A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researche...A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.展开更多
Liver cancer is one of the most common malignancies,and various pathogenic factors can lead to its occurrence and development.Among all primary liver cancers,hepatocellular carcinoma(HCC)is the most common.With extens...Liver cancer is one of the most common malignancies,and various pathogenic factors can lead to its occurrence and development.Among all primary liver cancers,hepatocellular carcinoma(HCC)is the most common.With extensive studies,an increasing number of molecular mechanisms that promote HCC are being discovered.Surgical resection is still the most effective treatment for patients with early HCC.However,early detection and treatment are difficult for most HCC patients,and the postoperative recurrence rate is high,resulting in poor clinical prognosis of HCC.Although immunotherapy takes longer than conventional chemotherapy to produce therapeutic effects,it persists for longer.In recent years,the emergence of many new immunotherapies,such as immune checkpoint blockade and chimeric antigen receptor T cell therapies,has given new hope for the treatment of HCC.展开更多
Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population wit...Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.展开更多
The goal of this study was to improve the solubility and oral bioavailability of tamibarotene by complexing it with hydroxypropyl-β-cyclodextrin(HP-β-CD).The inclusion complex of tamibarotene with hydroxypropyl-β-c...The goal of this study was to improve the solubility and oral bioavailability of tamibarotene by complexing it with hydroxypropyl-β-cyclodextrin(HP-β-CD).The inclusion complex of tamibarotene with hydroxypropyl-β-cyclodextrin(Am80-HP-β-CD)was prepared through a freeze-drying method at the mole ratio of 1:1(Am80:HP-β-CD).Fourier transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC)indicated the formation of Am80-HP-β-CD.In vitro dissolution studies showed that the solubility and dissolution percentage of Am80-HP-β-CD was improved substantially compared to Am80.An improved dissolution with approximately 97%drug release in 3 min was observed,in comparison with Am80 with approximately 60% release in 45 min.In vivo studies indicated that the AUC0-∞ has increased 2.79 times and the Cmax 4.37 times after the formation of inclusion complex.The decrease of tmaxindicated the Am80-HP-β-CD inclusion complex can be absorbed into blood faster.In short,the solubility and bio-availability of Am80 has notably increased with the complexation of HP-β-CD.Therefore,using the inclusion technique is a promising method to improve the solubility of insoluble drugs.展开更多
A simple, sensitive and accurate method based on high performance liquid chromato- graphy (HPLC) with diode array detector (DAD) was developed and validated for systematic quality evaluation of one type of traditi...A simple, sensitive and accurate method based on high performance liquid chromato- graphy (HPLC) with diode array detector (DAD) was developed and validated for systematic quality evaluation of one type of traditional Chinese medicine preparations named Xinkeshu (XKS) tablet. In this study, the chromatographic fingerprints of XKS tablet were developed first, 23 peaks were selected as the common peaks to evaluate the similarities among different batches of XKS samples, which were manufactured in a long time span of three years. Additionally, simultaneous quantification of six markers in XKS tablet, including Danshensu, Protocatechuic aldehyde, Puerarin, Daidzin, Salvianolic acid B and Daidzein, was performed. The validation results showed that the developed method was specific, accurate, precise and robust. The preliminary explanation on why a close similarity between fingerprints did not exactly mean similar contents of chemical components in samples was given. The contribution of each chromatographic peak to similarity was also evaluated. The developed method offers an efficient, reliable and practical approach for systematic quality evaluation of XKS tablet.展开更多
Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit an...Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.展开更多
pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments ...pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.展开更多
Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which wa...Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.展开更多
A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susc...A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.展开更多
