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1.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2501-2511, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812154

ABSTRACT

This study established a convenient, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, swertisin, N-nornuciferine, 6-feruloylspinosin, and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 µm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was adopted as the mobile phase for gradient elution. The nine components and two internal standards were completely separated within 8 min. The mass spectrometry detection was performed in multiple reaction monitoring(MRM) mode by positive and negative ion switching of electrospray ionization. The analytical method was validated in terms of specificity, selectivity, linear range, accuracy, precision, recovery, matrix effect, and stability. It could meet the requirement of pharmacokinetic research after oral administration of FZSS extract to beagle dogs. The results showed that the time to reach the peak concentration(T_(max)) of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, 6-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the follow-up research of FZSS.


Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Ziziphus , Animals , Dogs , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/administration & dosage , Ziziphus/chemistry , Male , Liquid Chromatography-Mass Spectrometry
2.
Metabolites ; 14(3)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38535331

ABSTRACT

Metabolic reprogramming has emerged as a prominent hallmark of cancer, characterized by substantial alterations in nutrient uptake and intracellular metabolic pathways. Consequently, intracellular metabolite concentrations undergo significant changes which can contribute to tumorigenesis through diverse mechanisms. Beyond their classical roles in regulating metabolic pathway flux, metabolites exhibit noncanonical functions that play a crucial role in tumor progression. In this review, we delve into the nonclassical functions of metabolites in the context of tumor progression, with a particular focus on their capacity to modulate gene expression and cell signaling. Furthermore, we discuss the potential exploitation of these nonclassical functions in the enhancement of cancer therapy.

3.
Meat Sci ; 212: 109473, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38422589

ABSTRACT

Earlier onset of rigor mortis is a critical physiological progress occurring in the development of pale soft and exudative (PSE) meat. However, how rigor cross-bridges denature under different physiological conditions and their impacts on water-holding capacity remains unclear. To address this scientific question, we firstly established a method to quantify the extent of rigor cross-bridge denaturation using skinned fibres prepared from porcine longissimus thoracis et lumborum muscle. Effects of pH and temperature on the kinetics of rigor cross-bridge denaturation, actomyosin denaturation and shrinkage of muscle fibre were studied. We then manipulated the number of rigor cross-bridges before the denaturation condition was initiated (pH 5.5, 38 °C). Results suggested that the loss of water-holding capacity in PSE meat is determined by the number of denatured rigor cross-bridges. Physiochemical analysis on myofibrils demonstrated that increase in protein oxidation, surface hydrophobicity and loss of electrostatic repulsive force between myofibrils may be involved in the mechanism.


Subject(s)
Muscle Fibers, Skeletal , Muscle, Skeletal , Swine , Animals , Myofibrils , Meat/analysis , Water
4.
Biomed Chromatogr ; 38(3): e5803, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38098275

ABSTRACT

In this present study, we developed a reliable and simple ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin and isomaltopaeoniflorin in beagle dog plasma. We also analyzed the pharmacokinetics of those components after oral administration of fried Radix Paeoniae Alba (FRPA) in beagle dogs. Plasma samples were processed by protein precipitation with methanol. Chromatographic separation was performed with a Waters HSS-T3 C18 column (100 × 2.1 mm, 1.8 µm, kept at 40°C) using multiple reaction monitoring mode. A gradient elution procedure was used with solvent A (0.02% formic acid-water) and solvent B (0.02% formic acid-acetonitrile) as mobile phases. Method validation was performed as US Food and Drug Administration guidelines, and the results met the acceptance criteria. The method we establish in this experiment was successfully applied to the pharmacokinetic study after oral administration of FRPA extract to beagle dogs.


Subject(s)
Drugs, Chinese Herbal , Formates , Tandem Mass Spectrometry , Dogs , Animals , Tandem Mass Spectrometry/methods , Chromatography, Liquid , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/pharmacokinetics , Solvents
5.
BMC Nephrol ; 24(1): 360, 2023 12 05.
Article in English | MEDLINE | ID: mdl-38053016

ABSTRACT

BACKGROUND: Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment. METHODS: A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients. RESULTS: The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera. CONCLUSION: Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.


