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Objective:To understand the effects of paliperidone palmitate (PP) long-acting injection on hospitalization, psychiatric symptoms, individual and social function of community patients with schizophrenia.Methods:From March 2021 to September 2022, 239 patients with schizophrenia in the community of Zhongshan city were treated with PP injection in a 1-month dosage form for 1 year.The hospitalization rate was compared before and after the treatment.The brief psychiatric rating scale (BPRS), modified overt aggression scales(MOAS), clinical global impressions-severity(CGI-S), and personal and social performance scale (PSP) were used to evaluate psychiatric symptoms and personal social function at baseline, at the end of the 8th week, the end of the 6th month and the end of the 12th month after treatment.Repeated measurement analysis of variance was used to compare the results at different times of treatment, and Logistic regression analysis was used to analyze the factors affecting treatment by SPSS 26.0.Results:One year after treatment the number of hospitalization was lower than that before (0(1) times, 0(0) times)( Z=-4.43, P<0.01), and the hospitalization days was lower than before (43(83.3) days, 0(0) days)( Z=-8.65, P<0.01) for the schizophrenic patients.The total BPRS score for schizophrenic patients decreased from (45.3±9.2) to (27.5±9.0) after 1 year of treatment( χ2=465.20, P<0.01), and the external aggressive behavior score was lower than the baseline score (1(7), 0(0))( F=308.36, P<0.01). The total effective rates were 30.5%(73/239), 77.4%(185/239) and 81.6%(195/239) after 8 weeks, 6 months and 1 year of treatment, respectively.The impairment in the four aspects of personal and social functioning were improved to varying degrees (all P<0.01). The severity of the disease was reduced 1 year after treatment.And the proportions of partial to very severe, moderate, none or mild were 10.0%(24/239), 56.5%(135/239), and 33.5%(80/239). Ordinal logistic regression analysis showed that younger age at treatment ( β=-0.08, OR=0.93, 95% CI=0.87-0.99) and older age at first onset ( β=0.07, OR=1.07, 95% CI=1.01-1.14) were associated with better treatment outcomes. Conclusion:Long-term injection of paliperidone palmitate can effectively improve the mental symptoms and individual social function of community patients with schizophrenia.
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ObjectiveTo explore the effect of paliperidone palmitate treatment on schizophrenic patients in the community. Methods446 schizophrenic patients who used paliperidone palmitate injection were selected in Shanghai. Before and after the treatment， the disease family burden scale， the concise evaluation scale of drug treatment compliance， the VAS100 score of treatment satisfaction， the short form of quality of life measurement scale， and the screening scale of social function defects were used to evaluate the effects of paliperidone palmitate injection. The data were statistically analyzed using SPSS 26.0 software. ResultsAfter using paliperidone palmitate injection， the total score of family burden （13.94±12.17）， the score of daily family activities （3.26±2.74）， the score of family entertainment activities （2.21±2.30）， and the score of family relationship （2.79±2.76） were significantly higher than those before the treatment （14.98±12.64， 3.51±2.88， 2.48±2.38， 3.11±2.87， respectively， all with P<0.05）. The scores of the World Health Organization on quality of life brief scale （62.89±11.94） and the medication compliance scale （28.11±5.64） were better than those before treatment （60.67±12.62 and 27.37±6.96， all with P<0.05）. Compared with the prior treatment without paliperidone palmitate injection， the number of readmissions after treatment was significantly reduced （P<0.01）. ConclusionThe treatment of paliperidone palmitate injection has significant effect， which can effectively reduce the disease family burden of Schizophrenic patients， improve their quality of life， enhance their drug compliance， reduce the readmission rate of patients， ensure long-term treatment effect and promote disease recovery.