Vascular endothelial growth factor receptor 2(VEGFR-2)and neuropilin-1(NRP-1)are two prominent antiangiogenic targets.They are highly expressed on vascular endothelial cells and some tumor cells.Therefore,targeting VE...Vascular endothelial growth factor receptor 2(VEGFR-2)and neuropilin-1(NRP-1)are two prominent antiangiogenic targets.They are highly expressed on vascular endothelial cells and some tumor cells.Therefore,targeting VEGFR-2 and NRP-1 may be a potential antiangiogenic and antitumor strategy.A7R,a peptide with sequence of Ala-Thr-Trp-Leu-Pro-Pro-Arg that was found by phage display of peptide libraries,can preferentially target VEGFR-2 and NRP-1 and destroy the binding between vascular endothelial growth factor 165(VEGF165)and VEGFR-2 or NRP-1.This peptide is a new potent inhibitor of tumor angiogenesis and a targeting ligand for cancer therapy.This review describes the discovery,function and mechanism of the action of A7R,and further introduces the applications of A7R in antitumor angiogenic treatments,tumor angiogenesis imaging and targeted drug delivery systems.In this review,strategies to deliver different drugs by A7R-modified liposomes and nanoparticles are highlighted.A7R,a new dual targeting ligand of VEGFR-2 and NRP-1,is expected to have efficient therapeutic or targeting roles in tumor drug delivery.展开更多
AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o -toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured b...AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o -toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally welltolerated by mice with less than 20% reduction in body weight. CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.展开更多
Introduction The formation of gelatin-containing mieroemulsionbased gels(MBGs) was first described in 1986 and the physical/structural characterization was carried out by a number of groups with a variety of techni...Introduction The formation of gelatin-containing mieroemulsionbased gels(MBGs) was first described in 1986 and the physical/structural characterization was carried out by a number of groups with a variety of techniques including tracer diffusion, electrical conductivity, NMR, X-ray and small angle neutron scattering. The MBGs were proposed to comprise an extensive, rigid, interconnected network of gelatin/water rods stabilized by a monolayer of surfactant, in coexistence with a po- pulation of conventional W/O microemulsion droplets.展开更多
Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase(IN) inhibitor approved by the United States Food and Drug Administration(US FDA), were designed, synth...Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase(IN) inhibitor approved by the United States Food and Drug Administration(US FDA), were designed, synthesized and characterized by ^1H NMR, IR and MS. The biological activities of these compounds against HIV-1 IN in vitro were evaluated. The assay results indicate that the replacement of pyrimidinone with furanone decreased the inhibitory activity of the compounds to HIV-1 IN. Compounds 3i, 3j and 3t show moderate inhibitory activity against HIV-1 IN and selectively inhibit the strand transfer reaction.展开更多
The title compound [2-(2,6-dioxacyclohexyl)-5-methoxylphenols]2 was synthesized by the reaction of 2-hydroxyl-3-methoxylbenzaldehyde and 1,3-propanediol in the presence of DMF-DMS adduct and characterized by IR spec...The title compound [2-(2,6-dioxacyclohexyl)-5-methoxylphenols]2 was synthesized by the reaction of 2-hydroxyl-3-methoxylbenzaldehyde and 1,3-propanediol in the presence of DMF-DMS adduct and characterized by IR spectrum, UV-Vis spectrum and X-ray crystallography. The title compound belongs to monoclinic, space group P21 with a = 9.8967(10), b = 8.2240(9), c = 13.3654(14) A^°, β= 90.016(2)°, C11H14O4, Mr = 210.22, V = 1087.8(2)A^°3, Z = 4, Dc = 1.284 Mg/m^3, F(000) = 448,μ = 0.098 mm^-1, the final R = 0.0300 and wR = 0.0761 for 2070 observed reflections with I 〉 2σ(I). The molecules are connected via intermolecular O-H…O hydrogen bonds into a 2D network structure. Moreover, theoretical investigations of the title compound with HF/6-31G(d) method were performed, and its stability, frontier molecular orbital composition and Mulliken charge distribution were also discussed. The compound is a bis-molecule. The two molecules stay together and could not be separated. Two crystallographically independent molecules exist in an asymmetric unit. The bond lengths and bond angles of the two molecules are slightly different with each other.展开更多
[Objectives] To study the anti-inflammatory activity and mechanism of tanshinone I,cryptotanshinone and 15,16-dihydrotanshinone I on HAECs induced by TNF-α. [Methods]Vitamin E was used as a positive control and TNF-...[Objectives] To study the anti-inflammatory activity and mechanism of tanshinone I,cryptotanshinone and 15,16-dihydrotanshinone I on HAECs induced by TNF-α. [Methods]Vitamin E was used as a positive control and TNF-α-induced human aortic endothelial cells( HAECs) were selected as the inflammation model cells. The m RNA levels of IL-6,ICAM-1,VCAM-1,and NF-κB were analyzed by quantitative RT-PCR. The protein expression of NF-κB,ICAM-1,VCAM-1 and phosphorylation of ERK1/2 were determined by Western blot. The adhesion of U937 to HAECs was assessed by BCECF/AM labeling assay. [Results] TNF-α-induced over-expression of IL-6,NF-κB,ICAM-1,and VCAM-1 in HAECs were down-regulated by tanshinone I( TAN),cryptotanshinone( CPT) and 15,16-dihydrotanshinone I( DHT) both in m RNA and protein levels,respectively. Meanwhile 15,16-dihydrotanshinone I and cryptotanshinone could inhibit phosphorylation of ERK1/2 and tanshinone I inhibited U937 adhesion to HAECs significantly. [Conclusions] Tanshinones could inhibit TNF-α induced inflammatory responses on HAECs and the mechanism might be related to inhibition of phosphorylation of ERK1/2 and blocking NF-κB signaling pathway.展开更多
