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Food & Function · 2023 ·Vol. 14 ·期 7 ·3083-3091 · IF 6.1

Saccharomyces cerevisiae: a patulin degradation candidate both in vitro and in vivo

Ruiyu Zhu,Shuo Shan,Su Zhou,Zhen Chen,Yuanfeng Wu,Wei Liao,Chao Zhao,Qiang Chu

Patulin is one of the mycotoxins that exists in abundance in fruits and derivative products and is easily exposed in daily life, leading to various toxicities such as genotoxicity, teratogenicity, immunotoxicity, and carcinogenicity in the human body, while the efficient removal or degradation measures are still in urgent demand. In this work, Saccharomyces cerevisiae, a natural yeast with both patulin degradation and intestine damage protection abilities, was first applied to prevent and decrease the hazard after patulin intake. In vitro, Saccharomyces cerevisiae KD (S. cerevisiae KD) could efficiently degrade patulin at high concentrations. In a Canenorhabditis elegans (C. elegans) model fed on S. cerevisiae KD, locomotion, oxidative stress, patulin residual, intestine damage, and gene expression were investigated after exposure to 50 μg mL−1 patulin. The results demonstrated that S. cerevisiae KD could efficiently degrade patulin, as well as weaken the oxidative stress and intestinal damage caused by patulin. Moreover, S. cerevisiae KD could regulate the gene expression levels of daf-2 and daf-16 through the IGF-1 signaling pathway to control the ROS level and glutathione (GSH) content, thus decreasing intestinal damage. In summary, this work uncovers the outstanding characteristic of an edible probiotic S. cerevisiae KD in patulin degradation and biotoxicity alleviation and provides enlightenment toward solving the hazards caused by the accumulation of patulin.

研究领域: 食品科学 · 毒理学 · 微生物学 · 分子生物学
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Frontiers in Pharmacology · 2023 · IF 5.6

Farrerol prevents Angiotensin II-induced cardiac remodeling in vivo and in vitro

He Jian,Xu Dengyue,Wang Lu,Yu Xiaohong

Cardiovascular disease has become the primary disease that threatens human health and is considered the leading cause of death. Cardiac remodeling, which is associated with cardiovascular disease, mainly manifests as cardiac hypertrophy, fibrosis, inflammation, and oxidative stress. Farrerol plays an important role in treating conditions such as inflammation, endothelial injury and tumors, and we speculated that Farrerol may also play an important role in mitigating cardiac hypertrophy and remodeling. We established a model of myocardial remodeling using Angiotensin II (Ang II) with concurrent intraperitoneal injection of Farrerol as an intervention. We used cardiac ultrasound, immunohistochemistry, Immunofluorescence, Wheat Germ Agglutinin, Dihydroethidium, Western Blot, qPCR and other methods to detect the role of Farrerol in cardiac remodeling. The results showed that Farrerol inhibited Ang II-induced cardiac hypertrophy; decreased the ratio of heart weight to tibia length in mice; reduced inflammation, fibrosis, and oxidative stress; and reduced the size of cardiomyocytes in vivo. Farrerol inhibited Ang II-induced cardiomyocyte hypertrophy, levels of oxidative stress, and the proliferation and migration of fibroblast in vitro. Our results revealed that Farrerol could inhibit Ang II-induced cardiac remodeling. Farrerol may therefore be a candidate drug for the treatment of myocardial remodeling.

研究领域: 心血管疾病 · 药理学 · 分子生物学
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Frontiers in Microbiology · 2019 · IF 4.259

Molecular Mechanisms of AhpC in Resistance to Oxidative Stress in Burkholderia thailandensis

Zhang Bing,Gu Huawei,Yang Yantao,Bai Haonan,Zhao Chao,Si Meiru,Su Tao,Shen Xihui

Burkholderia thailandensis is a model organism for human pathogens Burkholderia mallei and Burkholderia pseudomallei. The study of B. thailandensis peroxiredoxin is helpful for understanding the survival, pathogenic infection, and antibiotic resistance of its homologous species. Alkyl hydroperoxide reductase subunit C (AhpC) is an important peroxiredoxin involved in oxidative damage defense. Here, we report that BthAhpC exhibits broad specificity for peroxide substrates, including inorganic and organic peroxides and peroxynitrite. AhpC catalyzes the reduction of oxidants using the N-terminal conserved Cys57 as a peroxidatic Cys and the C-terminal conserved Cys171 and Cys173 as resolving Cys. These three conserved Cys residues play critical roles in the catalytic mechanism. AhpD directly interacts with AhpC as an electron donor, and the conserved Cys residues in active site of AhpD are important for AhpC reduction. AhpC is directly repressed by OxyR as shown by identifying the OxyR binding site in the ahpC promoter with a DNA binding assay. This work sheds light on the function of AhpC in the peroxides and peroxynitrite damage response in B. thailandensis and homologous species.

