Biochemical and biophysical research communications最新文献_第7页

Network pharmacology and molecular docking technology-based predictive study and potential targets analysis of icariin for the treatment of diabetic nephropathy

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-06 DOI: 10.1016/j.bbrc.2025.151434

Min Chen , Yujie Zhou , Jianglin Yang , Huixiong Yuan

Objective

Epimedium glycoside is a flavonoid compound in Epimedium, which has been found to alleviate various chronic diseases. The effect and mechanism of icariin on the treatment of diabetes nephropathy still need to be clarified. In this study, we conducted network pharmacology and molecular docking analysis to reveal the mechanism of icariin treating DKD, and then validated its efficacy using a cell model.

Method

The structure and targets of icariin were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP), and their targets were annotated. Retrieve DKD targets from OMIM, GeneCards, and TTD databases. We constructed a protein-protein interaction (PPI) network using the STRING platform and visualized the results using Cytoscape 3.9.1 software. We also conducted GO and KEGG enrichment analysis on icariin and then performed molecular docking between icariin and key targets. Finally, we established a cell model of DKD to evaluate the efficacy of icariin in treating DKD.

Result

A total of 77 icariin targets were associated with DKD. The GO and KEGG enrichment results showed that the therapeutic effect of icariin on DKD was significantly correlated with inflammatory response, cell apoptosis, epithelial-mesenchymal transition, and PI3K/AKT signaling pathway. The molecular docking results indicate that icariin has a high affinity for key targets EGER, AKT1, and IGF1. Cell experiments showed that icariin inhibited high glucose-induced EMT, fibrosis-related proteins, levels of inflammatory factors TGF-β1, IL-6, and TNF-α, as well as phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in renal tubular epithelial cells. In addition, icariin inhibited the increase in EGER and AKT1 mRNA levels caused by high glucose and alleviated the decrease in IGF1 mRNA levels.

Conclusion

Epimedium glycoside may protect DKD by targeting EGER, AKT1, and IGF1 to inhibit PI3K/AKT signaling, but the specific mechanism needs further exploration.

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引用次数: 0

Odorants have the potential to enhance the heterologous expression of human olfactory receptors: Evidence from ethyl 3-phenylglycidate and its effects on OR1A1, OR11G2, and OR2W1

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-06 DOI: 10.1016/j.bbrc.2025.151459

Ichie Ojiro , Ryusei Kaneko , Takahiro Kashiwagi , Ikuo Terada , Kunihide Hoshino , Yuko Terada , Keisuke Ito

Human olfactory receptors are G protein-coupled receptors that detect odorants and initiate olfactory signaling. Analyzing the olfactory receptor is important to elucidate the mechanism of olfaction. However, the expression of most human olfactory receptors in heterologous cell systems is challenging because of their poor stability and poor trafficking to the cell surface, which makes it difficult to analyze them. Here, we report a case in which an odorant enhanced the cell surface expression of human olfactory receptors. Using OR1A1 as a model olfactory receptor, we screened odorants and identified ethyl 3-phenylglycidate, which significantly increased both the total and cell surface expression levels of OR1A1 in a dose-dependent manner. This increase leads to an enhanced OR1A1 response to the agonist. Functional assays confirmed that ethyl 3-phenylglycidate acts as an agonist for OR1A1. Ethyl 3-phenylglycidate also enhances the expression of other human olfactory receptors, such as OR11G2 and OR2W1, which recognize ethyl 3-phenylglycidat as an agonist, like OR1A1. These findings indicate that ethyl 3-phenylglycidate stabilizes human olfactory receptors by binding to its ligand-binding pocket. Here, we showed the examples that treating human olfactory receptor-expressing cells with an odorant during the induction of hOR expression significantly increases the expression levels of the human olfactory receptor. Our findings provide a novel strategy to enhance the functional expression of human olfactory receptors, which will contribute to understanding of the functions of olfactory receptors as well as the mechanisms underlying olfactory perception.

