N, De Schutter C … +3 more , Flament S, Bray F, Pluquet O
Biochem Biophys Res Commun · 2026 Jun · PMID 42330887 · Publisher ↗
The endoplasmic reticulum (ER) chaperone Anterior Gradient 2 (AGR2) is overexpressed in various adenocarcinomas, promoting tumor progression and chemoresistance. However, its exact role in modulating the Unfolded Protein...
The endoplasmic reticulum (ER) chaperone Anterior Gradient 2 (AGR2) is overexpressed in various adenocarcinomas, promoting tumor progression and chemoresistance. However, its exact role in modulating the Unfolded Protein Response (UPR) and remodeling the cancer cell secretome under proteotoxic stress remains poorly understood. Using shRNA-mediated silencing of AGR2 combined with high-throughput LC-MS/MS proteomic analysis in OE19 gastroesophageal junction adenocarcinoma cells, we profiled the global changes in protein secretion under basal and tunicamycin-induced ER stress conditions. Proteomic screening identified 75 differentially secreted proteins, with AGR2 depletion triggering a widespread up-secretion phenotype. Bioinformatic analysis revealed enrichment in pathways related to glycolysis, antigen processing and presentation, and extracellular matrix components. Notably, the ER-resident chaperone GRP78 was identified as a critical hub protein within the secretome. AGR2 knockdown downregulated intracellular GRP78 expression, and compromised UPR activation. Under ER stress, the absence of AGR2 triggered a massive secretion of GRP78 in the extracellular space, which correlated with a significantly increased sensitivity to tunicamycin-induced cell death. These findings identify AGR2 as a key regulator of GRP78 proteostasis and ER retention. By controlling the balance between intracellular retention and extracellular release of GRP78, AGR2 supports adaptive ER stress response and may contribute to tumor cell survival in gastroesophageal junction adenocarcinoma.
In vitro alpha amylase and protein denaturation inhibitory activity of newer generation Schiff base Oxazolone derivatives: Synthesis, chemical characterization, molecular docking, MD simulation, DFT, ADMET, and bioactivity.
Saha S, Sarawat J, Elbouamri L … +1 more , Chtita S
Biochem Biophys Res Commun · 2026 Jun · PMID 42330886 · Publisher ↗
Chronic inflammation and diabetes mellitus are closely linked diseases and involved in metabolic dysfunction and disease pathogenesis. So, three new Oxazolone Schiff base derivatives (JS1A, JS2A and JS3A) were synthesize...
Chronic inflammation and diabetes mellitus are closely linked diseases and involved in metabolic dysfunction and disease pathogenesis. So, three new Oxazolone Schiff base derivatives (JS1A, JS2A and JS3A) were synthesized by a multi-step procedure, and then characterized by FTIR, H NMR, C NMR, mass spectrometry and elemental analysis. A series of synthetic compounds was screened by integrated computational and experimental studies to assess their antidiabetic and anti-inflammatory properties. Molecular docking studies with pancreatic α-amylase (4GQR) and cyclooxygenase-2 (6COX) revealed good binding interactions with the highest docking affinity of JS2A with both targets. Furthermore, the 100 ns molecular dynamics simulations showed that the protein-ligand complexes were stable, especially for JS2A. The synthesized derivatives have been analyzed using frontier molecular orbital and molecular electrostatic potential to identify suitable electronic properties, reactive sites, and interaction potentials. The drug-likeness, pharmacokinetic behavior, and low predicted toxicity were deemed acceptable based on ADMET prediction studies; improvements in solubility and permeability may be needed. All synthesized compounds showed α-amylase inhibitory and protein-denaturation inhibitory activities in vitro in a dose-dependent manner. Among the synthesized compounds, JS2A showed strong in vitro inhibitory activities against α-amylase and protein denaturation. Overall, these results indicate that Schiff base Oxazolone derivatives can be considered as multifunctional scaffolds with prospective antidiabetic and anti-inflammatory properties.
Midnolin maintains zebrafish body axis stability and a progressive neuromuscular regulatory cascade.
