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Polymer nanomaterials have been attracted more and more attention because of their advantages such as long circulation, reduced immunogenicity and less side effects, and have become a hot research topic in nanomaterials. However, the number of polymer nanomedicines successfully applied in clinical application is very limited, and the unsatisfactory pharmacokinetic behavior is one of the main reasons for thisresult. After polymer nanoparticles enter the body, they will release free drugs and polymer excipients. Polymer nanoparticles are the loaded drugs and free drugs are the active chemicals for efficacy, while polymer excipients may cause excipient drug interactions. Therefore, the focus of the pharmacokinetics study of polymer nanoparticles should not be only limited to the free drugs themselves, but should also focus on the loaded drugs, free drugs and polymer excipients. The dynamic changes of polymer excipients and their metabolites pose new requirements and challenges for the bioanalysis of polymer nanomedicines. The characteristics and application scope of common analytical methods for detection polymer nanomedicines including chromatographic assay will be discussed in this paper. Moreover, this review will also summarize the absorption, distribution, metabolism and excretion of polymer nanomedicines. We hope this review will provide reference for the pharmacokinetics study, safety and effectiveness evaluation of polymer nanomedicines.
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Liposome nanomedicine is a new drug preparation with nano scale, which is encapsulated by lipid bilayer vesicle structure. As a drug delivery carrier, liposome has many advantages such as good biocompatibility, biodegradation in vivo and strong targeting. The application of liposome nano drug delivery system can improve the pharmacokinetic behavior and efficacy of some drugs in vivo to a certain extent, and reduce toxic and side effects. After liposome nanomedicine enter into the body, free drugs will be released, so there will be loaded drugs and free drugs in the body. Loaded drugs are drug repositories, free drugs are related to their efficacy and adverse reactions. Therefore, the pharmacokinetics study of liposomes should focus on both loaded drugs and free drugs. Quantitative analysis of free drugs, liposome particles and their materials is a big challenge. The bioanalysis and pharmacokinetics of liposome nanomedicines will be introduced and discussed in this review. We hope this review will provide a reference for the development of liposome nanomedicine.
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@#Abstract: To report on two patients with Coronavirus Disease 2019 (COVID-19) combined with diffuse connective tissue disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection followed for nearly 3 years, in order to understand the long-term effects on the patients' immune system. Both patients were male, aged 81-82 years, and were hospitalized with fever on January 29, 2020 and February 10, 2020, respectively. Both were diagnosed with COVID-19 after positive SARS-CoV-2 polymerase chain reaction (PCR) tests. After receiving anti-infection treatment, cough suppressants, ex‐pectorants, and symptomatic supportive treatment, their body temperature returned to normal and two consecutive PCR tests were negative for SARS-CoV-2, and they were discharged from hospital. However, due to recurring fevers and varying degrees of rheumatic disease-related symptoms, both patients were readmitted to the hospital, indicating the presence of positive auto‐ antibodies and organ involvement. One patient recovered from COVID-19 with recurrent fever, joint pain, muscle aches and subcutaneous nodules, and was subsequently diagnosed with undifferentiated connective tissue disease. The other patient developed recurrent fever, mouth ulcers and rash after recovery from COVID-19 and was subsequently diagnosed with anti neutro phil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The patient was treated with glucocorticoids and immunosuppres sive drugs and the symptoms resolved rapidly and subsequent laboratory and imaging examinations showed stable condition. However, due to self-termination of medication, their symptoms quickly relapsed, and further treatment with glucocorticoids and immunosuppressive agents resulted in sustained stability of their condition. The erythrocyte sedimentation rate and hyper‐sensitive C-reactive protein remained within normal limits, and lung CT scans showed stable lesions with partial absorption.SARS-CoV-2 infection may have long-term effects on patients' immune systems, leading to abnormal immune responses and diffuse connective tissue disease. This suggests that regular follow-up observation of immune system-related diseases may be necessary for elderly patients with COVID-19.
