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Objective: To analyze the diagnostic efficacy of urinary lipoarabinomannan (LAM) antigen detection method in tuberculosis patients, and to provide an experimental basis for the clinical application of urinary LAM kit in China. Methods: From March to May 2023, 228 patients with lung diseases [134 male, 94 female, age 20-82 (44.8±16.7) years] were prospectively collected in Beijing Chest Hospital, Capital Medical University, including 143 pulmonary tuberculosis patients and 85 non-tuberculosis patients. Urine and sputum samples from patients were collected for traditional etiological detection and urinary LAM antigen detection. The screening results of each positive detection combination were analyzed, and the difference analysis and regression analysis were performed. Results: The detection sensitivity and specificity of the urinary LAM kit were 46.2% (95%CI: 37.9%-54.7%) and 96.5% (95%CI: 89.3%-99.1%), respectively, with an overall coincidence rate of 64.9%. The detection rate of LAM antigen detection and GeneXpert MTB/RIF (Xpert) combined (60.8%, 87/143) was significantly higher than that of Xpert alone (49.7%, 71/143), and the difference was statistically significant (P<0.05). The results of risk factor analysis showed that the risk of negative urinary LAM antigen test results increased significantly as the bacterial load decreased. Conclusions: Urine LAM antigen detection method has a high specificity and can be combined with traditional methods to effectively improve the detection rate. Urinary LAM antigen detection method still has limitations, such as the influence of bacterial load and the inability to distinguish nontuberculosis mycobacteria samples, which needs further experimental verification.
Subject(s)
HIV Infections , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Tuberculosis, Pulmonary/diagnosis , Tuberculosis/diagnosis , Lipopolysaccharides , Sensitivity and Specificity , Sputum/microbiologyABSTRACT
Antibody-mediated rejection (AMR) is a key factor affecting the long-term survival of renal allografts. Donor-specific antibody (DSA) is the etiology of AMR. So it is very important to accurately detect DSA. The single antigen bead (SAB) method, which is widely used in clinical practice, is prone to miss DSA detection and underestimate its mean fluorescence intensity (MFI). In this paper, the probability of missed detection of two SAB reagents was calculated by comparing common HLA alleles in China population, and the in vitro effect of antibody cross reaction on MFI value of DSA was revealed. The authors emphasized the clinical significance of the above two problems, tried to manage them by using functional epitope (eplet) analysis and give some clinical examples. Finally, the limitations of this correction method were analyzed.
Subject(s)
Kidney Transplantation , Graft Rejection/diagnosis , Graft Rejection/etiology , Isoantibodies , Tissue Donors , HumansABSTRACT
OBJECTIVE: To evaluate the effect of individualized antiplatelet therapy based on CYP2C19 genotype and platelet function on the prognosis of patients after percutaneous coronary intervention (PCI) compared with conventional antiplatelet therapy. PATIENTS AND METHODS: Patients diagnosed with acute coronary syndromes (ACS) in Shandong Provincial Qianfoshan Hospital from December 2014 to December 2017 were included in this prospective study and randomly divided into conventional (CA) and individualized antiplatelet therapy group (IA) at 1:1 ratio. Patients in the CA group received clopidogrel 75 mg once a day (QD). Group IA was divided into extensive, intermediate, and poor metabolizers according to the results of the CYP2C19 gene test. Three genotypes were given clopidogrel 75 mg QD, 75 mg twice daily (BID) and ticagrelor 90 mg BID respectively. After taking these medicines for a period of time, platelet function was monitored by thromboelastography (TEG) and MAADP values were recorded. MAADP indicates the adenosine diphosphate (ADP) induced platelet function that not inhibited by medicine. High platelet reactivity (HPR) was defined as MAADP > 47mm, indicating a high risk of thrombus, and MAADP ≤ 31 mm indicates a high risk of hemorrhage. For extensive metabolizers (EMs) and intermediate metabolizers (IMs) patients with HPR, the antiplatelet therapy would be changed by the clinician according to the patient's conditions. Major adverse cardiovascular events (MACE) and hemorrhage events were monitored during 1-year follow-up. RESULTS: The patients with MAADP > 47 mm were 89 (28.6%) in the IA group. There were 50 EMs patients with MAADP > 47 mm (33.3%). Of which, there were 2 cases which changed the dosage of clopidogrel to 75 mg BID, 14 cases who changed clopidogrel to ticagrelor. There were 36 IMs patients with MAADP > 47 mm (30.8%). Of which, there were 19 cases who changed clopidogrel to ticagrelor. There was no significant difference in the value of MAADP between EMs and IMs patients. Within 1 year after PCI, the occurrence of MACE in the IA group was significantly lower than that in the CA group (p=0.010). CONCLUSIONS: (1) Patients with a CYP2C19 loss-of-function (LOF) gene who take double doses of clopidogrel overcome the decreased efficacy of clopidogrel which partly due to CYP2C19 LOF gene, without increasing the risk of hemorrhage. (2) Individualized antiplatelet therapy based on CYP2C19 genotype and platelet function can significantly reduce the occurrence of MACE (mainly acute non-fatal myocardial infarction) after PCI without increasing the risk of moderate or severe hemorrhage.
