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Atherosclerosis is usually the underlying cause of cardiovascular diseases. With the change in diet structure and living environment, it has become an increasingly serious global health problem, posing a huge challenge to public health. Berberine, also known as flavonidol, is an isoquinoline-type quaternary alkaloid with purgative and detoxifying effects. Berberine and its derivatives have antibacterial, antiviral, anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, and atherosclerosis prevention effects, etc. Recent research results showed that berberine and its derivatives can play an important role in atherosclerosis prevention through a hypolipidemic effect, anti-oxidative stress and anti-inflammatory activity, improvement of vascular endothelial dysfunction, and regulation of intestinal microbiota. In this review paper, the research progress on the mechanism of action of berberine and its derivatives in the prevention of atherosclerosis was reviewed from the perspectives of a lipid-regulating effect, inhibition of oxidative stress and the inflammatory response, improvement of vascular endothelial dysfunction, and regulation of intestinal microbiota. The aim of this paper is to provide a theoretical basis for reducing the occurrence of atherosclerosis, improving the clinical symptoms of patients, and further developing berberine-based drugs.
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Objective To investigate the clinical effect of monosialotetrahexosyl ganglioside in the treatment of neonatal intracranial hemorrhage.Methods From January 2016 to December 2018,142 neonates with intracranial hemorrhage admitted to the Maternal and Child Health Hospital of Zhoushan were randomly divided into observation group (71 cases) and control group (71 cases) according to the digital table.The control group was treated with routine treatment,while the observation group was treated with ganglioside needle on the basis of the control group.Both two groups were treated for 14 days.The therapeutic effects,muscle tone recovery time,reflex recovery time and consciousness recovery time were compared.The changes of neurobehavioral assessment score (NABA score),TNF-αt,IL-1β,MMP-2,T IMP-1 and NSE levels before and after treatment were compared.Results The total effective rate of the observation group (92.96％) was higher than that of the control group (77.47％) (x2 =6.762,P ＜ 0.05).The recovery time of muscle tension,reflex and consciousness in the observation group [(7.68 ± 1.29) d,(6.83 ± 1.20) d and (8.34 ± 1.54) d] were shorter than those in the control group [(10.25 ± 2.31) d,(9.17 ±1.86) d and (10.53 ± 1.08) d] (t =8.185,8.908,9.811,all P ＜ 0.05).After treatment,the NABA score of the observation group [(40.37 ± 0.65) points] was higher than that of the control group [(37.16 ± 0.93) points] (t =23.838,P ＜ 0.05).The serum levels of TNF-α [(26.37 ± 4.25) pg/L],IL-1β [(16.74 ± 3.24) ng/L],MMP-2 [(78.39 ± 16.57)g/L],TIMP-1 [(179.32 ± 17.65) ng/mL] and NSE [(13.52 ± 2.19) g/L] in the observation group were lower than those in the control group [(53.21 ± 7.39) pg/L,(28.93 ± 5.64) ng/L,(97.42 ±12.63) g/L,(238.63 ± 28) ng/mL and (21.43 ± 2.89) μg/L] (t =26.529,15.792,7.696,14.938,1 8.381,all P ＜ 0.05).Conclusion Ganglioside has good therapeutic effect on neonatal intracranial hemorrhage.It can reduce the serum levels of TNF-α,IL-1β,MMP-2,TIMP-1 and NSE,and improve the neurobehavioral function of neonates.
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Bacterial resistance is an increasingly serious problem.Therefore,it is necessary to find new antibacterial drugs.Flavonoids are a class of polyphenolic chemicals with low molecular weight,which exhibit many beneficial properties for human health by the interaction of cellular targets,such as the key cell signaling pathways.Flavonoids have been extensively studied as one of the important sources of antimicrobial compounds.At present,antibacterial flavonoids can be divided into two categories.One is the natural,extracted from the plant or microbial secondary metabolites.The other is the product of chemical synthesis,i.e.the derivatives of flavonoids or chalcone.In this paper,the progress of antibacterial flavonoids by natural extraction and chemical synthesis were summarized.