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@#Abstract: Objective To analyze the pathogenic characteristics and epidemiological significance of human plague related strains in Qinghai Province in recent 30 years, so as to provide scientific basis for on-the-spot disposal and prevention and control measures of plague outbreak in Qinghai Province. Methods A total of 35 strains of Yersinia pestis isolated from 29 typical human plague outbreaks in Qinghai Province from 1980 to 2011 were selected and studied by biochemical fermentation experiments. Virulence factors detection of Fraction 1 antigen (Fra1), virulence antigen (VW), pigmentation (Pgm) and Yersinia pestis Ⅰ (PstⅠ), determinants and genotyping of differential regions (DFRs) were used to study the pathogenic characteristics. At the same time, according to the epidemic situation of human and animal plague in Qinghai Province in recent years, the current situation of plague prevention and control and epidemic characteristics were analyzed. Results The biotypes of 35 strains of Yersinia pestis were classical, and the biotypes of 29 strains (82.86%) were of Qinghai-Tibet Plateau type, mainly distributed in southern Qinghai and around lake areas, 2 strains (5.71%) belonged to Qilian Mountains type, mainly distributed in Qilian mountains, and 6 genotypes were identified by DFR. Among them, 16 were type 5, 12 were type 8, 2 were type 10, 1 was type 36, 3 were type 30 and 1 was type 1b, the strains of type 5 and 1b were mainly distributed around the lake and the southern foot of Qilian Mountains, while the strains of type 8, 10, 36 and 30 were mainly distributed in the southern part of Qinghai. Conclusions The pathogen of Yersinia pestis in Qinghai Plateau has complex biochemical types, the epidemic situation among animals is continuous year after year, the situation of prevention and control is serious, the occurrence and prevalence of plague seriously endanger people's health and social development, so it is necessary to do a solid job in the prevention and control of plague to ensure the safety of people's lives.
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@#Stress in medical education has been inevitable among medical students. However, the prevalence of stress among pre-clinical and clinical medical students differed by year of study. There were several stressors reported to affect medical students. Therefore, effective coping strategies were applied to manage the stress faced by medical students. The aim of this study was to determine the prevalence of stress, stressors and coping strategies comparing pre-clinical and clinical Universiti Tunku Abdul Rahman (UTAR) medical students, and the associated stressors and stress among them. This was a cross-sectional study with a study population of 223 medical students. Universal sampling was used. A self-administered questionnaire which included socio-demographic characteristics, the General Health Questionnaire (GHQ-12), the Medical Students Stressor Questionnaire (MSSQ) and the Brief COPE Inventory were used in this study. The overall prevalence of stress among medical students was 48.15%. Clinical students had a higher prevalence of stress (53.73%) compared to pre-clinical students (39.02%). Year 3 students had the highest prevalence of stress (64.58%) compared to other years of study. Nearly 1 out of 2 medical students were stressed (48.15%). Academic Related Stressor ranked the highest and Acceptance was the most practiced coping strategy. The only associated stressor with stress was Academic Related Stressor.
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[Objective]To investigate the effect of pantoprazole on skeletal muscle wasting in cancer cachexia and the possible mechanism.[Methods]24 male BALB/c mice were randomly divided into control group(NN),cancer cachexia group(CC),pantrop?razole treatment group(PPI). The mice in CC and PPI were inoculated subcutaneously with mouse colon adenocarcinoma C26 cells to establish a model of cancer cachexia. The mice in PPI group were gavaged with 75 mg/kg pantoprazole dissolving in physiological saline,while those in NN and CC group were gavaged with 0.1 mL/10 g physiological saline. The mice were killed 12d after treatment. The weight of gastrocnemius and tumour and the size of tumour were measured. The morphological change of skeletal muscle were evalu?ated by the method of stain with hematoxylin and eosin(H&E). The levels of IL-6 and TNF-αin serum were tested by ELISA. qRT-PCR was used to assess the expression of mRNA of Myod1 and myf5 in skeletal muscle. The protein expressions of MuRF1,MAFBx, Myod1 and myf5 were measured by Western blot.[Results]Compared with CC group ,pantoprazole can increase the weight of mice and gastrocnemius(39.8% and 24.2%,respectively),cross section area(25.4%),levels of mRNA and protein of Myod1 and myf5(P<0.05),while the levels of IL-6 and TNF-αdecreased(30.7%and 18.9%,respectively),as well as the levels of protein ex?pression of MuRF1 and MAFBx(P < 0.05).[Conclusion]Pantoprazole can attenuate the wasting of skeletal muscle,the potential mechanism may be related to the inhibition of inflammatory factors and UPS ,and up-regulation of Myod1 and myf5.
