EXPERIMENTAL ANIMALS
·
2024
·
IF 2.2
Xiaolong ZHAO,Longqi SHANG,Chunjian SHEN
Daphnetin has been demonstrated to exert beneficial effects on diabetes mellitus and renal complications. However, the role and molecular mechanism of daphnetin in diabetic cardiomyopathy (DCM) remain unclear. In this study, rats were injected with streptozotocin (STZ) to induce diabetes. The diabetic rats were then administered daphnetin (1 and 4 mg/kg) or dimethyl sulfoxide (DMSO) daily for 12 weeks. The results demonstrated that the diabetic rats exhibited elevated blood glucose levels, which were dose-dependently ameliorated by daphnetin. At 13 weeks following STZ injection, the rats exhibited typical diabetic signs, cardiac dysfunction, and evident pathological alterations in myocardial tissues. The administration of daphnetin to diabetic rats resulted in improvement in cardiac function, reductions in myocardial injury biomarkers, and the inhibition of myocardial fibrosis. Furthermore, daphnetin treatment suppressed inflammation and endoplasmic reticulum stress-induced apoptosis in a dose-dependent manner. Additionally, daphnetin exhibited partial blockade of the activation of mitogen-activated protein kinase pathways induced by diabetes. These findings indicate that daphnetin may be a promising therapeutic agent for the treatment of DCM.
CAS / MDL:
研究领域:
药理学
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心脏病学
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糖尿病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2024
·Vol. 90
·期 9
·
IF 3.9
Yuan Li,Shu-Fang Li,Lin Zhang,Ya-Ping Xue,Yu-Guo Zheng
Hydroxysteroid dehydrogenases (HSDHs) catalyze the oxidation/reduction of hydroxyl/keto groups of steroids with high regio- or stereoselectivity, playing an essential role in producing optically pure chemicals. In this work, a novel approach was developed to simultaneously improve the stability and activity of 7β-hydroxysteroid dehydrogenase (7β-HSDH) by combining B-factor analysis and computer-aided prediction. Several advantageous mutants were identified, and the most promising variant, S51Y/P202Y, exhibited 2.3-fold improvements in catalytic activity, 3.3-fold in half-life at 40°C, and 4.7-fold in catalytic efficiency (kcat/Km), respectively. Structural modeling analysis showed that the shortened reversible oxidation reaction catalytic distance and the strengthened residue interactions compared to the wild type were attributed to the improved stability and activity of the obtained mutants. To synthesize ursodeoxycholic acid cost-effectively by mutant S51Y/P202Y, a NAD-kinase was employed to facilitate the substitution of nicotinamide adenine dinucleotide phosphate (NADP+) with nicotinamide adenine dinucleotide (NAD+) in the whole-cell catalysis system. The substrate 7-ketolithocholic acid (100 mM) was converted completely in 0.5 h, achieving a space-time yield of 1,887.3 g L−1 d−1. This work provided a general target-oriented strategy for obtaining stable and highly active dehydrogenase for efficient biosynthesis.
研究领域:
生物技术
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酶工程
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生物化学
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化学生物学
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DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2024
·
IF 2.2
Jingzhi WANG,Zhongyu HUANG,Yiwen LI,Qian LI,Xi LI,Li CHEN
At present, there lacks a definitive pharmaceutical intervention or therapeutic approach for diabetes-associated cognitive impairment. Herein, we delved into the impact of electroacupuncture on cognitive function in high-fat diet/streptozocin (HFD/STZ)-induced T2DM mice and underlying mechanisms. Hippocampal insulin resistance was determined by western blot analysis. Cognitive function was evaluated by Morris water maze test. The morphology of the hippocampal neurons was observed through hematoxylin & eosin staining and Nissl staining. Synaptic plasticity was assessed by western blot analysis. Immunofluorescence, immunohistochemistry, western blot and real-time PCR were employed to detect the levels of ferroptosis markers, autophagy markers, and netrin-1. Electroacupuncture treatment exhibited ameliorative outcomes on spatial learning, memory function, hippocampal insulin resistance, neuronal damage, and synaptic plasticity in T2DM mice. Furthermore, it effectively suppressed neuronal ferroptosis within the hippocampus by upregulating GPX4 and SLC7A11 expression, and reducing 4-HNE expression. Meanwhile, electroacupuncture intervention increased the levels of Beclin1 and LC3II/LC3I, as well as decreased the levels of p62 and phosphorylated-mTOR in the hippocampus of T2DM mice, suggesting that electroacupuncture facilitated autophagy activation by inhibiting mTOR activity. 3-MA-mediated autophagy inhibition undermined the beneficial effects of electroacupuncture on neuronal ferroptosis and cognitive deficits in T2DM mice. Additionally, the beneficial effects of electroacupuncture on autophagy and ferroptosis was achieved by upregulation of netrin-1 in the hippocampus. Our study revealed that that electroacupuncture therapy inhibited neuronal ferroptosis via the activation of autophagy, thereby ameliorating cognitive deficits in T2DM mice.
