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
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
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
In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impur...In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impurities were synthesized and purified by column chromatography.Based on the results of NMR spectroscopy,IR spectroscopy,and MS,the two impurities were confirmed as 9-fluoro-11β,21-dihydroxy-16α,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione 21-myristate and stearate,respectively.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
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
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
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
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
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
Objective: to observe the therapeutic effect of dexamethasone palmitate injection on hoarseness caused by recurrent laryngeal nerve injury during thyroid surgery. Methods: 783 patients were divided into treatment grou...Objective: to observe the therapeutic effect of dexamethasone palmitate injection on hoarseness caused by recurrent laryngeal nerve injury during thyroid surgery. Methods: 783 patients were divided into treatment group (395 cases) and control group (388 cases). After thyroidectomy, the treatment group was sprayed with dexamethasone palmitate injection 1ml:4mg, while the control group was not sprayed with any drugs. The patients' hoarseness was observed on the 1st, 3rd, 7th and 30th day after operation. The GRBAS score, voice disorder index and VHI-13 Chinese version scale were used to evaluate the patients' voice. At the same time, the occurrence of severe adverse drug reactions, upper abdominal pain and hyperglycemia within 7 days after operation, and the infection in the operation area within 30 days after operation were observed. Results: the hoarseness in the treatment group was less than that in the control group on the 1st, 3rd and 7th day after operation (p<0.05), and there was no significant difference between the two groups on the 30th day after operation (p>0.05). There was no serious adverse drug reaction in the treatment group, upper abdominal pain and hyperglycemia within 7 days after operation, and there was no significant difference between the two groups within 30 days after operation (p>0.05). Conclusion: local application of dexamethasone palmitate injection during thyroid surgery has a certain therapeutic effect on reducing hoarseness caused by recurrent laryngeal nerve injury, but it has a limited therapeutic effect on recurrent laryngeal nerve injury which has not recovered its voice 30 days after operation.展开更多
This study provides different opinion for exploring the mechanism of catechin(CAT)relieving nonalcoholic steatohepatitis(NASH),it is more innovative to explore from the perspective of intestinal microorganism.Through ...This study provides different opinion for exploring the mechanism of catechin(CAT)relieving nonalcoholic steatohepatitis(NASH),it is more innovative to explore from the perspective of intestinal microorganism.Through in vitro fermentation experiments,CAT could improve the abundance of Enterococcus,and Enterococcus faecalis(EF)accounts for the vast majority of Enterococcus in human gut.The experimental results in vivo showed that EF group and CAT+EF group could reduce the body weight,liver index and epididymal fat index of NASH mice,and improve the changes of serum and liver indexes.Hematoxylin-eosin staining observation showed that these two groups have greatly improved the fatty degeneration,balloon degeneration and necrotic focus caused by NASH.The alleviation of CAT+EF group was more obvious.Results of targeted metabonomics showed that CAT could promote EF to produce more methyl palmitate(C_(16:0)),which plays a great role in relieving NASH.Our results indicated that EF could alleviate NASH and CAT+EF group had better alleviation may due to more production of methyl palmitate(C_(16:0))by EF.This study provides a new idea for CAT to alleviate NASH.展开更多