Subject(s)
Acute Coronary Syndrome/drug therapy , Clopidogrel/pharmacology , Cytochrome P-450 CYP2C19/genetics , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/pharmacology , Ticagrelor/pharmacology , Acute Coronary Syndrome/diagnosis , Blood Platelets/drug effects , Clopidogrel/administration & dosage , Cytochrome P-450 CYP2C19/metabolism , Dose-Response Relationship, Drug , Female , Genotype , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Platelet Function Tests , Ticagrelor/administration & dosageABSTRACT
Objective: To explore the effect of alcohol drinking on sputum culture conversion at the end of second month and outcome of smear-positive pulmonary tuberculosis (PTB) patients. Methods: Total 2 067 patients aged 18 years and above diagnosed and treated from 2008 to 2011 in 49 TB institutions from 8 provinces, antonomous regions and municipalities were enrolled, according to tuberculosis situation and regional distribution in China. Those patients were divided into three groups according to alcohol drinking, including never alcohol drinker group, ever-alcohol drinker group and current alcohol drinker group, respectively. Chi-square test was used to compare the following variables among the three groups: adverse action, lesions absorption, cavity size, sputum-culture results at the end of the 2(nd) month of treatment, and treatment outcome. Multivariate Logistic regression was used to explore that whether alcohol drinking was risk factor of poor treatment effect. Results: Among the 2 067 smear-positive PTB patients, never drinkers, ex-drinkers and current drinkers account for 55.2% (1 140/2 067), 36.5% (755/2 067), 8.3% (172/2 067), respectively. Among patients of never drinkers, ex-drinkers and current drinkers groups, sputum-culture conversion rate at the end of the 2(nd) month of treatment were 86.1%, 81.3% and 83.0%, respectively (χ(2)=6.782, P=0.033); the difference in treatment outcome was significant (χ(2)=13.620, P=0.034). Treatment success rate were 83.9%, 81.1% and 79.7%, respectively; failure rate was 6.4%, 10.3% and 9.9%, respectively, and fatality rate were 2.1%, 2.3% and 4.1%, respectively. Multivariate Logistic regression analysis showed that non-sputum conversion of the end of 2(nd) month and fatality rate of ex-drinkers were 1.431 and 1.668 times higher than never drinkers, respectively; non-sputum conversion of the end of 2(nd) month of current drinkers was 1.256 times higher than never drinkers. Conclusion: Alcohol drinking affects the treatment effectiveness of tuberculosis, which increased risk of culture-positive rate of the end of 2(nd) month and fatality rate.