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OBJECTIVE To explore whether diterpenoid 12-deoxyphorbol-13-palmitate （DP） from Euphorbia fischeriana can exert anti-leukemia effects through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal pathway， and to provide experimental evidence for developing it into a new anti-leukemia drug. METHODS Using LY294002 （PI3K specific inhibitor） as tool drug， the effects of 24 h DP treatment on the proliferation and apoptosis of human myeloid leukemia HL60 cells were detected by MTT method， Annexin Ⅴ-FITC/PI staining and AO-EB staining. ELISA method was used to detect lactic dehydrogenase （LDH） release and the activities of cysteinyl aspartate specific proteinase 3 （caspase-3） and caspase-9. The transcriptional level of caspase-3， caspase-9， forkhead box O3a （FoxO3a） and B cell lymphoma 2 interacting mediator of cell death （Bim） mRNA were detected by real-time quantitative polymerase chain reaction （qRT-PCR）. The protein expression of phosphorylated FoxO3a （p- FoxO3a） and phosphorylated Akt （p-Akt） were detected by Western blot method. The nuclear translocation of FoxO3a protein was detected by immunostaining combined with laser confocal microscopy. RESULTS 10 μmol/L DP and 10 μmol/L DP+LY294002 could inhibit the proliferation and induce the apoptosis of HL60 cells （P＜0.01）. After treatment of 5， 10， 20 μmol/L DP， HL60 cells showed typical morphological characteristics of apoptosis； DP could significantly increase the levels of LDH release and the activities of caspase-3 and caspase-9 （P＜0.05 or P＜0.01）， in dose-dependent manner. After treatment of 10 μmol/L DP and 10 μmol/L DP+LY294002， the transcriptional levels of caspase-3， caspase-9 and Bim mRNA were increased significantly （P＜0.05 or P＜0.01）， and transcriptional level of FoxO3a mRNA and protein expressions of p-FoxO3a and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. Nuclear translocation changes were observed in FoxO3a protein in 10 μmol/L DP+LY294002 group， and the change was more significant than that of LY294002 group. CONCLUSIONS DP can inhibit the proliferation and induce the apoptosis of HL60 cells via inhibiting PI3K/Akt signaling pathway.
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OBJECTIVE To establish a method for simultaneous determination of zeaxanthin ，β-carotene，β-cryptoxanthin palmitate and zeaxanthin dipalmitate in Lycium barbarum . METHODS L. barbarum was extracted with n-hexane-anhydrous ethanol-acetone-toluene（10∶6∶7∶7，V/V/V/V）by ultrasonic method. High performance liquid chromatography （HPLC）method was adopted. The determination was performed on YMC C 30 column with mobile phase A consisted of methanol-acetonitrile-water （81∶ 14 ∶ 5，V/V/V）and mobile phase B consisted of dichloromethane （gradient elution ）at the flow rate of 1.0 mL/min. The column temperature was set at 20 ℃. The detection wavelength was set at 450 nm，and sample size was 20 μL. Using zeaxanthin as control，the relative correction factors （RCFs）of β-carotene，β-cryptoxanthin palmitate and zeaxanthin dipalmitate were calculated ， and then the content of each component was calculated according to RCFs and compared with the results of external standard method（ESM）. RESULTS The linear range of zeaxanthin ，β-carotene，β-cryptoxanthin palmitate and zeaxanthin dipalmitate were 0.119 4-2.983 8，0.121 7-1.521 6，0.285 9-5.718 8，8.460 5-211.513 3 μg/mL（all R2＞0.999）. RSDs of precision ，repeatability and stability（16 h）tests were all less than 4％. The average recoveries were 103.34％，107.37％，105.64％，96.16％（RSD＜5％，n＝ 9）. The average RCFs of β-carotene，β-cryptoxanthin palmitate and zeaxanthin dipalmitate were 1.109，1.390，1.158. The relative errors of the content determination results by quantitative analysis of multi-components by singer marker （QAMS）and ESM were within ±1％. CONCLUSIONS The established HPLC-QAMS method is accurate and stable ，which can be used for the content determination and quality control of 4 carotenoids in L. barbarum .
