The current situation of medical staff's awareness about high alert medication was investigated in order to promote safe medication and standardized management of the high alert medication in China. Twenty questions ...The current situation of medical staff's awareness about high alert medication was investigated in order to promote safe medication and standardized management of the high alert medication in China. Twenty questions were designed concerning elementary knowledge of high alert medications, storage management, medication issues and risks. In order to understand the knowledge level and education status of high alert medication, a convenient survey was conducted among 300 medical staffs in Tianjin. Medical staff's average score of high alert medication knowledge was 12.43±0.27, and the average scores of elementary knowledge of high alert medication, storage management, medication issues and risks were 3.38±0.11, 2.46±0.14, 3.17±0.11 and 3.41±0.12 respectively. Occupation(F=4.86, P=0.003), education background(F=5.57, P=0.019) and professional titles(F=13.44, P≤0.001) contributed to the high alert medications knowledge scores. Currently, the most important channel to obtain high alert medication knowledge was hospital files or administrative rules, and clinical pharmacist seminars were the most popular education form. It was suggested that the high alert medication knowledge level of the medical staff needs to increase, and it might benefit from targeted, systematic and diverse training to the medical staff working in the different circulation nodes of the medications. Further research to develop and validate the instrument is needed.展开更多
Objective In 2017,China launched a new round of medical reform(NMR)to address the inaccessibility of high-priced drugs for patients with serious diseases.This study explored the impact of the NMR on the accessibility ...Objective In 2017,China launched a new round of medical reform(NMR)to address the inaccessibility of high-priced drugs for patients with serious diseases.This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies(mAbs),and the effective promotion policies after the NMR.Methods We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province,China.By interviewing hospital pharmacy experts,we identified the potential value of the current NMR in improving the access to therapeutic mAbs.Results The average availability of 13 mAbs increased by 8.1%in the surveyed hospitals of Hubei province after the NMR.The median unit price of 10 mAbs dropped by 34.3%.The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident(56.2%reduction).The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs.However,the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs.Conclusion Not all current NMR policies play a positive role in promoting the accessibility of mAbs.To further improve the accessibility of mAbs in the future in China,it is therefore critical to increase the investment in independent research and development of high-quality mAbs,establish localized guidelines for the rational use of mAbs in clinical practice,and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders.展开更多
Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult...Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult lymphohematopoietic system.Given the limitations of current therapies,there is a pressing need to develop new and effective drugs for DLBCL treatment.Methods A series of pyrrolidone derivatives were synthesized,and their antitumor activities were assessed,particularly against DLBCL cell lines.Structure-activity relationship(SAR)analysis was conducted to identify key structural components essential for activity.The most promising compound,referred to as compound 7,was selected for further mechanistic studies.The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting,and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis.Results The compound 7 exhibited good antitumor activity among the synthesized derivatives,specifically in DLBCL cell lines.SAR analysis highlighted the critical role ofα,β-unsaturated ketones in the antitumor efficacy of these compounds.Mechanistically,compound 7 was found to induce significant DNA damage,trigger an inflammatory response,cause mitochondrial dysfunction,and disrupt cell cycle progression,ultimately leading to apoptosis of DLBCL cells.Conclusion The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death.These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL.展开更多
Calcium carbonates are commonly administered as supplements for conditions of calcium deficiency.We report here pharmacokinetic characteristics of a novel formulation,calcium carbonate compound granules(CCCGs).forming...Calcium carbonates are commonly administered as supplements for conditions of calcium deficiency.We report here pharmacokinetic characteristics of a novel formulation,calcium carbonate compound granules(CCCGs).forming complexes of calcium carbonate and calcium citrate in water.CCCGs were compared to a kind of commonly?used calcium carbonate preparation(CC)in the market in 5-week-old mice that had been treated with omeprazole,to suppress gastric acid secretion,and in untreated control mice.The results showed that:(1)CCCGs had better water solubility than CC in vitro;(2)In control mice,calcium absorption rates after CCCGs administration were comparable to those after CC administration;(3)Inhibition of gastric acid secretion did not affect calcium absorption after CCCGs,but moderately decreased it after CC;(4)The presence of phytic acid or tannin did not affect calcium absorption rates after CCCGs but did for CC;and(5)In nonnal mice,CCCGs did not inhibit gastric emptying and intestinal propulsion,and did not alter the gastrointestinal honnones.The results suggest that CCCGs may be therapeutically advantageous over more commonly used calcium supplement formulations,particularly for adolescents,because of their stable calcium absorption characteristics and their relatively favorable adverse effect profile.展开更多
Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin agai...Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin(1, 2 and 4 μmol/L) could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.展开更多
The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (AngⅡ)-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate (STS) in the primary culture of neonatal rat cardiomyocyte...The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (AngⅡ)-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate (STS) in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction (RT-PCR). It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly (P〈0.01). After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group (P〈0.01). After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group (P〈0.05). After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ (P〈0.05 or P〈0.01). It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.展开更多
Peptides play crucial roles in various physiological and pathological processes. Consequently, the investigation of peptide-based drugs is a highlight in the research and development of new drugs. However, natural pep...Peptides play crucial roles in various physiological and pathological processes. Consequently, the investigation of peptide-based drugs is a highlight in the research and development of new drugs. However, natural peptides are not always ideal choices for clinical application due to their limited number and sometimes cytotoxicity to normal cells. Aiming to gain stronger or specific or novel biological effects and overcome the disadvantages of natural peptides, artificial hybrid peptides have been designed by combining the sequence of two or more different peptides with varied biological functions. Compared to natural peptides, hybrid peptides have shown better therapeutic potentials against bacteria, tumors, and metabolic diseases. In this review, design strategies, structure features and recent development of hybrid peptides are summarized;future directions for the research and development of hybrid peptide drugs are also discussed.展开更多
This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazola...This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.展开更多
The compounds from the root of Rhododendron molle G.Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral ...The compounds from the root of Rhododendron molle G.Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral data. Three compounds were separated from the root of Rhododendron molle G.Don and identified as Rhodojaponin-Ⅲ, taraxerol, β-sitosterol for the first time.展开更多
This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel α- and β-receptor blocking agent, 1-[4-(2-methoxyethyl) phenoxy]-3-...This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel α- and β-receptor blocking agent, 1-[4-(2-methoxyethyl) phenoxy]-3-[[2-(2- methoxyphenoxy) ethyl]amino]-2-propanol (T J0711), in rat plasma. GITC was used for precolunm derivatization of T J0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column (250 mm×4.6 mm ID, 5-μm particle size), with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water (58:42, v/v) containing 0.02% glacial acetic acid (v/v). Using the chromatographic conditions described, T J0711 enantiomers were well resolved with mean retention time of 10.2 and 11.5 min, respectively. Linear response (r〉0.999) was observed over the range of 0.125-12.5 μg/mL of TJ0711 hydrochloride enantiomers. The mean relative standard deviation (RSD%) of the results of within-day precision was ≤ 10%. The proposed method was found to be suitable and accurate for the quantitative determination of T J0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.展开更多
This study examined the effects of Bangdeyun on the expressions of nuclear factor-kappaB (NF-κB), interferon-gamma (IFN-y) and interleukin-10 (IL-10) in the endometrium of mice with embryo implantation dysfunct...This study examined the effects of Bangdeyun on the expressions of nuclear factor-kappaB (NF-κB), interferon-gamma (IFN-y) and interleukin-10 (IL-10) in the endometrium of mice with embryo implantation dysfunction (EID) during the implantation time (namely on pregnancy day 5, 6, 7 and 8) and explored the local immune regulatory effects of Bangdeyun. The gestational mice were randomly divided into normal group, model group and Bangdeyun-treated group. EID models of mice were established by using indomethacin. The endometrial expression of NF-κB was detected by immunohistochemistry and Western blotting. IFN-γ and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in the normal group, NF-κB and IFN-γ were weakly expressed and IL-10 was strongly expressed in the endometrium during the whole implantation period. In the model group, the expressions of NF-κB and IFN-T were increased on pregnancy day 5, 6 and 7, and IL-10 expression decreased during the whole implantation time when compared with those in the normal group (P〈0.01 for all). In the Bangdeyun-treated group, little amount of NF-κB and IFN-γ was expressed and IL-10 expression was strong, much the way they were expressed in the normal group (P〉0.05). The expressions of NF-κB and IFN-T were much lower in the Bangdeyun-treated group than those in the model group on pregnancy day 5, 6 and 7 (P〈0.01 for all), while the expression of IL-10 was much higher than in the model group during the whole implantation time (P〈0.01). It was suggested Bangderun may favor a shift from Thl- to Th2-type immune response, therefore inhibiting the maternal immune rejection, inducing the immune tolerance and improving the fetal implantation.展开更多
