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1.
NPJ Genom Med ; 9(1): 32, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811629

RESUMEN

Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal dysplasia that primarily affects females. The only known causative gene is IKBKG, and the most common genetic cause is the recurrent IKBKG△4-10 deletion resulting from recombination between two MER67B repeats. Detection of variants in IKBKG is challenging due to the presence of a highly homologous non-pathogenic pseudogene IKBKGP1. In this study, we successfully identified four pathogenic variants in four IP patients using a strategy based on single-tube long fragment read (stLFR) sequencing with a specialized analysis pipeline. Three frameshift variants (c.519-3_519dupCAGG, c.1167dupC, and c.700dupT) were identified and subsequently validated by Sanger sequencing. Notably, c.519-3_519dupCAGG was found in both IKBKG and IKBKGP1, whereas the other two variants were only detected in the functional gene. The IKBKG△4-10 deletion was identified and confirmed in one patient. These results demonstrate that the proposed strategy can identify potential pathogenic variants and distinguish whether they are derived from IKBKG or its pseudogene. Thus, this strategy can be an efficient genetic testing method for IKBKG. By providing a comprehensive understanding of the whole genome, it may also enable the exploration of other genes potentially associated with IP. Furthermore, the strategy may also provide insights into other diseases with detection challenges due to pseudogenes.

2.
Phys Med Biol ; 68(24)2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37549670

RESUMEN

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.


Asunto(s)
Terapia de Protones , Humanos , Dosis de Radiación , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Sincrotrones , Método de Montecarlo , Dosificación Radioterapéutica
3.
Microorganisms ; 11(7)2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37512995

RESUMEN

The mechanism underlying antimicrobial activity of conjugated bile acids against strains of lactic acid bacilli is not well understood. The purpose of this study was to investigate two typical conjugated bile acids (glycochenodeoxycholic acid and taurochenodeoxycholic acid) for their mechanisms of antimicrobial activity against four strains of different species of lactic acid bacilli at the physiological pH of the small intestine of humans. The bacterial cell membrane integrity, transmembrane potential, and transmembrane pH gradient were examined using the fluorescence probes SYTO 9 plus propidium iodide, 3,3'-dipropylthiadicarbocyanine iodide, and 5(6)-carboxyfluorescein diacetate N-succinimidyl ester, respectively. The intracellular ATP levels were measured by the firefly luciferase-based bioluminescence method. It was found that the antimicrobial activity of conjugated bile acids against the strains of lactic acid bacilli is strain-specific, and glycochenodeoxycholic acid showed significantly greater antimicrobial activity than taurochenodeoxycholic acid against the strains of lactic acid bacilli. The conjugated bile acids inhibited the growth of strains of lactic acid bacilli by disrupting membrane integrity, dissipating transmembrane potential, reducing the transmembrane pH gradient, and depleting intracellular ATP. In conclusion, the antimicrobial activity of conjugated bile acids against lactic acid bacilli is a multifactorial phenomenon. This study will provide valuable information for developing strategies to improve the ability of lactic acid bacilli to tolerate bile in vivo.

4.
Fa Yi Xue Za Zhi ; 38(4): 452-458, 2022 Aug 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-36426687

RESUMEN

OBJECTIVES: To reconstruct the cases of acceleration craniocerebral injury caused by blunt in forensic cases by finite element method (FEM), and to study the biomechanical mechanism and quantitative evaluation method of blunt craniocerebral injury. METHODS: Based on the established and validated finite element head model of Chinese people, the finite element model of common injury tool was established with reference to practical cases in the forensic identification, and the blunt craniocerebral injury cases were reconstructed by simulation software. The cases were evaluated quantitatively by analyzing the biomechanical parameters such as intracranial pressure, von Mises stress and the maximum principal strain of brain tissue. RESULTS: In case 1, when the left temporal parietal was hit with a round wooden stick for the first time, the maximum intracranial pressure was 359 kPa; the maximum von Mises stress of brain tissue was 3.03 kPa at the left temporal parietal; the maximum principal strain of brain tissue was 0.016 at the left temporal parietal. When the right temporal was hit with a square wooden stick for the second time, the maximum intracranial pressure was 890 kPa; the maximum von Mises stress of brain tissue was 14.79 kPa at the bottom of right temporal lobe; the maximum principal strain of brain tissue was 0.103 at the bottom of the right temporal lobe. The linear fractures occurred at the right temporal parietal skull and the right middle cranial fossa. In case 2, when the forehead and left temporal parietal were hit with a round wooden stick, the maximum intracranial pressure was 370 kPa and 1 241 kPa respectively, the maximum von Mises stress of brain tissue was 3.66 kPa and 26.73 kPa respectively at the frontal lobe and left temporal parietal lobe, and the maximum principal strain of brain tissue was 0.021 and 0.116 respectively at the frontal lobe and left temporal parietal lobe. The linear fracture occurred at the left posterior skull of the coronary suture. The damage evaluation indicators of the simulation results of the two cases exceeded their damage threshold, and the predicted craniocerebral injury sites and fractures were basically consistent with the results of the autopsy. CONCLUSIONS: The FEM can quantitatively evaluate the degree of blunt craniocerebral injury. The FEM combined with traditional method will become a powerful tool in forensic craniocerebral injury identification and will also become an effective means to realize the visualization of forensic evidence in court.


