{"title":"Triple probiotics attenuate colitis via inhibiting macrophage glycolysis dependent pro-inflammatory response.","authors":"Hantao Cai, Tianxin Li, Wanting Feng, Xian Wu, Yue Zhao, Tingting Wang","doi":"10.1016/j.bbrc.2024.151128","DOIUrl":"10.1016/j.bbrc.2024.151128","url":null,"abstract":"<p><p>Probiotics, a class of live microorganisms, play an important role in anti-inflammation, regulating immunity and optimizing intestinal microecological environment. In this study, we constructed a combination of three strains - Lactobacillus acidophilus, Bacillus bulgaricus, and Bacillus subtilis - to ferment triple probiotics Bornlisy. Our findings indicate that Bornlisy has a significant therapeutic effect in alleviating colitis in mice, further proofing its ability to suppress inflammation in colon, enhance intestinal barrier function and restore imbalanced intestinal microbiome. Then we found Bornlisy could modulate immune response by inhibiting macrophage glycolysis and ultimately attenuated the progression of colitis in mice. Our investigation into the therapeutic efficacy of Bornlisy in colitis revealed that triple probiotics offer a promising approach for the management of intestinal inflammation.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151128"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790950","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":"Neuroprotective effect of naringin by modulation of klotho and HMGB1- TLR4 axis in PTZ-induced kindling in mice.","authors":"Parvej Khan, Nilanjan Saha, Nidhi","doi":"10.1016/j.bbrc.2024.151080","DOIUrl":"10.1016/j.bbrc.2024.151080","url":null,"abstract":"<p><strong>Background: </strong>Naringin has demonstrated various neuroprotective effects; however, its anti-inflammatory and cognitive properties, particularly through the regulation of HMGB1-TLR4 and Klotho, have not been explored in the context of epilepsy.</p><p><strong>Method: </strong>Kindling was induced in Swiss albino mice by administering pentylenetetrazole (PTZ) 25 mg/kg intraperitoneally (i.p.). Naringin (40 mg/kg and 80 mg/kg) was administered orally for 6 weeks. The severity of seizures was assessed using the Racine scale. Cognitive function was evaluated by measuring step-down latency and transfer latency. The levels of GABA, glutamate, IL-1β, IL-1R1, IL-6, HMGB1, TLR4, TNF-α, Klotho, and ADAM-10 were quantified using enzyme-linked immunosorbent assay (ELISA) techniques.</p><p><strong>Results: </strong>Naringin significantly attenuated PTZ-induced seizures at both doses (p < 0.01 for 40 mg/kg; p < 0.0001 for 80 mg/kg) compared to the PTZ group. Additionally, it enhanced retention latency in both step-down latency (p < 0.01 for 40 mg/kg; p < 0.0001 for 80 mg/kg) and transfer latency (p < 0.05 for both doses) compared to the PTZ group. Furthermore, it increased Klotho and ADAM-10 levels in both the hippocampus and cortex (p < 0.01 for 40 mg/kg; p < 0.001 for 80 mg/kg, respectively). Levels of HMGB1, TLR4, and pro-inflammatory cytokines were significantly decreased in both the hippocampus and cortex compared to the PTZ group.</p><p><strong>Conclusion: </strong>Naringin exhibited anti-epileptic effects by regulating neurotransmitter levels and preventing PTZ-induced kindling. Additionally, it demonstrated neuroprotective effects on cognition and attenuated neuroinflammation. These findings suggest that naringin may be a potential therapeutic agent for epilepsy-associated cognitive dysfunction, warranting further studies for clinical translation.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151080"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791076","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 combined oxidative stress and extracellular matrix related predictive gene signature for keratoconus.","authors":"Zina Cheng, Jiahui Hao, Siying Cai, Pengfei Feng, Weiyi Chen, Xiaolu Ma, Xiaona Li","doi":"10.1016/j.bbrc.2024.151144","DOIUrl":"10.1016/j.bbrc.2024.151144","url":null,"abstract":"<p><p>Keratoconus (KC) is an ectatic cornea disease with high prevalence and asymptomatic at early stage, leading to decreased visual acuity and even cornea transplantation. However, the etiology mechanism of keratoconus is still poorly understood. Oxidative stress (OS) and extracellular matrix (ECM) remodeling play critical roles in keratoconus development. Here, based on keratoconus datasets from GEO database, we obtained 454 differentially expressed genes (DEGs), which were further intersected with oxidative stress (OS) and extracellular matrix (ECM) genesets from MSigDB database. A total of 17 OS- and ECM-related DEGs (OEDEGs) were identified. Feature genes were screened by least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms, and a six-gene (COL1A1, CYP1B1, MMP3, HMOX1, FOS and GDF15) classification model was developed utilizing Logistic regression (LR), Support Vector Machine (SVM) and Naïve Bayes (NB) algorithms respectively, which was further verified in internal and external cohort. Subsequently, a predictive nomogram was constructed for KC patients. Six signature genes showed a strong correlation with the infiltration level of macrophages M1, neutrophils and eosinophils. Additionally, in vitro qRT-PCR validated the decreased expression of signature genes in either keratoconus clinical samples or human cornea epithelial (HCE) cells grown on soft hydrogel substrate. Finally, we revealed that CYP1B1 and GDF15 regulate cellular proliferation and response to oxidative stress. In conclusion, the developed combined OS and ECM gene signature showed excellent performance for keratoconus prediction, providing beneficial perspectives for keratoconus pathogenesis.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151144"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806103","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":"PEG-modification enhances the targeted photothermal therapy of affibody-conjugated indocyanine green for precision cancer treatment.","authors":"Yanting Liu, Xuerui Bai, Henan Wang, Jian Wang, Shuang Li, Hongru Zhang, Fengwei Wang, Zhangyong Hong","doi":"10.1016/j.bbrc.2024.151155","DOIUrl":"10.1016/j.bbrc.2024.151155","url":null,"abstract":"<p><p>Photothermal therapy (PTT) is an innovative cancer treatment that leverages heat generated from near-infrared light exposure to induce tumor cell death. A major challenge in PTT is achieving precise delivery of the photothermal agent to tumor tissues to maximize efficacy and minimize off-target effects. In this study, we introduce a novel ligand-coupled photothermal reagent that addresses this challenge by leveraging the high-affinity HER2 affibody Z<sub>HER2:2891</sub> (referred to as Z<sub>HER2</sub>), conjugated with indocyanine green (ICG) for targeted delivery. Polyethylene glycol (PEG) was incorporated as a hydrophilic linker to further optimize photothermal conversion efficiency and enhance tumor-specific targeting. Among the conjugates tested, Z<sub>HER2</sub>-PEG<sub>1000</sub>-ICG, modified with a PEG chain of 1000 Da molecular weight, demonstrated exceptional performance. In vitro studies revealed that Z<sub>HER2</sub>-PEG<sub>1000</sub>-ICG specifically bound to HER2-expressing cells and effectively induced cell death. In vivo experiments using HER2-positive N87 tumor-bearing mice showed that Z<sub>HER2</sub>-PEG<sub>1000</sub>-ICG accumulated highly and specifically in tumor tissues over an extended period. Upon light irradiation, this conjugate caused a significant rise in temperature at the tumor site, resulting in complete tumor elimination with a single photothermal treatment. This PEG-modified affibody-ICG conjugate represents a precise and effective approach to PTT, offering a promising new therapeutic strategy for cancer treatment with the potential to significantly impact future cancer therapies.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151155"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812131","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}
Yakov I Mokin, Olga I Povarova, Sergey A Silonov, Iuliia A Antifeeva, Vladimir N Uversky, Konstantin K Turoverov, Irina M Kuznetsova, Alexander V Fonin
{"title":"Bioinformatics analysis of proteins interacting with different actin isoforms.","authors":"Yakov I Mokin, Olga I Povarova, Sergey A Silonov, Iuliia A Antifeeva, Vladimir N Uversky, Konstantin K Turoverov, Irina M Kuznetsova, Alexander V Fonin","doi":"10.1016/j.bbrc.2024.151165","DOIUrl":"10.1016/j.bbrc.2024.151165","url":null,"abstract":"<p><p>Actin is one of the most widespread and most conserved proteins. At the same time, six actin isoforms are known, encoded by different genes. These isoforms differ slightly in amino acid sequence and have similar structures, but differ in localization and functioning. During functioning, actin interacts with a large number of proteins, which are combined according to this feature into a pool of so-called actin-binding proteins. The question arises whether and how the proteins interacting with different actin isoforms differ. Since the pool of actin-binding proteins includes hundreds of proteins, it was logical to use bioinformatics analysis to solve the questions. In this work, it is shown that the functionality of the α-, β-, and γ-actin interactomes differ significantly, but their structural characteristics are close.