研究领域: 微生物学 · 分子生物学 · 传染病学
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WATER RESEARCH · 2021 · IF 11.236

Molecular composition of halobenzoquinone precursors in natural organic matter in source water

Jinxiu Lou,Huijie Lu,Wei Wang,Lizhong Zhu

Halobenzoquinones (HBQs) are emerging disinfection byproducts generated during the reaction of chlorine disinfectant with natural organic matter (NOM) in source water. In this study, the correlations between molecular weight and HBQs generation of river NOM was evaluated. The compositional and functional characteristics of primary HBQs precursors were revealed by using Orbitrap mass spectrometry combined with molecular tagging. The NOM fraction larger than 50 kDa resulted in approximately 9 times more HBQs (50.9 ± 2.7 ng/mgC) than low molecular weight fractions. Significant correlations were found between the yields of HBQs and lignin-like and highly oxygen compounds in NOM, suggesting their critical roles in HBQs formation. Derivatizating the aldehydes, ketones, hydroxyl and carboxyl groups in NOM could reduce HBQs yields by 90.7%–100%. Unraveling the molecular characteristics of HBQs precursors in NOM would greatly benefit the prediction of HBQs yields of different source water, and develop more efficient disinfection byproduct control strategies.

研究领域: 环境科学 · 分析化学
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2016 · IF 1.988

In situ thiolated alginate hydrogel: Instant formation and its application in hemostasis

Guanzhe Xu,Liang Cheng,Qintong Zhang,Yunlong Sun,Changlin Chen,Heng Xu,Yimin Chai,Meidong Lang

An in situ formed hydrogel was synthesized by sodium alginate and cysteine methyl ester, which turned the sodium alginate into thiolated alginate (SA-SH). SA-SH can in situ formed into hydrogel (SA-SS-SA) with a large amount of water through covalent bond in less than 20 s. The structure characterization showed that the mechanism of SA-SH gelation was thiol-disulfide transformation. The rheology and cytotoxicity experiments of SA-SS-SA hydrogel were also investigated, which indicated that SA-SS-SA hydrogel had an appropriate mechanical strength as well as an excellent biocompatibility. The SA-SS-SA hydrogel would degrade under certain conditions after a few days and its mechanism was disulfide alkaline reduction. Finally, the hemostatic property of SA-SH was tested by rat tail amputation experiment. The time to hemostasis of rat reduced from 8.26 min to 3.24 min, which proved that SA-SH had an excellent hemostatic property.

研究领域: 生物材料 · 高分子科学 · 生物医学工程 · 止血研究
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 8 ·7354 · IF 5.6

Isopropoxy Benzene Guanidine Ameliorates Streptococcus suis Infection In Vivo and In Vitro

Ning Han,Jie Li,Feifei Zhao,Yangyang Li,Jun Wang,Xiaolan Dai,Dongping Zeng,Wenguang Xiong,Zhenling Zeng

Streptococcus suis, an encapsulated zoonotic pathogen, has been reported to cause a variety of infectious diseases, such as meningitis and streptococcal-toxic-shock-like syndrome. Increasing antimicrobial resistance has triggered the need for new treatments. In the present study, we found that isopropoxy benzene guanidine (IBG) significantly attenuated the effects caused byS. suisinfection, in vivo and in vitro, by killingS. suisand reducingS. suispathogenicity. Further studies showed that IBG disrupted the integrity ofS. suiscell membranes and increased the permeability ofS. suiscell membranes, leading to an imbalance in proton motive force and the accumulation of intracellular ATP. Meanwhile, IBG antagonized the hemolysis activity of suilysin and decreased the expression ofSlygene. In vivo, IBG improved the viability ofS. suisSS3-infected mice by reducing tissue bacterial load. In conclusion, IBG is a promising compound for the treatment ofS. suisinfections, given its antibacterial and anti-hemolysis activity.Keywords:Streptococcus suis;isopropoxy benzene guanidine;antibacterial;anti-hemolysis;suilysin

CAS / MDL: 25535-16-4
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2023 · IF 4.2

Continuous Counter-Current Multistage Microextraction in a Novel Tube-In-Tube Microextractor

Junxin Chen,Caijin Zhou,Bingqi Xie,Jisong Zhang

Counter-current operation has been widely applied to enhance the extraction efficiency for systems with low distribution coefficients, which was hindered in microextraction because viscous force and surface tension dominate over gravity and inertial force. In this study, a novel design of a tube-in-tube microextractor relying on a poly tetra fluoroethylene membrane to construct a stable interface was proposed to conduct continuous counter-current extraction. Extraction kinetics for two systems with different distribution coefficients, membranes with different pore radii, and three flow rate ratios were measured as a function of residence time. For the system that toluene was used to extract 0.06 wt % phenol in water, 4.1 stages of extraction efficiency were achieved at a residence time of 9.8 min. A challenging case study (50 wt % acetone–water–toluene) was subsequently conducted to prove the high applicability for emulsion systems of this special microextractor. Lastly, a mathematical model was established and the predicted results of three flow rate ratios are in good agreement with experimental results.