Qingkailing (QKL)is a modern preparation exploited according to the traditional Chinese medicine theory.It becomes the second leading cause of adverse drug events (ADEs)in all traditional Chinese medicine injections.T...Qingkailing (QKL)is a modern preparation exploited according to the traditional Chinese medicine theory.It becomes the second leading cause of adverse drug events (ADEs)in all traditional Chinese medicine injections.The safety evaluation and rational use of QKL are of special importance.This retrospective study used data from Adverse Drug Reaction Monitoring Center of Hubei Province in China from January 2012 to December 2014.ADE cases induced by QKL were collected and analyzed according to patients'demographics,characteristics of drugs involved,characteristics of ADEs,causality,and outcomes.A total of 1330 qualified ADEs were included.Most ADEs occurred within 30 min after administration and the 0-10 years old age group had the highest number of ADEs.The common ADEs included anaphylactic reaction,dyspnea and nausea.Serious reactions accounted for 5.19%.Combination with cephalosporin (74/146,50.69%) caused more ADEs than other drugs did.Serious attention should be paid when QKL is used for children,and combination with cephalosporin should be avoided.展开更多
Fluorescent nanoparticles have good chemical stability and photostability,controllable optical properties and larger stokes shift.In light of their designability and functionability,the fluorescent nanoparticles are w...Fluorescent nanoparticles have good chemical stability and photostability,controllable optical properties and larger stokes shift.In light of their designability and functionability,the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications.To enhance the sensitivity and selectivity,the combination of the fluorescent nanoparticles with the molecularly imprinted polymer,i.e.molecularly imprinted fluorescent nanoparticles(MIFN),was an effective way.The sensor based on MIFN(the MIFN sensor)could be more compatible with the complex sample matrix,which was especially widely adopted in medical and biological analysis.In this mini-review,the construction method,detective mechanism and types of MIFN sensors are elaborated.The current applications of MIFN sensors in pharmaceutical analysis,including pesticides/herbicide,veterinary drugs/drugs residues and human related proteins,are highlighted based on the literature in the recent three years.Finally,the research prospect and development trend of the MIFN sensor are forecasted.展开更多
Triple-negative breast cancer(TNBC)is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed,and human epidermal growth factor receptor 2 is not amplified or overexpresse...Triple-negative breast cancer(TNBC)is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed,and human epidermal growth factor receptor 2 is not amplified or overexpressed either,which make the clinical diagnosis and treatment very challenging.Molecular imaging can provide an effective way to diagnose TNBC.Upconversion nanoparticles(UCNPs),are a promising new generation of molecular imaging probes.However,UCNPs still need to be improved for tumor-targeting ability and biocompatibility.This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles(CCm-UCNPs),owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes,and modified multifunctional UCNPs.This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo.By using this probe,MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo.Based on the tumor imaging and molecular classification results,the probe is also expected to be modified for drug delivery in the future,contributing to the treatment of TNBC.The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.展开更多
The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analys...The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.展开更多
AIM: To explore the possibility of repression of chloromycetin (Cm) acyl transferase by using external guided sequence (EGS) in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. ...AIM: To explore the possibility of repression of chloromycetin (Cm) acyl transferase by using external guided sequence (EGS) in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS: EGS directed against chloromycetin acetyl transferase gene (cat) was cloned to vector pEGFP-C1 which contains the kanamycin (Kin) resistance gene. The recombinant plasmid pEGFP-C1+EGScatl+cat2 was constructed and the blank vector without EGS fragment was used as control plasmids. By using the CaCl2 transformation method, the recombinant plasmids were introduced into the clinically isolated Cm resistant but Km sensitive E coli strains. Transformants were screened on LB agar plates containing Kin. Extraction of plasmids and PCR were applied to identify the positive clones. The growth curve of EGS transformed bacteria cultured in broth with Cm resistance was determined by using spectrophotometer at A600. Drug sensitivity was tested in solid culture containing Cm by using KB method. RESULTS: Transformation studies were carried out on 16 clinically isolated Cm-resistant (250 μg/mL of Cm) E colistrains by using pEGFP-C1-EGScatlcat2 recombinant plasmid. Transformants were screened on LB-agar plates containing Km after the transformation using EGS. Of the 16 tested strains, 4 strains were transformed successfully. Transformants with EGS plasmid showed growth inhibition when grown in liquid broth culture containing 200 μg/mL of Cm. In drug sensitivity test, these strains were sensitive to Cm on LB-agar plates containing 200 μg/mL of Cm. Extraction of plasmids and PCR amplification showed the existence of EGS plasmids in these four transformed strains. These results indicated that the Cat of the four clinical isolates had been suppressed and the four strains were converted to Cm sensitive ones. CONCLUSION: The EGS directed against Cat is able to inhibit the expression of Cat, and hence convert Cm- resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of converting the phenotype of clinical drug-resistant isolates strains to drug-sensitive ones.展开更多