Carbon-coated Ni,Co and Ni-Co alloy catalysts were prepared by the carbonization of the metal doped resorcinol-formaldehyde resins synthesized by the one-pot extended Stöber method.It was found that the introduct...Carbon-coated Ni,Co and Ni-Co alloy catalysts were prepared by the carbonization of the metal doped resorcinol-formaldehyde resins synthesized by the one-pot extended Stöber method.It was found that the introduction of Co remarkably reduced the carbon microsphere size.The metallic Ni,Co,and Ni-Co alloy particles(mainly 10-12 nm)were uniformly distributed in carbon microspheres.A charge transfer from Ni to Co appeared in the Ni-Co alloy.Compared with those of metallic Ni and Co,the d-band center of the Ni-Co alloy shifted away from and toward the Fermi level,respectively.In the in-situ aqueous phase hydrodeoxygenation of methyl palmitate with methanol as the hydrogen donor at 330℃,the decarbonylation/decarboxylation pathway dominated on all catalysts.The Ni-Co@C catalysts gave higher activity than the Ni@C and Co@C catalysts,and the yields of n-pentadecane and n-C6-n-C16 reached 71.6%and 92.6%,respectively.The excellent performance of Ni-Co@C is attributed to the electronic interactions between Ni and Co and the small carbon microspheres.Due to the confinement effect of carbon,the metal particles showed high resistance to sintering under harsh hydrothermal conditions.Catalyst deactivation is due to the carbonaceous deposition,and the regeneration with CO_(2) recovered the catalyst reactivity.展开更多
Elevated plasma levels of free fatty acids(FFAs)may contribute to insulin resistance(IR)that is characteristic of type 2 diabetes mellitus.In this study,we investigated the effects of two fatty acids,palmitate(PA)and ...Elevated plasma levels of free fatty acids(FFAs)may contribute to insulin resistance(IR)that is characteristic of type 2 diabetes mellitus.In this study,we investigated the effects of two fatty acids,palmitate(PA)and arachidonic acid(AA)on glycogenesis under insulin signaling in HepG2cells,a transformed hepatic carcinoma cell line.In the presence of 200μmol of palmitate,insulin(10−7 mol/L)stimulation of glycogenesis was inhibited,as evidenced by increased glucose in the medium and decreased intracellular glycogen.Wortmannin(WM),a specific inhibitor of PI3K,dramatically decreased the amount of intracellular glycogen in cells without PA incubation.However,glycogen in PA treated cells was not significantly changed by WM,indicating that PA may also act on PI3K.Interestingly,AA restored the effects of WM inhibition on glycogenesis in PA cells.Western blot analysis demonstrated that PA in the absence of WM increased phosphorylated glycogen synthase(inactive form of GS)and decreased phosphorylated protein kinase B(active form of PKB),causing a reduction of intracellular glycogen.AA,however,reversed the effects of PA on GS and PKB.Furthermore,inhibition of protein kinase C(PKC)by a specific inhibitor chelerythrine chloride(CC)abolished the inhibitory effect of PA on glycogen synthesis by decreasing phosphorylated GS and increasing phosphorylated PKB.However,the effect of CC in the presence of PA disappeared when AA was also present.Our results suggest that there is a disruption of the insulin signaling pathway between PKB and GS when the cells were exposed to PA,contributing to IR.PA may also interrupt the PKC signaling pathway.In contrast,AA could rescue glycogenesis impaired by PA.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
In this study,ascorbyl palmitate(AP)incorporated in nanostructured lipid carriers(NLCs-AP)was fabricated using the hot-homogenization method.The amounts of AP,Tween 80,glyceryl stearate,and oleic acid were optimized b...In this study,ascorbyl palmitate(AP)incorporated in nanostructured lipid carriers(NLCs-AP)was fabricated using the hot-homogenization method.The amounts of AP,Tween 80,glyceryl stearate,and oleic acid were optimized by Box-Behnken Design(BBD)to obtain a high percentage of encapsulation efficiency and loading efficiency.Then,the optimum NLCs-AP,free-AP with rosemary essential oil(REO),NLCs-AP with REO,and tert-Butylhydroquinone(TBHQ)at a concentration of 75 ppm were added to camelina oil.Then peroxide value(PV),anisidine value(AV),TOTOX value(TV),oxidative stability using Rancimat,total phenol content(TPC),and antioxidant activity in camelina oil samples were evaluated during 90 days of storage at the ambient temper-ature.The optimum NLCs-AP had a particle size of 133.4 nm and a PDI of 0.29.The transmission electron microscopy(TEM)showed a spherical and smooth surface of the optimum NLCs-AP.The results of differential scanning calorimetry(DSC)and Fourier transfer spectroscopy infrared(FTIR)analyses implied that there was no interaction between AP and NLCs.The Korsmeyer-Peppas model was the best model for the evaluation of the release kinetics.The amounts of PV,AV,and TV of camelina oil containing the optimum NLCs-AP were slightly higher than the oil containing TBHQ.The highest oxidative protection,TPC,and antioxidant activity percentage were achieved in camelina oil containing NLCs-AP with REO.Conclusively,the optimum NLCs-AP had excellent potential for encapsulation of AP,and the mixture of REO and NLCs-AP could be applied for giving suitable oxidative stability in camelina oil.展开更多