Objective:To study the preventive effect of Timosaponin BII(T-BII)-loaded temperature/ion-sensitive nasal in situ hydrogels(ISGs)on Alzheimer's disease(AD),its preparation technology,characteristics and in vivo ef...Objective:To study the preventive effect of Timosaponin BII(T-BII)-loaded temperature/ion-sensitive nasal in situ hydrogels(ISGs)on Alzheimer's disease(AD),its preparation technology,characteristics and in vivo effects were evaluated.Methods:The morphological and rheological properties were evaluated.The preventive effects of T-BII ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1(M1)expression and pathological changes.Results:Results revealed that T-BII ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1(CA1)area.Conclusion:T-BII ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine.This,thereby,lays forth a new treatment option for preventing AD.展开更多
Xiaojiang Hao,who obtained Master Degree from Kunming Institute of Botany(KIB),Chinese Academy of Sciences(CAS)in 1985,and Doctor in Pharmacy degree in Pharmacy from Institute for Chemical Research,Kyoto University,in...Xiaojiang Hao,who obtained Master Degree from Kunming Institute of Botany(KIB),Chinese Academy of Sciences(CAS)in 1985,and Doctor in Pharmacy degree in Pharmacy from Institute for Chemical Research,Kyoto University,in 1990,was born in Chongqing in July,1951.In 1991,he returned to KIB,CAS,as an Associate professor and served as the chair of the Department of Phytochemistry.In 1994,he was promoted to a full professor at the current institute.He served as the Deputy Director of KIB and the Director of Open Laboratory of Phytochemistry from 1995 to 1997,and the Director of KIB from 1997 to 2005.Professor Hao has published more than 450 peer-reviewed SCI papers,which have been cited over 6000 times.He has obtained one PCT patent and 23 patents in China.Due to his tremendous efforts,one candidate drug,phenchlobenpyrrone,has entered the Phase II clinical trail for the treatment of Alzheimer’s disease.Moreover,he won the First Prize of Natural Sciences in Yunnan Province for three times,and Ho Leung Ho Lee Fund Science and Technology Innovation Award in 2017.展开更多
BACKGROUND: Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE: To investigate the effect of low molecular weight heparin-supe...BACKGROUND: Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE: To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 (IL-6) overexpressing mice following local cerebral ischemia. DESIGN, TIME AND SETTING: Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005. MATERIALS: Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups: sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University. METHODS: Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment. MAIN OUTCOME MEASURES: The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy (x200). RESULTS: In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker. CONCLUSION: The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.展开更多
Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted muc...Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.展开更多
基金supported by the Natural Science Foundation of Beijing,No.L222126(to LD)。
文摘A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
基金Supported by the Natural Science Foundation of China,No.81172789,30972692 and 81373222National Basic Research Program of China 973 Program,No.2013CB531503National Mega Project on Major Infectious Diseases Prevention and Treatment,No.2012ZX10002006
文摘Liver cancer is one of the most common malignancies,and various pathogenic factors can lead to its occurrence and development.Among all primary liver cancers,hepatocellular carcinoma(HCC)is the most common.With extensive studies,an increasing number of molecular mechanisms that promote HCC are being discovered.Surgical resection is still the most effective treatment for patients with early HCC.However,early detection and treatment are difficult for most HCC patients,and the postoperative recurrence rate is high,resulting in poor clinical prognosis of HCC.Although immunotherapy takes longer than conventional chemotherapy to produce therapeutic effects,it persists for longer.In recent years,the emergence of many new immunotherapies,such as immune checkpoint blockade and chimeric antigen receptor T cell therapies,has given new hope for the treatment of HCC.
