Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the s...Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.展开更多
The present study shows that double-stranded RNA-dependent protein kinase （PKR） regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinom...The present study shows that double-stranded RNA-dependent protein kinase （PKR） regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinoma ceils （HepG2）. In various types of cells, saturated free fatty acids （FFAs）, such as palmitate, have been shown to induce cellular apoptosis by several mechanisms. Palmitate down-regulates the activity of PKR and thereby decreases the level of Bcl-2 protein, mediated in part by reduced activation of the NF-KB transcription factor. In addition to the level of Bel-2 protein, the phosphorylation of Bcl-2 at different amino acid residues, such as Ser70 and Ser87, is also important in regulating cellular apoptosis. The decrease in the phosphorylatiou of Bcl-2 at Ser70 upon exposure to palmitate is mediated by inhibition of PKR and possibly by c-Jun N-terminal kinase （JNK）, whereas the phosphory- lation of Bcl-2 at Ser87 is unaffected by palmitate or PKR. In summary, PKR mediates the regulation of the protein level and the phosphorylation status of Bel-2, providing a novel mechanism of palmitate-induced apoptosis in HepG2 cells.展开更多
In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was elimin...In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.展开更多
A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containin...A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containing the internal standard (IS), testosterone decanoate (TD), was extracted using a mixture of chloroform and methanol (9:1, v/v). Extracts were then centrifuged, dried and dissolved in acetonitrile. A chromatographic separation based on an isocratic elution was done using acetonitrile and water (85:15, v/v) as a mobile phase at a flow rate of 1.2 mL/min. The graph of the developed method was linear within the tested calibration range of 0.5 - 40 μg/mL. The overall extraction recovery of DXP from BALF samples was 84.3% ± 1.6%. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. This methodology has been applied to determine levels of DXP in BALF samples collected from rats treated with DXP large porous particles. The measured concentrations were successfully evaluated using a non-compartment pharmacokinetic model. Since the developed method requires only a microvolume (100 μL) of BALF sample for analysis, it is therefore particularly suitable for the evaluation of drug biodistribution in lung.展开更多
Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degr...Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degradation especially in an aqueous environment. The purpose of this study was to prepare microcapsules of VAP using combination maltodextrin and modified starches. Emulsion of VAP was prepared using cremophore RH 40 with Tween 80 in a homogenizer and formed emulsion was spray-dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 30% of VAP were produced using different concentration of wall materials. The prepared microcapsules were evaluated for their physical, morphological, in-vitro drug release and SEM study. The results showed that obtained microcapsules are nearly spherical in shape with a particle size ranged from 1 to 12 μm. The drug content and encapsulation efficiency (53% - 63%) of different batches were found within acceptable range. These stabilized drug loaded microcapsules were incorporated into silicone cream based formulation for convenient topical application and evaluated for its physicochemical parameters. The drug release study showed 80.18% to 83.43% of drug release from VAP microcapsules while topical formulations prepared by VAP microcapsules showed 67.09% to 71.45% drug release at the end of 24 hrs. The formulations were kept for 3 months stability study as per ICH guidelines and found to be stable.展开更多
AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into...AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into 4 groups:(1) control;(2) LPS;(3) Methyl palmitate; and(4) Lutein groups. Methyl palmitate(300 mg/kg, ip) was administered 3 times per week on alternating days while lutein(100 mg/kg, oral) was given once daily. After 1 wk of vehicle/methyl palmitate/lutein treatment, ALI was induced by a single dose of LPS(7.5 mg/kg, iv). After 24 h of LPS injection, animals were sacrificed then biochemical parameters and histopathology were assessed. RESULTS: Treatment with methyl palmitate attenuated ALI, as it significantly decreased the lung wet/dry weight(W/D) ratio, the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid(BALF) andhistopathological damage. However, methyl palmitate failed to decrease lactate dehydrogenase(LDH) activity in BALF. On the other hand, lutein treatment produced significant anti-inflammatory effects as revealed by significant decrease in accumulation of inflammatory cells in lung, LDH level in BALF and histopathological damage. Methyl palmitate and lutein significantly increased superoxide dismutase(SOD) and reduced glutathione(GSH) activities with significant decrease in the lung malondialdehyde(MDA) content. Importantly, methyl palmitate and lutein decreased the level of the inflammatory cytokine tumor necrosis factor-α(TNF-α) in the lung. Lutein also reduced LPS-mediated overproduction of pulmonary nitrite/nitrate(NO-2/NO-3), which was not affected by methyl palmitate pretreatment. CONCLUSION: These results demonstrate the potent protective effects of both methyl palmitate and lutein against LPS-induced ALI in rats. These effects can be attributed to potent antioxidant activities of these agents, which suppress inflammatory cell infiltration and regulated cytokine effects.展开更多
BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema ...BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema with subsequent respiratory arrest.Here,we present a case report of paliperidone palmitate-induced angioedema with a relatively mild clinical presentation compared with the previously reported case,and the patient's condition was not complicated by lifethreatening anaphylaxis.CASE SUMMARY A 79-year-old female,who had a major neurocognitive disorder due to Alzheimer's disease with behavioral disturbances.Paliperidone palmitate was offlabel used to control her aggression,irritability,and psychosis.After induction doses(150 mg and 100 mg intramuscularly,given 1 wk apart),she developed intermittent swelling of the face,eyelids,and lips on day 17 after the initial dose,and the edema was explicitly seen on day 20.The diagnosis was paliperidone palmitate-induced angioedema.The monthly injection dose was discontinued on day 33 after the initial dose.The angioedema was subsequently alleviated,and it had completely resolved by day 40 after the initial dose.CONCLUSION Paliperidone palmitate-induced angioedema is a rare condition and can present with a mild,intermittent facial edema,which may be overlooked in clinical practice.展开更多
Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incub...Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.展开更多
A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation ...A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.展开更多
High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology （RSM） based on 5-level, 3-vari...High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology （RSM） based on 5-level, 3-variable of centre composite rotatable design （CCRD） was used to evaluate the interactive effects of synthesis, of temperature （40-60 ℃）; amount of enzyme （0.1-0.4 g） and substrate molar ratio of oleyl alcohol to palmitic acid （1：1-4：1） on the percentage yield of wax ester. All reactions were fixed at 1 hour of reaction time. The optimum condition obtained from RSM for the reactions were temperature of 57.9 ℃, enzyme amount of 0.26 g and molar ratio of substrates of 2.92. The actual experimental yield was 91.2% under the optimum condition, which compared well with the maximum predicted value of 92.0%. Comparison of predicted and experimental values reveal good correspondence between them, implying that empirical models derived from RSM can be used to adequately describe the relationship between the factors and response in the synthesis of oleyl palmitate.展开更多
目的系统评价棕榈酸帕利哌酮注射液与其他抗精神病药长效针剂比较治疗精神分裂症的有效性和安全性。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、PsycINFO、CNKI、SinoMed、VIP、WanFang Data数据库,搜集关于棕...目的系统评价棕榈酸帕利哌酮注射液与其他抗精神病药长效针剂比较治疗精神分裂症的有效性和安全性。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、PsycINFO、CNKI、SinoMed、VIP、WanFang Data数据库,搜集关于棕榈酸帕利哌酮注射液对比其他抗精神病药长效针剂治疗精神分裂症的随机对照试验(RCT),检索时限均从建库至2023年4月30日。由2名研究者独立筛选、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.4软件进行Meta分析。结果共纳入12个RCT,包括4368例患者。Meta分析结果显示,棕榈酸帕利哌酮注射液组与利培酮长效针剂组的临床有效率差异无统计学意义(P>0.05),与其他抗精神病药长效针剂组的阳性和阴性症状量表(PANSS)总体评分改变值差异也无统计学意义(P>0.05)。与其他抗精神病药长效针剂组相比,棕榈酸帕利哌酮注射液组总退出率[RR=1.14,95%CI(1.06,1.24),P<0.01]和肌注部位异常的不良反应发生率[RR=2.08,95%CI(1.03,4.22),P=0.04]均显著增加。结论当前证据表明,与其他抗精神病药长效针剂相比,棕榈酸帕利哌酮注射液治疗精神分裂症的有效性并无明显差异,但部分不良反应发生率稍有增加。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。展开更多
基金supported by a National Natural Science Foundation of China grant(31701558)the Young Elite Scientists Sponsorship Program by CAST(2017QNRC001)+1 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,B90719028)the national first-class discipline program of Food Science and Technology(JUFSTR20180202).
文摘Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.
文摘The present study shows that double-stranded RNA-dependent protein kinase （PKR） regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinoma ceils （HepG2）. In various types of cells, saturated free fatty acids （FFAs）, such as palmitate, have been shown to induce cellular apoptosis by several mechanisms. Palmitate down-regulates the activity of PKR and thereby decreases the level of Bcl-2 protein, mediated in part by reduced activation of the NF-KB transcription factor. In addition to the level of Bel-2 protein, the phosphorylation of Bcl-2 at different amino acid residues, such as Ser70 and Ser87, is also important in regulating cellular apoptosis. The decrease in the phosphorylatiou of Bcl-2 at Ser70 upon exposure to palmitate is mediated by inhibition of PKR and possibly by c-Jun N-terminal kinase （JNK）, whereas the phosphory- lation of Bcl-2 at Ser87 is unaffected by palmitate or PKR. In summary, PKR mediates the regulation of the protein level and the phosphorylation status of Bel-2, providing a novel mechanism of palmitate-induced apoptosis in HepG2 cells.
文摘In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.
文摘A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containing the internal standard (IS), testosterone decanoate (TD), was extracted using a mixture of chloroform and methanol (9:1, v/v). Extracts were then centrifuged, dried and dissolved in acetonitrile. A chromatographic separation based on an isocratic elution was done using acetonitrile and water (85:15, v/v) as a mobile phase at a flow rate of 1.2 mL/min. The graph of the developed method was linear within the tested calibration range of 0.5 - 40 μg/mL. The overall extraction recovery of DXP from BALF samples was 84.3% ± 1.6%. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. This methodology has been applied to determine levels of DXP in BALF samples collected from rats treated with DXP large porous particles. The measured concentrations were successfully evaluated using a non-compartment pharmacokinetic model. Since the developed method requires only a microvolume (100 μL) of BALF sample for analysis, it is therefore particularly suitable for the evaluation of drug biodistribution in lung.