Asunto(s)
Traumatismos Craneocerebrales , Heridas no Penetrantes , Humanos , Análisis de Elementos Finitos , Fenómenos Biomecánicos , Cabeza
5.
Adv Sci (Weinh) ; 9(22): e2201166, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35652264

RESUMEN

Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/ß-catenin, TGF-ß, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy. Among these candidate molecules, phenyl-2-pyrimidinyl ketone 4-allyl-3-amino selenourea (CU27) is chosen for further identification because it proves to be the most effective compound over others on CSC inhibition. Through ingenuity pathway analysis, it is shown CU27 may inhibit CSC through a well-known stemness-related transcription factor c-Myc. Gene set enrichment analysis, dual-luciferase reporter assays, expression levels of typical c-Myc targets, molecular docking, surface plasmon resonance, immunoprecipitation, and chromatin immunoprecipitation are conducted. These results together suggest CU27 binds c-Myc bHLH/LZ domains, inhibits c-Myc-Max complex formation, and prevents its occupancy on target gene promoters. In mouse models, CU27 significantly sensitizes sorafenib-resistant tumor to sorafenib, reduces the primary tumor size, and inhibits CSC generation, showing a dramatic anti-metastasis potential. Taken together, CU27 exerts inhibitory effects on CSC and CSC-associated traits in hepatocellular carcinoma (HCC) via c-Myc transcription activity inhibition. CU27 may be a promising therapeutic to treat sorafenib-resistant HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Selenio , Selenio , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Detección Precoz del Cáncer , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Ratones , Simulación del Acoplamiento Molecular , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Selenio/metabolismo , Selenio/farmacología , Compuestos de Selenio/metabolismo , Compuestos de Selenio/farmacología , Sorafenib/metabolismo , Sorafenib/farmacología
6.
Fa Yi Xue Za Zhi ; 38(5): 573-578, 2022 Oct 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-36727171

RESUMEN

OBJECTIVES: To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification. METHODS: Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model. RESULTS: A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination (R2) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively. CONCLUSIONS: The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.


Asunto(s)
Redes Neurales de la Computación , Heridas no Penetrantes , Masculino , Humanos , Femenino , Programas Informáticos , Medicina Legal
7.
Zhonghua Nan Ke Xue ; 27(9): 771-779, 2021 Sep.
Artículo en Chino | MEDLINE | ID: mdl-34914251

RESUMEN

OBJECTIVE: To screen differentially expressed miRNAs in the testis of male rats exposed to cigarette smoke (CS) and identify the early molecular markers of CS-induced apoptosis of testicular cells. METHODS: We randomly divided 200 SPF male SD rats into blank control and low-dose (10 non-filter cigarettes/d), medium-dose (20 non-filter cigarettes/d) and high-dose (30 non-filter cigarettes/d) CS exposure groups. After 2, 4, 6, 8 and 12 weeks of CS exposure, we observed the histopathological changes of the testis by HE staining, detected the apoptosis of the testicular cells by TUNEL, and determined the expressions of caspase-3 and caspase-9 in the testis tissue by immunohistochemistry, RT-PCR and Western blot. Based on the laboratory results, we selected 4 testicular samples from the 12-week high-dose group and another 4 from the control for miRNA microarray-based screening, bioinformatics analysis, and verification of differentially expressed miRNAs in all the animals by RT-PCR. RESULTS: Compared with the controls, the CS-exposed rats showed dose- and time-dependent increase in the atrophy of the testis and significantly increased number of apoptotic testis cells from the 6th week of exposure (P < 0.05), with dramatically up-regulated expressions of caspase-3 (P < 0.01) and caspase-9 protein and mRNA (P < 0.05) in the testis tissue. Microarray-based screening and RT-PCR revealed 5 differentially expressed miRNAs in the testis of the CS-exposed rats, of which miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 were down-regulated, and miR-155-5p up-regulated, and the target genes of the differentially expressed miRNAs positively regulated the apoptosis of the testicular cells. CONCLUSIONS: The differentially expressed miRNAs miR-155-5p, miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 regulate CS-induced apoptosis of testicular cells, and may become biomarkers for early diagnosis and prognosis of CS-induced spermatogenesis obstruction.《.