Subject(s)
Cognitive Dysfunction , Gastrointestinal Microbiome , Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Gastrointestinal Microbiome/genetics , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Cognition
6.
Biomimetics (Basel) ; 8(7)2023 Nov 19.
Article in English | MEDLINE | ID: mdl-37999196

ABSTRACT

Under the conditions of conservation tillage, the existence of the root-soil complex greatly increases the resistance and energy consumption of stubble-cutting blades, especially in Northeast China. In this research, the corn root-soil complex in Northeast China was selected as the research object. Based on the multi-toothed structure of the leaf-cutting ant's mandibles and the unique bite mode of its mandibles on leaves, a gear-tooth, double-disk, bionic stubble-cutting device (BSCD) was developed by using a combination of power cutting and passive cutting. The effects of rotary speed, tillage depth, and forward speed on the torque and power of the BSCD were analyzed using orthogonal tests, and the results showed that all of the factors had a large influence on the torque and power, in the order of tillage depth > rotary speed > forward speed. The performance of the BSCD and the traditional power straight blade (TPSB) was explored using comparative tests. It was found that the optimal stubble-cutting rate of the BSCD was 97.4%. Compared with the TPSB, the torque of the BSCD was reduced by 15.2-16.4%, and the power was reduced by 9.2-11.3%. The excellent performance of the BSCD was due to the multi-toothed structure of the cutting edge and the cutting mode.

7.
Sci Robot ; 8(84): eadc9244, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37992192

ABSTRACT

In-hand object reorientation is necessary for performing many dexterous manipulation tasks, such as tool use in less structured environments, which remain beyond the reach of current robots. Prior works built reorientation systems assuming one or many of the following conditions: reorienting only specific objects with simple shapes, limited range of reorientation, slow or quasi-static manipulation, simulation-only results, the need for specialized and costly sensor suites, and other constraints that make the system infeasible for real-world deployment. We present a general object reorientation controller that does not make these assumptions. It uses readings from a single commodity depth camera to dynamically reorient complex and new object shapes by any rotation in real time, with the median reorientation time being close to 7 seconds. The controller was trained using reinforcement learning in simulation and evaluated in the real world on new object shapes not used for training, including the most challenging scenario of reorienting objects held in the air by a downward-facing hand that must counteract gravity during reorientation. Our hardware platform only used open-source components that cost less than 5000 dollars. Although we demonstrate the ability to overcome assumptions in prior work, there is ample scope for improving absolute performance. For instance, the challenging duck-shaped object not used for training was dropped in 56% of the trials. When it was not dropped, our controller reoriented the object within 0.4 radians (23°) 75% of the time.

8.
Sensors (Basel) ; 23(19)2023 Sep 24.
Article in English | MEDLINE | ID: mdl-37836893

ABSTRACT

Novel and practical low-temperature 3D printing technology composed of a low-temperature 3D printing machine and optimized low-temperature 3D printing parameters was successfully developed. Under a low-temperature environment of 0--20 °C, poly (vinyl alcohol) (PVA) matrix hydrogels including PVA-sodium lignosulphonate (PVA-LS) hydrogel and PVA-sodium carboxymethylcellulose (PVA-CMC) hydrogel exhibited specific low-temperature rheology properties, building theoretical low-temperature 3D printable bases. The self-made low-temperature 3D printing machine realized a machinery foundation for low-temperature 3D printing technology. Combined with ancillary path and strut members, simple and complicated structures were constructed with high precision. Based on self-compiling G-codes of path structures, layered variable-angle structures with high structure strength were also realized. After low-temperature 3D printing of path structures, excellent electrical sensing functions can be constructed on PVA matrix hydrogel surfaces via monoplasmatic silver particles which can be obtained from reduced reactions. Under the premise of maintaining original material function attributes, low-temperature 3D printing technology realized functionalization of path structures. Based on "3D printing first and then functionalization" logic, low-temperature 3D printing technology innovatively combined structure-strength design, 3D printable ability and electrical sensing functions of PVA matrix hydrogels.