研究领域:
神经科学
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糖尿病学
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认知科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2024
·
IF 3.7
Deyi Zhao,Miran Tang,Panjie Hu,Xiaowei Hu,Weijun Chen,Zhexiao Ma,Huanchang Chen,Haifeng Liu,Jianming Cao,Tieli Zhou
Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Escherichia coli (CREC) are frequently detected in clinical settings, restricting the use of carbapenems. Therefore, there is an urgent need for new antimicrobial strategies to address infections caused by CRKP and CREC. This study investigated the antibacterial, anti-biofilm, and anti-inflammatory effects of the cationic antimicrobial peptide Hs02, along with its potential antimicrobial mechanisms against CRKP and CREC. The results revealed that Hs02 had a low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against CRKP and CREC, effectively eliminating the bacteria within 30 min. Moreover, Hs02 significantly prevents biofilm formation and disrupts the established biofilms. Further mechanistic studies demonstrated that Hs02 specifically targeted and bound to bacterial outer membrane lipopolysaccharides (LPS), disrupted membrane permeability and integrity, which led to intracellular reactive oxygen species (ROS) accumulation. Furthermore, Hs02 neutralized LPS, thereby suppressing the production of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in murine macrophage RAW 264.7 cells. In vitro, hemolysis and cytotoxicity assays confirmed Hs02’s safety at the tested concentrations and proved that Hs02 improved the survival rate of Galleria mellonella larvae. In conclusion, the findings suggest that Hs02’s interaction with LPS and the resulting disruption of membrane integrity may be key factors driving its rapid bactericidal and anti-inflammatory effects.
研究领域:
微生物学
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药理学
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传染病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2024
·Vol. 90
·期 8
·
IF 3.9
Yating Li,Tong Xu,Yanqin Tu,Tong Li,Yifeng Wei,Yan Zhou
Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in Clostridia was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium Collinsella sp. zg1085, from marmot respiratory tract. In both the Clostridial and Collinsella pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (S)-3-hydroxy-5-oxohexanoate by a Mn2+-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the Collinsella pathway, (S)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP+-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO2 and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the Collinsella PGR, DPGC, and HOHA in E. coli enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with Olsenella profusa, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.
研究领域:
微生物学
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生物化学
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代谢途径
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酶学
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产品关联
DOI
PubMed
高影响因子
International Heart Journal
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2024
·Vol. 65
·期 6
·1095-1106
·
IF 1.2
Xiaoping Zhu,Shengnan Han,Yulu Geng,Wenzhi Ren,Fushi Quan
Stroke poses a serious risk to human health. The incidence of stroke is increasing year by year. In this study, a rat cerebral ischemiareperfusion (middle cerebral artery occlusion) model was established, and the reliability of this model was determined.The expression changes of key proteins of the BDNF TrkB pathway and synaptic plasticity markers (SYP, PSD-95, and MAP-2) were detected at different time points.The results showed that BDNF expression increased rapidly in the acute phase, and the expression of synaptic plasticity markers decreased, and blocking the BDNF-TrkB pathway with the specific blocker K252a also had a significant effect.This suggests that changes in the BDNF-TrkB signaling pathway can affect the synaptic plasticity in nerve cells of stroke patients.