Subject(s)
Alcohol Drinking , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Adolescent , Antitubercular Agents , China , Humans , SputumABSTRACT
Objective: To explore the diagnostic value of cerebrospinal fluid (CSF) adenosine deaminase (ADA) level in tuberculous meningitis. Methods: We retrospectively analyzed 139 patients (73 males, 66 females) who visited Beijing Chest Hospital for suspected TBM from January 2010 to June 2015. Of them, 99 patients were diagnosed to have TBM, with 45 males and 54 females, and a mean age of (33±15) years. Forty patients were diagnosed as having Non-TBM, with 28 males and 12 females, and a mean age of (35±18) years. All patients underwent lumbar puncture, and CSF ADA, routine, biochemical and bacteriological tests were performed. Thirty-five TBM patients reviewed CSF ADA test after treatment for 4 weeks, 8 weeks and 6 months. Results: The level of CSF ADA in TBM group was higher than that in the non-TBM group, the difference being statistically significant (5.6 U/L vs 2.3 U/L, P=0.000). When the cut-off value of the CSF ADA was 3.8 U/L , the sensitivity and specificity for diagnosis of TBM were 60.6% (95%CI 50.3%-70.1%) and 87.5% (95%CI 72.4%-95.3%), respectively, and the area under the ROC curve was 0.734.The CSF ADA level was (6.7±4.2) U/L in the 35 cases of TBM before treatment. After 4 weeks, 8 weeks and 6 months of anti-tuberculosis treatment, the CSF ADA levels were (4.5±3.3) U/L, (3.7±2.7) U/L and (2.0±1.5) U/L, respectively; all significantly decreased as compared to that before treatment (P<0.001). There was no significant change in the ADA level between 8 weeks and 4 weeks (P=0.128). After 6 months of treatment, the level of CSF ADA was significantly lower than those after 4 and 8 weeks' treatment (P<0.001). Conclusions: CSF ADA in TBM patients was significantly higher than in non-TBM patients. The sensitivity of CSF ADA level in the diagnosis of TBM was poor, but the specificity was better. CSF ADA was significantly reduced and showed dynamic changes with effective anti-tuberculosis treatment and maybe helpful in evaluating the effect of treatment.
Subject(s)
Adenosine Deaminase/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Tuberculosis, Meningeal/cerebrospinal fluid , Adolescent , Adult , Aged , Female , Humans , Male , Meningitis, Bacterial/enzymology , Middle Aged , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Tuberculosis, Meningeal/enzymology , Young AdultABSTRACT
The large surface roughness, low work function and high cost of transparent electrodes using multilayer graphene films can limit their application in organic photovoltaic (OPV) cells. Here, we develop single layer graphene (SLG) films as transparent anodes for OPV cells that contain light-absorbing layers comprised of the evaporable molecular organic semiconductor materials, zinc phthalocyanine (ZnPc)/fullerene (C60), as well as a molybdenum oxide (MoOx) interfacial layer. In addition to an increase in the optical transmittance, the SLG anodes had a significant decrease in surface roughness compared to two and four layer graphene (TLG and FLG) anodes fabricated by multiple transfer and stacking of SLGs. Importantly, the introduction of a MoOx interfacial layer not only reduced the energy barrier between the graphene anode and the active layer, but also decreased the resistance of the SLG by nearly ten times. The OPV cells with the structure of polyethylene terephthalate/SLG/MoOx/CuI/ZnPc/C60/bathocuproine/Al were flexible, and had a power conversion efficiency of up to 0.84%, which was only 17.6% lower than the devices with an equivalent structure but prepared on commercial indium tin oxide anodes. Furthermore, the devices with the SLG anode were 50% and 86.7% higher in efficiency than the cells with the TLG and FLG anodes. These results show the potential of SLG electrodes for flexible and wearable OPV cells as well as other organic optoelectronic devices.
ABSTRACT