CAS / MDL: 108-95-2
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FASEB JOURNAL · 2023 ·Vol. 37 ·期 4 ·e22866 · IF 4.8

Kcnma1 is involved in mitochondrial homeostasis in diabetes-related skeletal muscle atrophy

Shan-Yan Gao,Yong-Ping Liu,Ri Wen,Xin-Mei Huang,Ping Li,Yu-Hang Yang,Ni Yang,Tie-Ning Zhang

Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca 2+ - and voltage-gated K + channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-sh Kcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-sh Kcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.

CAS / MDL: 1330-20-7
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WATER RESEARCH · 2023 · IF 12.8

In-situ advanced oxidation of sediment iron for sulfide control in sewers

Yanchen Liu,Zhiqiang Zuo,He Li,Yaxin Xing,Dong Cheng,Miao Guo,Tao Liu,Min Zheng,Zhiguo Yuan,Xia Huang

Sulfide control is a significant problem in urban sewer management. Although in-sewer dosing of chemicals has been widely applied, it is prone to high chemical consumption and cost. A new approach is proposed in this study for effective sulfide control in sewers. It involves advanced oxidation of ferrous sulfide (FeS) in sewer sediment, to produce hydroxyl radical (·OH) in-situ , leading to simultaneous sulfide oxidation and reduction of microbial sulfate-reducing activity. Long-term operation of three laboratory sewer sediment reactors was used to test the effectiveness of sulfide control. The experimental reactor with the proposed in-situ advanced FeS oxidation substantially reduced sulfide concentration to 3.1 ± 1.8 mg S/L. This compares to 9.2 ± 2.7 mg S/L in a control reactor with sole oxygen supply, and 14.1 ± 4.2 mg S/L in the other control reactor without either iron or oxygen. Mechanistic investigations illustrated the critical role of ·OH, produced from the oxidation of sediment iron, in regulating microbial communities and the chemical sulfide oxidation reaction. Together these results demonstrate that incorporating the advanced FeS oxidation process in sewer sediment enable superior performance of sulfide control at a much lower iron dosage, thereby largely saving chemical use.

CAS / MDL: 5625-37-6
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PLoS One · 2023 ·Vol. 18 ·期 5 ·e0285613 · IF 3.7

Evaluation of microbial and vancomycin treatments in ulcerative colitis in murine models

Nihal Hasan,Hongyi Yang

Background Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. Methods Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. Results After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. Conclusion Our results concluded that treatment duration and preparation methods affect the microbial therapies’ efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.

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CHEMICAL RESEARCH IN TOXICOLOGY · 2023 · IF 4.1

In Vitro and In Vivo Metabolic Activation of Tolterodine Mediated by CYP3A

Aixuan Wang,Qiang Zhao,Minglu Liu,Yang Wang,Guode Zhao,Weiwei Li,Ying Peng,Jiang Zheng

Tolterodine (TOL) is an antimuscarinic drug used for the treatment of patients with overactive bladder presenting urinary frequency, urgency, and urge incontinence. During the clinical use of TOL, adverse events such as liver injury took place. The present study aimed at the investigation of the metabolic activation of TOL possibly associated with its hepatotoxicity. One GSH conjugate, two NAC conjugates, and two cysteine conjugates were found in both mouse and human liver microsomal incubations supplemented with TOL, GSH/NAC/cysteine, and NADPH. The detected conjugates suggest the production of a quinone methide intermediate. The same GSH conjugate was also observed in mouse primary hepatocytes and in the bile of rats receiving TOL. One of the urinary NAC conjugates was observed in rats administered TOL. One of the cysteine conjugates was found in a digestion mixture containing hepatic proteins from animals administered TOL. The observed protein modification was dose-dependent. CYP3A primarily catalyzes the metabolic activation of TOL. Ketoconazole (KTC) pretreatment reduced the generation of the GSH conjugate in mouse liver and cultured primary hepatocytes after TOL treatment. In addition, KTC reduced the susceptibility of primary hepatocytes to TOL cytotoxicity. The quinone methide metabolite may be involved in TOL-induced hepatotoxicity and cytotoxicity.

CAS / MDL: 128-08-5 78-67-1
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EBioMedicine · 2022 · IF 11.205

Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke

Xiaoqi Hong,Yujin Jian,Shenghao Ding,Jianpo Zhou,Xiaoli Zheng,Huimin Zhang,Butian Zhou,Canbin Zhuang,Jieqing Wan,Xiaoping Tong

Summary Background Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies. Methods We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke. Findings In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests. Interpretation Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke. Funding This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China ( 82271466 , 82171279 , 31970904 and 31571063 ), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning ( 1510000084 ), Shanghai Pujiang Talent Award ( 15PJ1404600 ), Shanghai Municipal Science and Technology Major Project ( 2018SHZDZX05 ) and Shanghai Science and Technology Project ( 17411954000 ).

CAS / MDL: 491-70-3
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