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引用次数: 0

Development and application of a high-titer VSV-based HCoV-NL63 pseudovirus system via C-terminal 14 amino acid truncation of spike

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-06 DOI: 10.1016/j.bbrc.2025.151458

Li-ting Shao , Ming-ming Wang , Yi-ming Wang , Tian Li , Fei Wang , Jie-rong Xin , Xin Zhang , Wei-guo Li , Xue-jun Wang , Sheng-qi Wang

To provide efficient tools for the development of novel antiviral drugs and vaccines of HCoV-NL63, it is urgently necessary to establish a safe, widely applicable, and high-titer NL63 pseudotyped particles (NL63pp) production system. In this research, we conducted a comparative analysis of several NL63pps, each with a truncated spike (S) protein missing part of its C-terminal amino acids. We discovered that deleting the C-terminal 14 amino acid sequence of the S protein (D14) led to a remarkable approximately 10-fold increase in the infection titer of VSV-based NL63pp. This value is higher than the titers of NL63pp packaged with S proteins having deletions of 18 or 24 amino acids at the C-terminus. Moreover, adding the VSV-G tag to the D14 C-terminus (D14V) resulted in an additional 30 % increase. We then constructed the recent prevalent HCoV-NL63 subgenotype C3 dual-reporter pseudovirus system C3-D14V, and found that C3-D14V had a higher infection efficiency. Utilizing this system, we investigated the susceptibility of several cell lines and observed that cells derived from liver (Huh7.5.1), small intestine (Caco-2) and lung (Calu-3) exhibited higher susceptibility. Furthermore, we applied this system to assess several bis-benzylisoquinoline alkaloids, notably, Cepharanthine demonstrated the highest inhibitory efficiency against NL63pp infection with EC₅₀ 0.61 μM. In conclusion, we have identified that S protein with a 14 amino acids deletion at the C-terminus significantly enhances the infection titer of HCoV-NL63 pseudovirus and provides an efficient VSV-based HCoV-NL63 dual-reporter (mCherry and luciferase2) pseudovirus system for various applications such as drug screening and antibody development in the future.

{"title":"Development and application of a high-titer VSV-based HCoV-NL63 pseudovirus system via C-terminal 14 amino acid truncation of spike","authors":"Li-ting Shao , Ming-ming Wang , Yi-ming Wang , Tian Li , Fei Wang , Jie-rong Xin , Xin Zhang , Wei-guo Li , Xue-jun Wang , Sheng-qi Wang","doi":"10.1016/j.bbrc.2025.151458","DOIUrl":"10.1016/j.bbrc.2025.151458","url":null,"abstract":"<div><div>To provide efficient tools for the development of novel antiviral drugs and vaccines of HCoV-NL63, it is urgently necessary to establish a safe, widely applicable, and high-titer NL63 pseudotyped particles (NL63pp) production system. In this research, we conducted a comparative analysis of several NL63pps, each with a truncated spike (S) protein missing part of its C-terminal amino acids. We discovered that deleting the C-terminal 14 amino acid sequence of the S protein (D14) led to a remarkable approximately 10-fold increase in the infection titer of VSV-based NL63pp. This value is higher than the titers of NL63pp packaged with S proteins having deletions of 18 or 24 amino acids at the C-terminus. Moreover, adding the VSV-G tag to the D14 C-terminus (D14V) resulted in an additional 30 % increase. We then constructed the recent prevalent HCoV-NL63 subgenotype C3 dual-reporter pseudovirus system C3-D14V, and found that C3-D14V had a higher infection efficiency. Utilizing this system, we investigated the susceptibility of several cell lines and observed that cells derived from liver (Huh7.5.1), small intestine (Caco-2) and lung (Calu-3) exhibited higher susceptibility. Furthermore, we applied this system to assess several bis-benzylisoquinoline alkaloids, notably, Cepharanthine demonstrated the highest inhibitory efficiency against NL63pp infection with EC<sub>50</sub> 0.61 μM. In conclusion, we have identified that S protein with a 14 amino acids deletion at the C-terminus significantly enhances the infection titer of HCoV-NL63 pseudovirus and provides an efficient VSV-based HCoV-NL63 dual-reporter (mCherry and luciferase2) pseudovirus system for various applications such as drug screening and antibody development in the future.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"751 ","pages":"Article 151458"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143312205","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}