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Objective To screen the 5 EV71 vaccine candidates which were isolated from MRC-5 cells to find one as the vaccine virus. Methods The ICR mother mouse were immunized by intraperitoneal injection with the 5 vaccine candidates which were made from monoclonal EV71 virus. Two weeks after booster immunization, the animals were allowed to mate, another booster was given after 2 weeks, and then attracted the milk mouse within 24 h with different types of virus by cranial cavity injection. The survival condition were recorded everyday, and the antibody titre(IgG) were detected by ELISA, the virus titre of intestine were detected by nest-PCR, and neutralizing antibodies were determined using a microassay with MRC-5 cells, and then the data were analyzed by SPSS16.0. Results The antibody titre of 5 virus immunized ICR mouse were improved with the increase in the immune times, and they got difference in neutralization capacity, the survival rate after fatal attract and the virus titre of the intestine. Conclusion It proved that the five vaccine candidates were different at the molecular level, cellular level and individual level. 123 strain was the best one in immunogenicity and immunoprotective property, which agreed with the vaccine requirement.
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<p><b>OBJECTIVE</b>To compare therapeutic effects of needle-knife therapy and acupuncture on cervical spondylosis.</p><p><b>METHODS</b>Multi-central clinical randomized controlled trial was adopted. The patients were divided into a needle-knife treatment group treated with needle-knife therapy at the upper and lower interspinal ligaments of the affected vertebral body and bilateral posterior joint capsules; and the acupuncture control group were treated with acupuncture at Laozhen, Ashi points and cervical Jiaji points, etc. The short-term and the long-term therapeutic effects were observed at the end of the therapeutic course and 6 months after the end of the therapeutic course.</p><p><b>RESULTS</b>The short-term therapeutic effect and the long-term therapeutic effect were 91.3% and 94.7% in the needle-knife treatment group and 59.4% and 56.6% in the acupuncture control group, respectively, with a very significant difference between the two groups (P < 0.01).</p><p><b>CONCLUSION</b>The needle-knife treatment in the therapeutic effect on cervical spondylosis is superior to acupuncture treatment.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acupuncture Therapy , Cervical Vertebrae , Spinal Osteophytosis , General Surgery , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To study the mechanisms of oridonin-induced U937 cell apoptosis, and to examine the role of ERK MAPK.</p><p><b>METHOD</b>MTT, Hoechst 33258 staining, DNA agarose gel electrophoresis and Western blot analysis were used.</p><p><b>RESULT</b>Oridonin inhibited U937 cell growth in a time- and dose-dependent manner. Apoptotic bodies were found with Hoechst 33258 staining after treatment with 27 micromol x L(-1) oridonin. Simultaneously, ERK phosphorylation was significant. ERK inhibitor PD98059 partially blocked the growth-inhibitory effect as well as DNA fragmentation. The expression of antiapoptotic mitochondrial protein Bcl-XL decreased time-dependently, and that of proapoptotic protein Bax increased. However, PD98059 reversed the effect of oridonin on Bcl-XL and Bax.</p><p><b>CONCLUSION</b>Oridonin induces U937 cell apoptosis through activation of ERK and alteration of the ratio of Bax/Bcl-XL.</p>
Subject(s)
Humans , Apoptosis , Cell Proliferation , DNA Fragmentation , Diterpenes , Pharmacology , Diterpenes, Kaurane , Pharmacology , Dose-Response Relationship, Drug , Extracellular Signal-Regulated MAP Kinases , Metabolism , Flavonoids , Pharmacology , Isodon , Chemistry , Phosphorylation , Plants, Medicinal , Chemistry , U937 Cells , bcl-2-Associated X Protein , Metabolism , bcl-X Protein , MetabolismABSTRACT
Aeromonas hydrophila CGMCC 0911 possessing type I polyhydroxyalkanoate (PHA) synthase gene (phaC) only accumulate copolyesters consisting of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx), abbreviated as PHBHHx, from lauric acid as sole carbon source but not from glucose. The gene encoding type I PHA synthase was interrupted by insertion of a chloramphenicol resistance gene (Cm). Conjugation of suicide plasmid pFH10 transformed A. hydrophila CGMCC 0911 into a recombinant organism with the disrupted type I PHA synthase gene (phaC:: Cm) , through an in vivo homologous recombination process, type I phaC of A. hydrophila genome was replaced by the disrupted phaC, and Cm gene was integrated into the genome of A. hydrophila, resulting in type I phaC-negative mutant, which was proved by DNA sequencing. Results of GC analysis showed that this mutant could not accumulate PHBHHx again but accumulate medium-chain-length (mcl) PHA from lauric acid or glucose as carbon source, clearly indicating the existence of another type I PHA synthase in the wild type A. hydrophila. It will play its function and accumulate mcl PHA only when type I PHA synthase was inactivated. into the genome of A. hydrophila, resulting in type I phaC-negative mutant, which was proved by DNA sequencing. Results of GC analysis showed that this mutant could not accumulate PHBHHx again but accumulate medium-chain-length (mcl) PHA from lauric acid or glucose as carbon source, clearly indicating the existence of another type II PHA synthase in the wild type A. hydrophila. It will play its function and accumulate mcl PHA only when type I PHA synthase was inactivated.