The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porci...The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear.In this study,we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus(PEDV)infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms.The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics.Among the altered intestinal bacteria,the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group.A strain of C.perfringens type A,named DQ21,was successfully isolated from the intestines of healthy piglets.The metabolites of swine C.perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2(IPEC-J2)cells,and PEDV infection and pathogenicity in suckling piglets.Palmitic acid(PA)was identified as one of those metabolites with metabolomic technology,and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets.PA also increased the neutralizing antibody titer in the immune sera of mice.Furthermore,PA mediated the palmitoylation of the PEDV S protein,which improved virion stability and membrane fusion,thereby enhancing viral infection.Overall,our study demonstrates a novel mechanism of PEDV infection,with implications for PEDV pathogenicity.展开更多
BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but th...BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.展开更多
Mussels are common anchoring organisms that adhere to the surfaces of various substrates with their byssus.The adhesion of mussel to substrates is contingent upon the presence of mussel foot proteins,of which Mytilus ...Mussels are common anchoring organisms that adhere to the surfaces of various substrates with their byssus.The adhesion of mussel to substrates is contingent upon the presence of mussel foot proteins,of which Mytilus edulis foot protein-1(Mefp-1)has been identified as the most abundant protein.It has been found that lipids are involved in the mussel adhesion process and can facilitate Mefp-1adhesion.In this research,the adhesion behavior of Mefp-1 on various substrate surfaces under the effect of typical seawater cations with or without the presence of lipid were investigated using a quartz crystal microbalance with dissipation(QCM-D).Results indicate that the presence of cations Ca^(2+),Mg^(2+),Na^(+),and K^(+)leads to varying degrees of reduction in the adhesion performance of Mefp-1 on different substrates.The degree of this reduction,however,was much alleviated in the presence of palmitic acid,which is involved in the mussel adhesion process.Therefore,the involvement of palmitic acid is advantageous for mussel protein adhesion to the substrate surface in the marine environment.This study illustrated the significant contribution of palmitic acid to mussel adhesion,which can help to better understand biofouling mechanisms and develop biomimetic adhesive materials.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In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impurities were synthesized and purified by column chromatography.Based on the results of NMR spectroscopy,IR spectroscopy,and MS,the two impurities were confirmed as 9-fluoro-11β,21-dihydroxy-16α,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione 21-myristate and stearate,respectively.
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.
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.
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Objective: to observe the therapeutic effect of dexamethasone palmitate injection on hoarseness caused by recurrent laryngeal nerve injury during thyroid surgery. Methods: 783 patients were divided into treatment group (395 cases) and control group (388 cases). After thyroidectomy, the treatment group was sprayed with dexamethasone palmitate injection 1ml:4mg, while the control group was not sprayed with any drugs. The patients' hoarseness was observed on the 1st, 3rd, 7th and 30th day after operation. The GRBAS score, voice disorder index and VHI-13 Chinese version scale were used to evaluate the patients' voice. At the same time, the occurrence of severe adverse drug reactions, upper abdominal pain and hyperglycemia within 7 days after operation, and the infection in the operation area within 30 days after operation were observed. Results: the hoarseness in the treatment group was less than that in the control group on the 1st, 3rd and 7th day after operation (p<0.05), and there was no significant difference between the two groups on the 30th day after operation (p>0.05). There was no serious adverse drug reaction in the treatment group, upper abdominal pain and hyperglycemia within 7 days after operation, and there was no significant difference between the two groups within 30 days after operation (p>0.05). Conclusion: local application of dexamethasone palmitate injection during thyroid surgery has a certain therapeutic effect on reducing hoarseness caused by recurrent laryngeal nerve injury, but it has a limited therapeutic effect on recurrent laryngeal nerve injury which has not recovered its voice 30 days after operation.
基金supported by the National Natural Science Foundation of China(32202200)Shanghai Excellent Academic/Technical Leaders Project(23XD1430500).