基金the National Key Development Plan for Precision Medicine Research(2017YFC0910004)Jinan Science Project(201602171),and Jinan Science and Technology Plan Project(201503009).
文摘Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.
文摘The goal of this study was to improve the solubility and oral bioavailability of tamibarotene by complexing it with hydroxypropyl-β-cyclodextrin(HP-β-CD).The inclusion complex of tamibarotene with hydroxypropyl-β-cyclodextrin(Am80-HP-β-CD)was prepared through a freeze-drying method at the mole ratio of 1:1(Am80:HP-β-CD).Fourier transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC)indicated the formation of Am80-HP-β-CD.In vitro dissolution studies showed that the solubility and dissolution percentage of Am80-HP-β-CD was improved substantially compared to Am80.An improved dissolution with approximately 97%drug release in 3 min was observed,in comparison with Am80 with approximately 60% release in 45 min.In vivo studies indicated that the AUC0-∞ has increased 2.79 times and the Cmax 4.37 times after the formation of inclusion complex.The decrease of tmaxindicated the Am80-HP-β-CD inclusion complex can be absorbed into blood faster.In short,the solubility and bio-availability of Am80 has notably increased with the complexation of HP-β-CD.Therefore,using the inclusion technique is a promising method to improve the solubility of insoluble drugs.
基金supported by the Major Projects of Independent Innovation Achievements of Shandong Province(No. 2010ZDZX1A0406)partly by the Scientific and Technological Projects of Shandong Province (No. 2009GG10002081)+1 种基金Independent Innovation Foundation of Shandong University(No. 2010TS054)Shandong Province Natural Science Foundation, China (No. ZR2011HM080)
文摘A simple, sensitive and accurate method based on high performance liquid chromato- graphy (HPLC) with diode array detector (DAD) was developed and validated for systematic quality evaluation of one type of traditional Chinese medicine preparations named Xinkeshu (XKS) tablet. In this study, the chromatographic fingerprints of XKS tablet were developed first, 23 peaks were selected as the common peaks to evaluate the similarities among different batches of XKS samples, which were manufactured in a long time span of three years. Additionally, simultaneous quantification of six markers in XKS tablet, including Danshensu, Protocatechuic aldehyde, Puerarin, Daidzin, Salvianolic acid B and Daidzein, was performed. The validation results showed that the developed method was specific, accurate, precise and robust. The preliminary explanation on why a close similarity between fingerprints did not exactly mean similar contents of chemical components in samples was given. The contribution of each chromatographic peak to similarity was also evaluated. The developed method offers an efficient, reliable and practical approach for systematic quality evaluation of XKS tablet.
基金Supported by National Science Foundation for Young Scientists of China, No.82001687National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases, No.2018ZX10301401+2 种基金National Postdoctoral Program for Innovative Talents, No.BX20190192China Postdoctoral Science Foundation, No.2020M672064National Basic Research Program of China, No.2013CB531503
文摘Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.