Zhao Y, Wu N, Liang L … +2 more , Liu Z, Ji G
Biochem Biophys Res Commun · 2026 Jun · PMID 42330885 · Publisher ↗
Midnolin (midn) is a conserved protein implicated in proteasomal degradation, yet its in vivo physiological role remains unclear. In this study, we investigated midn function using a zebrafish knockout model. midn was en...
Midnolin (midn) is a conserved protein implicated in proteasomal degradation, yet its in vivo physiological role remains unclear. In this study, we investigated midn function using a zebrafish knockout model. midn was enriched in the nervous system and somite muscles, with prominent localization in the brain primordium. CRISPR/Cas9-mediated midn deletion caused severe embryonic lethality (83.7% within 24 hpf) and increased apoptosis. Surviving mutants (14.6%) developed progressive body axis instability, including head tilting and abdominal asymmetry, with penetrance increasing from 8% at 4 mpf to 64% at 9 mpf. Adult mutants also exhibited reduced thigmotaxis and altered locomotor patterns. Transcriptomic profiling and scRNA-seq virtual knockout analysis identified muscle-associated lineages and programs as prominent sites of sensitivity to midn perturbation. Integrative analysis further suggested a candidate regulatory framework in which early changes in runx1, mafbb, and btg2 are associated with later dysregulation of neuromuscular junction -associated and muscle-structural genes, including robo3, cd81a, myog, and efemp2b. These findings demonstrate that midn is required for embryonic survival and long-term body axis stability, and implicate disrupted muscle-associated regulatory programs in midn-deficient phenotypes.
ILDR2 impairs antitumor surveillance by recruiting immunosuppressive CCR2 monocytes.
Nagatomo Y, Zhang C, Lu Y … +2 more , Widyagarini A, Nagai S
Biochem Biophys Res Commun · 2026 Jun · PMID 42323923 · Publisher ↗
B7 family co-inhibitory molecules play a crucial role in maintaining homeostasis and preventing chronic inflammation. However, they also impede antitumor immune responses. Immunoglobulin-like domain-containing receptor 2...
B7 family co-inhibitory molecules play a crucial role in maintaining homeostasis and preventing chronic inflammation. However, they also impede antitumor immune responses. Immunoglobulin-like domain-containing receptor 2 (ILDR2) is a B7 family member that modulates T cell activation. Previous studies demonstrated that its blockade synergizes with PD-L1 inhibition in mouse tumor models. Although ILDR2 likely contributes to immune evasion, the precise underlying mechanism remains unknown. Here, we investigated the effect of ILDR2 on the tumor microenvironment (TME) in a mouse squamous cell carcinoma (SCCVII) model. We generated ILDR2-expressing SCCVII cells (ILDR2-SCCVII) through transduction of the extracellular and transmembrane domains of ILDR2. Compared to control vector-transduced cells (Cont-SCCVII), ILDR2-SCCVII cells resulted in accelerated tumor growth and a reduced ratio of activated T cells in the TME 21 days after inoculation. At this late stage, most tumor-infiltrating leukocytes were Ly6C- F4/80 CD206 M2-like macrophages. Interestingly, at an earlier time point, we observed the increased infiltration of Ly6C F4/80/ monocytes-potential macrophage precursors-in ILDR2-SCCVII tumors. Whereas CCL2 expression was enhanced early after inoculation in both groups, its receptor CCR2 was more highly expressed on Ly6C F4/80/ monocytes specifically in the ILDR2-SCCVII group. Using our in-house anti-mILDR2 monoclonal antibody and ILDR2-Ig, we found that early recruited myeloid cells preferentially expressed ILDR2 and exhibited ILDR2-Ig binding. These results suggest that tumor-expressing ILDR2 interacts with myeloid cells during the early stages of tumor development, inducing premature monocyte accumulation via the CCL2-CCR2 axis. This early shift toward an M2 macrophage-mediated immunosuppressive environment likely accelerates tumor growth.
Ambra1 is essential for fasting-induced lipolysis via ATGL translocation to lipid droplets.
Kashikawa T, Akatsuka H, Suzuki T … +4 more , Hosokawa H, Yamamoto N, Hozumi K, Sato T
Biochem Biophys Res Commun · 2026 Jun · PMID 42322818 · Publisher ↗
Ambra1, a key regulator of protein homeostasis, controls both autophagy and ubiquitin-mediated proteasomal degradation. Although Ambra1 is implicated in metabolic regulation, its role in adipose tissue homeostasis remain...
