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1.
Braz. j. med. biol. res ; 54(8): e10850, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249328

ABSTRACT

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2′-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.


Subject(s)
Humans , Adenosine Deaminase , Dipeptidyl Peptidase 4 , Leukocytes, Mononuclear , Adenine , Lymphocytes
2.
Chinese Medical Journal ; (24): 2850-2856, 2021.
Article in English | WPRIM | ID: wpr-921172

ABSTRACT

BACKGROUND@#Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting.@*METHODS@#A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.@*RESULTS@#One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable.@*CONCLUSIONS@#The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.


Subject(s)
Adenine/therapeutic use , Adult , Alanine , Alkynes , Anti-HIV Agents/adverse effects , Benzoxazines , Central Nervous System , Cobicistat/therapeutic use , Cyclopropanes , Drug Combinations , Emtricitabine/therapeutic use , Female , HIV Infections/drug therapy , Humans , Male , Prospective Studies , Quality of Life , Quinolones , Tenofovir/analogs & derivatives
3.
Chinese Journal of Biotechnology ; (12): 2307-2321, 2021.
Article in Chinese | WPRIM | ID: wpr-887798

ABSTRACT

The CRISPR system is able to accomplish precise base editing in genomic DNA, but relies on the cellular homology-directed recombination repair pathway and is therefore extremely inefficient. Base editing is a new genome editing technique developed based on the CRISPR/Cas9 system. Two base editors (cytosine base editor and adenine base editor) were developed by fusing catalytically disabled nucleases with different necleobase deaminases. These two base editors are able to perform C>T (G>A) or A>G (T>C) transition without generating DNA double-stranded breaks. The base editing technique has been widely used in gene therapy, animal models construction, precision animal breeding and gene function analysis, providing a powerful tool for basic and applied research. This review summarized the development process, technical advantages, current applications, challenges and perspectives for base editing technique, aiming to help the readers better understand and use the base editing technique.


Subject(s)
Adenine , Animals , CRISPR-Cas Systems/genetics , Cytosine , DNA Breaks, Double-Stranded , Gene Editing
4.
Article in Chinese | WPRIM | ID: wpr-879189

ABSTRACT

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.


Subject(s)
Adenine , Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal/toxicity , Kidney , Rats , Tandem Mass Spectrometry , Technology
5.
Int. j. morphol ; 38(3): 530-535, June 2020. graf
Article in English | LILACS | ID: biblio-1098283

ABSTRACT

Dysregulated autophagy, whether excessive or downregulated, has been thought to be associated with neurodegenerative disorders including Parkinson's disease. Accordingly, the present study was carried out to investigate whether 3-methyladenine, an autophagy inhibitor, can modulate the effects of rotenone on dopaminergic neurons in primary mesencephalic cell culture. Cultures were prepared from embryonic mouse mesencephala at gestation day 14. Four groups of cultures were treated on the 10th DIV for 48 h as follows: the first was kept as an untreated control, the second was treated with 3-methyladenine alone (1, 10, 100, 200 mM), the third was treated with 20 nM rotenone and the fourth was co-treated with 20 nM rotenone and 3-methyladenine (1, 10, 100, 200 mM). On the 12th DIV, cultured cells were stained immunohistochemically against tyrosine hydroxylase and culture media were used to measure the levels of lactate dehydrogenase. 3methyladenine had no effects on both the survival of dopaminergic neurons and the release of lactate dehydrogenase. Rotenone significantly decreased the number of dopaminergic neurons and increased the levels of lactate dehydrogenase in the culture media. When cultures concomitantly treated with 3-methyladenine and rotenone, 3-methyladenine had no effect against rotenone-induced dopaminergic cell damage and lactate dehydrogenase release into the culture medium. In conclusion, the autophagy inhibitor 3-methyladenine could not modulate rotenone-induced dopaminergic cell damage in primary mesencephalic cell culture.