引用次数: 0

Aged mice overexpressing cellular repressor of E1A-stimulated genes 1 in adipose tissues exhibited increased liposarcoma incidence and shortened lifespan

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-06 DOI: 10.1016/j.bbrc.2025.151454

Michihiro Hashimoto , Ayumi Goto , Shanlou Qiao , Hitoshi Yamashita

Cellular repressor of E1A-stimulated genes 1 (CREG1) is a multifunctional secreted glycoprotein that regulates p16-dependent cellular senescence and cell differentiation and accelerates brown adipogenesis. We recently demonstrated that the CREG1 levels in serum, liver, and kidney were significantly increased in aged wild-type (WT) mice, where age-related renal impairment was further aggravated by promoting cellular senescence. Based on these findings, we hypothesized that the constitutive regulation of CREG1 expression in vivo may affect lifespan. In this study, we revealed that the average lifespan of adipocyte P2-CREG1 transgenic (Tg) mice was shorter than that of WT mice. Moreover, we determined that this reduced lifespan was associated with an increased incidence of liposarcoma (LPS). Our findings indicated that the development of LPS in Tg mice may be driven by chronic inflammation induced by the p19^Arf-mouse double minute 2 pathway in white adipose tissue (WAT). These findings indicate that long-term alterations in CREG1 expression in vivo may affect tumor development in the WAT.

{"title":"Aged mice overexpressing cellular repressor of E1A-stimulated genes 1 in adipose tissues exhibited increased liposarcoma incidence and shortened lifespan","authors":"Michihiro Hashimoto , Ayumi Goto , Shanlou Qiao , Hitoshi Yamashita","doi":"10.1016/j.bbrc.2025.151454","DOIUrl":"10.1016/j.bbrc.2025.151454","url":null,"abstract":"<div><div>Cellular repressor of E1A-stimulated genes 1 (CREG1) is a multifunctional secreted glycoprotein that regulates p16-dependent cellular senescence and cell differentiation and accelerates brown adipogenesis. We recently demonstrated that the CREG1 levels in serum, liver, and kidney were significantly increased in aged wild-type (WT) mice, where age-related renal impairment was further aggravated by promoting cellular senescence. Based on these findings, we hypothesized that the constitutive regulation of CREG1 expression <em>in vivo</em> may affect lifespan. In this study, we revealed that the average lifespan of adipocyte P2-CREG1 transgenic (Tg) mice was shorter than that of WT mice. Moreover, we determined that this reduced lifespan was associated with an increased incidence of liposarcoma (LPS). Our findings indicated that the development of LPS in Tg mice may be driven by chronic inflammation induced by the p19<sup>Arf</sup>-mouse double minute 2 pathway in white adipose tissue (WAT). These findings indicate that long-term alterations in CREG1 expression <em>in vivo</em> may affect tumor development in the WAT.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151454"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glp-1 mimetic of sitagliptin improved oxidative stress and liver function tests via suppressing NOX-4 enzyme in hepatic tissues of diabetic rats

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-06 DOI: 10.1016/j.bbrc.2025.151455

Mohammad Amin Hemmati , Behina Foroozanmehr , Ali Fardin , Habib Yaribeygi

Background and aim

Oxidative stress acts as a major underlying cause of liver dysfunction in individuals with uncontrolled diabetes mellitus. However, the role of NOX-4 (nicotinamide adenine dinucleotide phosphate oxidase-4) enzymes remains poorly understood. Furthermore, the potential benefits of Sitagliptin in addressing this issue are unclear. Therefore, this experimental study aimed to explore the role of the NOX-4 enzyme and evaluate the potential benefits of Sitagliptin in diabetes-associated impaired liver tests.