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Objective:To investigate the role of stress-inducible protein Sestrin2 (Sesn2) in the improvement of insulin resistance in rat L6 skeletal muscle cells treated with liraglutide.Methods:The establishment of insulin resistance model of rat L6 skeletal muscle cells was induced by palmitate. The experimental cells were divided into control group(Con group), palmitate 0.6 mmol/L treatment group(PA group), palmitate 0.6 mmol/L+ liraglutide 10 nmol/L treatment group(PA+ Lir10 group), palmitate 0.6 mmol/L+ liraglutide 100 nmol/L treatment group(PA+ Lir100 group), and palmitate 0.6 mmol/L+ liraglutide 1 000 nmol/L treatment group(PA+ Lir1000 group). The cell counting kit 8(CCK8) method was used to detect the cell activity in each group. Western blotting was used to detect the expression levels of glucose transporter 4(GLUT4), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), and Sesn2 protein in L6 cells. L6 cells were transfected with siRNA to inhibit the expression of Sesn2. The cells were treated with palmitate and liraglutide. Western blotting was used to detect the expression levels of Sesn2, Akt, p-Akt, and GLUT4 protein in L6 cells.Results:Compared with Con group, the cell survival rate, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression in PA group decreased significantly( P<0.05). After liraglutide intervention, the cell activity, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression of PA+ Lir100 and PA+ Lir1000 groups was increased( P<0.05). After inhibiting the expression of Sesn2, p-Akt/Akt ratio and GLUT4 protein in transfected si-Sesn2 and treated with 0.6 mmol/L palmitate group(PA+ si-Sesn2 group) and transfected si-Sesn2 and treated with 0.6 mmol/L palmitate+ liraglutide 100 nmol/L group (Lir100+ PA+ si-Sesn2 group) were significantly lower than those in transfection negative group (si-Con group; P<0.05). Even after liraglutide intervention, compared with PA+ si-Sesn2 group, p-Akt/Akt ratio and GLUT4 protein expression level were not significantly increased in Lir100+ PA+ si-Sesn2 group ( P>0.05). Conclusions:Palmitate could induce the decrease of p-Akt/Akt ratio and GLUT4 protein expression in L6 cells. Liraglutide upregulates the expression of Sesn2, which leads to the increase of p-Akt/Akt ratio and GLUT4 protein expression and contributes to the improvement of insulin resistance.
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This study was designed to explore the protective effect and underlying mechanism of catalpol on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD). High fat diet (HFD) was used to establish NAFLD model in the in vivo experiment, and the procedures of the experiments and animal care protocol were approved by the Animal Care and Use Committee of Jianghan University. Human liver cancer cell line HepG2 was treated with palmitate (PA) to establish a lipid toxicity model in the in vitro experiments. The results showed that catalpol significantly decreased the contents of serum total glyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), and aspartate transaminase (AST) in HFD-fed mice. Results of TUNEL staining and flow cytometry analyses revealed that catalpol significantly inhibited hepatocytes apoptosis in HFD-fed mice and PA-treated HepG2 cells. Moreover, catalpol treatment significantly reduced the endoplasmic reticulum stress-related protein expression levels of binding immunoglobulin protein (BiP), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), inositol-requiring kinase 1α (IRE1α), and transcriptional factor activating transcription factor 6 (ATF6), and apoptosis-related protein expression levels of C/EBP homology protein (CHOP), phosphorylated c-Jun N-terminal kinase (p-JNK), and cleaved cysteinyl aspartate specific proteinases (caspases)-12, -9, and -3 in HFD-fed mice and PA-treated HepG2 cells. Furthermore, endoplasmic reticulum stress agonist tunicamycin (TM) significantly reversed the inhibitory effect of catalpol on protein expression levels of BiP, p-PERK, IRE1α, and ATF6, subsequently the inhibitory effect of catalpol on expression levels of CHOP, p-JNK, Bcl-2, Bax, and cleaved caspases (-12, -9, and -3) was also attenuated in PA-treated HepG2 cells. Taken together, these findings demonstrated that catalpol could inhibit hepatocytes apoptosis and had a significant protective effect on liver injury, and its mechanism might be related to the relief of endoplasmic reticulum stress.
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Objective: To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW). Methods: We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase). Patients were randomized to PP3M or PP1M (noninferiority study A) and PP3M or placebo (study B) in DB phase. The subgroup analysis included Latin American (Argentina, Brazil, Colombia, Mexico) patients. Primary efficacy endpoints were relapse-free rates (study A) and time-to-relapse (study B). Results: In study A, 63/71 (88.7%) and in study B 38/43 (88.4%) Latin American patients completed the DB phase. In study A, relapse-free percentage was similar in Latin America (PP3M: 97%, PP1M: 100%) and ROW (PP3M: 91%, PP1M: 89%). In study B, median time-to-relapse was not estimable in the Latin American subgroup for either placebo or PP3M groups, nor for the ROW PP3M group; the median time-to-relapse in the ROW placebo group was 395 days. Caregiver burden improved in patients switching from oral antipsychotics (OL baseline) to PP3M/PP1M in DB phase (Involvement Evaluation Questionnaire score mean ± SD change, -9.4±15.16; p < 0.001). Treatment emergent adverse events with PP3M during DB phase were similar in Latin America (study A: 24/34 [70.6%]; study B: 15/21 [71.4%]) and ROW (study A: 318/470 [67.7%]; study B: 84/139 [60.4%]) subgroups. Conclusion: PP3M was efficacious and showed no new safety concerns in patients with schizophrenia from Latin America, corroborating ROW findings. Clinical trial registration: NCT01515423, NCT01529515
