Biochemical and biophysical research communications最新文献

{"title":"Fully functional hair follicle organ regeneration using organ-inductive potential stem cells with an accessory mesenchymal cell population in an in vitro culture system","authors":"Koh-ei Toyoshima ,&nbsp;Ayako Tsuchiya ,&nbsp;Miho Ogawa ,&nbsp;Miki Takase ,&nbsp;Tarou Irié ,&nbsp;Masayuki Yanagisawa ,&nbsp;Richard H. Kaszynski ,&nbsp;Hiroshi Fujimaki ,&nbsp;Kyoko Baba ,&nbsp;Takayuki Sugimoto ,&nbsp;Akira Takeda ,&nbsp;Akio Sato ,&nbsp;Takashi Tsuji","doi":"10.1016/j.bbrc.2026.153459","DOIUrl":"10.1016/j.bbrc.2026.153459","url":null,"abstract":"<div><div>Organ morphogenesis is essential for not only integrated organ functions in the body but also the determination of adult-tissue stem cells and their niche. Only hair follicle organs can cyclically regenerate in the variable bulbous germinative region as a form of programmed organ regeneration in adults. Here, we identified a cell population, hair follicle organ-intrinsic mesenchymal cells, with PDGFRα⁺/Sca1⁺/CD34^high+ mesenchymal cells, from the boundary zone of the epithelial stem cell niche by using the organ germ method, which plays essential roles in entering and promoting the downgrowth phase of the hair cycle. The bioengineered hair follicle germ reconstituted from bulge region-derived epithelial stem cells, dermal papillae and mesenchymal cells has full functions, including downgrowth, full-size hair follicle regeneration and the hair cycle, both in <em>in vitro</em> artificial skin and after intracutaneous skin transplantation. This study provides significant contributions to the basic and medical science of adult organ-inductive potential stem cells and their niches in organ morphogenesis and the adult hair cycle.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153459"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321250","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":"Protection mechanism of epalrestat on glutamate-induced retinal excitotoxicity model based on network pharmacology","authors":"Jiping Huang ,&nbsp;Shaomei Zhao ,&nbsp;Jining Huang ,&nbsp;Guocheng Yu ,&nbsp;Lian Liu","doi":"10.1016/j.bbrc.2026.153490","DOIUrl":"10.1016/j.bbrc.2026.153490","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to investigate the protective effect of epalrestat (EPS) and the molecular mechanisms that underlie its treatment of retinal excitotoxicity.</div></div><div><h3>Methods</h3><div>The corresponding targets of drug and disease were obtained from relevant databases, respectively. By constructing and analyzing connected networks, the targets, primary molecular function, biological processes, and signaling pathways associated with EPS were found. The binding affinity between EPS and potential targets was confirmed by molecular docking. Establishing an excitotoxicity model with glutamate to further evaluate network pharmacology results by gathering samples from R28 cells and measuring inflammatory factor levels, cell viability, oxidative stress indicators, and Nrf2/HO-1 signaling pathway expression.</div></div><div><h3>Results</h3><div>138 targets, including the NFE2L2 and HMOX1 that encode HO-1 and Nrf2, were shown to overlap between drug and disease by network pharmacology analysis. Molecular docking results revealed that EPS exerts therapeutic effects through multiple targets like Nrf2 and HO-1. In vitro experiments have shown that EPS reversed the effects of glutamate-induced apoptosis, which included a decrease in superoxide dismutase (SOD) and an increase in intracellular reactive oxygen species (ROS), malondialdehyde (MDA), TNF-α, IL-1β, and IL-6, by regulating the Nrf2/HO-1 signaling. Furthermore, by reducing glutamate-induced cell damage, the Nrf2 inhibitor ML385 further supports the important roles of Nrf2/HO-1 signaling in R28 cell antioxidant and anti-inflammatory responses.</div></div><div><h3>Conclusions</h3><div>EPS inhibits retinal excitotoxicity by acting as an antioxidant and anti-inflammatory through the Nrf2/HO-1 signaling pathway. EPS may have some clinical benefits in reducing retinal excitotoxicity-related retinopathy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153490"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347096","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":"Methyl divanillate enhances doxorubicin efficacy in TNBC cell lines through redox imbalance and apoptotic reprogramming","authors":"Adriano de Souza Pessoa ,&nbsp;Flávia Godoy Iano ,&nbsp;Mariana Liessa Rovis Sanches ,&nbsp;Emanuelle Pangoni de Carvalho ,&nbsp;Ana Lígia Pagnan ,&nbsp;Larissa