Methods

Male Wistar rats were randomly assigned to four groups: normal, normal-treated, diabetic, and diabetic-treated. Diabetes was induced by a single dose of Streptozotocin (45 mg/kg). Treated animals received Sitagliptin (20 mg/day, orally) for five weeks. Blood and tissue samples were collected at the end of the five-week period, and the required data were obtained using biochemical and genetic analysis methods.

Results

In untreated rats, STZ-induced diabetes led to increased NOX-4 enzyme expression in the liver and a reduction in the antioxidant enzymes SOD, CAT, and GLT, collectively contributing to heightened oxidative damage, as indicated by elevated MDA levels. These alterations were associated with elevated circulating levels of SGOT, SGPT, and ALP. However, Sitagliptin reversed these alterations in diabetic animals. It enhanced the activity of antioxidant enzymes, reduced NOX-4 enzyme expression and oxidative damage in liver tissues, and subsequently improved liver function test results.

Conclusion

NOX-4 oxidant enzyme appears to play a critical role in diabetes-induced oxidative stress and subsequent liver failure. However, Sitagliptin may offer extra-glycemic benefits by normalizing NOX-4 enzyme activity levels, thereby improving liver function test results.

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引用次数: 0

Cancer-associated mutation at glycine 400 in TIP60 disrupt its phase separation property and catalytic activity resulting in compromised DNA damage repair function of the cell

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-06 DOI: 10.1016/j.bbrc.2025.151457

Himanshu Gupta , Ashutosh Singh , Ashish Gupta

TIP60 is a tumor suppressor with histone acetyltransferase (HAT) activity, playing a crucial role in regulating chromatin architecture by acetylating histones to enhance accessibility for other regulatory factors. Its function is vital for several key cellular processes, including DNA damage repair, apoptosis, and autophagy. While the downregulation of TIP60 has been associated with various cancers, the effects of naturally occurring mutations in TIP60 on its function in malignancies remain poorly understood. In this study, we explored how cancer-related mutations in TIP60 impact its structure and function. Several deleterious and destabilizing missense mutations were identified and analyzed for structural changes. Molecular dynamics simulations revealed alterations in protein conformational stability and radius of gyration due to these mutations, supported by significant changes in TIP60's solvent accessibility and intramolecular hydrogen bonding. Biochemical assays with recombinant proteins showed a loss of catalytic activity in the G400W mutant. Live cell imaging indicated abnormal localization of the G400W mutant within the nucleus. Additionally, we observed aberrant phase separation of TIP60 caused by the G400W mutation. Notably, the G400W mutation impairs TIP60's catalytic function, preventing effective DNA repair and leaving the genome vulnerable to further mutations. Our findings highlight cancer-associated mutations in TIP60 that may contribute to the molecular mechanisms underlying cancer initiation and progression.