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Humans , Male , Female , Adolescent , Adult , Aged , Young Adult , Schizophrenia/drug therapy , Antipsychotic Agents/administration & dosage , Paliperidone Palmitate/administration & dosage , Recurrence , Time Factors , Placebo Effect , Double-Blind Method , Surveys and Questionnaires , Reproducibility of Results , Treatment Outcome , Kaplan-Meier Estimate , Secondary Prevention , Latin America , Middle AgedABSTRACT
Lipases (E.C. 3.1.1.3) are serine-hydrolases, and act on long chain fatty acid ester bonds. They exhibit specific and enantioselective activities, which are desirable for many industrial applications. This study aimed at screening and optimizing the production of lipases by wild yeast strains from a variety of substrates, as well as characterizing the enzyme. An initial selection was made in oxygenated oil-supplemented minimum medium, and the enzymatic activity of the supernatant was tested over p-nitrophenyl palmitate. One-hundred and twenty-four yeast strains from different substrates were tested, and twenty-three showed significantly higher lipolytic activity (p<0.01). One yeast in particular, QU110, showed best lipase production and therefore was selected for the optimization and characterization processes. This yeast exhibits enzyme secretion in initial pH 6.0, with olive oil and tryptone as carbon and nitrogen sources, respectively. There was a strong interaction between nitrogen source and initial pH, and pH 9.0seems to inhibit enzyme secretion. The crude enzyme (cell-free supernatant) shows stability in surfactants and n-hexane, but not in ethanol or methanol. A Response Surface Model was created and optimal enzyme activity conditions were observed at 36°C and pH 8.0. The lipase is appropriate for transesterification reactions, as the enzyme is more stable in strong apolar solvents than moderately apolar ones. Also, secretion by pH was not reported elsewhere, which should be further investigated and contribute for other yeast bioprocesses as well.
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Candida parapsilosis/cytology , Candida parapsilosis/physiology , Lipase , Nitrogen , Palmitates/analysisABSTRACT
OBJECTIVE: Whether long-acting injectable antipsychotics (LAI) are superior to oral antipsychotics remains a controversial question, and results vary depending on the study design. Our study was performed to compare outcomes of oral anti-psychotics and paliperidone palmitate (PP) in clinical practice by investigating the numbers of admissions and bed days. METHODS: We performed a retrospective observational mirror-image study at a single medical center, reviewing medical charts to obtain the clinical data. Forty-six patients with a diagnosis of schizophrenia or schizoaffective disorder who had received at least two doses of PP were included in the analysis. The Wilcoxon signed-rank test was used to compare the numbers of bed days and admissions 1 year before starting PP with those numbers at 1 year after. RESULTS: The mean number of admissions fell from 0.83 to 0.17 per patient (p < 0.0002), and the median fell from 1 to 0. The mean number of bed days decreased significantly, from 24.85 to 8.74 days (p < 0.006). The outcomes remained similar in sensitivity analyses set up with different mirror points. CONCLUSION: Our results indicate that initiating PP reduced the mean numbers of hospital admissions and bed days compared with prior oral medication. LAIs may thus be cost effective in practice; its use bringing about cost reductions greater than its purchase cost.
Subject(s)
Humans , Antipsychotic Agents , Diagnosis , Hospitalization , Paliperidone Palmitate , Psychotic Disorders , Retrospective Studies , SchizophreniaABSTRACT
Objective@#To investigate the therapeutic effect of long-acting paliperidone palmitate on schizophrenia and the expression of miR-132 and miR-320 in serum of patients with schizophrenia.@*Methods@#From January 2016 to December 2018, 68 patients with schizophrenia in Wenzhou Kangning Hospital were selected as treatment group.Sixty healthy people were selected as control group.The blood was taken before treatment and 12 months after treatment.The positive and negative symptom scales (PANSS) was recorded and evaluated, and the effect of long-acting injection of paliperidone palmitate on the expression of miR-132 and miR-320 in serum of patients with schizophrenia was detected by RT-PCR.@*Results@#Three months after treatment, the PANSS scores of the treatment group were significantly lower than those of the case group [(60.2±5.4)points vs.(84.5±4.7)points, t=12.02, 22.52, 27.16, 33.32, all P<0.01]. With the prolongation of treatment time, the treatment effect was most obvious at 12 months[(38.2±1.8)points]. The results of RT-PCR showed that compared with the control group [(1.74±0.92)%, (1.43±1.01)%], the expression of serum miR-132 and miR-320 in the treatment group was significantly decreased [(0.47±0.32)%, (0.53±0.37)%, t=13.96, 14.93, all P<0.01]. The long-acting injection of paliperidone palmitate significantly increased the expression of miR-132 and miR-320 in serum of patients with schizophrenia[(0.96±0.58), (1.16±1.07), t=11.08, 8.45, all P<0.01].@*Conclusion@#Long-acting paliperidone palmitate has a certain therapeutic effect on schizophrenia and can up-regulate the expression of miR-132 and miR-320 in serum of patients with schizophrenia.