Ambra1, a key regulator of protein homeostasis, controls both autophagy and ubiquitin-mediated proteasomal degradation. Although Ambra1 is implicated in metabolic regulation, its role in adipose tissue homeostasis remains unclear. In this study, Ambra1 conditional knockout mice exhibited impaired fasting-induced weight loss in white adipose tissue. Ambra1-deficient adipocytes exhibited defective lipolysis, accompanied by impaired translocation of adipose triglyceride lipase (ATGL), the rate-limiting lipolytic enzyme, to the surface of lipid droplets. However, ATGL translocation was restored by the inhibition of phosphodiesterase 3B, which antagonizes lipolysis by reducing protein kinase A activity. Collectively, these findings suggest that Ambra1 plays an important role in fasting-induced lipolysis via phosphodiesterase 3B-mediated ATGL control.
Canadine (tetrahydroberberine) as a GyrB-Targeting antibacterial lead against Acinetobacter baumannii: Integrated phenotypic, computational, and enzymatic evidence.
Alasiri A
Biochem Biophys Res Commun · 2026 Jun · PMID 42322817 · Publisher ↗
The global rise of antimicrobial resistance among Gram-negative hospital pathogens urgently demands new antibacterial candidates supported by both phenotypic activity and mechanistic evidence. Here, canadine (tetrahydrob...
The global rise of antimicrobial resistance among Gram-negative hospital pathogens urgently demands new antibacterial candidates supported by both phenotypic activity and mechanistic evidence. Here, canadine (tetrahydroberberine), a principal alkaloid of Hydrastis canadensis L., was evaluated as an antibacterial lead against berberine. Target nomination via reverse pharmacophore mapping (PharmMapper), followed by bacterial-target filtering, prioritized DNA gyrase subunit B (GyrB) for mechanistic investigation. Whole-cell antibacterial activity, assessed by broth microdilution against a panel of pathogenic bacteria, revealed that canadine exhibited consistently superior activity to berberine, including enhanced inhibition of Acinetobacter baumannii. Structure-based docking against the A. baumannii GyrB crystal structure (PDB: 7PQL), validated by redocking of the co-crystallized inhibitor (RMSD = 1.68 Å), yielded a favorable docking score for canadine (-10.5 kcal/mol), approaching that of the co-crystallized ligand (-10.8 kcal/mol) and outperforming berberine. Molecular dynamics simulations (100 ns) demonstrated stable canadine-GyrB complexes with lower conformational deviation and reduced energetic fluctuation relative to berberine. Interaction-energy decomposition identified van der Waals forces as the primary stabilizing contributions, with electrostatic interactions serving as secondary modulators. Binding free-energy calculations further supported favorable canadine-GyrB association (ΔG = -9.57 kcal/mol). In vitro E. coli DNA gyrase inhibition assays confirmed greater inhibitory potency for canadine over berberine. Collectively, these findings establish canadine as a mechanistically credible GyrB-targeting antibacterial lead with superior performance to berberine across phenotypic, computational, and biochemical assessments, warranting further optimization through structure-activity relationship studies, selectivity profiling, and translational evaluation against multidrug-resistant A. baumannii.
Dual transcriptomic analysis of Toxoplasma gondii infection in a human PBMC ex vivo model.
Acosta Dávila JA, Arenas-Soto AF, Aranda LA … +1 more , Gómez Marín JE
Biochem Biophys Res Commun · 2026 Jun · PMID 42322816 · Publisher ↗
The mechanisms governing host-parasite interactions in human toxoplasmosis remain insufficiently characterized, as research has relied on murine models that fail to capture human cellular responses. Murine resistance to...