Tercília Grizzo Thomassian ,&nbsp;Talita Mendes Oliveira Ventura ,&nbsp;Marília Afonso Rabelo Buzalaf ,&nbsp;Valdecir Farias Ximenes ,&nbsp;Rodrigo Cardoso de Oliveira","doi":"10.1016/j.bbrc.2026.153532","DOIUrl":"10.1016/j.bbrc.2026.153532","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) represents one of the most aggressive breast cancer subtypes, lacking effective targeted therapies and relying primarily on chemotherapy. In this study, we investigated the cytotoxic and molecular effects of doxorubicin (DOX) and methyl divanillate (DMV), alone or in combination, in three-dimensional spheroid models derived from MDA-MB-231 (claudin-low) and HCC70 (basal-like) TNBC cell lines. Combined DOX/DMV treatment significantly reduced spheroid viability and was associated with increased reactive oxygen species (ROS) accumulation and thiol depletion, thereby indicating redox imbalance and cytoskeletal disruption. Immunofluorescence further confirmed actin filament disorganization and nuclear instability under combined therapy. Integrated qPCR and proteomic analyses revealed lineage-dependent modulation of apoptotic signaling in MDA-MB-231 spheroids, DOX/DMV broadly suppressed apoptosis-associated proteins, whereas in HCC70 spheroids, the combination upregulated key intrinsic apoptotic regulators, including caspases and mitochondrial stress-related proteins. Furthermore, gene expression analysis, gelatin zymography, and proteomic profiling demonstrated that DOX and DMV modulated metalloproteinase (MMP) activity and cytoskeletal remodeling, with combination therapy promoting MMP9 suppression and widespread downregulation of actin cytoskeleton regulators in MDA-MB-231 spheroids, while inducing cytoskeletal reinforcement–associated profiles in HCC70 spheroids. Transgelin-2 expression also exhibited divergent patterns between the cell lines at both transcript and protein levels. Collectively, our findings indicate that DOX/DMV combination therapy exerts synergistic interaction, as determined by Combination Index analysis (CI = 0.3 for MDA-MB-231 spheroids and CI = 0.8 for HCC70 spheroids), resulting in enhanced cytotoxicity associated with oxidative stress, apoptotic pathway modulation, and cytoskeletal remodeling in a subtype-dependent manner. These results underscore the potential of DMV as a redox-modulating adjuvant to enhance chemotherapy efficacy in TNBC, while highlighting the importance of tumor subtype context in determining therapeutic responses.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153532"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347098","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":"Orexin-A signaling modulates dopamine neurons and palatable food seeking: potential involvement of μ-opioid receptor signaling pathway","authors":"Xiao Luan ,&nbsp;Yang Liu ,&nbsp;Xiaoqian Zhang ,&nbsp;Xiangrong Sun ,&nbsp;Feifei Guo ,&nbsp;Mi Wang","doi":"10.1016/j.bbrc.2026.153531","DOIUrl":"10.1016/j.bbrc.2026.153531","url":null,"abstract":"<div><h3>Aims</h3><div>Obesity is associated with binge eating and abnormal activation of the reward pathway. Hypothalamic neuropeptides such as orexin-A and μ-opioid receptor signaling are closely involved in feeding behavior and reward processing; however, the interaction between orexin-A and μ-opioid receptor signaling in palatable food seeking remains unclear.</div></div><div><h3>Materials and methods</h3><div>We used fluorogold retrograde tracing to examine neural projection between the perifornical region (PeF) and the ventral tegmental area (VTA). Immunohistochemical staining was performed to assess the distribution of orexin-A receptor 1 (OX1-R) and tyrosine hydroxylase (TH) neurons in the VTA. Subsequently, drugs were administered into the VTA to investigate the interactions between orexin-A and μ-opioid receptor antagonist naltrexone (NTX) in regulating palatable food seeking and the firing frequency of VTA dopamine (DA) neurons.</div></div><div><h3>Key findings</h3><div>Fluorogold-labeled orexin-A neurons were observed in the PeF, and co-localization of OX1R and TH neurons was detected in the VTA. Furthermore, electrical stimulation (ES) of the PeF or administration of orexin-A into the VTA increased the expression of c-Fos in TH-positive neurons, providing an anatomical basis for this study. Microinjection of orexin-A into the VTA promoted palatable food seeking in rats, an effect that was completely blocked by pre-administration of the OX1R antagonist SB-334867. In addition, orexin-A and NTX were found to modulate the firing frequency of VTA DA neurons, suggesting that orexin-A and μ-opioid receptor signaling may regulate palatable food seeking through their actions on VTA DA neurons.