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Materials Today Bio · 2024 · IF 8.7

Melatonin-loaded bioactive microspheres accelerate aged bone regeneration by formation of tunneling nanotubes to enhance mitochondrial transfer

Huacui Xiong,Huanhuan Qiu,Chunhui Wang,Yonghao Qiu,Shuyi Tan,Ke Chen,Fujian Zhao,Jinlin Song

The repair of bone defects in the elderly individuals is significantly delayed due to cellular senescence and dysfunction, which presents a challenge in clinical settings. Furthermore, there are limited effective methods available to promote bone repair in older individuals. Herein, melatonin-loaded mesoporous bioactive glasses microspheres (MTBG) were successfully prepared based on their mesoporous properties. The repair of bone defects in aged rats was significantly accelerated by enhancing mitochondrial function through the sustained release of melatonin and bioactive ions. MTBG effectively rejuvenated senescent bone marrow mesenchymal stem cells (BMSCs) by scavenging excessive reactive oxygen species (ROS), stabilizing the mitochondrial membrane potential (ΔΨm), and increasing ATP synthesis. Analysis of the underlying mechanism revealed that the formation of tunneling nanotubes (TNTs) facilitated the intercellular transfer of mitochondria, thereby resulting in the recovery of mitochondrial function. This study provides critical insights into the design of new biomaterials for the elderly individuals and the biological mechanism involved in aged bone regeneration.

CAS / MDL: 73-31-4
研究领域: 生物材料 · 组织工程 · 老年学 · 细胞生物学 · 再生医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science Advances · 2024 ·Vol. 10 ·期 28 · IF 11.7

Prodrug-inspired adenosine triphosphate–activatable celastrol-Fe(III) chelate for cancer therapy

Hanrong Li,Yifan Li,Lingpu Zhang,Nan Wang,Dong Lu,Dongsheng Tang,Yitong Lv,Jinbo Zhang,Heben Yan,He Gong,Ming Zhang,Kaili Nie,Yi Hou,Yingjie Yu,Haihua Xiao,Chaoyong Liu

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)–responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS–rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.

研究领域: 药理学 · 纳米技术 · 癌症研究 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2024 · IF 8.5

Metabolomics, volatolomics, and bioinformatics analyses of the effects of ultra-high pressure pretreatment on taste and flavour parameters of cured Culter alburnus

Dongyin Liu,Mingzhu Zhou,Hongyuan Tan,Guangquan Xiong,Lan Wang,Liu Shi,Chuan Li,Wenjin Wu,Yu Qiao

The effects of ultra-high pressure (UHP) pretreatment (50–250 MPa) on the fish curing were studied. UHP increased the overall volatile compound concentration of cured fish. Among 50–250 MPa five treatment groups, 150 MPa UHP group exhibited the highest total free amino acid content (294.34 mg/100 g) with that of the control group being 92.39 mg/100 g. The activity of cathepsin L was increased under 50–200 MPa UHP treatment (62.28–58.15 U/L), compared with that in the control group (53.80 U/L). UHP treatment resulted in a significant increase in small molecule compounds, especially the amino acid dipeptides and ATP metabolic products. Under UHP treatments, the bacterial phyla Actinobacteriota (1.04–5.25 %), Bacteroidota (0.20–4.47 %), and Deinococcota (0.00–0.05 %) exhibited an increased abundance, and they promoted taste and flavor formation . Our results indicated that UHP is a promising pretreatment method to improve taste and flavour in cured fish by affecting the microorganisms, cathepsin, and proteins.