The mechanisms governing host-parasite interactions in human toxoplasmosis remain insufficiently characterized, as research has relied on murine models that fail to capture human cellular responses. Murine resistance to Toxoplasma gondii depends on the IL-12/IFN-γ axis and immunity-related GTPases (IRGs); however, these differ in humans due to the absence of TLR11/12 and a distinct IRG repertoire. We implemented the EXMOWS (ex vivo model without supplements) to investigate early human host-parasite interactions without the biological artifacts induced by fetal bovine serum (FBS) or cryopreservation. Peripheral blood mononuclear cells (PBMCs) were freshly isolated from five healthy individuals (three Toxoplasma IgG+, two seronegative) and infected with T. gondii (RH strain; multiplicity of infection, 1:3) in supplement-free media. Global transcriptional profiling was performed using dual RNA-seq at 0, 1, and 6 h post-infection (hpi). We identified differentially expressed host genes (DEGs), characterized by potent early activation of innate immune sensing, nuclear factor-κB (NF-κB) signalling, and type I/II interferon signalling pathways. Key overexpressed hubs included IL1B, IL1A, CXCL8, IL6, and TNF, whereas NFBIA and IL10 were significantly downregulated. Simultaneously, T. gondii modulated hundreds of genes, including major virulence factors, such as ROP16, ROP18, GRA7, and GRA15. The EXMOWS model reveals that human primary cells initiate a robust transcriptional Th1 and NF-κB response within 6 h of infection, potentially preceding or overcoming early parasite-mediated suppressive mechanisms. These results provide a standardized, high-resolution framework for identifying protective molecular signatures in human toxoplasmosis.
Single-cell analysis revealed potential mechanisms of biomarkers related to polyamine metabolism in osteoarthritis.
Zhang K, Zhang Y, Chen S … +6 more , Liu Z, Yang W, Yu Y, Lv Z, Feng Y, Zhang Y
Biochem Biophys Res Commun · 2026 Jun · PMID 42322815 · Publisher ↗
Many studies have shown that polyamine metabolism is associated with the development of osteoarthritis (OA), but the exact mechanism is unclear. In this study, OA datasets were obtained from the public database to screen...
Many studies have shown that polyamine metabolism is associated with the development of osteoarthritis (OA), but the exact mechanism is unclear. In this study, OA datasets were obtained from the public database to screen differentially expressed genes (DEGs). Key module genes for polyamine metabolism were identified through weighted gene co-expression network analysis (WGCNA). We identified 129 DEGs and 1210 key module genes associated with polyamine metabolism, revealing 29 candidate genes with significant involvement in key biological functions and pathways, including the PI3K-Akt and hippo signaling pathways. The potential biomarkers underwent feature selection through machine learning to determine their diagnostic effectiveness via receiver operating characteristic (ROC) curve. Specific, COL5A3, COL6A1, and PNPLA2, demonstrated diagnostic potential with area under the curve (AUC) value above 0.7. In addition, single-cell analyses showed significant differences in biomarkers between OA and control in both hypertrophic chondrocyte (HTC) and fibrocartilage chondrocytes (FC). Finally, human chondrosarcoma cell line (SW1353) was treated with interleukin-1β to establish an OA cell model for the verification of biomarker expression. RT-qPCR results showed that COL5A3, COL6A1, and PNPLA2 were significantly downregulated in the OA group, which was consistent with the results of public database. In conclusion, combined with database analysis and cellular experiments, this study confirmed that COL5A3, COL6A1 and PNPLA2 were potential biomarkers for OA, which provided support for exploring related molecular mechanisms and screening biomarkers of the disease.
Piperlongumine attenuates knee osteoarthritis progression by eliminating senescent meniscus cells and chondrocytes.
Endo K, Ozeki N, Koga H … +1 more , Sekiya I
Biochem Biophys Res Commun · 2026 Jun · PMID 42322814 · Publisher ↗
OBJECTIVE: Cellular senescence in cartilage is a driver of knee osteoarthritis (OA) progression, but its role in the meniscus remains unclear. This study investigated whether senescent cells accumulate in both meniscus a...