Objective: To investigate the features and influencing factors of self-discrimination among patients with HIV/AIDS according to sex. Methods: A total of 2 432 HIV/AIDS patients were recruited in Yunnan, Henan, Hubei, Jiangsu, Shanxi, Jilin, and Inner Mongolia provinces by a multistage stratified cluster sampling method, based on HIV epidemic and transmission modes, from May 2013 to October 2013. All participants were ≥18 years old, and we excluded those with mental disorders, hearing loss or other factors that prevented them from properly answering questions, and those who were unwilling to participate. A self-designed questionnaire was conducted to collect information about self-discrimination features and social behavior changes among HIV/AIDS patients. Differences in performance and self-discrimination features between participants of different sexes were compared using the chi-squared test. Factors influencing self-discrimination were analyzed by sex, using unconditional logistic regression. Results: Of the 2 432 cases, 78.9%(1 918 cases)were male and 21.1%(514 cases)female. The proportion of self-discrimination overall was 76.1%(1 850 cases); this proportion among female HIV/AIDS patients was 80.5%(414 cases), which was higher than that among men(74.9%, 1 436 cases)(χ2=7.17, P=0.007). Of the 11 forms of self-discrimination performance, proportions of feeling guilt, shame, and self-abasement among participants were greater than 50%. Proportions of feeling shame, inferiority, and blaming others among females were 61.3%, 59.5%, and 45.3%, respectively, which were higher than these among males(49.8%, 50.0%, 28.4%, respectively)(P<0.01). Multivariate unconditional logistic regression analysis showed that the risk of self-discrimination among those with HIV confirmatory testing time ≥1 year was higher than those with HIV confirmatory testing time <1 year(females: OR=35.67, 95%CI:17.28-73.64; males: OR=8.74, 95% CI:6.79-11.25). Compared with other occupations, the risk of self-discrimination among male farm workers was higher(OR=1.62, 95% CI:1.03-2.54). The risks of self-discrimination in males who had been infected with HIV by transmission routes of blood transfusion or blood collection(OR=2.38, 95% CI:1.31-4.30), injection drug use(OR=1.78, 95% CI:1.09-2.91), and male-to-male sexual behavior(OR=1.48, 95%CI:1.08-2.03)were higher than in males infected via heterosexual behavior. Conclusion: Female HIV/AIDS patients are more likely to engage in self-discrimination than male patients. Self-discrimination mainly takes the form of feeling remorse, shame, and inferiority. Confirmatory testing time ≥1 year, occupation as a farm work, and routes of transmission via blood transfusion or collection, injection drug use, and male-to-male sexual behavior are influencing factors of self-discrimination among male HIV/AIDS patients. Confirmatory testing time ≥1 year is the influencing factor of self-discrimination among female HIV/AIDS patients.
Subject(s)
Guilt , HIV Infections/psychology , Self Concept , Shame , Acquired Immunodeficiency Syndrome/psychology , Adult , China , Female , HIV Infections/diagnosis , Humans , Logistic Models , Male , Mass Screening , Risk Factors , Sex Factors , Sexual Behavior , Social Discrimination , Surveys and QuestionnairesABSTRACT
The relatively high sheet resistance, low work function and poor compatibility with hole injection layers (HILs) seriously limit the applications of graphene as transparent conductive electrodes (TCEs) for organic light emitting diodes (OLEDs). Here, a graphene oxide/graphene (GO/G) vertical heterostructure is developed as TCEs for high-performance OLEDs, by directly oxidizing the top layer of three-layer graphene films with ozone treatment. Such GO/G heterostructure electrodes show greatly improved optical transmittance, a large work function, high stability, and good compatibility with HIL materials (MoO3 in this work). Moreover, the conductivity of the heterostructure is not sacrificed compared to the pristine three-layer graphene electrodes, but is significantly higher than that of pristine two-layer graphene films. In addition to high flexibility, OLEDs with different emission colors based on the GO/G heterostructure TCEs show much better performance than those based on indium tin oxide (ITO) anodes. Green OLEDs with GO/G heterostructure electrodes have the maximum current efficiency and power efficiency, as high as 82.0 cd A(-1) and 98.2 lm W(-1), respectively, which are 36.7% (14.8%) and 59.2% (15.0%) higher than those with pristine graphene (ITO) anodes. These findings open up the possibility of using graphene for next generation high-performance flexible and wearable optoelectronics with high stability.