文摘Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degradation especially in an aqueous environment. The purpose of this study was to prepare microcapsules of VAP using combination maltodextrin and modified starches. Emulsion of VAP was prepared using cremophore RH 40 with Tween 80 in a homogenizer and formed emulsion was spray-dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 30% of VAP were produced using different concentration of wall materials. The prepared microcapsules were evaluated for their physical, morphological, in-vitro drug release and SEM study. The results showed that obtained microcapsules are nearly spherical in shape with a particle size ranged from 1 to 12 μm. The drug content and encapsulation efficiency (53% - 63%) of different batches were found within acceptable range. These stabilized drug loaded microcapsules were incorporated into silicone cream based formulation for convenient topical application and evaluated for its physicochemical parameters. The drug release study showed 80.18% to 83.43% of drug release from VAP microcapsules while topical formulations prepared by VAP microcapsules showed 67.09% to 71.45% drug release at the end of 24 hrs. The formulations were kept for 3 months stability study as per ICH guidelines and found to be stable.
文摘AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into 4 groups:(1) control;(2) LPS;(3) Methyl palmitate; and(4) Lutein groups. Methyl palmitate(300 mg/kg, ip) was administered 3 times per week on alternating days while lutein(100 mg/kg, oral) was given once daily. After 1 wk of vehicle/methyl palmitate/lutein treatment, ALI was induced by a single dose of LPS(7.5 mg/kg, iv). After 24 h of LPS injection, animals were sacrificed then biochemical parameters and histopathology were assessed. RESULTS: Treatment with methyl palmitate attenuated ALI, as it significantly decreased the lung wet/dry weight(W/D) ratio, the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid(BALF) andhistopathological damage. However, methyl palmitate failed to decrease lactate dehydrogenase(LDH) activity in BALF. On the other hand, lutein treatment produced significant anti-inflammatory effects as revealed by significant decrease in accumulation of inflammatory cells in lung, LDH level in BALF and histopathological damage. Methyl palmitate and lutein significantly increased superoxide dismutase(SOD) and reduced glutathione(GSH) activities with significant decrease in the lung malondialdehyde(MDA) content. Importantly, methyl palmitate and lutein decreased the level of the inflammatory cytokine tumor necrosis factor-α(TNF-α) in the lung. Lutein also reduced LPS-mediated overproduction of pulmonary nitrite/nitrate(NO-2/NO-3), which was not affected by methyl palmitate pretreatment. CONCLUSION: These results demonstrate the potent protective effects of both methyl palmitate and lutein against LPS-induced ALI in rats. These effects can be attributed to potent antioxidant activities of these agents, which suppress inflammatory cell infiltration and regulated cytokine effects.
文摘BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema with subsequent respiratory arrest.Here,we present a case report of paliperidone palmitate-induced angioedema with a relatively mild clinical presentation compared with the previously reported case,and the patient's condition was not complicated by lifethreatening anaphylaxis.CASE SUMMARY A 79-year-old female,who had a major neurocognitive disorder due to Alzheimer's disease with behavioral disturbances.Paliperidone palmitate was offlabel used to control her aggression,irritability,and psychosis.After induction doses(150 mg and 100 mg intramuscularly,given 1 wk apart),she developed intermittent swelling of the face,eyelids,and lips on day 17 after the initial dose,and the edema was explicitly seen on day 20.The diagnosis was paliperidone palmitate-induced angioedema.The monthly injection dose was discontinued on day 33 after the initial dose.The angioedema was subsequently alleviated,and it had completely resolved by day 40 after the initial dose.CONCLUSION Paliperidone palmitate-induced angioedema is a rare condition and can present with a mild,intermittent facial edema,which may be overlooked in clinical practice.
基金supported by Nantong Science and Technology Project(MS12018020,MS12018041)Jiangsu Government Scholarship for Overseas Studies(JS-2017-200)+1 种基金the Doctoral Scientific Research Foundation of Nantong University(135420505015)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(11KJB180010).
文摘Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.
文摘A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.
文摘High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology （RSM） based on 5-level, 3-variable of centre composite rotatable design （CCRD） was used to evaluate the interactive effects of synthesis, of temperature （40-60 ℃）; amount of enzyme （0.1-0.4 g） and substrate molar ratio of oleyl alcohol to palmitic acid （1：1-4：1） on the percentage yield of wax ester. All reactions were fixed at 1 hour of reaction time. The optimum condition obtained from RSM for the reactions were temperature of 57.9 ℃, enzyme amount of 0.26 g and molar ratio of substrates of 2.92. The actual experimental yield was 91.2% under the optimum condition, which compared well with the maximum predicted value of 92.0%. Comparison of predicted and experimental values reveal good correspondence between them, implying that empirical models derived from RSM can be used to adequately describe the relationship between the factors and response in the synthesis of oleyl palmitate.
