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The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.
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Objective: To explore the effects of pregnancy complicated with moyamoya disease on maternal and fetal outcomes. Methods: The general clinical data and maternal and fetal outcomes of 20 pregnancies of 15 patients with moyamoya disease admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2022 were retrospectively analyzed. Results: (1) General information: among the 20 pregnancies of 15 clearly diagnosed pregnant women complicated with moyamoya disease, 12 were diagnosed before pregnancy (60%, 12/20), 3 were diagnosed during pregnancy (15%, 3/20), and 5 were diagnosed during puerperal period (25%, 5/20). There were 7 cases of primipara (35%, 7/20) and 13 cases of multipara (65%, 13/20). (2) Pregnancy complications and maternal and infant outcomes: among the 20 pregnancies of 15 pregnant women with moyamoya disease, there were 9 pregnancy complications (45%, 9/20), including 5 gestational hypertension (25%, 5/20), 2 severe pre-eclampsia (10%, 2/20), 1 hyperlipidemia and 1 gestational diabetes mellitus (5%, 1/20). There were 2 case of drug abortion in the first trimester, 3 cases of labor induction in the second trimester, and 15 cases of delivery during the third trimester. All the 15 deliveries were cesarean section, of which 11 (11/15) were cesarean sections with medical indications, and 4 (4/15) were cesarean sections caused by personal factors. General anesthesia was used in 5 cases (5/15), epidural block anesthesia in 7 cases (7/15), and combined spinal and epidural anesthesia in 3 cases (3/15). The median gestational age of 15 neonates was 37.2 weeks (34.0 to 40.8 weeks), with 10 cases (10/15) were full-term infants, and 5 (5/15) were preterm infants (3 of which were associated with hypertensive disorder complicating pregnancy). The birth weight of 15 neonates was (2 853±454) g. Four neonates were admitted to neonatal intensive care unit (NICU), of which 3 cases were admitted to NICU due to premature delivery and 1 case was admitted to NICU due to neonatal jaundice. There was no neonatal asphyxia or death. All neonates were followed up from 4 months to 6 years after birth, and all grew well. (3) Neurological symptoms during pregnancy: 8 cases (40%, 8/20) had neurological symptoms during pregnancy, and 6 cases (30%, 6/20) had hemorrhagic symptoms, of which 3 cases occurred during the puerperal period (3/6). There were 2 cases of ischemic symptoms (10%, 2/20), all of which occurred during the puerperal period (2/2). (4) Analysis of factors related to the occurrence of cerebral hemorrhage: the incidence of cerebral hemorrhage in patients with moyamoya disease diagnosed before pregnancy was significantly lower than that in those without a clear diagnosis, and the incidence of cerebral hemorrhage in women with moyamoya disease was lower than that in primipara (all P<0.01). The incidence of cerebral hemorrhage in moyamoya patients without hypertensive disorder complicating pregrancy was lower than that in patients with hypertensive disorder complicating pregrancy, but the difference was not statistically significant (P>0.05). Conclusions: Pregnancy combined with moyamoya disease has adverse effects on maternal and infant outcomes, and the incidence of pregnancy complications increases. Cerebral hemorrhage occurres in prenatal and puperium, while cerebral ischemia occurres mainly in puperium.
Subject(s)
Infant , Pregnancy , Infant, Newborn , Female , Humans , Pregnancy Outcome , Cesarean Section , Pregnant Women , Infant, Premature , Moyamoya Disease/complications , Retrospective Studies , Pregnancy Complications/epidemiology , Cerebral HemorrhageABSTRACT
AIM: To investigate the effect of scleral slap invagination and trabeculectomy combined with amniotic membrane implantation in the treatment of glaucoma.?METHODS:From May 2013 to June 2017, 98 cases (116 eyes ) with glaucoma were treated in our hospital. According to the random number table method, the patients were divided into two groups: the observation group of 45 cases (58 eyes) with scleral slap invagination surgery combined with amniotic membrane transplantation into operation, the control group of 53 cases ( 58 eyes ) with trabeculectomy combined with amniotic membrane implantation. Postoperatively patients were followed up for 3mo to observe IOP control;using MEN-C90 type blood rheology analyzer to detect the whole blood viscosity, plasma viscosity, hematocrit and blood viscosity changes, using the Doppler flow imaging ( CDFI) technique for the detection of ophthalmic artery end diastolic velocity ( EDV ) , RI, and the peak systolic velocity ( PSV ) and other hemodynamic parameters change.?RESULTS:One week and 3mo after the surgery, mean IOP of the observation group was 12. 18 ± 0. 98mmHg, 12. 23 ± 0. 94mmHg, the control group was 14. 49 ±1. 64mmHg, 14. 62 ± 1. 59mmHg, the difference was statistically significant (P<0. 05); IOP successful-control rate of observation group after operation was 81. 0％, more than that of the control group ( 61. 3％), the difference was statistically significant (P<0. 05). At 1wk and 3mo after operation high blood viscosity, plasma viscosity, hematocrit and blood viscosity of two groups decreased significantly compared with the preoperative (P<0. 05); those of the observation group were better than those of the control group (P<0. 05). At 1wk and 3mo after operation, EDV and PSV of the two groups increased significantly, RI decreased significantly, compared with the preoperative differences were statistically significant ( P < 0. 05 ), those of the observation group were better than those of the control group (P<0. 05).? CONCLUSION: The combination of scleral slap invagination and amniotic membrane implantation has a significant effect on glaucoma patients, the effect of intraocular pressure control is good, the postoperative complications are low, and the safety of the patients is high.
