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1.
Acta Pharmaceutica Sinica ; (12): 2665-2673, 2020.
Artículo en Chino | WPRIM | ID: wpr-837526

RESUMEN

In this study, the effect of benzo[α]pyrene (BaP) on chaperone-mediated autophagy (CMA) in a simulated hypoxia environment was observed and the relationship to heat shock protein 90 (HSP90) was clarified. With HSP90 inhibitor geldanamycin (GA) and HSP90α silenced, the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), HSP90, heat shock cognate protein 70 (HSC70), and lysosomal associated protein 2A (LAMP-2A) of A549 cells on hypoxic environment by BaP were tested. Alkaline comet experiment, immunofluorescence γ-H2AX focus experiment, quantitative real-time PCR (qPCR), and Western blot analyses were used to clarify the relationship between the DNA damage of different concentrations of BaP in A549 cells and the mRNA and protein expression of CMA-related factors. The results show that hypoxia can promote the expression of mRNA and protein of CMA-related factors in A549 cells. This study found that BaP has an inhibitory effect on CMA under the hypoxic environment. The inhibition or silencing of HSP90 will enhance the inhibitory effect of BaP on CMA. In a normoxic environment, BaP causes DNA damage and promotes CMA.

2.
China Journal of Chinese Materia Medica ; (24): 3013-3019, 2020.
Artículo en Chino | WPRIM | ID: wpr-828021

RESUMEN

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.


Asunto(s)
Humanos , Betacoronavirus , China , Infecciones por Coronavirus , Quimioterapia , Medicina Tradicional Mongoliana , Pandemias , Neumonía Viral , Quimioterapia
3.
China Journal of Chinese Materia Medica ; (24): 5429-5437, 2020.
Artículo en Chino | WPRIM | ID: wpr-878777

RESUMEN

Autophagy is a highly conservative and multi-component activated energy metabolism and self-renewal mechanism, which plays a crucial regulatory role in maintaining the normal physiological state of cells and is involved in various pathological processes. In recent years, the mechanism study has made great progress in regulating autophagy with effective components of Chinese materia medica(CMM),which are reported to prevent and treat cancers, neurodegenerative diseases, cardiovascular diseases and metabolic and immune-related diseases. This review outlines the molecular regulation mechanisms of cell autophagy with CMM components in controlling the above-mentioned diseases. There are many relevant reports on the regulatory mechanisms of autophagy in tumor and cardiovascular cells with CMM monomers. The main chemical structural types are alkaloids, saponins, polyphenols, flavonoids and terpenes. And m-TOR pathway is the main mechanism relating to the regulatory mechanisms of autophagy with CMM. Therefore, the regulatory mec-hanisms of cell autophagy become a new research targeting strategy of therapies with CMM. This review provides evidences for the effectiveness and scientificity of CMM in regulating autophagy, in the expectation of providing references for the in-depth studies of CMM in the field of autophagy and the development of natural autophagy regulators.


Asunto(s)
Humanos , Pueblo Asiatico , Autofagia , Medicamentos Herbarios Chinos/farmacología , Materia Medica , Medicina Tradicional China , Saponinas
4.
Chinese Journal of Pharmacology and Toxicology ; (6): 954-954, 2017.
Artículo en Chino | WPRIM | ID: wpr-666612

RESUMEN

OBJECTIVE TNF- related apoptosis- inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors. However, most breast cancer cells are resistant to TRAIL- induced apoptosis. Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance. METHODS To identify modulators of TRAIL-induced apoptosis, we carried out a genome wide siRNA screen. To validate the screening result, we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model. Finally, we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy. RESULTS We unexpectedly identified androgen receptor (AR) to be responsible for TRAIL resistance. While AR is classically viewed as the key factor in prostate cancer progression, we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple- negative breast cancers (TNBC) that are highly aggressive with poor prognosis. Importantly, breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance. AR overexpression in MDA- MB- 231 and MDA- MB- 436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis. AR overexpression also induced TRAIL resistance in breast tumors in vivo. Further, we observed an upregulation of the TRAIL receptor, death receptor 5 (DR5) in breast cancer cells, following the removal or inhibition of AR by its antagonists Casodex and MDV3100. Treatment with AR antagonists also enhanced TRAIL- induced breast cancer cell apoptosis. CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis, in part, by suppressing DR5 expression, and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.