研究领域: 食品科学 · 代谢组学 · 挥发组学 · 生物信息学
✓ 已验证 DOI PubMed 高影响因子
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Food Biophysics · 2015 ·Vol. 10 ·期 4 ·447-455 · IF 1.63

Ca2+-Induced Conformational Changes of Myosin from Silver Carp (Hypophthalmichthys molitrix) in Gelation

Cao Liwei,Su Sisi,Regenstein Joe M.,Xiong Shanbai,Liu Ru

The role of Ca 2+ in gelation of myosin extracted from silver carp ( Hypophthalmichthys molitrix ) was investigated. Compared with the control, myosin with CaCl 2 showed higher turbidity and larger particle size, indicating that CaCl 2 contributed to myosin aggregation. Addition of CaCl 2 decreased the myosin thermostability and promoted the unfolding of myosin α-helical structure during heating. Moreover, CaCl 2 could increase surface hydrophobicity at low temperatures (20–40 °C) and promoted hydrophobic interactions. Meanwhile, it decreased the temperature of disulfide bond formation by about 10 °C. Addition of 10–40 mM CaCl 2 favored activation of the Ca 2+ -ATPase activity at 20 to 30 °C, but not obvious with elevated temperatures. Ca 2+ -ATPase activity of myosin was undetectable when heated above 60 °C because of severe structural damage of myosin heads. G’ at both the first and second peaks increased with increasing CaCl 2 concentration. Therefore, CaCl 2 was beneficial for gelation of myosin by inducing the unfolding of myosin and enhancing disulfide bonds along with hydrophobic interactions between neighboring myosin molecules.

研究领域: 食品科学 · 生物化学 · 蛋白质化学
✓ 已验证 DOI 高影响因子
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JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE · 2015 ·Vol. 52 ·期 12 ·8196-8203 · IF 2.203

Antibacterial mechanism and activities of black pepper chloroform extract

Zou Lan,Hu Yue-Ying,Chen Wen-Xue

Black pepper extracts reportedly inhibit food spoilage and food pathogenic bacteria. This study explored the antimicrobial activity of black pepper chloroform extract (BPCE) against Escherichia coli and Staphylococcus aureus. The antibacterial mechanism of BPCE was elucidated by analyzing the cell morphology, respiratory metabolism, pyruvic acid content, and ATP levels of the target bacteria. Scanning electron micrographs showed that the bacterial cells were destroyed and that plasmolysis was induced. BPCE inhibited the tricarboxylic acid pathway of the bacteria. The extract significantly increased pyruvic acid concentration in bacterial solutions and reduced ATP level in bacterial cells. BPCE destroyed the permeability of the cell membrane, which consequently caused metabolic dysfunction, inhibited energy synthesis, and triggered cell death.

研究领域: 微生物学 · 食品科学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF APPLIED MICROBIOLOGY · 2018 ·Vol. 124 ·期 5 ·1060-1070 · IF 2.16

Effects of glutaraldehyde–didecyldimethylammonium bromide combined disinfectant on the cell surface of Staphylococcus aureus

Lin W.,Yi J.,Zhang Y.,Deng Z.,Chen Q.,Niu B.

AimsThe effects of a new glutaraldehyde–didecyldimethylammonium bromide combination disinfectant (GD) on the cell surface of Staphylococcus aureus, a representative Gram‐positive bacterium, were investigated in this study.Methods and ResultsResults of bacterial surface structural analysis showed that GD significantly changed the bacterial morphology. The membrane fluidity decreased and outer membrane permeabilization increased after contact with GD. Furthermore, the integrity of the cytoplasmic membrane was destroyed by over 99% after exposure to GD for a short time. Bacterial ATPase activity correlated negatively with the treatment of GD over time, and proteins were degraded. Assays of intracellular component leakage indicated that GD caused the rapid leakage of K+, Mg2+, ATP molecules, and proteins into the extracellular environment.ConclusionsThe effects of GD against S. aureus are probably attributable to the removal of the permeability barrier, changes in the S. aureus morphology, changes in the structures and functions of the cell membrane, leakage of intracellular substances and disturbance of the intracellular homeostasis. As a result, this irreversible damage accelerated the death of S. aureus.Significance and Impact of the StudyIn an earlier study, the bactericidal mechanism of GD against Escherichia coli was investigated. Hence, this study focused on the action of mechanism of GD against S. aureus. It is important to clarify the disinfectant bactericidal mechanisms of GD against bacterium, in general, and this study provides theoretical support to the prevention of bacterial resistance.