{"title":"Cancer-associated mutation at glycine 400 in TIP60 disrupt its phase separation property and catalytic activity resulting in compromised DNA damage repair function of the cell","authors":"Himanshu Gupta , Ashutosh Singh , Ashish Gupta","doi":"10.1016/j.bbrc.2025.151457","DOIUrl":"10.1016/j.bbrc.2025.151457","url":null,"abstract":"<div><div>TIP60 is a tumor suppressor with histone acetyltransferase (HAT) activity, playing a crucial role in regulating chromatin architecture by acetylating histones to enhance accessibility for other regulatory factors. Its function is vital for several key cellular processes, including DNA damage repair, apoptosis, and autophagy. While the downregulation of TIP60 has been associated with various cancers, the effects of naturally occurring mutations in TIP60 on its function in malignancies remain poorly understood. In this study, we explored how cancer-related mutations in TIP60 impact its structure and function. Several deleterious and destabilizing missense mutations were identified and analyzed for structural changes. Molecular dynamics simulations revealed alterations in protein conformational stability and radius of gyration due to these mutations, supported by significant changes in TIP60's solvent accessibility and intramolecular hydrogen bonding. Biochemical assays with recombinant proteins showed a loss of catalytic activity in the G400W mutant. Live cell imaging indicated abnormal localization of the G400W mutant within the nucleus. Additionally, we observed aberrant phase separation of TIP60 caused by the G400W mutation. Notably, the G400W mutation impairs TIP60's catalytic function, preventing effective DNA repair and leaving the genome vulnerable to further mutations. Our findings highlight cancer-associated mutations in TIP60 that may contribute to the molecular mechanisms underlying cancer initiation and progression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151457"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427556","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}

引用次数: 0

Multi-omics profiles reveal immune microenvironment alterations associated with PD-L1 checkpoint in acute pancreatitis in the early phase

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-05 DOI: 10.1016/j.bbrc.2025.151451

Di Wu , Wenhao Cai , Zehao Wu , Yilin Huang , Rajarshi Mukherjee , Jie Peng , Wei Huang , Qiang Li , Qing Xia , Kuirong Jiang

Background

Acute pancreatitis (AP) initiates as primarily sterile local inflammation that triggers pro-inflammatory response, which is subsequently counterbalanced by an anti-inflammatory response. Immune checkpoints, such as PD-1/PD-L1, play a pivotal role in modulating these responses to prevent excessive immune activation and associated inflammatory damage. This study aimed to investigate the underlying mechanisms of these processes in both murine and human AP.

Methods

We conducted a comprehensive integration of data from cerulein-induced AP mouse models (CER-AP), utilizing single-cell RNA sequencing and digital spatial profiling for pancreatic samples, as well as single-cell Cytometry by Time Of Flight (CyTOF) for blood samples. Additionally, bulk-RNA sequencing performed on blood samples from AP patients was employed to investigate innate and adaptive immune changes at early stage of the disease.

Results

Across the four analytical approaches, we observed consistent immune cell type distributions. Our integrative analysis revealed a significant imbalance between increased innate immune cells, including neutrophils, macrophages, and monocytes, and decreased adaptive immune cells, including CD4⁺ and CD8⁺ T cells, in early-stage AP. Notably, the PD-1/PD-L1 related pathway exhibited substantial alterations, especially in the acinar cells, T cells, B cells, macrophages, and neutrophils at the early stage of disease. Moreover, we observed a significant reduction in PD-L1 expression in the blood and regulatory T cells of CyTOF mice at the CyTOF level.

Conclusion

This multi-omics analysis deciphers a distinct imbalance between increased innate immunity and decreased adaptive immunity during the early phase of AP. The PD-L1 checkpoint emerges as a key regulator of immune homeostasis and a critical factor in the pathogenesis of AP.