文摘pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.
文摘Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.
基金supported by Major R&D Program of New Drugs-National S&T Key Special Subject of China (No.2009ZX09103-115)National Natural Science Foundation of China(No.20872081)Natural Science Foundation of Shandong(No.Y2006C31)
文摘A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.
基金funded by National Natural Science Foundation of China(No.81302686)Primary Research&Developement Plan of Shandong Province(No.2016GSF201083)
文摘Vascular endothelial growth factor receptor 2(VEGFR-2)and neuropilin-1(NRP-1)are two prominent antiangiogenic targets.They are highly expressed on vascular endothelial cells and some tumor cells.Therefore,targeting VEGFR-2 and NRP-1 may be a potential antiangiogenic and antitumor strategy.A7R,a peptide with sequence of Ala-Thr-Trp-Leu-Pro-Pro-Arg that was found by phage display of peptide libraries,can preferentially target VEGFR-2 and NRP-1 and destroy the binding between vascular endothelial growth factor 165(VEGF165)and VEGFR-2 or NRP-1.This peptide is a new potent inhibitor of tumor angiogenesis and a targeting ligand for cancer therapy.This review describes the discovery,function and mechanism of the action of A7R,and further introduces the applications of A7R in antitumor angiogenic treatments,tumor angiogenesis imaging and targeted drug delivery systems.In this review,strategies to deliver different drugs by A7R-modified liposomes and nanoparticles are highlighted.A7R,a new dual targeting ligand of VEGFR-2 and NRP-1,is expected to have efficient therapeutic or targeting roles in tumor drug delivery.
基金Supported by National Natural Science Foundation of China, No.30472038 Department of Science and Technology of Shandong Province, China and Japan-China Medical Association
文摘AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o -toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally welltolerated by mice with less than 20% reduction in body weight. CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.
基金Supported by the Natural Science Foundation of Shandong Province in China(No.Y2003B01).
文摘Introduction The formation of gelatin-containing mieroemulsionbased gels(MBGs) was first described in 1986 and the physical/structural characterization was carried out by a number of groups with a variety of techniques including tracer diffusion, electrical conductivity, NMR, X-ray and small angle neutron scattering. The MBGs were proposed to comprise an extensive, rigid, interconnected network of gelatin/water rods stabilized by a monolayer of surfactant, in coexistence with a po- pulation of conventional W/O microemulsion droplets.
基金Supported by the National Natural Science Foundation of China(No.20872082)the Natural Science Foundation of Shandong Province,China(No.Y2007C060)
文摘Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase(IN) inhibitor approved by the United States Food and Drug Administration(US FDA), were designed, synthesized and characterized by ^1H NMR, IR and MS. The biological activities of these compounds against HIV-1 IN in vitro were evaluated. The assay results indicate that the replacement of pyrimidinone with furanone decreased the inhibitory activity of the compounds to HIV-1 IN. Compounds 3i, 3j and 3t show moderate inhibitory activity against HIV-1 IN and selectively inhibit the strand transfer reaction.
基金Supported by the Postgraduate Foundation of Taishan University (No. Y07-2-16)
文摘The title compound [2-(2,6-dioxacyclohexyl)-5-methoxylphenols]2 was synthesized by the reaction of 2-hydroxyl-3-methoxylbenzaldehyde and 1,3-propanediol in the presence of DMF-DMS adduct and characterized by IR spectrum, UV-Vis spectrum and X-ray crystallography. The title compound belongs to monoclinic, space group P21 with a = 9.8967(10), b = 8.2240(9), c = 13.3654(14) A^°, β= 90.016(2)°, C11H14O4, Mr = 210.22, V = 1087.8(2)A^°3, Z = 4, Dc = 1.284 Mg/m^3, F(000) = 448,μ = 0.098 mm^-1, the final R = 0.0300 and wR = 0.0761 for 2070 observed reflections with I 〉 2σ(I). The molecules are connected via intermolecular O-H…O hydrogen bonds into a 2D network structure. Moreover, theoretical investigations of the title compound with HF/6-31G(d) method were performed, and its stability, frontier molecular orbital composition and Mulliken charge distribution were also discussed. The compound is a bis-molecule. The two molecules stay together and could not be separated. Two crystallographically independent molecules exist in an asymmetric unit. The bond lengths and bond angles of the two molecules are slightly different with each other.