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151165"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827295","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":"Doxorubicin inhibits SIRT2 and NF-kB p65 phosphorylation in Brest cell-line cancer.","authors":"Abdelmalek Rezgui, Rechda Amel Tachour, Houdhaifa Layaida, Rania Derguine, Fatma Zahra Hab, Anfel Benmanseur, Brahim Matougui, Rym Agred, Widad Sobhi","doi":"10.1016/j.bbrc.2024.151162","DOIUrl":"10.1016/j.bbrc.2024.151162","url":null,"abstract":"<p><p>Doxorubicin (DOXO) is a widely used anti-cancer agent, yet the precise mechanism underlying the induction of tumor cell death remains unclear. This study aimed to elucidate new mechanisms by which doxorubicin induces apoptosis in the EMT6 mouse breast carcinoma cell line. The role of doxorubicin was assessed using the XTT assay. The assessment of oxidative stress markers, alongside the analysis of SIRT2 and NF-κB p65 (RelA) phosphorylation inhibition, was conducted. In silico studies, including density functional theory (DFT) calculations and molecular docking simulations, were employed to characterize the molecular interactions between doxorubicin and SIRT2. Additionally, doxorubicin was assessed for its capacity to modulate gene expression and associated pathways using multiple bioinformatics tools and web-based platforms. Our finding indicates that Doxorubicin induced apoptosis in EMT6 cells with an IC50 of 8,32 μM. At lower concentrations, doxorubicin enhances the oxidative balance and promotes cell viability. At high concentrations, doxorubicin inhibits SIRT2. Furthermore, an experimental investigation revealed that doxorubicin inhibits RelA phosphorylation. The results also showed that doxorubicin modulated the expression of 19 genes involved in different pathways and several transcription factors. The results of implementing the gene set with SIRT2 and RELA consolidated the experimental results. In conclusion, Doxorubicin was observed to induce EMT6 apoptosis through the inhibition of SIRT2 and RelA proteins. The outcomes of both experimental and bioinformatic studies provide a novel perspective on the biological effects of doxorubicin and underscore the potential of inhibiting the SIRT2-RelA axis as a promising biological target for cancer therapy.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151162"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845670","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":"Thermodynamic role of receptor phosphorylation barcode in cannabinoid receptor desensitization.","authors":"Eun Ha Heo, Ravinder Abrol","doi":"10.1016/j.bbrc.2024.151100","DOIUrl":"10.1016/j.bbrc.2024.151100","url":null,"abstract":"<p><p>The endocannabinoid signaling system is comprised of CB1 and CB2 G protein-coupled receptors (GPCRs). CB2 receptor subtype is predominantly expressed in the immune cells and signals through its transducer proteins (Gi protein and β-arrestin-2). Arrestins are signaling proteins that bind to many GPCRs after receptor phosphorylation to terminate G protein signaling (desensitization) and to initiate specific G protein-independent arrestin-mediated signaling pathways via a \"phosphorylation barcode\", that captures sequence patterns of phosphorylated Ser/Thr residues in the receptor's intracellular domains and can lead to different signaling effects. The structural basis for how arrestins and G proteins compete with the receptor for biased signaling and how different barcodes lead to different signaling profiles is not well understood as there is a lack of phosphorylated receptor structures in complex with arrestins. In this work, structural models of β-arrestin-2 were built in complex with the phosphorylated and unphosphorylated forms of the CB2 receptor. The complex structures were relaxed in the lipid bilayer environment with molecular dynamics (MD) simulations and analyzed structurally and thermodynamically. The β-arrestin-2 complex with the phosphorylated receptor was more stable than the non-phosphorylated one, highlighting the thermodynamic role of the receptor phosphorylation. It was also more stable than any of the G protein complexes with CB2 suggesting that phosphorylation signals receptor desensitization (end of G protein signaling) and arrest of the receptor by arrestins. These models are beginning to provide the thermodynamic landscape of CB2 signaling, which can help bias signaling towards therapeutically beneficial pathways in drug discovery applications.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151100"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852289","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}
Viktor A Anashkin, Alexander V Bogachev, Marina V Serebryakova, Elena G Zavyalova, Yulia V Bertsova, Alexander A Baykov