文摘This study provides different opinion for exploring the mechanism of catechin(CAT)relieving nonalcoholic steatohepatitis(NASH),it is more innovative to explore from the perspective of intestinal microorganism.Through in vitro fermentation experiments,CAT could improve the abundance of Enterococcus,and Enterococcus faecalis(EF)accounts for the vast majority of Enterococcus in human gut.The experimental results in vivo showed that EF group and CAT+EF group could reduce the body weight,liver index and epididymal fat index of NASH mice,and improve the changes of serum and liver indexes.Hematoxylin-eosin staining observation showed that these two groups have greatly improved the fatty degeneration,balloon degeneration and necrotic focus caused by NASH.The alleviation of CAT+EF group was more obvious.Results of targeted metabonomics showed that CAT could promote EF to produce more methyl palmitate(C_(16:0)),which plays a great role in relieving NASH.Our results indicated that EF could alleviate NASH and CAT+EF group had better alleviation may due to more production of methyl palmitate(C_(16:0))by EF.This study provides a new idea for CAT to alleviate NASH.
基金support from the National Natural Science Foundation of China(Grant Nos.21576193,21176177).
文摘Carbon-coated Ni,Co and Ni-Co alloy catalysts were prepared by the carbonization of the metal doped resorcinol-formaldehyde resins synthesized by the one-pot extended Stöber method.It was found that the introduction of Co remarkably reduced the carbon microsphere size.The metallic Ni,Co,and Ni-Co alloy particles(mainly 10-12 nm)were uniformly distributed in carbon microspheres.A charge transfer from Ni to Co appeared in the Ni-Co alloy.Compared with those of metallic Ni and Co,the d-band center of the Ni-Co alloy shifted away from and toward the Fermi level,respectively.In the in-situ aqueous phase hydrodeoxygenation of methyl palmitate with methanol as the hydrogen donor at 330℃,the decarbonylation/decarboxylation pathway dominated on all catalysts.The Ni-Co@C catalysts gave higher activity than the Ni@C and Co@C catalysts,and the yields of n-pentadecane and n-C6-n-C16 reached 71.6%and 92.6%,respectively.The excellent performance of Ni-Co@C is attributed to the electronic interactions between Ni and Co and the small carbon microspheres.Due to the confinement effect of carbon,the metal particles showed high resistance to sintering under harsh hydrothermal conditions.Catalyst deactivation is due to the carbonaceous deposition,and the regeneration with CO_(2) recovered the catalyst reactivity.
基金This study was supported by grants from the Natural Science Foundation of the Hubei Province(2003ABA137)Research Foundation of the Health Department of Hubei Province(NX200403).
文摘Elevated plasma levels of free fatty acids(FFAs)may contribute to insulin resistance(IR)that is characteristic of type 2 diabetes mellitus.In this study,we investigated the effects of two fatty acids,palmitate(PA)and arachidonic acid(AA)on glycogenesis under insulin signaling in HepG2cells,a transformed hepatic carcinoma cell line.In the presence of 200μmol of palmitate,insulin(10−7 mol/L)stimulation of glycogenesis was inhibited,as evidenced by increased glucose in the medium and decreased intracellular glycogen.Wortmannin(WM),a specific inhibitor of PI3K,dramatically decreased the amount of intracellular glycogen in cells without PA incubation.However,glycogen in PA treated cells was not significantly changed by WM,indicating that PA may also act on PI3K.Interestingly,AA restored the effects of WM inhibition on glycogenesis in PA cells.Western blot analysis demonstrated that PA in the absence of WM increased phosphorylated glycogen synthase(inactive form of GS)and decreased phosphorylated protein kinase B(active form of PKB),causing a reduction of intracellular glycogen.AA,however,reversed the effects of PA on GS and PKB.Furthermore,inhibition of protein kinase C(PKC)by a specific inhibitor chelerythrine chloride(CC)abolished the inhibitory effect of PA on glycogen synthesis by decreasing phosphorylated GS and increasing phosphorylated PKB.However,the effect of CC in the presence of PA disappeared when AA was also present.Our results suggest that there is a disruption of the insulin signaling pathway between PKB and GS when the cells were exposed to PA,contributing to IR.PA may also interrupt the PKC signaling pathway.In contrast,AA could rescue glycogenesis impaired by PA.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