Se estima que la autofagia desregulada, ya sea excesiva o con baja regulación, está asociada con trastornos neurodegenerativos, incluyendo la enfermedad de Parkinson. En consecuencia, el se realizó este estudio para investigar si la 3metiladenina, un inhibidor de la autofagia,puede modular los efectos de la rotenona en las neuronas dopaminérgicas en el cultivo primario de células mesencefálicas. Los cultivos se prepararon a partir de mesencéfalo de ratón embrionario el día 14 de gestación. Cuatro grupos de cultivos se trataron en el 10º DIV durante 48 h de la siguiente manera: el primer grupo se mantuvo como un control no tratado, el segundo se trató con 3-metiladenina sola (1, 10, 100, 200 mM), el tercer grupo se trató con rotenona 20 nM y el cuarto se trató conjuntamente con rotenona 20 nM y 3-metiladenina (1, 10, 100, 200 mM). En el 12º DIV; las células cultivadas fueron tratadas mediante tinción inmunohistoquímica en tirosina hidroxilasa y se usaron medios de cultivo para medir los niveles de lactato deshidrogenasa. La 3-metiladenina no tuvo efectos tanto en la supervivencia de las neuronas dopaminérgicas como en la liberación de lactato deshidrogenasa. La rotenona disminuyó significativamente el número de neuronas dopaminérgicas y se observó un aumento de los niveles de lactato deshidrogenasa en los medios de cultivo. Cuando los cultivos tratados concomitantemente con 3-metiladenina y rotenona, la 3metiladenina no tuvo efecto contra el daño celular dopaminérgico inducido por la rotenona y la liberación de lactato deshidrogenasa en el medio de cultivo. En conclusión, el inhibidor de la autofagia 3-metiladenina no moduló el daño celular dopaminérgico inducido por la rotenona en el cultivo celular mesencefálico primario.


Subject(s)
Animals , Mice , Parkinson Disease , Rotenone/toxicity , Adenine/analogs & derivatives , Autophagy , Mesencephalon , Adenine/pharmacology , Cells, Cultured , Cell Death/drug effects , Dopaminergic Neurons/drug effects , L-Lactate Dehydrogenase/analysis
6.
J. coloproctol. (Rio J., Impr.) ; 40(2): 135-142, Apr.-Jun. 2020. tab, graf, ilus
Article in English | LILACS | ID: biblio-1134976

ABSTRACT

ABSTRACT Colorectal cancer is one of the most important malignancies in the classification of gastrointestinal cancers. One of the predisposing factors at molecular level for this cancer is via WNT signaling which is associated with the vast numbers of different genes. Thus, in this study, we aimed to investigate whether Adenomatous Polyposis Coli gene (APC) mutation of rs41115in two locations such as 132.002 and 131.989 acts as a trigger or cause of colorectal cancer. Relatively, 30 blood samples of colorectal cancer patients and 30 normal blood samples as control group after colonoscopy and also confirmation of pathology report at Rohani Hospital in Babol (Iran) were investigated. The primers were designed in order to be included the rs41115 to identify the particular polymorphisms of gene. The polymerase chain reaction (PCR direct sequencing method) was used. Conclusively, deletion of adenine in two specific locations such as 131.989 and 132.002 has been identified, but there was no relationship between rs41115 polymorphisms located in adenomatous polyposis coli gene and colorectal cancer.


RESUMO O câncer colorretal é uma das neoplasias malignas mais importantes na classificação dos cânceres gastrointestinais. Um dos fatores predisponentes no âmbito molecular para esse câncer é através da via de sinalização WNT, que está associada a um grande número de genes diferentes. Portanto, neste estudo, objetivamos investigar se a mutação rs41115 do gene da polipose adenomatosa do cólon (Adenomatous Polyposis Coli - APC) em dois locais como 132.002 e 131.989 atua como gatilho ou como causa do câncer colorretal. Relativamente, 30 amostras de sangue de pacientes com câncer colorretal e 30 amostras de sangue normal (grupo controle) foram analisadas após a colonoscopia, bem como a confirmação do laudo da patologia no Rohani Hospital em Babol (Irã). Os primers foram projetados de modo a incluir o rs41115 para identificar os polimorfismos particulares do gene. A reação em cadeia da polimerase (método de sequenciamento direto por PCR) foi utilizada. Conclusivamente, a deleção de adenina em dois locais específicos, como 131.989 e 132.002, foi identificada, mas não houve relação entre o polimorfismo rs41115 localizado no gene da polipose adenomatosa do cólon e o câncer colorretal.


