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According to the traditional Chinese medicine(TCM) theory, coronary heart disease(CHD) is mainly caused by heart vessel obstruction due to Qi stagnation, blood stasis, and phlegm turbidity. Chest impediment with combined phlegm and stasis is a common syndrome of CHD, with the manifestations of chest tightness, chest pain, and asthma. Lymphatic system is one of the important immune systems in the human body and has a close relationship with the Qi and blood movement in TCM. The dysfunction of the lymphatic system may lead to metabolism disorders, the generation of dampness pathogen which turns into sticky and difficult-to-dissolve phlegm turbidity. Moreover, it can affect blood circulation and coagulation, causing slow blood flow, increased blood viscosity, and microcirculation disorders. Alterations in lymphatic hydrodynamics may affect the interaction between blood circulation and the lymphatic system. A variety of small molecule drugs and TCM can treat cardiovascular diseases by targeting the lymphatic system. This review discusses the role of the lymphatic system in CHD based on the theory of combined phlegm and stasis, involving the influences of mechanical factors on lymphatic function and the effects and pharmacological mechanisms of TCM and chemicals that target lymphocyte function and lymphatic circulation. By expounding the development process of combined phlegm and stasis in CHD from the lymphatic system, this paper aims to provide new ideas for deciphering pharmacological mechanisms of TCM for resolving phlegm and stasis.
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Humans , Coronary Disease , Medicine, Chinese Traditional , Mucus , Lymphatic System , HeartABSTRACT
The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.
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Objective:To analyze the clinical and molecular genetic characteristics of a Chinese family with congenital cataract-microcornea syndrome.Methods:The method of pedigree investigation was adopted.A Chinese Han family with congenital cataract-microcornea syndrome was recruited in Xiamen Eye Center of Xiamen University.All the family members received detailed ophthalmologic examination including the best corrected visual acuity, intraocular pressure measurement by handheld applanation tonometry, slit lamp biomicroscopy, color fundus photography, B-scan ultrasonography, corneal diameter, anterior segment optical coherence tomography, ultrasound biomicroscopy, corneal endoscopy, and corneal topography.Genomic DNA was extracted from peripheral venous blood from some patients and unaffected family members.Targeted high-throughput DNA sequencing was performed on the proband.The sequencing chip contained 188 known pathogenic genes related to lens abnormalities.Suspected pathogenic genes were verified by Sanger sequencing in phenotypically normal family members to identify the co-segregation and the disease-causing gene.Bioinformatics analysis was performed to analyze the pathogenicity of variants by REVEL.Conserved protein domains were analyzed by InterPro.Physicochemical property of the mutant protein was analyzed by ProtParam.The deleteriousness of the protein was predicted by PolyPhen-2.Homology of the variants in pathogenic gene was analyzed by NCBI website to compare the conservation among various species.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-LW-2009-003).Written informed consent was obtained from each subject prior to entering the study cohort.Results:There were 39 members of 4 generations in this family including 11 patients with an autosomal dominant inheritance pattern.Clinical features of the patients included congenital cataract and microcornea.No obvious abnormality was found in ophthalmic and general examination.A heterozygous mutation c. 61C>T in the CRYAA gene was found, resulting in the mutation of the amino acid from arginine to tryptophan (p.Arg21Trp) at position 21, consistent with co-segregation.The number of cationic cluster in the mutant protein decreased, and the hydrophilicity and stability were reduced.The variant was predicted to be deleterious and was highly conserved in multiple species. Conclusions:A novel heterozygous mutation c.61C>T p. Arg21Trp in CRYAA gene is considered as the causal gene of this family.It is the first time this variant has been reported in China.
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OBJECTIVE@#To establish a stable mouse model of acquired aplastic anemia.@*METHODS@#Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed.@*RESULTS@#In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes.@*CONCLUSION@#The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.