CAS / MDL: 2390-68-3
研究领域: 微生物学 · 药理学 · 传染病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Stem Cell Research & Therapy · 2024 ·Vol. 15 ·期 1 ·1-21 · IF 7.1

LncRNA SNHG1 enhances cartilage regeneration by modulating chondrogenic differentiation and angiogenesis potentials of JBMMSCs via mitochondrial function regulation

Liu Hua,Liu Huina,Yang Qiubo,Fan Zhipeng

Background Cartilage is a kind of avascular tissue, and it is difficult to repair itself when it is damaged. In this study, we investigated the regulation of chondrogenic differentiation and vascular formation in human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) by the long-chain noncoding RNA small nucleolar RNA host gene 1 (SNHG1) during cartilage tissue regeneration. Methods JBMMSCs were isolated from the jaws via the adherent method. The effects of lncRNA SNHG1 on the chondrogenic differentiation of JBMMSCs in vitro were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Pellet experiment, Alcian blue staining, Masson’s trichrome staining, and modified Sirius red staining. RT-qPCR, matrix gel tube formation, and coculture experiments were used to determine the effect of lncRNA SNHG1 on the angiogenesis in JBMMSCs in vitro. A model of knee cartilage defects in New Zealand rabbits and a model of subcutaneous matrix rubber suppositories in nude mice were constructed for in vivo experiments. Changes in mitochondrial function were detected via RT-qPCR, dihydroethidium (DHE) staining, MitoSOX staining, tetramethyl rhodamine methyl ester (TMRM) staining, and adenosine triphosphate (ATP) detection. Western blotting was used to detect the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). Results Alcian blue staining, Masson’s trichrome staining, and modified Sirius Red staining showed that lncRNA SNHG1 promoted chondrogenic differentiation. The lncRNA SNHG1 promoted angiogenesis in vitro and the formation of microvessels in vivo. The lncRNA SNHG1 promoted the repair and regeneration of rabbit knee cartilage tissue. Western blot and alcian blue staining showed that the JAK inhibitor reduced the increase of STAT3 phosphorylation level and staining deepening caused by SNHG1. Mitochondrial correlation analysis revealed that the lncRNA SNHG1 led to a decrease in reactive oxygen species (ROS) levels, an increase in mitochondrial membrane potential and an increase in ATP levels. Alcian blue staining showed that the ROS inhibitor significantly alleviated the decrease in blue fluorescence caused by SNHG1 knockdown. Conclusions The lncRNA SNHG1 promotes chondrogenic differentiation and angiogenesis of JBMMSCs. The lncRNA SNHG1 regulates the phosphorylation of STAT3, reduces the level of ROS, regulates mitochondrial energy metabolism, and ultimately promotes cartilage regeneration.

CAS / MDL: 329-98-6
研究领域: 干细胞生物学 · 再生医学 · 分子生物学 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioengineered · 2022 · IF 6.832

A novel epigenetic marker, Ten-eleven translocation family member 2 (TET2), is identified in the intractable epileptic brain and regulates ATP binding cassette subfamily B member 1 (ABCB1) in the blood–brain barrier

Fan-Cheng Kong,Li-Qin Lang,Jie Hu,Xia-Ling Zhang,Ming-Kang Zhong,Chun-Lai Ma

Drug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Here, we quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain hemorrhage controls (n = 10) by immunochemical staining. TET2 and ATP binding cassette subfamily B member 1 (ABCB1) expression patterns were determined in the isolated brain capillaries of DRE patients. TET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed no differences in expression. We also found that a particularly strong expression of TET2 in the vascular tissue of DRE patients. ABCB1 and TET2 have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In blood–brain barrier (BBB) model, TET2 depletion can cause attenuated expression and function of ABCB1. Data from a cohort study and experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE.