Subject(s)
Humans , Male , Female , Polymorphism, Genetic , Colorectal Neoplasms/pathology , Genes, APC , Adenine , Signal Transduction/genetics , Polymerase Chain Reaction , Colonoscopy , Adenomatous Polyposis Coli/pathology
7.
Int. braz. j. urol ; 46(1): 70-80, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056356

ABSTRACT

ABSTRACT Objective: To analyze the compositions of upper urinary tract stones and investigate their distributions in different gender and age groups. Materials and Methods: Patients diagnosed with upper urinary tract stone disease between December 2014 and March 2018 were retrospectively reviewed. Patient's age, gender, BMI, comorbidities, stone event characteristics, and compositions were collected, and proportions of stone components in different gender and age groups were analyzed. Results: A total of 1532 stone analyses were performed (992 from males and 540 from females). The mean age was younger in males (p <0.001). Males included more cases with larger BMI, hyperuricemia, and obesity, while females had more urinary tract infections. Multiple components were present in 61.8% of stones. Calcium oxalate (CaOx) (67.0%) was the most common component, followed by uric acid (UA) (11.8%), infection stone (11.4%), calcium phosphate (CaP) (8.0%), cystine (1.1%), brushite (0.4%), and 2, 8-dihydroxyadenine (0.2%). Men contributed with more CaOx stones than women at age 30-49 years (all p <0.01) and more UA stones at 30-59 years (all p <0.05). Women contributed with more infection stones than men in age groups 30-49 and 60-69 years (all p <0.05), and more CaP stones at 30-49 years. The prevalence peak was 50-59 years in men and 60-69 years in women. Both genders had the lowest prevalence in adolescence. Prevalence of UA stones increased while that of infection stones decreased with aging in both genders. Conclusions: Age and sex had a strong association with distribution of stone compositions in this Chinese cohort.


Subject(s)
Humans , Male , Female , Adult , Urinary Calculi/epidemiology , Urinary Calculi/chemistry , Risk Factors , Uric Acid/analysis , Calcium Oxalate/analysis , Calcium Phosphates/analysis , Adenine/analysis , Adenine/analogs & derivatives , Urinary Calculi/etiology , Logistic Models , China/epidemiology , Sex Factors , Prevalence , Retrospective Studies , Age Factors , Sex Distribution , Age Distribution , Middle Aged
8.
Article in Chinese | WPRIM | ID: wpr-828093