</div></div><div><h3>Significance</h3><div>This study sheds light on the interaction between orexin-A and the μ-opioid system in regulating palatable food seeking and the firing frequency of VTA DA neurons.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153531"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321255","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":"Millimeter-scale, high-density three-dimensional constructs recapitulate hot and cold tumor microenvironment","authors":"Kazuki Yokota,&nbsp;Nobutaka Yasuma,&nbsp;Peizheng Wu,&nbsp;Masataka Hakamada,&nbsp;Mamoru Mabuchi","doi":"10.1016/j.bbrc.2026.153527","DOIUrl":"10.1016/j.bbrc.2026.153527","url":null,"abstract":"<div><div>The tumor microenvironment (TME) exerts a pivotal influence on malignant phenotypes, including invasion, metastasis, immune evasion, and therapeutic resistance, thereby dictating clinical outcomes and patient prognosis. Consequently, a comprehensive elucidation of TME dynamics is of paramount importance. To address this, the development of in vitro tumor models capable of faithfully recapitulating its inherent complexity is indispensable. In this study, we engineered millimeter-scale, high-density 3D tumor constructs that recapitulate the intricate architectural and functional hallmarks of the in vivo TME. Within this biomimetic platform, reciprocal crosstalk with cancer cells induced the differentiation of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Furthermore, we successfully modeled divergent immunophenotypes, characterized as \"hot\" and \"cold\" tumors, and integrated a hierarchical vascular network comprising venous and capillary-like structures. Collectively, this construct accurately mirrors the in vivo TME, providing a robust platform for modeling complex tumor ecosystems and offering substantial potential to catalyze advancements in cancer research and drug discovery.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153527"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316259","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":"Genistein alleviates Osteoporosis by inhibiting the differentiation and autophagy of osteoclasts via regulating the CYLD/p62/RANKL axis","authors":"Jungao Zhu ,&nbsp;Xiaoqin Huang ,&nbsp;Chuanchuan Li ,&nbsp;Weixian Liu ,&nbsp;Xiaoqing Zhong","doi":"10.1016/j.bbrc.2026.153457","DOIUrl":"10.1016/j.bbrc.2026.153457","url":null,"abstract":"<div><div>Osteoporosis is a highly prevalent metabolic bone disorder characterized by an imbalance in bone remodeling, primarily due to excessive osteoclast-mediated bone resorption. The present study systematically investigates the protective effects of genistein, a naturally occurring soy isoflavone, against osteoporosis by targeting osteoclast differentiation and autophagy, as well we the underlying mechanism. Using RANKL-stimulated RAW264.7 cells as an in vitro model, we found that genistein treatment significantly and dose-dependently inhibited osteoclast formation and autophagic activity, which was evidenced by reduced tartrate-resistant acid phosphatase (TRAP) activity, fewer autophagic vacuoles observed under transmission electron microscopy, decreased protein levels of LC3-II/I and Beclin1, and increased expression of p62. Mechanistic studies revealed that genistein upregulates the deubiquitinase CYLD, which stabilizes p62 through deubiquitylation, leading to inhibition of the RANKL signaling pathway. Importantly, the anti-osteoclastogenic effects of genistein were markedly attenuated upon CYLD or p62 knockdown or upon induction of autophagy with rapamycin. In an ovariectomized (OVX) rat model of postmenopausal osteoporosis, genistein administration (5 or 10 mg/kg/day) effectively ameliorated bone loss, as confirmed by micro-CT analyses showing improvements in bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular separation (Tb.Sp). Consistent with in vitro findings, genistein reduced osteoclast numbers and modulated autophagy markers in femoral tissues. Collectively, these results demonstrate that genistein mitigates osteoporosis by suppressing osteoclast differentiation and autophagy through regulating the CYLD/p62/RANKL axis, highlighting its promising potential as a natural therapeutic agent for osteoporosis treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153457"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324611","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":"Light and