9.
Polymers (Basel) ; 15(15)2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37571068

ABSTRACT

The novel conductive polyvinylidene fluoride (PVDF) fibrous membrane with high conductivity and sensitivity was successfully prepared via electrostatic spinning and efficient silver reduction technology. Based on the selective dissolution of porogen of polyvinylpyrrolidone (PVP), the porous PVDF fibrous membrane with excellent adsorbability and mechanical strength was obtained, providing a structure base for the preparation of conductive PVDF fibrous membrane with silver nanoparticles (AgNPs-PVDF). The Ag+ in the AgNO3 mixed solution with PVP was absorbed and maintained in the inner parts and surface of the porous structure. After the reducing action of ascorbic acid-mixed solution with PVP, silver nanoparticles were obtained tightly in an original porous PVDF fibrous membrane, realizing the maximum conductivity of 2500 S/m. With combined excellent conductivity and mechanical strength, the AgNPs-PVDF fibrous membrane effectively and sensitively detected strain signals of throat vocalization, elbow, wrist, finger, and knee (gauge factor of 23). The electrospun conductive AgNPs-PVDF combined the characteristics of low resistance, high mechanical strength, and soft breathability, which provided a new and effective preparation method of conductive fibers for practical application in wearable devices.

10.
Bull Environ Contam Toxicol ; 110(5): 83, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37093286

ABSTRACT

This field study explored safe rice production in Cd-contaminated red paddy soil by application of the combined Si-/Se- containing foliar inhibitors (Si or Se) and the mixture amendments of quicklime (Q), polyacrylamide (A), or/and sepiolite (S) at low (1) and high (2) application rates. The results showed that all treatments increased soil pH and decreased total P and soil organic matter (excluding QSe2). With the increasing application rates, QAS significantly decreased the available Cd because of the enhanced stabilization, while QSi and QSe significantly increased the available Cd because of the inhibited plant uptake. After remediation, QA1, QSi2, and QSe2 most effectively decreased the uptake Cd by rice to meet the threshold of National Food Safety Standard of China. The treatments excluding Q1, QA1, QSi1, and QSi2 did not dramatically change the bacterial community structure in soil. Collectively, QSe2 was recommended for remediating Cd-contaminated red paddy soil.


Subject(s)
Oryza , Soil Pollutants , Cadmium/analysis , Oryza/chemistry , Soil Pollutants/analysis , Environmental Pollution , Soil/chemistry
11.
Microsc Res Tech ; 86(5): 589-599, 2023 May.
Article in English | MEDLINE | ID: mdl-36715138

ABSTRACT

In this paper, the microstructure characteristics and mechanical properties (including nano-indentation, tensile, and penetration behaviors) of the scales from pinecone fish (Monocentris japonica) were investigated. The M. japonica scales display a unique hierarchical structure and consist of three layers: an outer bone layer with high mineralization, an intermediate bone layer with obvious pore structures, and an inner collagen layer composed of multiple plies of collagen fibers. The hardness and indentation modulus of the three structural layers exhibit gradient changes, and decrease gradually from the outer layer to the inner layer. Tensile tests show that the tensile response and failure modes of the scales are different under dry and hydrated conditions. The dry scales have higher tensile strength (46.35 MPa) and Young's modulus (0.74 GPa), while the hydrated scales exhibit higher ultimate strain (20.18%) and toughness (4.57 MPa). Penetration tests indicate that the scales have a significantly high resistance to penetration, and increase the penetration force by more than six times compared with the descaled skin. Furthermore, the structure-property relationship of the M. japonica scales was discussed. It is found that the hard outer layer and the porous intermediate layer help to disperse the stress, and the soft inner layer containing collagen fiber plies helps to deflect the crack propagation, which are responsible for the excellent mechanical properties of the scales. The outcome of this study can provide a valuable biomimetic design inspiration for lightweight and high-strength composite materials in engineering fields. RESEARCH HIGHLIGHTS: Microstructure characteristics and mechanical properties of the Monocentris japonica scales were investigated. The M. japonica scales can be divided into three layers rather than two layers. The M. japonica scales exhibited high tensile strength and penetration resistance.