ABSTRACT

The aim of this paper was to study the effect of Wubi Shanyao Pills on sexual dysfunction in rats with kidney-Yang deficiency and to investigate its possible mechanism. Adenine(100 mg·kg~(-1)) was administered to male SD rats for 8 weeks to establish kidney-Yang deficiency model, and at the same time, Wubi Shanyao Pills(2, 1, 0.5 g·kg~(-1)) were administered to rats for 8 weeks. The syndrome manifestation of kidney-Yang deficiency was observed in rats and the scores of symptoms were evaluated. Sexual behavior indexes(incubation period and times of capture, straddle and ejaculation) were measured by mating experiment. The levels of serum testosterone(T), estradiol(E_2), follicle stimulating hormone(FSH), luteinizing hormone(LH), and gonadotropin releasing hormone(GnRH) were measured by radioimmunoassay. The wet weights of testis and seminal vesicle were measured. The content of fructose in seminal plasma was detected by UV spectrophotometry. The pathological changes of testis and epididymis were observed by HE staining. The expression levels of transforming growth factor(TGF-β1) and cytochrome P450 aromatase(CYP19) in testis were detected by immunohistochemistry and Western blot. The results showed that Wubi Shanyao Pills could significantly reduce the score of kidney-Yang deficiency syndrome, improve the symptoms of kidney-Yang deficiency syndrome, shorten capture, straddle and ejaculation latency, increase capture and straddle times, increase serum T, LH, FSH, E_2 and GnRH levels, increase the wet weight of testis and seminal vesicle and fructose content in seminal plasma, improve the pathological structure of testis and epididymis, and inhibit the expression of TGF-β1 and increase CYP19 in testis of the model rats. Therefore, Wubi Shanyao Pills can significantly improve sexual dysfunction in rats with kidney-Yang deficiency, and its mechanism may be related to regulating the low function of hypothalamus pituitary gonad(HPG) axis and improving the disorder of sex hormone secretion. In addition, it may be also related to inhibiting the expression of testicular TGF-β1, increasing the expression of CYP19 protein, and then regulating the amount of T converted to E_2.


Subject(s)
Adenine , Animals , Follicle Stimulating Hormone , Gonadotropin-Releasing Hormone , Luteinizing Hormone , Male , Rats , Rats, Sprague-Dawley , Testis , Testosterone , Yang Deficiency
9.
Article in English | WPRIM | ID: wpr-827465

ABSTRACT

OBJECTIVE@#To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.@*METHODS@#A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.@*RESULTS@#The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.@*CONCLUSION@#Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).


Subject(s)
Adenine , Therapeutic Uses , Adult , Antiviral Agents , Therapeutic Uses , Double-Blind Method , Drug Therapy, Combination , Drugs, Chinese Herbal , Therapeutic Uses , Female , Hepatitis B e Antigens , Allergy and Immunology , Hepatitis B, Chronic , Drug Therapy , Allergy and Immunology , Humans , Male , Medicine, Chinese Traditional , Organophosphonates , Therapeutic Uses , Young Adult
10.
Article in English | WPRIM | ID: wpr-728016

ABSTRACT

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons (100 µM, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner (1–50 µM) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of Ca²⁺ and ROS, mitochondrial membrane potential (ΔΨ(m)) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.


Subject(s)
Adenine , Brain , Cell Death , Cell Survival , Cell-Free System , Glutamic Acid , Heme Oxygenase-1 , Membrane Potential, Mitochondrial , Mitochondria , Neurodegenerative Diseases , Neurons , Reactive Oxygen Species
11.
Article in English | WPRIM | ID: wpr-764304

ABSTRACT

BACKGROUND: NAD(P)H:quinone oxidoreductase-1 (NQO1) is a widely-distributed flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes. This reduces quinone levels and thereby minimizes generation of excess reactive oxygen species (ROS) formed by redox cycling, and concurrent depletion of intracellular thiol pools. Ajoene is derived from crushed garlic. It is formed by a reaction involving two allicin molecules, and is composed of allyl sulfide and vinyl disulfide. Ajoene is present in two isomers, E- and Z-form. METHODS: Expression of antioxidant enzymes and nuclear factor E2-related factor-2 (Nrf2) was measured by Western blot analysis. NQO1 promoter activity was assessed by the luciferase reporter gene assay. ROS accumulation was monitored by using the fluorescence-generating probe 2′,7′-dichlorofluorescein diacetate. The intracellular glutathione levels were measured by using a commercially available kit. RESULTS: Z-ajoene significantly up-regulated the expression of representative antioxidant enzyme NQO1 in non-tumorigenic breast epithelial MCF-10A cells at non-toxic concentrations. Z-ajoene enhanced up-regulation and nuclear translocation of Nrf2, which plays a pivotal role in the induction of many genes encoding antioxidant enzymes and other cytoprotective proteins. Z-ajoene treatment also increased the activity of nqo1-promoter harboring antioxidant response element consensus sequences in MCF-10A cells. Silencing of Nrf2 by small interfering RNA abrogated ajoene-induced expression of NQO1. Z-ajoene activated extracellular signal-regulated kinase (ERK). Inhibition of ERK activation by U0126 abrogated ability of Z-ajoene to activate Nrf2 and to induce NQO1 expression. Intracellular ROS accumulation was observed after treatment with Z-ajoene, whereas the E-isoform was not effective. The inhibition of ROS by treatment with N-acetylcysteine, a radical scavenger, abrogated Z-ajoene-induced expression of NQO1 as well as activation of ERK and Nrf2, suggesting that Z-ajoene augments the Nrf2-dependent antioxidant defense via ROS generation and ERK activation. CONCLUSIONS: Z-ajoene induces NQO1 expression in MCF-10A cells through ROS-mediated activation of Nrf2.