brassinosteroids differentially modulate Arabidopsis seedling root growth in a largely independent manner","authors":"Hao Peng,&nbsp;Ying Zhai","doi":"10.1016/j.bbrc.2026.153538","DOIUrl":"10.1016/j.bbrc.2026.153538","url":null,"abstract":"<div><div>Brassinosteroids (BRs) are a class of steroid phytohormones that promote plant growth and tolerance to both biotic and abiotic stress. BAS1/CYP734A1, SOB7/CYP72C1, and BEN1 are three BR-inactivating enzymes characterized in <em>Arabidopsis thaliana</em>. The triple-null mutant <em>bas1-2 sob7-1 ben1-3</em> exhibits strong BR-overproducing phenotypes. The CYP734A cytochrome P450 protein family is highly conserved across plant species. Ectopic overexpression of grapevine CYP734A15 in Arabidopsis causes severe BR-deficient phenotypes. BRs differentially modulate hypocotyl growth in photomorphogenic and skotomorphogenic seedlings. However, little is known about the potential involvement of light in BR-regulated seedling root growth. In this research, we grew Arabidopsis seedlings of the wild-type (WT) Col-0, the BR-overproducing mutant <em>bas1-2 sob7-1 ben1-3</em>, and two BR-deficient CYP734A15 overexpression mutants <em>CYP734A15ox-3</em> and <em>CYP734A15ox-4</em> in either continuous white light or constant darkness, with treatments of either brassinolide (BL, the most bioactive, naturally occurring BR) or the BR biosynthesis inhibitor brassinazole (BRZ) at a wide range of concentrations. Primary root length measurement results showed that light promoted seedling root growth regardless of endogenous BR levels. Both endogenous and exogenous BRs suppressed seedling root growth independently of light. BRZ treatments also suppressed root elongation in light-grown seedlings regardless of endogenous BR levels, probably due to its toxic effects. In the dark, BRZ still slightly suppressed root elongation in <em>CYP734A15ox-3/4</em> seedlings but the effect switched to moderate promotion for roots growth in Col-0 and <em>bas1-2 sob7-1 ben1-3</em>. Collectively, our work suggests that light and BRs differentially modulate Arabidopsis seedling root growth in a largely independent manner.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153538"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321217","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":"The divergent LARP1 PAM2 motif adopts a non-canonical conformation for MLLE binding","authors":"Ali Behvarmanesh ,&nbsp;Guennadi Kozlov ,&nbsp;Tara Sprules ,&nbsp;Kalle Gehring","doi":"10.1016/j.bbrc.2026.153517","DOIUrl":"10.1016/j.bbrc.2026.153517","url":null,"abstract":"<div><div>Cytoplasmic poly(A)-binding protein (PABPC1) binds the mRNA poly(A) tail via its RNA recognition motifs (RRMs) and recruits factors involved in mRNA metabolism through its C-terminal MLLE domain. The MLLE domain recognizes short PAM2 motifs found in a wide range of regulatory proteins known as PAM2-containing proteins (PACs). Members of the La-related protein (LARP) family, specifically LARP1 and LARP4, which are involved in poly(A) tail protection, contain atypical PAM2 sequences that diverge from the canonical consensus yet retain MLLE binding. The molecular basis of this interaction is not fully understood for LARP1. Here, we combined nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry (ITC), and AlphaFold3 modeling to characterize the interaction between the LARP1 PAM2 motif and the MLLE domain of PABPC1. NMR chemical shift perturbations and heteronuclear NOE analyses defined the MLLE-binding segment, i.e. PAM2 motif, within LARP1. Mutagenesis studies and ITC confirmed the essential role of phenylalanine 496 for MLLE binding. AlphaFold3 modeling corroborated these findings with the prediction of a single turn α-helix in the PAM2 motif. Together, these results define a non-canonical PAM2-MLLE interaction and reveal unexpected plasticity in the recognition of PAM2 motifs by the MLLE domain.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153517"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321221","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":"Systematic pharmacology-guided analysis of the therapeutic mechanism of Sedum sarmentosum against chronic liver injury","authors":"Jingxin Mao ,&nbsp;Chen Wang ,&nbsp;Tingting Li ,&nbsp;Qian Shao ,&nbsp;Qing Hu","doi":"10.1016/j.bbrc.2026.153514","DOIUrl":"10.1016/j.bbrc.2026.153514","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To study the molecular mechanism of active compounds in &lt;em&gt;Sedum sarmentosum&lt;/em&gt; Bunge. (&lt;em&gt;SS&lt;/em&gt;) for treating chronic liver injury (CLI) induced by &lt;span&gt;d&lt;/span&gt;-galactosamine (DalN) combined with Lipopolysaccharide (LPS).