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Bacterial resistance is an increasingly serious problem.Therefore,it is necessary to find new antibacterial drugs.Flavonoids are a class of polyphenolic chemicals with low molecular weight,which exhibit many beneficial properties for human health by the interaction of cellular targets,such as the key cell signaling pathways.Flavonoids have been extensively studied as one of the important sources of antimicrobial compounds.At present,antibacterial flavonoids can be divided into two categories.One is the natural,extracted from the plant or microbial secondary metabolites.The other is the product of chemical synthesis,i.e.the derivatives of flavonoids or chalcone.In this paper,the progress of antibacterial flavonoids by natural extraction and chemical synthesis were summarized.
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Objective To understand the cognitive and behavioral characteristics of AIDS between male-male in college students, and to provide evidence for the prevention and control strategies. Methods Using cluster random sampling method, the questionnaire survey including basic situation, the perception of HIV/AIDS of male male actors, sexual behavior and condom use and HIV/AIDS counseling detection, was used to investigate in male students of 8 universities at Beijing fangshan distric. Results A total of 2444 male college students were surveyed, 138 cases with male-male behavior were detected, and the detection rate was 5.65％. The detection rate (18.31％) of the junior college students was statistically higher than that of first-year college students (4.28％) and sophomores (6.52％, P<0.017). The awareness rates of four relevant knowledge about HIV/AIDS for 138 students were 25.36％, 15.22％, 9.42％and 13.77％respectively. The 44.93％male-male in college students had first sexual intercourse were younger than 18 years old. The proportion of students with first time male-male behavior and age <18 years was higher in the first-year college students (58.9％) than that of sophomores and junior college students (30.77％, 26.92％). The incidence rate of bisexuality was 43.48％ in male-male behavior, and 73.91％ was polysexual partners. The correct usage rate of condom was 31.16％. AIDS counseling detection rate was 27.54％. Conclusion The detection rate is higher in students with male-male behavior, and the awareness rate of AIDS-related knowledge is lower. A variety of high risk sexual behaviors are prevalent, so it is necessary to strengthen HIV/AIDS education and HIV/AIDS related knowledge for college students.
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Objective To study the photodynamic therapeutical efficacy of a novel photosensitizer DTP on sensitive gastric cancer cells (SGC7901) and vincristine-resistant gastric cancer cells (SGC7901/VCR).Methods The P-gp expression on the SGC7901 and SGC7901/VCR cell membrane was indirectly confirmed by fluorescence microscopy.The survival rates of SGC7901 and SGC7901/VCR cells were evaluated by cell counting kit (CCK-8) after photodynamic therapy with DTP.The intracellular DTP uptake levels of two types of cell were determined using a fluorescence spectrophotometer,and the intracellular DTP distributions were observed by laser scanning confocal microscopy.Results The novel photosensitizer DTP has considerable photodynamic cytotoxic effect on SGC7901 and SGC7901/VCR cells.However,this effect on the SGC7901NCR cells was relatively weak (P＜0.05),and could not be enhanced by P-gp inhibitor verapamil or cyclosporine A(P＞0.05).The DTP uptake level in SGC7901 cells was higher than that in SGC7901/VCR cells (P＜0.05),and could not be enhanced by P-gp inhibitor verapamil and cyclosporin A (P＞0.05).It was found that DTP distributed in the lysosomes of SGC7901 cells and in the lysosomes and mitochondria of SGC7901/VCR cells.Conclusions The novel photosensitizer DTP is not the substrate of multidrug transporter P-gp,and its weaker photodynamic cytotoxic effect on SGC7901/VCR cells is independent of the P-gp overexpression on its cell membrane,which may be related to the distribution of intracellular DTP in the two types of cell.