CAS / MDL:
研究领域:
神经科学
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分子生物学
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中风研究
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产品关联
DOI
PubMed
高影响因子
mSystems
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2024
·
IF 5
Jiaming Zhang,Xiaoxia Yu,Weidong Li,Yunjing Jiang,Liangran Zhang,Shunxin Wang
A good quality egg is essential for a successful pregnancy and early embryo development. Oocyte development is vulnerable to environmental exposures. Bisphenol S (BPS) is widely used as a replacement for its analog bisphenol A, but the reproductive toxicity of BPS has been of great concern. In this study, we showed that BPS exposure induces dysbiosis of the gut microbiota, which further leads to intestinal permeability and inflammation, and ultimately impairs oocyte quality. More importantly, we found that alginate oligosaccharide reshapes the gut microbiota to improve gut homeostasis, thereby preventing the deleterious effects of BPS on the gut and oocytes. Overall, this study not only demonstrates that BPS exposure impairs the intestine and oocytes by inducing dysbiosis of the gut microbiota but also develops a preventive strategy.
研究领域:
生殖生物学
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环境毒理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
International Heart Journal
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2024
·
IF 1.2
Xiaoyu Shen,Jiamei Zhang,Zhou Zhou,Ruiqun Yu
Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL) -1β/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.
研究领域:
心脏病学
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细胞生物学
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分子生物学
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糖尿病
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病理学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2024
·
IF 2.2
Dan LI,Le WANG,Shufeng SHI,Xiaofeng DENG,Xuehan ZENG,Yunong LI,Shulin LI,Peng BAI
Acupuncture has obvious therapeutic effect on intracerebral hemorrhage (ICH). miR-34a-5p regulated by acupuncture was found to attenuate neurological deficits in ICH. However, the underlying mechanisms are unclear. Ubiquitin Like 4A (UBL4A) has not been studied in ICH. SD rats were injected with autologous blood to induce ICH and treated with Baihui-penetrating-Qubin acupuncture. Acupuncture resulted in an increase in forelimb placing test scores, and a decrease in corner test scores and brain water content of ICH rats. Histopathological examination showed that acupuncture inhibited ICH-induced inflammation, decreased damaged neurons and increased UBL4A expression. UBL4A overexpression increased cell viability, inhibited apoptosis, reduced ROS level and increased MnSOD activity, mitochondrial membrane potential and mtDNA level in rat embryonic primary cortical neurons. miR-34a-5p knockdown increased UBL4A expression, apoptosis rate and ROS level in hemin-treated neurons. Dual luciferase assays showed that miR-34a-5p bound to UBL4A. Apoptotic cells and ROS level were increased in hemin-treated neurons with UBL4A and miR-34a-5p knockdown. We firstly demonstrate the inhibitory effect of UBL4A on neuronal apoptosis, and the regulation relationship between UBL4A and miR-34a-5p. This study provides a new candidate target for ICH treatment and more basis for elucidating the molecular mechanism of acupuncture. In the future, we will conduct a deeper exploration of the effects of UBL4A on ICH.
研究领域:
神经科学
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分子生物学
·
针灸
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神经病学
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产品关联
DOI
PubMed
高影响因子
mSphere
·
2024
·
IF 3.7
Chen Tang,Haifeng Wang,Xianjiang Jin,Wenwen Li,Yonglin Wang
Verticillium dahliae causes Verticillium wilt in more than 200 plant species worldwide. As a soilborne fungus, it forms melanized microsclerotia and colonizes the xylem of host plants. Our previous study revealed a subfamily of C2H2-homeobox transcription factors in V. dahliae, but their biological roles remain unknown. In this study, we systematically characterized the functions of seven C2H2-homeobox transcription factors in V. dahliae. Deletion of VdChtf3 and VdChtf6 significantly decreased the production of melanized microsclerotia, and knockout of VdChtf1 and VdChtf4 enhanced virulence. Loss of VdChtf2 and VdChtf6 increased conidium production, whereas loss of VdChtf5 and VdChtf7 did not affect growth, conidiation, microsclerotial formation, or virulence. Further research showed that VdChtf3 activated the expression of genes encoding pectic enzymes to participate in microsclerotial formation. In addition, VdChtf4 reduced the expression of VdSOD1 to disturb the scavenging of superoxide radicals but induced the expression of genes related to cell wall synthesis to maintain cell wall integrity. These findings highlight the diverse roles of different members of the C2H2-homeobox gene family in V. dahliae.