Subject(s)
Animals , Female , Mice , Anemia, Aplastic , Bone Marrow , Cyclophosphamide , Cyclosporine , Mice, Inbred BALB CABSTRACT
Objective:To explore the characteristics of local brain neural activity in post stroke aphasia (PSA) patients in different frequency bands and the relationship between Western Aphasia Battery (WAB) scores and specific frequency bands. Methods:From March, 2015 to May, 2018, 15 PSA patients, and 15 healthy adults as controls matched for age, gender and education were recruited. They were assessed with WAB and scaned with resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) on the frequency bands of 0.01-0.08 Hz, 0.027-0.073 Hz, and 0.01-0.027 Hz were calculated. The ALFF and fALFF in different frequency bands were extracted and the correlation with the WAB scores in the patients were analyzed. Results:On 0.01-0.08 Hz, ALFF increased in the right precentral gyrus in the patients. On 0.027-0.073 Hz, ALFF increased values in the right precentral gyrus, and fALFF decreased in the right cerebellar Crus2 region; fALFF in the right cerebellar Crus2 region negatively correlated with the scores of information content (r = -0.576, P = 0.025), auditory comprehension (r = -0.658, P = 0.008), repetition (r = -0.616, P = 0.014) and aphasia quotient (r = -0.611, P = 0.016) of WAB. On 0.01-0.027 Hz, the fALFF decreased in the left inferior parietal limbic gyrus, and positively correlated with the scores of information content (r = 0.538, P = 0.039) and aphasia quotient (r = 0.526, P = 0.044). Conclusion:Resting-state fALFF abnormalities in PSA patients are frequency-dependent, which associate with some frequency-specific neurofunctional alterations.
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Aim To investigate the role of eNOS/PKG- 1 pathway in L-arginine (L-arg) intervention in right ventricular remodeling induced by monocrotaline (MCT) in Sprague Dawley (SD) rats with the aid of the tool medicine L-NAME. Methods Twenty SD rats were randomly divided into control group, MCT group, L-Arg group and L-Arg + L-NAME group. The general condition of rats was observed; the right ventricular pressure of rats was measured by right heart catheterization; the rats and the right ventricle were weighed and the right ventricular mass index was calculated; the morphological changes of the right ventricular were observed by H&E staining; the protein expressions of cTnl, eNOS and PKG-1 were detected by Western blot in the right ventricular. Results Compared with control group, right ventricular max pressure and right ventricular mass index significantly increased ( P < 05) ; the weight of rats in MCT group was significantly reduced ( P < 0. 05); the right ventricular myocytes were hypertrophic, disordered and infiltrated with inflammatory cells; the protein expression of cTnl was obviously up-regulated ( P < 0. 05 ) ; the protein expressions of eNOS and PKG-1 were significantly down- regulated ( P < 0. 05 ) . L-arg could significantly improve the above changes ( P < 0. 05 ). However, the effects of L-arg were inhibited by eNOS inhibitor L- NAME. Conclusions L-arg can improve the right ventricular remodeling in rats induced by MCT, and the mechanism may be related to the up-regulation of the protein levels of eNOS and PKG-1.
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Abstract; Aim To explore the effect of icariin (ISO) in mice. Methods C57BL/6 mice were ran- (ICA) on myocardial fibrosis induced by isoproterenol domly divided into control group, ISO group, low-dose (15 mg • kg"1), middle-dose (30 mg • kg"1) and high-dose (60 mg • kg"1) of ICA-treated group and Losartan-treated group ( 9 mg • kg"1 ). The control group was subcutaneously injected with normal saline, and the other groups were subcutaneously injected with ISO (5 mg • kg"1, qd) continuously 14 days to established the myocardial fibrosis model. The ICA-treated groups and Losartan-treated group were simultaneously intragastrically administered of ICA or Losartan, respectively. And the other groups received the same a- mount of double distilled water. The left ventricular e- jection fraction (LVEF) and the left ventricular fraction shortening rate ( LVFS) were evaluated by the small animal ultrasound. The heart mass index (HMI) was calculated. The left ventricular collagen deposition was detected by Masson staining. The protein expressions of a-SMA, MMP-2, MMP-9 and TIMP-1 in the left ventricular tissue were detected by Western blot. Results ICA (30, 60 mg • kg"1) and Losartan could inhibit the decreased LVEF and LVFS, the increased HMI and left ventricular collagen deposition, the up- regulated a-SMA and MMP-9 protein expression, the down-regulated MMP-2 and TIMP-1 protein expression in the left ventricular tissues induced by ISO. Conclusions ICA can improve myocardial fibrosis induced by ISO in mice, and the underlying mechanism may be related to the regulation of the protein expression of a- SMA and MMPs/TIMP-1.