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Objective To investigate susceptibility and antibacterial activity of cationic porphyfin derivative mediated photodynamic antimicrobial chemotherapy (CPD-PACT) against Pseudomonas aeruginosa,to provide experimental evidence for its high efficiency antibacterial activity.Methods The impacts of culture environments on minimum inhibitory concentration (MIC) were measured by double dilution method.The formation of inhibition zone was determined by diffusion plate method.The postantibiotic effect was analyzed by colony forming units.The viability and morphology of Pseudomonas aeruginosa were observed by confocal laser scanning microscopy (CLSM).Results The inoculum size of bacterial had a certain effect on the MIC.The MIC values increased as the pH of medium rose.When the calf serum content of culture medium increased,the MIC rose in light reaction and dropped in dark reaction.The diameter of inhibition zone mainly depended on the laser energy density,but not the concentration of photosensitizer.Though CPD possessed strong antimicrobial activity and persistent suppression on bacterial growth,the surviving Pseudomonas aeruginosa would soon continue to proliferate after PACT.The fluorescence images captured by CLSM showed that CPD-PACT could destroy the membrane integrity,leak the cytoplasmic component,decrease the bacterial activity and finally lead Pseudomonas aeruginosa to death.Conclusions CPD has strong inhibitory activity and obvious postantibiotic effect on Pseudomonas aeruginosa,which is suitable to be developed as an drug candidate for PACT.
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Objective To study the radiation protection effect of sugar polyphenols A obtained by structured modification using mouse model of radiation injury induced by 137Cs γ-ray.Methods Total 42 male Kunming mice aged 4-6 weeks were randomly divided into six groups:negative control group (NCG),positive control group (PCG),irradiation control group (ICG) as well as three irradiation experimental groups.The radiation injury model was developed by once whole-body irradiation with 6.0 Gy 137Cs γ-ray.The mice in three experimental groups were fed sugar polyphenols A respectively with doses of 0.05,0.10 and 0.20 g/kg,for 14 d before irradiation,and continuously fed with the drug for 7 d after the irradiation.After that the mice were sacrificed,and the organ index,hematological parameters,spleen colony number,bone marrow DNA content and nucleated cells in bone-marrow were tested to evaluate the effect of sugar polyphenols A.Results Compared with the ICG,the irradiation experimental groups with the sugar polyphenols A doses of 0.05,0.10,0.20 g/kg showed reductions in irradiation injuries of immune system and hematopoietic system,which makes the significant increases of the spleen indexes (Z=-2.364,-3.003 and -2.747,P＜0.05) and the number of endogenous spleen colony (Z=-2.458,-2.141 and-2.206,P＜0.05).In the groups with the doses of 0.05 and 0.2 g/kg,the number of white blood cells were significantly increased (Z=-2.652 and-2.139,P＜0.05).Besides,in the group with the dose of 0.2 g/kg,the level of red blood cells (Z=-2.364,P＜0.05),bone marrow DNA content (Z=-2.492,P＜0.05) and nucleated cells in bone-marrow (Z=-2.492,P＜0.05) were also increased compared with the ICG.Conclusions Sugar polyphenols A has the positive effects on the recovery of immune and hematopoietic function of mice through improving the organ index,endogenous spleen colony number,peripheral white blood cell number,bone marrow DNA content and nucleated cells in bone-marrow,which can reduce the injury induced by ionizing radiation.
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Objective To study the photodynamic therapy (PDT) mediated by a novel porphyrin-typed photosensitizer on human hepatic carcinoma HepG2 cell and the mechanisms.Methods Experiments were derided into four groups:control group,PDT group,photosensitizer group and photosensitizer+PDT group.The photostability of novel photosensitizer upon repetitive illumination was evaluated by bleaching method,and cell survival rate was determined by MTT assay.Cellular uptake of novel photosensitizer was measured with luminescence spectrometer,and cellular localization ofphotosensitizer was observed by laser scanning confocal microscopy (LSCM).Furthermore,apoptotic cell was detected with Hoechst 333342 staining.Results Novel photosensitizer was stable after repetitive light irradiation,and PDT or photosensitizer alone showed no dark cytotoxicity toward HepG2 cell (P＞0.05),but intense killing was observed in photosensitizer+PDT group (P＜0.05).The IC50 is 1.21 μmol/L.Cellular uptake of novel photosensitizer was concentration-dependent and the highest uptake is at concentration of 12.5 μmol/L.Novel photosensitizer localizes in lysosomes of HepG2 cell,and the death mode of HepG2 cell was mainly apoptosis.Conclusions Novel photosensitizer exerts profound cytotoxic effects on HepG2 cell mainly through the initiation of secondary cell apoptosis by lysosome destruction.