研究领域:
真菌学
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植物病理学
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转录调控
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2024
·
IF 3.7
Yanjun Xie,Fangyi Xu,Huali Dong,Jianfeng Mao,Chuanling Zhang
The colonization of Enterococcus in the female vagina leads to neonatal and pediatric enterococcal septicemia. Linezolid (LZD) is a kind of mainstream drug for treating multidrug-resistant Gram-positive infections. OptrA is the main LZD-resistance gene at Enterococci in human isolates. It is essential to explore the prevalence of optrA-carrying Enterococcus in vaginal secretions of late pregnant women and the drug resistance of optrA. From May to June 2023, this study recruited 340 volunteers in late pregnancy (35–40 weeks of pregnancy) to provide non-repetitive vaginal discharge samples. Luria-Bertani broth and florfenicol (10 µg/mL) were used to enrich bacteria. Enterococci was identified through time-of-flight mass spectrometry. Additionally, antimicrobial susceptibility, polymerase chain reaction, and next-generation sequencing assays were applied to this study. Fifty-four optrA-carrying Enterococcus strains were obtained, the proportion of the whole vagina of late pregnant women was 15.88% (54 out of 340), and Enterococcus faecalis account the highest proportion. All optrA-carrying Enterococcus were resistant to at least three drugs. Tetracycline, chloramphenicol, erythromycin, and LZD have higher bacterial resistance rates. Genetic environment analysis revealed that IS1216E, fexA, and erm(A) may synergistically exert multidrug resistance with optrA. It is necessary to strengthen the surveillance of optrA-carrying Enterococcus in pregnant women. This study provides scientific support for controlling hospital infections and managing antibiotic-resistant bacteria, and provides a scientific basis for rational clinical medication.
研究领域:
微生物学
·
妇产科学
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感染病学
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产品关联
DOI
PubMed
高影响因子
Journal of Thoracic Disease
·
2024
·Vol. 16
·期 11
·7941
·
IF 2.1
Guowen Zou,Lei Jiang,Bin Xu,Jingyuan Xu,Zhikai Zeng,Lingchun Xia,Jian Tang,Bentong Yu
The scarcity of viable donor lungs is a formidable obstacle in lung transplantation (LTx) surgery. This issue significantly hinders the availability of this life-saving procedure for patients in need. To alleviate this shortage, researchers have turned to ex vivo lung perfusion (EVLP) technology as a means to evaluate and potentially repair marginal donor lungs, thereby increasing the donor pool and improving access to transplantation. However, it is important to note that the current capabilities of EVLP technology are still somewhat limited, and further research, development, and optimization are necessary to maximize its potential. To advance this field of study, animal experiments play a crucial role in providing a controlled environment for exploring the possibilities and limitations of EVLP. Among the various animal models available, the small animal EVLP platform for rats stands out by virtue of its simplicity, convenience, and cost-effectiveness. This platform offers researchers a unique opportunity to gain valuable insights into the workings of EVLP and its potential applications in LTx. However, conducting these experiments is not without its challenges. The complexity of the procedure requires a deep understanding of the relevant considerations and operational skills. To ensure the success of these experiments, it is essential that researchers have a comprehensive grasp of the intricacies involved. Drawing upon our practical experience over the past 3 years, our Jiangxi team has systematically refined and summarized the specific details of a rat EVLP experiment in this paper. It encompasses a comprehensive overview of the experimental setup, procedural steps, and potential pitfalls that should be kept in mind. We believe that this information will serve as a valuable resource for researchers in the field, providing them with a solid foundation upon which to build their own experiments and further advance the study of EVLP in LTx.
研究领域:
移植外科
·
肺病学
·
实验动物科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）