{"title":"Multi-omics profiles reveal immune microenvironment alterations associated with PD-L1 checkpoint in acute pancreatitis in the early phase","authors":"Di Wu , Wenhao Cai , Zehao Wu , Yilin Huang , Rajarshi Mukherjee , Jie Peng , Wei Huang , Qiang Li , Qing Xia , Kuirong Jiang","doi":"10.1016/j.bbrc.2025.151451","DOIUrl":"10.1016/j.bbrc.2025.151451","url":null,"abstract":"<div><h3>Background</h3><div>Acute pancreatitis (AP) initiates as primarily sterile local inflammation that triggers pro-inflammatory response, which is subsequently counterbalanced by an anti-inflammatory response. Immune checkpoints, such as PD-1/PD-L1, play a pivotal role in modulating these responses to prevent excessive immune activation and associated inflammatory damage. This study aimed to investigate the underlying mechanisms of these processes in both murine and human AP.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive integration of data from cerulein-induced AP mouse models (CER-AP), utilizing single-cell RNA sequencing and digital spatial profiling for pancreatic samples, as well as single-cell Cytometry by Time Of Flight (CyTOF) for blood samples. Additionally, bulk-RNA sequencing performed on blood samples from AP patients was employed to investigate innate and adaptive immune changes at early stage of the disease.</div></div><div><h3>Results</h3><div>Across the four analytical approaches, we observed consistent immune cell type distributions. Our integrative analysis revealed a significant imbalance between increased innate immune cells, including neutrophils, macrophages, and monocytes, and decreased adaptive immune cells, including CD4<sup>+</sup> and CD8<sup>+</sup> T cells, in early-stage AP. Notably, the PD-1/PD-L1 related pathway exhibited substantial alterations, especially in the acinar cells, T cells, B cells, macrophages, and neutrophils at the early stage of disease. Moreover, we observed a significant reduction in PD-L1 expression in the blood and regulatory T cells of CyTOF mice at the CyTOF level.</div></div><div><h3>Conclusion</h3><div>This multi-omics analysis deciphers a distinct imbalance between increased innate immunity and decreased adaptive immunity during the early phase of AP. The PD-L1 checkpoint emerges as a key regulator of immune homeostasis and a critical factor in the pathogenesis of AP.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"751 ","pages":"Article 151451"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349134","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}

引用次数: 0

Salusin-α attenuates lipid accumulation of C57BL/6 mice with Non-alcoholic fatty liver

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-05 DOI: 10.1016/j.bbrc.2025.151452

Ke-qian Chen , Tao Zeng , Wen-rui Tang , Shu-zhi Wang

With the development of society and economy, Non-alcoholic fatty liver disease (NAFLD) has gradually affected people's health. It is very important to find an effective treatment for NAFLD. Salusin-α is a kind of cardiovascular active peptide that can reduce blood pressure and slow down the heart rate. Studies have shown that Salusin-α can inhibit the development of atherosclerosis by regulating lipid metabolism. However, whether Salusin-α can inhibit the lipid accumulation of C57BL/6 mice with NAFLD has not been reported. Our study found that Salusin-α ameliorated lipid accumulation of NAFLD mice. Salusin-α has a good prospect in the treatment of NAFLD.

引用次数: 0

Lactobacillus rhamnosus GG ameliorates atherosclerosis via suppression of oxidative stress and inflammation by reshaping the gut microbiota

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-05 DOI: 10.1016/j.bbrc.2025.151417

Yajuan Liu , Zhixia Bai , Ru Yan , Junbai Ma , Liting Wang , Yiwei Li , Yuanyuan Liu , Huiyan Ma , Ting Wang , Libo Yang , Jian Liu , Wenke Shen , Xiaoxia Zhang , Shaobin Jia , Hao Wang

Objective

With growing awareness of probiotics' benefits, more studies are exploring their efficacy and mechanisms in reducing atherosclerosis (AS). This study aimed to investigate the potential therapeutic effects of Lactobacillus rhamnosus GG (LGG) on atherosclerotic mice and underlying mechanisms.

Design

ApoE^−/− mice were gavaged with a dose of 2 × 10⁹ CFU LGG per mouse once daily, while both ApoE^−/− and C57BL/6J mice received normal saline as controls. After 15 weeks, en face Oil Red O staining and aortic sinus morphometry were used to assess the effects of LGG intervention on AS. The expression of the Nrf2/HO-1 pathway, along with oxidative stress and inflammation, was measured in the aortic sinus, aortas, or plasma. Immune cells were analyzed by flow cytometry. 16S rRNA gene sequencing analysis evaluated structural changes in the intestinal microbiota.