OBJECTIVE: Cellular senescence in cartilage is a driver of knee osteoarthritis (OA) progression, but its role in the meniscus remains unclear. This study investigated whether senescent cells accumulate in both meniscus and cartilage during OA, aiming to identify senolytic drugs for their selective elimination. METHODS: Senescence and senescence-associated secretory phenotype (SASP) marker expression was assessed in meniscus and cartilage of OA-induced rats. Rat meniscus cells (MCs) and chondrocytes (CCs) were rendered senescent with H2O2 and treated with candidate senolytics, including piperlongumine (PL). Transcriptomic analysis was performed to explore the PL mechanism. PL effects were also tested in OA patient-derived MCs and CCs. Finally, PL was administered to OA rats to evaluate its effect on OA progression. RESULTS: Senescence markers (p16, p21) and SASP factors (MMP3, MMP9, MMP13, MCP1) were upregulated in the OA rat meniscus and cartilage. PL outperformed other senolytics, selectively eliminating senescent MCs and CCs without harming normal cells. Transcriptomic analysis revealed that PL altered reactive oxygen species (ROS)-related pathways specifically in senescent cells, while cotreatment with ROS scavengers completely blocked PL-induced cell death. In human OA MCs and CCs, PL reduced senescent cell numbers and enhanced glycosaminoglycan production. In OA rats, PL treatment alleviated meniscus and cartilage degeneration, decreased senescence and SASP marker expression, and suppressed synovitis. CONCLUSION: This study provides the first direct evidence of meniscal senescence in OA and demonstrates that PL can selectively clear senescent MCs and CCs, attenuating OA progression. These findings highlight the strong potential of PL as a disease-modifying OA drug.
Corrigendum to "Lactoferrin inhibits dexamethasone-induced chondrocyte impairment from osteoarthritic cartilage through up-regulation of extracellular signal-regulated kinase 1/2 and suppression of FASL, FAS, and Caspase 3" [Biochem. Biophys. Res. Commun. 441 (1) (2013) 249-255].
Tu Y, Xue H, Francis W … +4 more , Davies AP, Pallister I, Kanamarlapudi V, Xia Z
Biochem Biophys Res Commun · 2026 Aug · PMID 42321025 · Publisher ↗
Abstract loading — click title to view on PubMed.
A conserved strand-swap mechanism drives heterodimerization of E-cadherin and P-cadherin.
Kumari P, Ghosh D, Samanta D
Biochem Biophys Res Commun · 2026 Jun · PMID 42320300 · Publisher ↗
Cadherins are cell surface glycoproteins that mediate calcium-dependent cell-to-cell adhesion and maintain tissue integrity. Among classical cadherins, E-cadherin and P-cadherin are often co-expressed in epithelial tissu...
Cadherins are cell surface glycoproteins that mediate calcium-dependent cell-to-cell adhesion and maintain tissue integrity. Among classical cadherins, E-cadherin and P-cadherin are often co-expressed in epithelial tissues and contribute to adherens junction formation. E-cadherin is the principal component of adherens junctions in most epithelial cells, whereas P-cadherin is co-expressed with E-cadherin but is localized predominantly to the basal proliferative layer of epithelia. Although heterophilic interactions between these cadherins have been observed, the biophysical properties and molecular determinants governing their heterodimerization remain poorly defined. Here, we present a comprehensive biophysical characterization of the E-cadherin: P-cadherin heterodimer using surface plasmon resonance (SPR) and structure-guided mutational analyses. SPR studies revealed a direct, calcium-dependent interaction between their extracellular domains, with micromolar affinities that are physiologically relevant and comparable to those reported for classical cadherin interactions. Furthermore, structure-guided mutational analyses targeting residues within the membrane-distal ectodomain demonstrated that key residues identified in canonical strand-swap dimerization are also essential for the heterodimer formation.
Integrated multi-omics identification and experimental validation of ACSL4-associated ferroptotic lipid remodeling in drug-induced acute liver failure.
Wang Y, Wang Y, Yuan J … +3 more , Dong S, Zhao X, Jia J
Biochem Biophys Res Commun · 2026 Jun · PMID 42320299 · Publisher ↗
BACKGROUND: Acute liver failure due to Drug-induced liver injury (DILI-ALF) is a life-threatening syndrome with rapid progression and high mortality. Although oxidative stress and lipid peroxidation are implicated, the m...