Alzheimer's disease(AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta(Aβ) peptide in human brains. Oxidative stress and...Alzheimer's disease(AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta(Aβ) peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides(200, 400 and 800 mg/kg, p.o.) for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase(SOD), glutathione(GSH), acetylcholine esterase(ACh E), and the content of malondialdehyde(MDA) as well as the level of nitric oxide(NO) in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2'-deoxyguanosine(8-OHd G), tumor necrosis factor-α(TNF-α), interleukin 1β(IL-1β) and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase(i NOS) and nuclear factor κB(NF-κB) were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides(400 or 800 mg/kg). All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.展开更多
A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT),a semi-synthetic cephamycin antibiotic,in human plasma.CTT and the internal standard chloramphenicol we...A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT),a semi-synthetic cephamycin antibiotic,in human plasma.CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid.Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80,v/v) at a flow rate of 1.0 mL/min.The column effluent was monitored by UV detection at 300 nm.The column temperature was maintained at 40°C.This method demonstrated good linearity in the range of 0.525-300.0 μg/mL,with correlation coefficients greater than 0.99.The limit of quantification (LOQ) was 0.525 μg/mL in human plasma.Intra-and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD).The accuracy,when expressed by the bias,ranged from 0.57% to 4.04%.The mean extraction recovery of CTT was higher than 40.94%.The method was found to be precise,accurate,and specific for CTT quantitative analysis,and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.展开更多
D-a-tocopherol polyethylene glycol 1000 succinate(TPGS)is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA.It's widely applied as a multifunctional drug carrier for nanomedicine.The advantages of...D-a-tocopherol polyethylene glycol 1000 succinate(TPGS)is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA.It's widely applied as a multifunctional drug carrier for nanomedicine.The advantages of TPGS include P-glycoprotein(P-gp)inhibition,penetration promotion,apoptosis induction via mitochondrial-associated apoptotic pathways,multidrug resistant(MDR)reversion,metastasis inhibition and so on.TPGS-based drug delivery systems which are responding to extermal stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect,through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior.In this review,TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed,including pH-responsive,redox-responsive and multi-responsive systems in various formulations.The achievements,mechanisms and diffcrent characteristics of TPGS-bascd stimuli-responsive drug-delivery systems in tumor therapy were also outlined.展开更多
Phenolic compounds such as chlorogenic acid,cryptochlorogenic acid,neochlorogenic acid and caffeic acid are widely distributed in fruits,vegetables and traditional Chinese medicines with a wide range of biological act...Phenolic compounds such as chlorogenic acid,cryptochlorogenic acid,neochlorogenic acid and caffeic acid are widely distributed in fruits,vegetables and traditional Chinese medicines with a wide range of biological activities.Tyrosinase plays a critical role in the food industry,but recent studies have proposed unexplored aspects of clinical application.Tyrosinase-catalyzed oxidation of four polyphenols as well as its underlying mechanism remains unclear.In the current work,we investigated the kinetic properties of tyrosinase-catalyzed oxidation of the four polyphenols of interest.To measure the unstable o-quinone products,an analytical method using 3-methyl-2-benzothiazolinone hydrazone(MBTH)was established.The optimal incubation time,buffer pH,temperature and enzyme concentration for the enzyme activity in the presence of each polyphenol of interest were investigated.Under the final optimized conditions,the kinetics and substrate specificity of four polyphenols were examined.K inetic data showed that tyrosinase had the greatest substrate affinity to chlorogenic acid compared with its isomers and caffeic acid.The catalytic efficiency with chlorogenic acid was 8-to 15-fold higher than that with the other 3 polyphenols.Molecular docking study demonstrated that the tight binding of chlorogenic acid at the peripheral site should be the major reason for the specificity to chlorogenic acid.In light of this,the rational design of high-affinity inhibitors against tyrosinase may focus on the binding of both the Cu site and peripheral site.This study will supply a basis for the selection of phenolic acids in food industry and health carc.展开更多