基金Supported by the National Natural Science Foundation of China(81274031)
文摘[Objectives] To study the anti-inflammatory activity and mechanism of tanshinone I,cryptotanshinone and 15,16-dihydrotanshinone I on HAECs induced by TNF-α. [Methods]Vitamin E was used as a positive control and TNF-α-induced human aortic endothelial cells( HAECs) were selected as the inflammation model cells. The m RNA levels of IL-6,ICAM-1,VCAM-1,and NF-κB were analyzed by quantitative RT-PCR. The protein expression of NF-κB,ICAM-1,VCAM-1 and phosphorylation of ERK1/2 were determined by Western blot. The adhesion of U937 to HAECs was assessed by BCECF/AM labeling assay. [Results] TNF-α-induced over-expression of IL-6,NF-κB,ICAM-1,and VCAM-1 in HAECs were down-regulated by tanshinone I( TAN),cryptotanshinone( CPT) and 15,16-dihydrotanshinone I( DHT) both in m RNA and protein levels,respectively. Meanwhile 15,16-dihydrotanshinone I and cryptotanshinone could inhibit phosphorylation of ERK1/2 and tanshinone I inhibited U937 adhesion to HAECs significantly. [Conclusions] Tanshinones could inhibit TNF-α induced inflammatory responses on HAECs and the mechanism might be related to inhibition of phosphorylation of ERK1/2 and blocking NF-κB signaling pathway.
基金This study was funded by the Beijing Natural Science Foundation(7202147).
文摘Objective:To study the preventive effect of Timosaponin BII(T-BII)-loaded temperature/ion-sensitive nasal in situ hydrogels(ISGs)on Alzheimer's disease(AD),its preparation technology,characteristics and in vivo effects were evaluated.Methods:The morphological and rheological properties were evaluated.The preventive effects of T-BII ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1(M1)expression and pathological changes.Results:Results revealed that T-BII ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1(CA1)area.Conclusion:T-BII ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine.This,thereby,lays forth a new treatment option for preventing AD.
文摘Xiaojiang Hao,who obtained Master Degree from Kunming Institute of Botany(KIB),Chinese Academy of Sciences(CAS)in 1985,and Doctor in Pharmacy degree in Pharmacy from Institute for Chemical Research,Kyoto University,in 1990,was born in Chongqing in July,1951.In 1991,he returned to KIB,CAS,as an Associate professor and served as the chair of the Department of Phytochemistry.In 1994,he was promoted to a full professor at the current institute.He served as the Deputy Director of KIB and the Director of Open Laboratory of Phytochemistry from 1995 to 1997,and the Director of KIB from 1997 to 2005.Professor Hao has published more than 450 peer-reviewed SCI papers,which have been cited over 6000 times.He has obtained one PCT patent and 23 patents in China.Due to his tremendous efforts,one candidate drug,phenchlobenpyrrone,has entered the Phase II clinical trail for the treatment of Alzheimer’s disease.Moreover,he won the First Prize of Natural Sciences in Yunnan Province for three times,and Ho Leung Ho Lee Fund Science and Technology Innovation Award in 2017.
文摘BACKGROUND: Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE: To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 (IL-6) overexpressing mice following local cerebral ischemia. DESIGN, TIME AND SETTING: Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005. MATERIALS: Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups: sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University. METHODS: Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment. MAIN OUTCOME MEASURES: The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy (x200). RESULTS: In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker. CONCLUSION: The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.
基金Key Research Base of Philosophy and Social Sciences in Shaanxi Province,Shaanxi Health Culture Research Center Projects(Grand JKWH2019-Q19).
文摘Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.