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Objective Nanoparticles are widely investigated and applied in clinical diagnosis and treatment as drug carrier,and their transmembrane process is related to their biological effects.The aim of this study was to investigate the interaction of fluorescein-labeled PLGA nanoparticles and HL60 cells via fluorescence tracking.Methods The transmembrane process of nanoparticles was quantitatively analyzed by laser scanning confocal microscopy.Results The analyzing results showed that the interaction of fluorescein-labeled PLGA nanoparticles and HL60 cells was strongly temperature-dependent.The receptor-mediated endocytosis mechanism played an important role in the transmembrane process for cellular uptake of nanopaticles.Conclusions This study provides a theoretical basis for design and application of nano-medicines.
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Objective To prepare a novel brain active-targeting endomorphin (EM) loaded hyperbranched polyglycerols-poly (lactic-co-glycolic acid) (HBPG-PLGA) nanoparticles (NPs) and study its mechanism of passing across blood brain barrier (BBB) in brain microvascular endothelial cells (BMEC).Methods The OX26 (transferring receptor monoclonal antibody) conjugated EM loaded HBPG-PLGA NPs was constructed according to water-in-oil-in-water emulation solvent evaporation technique as a novel biodegradable brain active-targeting drug delivery system.The properties of the NPs were evaluated by transmission electron microscope (TEM) in vitro.Through flow cytometry and laser scanning confocal microscope,the mechanism of passing across BBB was evaluated.Results The preparation methodology of NPs was optimized and established.The mean diameter was (170±20) nm and Zeta potential was about-27 mV.Core-shell construction was showed on TEM.Cellular uptake study showed that the uptake of NPs was via a caveolae-mediated endocytic pathway,then endomorphin and carrier were divided into two parts in BMEC.Conclusions The OX26 conjugated EM loaded NPs were stable,and demonstrate remarkable effects on crossing BBB.Cellular uptake by BMEC is a very important mechanism of the NPs' brain activating-targeting effect.
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Objective To investigate the photochemotherapeutic effect and the main affecting factors of PSD-007 on human cervical cancer Hela in vitro.Methods Hela cells were treated with different concentrations of PSD-007 (0,3.125,6.25,12.5,25,50,100 μg/ml) for 2 h under the influence of low-level laser (635 nm) therapy at different doses (0,0.6,1.2,2.4,4.8,9.6 J/cm2).Then the OD values and survival rates of Hela cells were measured by MTT assay compared with breast cancer cells MCF-7 in same treatment.Hela cells were treated with 12.5 μg/ml of PSD-007 for 2 h and were treated with different intensities of laser (1.2,2.4,4.8 J/cm2).The cellular apoptosis rate and cell cycle phase distribution of Hela were measured by a flow cytometry (FCM).Results Survival rates of Hela cells declined with more than 25 μg/ml of PSD-007 only,and significant difference in the inhibitory between the PDT group and control group was observed (P＜0.05).The survival rates of Hela after PDT was decreased by the concentration of sensitizer and dose of laser.There were no significant differences of cell survival rates among the groups with concentrations more than 12.5 μg/ml and laser energy density more than 4.8 J/cm2.The FCM assay showed a G0/G1 cell cycle arrest in a time-dependent manner.Conclusions PSD-007 has a photodynamic effect on Hela in vitro.Photodynamic effect of PSD-007 was more significant in Hela than MCF-7.Less photosensitizer and laser energy density were needed.
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Objective To evaluate the combined effects of photodynamic therapy (PDT) with PSD-007 and cytarabine (Ara-c) on human acute promyelocyte leukemia cell HL-60.Methods The experiments were divided into four groups:control group,PDT-only groups (PDT 1-4 groups:the combination of PSD-007 concentrations (5 μg/ml and 7.5 μg/ml) and the energy density of laser (EDL) (1.2 J/cm2 and 2.4 J/cm2),Ara-c-only groups (Ara-c A group:0.3μg/ml,Ara-c B group:1.2μg/ml) and combination groups (the pair-wise combinations of the PDT doses and Ara-c doses above).All combination groups were treated with three treating methods,including P24A (the cells were treated with PDT for 24 h,and then cocultured with Ara-c for another 24 h),A24P (treated with Ara-c for 24 h before PDT,and then cocultured with PDT for 24 h),and PA24 (treated with the Ara-c and PDT for 24 h).CCK-8 method was used to test the cell viability,and the combined effect was analyzed using King formula.The changes of cell cycles were analyzed using flow cytometry.Results In the case of low-dose PDT,the combination groups showed coordinated effect with all three methods,whereas in the case of high-dose PDT,they showed additive or coordinated effect in P24A and A24P,but it showed antagonistic effect in the schedule of PA24.Cell cycles were inhibited to G0/G1 phase by both PDT and Ara-c.Conclusions Coordinated effects could be found when HL-60 cells were treated with the combination of Ara-c and PDT.The effects depended on the dose of Ara-c and PDT and the operation schedules.The effects at low dose were more obvious than that of high dose,and allowing a 24 h period in between the addition of PDT and Ara-c also promoted the effects.