基金supported by grants from Basic Scientific Research Business Expenses Foundation of Huazhong University of Science and Technology,China(No2014QN136)Natural Science Foundation of Hube Province,China(No.2014CFB955)
文摘The current situation of medical staff's awareness about high alert medication was investigated in order to promote safe medication and standardized management of the high alert medication in China. Twenty questions were designed concerning elementary knowledge of high alert medications, storage management, medication issues and risks. In order to understand the knowledge level and education status of high alert medication, a convenient survey was conducted among 300 medical staffs in Tianjin. Medical staff's average score of high alert medication knowledge was 12.43±0.27, and the average scores of elementary knowledge of high alert medication, storage management, medication issues and risks were 3.38±0.11, 2.46±0.14, 3.17±0.11 and 3.41±0.12 respectively. Occupation(F=4.86, P=0.003), education background(F=5.57, P=0.019) and professional titles(F=13.44, P≤0.001) contributed to the high alert medications knowledge scores. Currently, the most important channel to obtain high alert medication knowledge was hospital files or administrative rules, and clinical pharmacist seminars were the most popular education form. It was suggested that the high alert medication knowledge level of the medical staff needs to increase, and it might benefit from targeted, systematic and diverse training to the medical staff working in the different circulation nodes of the medications. Further research to develop and validate the instrument is needed.
基金supported by the grants from the National Natural Science Foundation of China(No.70903025,No.71373089).
文摘Objective In 2017,China launched a new round of medical reform(NMR)to address the inaccessibility of high-priced drugs for patients with serious diseases.This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies(mAbs),and the effective promotion policies after the NMR.Methods We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province,China.By interviewing hospital pharmacy experts,we identified the potential value of the current NMR in improving the access to therapeutic mAbs.Results The average availability of 13 mAbs increased by 8.1%in the surveyed hospitals of Hubei province after the NMR.The median unit price of 10 mAbs dropped by 34.3%.The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident(56.2%reduction).The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs.However,the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs.Conclusion Not all current NMR policies play a positive role in promoting the accessibility of mAbs.To further improve the accessibility of mAbs in the future in China,it is therefore critical to increase the investment in independent research and development of high-quality mAbs,establish localized guidelines for the rational use of mAbs in clinical practice,and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders.
基金financially supported by the National Natural Science Foundation of China(No.81903461)the Natural Science Foundation of Hubei Province(No.ZRMS2023000340).
文摘Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult lymphohematopoietic system.Given the limitations of current therapies,there is a pressing need to develop new and effective drugs for DLBCL treatment.Methods A series of pyrrolidone derivatives were synthesized,and their antitumor activities were assessed,particularly against DLBCL cell lines.Structure-activity relationship(SAR)analysis was conducted to identify key structural components essential for activity.The most promising compound,referred to as compound 7,was selected for further mechanistic studies.The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting,and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis.Results The compound 7 exhibited good antitumor activity among the synthesized derivatives,specifically in DLBCL cell lines.SAR analysis highlighted the critical role ofα,β-unsaturated ketones in the antitumor efficacy of these compounds.Mechanistically,compound 7 was found to induce significant DNA damage,trigger an inflammatory response,cause mitochondrial dysfunction,and disrupt cell cycle progression,ultimately leading to apoptosis of DLBCL cells.Conclusion The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death.These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL.
文摘Calcium carbonates are commonly administered as supplements for conditions of calcium deficiency.We report here pharmacokinetic characteristics of a novel formulation,calcium carbonate compound granules(CCCGs).forming complexes of calcium carbonate and calcium citrate in water.CCCGs were compared to a kind of commonly?used calcium carbonate preparation(CC)in the market in 5-week-old mice that had been treated with omeprazole,to suppress gastric acid secretion,and in untreated control mice.The results showed that:(1)CCCGs had better water solubility than CC in vitro;(2)In control mice,calcium absorption rates after CCCGs administration were comparable to those after CC administration;(3)Inhibition of gastric acid secretion did not affect calcium absorption after CCCGs,but moderately decreased it after CC;(4)The presence of phytic acid or tannin did not affect calcium absorption rates after CCCGs but did for CC;and(5)In nonnal mice,CCCGs did not inhibit gastric emptying and intestinal propulsion,and did not alter the gastrointestinal honnones.The results suggest that CCCGs may be therapeutically advantageous over more commonly used calcium supplement formulations,particularly for adolescents,because of their stable calcium absorption characteristics and their relatively favorable adverse effect profile.