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Objective: To screen the accelerated oxidation environment with the most drastic changes in the volatile oil composition of Foeniculi Fructus, and to optimize the type and concentration of antioxidants. Method: The volatile oil of Foeniculi Fructus was extracted by steam distillation. Taking thiobarbituric acid reactive substances (TBARS) value and peroxide value (POV) as evaluation indexes, response surface method was used to investigate the effects of temperature, concentrations of ferrous ion (Fe2+) and azoamidine initiator V50 (AAPH) on volatile oil components of Foeniculi Fructus and its oxidation products. TBARS and POV were detected by ultraviolet chromatography. The oxidative environment with the most drastic changes of volatile oil composition of Foeniculi Fructus was screened. The type and concentration of antioxidants were selected by single factor experiments. The change discipline of volatile oil in Foeniculi Fructus after added different concentrations of antioxidants were analyzed by GC-MS. Result: The worst oxidizing environment for volatile oil of Foeniculi Fructus was as follows:temperature at 42.5℃,AAPH concentration of 1 g·L-1,Fe2+ concentration of 20.85 mg·L-1. Ascorbyl palmitate with concentrations of 0.2 mol·L-1 and 0.8 mol·L-1 could effectively improve the stability of volatile oil from Foeniculi Fructus. Conclusion: Under the accelerated oxidation environment, the terpenes in volatile oil from Foeniculi Fructus are significantly changed, but its stability can be improved by ascorbyl palmitate.
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Objective@#To investigate the effect of α-melanocyte-stimulating hormone(α-MSH) on the expression of mRNA and long noncoding RNA (lncRNA) in retinal vascular endothelial cells stimulated by hyperglycemia and hyperlipidemia.@*Methods@#The simian retinal vascular endothelial cells (RF/6A)were cultured and divided into normal control group, model control group, 0.1 μmol/L α-MSH group, 0.5 μmol/L α-MSH group and 1.0 μmol/L α-MSH group.The cells were stained with CM-H2DCFDA to detect cell antioxidant capacity.The optimal concentration of α-MSH was screened.The cells from normal control group, model control group and α-MSH treatment group were collected at 24 hours after treatment, the total RNA was extracted, the cDNA library was constructed, and the high throughput RNA sequencing (RNA-seq) was carried out with bioinformatics analysis to analyze the expression profiling of mRNA and lncRNA.@*Results@#The fluorescence intensity of cells in 0.5 μmol/L α-MSH group was significantly lower than that in model control group (P<0.05). α-MSH of 0.5 μmol/L was chosen as the optimal concentration for subsequent experiments.Compared with the model control group, 243 mRNAs were significantly down-regulated, while 81 mRNAs were up-regulated in the α-MSH treatment group; 53 lncRNAs were markedly up-regulated and 6 lncRNAs were down-regulated in the α-MSH treatment group.Bioinformatics analysis showed that the major enrichment pathways of the down-regulated genes were transforming growth factor-β(TGF-β) signaling pathway, focal adhesion signaling pathway and extracellular matrix (ECM) receptor interactions pathways, and the main biological process involved was the regulation of small GTPase-mediated signal transduction.The co-expression gene enrichment pathways of differentially expressed lncRNA included ECM receptor interaction and hypoxia inducible factor-1(HIF-1) pathway, et al.These pathways were mainly involved in the biological processes, such as axon guidance and positive regulation of transcription from RNA polymerase Ⅱ promoter.@*Conclusions@#Under hyperglycemia and hyperlipidemia, the influence of α-MSH on the transcriptome of the retinal vascular endothelial cells manifests the downregulation of mRNA and upregulation of lncRNA.α-MSH may upregulate the lncRNA expression, which downregulates the downstream mRNA expression.