Subject(s)
Acetylcysteine , Adenine , Antioxidant Response Elements , Azo Compounds , Blotting, Western , Breast , Consensus Sequence , Epithelial Cells , Flavoproteins , Garlic , Genes, Reporter , Glutathione , Humans , Luciferases , NF-E2-Related Factor 2 , Oxidation-Reduction , Phosphotransferases , Quinones , Reactive Oxygen Species , RNA, Small Interfering , Up-Regulation
12.
Article in English | WPRIM | ID: wpr-773607

ABSTRACT

Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named (-) ethyl 1, 4-di-O-caffeoylquinate (1) and (-) methyl 1, 4-di-O-caffeoylquinate (2), together with 35 known compounds (3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1 (IC 11.94 μmol·L) and 2 (IC 15.04 μmol·L) showed a good inhibitory activity. The current results supported the medical use of the plant.


Subject(s)
Adenine , Chemistry , Drugs, Chinese Herbal , Chemistry , Pharmacology , Enzyme Activation , Flavonoids , Chemistry , Gnaphalium , Chemistry , Gout Suppressants , Chemistry , Pharmacology , Hydroxybenzoates , Chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phytochemicals , Chemistry , Pharmacology , Plant Components, Aerial , Chemistry , Plant Extracts , Chemistry , Pharmacology , Quinic Acid , Chemistry , Xanthine Oxidase
13.
Article in English | WPRIM | ID: wpr-812396

ABSTRACT

Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named (-) ethyl 1, 4-di-O-caffeoylquinate (1) and (-) methyl 1, 4-di-O-caffeoylquinate (2), together with 35 known compounds (3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1 (IC 11.94 μmol·L) and 2 (IC 15.04 μmol·L) showed a good inhibitory activity. The current results supported the medical use of the plant.


Subject(s)
Adenine , Chemistry , Drugs, Chinese Herbal , Chemistry , Pharmacology , Enzyme Activation , Flavonoids , Chemistry , Gnaphalium , Chemistry , Gout Suppressants , Chemistry , Pharmacology , Hydroxybenzoates , Chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phytochemicals , Chemistry , Pharmacology , Plant Components, Aerial , Chemistry , Plant Extracts , Chemistry , Pharmacology , Quinic Acid , Chemistry , Xanthine Oxidase
14.
Journal of Bone Metabolism ; : 153-159, 2018.
Article in English | WPRIM | ID: wpr-716571

ABSTRACT

BACKGROUND: High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. METHODS: CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. RESULTS: Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P < 0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P < 0.01). CONCLUSIONS: Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.


Subject(s)
Adenine , Animals , Diet , Enzyme-Linked Immunosorbent Assay , Fibroblast Growth Factors , Fibroblasts , Humans , Models, Animal , Mortality , Osteocytes , Phosphates , Rats , Renal Insufficiency , Renal Insufficiency, Chronic , Risk Factors , Sevelamer , Spectrophotometry
15.
Article in English | WPRIM | ID: wpr-727581

ABSTRACT

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines TNF-α and IL-6 and inflammatory lipid mediators, prostaglandin E₂ and leukotriene B₄. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed IκB phosphorylation, nuclear translocation of nuclear factor κB (NF-κB), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of TNF-α, IL-6 and IL-13 and also hindered phosphorylation of NF-κB and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of TNF-α and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.