基金supported by the National Natural Science Foundation of China(No.81173065)
文摘Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin(1, 2 and 4 μmol/L) could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.
基金a grant from National Natural Sciences Foundation of China (No. 30500657)
文摘The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (AngⅡ)-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate (STS) in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction (RT-PCR). It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly (P〈0.01). After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group (P〈0.01). After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group (P〈0.05). After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ (P〈0.05 or P〈0.01). It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.
基金This work was supported by the National Natural Science Foundation of China (Nos. 31471208 and 31671195)the Academic Frontier Youth Team Project of HUST (2015).
文摘Peptides play crucial roles in various physiological and pathological processes. Consequently, the investigation of peptide-based drugs is a highlight in the research and development of new drugs. However, natural peptides are not always ideal choices for clinical application due to their limited number and sometimes cytotoxicity to normal cells. Aiming to gain stronger or specific or novel biological effects and overcome the disadvantages of natural peptides, artificial hybrid peptides have been designed by combining the sequence of two or more different peptides with varied biological functions. Compared to natural peptides, hybrid peptides have shown better therapeutic potentials against bacteria, tumors, and metabolic diseases. In this review, design strategies, structure features and recent development of hybrid peptides are summarized;future directions for the research and development of hybrid peptide drugs are also discussed.
基金supported by a grant from National Natural Sciences Foundation of China (No.30873171)
文摘This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.
文摘The compounds from the root of Rhododendron molle G.Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral data. Three compounds were separated from the root of Rhododendron molle G.Don and identified as Rhodojaponin-Ⅲ, taraxerol, β-sitosterol for the first time.
基金supported by a grant from a science andtechnology research program of Hubei provincial government(No.2003AA301B05)the Wuhan New Drug Development Program(No.20066002103)
文摘This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel α- and β-receptor blocking agent, 1-[4-(2-methoxyethyl) phenoxy]-3-[[2-(2- methoxyphenoxy) ethyl]amino]-2-propanol (T J0711), in rat plasma. GITC was used for precolunm derivatization of T J0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column (250 mm×4.6 mm ID, 5-μm particle size), with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water (58:42, v/v) containing 0.02% glacial acetic acid (v/v). Using the chromatographic conditions described, T J0711 enantiomers were well resolved with mean retention time of 10.2 and 11.5 min, respectively. Linear response (r〉0.999) was observed over the range of 0.125-12.5 μg/mL of TJ0711 hydrochloride enantiomers. The mean relative standard deviation (RSD%) of the results of within-day precision was ≤ 10%. The proposed method was found to be suitable and accurate for the quantitative determination of T J0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.
基金supported by a grant from National Natural Science Foundation of China (No. 30801538)
文摘This study examined the effects of Bangdeyun on the expressions of nuclear factor-kappaB (NF-κB), interferon-gamma (IFN-y) and interleukin-10 (IL-10) in the endometrium of mice with embryo implantation dysfunction (EID) during the implantation time (namely on pregnancy day 5, 6, 7 and 8) and explored the local immune regulatory effects of Bangdeyun. The gestational mice were randomly divided into normal group, model group and Bangdeyun-treated group. EID models of mice were established by using indomethacin. The endometrial expression of NF-κB was detected by immunohistochemistry and Western blotting. IFN-γ and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in the normal group, NF-κB and IFN-γ were weakly expressed and IL-10 was strongly expressed in the endometrium during the whole implantation period. In the model group, the expressions of NF-κB and IFN-T were increased on pregnancy day 5, 6 and 7, and IL-10 expression decreased during the whole implantation time when compared with those in the normal group (P〈0.01 for all). In the Bangdeyun-treated group, little amount of NF-κB and IFN-γ was expressed and IL-10 expression was strong, much the way they were expressed in the normal group (P〉0.05). The expressions of NF-κB and IFN-T were much lower in the Bangdeyun-treated group than those in the model group on pregnancy day 5, 6 and 7 (P〈0.01 for all), while the expression of IL-10 was much higher than in the model group during the whole implantation time (P〈0.01). It was suggested Bangderun may favor a shift from Thl- to Th2-type immune response, therefore inhibiting the maternal immune rejection, inducing the immune tolerance and improving the fetal implantation.
基金the National Science Foundation for Young Scientists of China(No.71503089)the Fundamental Research Fund for the Central Universities(No.2016YXMS146).