BACKGROUND: Acute liver failure due to Drug-induced liver injury (DILI-ALF) is a life-threatening syndrome with rapid progression and high mortality. Although oxidative stress and lipid peroxidation are implicated, the molecular mechanisms underlying DILI-ALF remain incompletely understood. This study aimed to explored the molecular mechanisms of DILI-ALF. METHODS: We performed an integrated analysis combining proteomic profiling of liver tissues from patients with DILI-ALF, reanalysis of public single-cell transcriptomic data, and experimental validation in human liver tissues and an acetaminophen (APAP)-induced liver failure model. Lipid peroxidation, ultrastructural changes, and ACSL4 expression were assessed using biochemical assays, transmission electron microscopy, western blotting, immunohistochemistry. RESULTS: Proteomic analysis revealed significant enrichment of lipid peroxidation and ferroptosis-related pathways in DILI-ALF, with ACSL4 identified as a prominently dysregulated molecule. Single-cell transcriptomic analysis further showed increased ACSL4 expression in specific hepatocytes populations during DILI-ALF. In liver tissues from patients with DILI-ALF, increased ACSL4 expression was accompanied by elevated malondialdehyde and lipid peroxide levels, as well as mitochondrial abnormalities consistent with ferroptosis-associated injury. Similar findings were observed in APAP-induced mouse livers, whereas inhibition of ACSL4 could significantly attenuated levels of lipid peroxidation and liver injury. CONCLUSION: These study identifies and validates an ACSL4-associated ferroptotic lipid peroxidation signature and support the involvement of ferroptosis-related lipid remodeling in the pathogenesis of in DILI-ALF. ACSL4 may represent a potential biomarker and therapeutic target for this severe condition.
Exosome-like nanoparticles derived from Salvia miltiorrhiza promote diabetic wound healing by reducing oxidative stress and inflammation.
Bai B, Song Y, Tian L
Biochem Biophys Res Commun · 2026 Jun · PMID 42320298 · Publisher ↗
Chronic non-healing wounds remain a major cause of amputation and mortality for diabetic patients. Therefore, finding effective treatment options has become a significant issue that biomedical research needs to address....
Chronic non-healing wounds remain a major cause of amputation and mortality for diabetic patients. Therefore, finding effective treatment options has become a significant issue that biomedical research needs to address. Nanovesicles that resemble exosomes participate in intercellular communication in plants and may transfer bioactive substances between animals and plants with implications for regenerative medicine. Salvia miltiorrhiza, a traditional medicinal plant, has been used for centuries to treat cardiovascular diseases, infections, inflammation, and wounds. However, little is known of exosome-like nanovesicles derived from Salvia miltiorrhiza (SmELNs), including any actions to promote wound healing in diabetic patients. SmELNs were isolated and identified in the current work and assessment of their impact on proliferation, migration and angiogenesis in vitro indicated the potential to promote diabetic wound healing. In diabetic mouse wound models, subcutaneous SmELN rescued the delayed wound healing caused by streptozotocin-induced diabetes, promoted the formation of new blood vessels and did not damage internal organs in vivo. Subsequent studies further revealed that SmELN reduced reactive oxygen species production in response to high blood sugar and reduced secretion of inflammatory factors, IL-6, IL-1β and TNF-α. These findings suggest that the SmELN-enriched preparation represents a promising natural nanotherapeutic candidate for diabetic wound repair, potentially through attenuation of oxidative stress and inflammatory responses.
Bombyx mori p53 requires multiple domains for transcription-dependent apoptosis induction.
Sugiura W, Ikeda M, Hamajima R
Biochem Biophys Res Commun · 2026 Jun · PMID 42320297 · Publisher ↗
The transcription factor p53 is widely conserved among vertebrates and invertebrates and regulates various stress responses, including apoptosis. p53 proteins identified in the lepidopteran insects Bombyx mori (Bm-p53) a...