Subject(s)
Adenine Nucleotides , Adenine , Animals , Bone Marrow , Cell Line , Cell Wall , Colitis , Cytokines , Dextrans , Gram-Negative Bacteria , Hypersensitivity , Inflammation , Interleukin-13 , Interleukin-6 , Lymphocytes , Macrophages , Mammals , Mast Cells , Mice , Mitogen-Activated Protein Kinases , Nucleic Acids , Peritoneal Cavity , Phosphorylation , Protein Kinases , Sodium , Toll-Like Receptor 4
16.
Article in English | WPRIM | ID: wpr-713541

ABSTRACT

BACKGROUND/AIMS: NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-mediated oxidative stress plays a key role in promotion of oxidative injury in the cardiovascular system. The aim of this study is to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic patients and to assess the correlation between NOX activity and the functions EPCs. METHODS: A total of 30 hyperlipidemic patients were enrolled for this study and 30 age-matched volunteers with normal level of plasma lipids served as controls. After the circulating EPCs were isolated, the EPC functions (migration, adhesion and tube formation) were evaluated and the status of NOX (expression and activity) was examined. RESULTS: Compared to the controls, hyperlipidemic patients showed an increase in plasma lipids and a reduction in EPC functions including the attenuated abilities in adhesion, migration and tube formation, concomitant with an increase in NOX expression (NOX2 and NOX4), NOX activity, and reactive oxygen species production. The data analysis showed negative correlations between NOX activity and EPC functions. CONCLUSIONS: There is a positive correlation between the NOX-mediated oxidative stress and the dysfunctions of circulating EPCs in hyperlipidemic patients, and suppression of NOX might offer a novel strategy to improve EPCs functions in hyperlipidemia.


Subject(s)
Adenine , Cardiovascular System , Endothelial Progenitor Cells , Humans , Hyperlipidemias , NADP , NADPH Oxidases , Oxidative Stress , Oxidoreductases , Plasma , Reactive Oxygen Species , Statistics as Topic , Volunteers
17.
Article in English | WPRIM | ID: wpr-198625

ABSTRACT

In this study, we investigated whether adenosine, adenine, uridine and homogentisic acid derived from Pinellia ternata affect the secretion, production and gene expression of MUC5AC mucin from airway epithelial cells. Confluent NCI-H292 cells were pretreated with adenosine, adenine, uridine or homogentisic acid for 30 min and then stimulated with PMA (phorbol 12-myristate 13-acetate) for 24 h. The MUC5AC mucin gene expression, mucin protein production and secretion were measured by RT-PCR and ELISA, respectively. The results were as follows: (1) Adenine and homogentisic acid decreased PMA-induced MUC5AC mucin gene expression, although adenosine and uridine did not affect the mucin gene expression; (2) Adenosine, adenine, uridine and homogentisic acid inhibited PMA-induced MUC5AC mucin production; (3) Homogentisic acid inhibited the secretion of MUC5AC mucin from NCI-H292 cells. These results suggest that, among the four compounds examined, homogentisic acid showed the regulatory effect on the steps of gene expression, production and secretion of mucin, by directly acting on airway epithelial cells.