Subject(s)
Acyltransferases , Genetics , Metabolism , Aeromonas , Genetics , Bacterial Proteins , Genetics , Metabolism , Genes, Transgenic, Suicide , Genetics , Mutation , Polyhydroxyalkanoates , GeneticsABSTRACT
Metabolic engineering provide powerful tools for the systematic manipulation of cellular metabolic activities. The ptsG gene for glucose-specific transporter Enzyme II CBGlc of the phosphotransferase system was knock-out so as to reduce the accumulation of acetic acid in the high cell-density culture of Escherichia coli on excess glucose. The chloramphenicol-resistant cassette with short shared sequences on both ends generated by PCR was electroporated into Escherichia coli DH5alpha and JM109. Recombination between linear DNA cassettes and Escherichia coli chromosomes took place by Red recombinase functions. Therefore, the ptsG gene was disrupted to construct the mutants called DH5alphaP and JM109P. There was no difference between the mutants and parent strains in LB media.However, in LB media supplemented with glucose, the mutants of Escherichia coli deficient in ptsG showed greater biomass, together with exploiting more glucose. The maximal cell density obtained with DH5alphaP was approximately 3 times more than that of DH5alpha, then the result of JM109P increased fourfold. The products of recombinant protein TNF respectively accounted for 24.3% of total cellular protein in DH5alphaP with A600 8.28 and 20.8% of total cellular protein in JM109P with A600 7.62. The specific volume expression amount of TNF was greater in the ptsG mutant than in its parent strain. These results demonstrate that the ptsG-mutant strains will be available for high cell-density culture.
Subject(s)
Culture Media , Escherichia coli , Genetics , Fermentation , Mutation , Phosphoenolpyruvate Sugar Phosphotransferase System , Genetics , Polymerase Chain Reaction , Recombinant Proteins , Tumor Necrosis Factor-alphaABSTRACT
A recombinant immunotoxin named CEA/PE38/KDEL was constructed, which was composed of anti-CEA single-chain Fv and the truncated and modified form of Pseudomonas exotoxin (PE38/KDEL). The CEA/PE38/KDEL immunotoxin was expressed in the E. coli strain BL21 (DE3)-star as inclusion bodies. The denatured inclusion bodies were purified with Ni-NTA chelate agarose, then the constant gradient dialysis was used to perform the refolding of the CEA/PE38/KDEL immunotoxin. Results of FACS and MTT assay indicate that the refolded immunotoxins keep potent and specific cytotoxicity to tumor cells bearing CEA antigens.
Subject(s)
Humans , ADP Ribose Transferases , Genetics , Pharmacology , Antibodies , Genetics , Metabolism , Pharmacology , Antineoplastic Agents , Metabolism , Pharmacology , Bacterial Toxins , Genetics , Pharmacology , Carcinoembryonic Antigen , Allergy and Immunology , Cloning, Molecular , Escherichia coli , Genetics , Metabolism , Exotoxins , Genetics , Pharmacology , Immunoglobulin Fragments , Genetics , Immunotoxins , Genetics , Metabolism , Pharmacology , Protein Renaturation , Recombinant Fusion Proteins , Genetics , Pharmacology , Virulence Factors , Genetics , PharmacologyABSTRACT
AIM: To study the effect of oridonin on the phagocytosis of apoptotic U937 cells by macrophage-like cells. METHODS: DNA agarose gel electrophoresis, Giemsa staining, Hoechst 33258 staining and photomicroscopical observation were used. RESULTS: UV irradiation (2.4 J/cm~2, 4 min) induced U937 cell apoptosis. Marked DNA fragmentation in agarose gel electrophoresis was observed. Oridonin augmented phagocytosis of apoptotic U937 cells by U937 cell-derived macrophages in a time- and dose-dependent manner. However, less effect on synthetic fluoresbrite micropheres was observed. The oridonin-augmented phagocytosis was attenuated by anti-human TNF? or anti-human IL-1? antiserum. In addition, the similar effect of phagocytosis was observed in oridonin-treated human monocyte-derived macrophages at 4 day maturation. CONCLUSION: Oridonin enhances phagocytosis of apoptotic U937 cells by macrophage-like cells. The releases of TNF? and IL-1? are involved in this mechanism.