The transcription factor p53 is widely conserved among vertebrates and invertebrates and regulates various stress responses, including apoptosis. p53 proteins identified in the lepidopteran insects Bombyx mori (Bm-p53) and Spodoptera frugiperda exhibit proapoptotic activity through transient expression; however, the mechanism of apoptosis induction by lepidopteran p53 remains unclear, particularly regarding the domains required and the role of transcriptional activity. Here, we investigated the domains required for Bm-p53 activity using transient expression assays with domain/region deletion mutants. Bm-p53 contains three domains-TAD (transcriptional activation domain), DBD (DNA-binding domain), and NLS (nuclear localization signal)-which are conserved in mammalian and Drosophila p53s. However, Bm-p53 lacks an oligomerization domain, which is conserved in the C-terminal region of mammalian and Drosophila p53s. We found that all examined domains/region-TAD, DBD, NLS, and the C-terminal region (CR)-are crucial for the full proapoptotic activity of Bm-p53. Additionally, Bm-p53 can activate transcription from a promoter containing human p53-binding sites. This activity is completely lost in cells expressing Bm-p53 with deletions in the DBD, NLS, and CR, whereas TAD deletion results in a modest reduction. Both the proapoptotic and transcriptional activities were suppressed in Bm-p53 with point mutations corresponding to human p53 mutational hotspots. Collectively, our findings demonstrate that Bm-p53 induces apoptosis primarily through transcriptional activation of downstream genes, requiring nuclear localization via the NLS and DNA binding via the DBD, and supported by the TAD and CR. Notably, transcription-independent mechanisms may also contribute to apoptosis induction, indicating a more complex regulatory model of Bm-p53 function.
Mitochondrial translocation of p210 BCR-ABL rewires downstream signaling by selectively suppressing ERK activation.
Okuda Y, Watanabe-Takahashi M, Nishikawa K
Biochem Biophys Res Commun · 2026 Jun · PMID 42320296 · Publisher ↗
Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the fusion protein p210 BCR-ABL. In addition to activating canonical cytosolic signaling pathways, p210 BCR-ABL has been shown to translocate to t...
Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the fusion protein p210 BCR-ABL. In addition to activating canonical cytosolic signaling pathways, p210 BCR-ABL has been shown to translocate to the mitochondria upon mitochondrial damage through the interaction between its pleckstrin homology domain and cardiolipin, a mitochondria-specific phospholipid. We recently demonstrated that a fraction of p210 BCR-ABL localizes to the mitochondria in CML cells and promotes cell survival through mitochondria-associated signaling. However, whether mitochondria translocation of p210 BCR-ABL affects the major downstream signaling pathways activated by p210 BCR-ABL remains unclear. Here, we investigated the effects of mitochondrial translocation of p210-BCR-ABL on the JAK2/STAT5-, PI3K/AKT-, and RAS/MAPK-pathways using HEK293T cells expressing p210 BCR-ABL. Carbonyl cyanide m-chlorophenylhydrazone (CCCP), which induces mitochondrial damage and subsequent mitochondrial translocation of p210 BCR-ABL, markedly reduced ERK activation, whereas STAT5 and AKT activation were largely unaffected. Consistently, phosphorylation of SHC1, an adaptor protein directly phosphorylated by p210 BCR-ABL and required to ERK activation, was also suppressed by CCCP treatment. In contrast, CCCP did not affect EGF-induced ERK activation, indicating that the observed effect was specific for p210 BCR-ABL signaling. Moreover, N-acetylcysteine inhibited CCCP-induced reactive oxygen species production, prevented mitochondrial translocation of p210 BCR-ABL, and fully restored ERK-activation. These findings suggest that intercellular relocation of p210 BCR-ABL dynamically rewires downstream signaling networks, potentially optimizing the signaling balance required for CML cell survival and proliferation.
Complement-coupled erythrocyte platform for rapid enrichment of candidate NLRP3 modulators.
Shi L, Liu W, Xie X … +3 more , Zhang Y, Liu Q, Chen S
Biochem Biophys Res Commun · 2026 Jun · PMID 42320295 · Publisher ↗
Despite the validation of NLRP3 as a therapeutic target for inflammatory disorders, conventional cell-based screens for NLRP3 modulators remain resource-intensive and technically demanding. Here, we report a phenotypic s...