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Objective To study the cytotoxicity against brain microvessel endothelial cells and blood compatibility in rats of OX26 conjugated endomorphin (EM) loaded hyperbranched polyglycerols-poly(lactic-co-glycolic acid)(HBPG-PLGA) nanoparticles.Methods Prepared nanoparticles were divided into group B (HBPG-PLGA nanoparticles),group EP (EM-HBPG-PLGA nanoparticles) and group OEP (OX26-EM-HBPG-PLGA nanoparticles).The cytotoxicity against brain microvessel endothelial cells (BMECs) of nanoparticles of different groups were measured by MTT test,haemolysis test,normal haemotological parameter and several primary items of coagulation system were tested after nanoparticles of different groups and different dosages injection on rats.Results ①All the three groups of nanoparticles induced decreased cell viability in a dose dependent manner in MTT test,whereas all groups of nanoparticles showed low cytotoxicity against the BMECs during 30 to 600 μg/ml.②There was no significant difference in haemolysis ratio (P＞0.05) and normal haemotological parameter (P＞0.05).③There was no significant difference between the low dosage of all the three groups of nanoparticles and the control group on the function of coagulation system in rats (P＞0.05).④Compared with C group,high dose groups demonstrated longer prothrombin time (PT),activeated partial thromboplasting time (APTT) and lower fibrinogen (Fbg) (P＜0.05).At the same time,compared with the low dose subgroups,PT and APTT were prolonged,Fbg significantly decreased in the high dose subgroups (P＜0.05 or P＜0.01).Conclusion OX26 coupled with EM-HBPG-PLGA nanoparticles showed low cytotoxicity against BMECs and had no significant effect on the coagulation system in rats with low concentration and low dosage.
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Objective To explore the physical/chemical properties and effect of photodynamic therapy (PDT) of iminodiacetic acid modified tetraphenylporphyrin on mice bearing H22 liver cancer.Methods The UV absorbance spectrum,singlet oxygen yield and lipid-water partition coefficient were measured by UV spectrophotometry.Mice bearing H22 liver cancer as animal model were divided into control group (no drug,no light),light treated group (no drug,only light),drug treated group (only drug,no light),experimental once group (with drug and light,once) and experimental twice group (with drug and light,twice,PDT twice).Tumor inhibition rate and index of liver,spleen,lung,thymus of the mice were calculated to evaluate the antitumor activity of iminodiacetic acid modified tetraphenyl porphyrin-PDT.Results The iminodiacetic acid modified tetraphenylporphyrin had absorption at 650 nm,while its singlet oxygen yield and lipid-water partition coefficient were 2.30 and 0.52,respectively.No antitumor effect on mice bearing H22liver cancer for light treated group and drug treated group respectively.However,significant antitumor effect (P＜0.001)was found at experimental group.The maximum tumor inhibition rate could be 95.15％ for PDT twice group.No significant differences were observed on weight gain and liver,lung,spleen,thymus index in each group.Conclusion Iminodiacetic acid modified tetraphenylporphyrin with high singlet oxygen yield,low toxicity and significant in vivo anti-tumor activity,is suitable to be developed as an anti-tumor drug candidate for photodynamic therapy.