研究领域: 神经病学 · 表观遗传学 · 药理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Science Advances · 2024 ·Vol. 10 ·期 42 · IF 11.7

Bioenergetic-active exosomes for cartilage regeneration and homeostasis maintenance

Xulong Liu,Shangtong Jiang,Ting Jiang,Ziyang Lan,Xin Zhang,Zhenyu Zhong,Xiaodan Wu,Cunjing Xu,Yingying Du,Shengmin Zhang

Cartilage regeneration relies on adequate and continuous bioenergy supply to facilitate cellular differentiation and extracellular matrix synthesis. Chondrocytes frequently undergo energy stress under pathological conditions, characterized by disrupted cellular metabolism and reduced adenosine triphosphate (ATP) levels. However, there has limited progress in modulating energy metabolism for cartilage regeneration thus far. Here, we developed bioenergetic-active exosomes (Suc-EXO) to promote cartilage regeneration and homeostasis maintenance. Suc-EXO exhibited a 5.42-fold increase in ATP content, enabling the manipulation of cellular energy metabolism by fueling the TCA cycle. With continuous energy supply, Suc-EXO promoted BMSC chondrogenic differentiation via the P2X7-mediated PI3K-AKT pathway. Moreover, Suc-EXO improved chondrocyte anabolism and mitochondrial homeostasis via the P2X7-mediated SIRT3 pathway. In a rabbit cartilage defect model, the Suc-EXO–encapsulated hydrogel notably promoted cartilage regeneration and maintained neocartilage homeostasis, leading to 2.26 and 1.53 times increase in Col2 and ACAN abundance, respectively. These findings make a remarkable breakthrough in modulating energy metabolism for cartilage regeneration, offering immense potential for clinical translation.

研究领域: 再生医学 · 细胞代谢 · 组织工程 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Antibiotics-Basel · 2024 ·Vol. 13 ·期 6 ·528 · IF 4.3

Deciphering the Antibacterial Mechanisms of 5-Fluorouracil in Escherichia coli through Biochemical and Transcriptomic Analyses

Muchen Zhang,Huangwei Song,Siyuan Yang,Yan Zhang,Yunrui Tian,Yang Wang,Dejun Liu

The emergence of carbapenem-resistant Gram-negative pathogens presents a clinical challenge in infection treatment, prompting the repurposing of existing drugs as an essential strategy to address this crisis. Although the anticancer drug 5-fluorouracil (5-FU) has been recognized for its antibacterial properties, its mechanisms are not fully understood. Here, we found that the minimal inhibitory concentration (MIC) of 5-FU againstEscherichia coliwas 32–64 µg/mL, including strains carryingblaNDM-5, which confers resistance to carbapenems. We further elucidated the antibacterial mechanism of 5-FU againstE. coliby using genetic and biochemical analyses. We revealed that the mutation of uracil phosphoribosyltransferase-encoding geneuppincreased the MIC of 5-FU againstE. coliby 32-fold, indicating the role of theuppgene in 5-FU resistance. Additionally, transcriptomic analysis ofE. colitreated with 5-FU at 8 µg/mL and 32 µg/mL identified 602 and 1082 differentially expressed genes involved in carbon and nucleic acid metabolism, DNA replication, and repair pathways. The biochemical assays showed that 5-FU induced bacterial DNA damage, significantly increased intracellular ATP levels and the NAD+/NADH ratio, and promoted reactive oxygen species (ROS) production. These findings suggested that 5-FU may exert antibacterial effects onE. colithrough multiple pathways, laying the groundwork for its further development as a therapeutic candidate against carbapenem-resistant bacterial infections.