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Hepatic stellate cells (HSCs) are non-parenchymal pericytes resided in liver. In chronic liver injury, the cells are activated from quiescent state into myofibroblasts, and then drive liver fibrosis. The process, activated HSCs secreting extracellular matrix, is crucial to liver fibrosis, which needs enormous energy and triggers the metabolic reprogramming including Warburg effect, degradation of lipid droplets with increasing lipid metabolism and the change of amino acid metabolism. This paper mainly reviews the glucose, lipid and protein metabolic reprogramming of HSCs during the development of liver fibrosis and its potential applications, controbuting to design novel targeted therapies against liver fibrosis.
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Objective:To study the effect of right brain language network in post-stroke aphasia (PSA) patients with left hemisphere injury. Methods:From December, 2018 to June, 2019, twelve PSA patients with left hemisphere injury, and twelve matched healthy controls were recruited to accept rest-state functional magnetic resonance imaging (f-MRI) scan, and analyzed the characteristics of right brain function network with Dual Stream model. Results:There were two patients lost. Compared with the controls, for dorsolateral lingual pathway, the functional connections increased from superior marginal gyrus to middle frontal gyrus and inferior frontal gyrus of trigone in the patients, while those decreased from posterior central gyrus to inferior frontal gyrus of insula. For ventral lingual pathway, the functional connection increased from angular gyrus to orbital inferior frontal gyrus. For ventral and dorsolateral double-pathway, the functional connections increased from temporal lobe to lenticular pallidum and angular gyrus, from caudate nucleus to inferior frontal gyrus of insula, from lenticular putamen nucleus to middle frontal gyrus and trigonometry, while it decreased from superior marginal gyrus and temporal lobe to inferior frontal gyrus of insula. There was a negative correlation between the functional connection from inferior frontal gyrus to lenticular putamen and repeating (r = -0.720, P < 0.05), between the functional connection from inferior frontal gyrus to the caudate nucleus to speaking and repeating (r < -0.696, P < 0.05). In terms of network index, there were significant differences between the patients and the controls in both local and global indexes for language key brain area in right brain (|t| > 2.143, P < 0.05). Conclusion:The functional network has reorganized in right hemisphere of PSA patients. However, the increase of connection between language critical cortex and subcortical nuclei may play a role in improvement of language function.
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Myocardial injury from coronavirus disease-2019 (COVID-19) is a clinical sign after the novel coronavirus infection, which can be seen in common type and severe type in acute stage, or after recovery of COVID-19. From the mouth and nose, the epidemic and pathogenic factors enter the lung, involving the heart, so that Qi and blood are blocked and developed into myocardial injury. More than 100 patients with COVID-19 and rehabilitation were treated, and we found that some patients infected with novel coronavirus had palpitation, shortness of breath, chest pain, chest oppression, fatigue and other symptoms. Electrocardiogram(ECG) showed myocardial ischemia injury and increased myocardial enzymes, due to the pathological changes of warm pathogen, first invading the lung and reversely spreading to the heart. Myocardial injury due to infection of novel coronavirus, on the one hand, made the patients weak and conditions lingering and hard to heal after COVID-19 was recovered in discharged patients. On the other hand, myocardial injury in severe cases could easily aggravate the disease and even threaten life. According to the different stages of the disease, the severity of the disease, and the patients' physique in the recovery period, different treatment methods were adopted. For the myocardial injury in patients with acute severe COVID-19, Shengmaiyin and Emergency Huiyangtang can be taken， if the poisonous heat disturbs the mind, we can use Angong Niuhuangwan and Zhibaodan as appropriate. For myocardial injury occurred in common type of COVID-19, Zhuye Shigaotang and Shenxiantang can be used. For the pathological changes mainly including myocardial injury after clinical recovery of COVID-19, we can use Shengxiantang, Yangxintang, Chaixiantang and so on. Methods of detoxification, tonifying Qi and Yin, invigorating Qi and ascending Qi collapse, blood circulation and phlegm resolving were used for treatment of myocardial injury from COVID-19, which can not only effectively improve clinical symptoms, but also restore creatine kinase isoenzyme-MB(CPK-MB) and ECG levels to obtain satisfactory results. All of these could reflect that TCM has a notable advantage in the prevention and treatment of this disease.