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A novel near-infrared (NIR) diffuse correlation spectroscopy (DCS) has recently been developed for noninvasive monitoring of tumor blood flow during photodynamic therapy (PDT).DCS offers several attractive new features for tumor blood flow measurement such as noninvasiveness,portability,low cost,high temporal resolution and relatively large penetration depth.DCS technology has been utilized for continuous measurement of tumor blood flow before,during and after PDT in both animals and humans.The ultimate goal is to predict treatment outcomes from the measured tumor hemodynamic responses to PDT.
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Objective To study the tooth whitening effect of boron-dipyrromethene (BODIPY) as a photosensitive drug combining photodynamic therapy (PDT) and the influence on the surface of the enamel.Methods After oxidation of hydrogen peroxide or BODIPY by photodynamic therapy,the extracted teeth were evaluated by Vita shade guides matching.The change of surface enamel on the crystals and microstructure was observed by scanning electron microscopy (SEM).Results The teeth treated with BODIPY by PDT were smooth and whitened with the remineralization of teeth surface in morphology.While the teeth treated with hydrogen peroxide were whitened obviously but the surface morphology of the teeth was demineralized seriously.Conclusion The results suggest that PDT is effective for teeth whitening and can promote the remineralization of teeth surface enamel with BODIPY as a photosensitive drug.PDT is expected to become a new method for tooth whitening.
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Objective To develop liposome loaded with paclitaxel for the treatment of lung cancer,novel phosphatidyl polyethyleneglycol monomethyl ether liposomes were prepared and studied.Methods A series of phosphatidyl polyethyleneglycol monomethyl ether liposomes were synthesized.Liposomes with or without drug were prepared by ultrasound.The entrapment efficiency and size of drug loaded liposomes were evaluated.The influence of liposomes to A549 lung cancer cell was investigated by MTT method.The cell uptake of liposome was observed by laser confocal scan microscope.Results The liposome loaded with paclitaxel had an entrapment efficiency of 83％ and size of 100～200 nm.The MTT results showed phosphatidyl polyethyleneglycol monomethyl ether liposomes loaded paclitaxel have inhibition effect to A549 cells with long circulation,while liposomes without paclitaxel have not inhibition effect.Conclusion Drug loaded polyethyleneglycol monomethyl ether liposomes have sustained delivery to paclitaxel.They have potential application in the therapy of cancer.
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ObjectiveTo prepare recombinant human basic fibroblast growth factor (rhbFGF) loaded magnesium-poly(D,L-lactide-co-glycolide) (Mg-PLGA) stent and to evaluate its angiogenesis effect in rat model of hindlimb ischemia.MethodsThe stent was prepared with spiral magnesium (Mg) and loaded with therapeutic agent rhbFGF and PLGA matrix.In vitro drug release study was carried out and the effect was evaluated using a standard animal model of rat hindlimb ischemia.A mechanical drill was conducted and the stent was implanted.The concentrations of Mg2+ in the muscle adjacent to the stent,rat plasma,urine and stools of the experimental animals were tested to analyze the degradation and metabolism of metal Mg.Immunohistochemical staining was performed to evaluate the angiogenesis effect of the stent.ResultsThe drug loaded in the stent could release continuously for about 4 weeks.The concentrations of Mg2+ in the rat plasma,urine and stools were within normal range.Immunohistochemical and quantitative analysis showed that the effect of Mg-PLGA-rhbFGF stent on angiogenesis of rat limb ischemia was better than that of the control group.ConclusionRhbFGF loaded MgPLGA stent could promote angiogenesis of rat limb ischemia,and it may provide theoretical basis for the critical patients suffered from lower limb ischemic disease.
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Objective Porphyrin, when conjugated with glucose, will be improved in its water solubility and biocompatibility. Methods In this paper, based on 4- (2, 3, 4, 6-tetra-O-acetyl-β-D-glucosyloxy)benzaldehyde and pyrrole, glucose conjugated porphyrins were synthesized in an optimized process, while porphyrin dimer was synthesized by the Ag-promoted coupling reaction of glycoconjugated porphyrin monomer.Results The compounds were characterized by 1H NMR and MS. Results showed that porphyrin conjugated with two glucose units has slight water solubility, while porphyrin conjugated with three or four glucose units has excellent water solubility. Conclusion Glucoconjugation improves water-solubility of porphyrins, which will enlarge its application in biological fields.