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Objective To explore the role of P-glycoprotein(P-gp)on cellular uptake and metabolism in the transmembrane transport of quercitrin.Methods Caco-2 cell monolayer and P-gp inhibitor Cyclosporin A(CysA)were used in the study.Quercitrin, quercetin,isorhamnetin and tamarixetin were determined by LC-MS to study cellular uptake and metabolism of quercitrin on Caco-2 cells.Results Uptake of quercitrin by Caco-2 cells:in different concentration groups of quercitrin coincubating with and without Cy?sA,intracellular accumulation presented the following characteristics:the amount of quercitrin first rose,reached the peak in 60 min and then declined to a steady-state in 120 min.And meanwhile there were significant differences between the two different processing groups incubating with and without CysA(P<0.05);quercetin was detected in all groups(3.0,9.0 and 27.0 mg/L).But in the higher concentration groups incubating with and without CysA,the intracellular quercetin presented a characteristics similar to its original glycosides and showed a significant difference(P<0.05),while the other groups showed no concentration-and time-dependence.At the same time,isorhamnetin and tamarixetin were detected in two higher concentration groups incubating with and without CysA, which showed the trend similar to the original glycosides but no significant difference was obtained between the two processing groups(P>0.05).Isorhamnetin and tamarixetin were not detected in the low and middle concentration groups.Transmembrane transport:on the basal lateral of all groups,the content of the quercitrin in 150 min incubation time showed a trend of continuous rise,and there was no significant difference between the two processing groups.Quercetin,isorhamnetin and tamarixetin were not detected.Conclu?sion Intact quercitrin could be absorbed into the Caco-2 cells and transported across the Caco-2 cell monolayer,and suffered a series of further metabolism in the Caco-2 cells and the basal side of Caco-2 cell monolayer,leading to different characteristics between intra?cellular accumulation and transmembrane transport.P-gp reduces the transmembrane transport of quercitrin by its efflux function,but did not involved in quercitrin metabolism.
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Eighteen compounds were isolated from the 95% ethanol extract of fresh tubers of Dioscorea bulbifera by column chromatography over silica gel,Sephadex LH-20, and ODS. Their structures were elucidated by spectroscopic data analysis as 6-hydroxy-2,10,10-trimethoxy-anthracen-9-one(1), diosgenin (2), stigmasterol(3), 3, 7-dimethoxy-5, 3', 4'-trihydroxyflavone(4), 2, 7-dihydroxy-3, 4-dimethoxyphenanthrene(5), 3, 7-dihydroxy-2, 4-dimethoxy phenanthrene(6), 2, 7-dihydroxy-4-methoxyphenanthrene (7), 2, 7-dihydroxy-3, 4-dimethoxy-9, 10-dihydroxy phenanthrene(8), azelaic acid (9), 8-epidiosbulbin E acetate (10), 1, 7-bis-(4-hydroxyphenyl)-4E, 6E-heptadien-3-one(11), diosbulbin B(12), pentacosanoic acid 2', 3'-dihydroxypropyl ester(13), 2, 7-dihydroxy-4-methoxy-9, 10-dihydroxy-phenanthrene (14), 1, 7-bis-(4-hydroxyphenyl)-1E, 4E, 6E-heptatrien-3-one (15), 6-ethoxy-1H-pyrimidine-2, 4-dione (16), 3, 5, 4'-trihydroxy-bibenzyl (17), and diosbulbin F (18). Compound 1 is a new compound, and compounds 7, 9, 13, and 16 were isolated from this plant for the first time.
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To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.
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To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.