文摘Qingkailing (QKL)is a modern preparation exploited according to the traditional Chinese medicine theory.It becomes the second leading cause of adverse drug events (ADEs)in all traditional Chinese medicine injections.The safety evaluation and rational use of QKL are of special importance.This retrospective study used data from Adverse Drug Reaction Monitoring Center of Hubei Province in China from January 2012 to December 2014.ADE cases induced by QKL were collected and analyzed according to patients'demographics,characteristics of drugs involved,characteristics of ADEs,causality,and outcomes.A total of 1330 qualified ADEs were included.Most ADEs occurred within 30 min after administration and the 0-10 years old age group had the highest number of ADEs.The common ADEs included anaphylactic reaction,dyspnea and nausea.Serious reactions accounted for 5.19%.Combination with cephalosporin (74/146,50.69%) caused more ADEs than other drugs did.Serious attention should be paid when QKL is used for children,and combination with cephalosporin should be avoided.
基金This work is supported by the National Natural Science Foundation of China(No.21804105)by the Fundamental Research Funds for the Central Universities(No.5003515037)supported by the Huazhong University of Science and Technology Start-up Fund to Xu YU.
文摘Fluorescent nanoparticles have good chemical stability and photostability,controllable optical properties and larger stokes shift.In light of their designability and functionability,the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications.To enhance the sensitivity and selectivity,the combination of the fluorescent nanoparticles with the molecularly imprinted polymer,i.e.molecularly imprinted fluorescent nanoparticles(MIFN),was an effective way.The sensor based on MIFN(the MIFN sensor)could be more compatible with the complex sample matrix,which was especially widely adopted in medical and biological analysis.In this mini-review,the construction method,detective mechanism and types of MIFN sensors are elaborated.The current applications of MIFN sensors in pharmaceutical analysis,including pesticides/herbicide,veterinary drugs/drugs residues and human related proteins,are highlighted based on the literature in the recent three years.Finally,the research prospect and development trend of the MIFN sensor are forecasted.
基金the National Natural Science Foundation of China(Nos.81630049 and 81501532).
文摘Triple-negative breast cancer(TNBC)is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed,and human epidermal growth factor receptor 2 is not amplified or overexpressed either,which make the clinical diagnosis and treatment very challenging.Molecular imaging can provide an effective way to diagnose TNBC.Upconversion nanoparticles(UCNPs),are a promising new generation of molecular imaging probes.However,UCNPs still need to be improved for tumor-targeting ability and biocompatibility.This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles(CCm-UCNPs),owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes,and modified multifunctional UCNPs.This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo.By using this probe,MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo.Based on the tumor imaging and molecular classification results,the probe is also expected to be modified for drug delivery in the future,contributing to the treatment of TNBC.The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.
基金the National Natural Science Foundation of China(No.81801621,No.81572723,No.81872253).
文摘The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.
基金Supported by the National Natural Science Foundation of China,No. 39570846
文摘AIM: To explore the possibility of repression of chloromycetin (Cm) acyl transferase by using external guided sequence (EGS) in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS: EGS directed against chloromycetin acetyl transferase gene (cat) was cloned to vector pEGFP-C1 which contains the kanamycin (Kin) resistance gene. The recombinant plasmid pEGFP-C1+EGScatl+cat2 was constructed and the blank vector without EGS fragment was used as control plasmids. By using the CaCl2 transformation method, the recombinant plasmids were introduced into the clinically isolated Cm resistant but Km sensitive E coli strains. Transformants were screened on LB agar plates containing Kin. Extraction of plasmids and PCR were applied to identify the positive clones. The growth curve of EGS transformed bacteria cultured in broth with Cm resistance was determined by using spectrophotometer at A600. Drug sensitivity was tested in solid culture containing Cm by using KB method. RESULTS: Transformation studies were carried out on 16 clinically isolated Cm-resistant (250 μg/mL of Cm) E colistrains by using pEGFP-C1-EGScatlcat2 recombinant plasmid. Transformants were screened on LB-agar plates containing Km after the transformation using EGS. Of the 16 tested strains, 4 strains were transformed successfully. Transformants with EGS plasmid showed growth inhibition when grown in liquid broth culture containing 200 μg/mL of Cm. In drug sensitivity test, these strains were sensitive to Cm on LB-agar plates containing 200 μg/mL of Cm. Extraction of plasmids and PCR amplification showed the existence of EGS plasmids in these four transformed strains. These results indicated that the Cat of the four clinical isolates had been suppressed and the four strains were converted to Cm sensitive ones. CONCLUSION: The EGS directed against Cat is able to inhibit the expression of Cat, and hence convert Cm- resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of converting the phenotype of clinical drug-resistant isolates strains to drug-sensitive ones.