Despite the validation of NLRP3 as a therapeutic target for inflammatory disorders, conventional cell-based screens for NLRP3 modulators remain resource-intensive and technically demanding. Here, we report a phenotypic screening platform based on spectosis, a complement-driven erythrocyte death pathway mechanistically coupled to NLRP3 signaling. By monitoring complement-mediated hemolysis, this system enables high-throughput phenotypic enrichment of compounds for subsequent evaluation. A diverse library of 1000 small molecules was screened using a permissive primary threshold of 20% inhibition to ensure comprehensive coverage, yielding 365 initial actives. These underwent three rounds of confirmatory screening under identical conditions, yielding 11 validated hits that consistently passed all rounds. Importantly, counter-screening against terminal complement component C9 deposition showed that ten of these eleven compounds did not reduce C9 deposition, indicating that the majority of hits do not act via direct complement suppression. Translational validation in THP-1 macrophages identified five candidates that effectively attenuated both IL-1β maturation and LDH release, consistent with NLRP3 pathway modulation. This erythrocyte-based platform thus enables rapid, cost-effective enrichment of candidate chemotypes with potential NLRP3-related activity from large chemical libraries while circumventing the throughput limitations of conventional macrophage-based assays.
Model-Derived Mechanistic Insights into Structural, Surface, and Physicochemical Determinants Underlying Enzyme pH Adaptation.
Zhang J, Ruan H, Zhang J … +3 more , Li Y, Li Y, Luo G
Biochem Biophys Res Commun · 2026 Jun · PMID 42314541 · Publisher ↗
The optimal pH is a core functional parameter determining the catalytic efficiency and stability of enzymes, which is crucial for the optimization of industrial biocatalysts processes. To address the challenges of time-c...
The optimal pH is a core functional parameter determining the catalytic efficiency and stability of enzymes, which is crucial for the optimization of industrial biocatalysts processes. To address the challenges of time-consuming and costly traditional experimental determinations, as well as the insufficient feature representation capabilities of existing computational models, we herein propose a multi-source attention Kolmogorov-Arnold Network model, named EnzMSA-KAN, for predicting enzyme optimal pH. This model achieves deep feature fusion and efficient regression through a three-stage architectural innovation. First, a feature fusion module is constructed to integrate protein sequence evolutionary information, residue physicochemical properties, and global statistical features, adaptively and dynamically adjusting the weight contributions of different source information to pH adaptation. Second, a two-layer Graph Attention Network is employed to capture spatial topology and sequence dependencies between residues, while a multi-head attention pooling mechanism is introduced to automatically focus on key functional regions such as active sites and surface charge distributions. Finally, a regularized KAN regression head is utilized to replace traditional fully connected layers, achieving accurate fitting of the complex non-linear relationships between the enzyme microenvironment and optimal pH based on learnable univariate function bases. Experiments on a benchmark dataset of 1554 enzyme sequences demonstrate that the model achieves a test set MAE of 0.57, RMSE of 0.81, and R of 0.52, significantly outperforming existing mainstream methods. Moreover, attention visualization results verify the model's effective capture of key functional residues, endowing the prediction results with good biological interpretability. This research not only provides an efficient tool for enzyme function prediction but also offers a new computational paradigm for the rational design and engineering of industrial enzymes.
Overexpression effects of 4.1B protein on epilepsy and excitatory synaptic transmission in mice.
Zhou X, Xu X, Jiang W
Biochem Biophys Res Commun · 2026 Jun · PMID 42314540 · Publisher ↗
Protein 4.1B, part of the evolutionarily conserved protein 4.1 family known for its role as cytoskeletal adaptors, is involved in the localization of NMDA receptors. However, its significance in epilepsy is not well unde...
Protein 4.1B, part of the evolutionarily conserved protein 4.1 family known for its role as cytoskeletal adaptors, is involved in the localization of NMDA receptors. However, its significance in epilepsy is not well understood. Considering the crucial role of the imbalance between synaptic excitation and inhibition in the development of epilepsy, we proposed that 4.1B might influence the progression of chronic epilepsy by affecting synaptic transmission. Our findings indicated a marked decrease in 4.1B protein levels in the hippocampus and temporal cortex of mice with chronic epilepsy. Immunohistochemical studies showed that 4.1B is mainly found in neurons. Increasing the expression of 4.1B notably lowered the frequency of spontaneous seizures during the chronic phase, and electrophysiological assessments revealed a significant decrease in the amplitude of miniature excitatory postsynaptic currents (mEPSCs). Overall, these results imply that 4.1B plays a role in the development of chronic epilepsy by altering excitatory synaptic transmission and could serve as a potential therapeutic target for epilepsy.
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