ABSTRACT
OBJECTIVE: To investigate the quality of life and its related factors among HIV/AIDS patients from HIV serodiscordant couples in Zhoukou city of Henan province. METHODS: During January to May in 2015, by the convenience sample, World Health Organization Quality of Life Questionnaire for Brief Version (WHOQOL-BREF) (Chinese version) and a self-edited questionnaire were used to investigate 1 251 HIV/AIDS patients who were confirmed with HIV positive by local CDC, registered in"HIV serodiscordant family" and agreed to participate in a face-to-face interview with above 18 year-old based on the local CDC , township hospitals and village clinics of 9 counties and 1 district of Zhoukou city, excluding the HIV/AIDS patients who were in divorce, death by one side, unknowing about his HIV status, with mental illness and disturbance of consciousness, incorrectly understanding the content of the questionnaire, and reluctant to participate in this study. The scores of quality of life of physical, psychological, social relations, and environmental domain were calculated. The related factors of the scores of different domains were analyzed by Multiple Two Classification Unconditioned Logistic Regression. RESULTS: The scores of investigation objects in the physical, psychological, social relations, and environmental domain were 12.00± 2.02, 12.07 ± 2.07, 11.87 ± 1.99, and 11.09 ± 1.84, respectively. The multiple Unconditioned Logistic Regression analysis indicated that age <40 years, on ART and no other sickness in last two weeks were beneficial factors associated with physical domain with OR (95%CI): 0.61 (0.35-1.06), 0.52 (0.30-0.90), and 1.66 (1.09-2.52), respectively. The possibility of no poverty and no other sickness in last two weeks increased to 0.15(0.09-0.26) and 1.57(1.06-2.33) times of those who was in poverty and with other sickness in last two weeks in physical domain. The possibility of participants who were below 40 years old and with children increased to 0.58 (0.34-0.98) and 0.37 (0.23-0.57) times of who were above 40 years old and without children in psychological domain. The factors of with AIDS related symptoms, no children and with other sickness in last two week were found to be significantly associated with environmental domain with OR (95%CI): 0.65 (0.48-0.88), 0.66 (0.51-0.85), and 0.65 (0.51-0.84), respectively . CONCLUSION: The scores of every domain of quality of life in HIV serodiscordant couples of Zhoukou city were good. Age, whether having AIDS related symptoms, whether to accept ART , children, status of poverty, and whether suffering from other diseases in last two weeks were the main factors associated with the quality of life.
Subject(s)
Family Characteristics , HIV Infections/psychology , HIV Seropositivity/psychology , Quality of Life , Acquired Immunodeficiency Syndrome , Adult , Anti-HIV Agents/therapeutic use , China , Female , HIV Infections/drug therapy , HIV Seropositivity/drug therapy , Humans , Interviews as Topic , Male , Middle Aged , Socioeconomic Factors , Surveys and Questionnaires , World Health OrganizationABSTRACT
We previously demonstrated that inactivation of Rho-kinase by hydroxyfasudil could impact N-methyl-d-aspartate (NMDA) excitatory interneurons in the hippocampus and attenuate the spatial learning and memory dysfunction of rats caused by chronic forebrain hypoperfusion ischemia. Complementary interactions between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA form the molecular basis of synaptic plasticity and cognitive performance. However, whether the GABAergic inhibitory interneurons are involved in the mechanisms underlying these processes remains unclear. Here, we further examined the role of GABAergic interneurons in the neuroprotective effect of the Rho-kinase inhibitor. Chronic forebrain ischemia was induced in Wistar rats by bilateral common carotid artery occlusion (BCAO). The general synaptic transmission and long-term potentiation (LTP) of hippocampal CA3 neurons were evaluated at 30 days after sham surgery or BCAO. Real-time PCR and Western blot analyses were conducted to determine the effect of the Rho-kinase inhibitor hydroxyfasudil on GABAergic inhibitory interneuron expression and function after ischemia. Hydroxyfasudil showed no significant effect on general synaptic transmission, but it could abolish the inhibition of LTP induced by chronic forebrain ischemia. Moreover, the mRNA and protein levels of GABAA and GABAB in three brain regions after ischemia were markedly decreased, and hydroxyfasudil could up-regulate all mRNA and protein expression levels in these areas except for GABAA mRNA in the cerebral cortex and striatum. Using phosphorylation antibodies against specific sites on the GABAA and GABAB receptors, we further demonstrated that hydroxyfasudil could inhibit GABAergic interneuron phosphorylation triggered by the theta burst stimulation. In summary, our results indicated that the inactivation of Rho-kinase could enhance GABAA and GABAB expressions by different mechanisms to guarantee the induction of hippocampal LTP, and it could decrease the phosphorylation level of GABAergic inhibitory interneurons to promote the LTP induction rate and magnitude, hence improving the cognitive deficit suffered after chronic forebrain ischemia.
Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Brain Ischemia/drug therapy , Long-Term Potentiation/drug effects , Prosencephalon/drug effects , Protein Kinase Inhibitors/pharmacology , rho-Associated Kinases/antagonists & inhibitors , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , Animals , Brain Ischemia/physiopathology , Chronic Disease , Disease Models, Animal , Interneurons/drug effects , Interneurons/physiology , Long-Term Potentiation/physiology , Male , Phosphorylation/drug effects , Prosencephalon/physiopathology , RNA, Messenger/metabolism , Random Allocation , Rats, Wistar , Receptors, GABA-A/metabolism , Receptors, GABA-B/metabolism , Up-Regulation/drug effects , rho-Associated Kinases/metabolismABSTRACT
Since the total flavonoid extract (TFE) of Epimedium herb was found to prevent osteoporosis induced by ovariectomy in rats, we have been attempting to identify the exact compound responsible for the bone-strengthening activity. In this experiment, four flavonoid extracts were obtained from Epimedium sagittatum (Siebold & Zucc.) Maxim, which contained 25.3%, 51.2%, 82.3% and 99.2% icariin respectively. They were separately supplemented into the culture media of newborn rat calvarial osteoblasts (ROB) or primary rat bone marrow stroma cells (rMSCs) at 0.1, 1, 10 and 100 microg/ml respectively, in order to observe their effects on the cells. Not any appreciable effect was found on the differentiation of ROB, but an enhancing effect on the osteogenic differentiation of rMSCs was found, and the enhancing degree was icariin-dependent, that is, a higher concentration of icariin in the extract caused more mineralized bone nodules and higher calcium deposition levels. The gene expressions involved in osteogenesis were also improved which was revealed by RT-PCR, including alkaline phosphatase, bone matrix protein (osteocalcin, osteopontin, bone sialoprotein) and cytokines (TGF-beta1 and IGF-I). The effect of icariin on cell proliferation was assayed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Icariin inhibited the proliferation of rMSCs and ROB when its concentration was higher than 10(-5) microM (6.7 microg/ml), no stimulative effect was found. The above results indicated that icariin may exert bone-strengthening activity by enhancing the osteogenic differentiation of MSCs, which partially explains the anti-osteoporosis action of Epimedium herb.
Subject(s)
Bone Development/drug effects , Bone Marrow Cells/drug effects , Cell Differentiation/drug effects , Flavonoids/pharmacology , Osteoblasts/drug effects , Skull/cytology , Stromal Cells/drug effects , Animals , Animals, Newborn , Calcium/metabolism , Cell Proliferation/drug effects , Cell Separation , Chromatography, High Pressure Liquid , Epimedium/chemistry , Flavonoids/chemistry , Flavonoids/isolation & purification , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Antioxidative effects of the main polyphenolic components extracted from green tea leaves, i.e. (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and gallic acid (GA), against free radical initiated peroxidation of human low density lipoprotein (LDL) were studied. The peroxidation was initiated either thermally by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), or photochemically by a triplet sensitizer benzophenone (BP). The reaction kinetics was monitored by the uptake of oxygen and the depletion of alpha-tocopherol (TOH) presented in the native LDL. Kinetic analysis of the antioxidation process demonstrates that these green tea polyphenols are effective antioxidants against both AAPH-initiated and BP-photosensitized LDL peroxidation. The antioxidative action of the green tea polyphenols includes trapping the initiating and/or propagating peroxyl radicals with the activity sequence EC>EGCG>ECG>EGC>GA for the AAPH initiated peroxidation, and reducing the alpha-tocopheroxyl radical to regenerate alpha-tocopherol with the activity sequence of ECG>EC>EGCG>EGC>GA and ECG>EGCG>GA>EC>EGC for the AAPH-initiated and BP-photosensitized peroxidations respectively.
Subject(s)
Antioxidants/pharmacology , Lipid Peroxidation/drug effects , Lipoproteins, LDL/drug effects , Phenols/pharmacology , Polymers/pharmacology , Tea/chemistry , Catechin/analogs & derivatives , Catechin/pharmacology , Flavonoids/pharmacology , Free Radicals/metabolism , Gallic Acid/pharmacology , Humans , In Vitro Techniques , Kinetics , Lipid Peroxidation/radiation effects , Lipoproteins, LDL/blood , Lipoproteins, LDL/metabolism , Phenols/chemistry , Phenols/isolation & purification , Photochemistry , Polymers/chemistry , Polymers/isolation & purificationABSTRACT
To better understand the effects of p53 on the process of photodynamic therapy (PDT)-induced cell death, we introduced a wild-type p53 gene into the HT29 colorectal carcinoma cell line, which bears an endogenous mutant p53, using a lipofectin system. The influence of p53 status on the sensitivity induced by 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization was then examined. The results indicate that infection with wild-type p53 induces a growth arrest but does not induce cell death, and sensitizes the cells to PDT. At a concentration of 5 microM 2-BA-2-DMHA with a red light of 18 J/cm2 (lambda = 600-700 nm), the survival is reduced from 58.72% in HT29 cells to 13.49% in wild-type p53-infected HT29 cells. Apoptosis following PDT appears earlier in HT29 cells infected with wild-type p53 than in parent HT29 cells and empty vector-infected HT29 cells. These findings suggest that although wild-type p53 is, by itself, insufficient to induce apoptosis in cells with p53 mutation, it enhances the photosensitivity of 2-BA-2-DMHA by strongly potentiating the induction of apoptosis.