Subject(s)
Mechanical Phenomena , Skin , Animals , Tensile Strength , Collagen/analysis , Fishes
12.
Curr Drug Metab ; 24(1): 28-69, 2023.
Article in English | MEDLINE | ID: mdl-36650621

ABSTRACT

Herb medicine has a long history of application and is still used worldwide. With the development of complementary and alternative medicine, the interaction between herb and drugs has attracted more and more attention. Herb-drug interactions (HDI) could cause decreased efficiency, increased toxicity, and affect the drug absorption and disposition processes due to the interference of their pharmacological or pharmacokinetic effects. Hence, the mechanisms and results of herb-pharmacokinetic interactions should be comprehensively summarized. Here, we have summarized the mechanisms of HDI and pharmacokinetic interactions in the last ten years based on searching on PubMed, Science Direct, and Web of Science with different keywords. Besides, the pharmacokinetic interactions were related to nine commonly used herbs and drugs, including Ginseng, Salvia miltiorrhiza, Ginkgo biloba, Garlic, Coptis chinensis, St. John's wort, Ginger, Licorice, Silythistle and Fructus Schisandrae. This review provides an overview of HDI to provide a reference for the rational and safe clinical use of herbs and drugs.


Subject(s)
Biological Products , Plants, Medicinal , Humans , Herb-Drug Interactions
13.
Polymers (Basel) ; 14(22)2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36433165

ABSTRACT

Natural fibers and their composites have attracted much attention due to the growing energy crisis and environmental awareness. In this work, a natural lignocellulosic fiber was extracted from cow dung waste and its potential use as reinforcing material in resin-based polymer composites was evaluated. For this purpose, cow dung fiber-reinforced composites (CDFC) were fabricated, and their mechanical and morphological properties were systematically investigated and compared with corn stalk fiber composites (CSFC) and sisal fiber composites (SFC). The results showed that the addition of cow dung fibers reduced the density of the polymer composites, increased the water absorption, and enhanced the impact strength and shear strength. The highest impact and shear strengths were obtained at 6 wt.% and 9 wt.% of fiber loading, respectively, which increased by 23.8% and 34.6% compared to the composite without the fibers. Further comparisons revealed that at the same fiber addition level, the CDFC exhibited better mechanical properties than the CSFC; notably, the CDFC-3 (adding 3 wt.% of fiber loading) had an impact strength closer to the SFC-3. Furthermore, an SEM analysis suggested that the cow dung fibers exhibited a rough and crinkly surface with more node structures, and presented good interfacial bonding with the composite matrix. This work revealed that cow dung fibers are a promising candidate as reinforcement for resin-based polymer composites, which promotes an alternative application for cow dung waste resources in the automotive components field.

14.
Front Pharmacol ; 13: 928983, 2022.
Article in English | MEDLINE | ID: mdl-35935836

ABSTRACT

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a star medication used to treat non-small-cell lung carcinomas (NSCLCs). It has caused broad public concern that osimertinib has relatively low stability in plasma. We explored why osimertinib and its primary metabolites AZ-5104 and AZ-7550 are unstable in rat plasma. Our results suggested that it is the main reason inducing their unstable phenomenon that the Michael addition reaction was putatively produced between the Michael acceptor of osimertinib and the cysteine in the plasma matrix. Consequently, we identified a method to stabilize osimertinib and its metabolite contents in plasma. The assay was observed to enhance the stability of osimertinib, AZ-5104, and AZ-7550 significantly. The validated method was subsequently applied to perform the pharmacokinetic study for osimertinib in rats with the newly established, elegant, and optimized ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) strategy. The assay was assessed for accuracy, precision, matrix effects, recovery, and stability. This study can help understand the pharmacological effects of osimertinib and promote a solution for the similar problem of other Michael acceptor-contained third-generation EGFR-TKI.