Subject(s)
Animals , Female , Pregnancy , Rats , Acupuncture Therapy , Methods , Blotting, Western , Embryo Implantation , Genetics , Endometrium , Metabolism , Gene Expression Regulation, Developmental , Hormone Antagonists , Pharmacology , Immunohistochemistry , Mifepristone , Pharmacology , Progestins , Pharmacology , Random Allocation , Rats, Wistar , Receptors, Interleukin-8A , Genetics , Metabolism , Receptors, Interleukin-8B , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Treatment Outcome , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To explore the improvement effect of vitamins B1, B2, PP supplementation to the metabolism changes of carbohydrates, lipids, protein and energy in mice exposed to acute hypoxia.</p><p><b>METHODS</b>Fifty male Kunming mice were randomly divided into normal, acute hypoxia, acute hypoxia plus 2 times, 4 times and 8 times vitamins B1, B2, PP supplemented groups. All mice were fed corresponding diets for two weeks and then except the normal group were exposed to a simulated altitude of 6 000 meters for 8 hours. The changes of glucose, pyruvate, lactate, urea nitrogen, free fatty acids and beta-hydroxybutyric acid from serum, liver glycogen and blood adenosine triphosphate (ATP) concentration were measured.</p><p><b>RESULTS</b>After being exposed to acute hypoxia, the mice glucose, liver glycogen, pyruvate, lactate, free fatty acids, beta-hydroxybutyric acid and urea nitrogen level were increased significantly (P < 0.05), while blood ATP concentration was decreased. In the vitamins B1, B2 and PP supplemented groups, these changes were improved.</p><p><b>CONCLUSION</b>The significant changes in carbohydrate, lipid and protein metabolism were observed in mice exposed to acute hypoxia, and the supplementation of vitamins B1, B2 and PP was proved to be beneficial in improving some metabolic pathways. It is suggested that the supplemented dose of four times was good.</p>
Subject(s)
Animals , Male , Mice , Carbohydrate Metabolism , Hypoxia , Metabolism , Lipid Metabolism , Niacinamide , Proteins , Metabolism , Riboflavin , Thiamine , Vitamin B ComplexABSTRACT
<p><b>OBJECTIVE</b>To investigate the metabolic changes of mice serum after loaded swimming and to provide a basis for the study of anti-fatigue functional food.</p><p><b>METHODS</b>The male Kunming mice were randomly divided into four group, fed an AIN-93 diet for 14 days, and forced to swim for 30, 60 or 120 min, respectively, with a load on their tails. The mice were executed after swimming immediately and the changes of serum metabolic profiles were analyzed using metabolomic approach. The spectrum was acquired by using Carr Purcell Meiboom Gill (CPMG) or Longitudinal Eddy Current Delay (LED) sequence, and transformed into 1H NMR spectrogram via Fourier transformation. All the data were analyzed by principal component analysis by using the SIMCA-P+ software.</p><p><b>RESULTS</b>The serum metabolic profiles changed significantly after loaded swimming. Serum beta-hydroxybutyric acid, acetate, lactate, lipid were increased and glucose, choline, phosphorylcholine, alanine and phosphatidylcholine decreased. These changes were time dependent.</p><p><b>CONCLUSION</b>The changes of serum metabolic profiles after loaded swimming were time dependent, especially for lipid metabolite.Further study based on the interaction of choline and lipid metabolism may contribute to understand the mechanism of fatigue.</p>
Subject(s)
Animals , Male , Mice , Choline , Metabolism , Fatigue , Blood , Metabolism , Lipid Metabolism , Metabolome , Physical Exertion , Physiology , Swimming , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To explore metabolic changes after acute hypoxia and modulating effect of vitamins B₁, B₂, and PP supplementation in mice exposed to acute hypoxia.</p><p><b>METHODS</b>Fifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B₁, B₂, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles.</p><p><b>RESULTS</b>There were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B₁, B₂, and PP supplementation, all these metabolic changes gradually recovered.</p><p><b>CONCLUSIONS</b>Significant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B₁, B₂, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B₁, B₂, and PP should be increased under hypoxia condition.</p>
Subject(s)
Animals , Male , Mice , Acute Disease , Dose-Response Relationship, Drug , Hypoxia , Blood , Metabolism , Lipid Metabolism , Magnetic Resonance Spectroscopy , Metabolomics , Methods , Mice, Inbred Strains , Niacinamide , Therapeutic Uses , Nutritional Physiological Phenomena , Principal Component Analysis , Riboflavin , Therapeutic Uses , Thiamine , Therapeutic Uses , Vitamin B Complex , Therapeutic UsesABSTRACT
<p><b>AIM</b>To report the preliminary result of the HIV inhibitor screening based on cheminformatics tools and the traditional Chinese medicine database.</p><p><b>METHODS</b>Database search was carried out with saquinavir molecule as a template, further screening was made with docking. Detailed studies using molecular dynamics simulation of 50 ps and 200 ps were made with respect to a potential leading compound, leucovorin.</p><p><b>RESULTS</b>The leucovorin molecule distinguished from other molecules as a potential drug candidate and is subject to extensive studies. The bonding profile and energy were calculated with MD simulations.</p><p><b>CONCLUSION</b>Our results could be very helpful when we modify leucovorin or design new inhibitors against HIV.</p>