Results

LGG-treated ApoE^−/− mice showed a significant reduction of AS progression by suppressing oxidative stress and inflammation. Mechanistically, LGG intervention significantly increased the levels of Nrf2/HO-1 in the aortic sinus of ApoE^−/− mice. Moreover, decreased aortic macrophages and elevated blood regulatory T cells (Tregs) were found with LGG intervention in the murine AS model. Moreover, compared to C57BL/6J mice, ApoE^−/− mice exhibited disrupted intestinal flora. Nonetheless, LGG intervention restored their intestinal flora to a composition resembling that of C57BL/6J mice, thereby increasing the abundance of beneficial bacteria.

Conclusion

LGG significantly attenuates AS by reducing oxidative stress and inflammation probably via activating the Nrf2/HO-1 pathway. Remarkably, LGG modulates gut microbiota, further enhancing its protective efficacy against AS.

{"title":"Lactobacillus rhamnosus GG ameliorates atherosclerosis via suppression of oxidative stress and inflammation by reshaping the gut microbiota","authors":"Yajuan Liu , Zhixia Bai , Ru Yan , Junbai Ma , Liting Wang , Yiwei Li , Yuanyuan Liu , Huiyan Ma , Ting Wang , Libo Yang , Jian Liu , Wenke Shen , Xiaoxia Zhang , Shaobin Jia , Hao Wang","doi":"10.1016/j.bbrc.2025.151417","DOIUrl":"10.1016/j.bbrc.2025.151417","url":null,"abstract":"<div><h3>Objective</h3><div>With growing awareness of probiotics' benefits, more studies are exploring their efficacy and mechanisms in reducing atherosclerosis (AS). This study aimed to investigate the potential therapeutic effects of <em>Lactobacillus rhamnosus</em> GG (LGG) on atherosclerotic mice and underlying mechanisms.</div></div><div><h3>Design</h3><div><em>ApoE</em><sup><em>−/−</em></sup> mice were gavaged with a dose of 2 × 10<sup>9</sup> CFU LGG per mouse once daily, while both <em>ApoE</em><sup>−/−</sup> and C57BL/6J mice received normal saline as controls. After 15 weeks, en face Oil Red O staining and aortic sinus morphometry were used to assess the effects of LGG intervention on AS. The expression of the Nrf2/HO-1 pathway, along with oxidative stress and inflammation, was measured in the aortic sinus, aortas, or plasma. Immune cells were analyzed by flow cytometry. 16S rRNA gene sequencing analysis evaluated structural changes in the intestinal microbiota.</div></div><div><h3>Results</h3><div>LGG-treated <em>ApoE</em><sup><em>−/−</em></sup> mice showed a significant reduction of AS progression by suppressing oxidative stress and inflammation. Mechanistically, LGG intervention significantly increased the levels of Nrf2/HO-1 in the aortic sinus of <em>ApoE</em><sup><em>−/−</em></sup> mice. Moreover, decreased aortic macrophages and elevated blood regulatory T cells (Tregs) were found with LGG intervention in the murine AS model. Moreover, compared to C57BL/6J mice, <em>ApoE</em><sup><em>−/−</em></sup> mice exhibited disrupted intestinal flora. Nonetheless, LGG intervention restored their intestinal flora to a composition resembling that of C57BL/6J mice, thereby increasing the abundance of beneficial bacteria.</div></div><div><h3>Conclusion</h3><div>LGG significantly attenuates AS by reducing oxidative stress and inflammation probably via activating the Nrf2/HO-1 pathway. Remarkably, LGG modulates gut microbiota, further enhancing its protective efficacy against AS.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"751 ","pages":"Article 151417"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of NaCl on Bi-functionality of a chimeric enzyme for aromatic amino acid biosynthesis in Prevotella and Porphyromonas bacteria

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-04 DOI: 10.1016/j.bbrc.2025.151430