15.
Biomed Chromatogr ; 36(12): e5488, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36001467

ABSTRACT

Astragalus Membranaceus (AM) is widely applied in Chinese herbal compound formulas for treating various kinds of diseases. However, relative pharmacokinetics data on AM in nonrodents is still lacking. Here, an UPLC-MS/MS method for determining the six main compounds of AM was developed. The chromatographic separation was carried out by a Waters Acquity UPLC HSS T3 column (100 × 2.1 mm, 1.8 µm) with gradient elution of water-formic acid (99.98:0.02, v/v) and acetonitrile-formic acid (99.98:0.02, v/v) at a flow rate of 0.3 ml/min within 11 min. Analyses of all compounds were conducted in multiple reaction monitoring mode with a positive/negative ion-switching mode of an electrospray ionization source in a single run. The analytical method was validated in terms of specificity, linearity, accuracy, precision, stability, etc. The method showed excellent linearity (r > 0.999) over certain concentration ranges. The intra-day and inter-day precisions were evaluated, and the RSD values were <12.4%. Furthermore, the validated method was successfully applied to determine the six components in plasma after oral administration of AM aqueous extract to beagle dogs and the pharmacokinetic parameters were obtained. Together, this study provides a reference for medication in the clinical practice of AM.


Subject(s)
Astragalus propinquus , Tandem Mass Spectrometry , Dogs , Animals , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Administration, Oral , Water , Reproducibility of Results
16.
Huan Jing Ke Xue ; 43(7): 3763-3772, 2022 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-35791559

ABSTRACT

The study of heavy metal pollution in mine soil of the Yangtze River Economic Belt is important for promoting the ecological restoration of mines and the construction of green mines in the Yangtze River Economic Belt. For this study, we collected the relevant research on the pollution of heavy metals in the mine soil of the Yangtze River Economic Belt from 2006 to 2020 and studied the pollution status, distribution law, and health risk of heavy metals by using the land accumulation index method, Kriging interpolation method, and health risk assessment method. The results showed that the average contents of Pb, Cd, Cr, Hg, As, Zn, Ni, and Cu in mine soil far exceeded the background value in China, and the accumulation degree of Cd and Hg was significant. The pollution evaluation results showed that the pollution degree of the eight heavy metals was Cd>Hg>Pb>Zn>Cu>As>Ni>Cr, the pollution degree of Cd and Hg was the highest, and more than 60% of the sample points were at medium pollution. The pollution evaluation showed that the soil pollution of tin and lead-zinc mines was more prominent than that of other minerals. The health risk assessment indicated that oral intake was the main intake route for non-carcinogenic and carcinogenic risks, the total non-carcinogenic and carcinogenic risk index was within the unacceptable range, and the non-carcinogenic and carcinogenic risk of mine soil in the middle and upper reaches of the Yangtze River Economic Belt was significantly higher than that in the lower reaches.


Subject(s)
Mercury , Metals, Heavy , Soil Pollutants , Cadmium , Environmental Monitoring , Environmental Pollution/analysis , Lead , Metals, Heavy/analysis , Risk Assessment , Rivers , Soil , Soil Pollutants/analysis
17.
Front Pharmacol ; 13: 827668, 2022.
Article in English | MEDLINE | ID: mdl-35264960

ABSTRACT

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4'-teterahydroxystilbene-2-O-ß-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-ß-D-glucoside (EG), and physcion-8-O-ß-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