Subject(s)
Adenine , Adenosine , Biological Products , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Gene Expression , Homogentisic Acid , Mucins , Pinellia , Uridine
18.
Article in Chinese | WPRIM | ID: wpr-328266

ABSTRACT

<p><b>OBJECTIVE</b>To explore clinical efficacy of Yiguanjian Decoction (YD) combined Adefovir Dipivoxil Tablet (ADT) in treating HBeAg negative chronic viral hepatitis B (CVHB) active compensated liver cirrhosis (LC) patients.</p><p><b>METHODS</b>Totally 68 HBeAg negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group using random digit table, 34 in each group. Patients in the control group took ADT alone, 10 mg each time, once per day. Those in the treatment group additionally took YD, one dose per day. The therapeutic course for all was 48 weeks. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) were detected once in every two weeks. Hepatitis B virus (HBV)-DNA and four items of serum liver fibrosis [procollagen type I (PCN), hyaluronidase (HA), procollagen III peptide (PCIII), laminin (LN)] were detected once per every 4 weeks. Abdominal ultrasound B was performed before and after treatment. The inner diameter of the portal vein and the size of spleen were recorded. The fibrosis degree of liver was evaluated using Fibroscan. Efficacy of Chinese medicine (CM) was evaluated between the two groups before and after treatment using CM syndrome integrals. Efficacy of Western medicine (WM) was also evaluated between the two groups using Child-Pugh grading. Results Compared with before treatment in the same group, ALT and AST levels restored to normal levels, HBV-DNA turned negative (HBV-DNA < or = 1 x 10(2)) in the two groups after 48-week treatment. Besides, levels of TBil, ALB, PCIV, HA, PCIII, and LN obviously decreased (P < 0.05, P < 0.01). Results of ultrasound B showed the inner diameter of the portal vein and the size of spleen decreased. Fibroscan results showed that the elasticity value of the liver obviously decreased (P < 0.05). Besides, post-treatment levels of PCIV, HA, PCEJ, and LN, and the elasticity value of the liver decreased more obviously in the treatment group than in the control group (P < 0.01). There was no statistical difference in post-treatment levels of ALT, AST, TBil, ALB, inner diameter of the portal vein, or the size of spleen between the two groups (P > 0.05). Compared with before treatment in the same group, scores of Chinese medical syndrome and Child-Pugh scores decreased in the two groups after treatment (P < 0.05, P < 0.01). Besides, scores of Chinese medical syndrome decreased more obviously in the treatment group than in the control group (P < 0.05). The effective rate was 8824% (30/34) in the treatment group, higher than that of the control group [67.65% (23/34)] with statistical difference (P <0.05). Conclusion Combined treatment of YD and ADT could significantly improve symptoms of CM and fibrosis degree of liver of HBeAg negative CVHB active compensated LC patients.</p>


Subject(s)
Adenine , Therapeutic Uses , Alanine Transaminase , Blood , Antiviral Agents , Therapeutic Uses , Aspartate Aminotransferases , Blood , Bilirubin , Blood , DNA, Viral , Blood , Drugs, Chinese Herbal , Therapeutic Uses , Hepatitis B e Antigens , Blood , Hepatitis B, Chronic , Drug Therapy , Humans , Liver Cirrhosis , Drug Therapy , Virology , Organophosphonates , Therapeutic Uses , Tablets
19.
Article in English | WPRIM | ID: wpr-138549

ABSTRACT

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.


Subject(s)
Adenine/analogs & derivatives , Adult , Aged , Antiviral Agents/therapeutic use , DNA, Viral/analysis , Drug Resistance, Viral , Drug Therapy, Combination , Female , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Male , Middle Aged , Organophosphonates/therapeutic use , Polymerase Chain Reaction , Republic of Korea , Retrospective Studies , Tenofovir/therapeutic use , Treatment Outcome
20.
Article in English | WPRIM | ID: wpr-138548

ABSTRACT

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.


Subject(s)
Adenine/analogs & derivatives , Adult , Aged , Antiviral Agents/therapeutic use , DNA, Viral/analysis , Drug Resistance, Viral , Drug Therapy, Combination , Female , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Male , Middle Aged , Organophosphonates/therapeutic use , Polymerase Chain Reaction , Republic of Korea , Retrospective Studies , Tenofovir/therapeutic use , Treatment Outcome
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