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@#AIM: To investigate the clinical effect of vitamin A Palmitate Eye Gel combined with Tobramycin Eye Drops on corneal epithelial injury.<p>METHODS: Totally 80 patients(100 eyes)with corneal epithelial injury who came to our hospital from May 2015 to March 2016 were randomly divided into treatment group(50 eyes)and control group(50 eyes). The treatment group was treated with vitamin A Palmitate Eye Gel combined with Tobramycin Eye Drops, while the control group was treated with Tobramycin Eye Drops only. The curative effect of two groups was compared after 2wk and 4wk of treatment.<p>RESULTS: The cure rate was 80% and the effective rate was 94% in the treatment group. The cure rate was 70% and the effective rate was 78% in the control group. There was significant difference in the effective rate between the two groups(<i>P</i><0.05). The results of SⅠt and BUT test showed that the time of treatment group was significantly longer than that of control group(<i>P<</i>0.01). The score of symptoms and signs in the treatment group was significantly lower than that in the control group after 2wk of treatment(<i>P<</i>0.01), but there was no significant between treatment groups and control grouop after 4wk of treatment(<i>P></i>0.05).<p>CONCLUSION: Vitamin A Palmitate Eye Gel combined with Tobramycin Eye Drops can significantly improve dry eye symptoms and effectively shorten the healing time of corneal epithelium. It is an effective method to treat corneal epithelial injury.
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Objective To investigate the therapeutic effect of long －acting paliperidone palmitate on schizophrenia and the expression of miR －132 and miR －320 in serum of patients with schizophrenia.Methods From January 2016 to December 2018,68 patients with schizophrenia in Wenzhou Kangning Hospital were selected as treatment group.Sixty healthy people were selected as control group.The blood was taken before treatment and 12 months after treatment.The positive and negative symptom scales ( PANSS) was recorded and evaluated ,and the effect of long－acting injection of paliperidone palmitate on the expression of miR －132 and miR－320 in serum of patients with schizophrenia was detected by RT －PCR.Results Three months after treatment ,the PANSS scores of the treatment group were significantly lower than those of the case group [( 60.2 ±5.4 ) points vs.( 84.5 ± 4.7)points,t＝12.02,22.52,27.16,33.32,all P＜0.01].With the prolongation of treatment time ,the treatment effect was most obvious at 12 months[(38.2 ±1.8)points].The results of RT－PCR showed that compared with the control group [(1.74 ±0.92)%,( 1.43 ±1.01)%],the expression of serum miR －132 and miR －320 in the treatment group was significantly decreased [(0.47 ±0.32)%,(0.53 ±0.37)%,t＝13.96,14.93,all P＜0.01]. The long －acting injection of paliperidone palmitate significantly increased the expression of miR －132 and miR－320 in serum of patients with schizophrenia [(0.96 ±0.58),(1.16 ±1.07),t＝11.08,8.45,all P＜0.01]. Conclusion Long－acting paliperidone palmitate has a certain therapeutic effect on schizophrenia and can up －regulate the expression of miR－132 and miR－320 in serum of patients with schizophrenia.
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Objective To investigate the effect of α-melanocyte-stimulating hormone (α-MSH ) on the expression of mRNA and long noncoding RNA ( lncRNA ) in retinal vascular endothelial cells stimulated by hyperglycemia and hyperlipidemia. Methods The simian retinal vascular endothelial cells (RF/6A)were cultured and divided into normal control group,model control group,0. 1μmol/Lα-MSH group,0. 5μmol/Lα-MSH group and 1. 0μmol/L α-MSH group. The cells were stained with CM-H2 DCFDA to detect cell antioxidant capacity. The optimal concentration of α-MSH was screened. The cells from normal control group,model control group andα-MSH treatment group were collected at 24 hours after treatment,the total RNA was extracted,the cDNA library was constructed,and the high throughput RNA sequencing ( RNA-seq ) was carried out with bioinformatics analysis to analyze the expression profiling of mRNA and lncRNA. Results The fluorescence intensity of cells in 0. 5 μmol/L α-MSH group was significantly lower than that in model control group ( P<0. 05 ) .α-MSH of 0. 5μmol/L was chosen as the optimal concentration for subsequent experiments. Compared with the model control group, 243 mRNAs were significantly down-regulated,while 81 mRNAs were up-regulated in the α-MSH treatment group;53 lncRNAs were markedly up-regulated and 6 lncRNAs were down-regulated in the α-MSH treatment group. Bioinformatics analysis showed that the major enrichment pathways of the down-regulated genes were transforming growth factor-β( TGF-β) signaling pathway,focal adhesion signaling pathway and extracellular matrix ( ECM) receptor interactions pathways, and the main biological process involved was the regulation of small GTPase-mediated signal transduction. The co-expression gene enrichment pathways of differentially expressed lncRNA included ECM receptor interaction and hypoxia inducible factor-1(HIF-1) pathway,et al. These pathways were mainly involved in the biological processes, such as axon guidance and positive regulation of transcription from RNA polymerase Ⅱ promoter. Conclusions Under hyperglycemia and hyperlipidemia, the influence of α-MSH on the transcriptome of the retinal vascular endothelial cells manifests the downregulation of mRNA and upregulation of lncRNA. α-MSH may upregulate the lncRNA expression,which downregulates the downstream mRNA expression.