18.
Adv Sci (Weinh) ; 9(8): e2104055, 2022 03.
Article in English | MEDLINE | ID: mdl-35048565

ABSTRACT

DNA repair confers the resistance of tumor cells to DNA-damaging anticancer therapies, while how reprogrammed metabolism in tumor cells contributes to such process remains poorly understood. Pyruvate kinase M2 isoform (PKM2) catalyzes the conversion of phosphoenolpyruvate to pyruvate and regulates the last rate-limiting step of glycolysis. Here it is shown that the glycolytic metabolite pyruvate enhances DNA damage repair by facilitating chromatin loading of γH2AX, thereby promoting the radiation resistance of glioma cells. Mechanistically, PKM2 is phosphorylated at serine (S) 222 upon DNA damage and interacts with FACT complex, a histone chaperone comprising SPT16 and SSRP1 subunit. The pyruvate produced by PKM2 directly binds to SSRP1, which increases the association of FACT complex with γH2AX and subsequently facilitates FACT-mediated chromatin loading of γH2AX, ultimately promoting DNA repair and tumor cell survival. Intriguingly, the supplementation of exogenous pyruvate can also sufficiently enhance FACT-mediated chromatin loading of γH2AX and promotes tumor cell survival upon DNA damage. The levels of PKM2 S222 phosphorylation correlate with the malignancy and prognosis of human glioblastoma. The finding demonstrates a novel mechanism by which PKM2-produced pyruvate promotes DNA repair by regulating γH2AX loading to chromatin and establishes a critical role of this mechanism in glioblastoma radiation resistance.


Subject(s)
Glioblastoma , Cell Line, Tumor , Chromatin , DNA-Binding Proteins/genetics , Glioblastoma/genetics , Glioblastoma/metabolism , Glioblastoma/pathology , High Mobility Group Proteins/genetics , Histones , Humans , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , Pyruvic Acid/metabolism , Transcriptional Elongation Factors/genetics
19.
Biomed Chromatogr ; 36(3): e5283, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34816469

ABSTRACT

A sensitive and specific ultra-performance liquid chromatographic-tandem mass spectrometric method was developed and validated to simultaneously determine periplocin, periplocymarin (PM), periplogenin (PG), periplocoside M (PSM) and periplocoside N (PSN) in rat plasma. Acetonitrile was employed to precipitate plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a Waters HSS T3 column with a gradient elution using water and acetonitrile both containing 0.1% formic acid and 0.1 mm ammonium formate within 8 min. Detection was performed in positive ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. Using this method, the concentrations of periplocin, PM, PG, PSM and PSN were established after oral administration of Cortex Periplocae extract to rats, and the pharmacokinetic characteristics of periplocin, PM, PG, PSM and PSN were assessed. Generally, PM, PG, PSM and PSN were eliminated slowly and their half-lives were all >8 h. In addition, the systemic exposure of PSM showed significant differences between genders with more than 10 times higher area under the concentration-time curve in female rats than in male rats. The findings of this study provide useful information for further research on Cortex Periplocae.


Subject(s)
Digitoxigenin , Tandem Mass Spectrometry , Administration, Oral , Animals , Cardiac Glycosides , Chromatography, High Pressure Liquid/methods , Digitoxigenin/analogs & derivatives , Female , Male , Rats , Reproducibility of Results , Saponins , Tandem Mass Spectrometry/methods
20.
Materials (Basel) ; 14(18)2021 Sep 18.
Article in English | MEDLINE | ID: mdl-34576632

ABSTRACT

In this paper, we aim to evaluate the tribological, mechanical, and morphological performance of resin-based friction composites reinforced by sisal fibers with different shapes, namely helical, undulated, and straight shapes. The experimental results show that the shape of the sisal fibers exerts a significant effect on the impact property of the composite materials but no obvious influence on the density and hardness. The friction composite containing the helical-shaped sisal fibers exhibits the best overall tribological behaviors, with a relatively low fade (9.26%), high recovery (98.65%), and good wear resistance (2.061 × 10-7 cm3∙N-1∙m-1) compared with the other two composites containing undulated-shaped fibers and straight-shaped fibers. The impact fracture surfaces and worn surfaces of the composite materials were inspected by scanning electron microscopy, and we demonstrate that adding helical-shaped sisal fibers into the polymer composites provides an enhanced fiber-matrix interface adhesion condition and reduces the extent of fiber debonding and pullout, effectively facilitating the presence of more secondary plateaus on the friction surface, which are responsible for the enhanced tribological and mechanical properties. The outcome of this study reveals that sisal fibers with a helical shape could be a promising candidate as a reinforcement material for resin-based brake friction composite applications.

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