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The common targets of drugs and diseases were screened through the database, the interaction network was constructed using network pharmacology, the core targets were screened through topological analysis, and the protein-protein interaction (PPI) network was constructed. The gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were used to find the signal pathways related to the treatment of CLI by active compounds from &lt;em&gt;SS.&lt;/em&gt; The libdock-score of components was calculated through molecular docking and the core targets were obtained. C57BL/6J mice were treated with LPS + DalN to established CLI models. C57BL/6J mice were randomly divided into 6 groups, each group received intraperitoneal injection of 30 mg/mL D-Galn +2 μg/mL LPS for continuous 8 weeks except control group, once for 2 days. The administration method for mice is as following: Control group (con, intragastric, ig. equal amount of physiological saline water), LPS + D-Galn group (mod, intraperitoneal, ip. 30 mg/mL D-Galn+2 μg/mL LPS + ig. equal amount of physiological saline water), low dose group (low dose, ip. 30 mg/mL D-Galn+2 μg/mL LPS + ig. 20 mg/kg quercetin+20 mg/kg isorhamnetin), middle dose group (middle dose, ip. 30 mg/mL D-Galn+2 μg/mL LPS + ig. 30 mg/kg quercetin+30 mg/kg isorhamnetin), high dose group (high dose, ip. 30 mg/mL D-Galn+2 μg/mL LPS + ig. 40 mg/kg quercetin+40 mg/kg isorhamnetin). The contents of aspartate aminotransferase (AST) and glutamate aminotransferase (ALT) in serum and malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) and catalase (CAT) in liver tissue were detected. The feces were collected and the gut microbiota of mice in each group was analyzed by 16s rDNA high-throughput sequencing technology. Liver tissues were collected from mice in each groups, and Western blot was performed to quantify the relative expression levels of the target core proteins.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Result&lt;/h3&gt;&lt;div&gt;125 potential targets for CLI and 94 signaling pathways were identified, and the key gene targets for anti-CLI potential of &lt;em&gt;SS&lt;/em&gt; were AKT1, TP53, VEGFA, CASP3, IL-6, JUN respectively. The active compounds of &lt;em&gt;SS&lt;/em&gt; that exhibits the properties of anti-CLI may be quercetin and isorhamnetin. In addition, quercetin and isorhamnetin may significantly improve the CLI which induced by DalN + LPS &lt;em&gt;via&lt;/em&gt; reducing the levels of AST, ALT, LDH, MDA and ROS, and increasing the levels of SOD and CAT. Significant differences in microbial communities between model group and other groups were found. Compared to model group, &lt;em&gt;Phascolarctobacterium&lt;/em&gt;, &lt;em&gt;Bacteroides&lt;/em&gt;, &lt;em&gt;Lactobacillus&lt;/em&gt; w","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153514"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321183","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":"A novel pyrophosphatase activity of SiaD, a diguanylate cyclase of Pseudomonas aeruginosa","authors":"Anirban Adhikary ,&nbsp;Moumita Ghosh ,&nbsp;Deepti Jain","doi":"10.1016/j.bbrc.2026.153528","DOIUrl":"10.1016/j.bbrc.2026.153528","url":null,"abstract":"<div><div>Diguanylate cyclases (DGCs) are key regulators of signaling and transcription in bacterial cells. The DGC SiaD is activated upon binding to unphosphorylated SiaC and synthesizes cyclic-di-GMP from two GTP molecules, thereby elevating intracellular levels of the secondary messenger. The c-di-GMP acts on downstream effectors, leading to the switching <em>of Pseudomonas aeruginosa</em> cells from a free-swimming to a sessile biofilm state. Here, we report that SiaD harbors a novel pyrophosphatase activity that is independent of its diguanylate cyclase function as well as its interaction with SiaC. The activity is divalent metal ion-dependent, and the second acidic residue of the signature GGEEF motif of the DGC domain is critical for catalysis. Furthermore, a positively charged Arg also plays a crucial role in catalysis by stabilizing the bound substrate. The discovery of this dual functionality suggests that pyrophosphatase activity may be crucial for driving DGC activity and has potential biotechnological applications.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"810 ","pages":"Article 153528"},"PeriodicalIF":2.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324658","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}