Yu Bai, Chenwei Dai

3-Deoxy-D-arabino heptulosonate-7-phosphate synthase (DAH7PS) and chorismate mutase (CM) are key enzymes in the shikimate pathway responsible for aromatic amino acid biosynthesis in bacteria. This study investigated the functional interplay between the DAH7PS and CM domains within the bifunctional enzyme PniDAH7PS-CM from Prevotella nigrescens, a representative of the chimeric enzyme group DAH7PS-CM that is primarily distributed in the Prevotella and Porphyromonas genera. Analysis of the surface polarity demonstrated that DAH7PS and CM domains rely on hetero-domain polar interactions for their catalytic functions, rather than hydrophobic contacts. We evaluated the effects of NaCl on the catalytic activity, conformation, thermal stability, and molecular aggregation of PniDAH7PS-CM at varying NaCl concentrations (0, 150, and 300 mM). Results demonstrated that increasing NaCl concentrations significantly reduced the enzymatic activities of both DAH7PS and CM, with a complete loss of DAH7PS function at 300 mM NaCl. Notably, high NaCl concentrations promoted a more extended conformation of PniDAH7PS-CM and interfere with enzyme aggregation, suggesting that NaCl modulates the inter-domain interactions. Our findings suggest that Na⁺ ions, as kosmotropic agents, likely via enhancing the hydration layer on the enzyme's surface, stabilizes PniDAH7PS-CM structure but disrupting essential polar interactions for catalysis. Conversely, Cl⁻ ions may act as chaotropic agents, further impairing these interactions. This study illuminates the balance between salt ion concentration and enzyme functionality, offering insights for developing therapeutic strategies targeting bacterial metabolism and growth in the context of periodontal diseases.

{"title":"Regulation of NaCl on Bi-functionality of a chimeric enzyme for aromatic amino acid biosynthesis in Prevotella and Porphyromonas bacteria","authors":"Yu Bai, Chenwei Dai","doi":"10.1016/j.bbrc.2025.151430","DOIUrl":"10.1016/j.bbrc.2025.151430","url":null,"abstract":"<div><div>3-Deoxy-D-<em>arabino</em> heptulosonate-7-phosphate synthase (DAH7PS) and chorismate mutase (CM) are key enzymes in the shikimate pathway responsible for aromatic amino acid biosynthesis in bacteria. This study investigated the functional interplay between the DAH7PS and CM domains within the bifunctional enzyme <em>Pni</em>DAH7PS-CM from <em>Prevotella nigrescens</em>, a representative of the chimeric enzyme group DAH7PS-CM that is primarily distributed in the <em>Prevotella</em> and <em>Porphyromonas</em> genera. Analysis of the surface polarity demonstrated that DAH7PS and CM domains rely on hetero-domain polar interactions for their catalytic functions, rather than hydrophobic contacts. We evaluated the effects of NaCl on the catalytic activity, conformation, thermal stability, and molecular aggregation of <em>Pni</em>DAH7PS-CM at varying NaCl concentrations (0, 150, and 300 mM). Results demonstrated that increasing NaCl concentrations significantly reduced the enzymatic activities of both DAH7PS and CM, with a complete loss of DAH7PS function at 300 mM NaCl. Notably, high NaCl concentrations promoted a more extended conformation of <em>Pni</em>DAH7PS-CM and interfere with enzyme aggregation, suggesting that NaCl modulates the inter-domain interactions. Our findings suggest that Na⁺ ions, as kosmotropic agents, likely via enhancing the hydration layer on the enzyme's surface, stabilizes <em>Pni</em>DAH7PS-CM structure but disrupting essential polar interactions for catalysis. Conversely, Cl⁻ ions may act as chaotropic agents, further impairing these interactions. This study illuminates the balance between salt ion concentration and enzyme functionality, offering insights for developing therapeutic strategies targeting bacterial metabolism and growth in the context of periodontal diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"751 ","pages":"Article 151430"},"PeriodicalIF":2.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350222","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}

引用次数: 0