CAS / MDL: 51-21-8
研究领域: 微生物学 · 药理学 · 遗传学 · 生物化学 · 传染病学
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PLoS One · 2016 ·Vol. 11 ·期 4 ·e0151479 · IF 3.057

Cd-Resistant Strains of B. cereus S5 with Endurance Capacity and Their Capacities for Cadmium Removal from Cadmium-Polluted Water

Huiqing Wu,Qingping Wu,Guojie Wu,Qihui Gu,Linting Wei

The goal of this study was to identify Cd-resistant bacterial strains with endurance capacity and to evaluate their ability to remove cadmium ions from cadmium-polluted water. The Bacillus cereusS5 strain identified in this study had the closest genetic relationship with B . cereus sp. Cp1 and performed well in the removal of Cd 2+ ions from solution. The results showed that both the live and dead biomasses of the Cd 2+ -tolerant B . cereus S5 strain could absorb Cd 2+ ions in solution but that the live biomass of the B . cereus S5 strain outperformed the dead biomass at lower Cd 2+ concentrations. An analysis of the cadmium tolerance genes of B . cereus S5 identified ATPase genes that were associated with cadmium tolerance and involved in the ATP pumping mechanism. The FTIR spectra revealed the presence of amino, carboxyl and hydroxyl groups on the pristine biomass and indicated that the cadmium ion removal ability was related to the structure of the strain. The maximum absorption capacity of the B . cereus S5 strain in viable spore biomass was 70.16 mg/g (dry weight) based on a pseudo-second-order kinetic model fit to the experimental data. The Langmuir and Langmuir-Freundlich isotherm adsorption models fit the cadmium ion adsorption data well, and the kinetic curves indicated that the adsorption rate was second-order. For Cd 2+ concentrations (mg/L) of 1–109 mg/L, good removal efficiency (>80%) was achieved using approximately 3.48–10.3 g/L of active spore biomass of the B . cereus S5 strain. A cadmium-tolerant bacteria-activated carbon-immobilized column could be used for a longer duration and exhibited greater treatment efficacy than the control column in the treatment of cadmium-polluted water. In addition, a toxicity assessment using mice demonstrated that the biomass of the B . cereus S5 strain and its fermentation products were non-toxic. Thus, the isolated B . cereus S5 strain can be considered an alternative biological adsorbent for use in emergency responses to severe cadmium pollution and in the routine treatment of trace cadmium pollution.

研究领域: 环境微生物学 · 生物修复 · 水处理 · 毒理学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Structural characteristics of a polysaccharide from Armillariella tabescens and its protective effect on colitis mice via regulating gut microbiota and intestinal barrier function

Yuan-Yuan Li,Jing-Wen Sun,Lei Chen,Yong-Ming Lu,Qing-Xi Wu,Chao Yan,Yan Chen,Mei Zhang,Wen-Na Zhang

A new polysaccharide fraction (ATP) was obtained from Armillariella tabescens mycelium. Structural analysis suggested that the backbone of ATP was →4)- α -D-Glc p (1 → 2)- α -D-Gal p (1 → 2)- α -D-Glc p (1 → 4)- α -D-Glc p (1→, which branched at O-3 of →2)- α -D-Glc p (1 → and terminated with T- α -D-Glc p or T- α -D-Man p . Besides, ATP significantly alleviated ulcerative colitis (UC) symptoms and inhibited the production of pro-inflammation cytokines (IL-1 β , IL-6). Meanwhile, ATP could improve colon tissue damage by elevating the expression of MUC2 and tight junction proteins (ZO-1, occludin and claudin-1) levels and enhance intestinal barrier function through inhibiting the activation of MMP12/MLCK/ p -MLC2 signaling pathway. Further studies exhibited that ATP could increase the relative abundance of beneficial bacteria such as f. Muribaculacese , g. Muribaculaceae , and g. Alistips , and decrease the relative abundance of g. Desulfovibrio , g. Colidextribacter , g. Ruminococcaceae and g .Oscillibacter , and regulate the level of short-chain fatty acids. Importantly, FMT intervention with ATP-derived microbiome certified that gut microbiota was involved in the protective effects of ATP on UC. The results indicated that ATP was potential to be further developed into promising therapeutic agent for UC.

研究领域: 药理学 · 免疫学 · 胃肠病学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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