5.
Chinese Journal of Pharmacology and Toxicology ; (6): 1015-1016, 2017.
Artículo en Chino | WPRIM | ID: wpr-666438

RESUMEN

OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways. METHODS Murine precision cut lung slices (PCLS) and trachea were prepared, placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally (1.0 ms, 50 V, 0.1- 30 Hz). To measure PCLS constriction, changes in airway luminal area in response to electric field stimulation (EFS) were captured as video images quantified using Image J software. For trachea, changes in isometric tension were recorded using Grass force transducers. Frequency response curves were generated in the absence and the presence of the inhibitors magnesium, atropine and capsaicin and responses analyzed and compared using a student' s t- test (P<0.05). RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve. Neuron-specific stimulation was verified by Mg2+ blockade. Maximum airway constriction to 30 Hz EFS in PCLS was (51.8±3.0)% while tracheal constriction averaged (551±80)mg. Interestingly, in PCLS the muscarinic receptor antagonist atropine (10 μmol · L- 1) blocked (99.5 ± 7.2)% of EFS induced constriction at 1 Hz, but only blocked (23.3±3.8)% of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response. Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways. CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters. These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.

6.
Journal of Forensic Medicine ; (6): 52-54, 2014.
Artículo en Chino | WPRIM | ID: wpr-983882

RESUMEN

OBJECTIVE@#To study ApoB gene genetic polymorphism of Han nationality and Mongolian nationality in midwest area of Inner Mongolia.@*METHODS@#Some unrelated individuals of Han nationality and Mongolian nationality in midwest area of Inner Mongolia were selected. Polymerase chain reaction-restriction fragment length polymorphism technology was used to check the presence of Xba I (X+) and EcoR I (E-) sites of rare alleles. The genotype frequency, allelic frequency and population genetics parameters were calculated.@*RESULTS@#The frequencies of Xba I (X+) and EcoR I (E-) rare alleles were 2% and 4.6% in Han population. There was no Xba I (X+) or EcoR I (E-) rare alleles found in Mongolian nationality.@*CONCLUSION@#The allelic frequencies of ApoB gene Xba I and EcoR I sites are very different in different races. These sites may be used in identification of ethnicity.


Asunto(s)
Humanos , Alelos , Apolipoproteína B-100/genética , Pueblo Asiatico/genética , China , Etnicidad , Frecuencia de los Genes , Genotipo , Mongolia , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción
7.
Journal of Biomedical Engineering ; (6): 1200-1208, 2013.
Artículo en Chino | WPRIM | ID: wpr-259740

RESUMEN

The electrical pain perception were determined in healthy Chinese adults and factors were assessed. The anxiety-depression state of one hundred healthy Chinese were evaluated and the general information was recorded. Then electrical pain perception (perception threshold, pain threshold, pain tolerance) were assessed by neuromuscular monitor at the same time. Further study of influence factors such as gender, age, body mass index (BMI), left and right sides, degree of anxiety and depression, etc. were carried out on the pain perception. The results showed that 95% of the reference range of electrical perception threshold, pain threshold, pain tolerance were 4-7mA, 7 26mA and 15-60mA, respectively. The bilateral pain perception in males were significantly higher than that in females. There was no difference of effect between left and right sides. Age was positive related to pain perception, degree of depression was negative related to pain perception. BMI, degree of anxiety did not show association with pain perception. Therefore, gender, age and degree of depression were significantly related to electrical pain perception in healthy Chinese adults.


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Ansiedad , Índice de Masa Corporal , Depresión , Estimulación Eléctrica , Percepción del Dolor , Umbral del Dolor , Valores de Referencia
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