文摘In this study,ascorbyl palmitate(AP)incorporated in nanostructured lipid carriers(NLCs-AP)was fabricated using the hot-homogenization method.The amounts of AP,Tween 80,glyceryl stearate,and oleic acid were optimized by Box-Behnken Design(BBD)to obtain a high percentage of encapsulation efficiency and loading efficiency.Then,the optimum NLCs-AP,free-AP with rosemary essential oil(REO),NLCs-AP with REO,and tert-Butylhydroquinone(TBHQ)at a concentration of 75 ppm were added to camelina oil.Then peroxide value(PV),anisidine value(AV),TOTOX value(TV),oxidative stability using Rancimat,total phenol content(TPC),and antioxidant activity in camelina oil samples were evaluated during 90 days of storage at the ambient temper-ature.The optimum NLCs-AP had a particle size of 133.4 nm and a PDI of 0.29.The transmission electron microscopy(TEM)showed a spherical and smooth surface of the optimum NLCs-AP.The results of differential scanning calorimetry(DSC)and Fourier transfer spectroscopy infrared(FTIR)analyses implied that there was no interaction between AP and NLCs.The Korsmeyer-Peppas model was the best model for the evaluation of the release kinetics.The amounts of PV,AV,and TV of camelina oil containing the optimum NLCs-AP were slightly higher than the oil containing TBHQ.The highest oxidative protection,TPC,and antioxidant activity percentage were achieved in camelina oil containing NLCs-AP with REO.Conclusively,the optimum NLCs-AP had excellent potential for encapsulation of AP,and the mixture of REO and NLCs-AP could be applied for giving suitable oxidative stability in camelina oil.
基金supported by the National Natural Science Foundation of China(U23A20236)the Key Research and Development Program,Guidance Projects of Heilongjiang Province,China(GZ20220029)。
文摘The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear.In this study,we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus(PEDV)infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms.The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics.Among the altered intestinal bacteria,the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group.A strain of C.perfringens type A,named DQ21,was successfully isolated from the intestines of healthy piglets.The metabolites of swine C.perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2(IPEC-J2)cells,and PEDV infection and pathogenicity in suckling piglets.Palmitic acid(PA)was identified as one of those metabolites with metabolomic technology,and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets.PA also increased the neutralizing antibody titer in the immune sera of mice.Furthermore,PA mediated the palmitoylation of the PEDV S protein,which improved virion stability and membrane fusion,thereby enhancing viral infection.Overall,our study demonstrates a novel mechanism of PEDV infection,with implications for PEDV pathogenicity.
基金Supported by the Natural Science Foundation of China,No.81471081the Natural Science Foundation of Fujian Province,No.2023D009+1 种基金the Natural Science Foundation of Xiamen City,No.3502Z202373104 and No.3502Z20227162Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University,No.PM201809170005。
文摘BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.
基金Supported by the National Natural Science Foundation of China(No.41776177)the Qingdao Marine Science and Technology Pilot National Laboratory Fund(Nos.2016ASKJ14,QNLM2016ORP0403)。
文摘Mussels are common anchoring organisms that adhere to the surfaces of various substrates with their byssus.The adhesion of mussel to substrates is contingent upon the presence of mussel foot proteins,of which Mytilus edulis foot protein-1(Mefp-1)has been identified as the most abundant protein.It has been found that lipids are involved in the mussel adhesion process and can facilitate Mefp-1adhesion.In this research,the adhesion behavior of Mefp-1 on various substrate surfaces under the effect of typical seawater cations with or without the presence of lipid were investigated using a quartz crystal microbalance with dissipation(QCM-D).Results indicate that the presence of cations Ca^(2+),Mg^(2+),Na^(+),and K^(+)leads to varying degrees of reduction in the adhesion performance of Mefp-1 on different substrates.The degree of this reduction,however,was much alleviated in the presence of palmitic acid,which is involved in the mussel adhesion process.Therefore,the involvement of palmitic acid is advantageous for mussel protein adhesion to the substrate surface in the marine environment.This study illustrated the significant contribution of palmitic acid to mussel adhesion,which can help to better understand biofouling mechanisms and develop biomimetic adhesive materials.