{"title":"Rapid kinetics of H<sup>+</sup> transport by membrane pyrophosphatase: Evidence for a \"direct-coupling\" mechanism.","authors":"Viktor A Anashkin, Alexander V Bogachev, Marina V Serebryakova, Elena G Zavyalova, Yulia V Bertsova, Alexander A Baykov","doi":"10.1016/j.bbrc.2024.151203","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151203","url":null,"abstract":"<p><p>Stress resistance-conferring membrane pyrophosphatase (mPPase) found in microbes and plants couples pyrophosphate hydrolysis with H<sup>+</sup> transport out of the cytoplasm. There are two opposing views on the energy-coupling mechanism in this transporter: the pumping is associated with either pyrophosphate binding to mPPase or the hydrolysis step. We used our recently developed stopped-flow pyranine assay to measure H<sup>+</sup> transport into mPPase-containing inverted membrane vesicles on the timescale of a single turnover. The vesicles were prepared from Escherichia coli overproducing the H<sup>+</sup>-translocating mPPase of Desulfitobacterium hafniense. Pyrophosphate induced linear accumulation of H<sup>+</sup> in the vesicles, without evident lag or burst. In contrast, the binding of three nonhydrolyzable pyrophosphate analogs essentially induced no H<sup>+</sup> accumulation. These findings are inconsistent with the \"pumping-before-hydrolysis\" model of mPPase functioning and support the alternative model positing the hydrolysis reaction as the source of the transported H<sup>+</sup> ions. mPPase is thus a first \"directly-coupled\" proton pump.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151203"},"PeriodicalIF":2.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871115","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":"Inflammasome regulation by the cell surface ecto-5'-nucleotidase of the oral commensal, Streptococcus oralis.","authors":"Natsuno Nakamura, Hirobumi Morisaki, Momoe Itsumi, Nobuo Okahashi, Haruka Fukamachi, Ayako Sato, Miki Kadena, Mariko Kikuchi, Shohei Matsui, Takahiro Funatsu, Hirotaka Kuwata","doi":"10.1016/j.bbrc.2024.151206","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151206","url":null,"abstract":"<p><p>Streptococcus oralis is a commensal oral bacterium that acts as an opportunistic pathogen, causing systemic diseases, such as infective endocarditis and aspiration pneumonia. However, the specific molecular mechanisms underlying its transition from commensal to pathogenic state remain unclear. In this study, to further elucidate the mechanisms underlying virulence expression, we identified and characterized the cell surface-associated ecto-5'-nucleotidase (Nt5e) in S. oralis. Biochemical analysis revealed Nt5e as a metal-dependent enzyme dephosphorylating ATP and producing adenosine, an immunosuppressive molecule that inhibits macrophage activation. Additionally, Nt5e was a critical regulator of innate immunity, particularly inflammasome activation, via environmental ATP metabolism. Analysis of an isogenic nt5e deletion mutant and its complemented strain revealed that cell surface-associated Nt5e played a crucial role in degrading extracellular ATP. The Nt5e-orchestrated mechanism possibly maintained the host-bacteria homeostasis under normal conditions, whereas its dysregulation facilitated pathogenicity in specific circumstances. Our study provides new insights into the mechanisms by which oral commensals modulate host immune responses and highlights Nt5e as a potential therapeutic target for S. oralis-associated systemic diseases.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151206"},"PeriodicalIF":2.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884861","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}
Hongru Li, Xuan Wang, Xiangyang Liang, Meiqi Meng, Haixia Zhang, Zixin Li, Yushan Lin, Jihong Li, Cuiqing Ma
{"title":"Verapamil inhibits ferroptosis in septic acute lung injury by blocking L-type calcium channels.","authors":"Hongru Li, Xuan Wang, Xiangyang Liang, Meiqi Meng, Haixia Zhang, Zixin Li, Yushan Lin, Jihong Li, Cuiqing Ma","doi":"10.1016/j.bbrc.2024.151202","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151202","url":null,"abstract":"<p><p>Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), result from pulmonary edema and alveolar-capillary barrier disruption due to inflammation, often triggered by conditions like sepsis. Sepsis-induced ALI (SALI) involves extensive damage to vascular endothelium and alveolar epithelium, leading to respiratory failure. Our study explores ferroptosis, an iron-dependent cell death pathway, and calcium dysregulation in SALI. Elevated cytosolic calcium early in ferroptosis exacerbates lipid peroxidation and cellular damage. We investigated verapamil, a calcium channel blocker, and found it reduces calcium influx, alleviates iron overload, and decreases oxidative stress, protecting against ferroptosis-induced apoptosis in lung cells. These insights suggest targeting ferroptosis pathways, including calcium and iron homeostasis, may offer new therapeutic strategies for SALI, potentially improving outcomes in ALI/ARDS.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151202"},"PeriodicalIF":2.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871123","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}