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The non-specific administration of antitumor drugs is the main cause for the side effects of chemotherapy drugs on normal tissues. The application of nanotechnology in the delivery of anti-tumor drugs is one of the important ways to improve the therapeutic effect and to reduce the side effects. The current study aimed to synthesize pH responsive poly (methoxy-ethylene glycol)-poly(lactic acid)-poly-(β-amino ester) (PBAE) triblock copolymers to deliver docetaxel (DTX) and improve the anti-tumor activity of DTX. PBAE was synthesized by ring opening polymerization and Michael addition reaction, its structure and molecular weight was characterized by 1H NMR, the dissociation constant of base (pKb) were determined by acid-base titration method. The critical micelles concentration (CMC) of copolymers was measured by pyrene fluorescence spectroscopy. DTX loaded copolymer micelles were prepared by membrane hydration method. The size and its distribution as well as the stability of micelles were determined by laser light scattering analysis. The drug loading content (DL), entrapment efficiency (EE) and cumulative drug release from micelles were evaluated by high-performance liquid chromatography (HPLC). The sizes of DTX drug-loaded micelles were in the range of 10 to 100 nm with narrow distribution. DL of DTX in PBAE1 and PBAE2 micelles was (5.3 ± 0.10) % and (4.9 ± 0.05) %, respectively, with EE was (93.8 ± 1.70) % and (87.2 ± 4.10) %, respectively. The drug-loaded micelles showed pH sensitive drug release properties under weak acidic conditions, which showed potential drug release of DTX under mild acidic tumor environment. A mouse Lewis lung carcinoma model was established to evaluate the therapeutic efficacy of micellar DTX formulations. Significant inhibitory effect of the nanodrugs was observed with DTX dosages of 10 and 20 mg·kg-1, respectively. Moreover, the pH responsive PBAE1-DTX micellar drug exhibited stronger therapeutic efficacy on mice xenograft tumor, as compared with the non pH sensitive micellar drug (PELA-DTX) and free DTX. All animal experiments were performed according to the animal ethical standards and approved by the Animal Experiments and Ethical Committee of China Academy of Chinese Medical Sciences (No. 2017090110). The in vivo anti-tumor activity studies showed that the tumor volume growth rates of mice in different drug-administered groups were: PBAE1-DTX 20 mg·kg-1 < PBAE1-DTX 10 mg·kg-1 < PELA-DTX 10 mg·kg-1 < DTX 10 mg·kg-1 < normal saline, with the PBAE1-DTX group as the most potent group for tumor inhibition. The current pH sensitive DTX nano-micelles showed high potential in further studies to promote the application of nano DTX formulations for tumor treatment.
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According to drug design flattening principle and using podophyllotoxin or 4'-demethylepipodophyllotoxin and aldehydes as starting material,a series of podophyllotoxin derivatives containing an imine structure with low toxicity were highly effective synthesized. Nine target compounds were successfully synthesized,and their structures were confirmed by ~1H-NMR,HR-ESI-MS and melting point data analysis. Using etoposide as positive control drug,nine target compounds were screened for cytotoxicity against He La cells in vitro by MTT method. The antitumor activity screening results showed that compound 6 b,6 d,6 e,6 f,6 g,6 i exhibited higher inhibitory rate against He La cells than those of control drug VP-16. It provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Drug Screening Assays, Antitumor , Podophyllotoxin/pharmacology , Structure-Activity RelationshipABSTRACT
Objective: To modify the structure of podophyllotoxin derivatives and evaluate the antitumor activities of the derivatives. Methods: The target compounds were synthesized by multi-step reaction with podophyllotoxin and aldehyde compound as starting material.. MTT assay was used to test antitumor activity of all the target compounds on Hela cells, K562 cells, and K562/A02 cell. Results: Eleven novel derivatives were synthesized which had not been reported in any literature and the structures were characterized by 1H-NMR, 13C-NMR, HR-ESI-MS and melting point determination analysis. The antitumor activity screening results showed that all the target compounds had different degrees of cytotoxic activity in vitro. Most of the compounds had significant anti-MDR activity in vitro. Conclusion: Through structural modification of podophyllotoxin derivatives, the antineoplastic activities are enhanced.