基金supported by the grants from the National Nature Science Foundation of China(No.81173065)Wuhan Science and Technology Plan Foundation(No.2012605-23182)
文摘Alzheimer's disease(AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta(Aβ) peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides(200, 400 and 800 mg/kg, p.o.) for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase(SOD), glutathione(GSH), acetylcholine esterase(ACh E), and the content of malondialdehyde(MDA) as well as the level of nitric oxide(NO) in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2'-deoxyguanosine(8-OHd G), tumor necrosis factor-α(TNF-α), interleukin 1β(IL-1β) and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase(i NOS) and nuclear factor κB(NF-κB) were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides(400 or 800 mg/kg). All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.
基金supported by a grant of the Guangzhou Boji Clinical Research Center of New Drugs,Guangzhou,Guangdong,China
文摘A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT),a semi-synthetic cephamycin antibiotic,in human plasma.CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid.Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80,v/v) at a flow rate of 1.0 mL/min.The column effluent was monitored by UV detection at 300 nm.The column temperature was maintained at 40°C.This method demonstrated good linearity in the range of 0.525-300.0 μg/mL,with correlation coefficients greater than 0.99.The limit of quantification (LOQ) was 0.525 μg/mL in human plasma.Intra-and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD).The accuracy,when expressed by the bias,ranged from 0.57% to 4.04%.The mean extraction recovery of CTT was higher than 40.94%.The method was found to be precise,accurate,and specific for CTT quantitative analysis,and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.
基金This study was supported by the National Natural Science Foundation of China(No.81871473)and the Natural Science Foundation of Zhejiang Chinese Medical University(No.2018ZZ11).
文摘D-a-tocopherol polyethylene glycol 1000 succinate(TPGS)is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA.It's widely applied as a multifunctional drug carrier for nanomedicine.The advantages of TPGS include P-glycoprotein(P-gp)inhibition,penetration promotion,apoptosis induction via mitochondrial-associated apoptotic pathways,multidrug resistant(MDR)reversion,metastasis inhibition and so on.TPGS-based drug delivery systems which are responding to extermal stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect,through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior.In this review,TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed,including pH-responsive,redox-responsive and multi-responsive systems in various formulations.The achievements,mechanisms and diffcrent characteristics of TPGS-bascd stimuli-responsive drug-delivery systems in tumor therapy were also outlined.
基金The study was supported by grants from the National Natural Science Foundation of China(No.81773811)Yunnan Applied Basic Research Project(No.2017FB074)+1 种基金the Yunnan Provincial Tobacco Monopoly Bureau Grants(No.2017YN09)the Fundamental Research Funds for the Central Universities(No.2020kfyXGYJ061).
文摘Phenolic compounds such as chlorogenic acid,cryptochlorogenic acid,neochlorogenic acid and caffeic acid are widely distributed in fruits,vegetables and traditional Chinese medicines with a wide range of biological activities.Tyrosinase plays a critical role in the food industry,but recent studies have proposed unexplored aspects of clinical application.Tyrosinase-catalyzed oxidation of four polyphenols as well as its underlying mechanism remains unclear.In the current work,we investigated the kinetic properties of tyrosinase-catalyzed oxidation of the four polyphenols of interest.To measure the unstable o-quinone products,an analytical method using 3-methyl-2-benzothiazolinone hydrazone(MBTH)was established.The optimal incubation time,buffer pH,temperature and enzyme concentration for the enzyme activity in the presence of each polyphenol of interest were investigated.Under the final optimized conditions,the kinetics and substrate specificity of four polyphenols were examined.K inetic data showed that tyrosinase had the greatest substrate affinity to chlorogenic acid compared with its isomers and caffeic acid.The catalytic efficiency with chlorogenic acid was 8-to 15-fold higher than that with the other 3 polyphenols.Molecular docking study demonstrated that the tight binding of chlorogenic acid at the peripheral site should be the major reason for the specificity to chlorogenic acid.In light of this,the rational design of high-affinity inhibitors against tyrosinase may focus on the binding of both the Cu site and peripheral site.This study will supply a basis for the selection of phenolic acids in food industry and health carc.