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This study was designed to investigate the role of CD36 in palmitic acid (PA)-induced apoptosis of astrocytes and the potential mechanisms of the action. MTT assay was used to detect cell viability and TUNEL assay to detect cell apoptosis. It was found that PA significantly decreased astrocyte cell viability and increased cell apoptosis. The uptake of BODIPY FL C16 by astrocytes was measured by flow cytometry. The results showed that CD36 played a key role in the process of PA uptake by astrocytes. The changes of intracellular calcium concentration were detected by FLIPR real-time fluorescence recording system. It was found that IP3R mediated PA signal to induce intracellular calcium release and finally caused endoplasmic reticulum calcium depletion. The intracellular ROS level was detected with CM-H2DCFDA fluorescence staining. The ROS level was induced by PA in astrocytes. The effect was blocked by CD36 inhibitor SSO through inhibition of the uptake of PA. PA-induced calcium overload and ROS increase were prevented by IP3R inhibitor APB. SSO, APB and antioxidant NAC all had significant inhibitory effects on PA-induced astrocyte cell viability decrease. In conclusion, CD36 mediates the translocation of PA into astrocytes, which leads to calcium overload, oxidative stress and eventually cell apoptosis.
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Objective To study chemical constituents from the flowers of Chrysanthemum indicum. Methods The chemical constituents of C. indicum were isolated and purified by various chromatographic techniques, including thin-layer chromatography, silica gel, ODS reversed-phase silica gel, and Sephadex LH-20 for column chromatography, and their structures were identified by NMR spectral analysis. Results Fourteen compounds were isolated and identified as stigmata-4-ene-3-one (1), calenduladiol-3β-O- palmitate (2), 16β,22α-dihydroxypseudotaraxasterol-3β-O-palmitate (3), α-amyrin (4), urs-12-ene-3β,16β-diol (5), 3β-hydroxyurs- 12-ene-11-one (6), arnidiol (7), maniladiol (8), 3β-hydroxyolean-12-ene-11-one (9), luteolin (10), apigenin (11), apigenin-7,4’- dimethyl ether (12), genkwanin (13), and 1-linoleic acid glycerate (14). Conclusion Compounds 1-6, 10-12, and 14 are isolated from the flowers of C. indicum for the first time.
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Objective To explore the effect of high sn-2 palmitate infant formula (HPIF) on stool frequency and consistency,fatty acids,calcium and magnesium contents in infants.Methods A prospective,double-blind,randomized,controlled clinical study was conducted including 94 healthy mature infants of single birth and appropriate for gestational age,born from June 2013 to December 2014.All eligible infants were enrolled within 21 days after birth.All the infant formula fed subjects were divided randomly into two groups as standard infant formula (IF) group and high sn-2 palmitate infant formula (HPIF) group.Breast-fed infants were enrolled as control group (BF group).All infants were followed up until 90 days old.The growth indexes and defecation status of the three groups were monitored dynamically.Meanwhile,stool fatty acid profile and mineral contents were also detected.Results There was no significant difference in head circumference,body length and body weight among the three groups at enrollment,42 days and 90 days old.The stool frequency and mushy stool frequency of HPIF and IF groups were significantly lower than that of BF group at 42 days and 90 days old;formed stool frequency was higher in HPIF and IF groups than in BF group.The fecal palmitic acid level in dry feces was significantly higher in HPIF and IF groups than in BF group [(31.1 ± 9.8),(30.9± 10.7) vs.(10.8± 8.8) mg/g] at 42 days old.At 90 days old,the fecal palmitic acid level in dry feces was significantly lower in HPIF group than in IF group [(24.3± 9.8) vs.(29.9± 7.9) mg/mg],while was significantly higher in both infant formula fed groups than in BF group [(8.9± 8.4) mg/g].The fecal calcium level in dry feces of HPIF and IF groups were significantly higher than that of BF group [(38.3± 14.0),(38.8± 15.5) vs.(21.3± 13.7) mg/g] at 42 days old.At 90 days old,the fecal calcium level in dry feces of HPIF group was significantly lower than that of IF group [(31.1 11.2) vs.(45.9 ± 16.5) mg/g,dry stool] and significantly higher than that of BF group [(21.5 ± 9.9) mg/g].The fecal magnesium level was similar between HPIF and IF groups,and significantly higher than that of BF group at 42 days and 90 days old.The fecal calcium level was positively correlated with the content of fecal palmitic acid among three groups (r =0.43,P＜ 0.01).Conclusions Breast milk is the best food for infants.Compared with standard infant formula,feeding with high sn-2 palmitate infant formula can reduce the fecal excretion of calcium and palmitic acid,making it closer to the level of breast-fed infants.