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According to drug design flattening principle,a series of novel indole podophyllotoxin derivatives which were introduced different indole substituents in C-4 position on the basis of podophyllotoxin nucleus were synthesized with the starting material podophyllotoxin and 1 H-indole-5-carboxylic acid. Its anti-tumor activity in vitro was tested in order to screen for high-efficiency and low-toxic compounds. Six target compounds were synthesized,and were confirmed by~1 H-NMR,~(13)C-NMR,HR-ESI-MS and melting point determination analysis. All these target compounds were not reported by previous literature. Using etoposide as positive control drug,all the target compounds were screened for cytotoxicity against He La cells,K562 cells and K562/A02 cell in vitro by MTT method. The antitumor activity screening results showed that compounds 4 b,4 e,4 f exhibited higher inhibitory rate against He La cells and K562 cells than those of control drug VP-16. This route has the advantages on simple operation and reasonable design,provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Drug Screening Assays, Antitumor , HeLa Cells , Indoles , Pharmacology , K562 Cells , Podophyllotoxin , Pharmacology , Structure-Activity RelationshipABSTRACT
Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.
Subject(s)
Animals , Mice , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Docetaxel , Pharmacology , Drug Carriers , Lung Neoplasms , Drug Therapy , Pathology , Micelles , Nanoparticles , Particle Size , TaxoidsABSTRACT
OBJECTIVE@#To investigate the differentiation of acute promyelocytic leukemia (APL) cells induced by adenosine targeting Prx III.@*METHODS@#HL-60 cells were divided into four groups: control group, all-trans retinoic acid (ATRA) group, adenanthin group and ATRA+adenanthin group. Cell morphologic changes were observed under optical microscope. The influence of adenanthin on the differentiation of HL-60 was observed by nitro blue tetrazolium chloride (NBT) test. Cell surface differentiation antigens CD11b expression was measured by flow cytometry. The protein expression of Prx III was detected by immunohistochemical assay.@*RESULTS@#Adenanthin could induce the differentiation of HL-60 cells; the NBT reduction positive rate in ATRA+adenanthin group was significantly higher than that in ATRA group and adenanthin group (P＜0.05). The percentage of CD11b positive cells in ATRA+adenanthin group (43.62％±1.38％) was higher than that in adenanthin group (28.15％±1.78％), ATRA group (36.72％±1.33％) and control group (7.99％±1.78％) (P＜0. 05). The content of Prx Ⅲ protein in adenanthin group was significantly higher than that in control group and ATRA group (P＜0.05).@*CONCLUSION@#Adenanthin and ATRA have a synergistic effect on the differentiation and maturation of HL-60 cells, and its mechanism may be related with regulation of Prx III expression.
Subject(s)
Humans , Cell Differentiation , Diterpenes, Kaurane , HL-60 Cells , Leukemia, Promyelocytic, Acute , Peroxiredoxin III , TretinoinABSTRACT
Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.
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OBJECTIVE@#To study the features of serum metabolites in preterm infants based on gas chromatography-mass spectrometry (GC-MS), and to find differentially expressed metabolites in the serum of preterm infants.@*METHODS@#Serum samples were collected from 19 preterm infants and 20 full-term infants before feeding. GC-MS was used to measure metabolic profiles, and the metabolic features of 397 serum metabolites in preterm infants were analyzed.@*RESULTS@#There was a significant difference in serum metabolic features between the preterm and full-term infants before feeding. There were significant differences between the full-term and preterm infants in the levels of metabolites such as O-phosphonothreonine, digicitrin, tannic acid, and fructose-1,6-diphosphate (P<0.01), suggesting that the above differentially expressed metabolites were highly differentiated between the preterm and full-term infants. Most differentially expressed metabolites were involved in the metabolic pathways such as ABC transporters, β-alanine and pyrimidines and were correlated with some clinical parameters (albumin and total bilirubin) (P<0.05).@*CONCLUSIONS@#There is a significant difference in serum metabolites between preterm and full-term infants before feeding. Metabolomics plays an important role in improving metabolic disorders and exploring metabolism-related diseases in preterm infants.
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Humans , Infant, Newborn , Gas Chromatography-Mass Spectrometry , Infant, Premature , Metabolic Networks and Pathways , Metabolome , MetabolomicsABSTRACT
Neuronal death is thought to be irreversible. In optic nerve-related diseases, the death and axonal loss of retinal ganglion cells could lead to irreversible visual impairment. A large number of studies support the hypothesis that the peroxisome proliferator-activated receptors (PPARs), once activated by particular ligands, could have a potential neuroprotective effect on the peripheral organs and the central nervous system suffering from acute or chronic injury. Optic nerve belongs to the extension of white matter in the central nervous system and shares similar pathophysiological processes with the central nervous system, which makes PPARs a hot spot in the field of optic nerve protection. This paper reviewed the effect of PPARs in optic nerve protection and its possible mechanism.