Subject(s)
Perylene/analogs & derivatives , Photochemotherapy , Photosensitizing Agents/pharmacology , Quinones/pharmacology , Tumor Suppressor Protein p53/physiology , Apoptosis , G1 Phase , HT29 Cells , Humans , Mutation , Perylene/pharmacology , Tumor Cells, CulturedABSTRACT
The bcl-2 oncoprotein directly prolongs cellular survival by blocking apoptosis and its overexpression is associated with cellular resistance to killing by chemotherapeutic drugs and gamma-irradiation. Meanwhile, it has been shown that bcl-2 antisense oligonucleotide can induce apoptosis or increase toxicity of the treatment in tumors in vivo and in vitro. However, it is difficult to obtain stable transfection by this approach and there are no reports about the effect of an antisense bcl-2 on the sensitivity to oxidative stress induced by photodynamic therapy (PDT). Here we investigated the effect of an antisense bcl-2 RNA retrovirus vector transfer on the sensitivity of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization in a human gastric adenocarcinoma MGC803 cell line. The results indicate that antisense bcl-2-infected MGC803 cells expressed exogenous antisense bcl-2 mRNA measured by reverse transcription polymerase chain reaction and significantly reduced bcl-2 protein determined by western blotting analysis. The decreased expression of bcl-2 protein was accompanied by increased phototoxicity and susceptibility to apoptosis induced by 2-BA-2-DMHA PDT. Our finding suggests that reduction of bcl-2 protein in gastric cancers, and possibly also in a variety of other tumors, may be a novel and rational approach to improve photosensitivity and the treatment outcome.
Subject(s)
Adenocarcinoma/drug therapy , Photochemotherapy , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Antisense/genetics , Retroviridae/genetics , Stomach Neoplasms/drug therapy , Adenocarcinoma/pathology , Base Sequence , DNA Primers , Genetic Vectors , Humans , Perylene/analogs & derivatives , Perylene/therapeutic use , Photosensitizing Agents/therapeutic use , Quinones/therapeutic use , Stomach Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
The peroxidation of human low density lipoprotein (LDL) was initiated by water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) and copper and inhibited by vitamin C (VC) and its lipophillic derivatives ascorbyl-6-caprylate (VC-8), 6-laurate (VC-12) and 6-palmitate (VC-16), respectively. The peroxidation was monitored by oxygen uptake, by decay of alpha-tocopherol and by formation of lipid oxidation products. Kinetic analysis of the antioxidation process demonstrates that the VCs can work synergistically with endogenous antioxidants (vitamin E, ubiquinol-10, beta-carotene etc.) in LDL to suppress the peroxidation and that the synergistic effect of the lipophilic VCs is appreciably higher than that of their lipophobic parent molecule. It is also shown that VC and especially the lipophilic VCs, are much more effective in inhibition of copper-induced than AAPH-induced LDL peroxidation.
Subject(s)
Ascorbic Acid/metabolism , Lipid Metabolism , Lipid Peroxidation , Lipoproteins, LDL/metabolism , Amidines/pharmacology , Antioxidants/pharmacology , Copper/metabolism , Free Radicals , Humans , Lipid Peroxidation/drug effects , Oxidants/pharmacology , Oxygen Consumption , Solubility , Spectrophotometry, UltravioletABSTRACT
Six new compounds, an iridoid glucoside, 6- O-methyl-epiaucubin, three iridoids, artselaenins A, B, C, a phenylethanoid glycoside, artselaeroside A, and a phenylpropanoid glycoside, artselaeroside B, as well as fourteen known compounds, nine iridoid glycosides and five phenylpropanoid glycosides were isolated from the whole plants (including roots, stems, leaves and flowers) of Pedicularis artselaeri. Their structures were identified mainly by spectral evidence.