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AIM:To investigate the role of fatty acid translocase(FAT/CD36)on palmitate-induced inflam-mation in human monocyte-derived macrophage THP-1.METHODS:THP-1 cells were treated with palmitate(0,0.1 and 0.2 mmol/L)for 24 h.Transwell chamber assay was used to examine the migration ability of THP-1 cells.The mRNA ex-pression of CD36,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and monocyte chemotactic protein 1(MCP-1) was measured by real-time PCR.The protein levels of TNF-αand IL-6 in the supernatant of cultured cells were measured by ELISA.The protein level of CD36 was examined by Western blot.Small interfering RNA(siRNA)targeting CD36 (siCD36)was used to inhibit the expression of CD 36 in the THP-1 cells,and the changes of the cell migration and inflam-matory response were monitored as mentioned above.RESULTS:Palmitate increased the expression of CD36 in the THP-1 cells(P<0.05).Palmitate also up-regulated inflammatory cytokine and chemokine levels,and the differences were sta-tistically significant(P<0.05).Compared with control group,palmitate promoted migration of THP-1 cells.siCD36 was transfected into the THP-1 cells and the silencing efficiency was approximately 54%.The protein levels of TNF-αand IL-6 were also decreased in siCD36 group compared with scrambled RNA(scrRNA)group,and the differences were statisti-cally significant(P<0.05).The migrated cells in siCD36 group were significantly less than those in scrRNA group(P<0.05).CONCLUSION:Palmitate promotes migration ability and triggers inflammatory response in the THP-1 macropha-ges by upregulating CD36 expression.
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·AIM: To observe the efficacy of vitamin A palmitate eye gel and carboxymethylcellulose sodium eye drops on prevention of dry eye after phacoemulsification. ·METHODS: Ninety patients ( ninety eyes ) with age-related cataract enrolled in our hospital from March 2016 to August 2017 were performed phacoemulsification with intraocular lens implantation. They were randomly divided into three groups as control group ( n = 30 ), treated group Ⅰ ( n=30) and treated group Ⅱ ( n=30). The control group was administered with tobramycin and dexamethasone eye drops for 15d as the basis therapy. In treated group Ⅰ, patients were administered with carboxymethylcellulose sodium eye drops for 30d based on the treatment of the control group. The treated groupⅡ was administered with vitamin A palmitate eye gel for 30d on the basis of the treated group Ⅰ. The dry eye symptom score, corneal fluorescence ( FL ) staining scores, breakup time of tear film ( BUT) and Schirmer Ⅰtest ( SⅠt) without topical anesthesia were examined in 1d before operation and 15d and 30d after operation. · RESULTS: There were no statistically significant differences in subjective symptom scores of dry eye, BUT values, FL scores, and SⅠt values among the three groups before treatment (P>0. 05). After treatment, dry eye symptom scores, FL scores, and S Ⅰ t values increased at first and then decreased with time. BUT values decreased at first and then increased. Fifteen and thirty days after surgery, dry eye symptom scores, FL scores, and SⅠt values were significantly lower in the treated group Ⅰ and the treated group Ⅱ than in the control group. While BUT values were significantly higher than that in the control group. The dry eye symptom scores and S Ⅰ t value of treated group Ⅱ were significantly lower than the treated groupⅠ, and the BUT value was significantly higher than that of the treated group Ⅰ(P<0. 05). · CONCLUSION: Phacoemulsification combined with intraocular lens implantation has a certain damage of ocular surface tissue on the initial stage. The application of vitamin A palmitate eye gel combined carboxymethylcellulose sodium eye drops can improve the dry eye symptoms.