Asunto(s)
MicroARNs , Testículo , Animales , Masculino , MicroARNs/genética , ARN Mensajero , Ratas , Ratas Sprague-Dawley , Fumar
8.
Cladistics ; 37(6): 717-727, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34841589

RESUMEN

The polygrammoids (Polypodiaceae) are the most species-rich and diversified epiphytic fern lineages, and hold an important role to understand the deep diverging events and rapid adaptation to changing environments in the plant tree of life. Despite progress in the phylogeny of this group of ferns in previous multilocus phylogenetic studies, uncertainty remains especially in backbone relationships among closely related clades, and the phylogenetic placement of recalcitrant species or lineages. Here, we investigated the deep phylogenetic relationships within Polypodiaceae by sampling all major lineages and using 81 plastid genomes (plastomes), of which 70 plastomes were newly sequenced with high-throughput sequencing technology. Based on parsimony, maximum-likelihood, Bayesian and multispecies coalescent analyses of genome skimming data, we achieved a better resolution of the backbone phylogeny of Polypodiaceae. Using simulated data matrices, we detected that potential phylogenetic artefacts, such as long-branch attraction and insufficient taxonomic sampling, may have a confounding impact on the incongruence of phylogenetic inferences. Furthermore, our phylogenetic analyses offer greater resolution than previous multilocus studies, providing a robust framework for future phylogenetic implications on the subfamilial taxonomy of Polypodiaceae. Our phylogenomic study not only demonstrates the advantage of a character-rich plastome dataset for resolving the recalcitrant lineages that have undergone rapid radiation, but also sheds new light on integrative explorations understanding the evolutionary history of large fern groups in the genomic era.


Asunto(s)
Plastidios/genética , Polypodiaceae/genética , Genoma de Plastidios , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Plastidios/clasificación , Polypodiaceae/clasificación
9.
Artículo en Inglés | MEDLINE | ID: mdl-34257681

RESUMEN

BACKGROUND: Depression is a common mental disease that lacks effective therapeutic drugs with good curative effects and few adverse reactions. Traditional Chinese medicine (TCM) has the advantages of multiple components, multiple channels, and fewer adverse reactions in the treatment of depression. Although Xingpi Jieyu Decoction (XPJYD) demonstrates a good therapeutic effect on depression, the pharmacological mechanism underlying its antidepressant effect is still unclear. METHODS: We used a network pharmacology strategy, including the construction and analysis of a complex drug-disease network, to explore the complex mechanism of XPJYD treatment of depression. In addition, molecular docking technology was used to preliminarily study the binding ability of the potential active components and core therapeutic targets of XPJYD. RESULTS: The network pharmacology results showed 42 targets of XPJYD that are involved in depression. PPI network analysis demonstrated that the top 10 core targets were AKT1, VEGFA, MAPK8, FOS, ESR1, NR3C1, IL6, HIF1A, NOS3, and AR. The molecular docking results showed that the binding energies of beta sitosterol with AR, FOS, AKT1, VEGFA, NR3C1, and NOS3 were less than -7.0 kcal·mol-1, indicating a good docking effect. The GO enrichment analysis results showed that the XPJYD antidepression mechanism mainly involves the following biological processes such as apoptotic signaling pathway, cellular response to lipid, inflammatory response, and others. The KEGG analysis results indicated that XPJYD may regulate 13 pathways such as PI3K-Akt signaling pathway and estrogen signaling pathway in the treatment of depression. CONCLUSIONS: This study reflects the characteristics of the mechanism of action by which XPJYD treats depression, which includes multiple components, multiple targets, and multiple pathways, and provides a biological basis for further verification and a novel perspective for drug discovery in depression.

10.
Nat Commun ; 12(1): 60, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397900

RESUMEN

Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.


Asunto(s)
Nanoporos , Análisis de Secuencia de ADN , Línea Celular , Cromosomas Humanos/genética , Genoma Humano , Humanos , Retinoblastoma/genética , Programas Informáticos
11.
FEBS Lett ; 595(1): 68-84, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33040326

RESUMEN

Hepatocellular carcinoma (HCC) is the most common liver cancer with high mortality. Here, we found that hnRNPU is overexpressed in HCC tissues and is correlated with the poor prognosis of HCC patients. Besides, hnRNPU is of high significance in regulating the proliferation, apoptosis, self-renewal, and tumorigenic potential of HCC cells. Mechanismly, c-Myc regulates hnRNPU expression at the transcriptional level, and meanwhile, hnRNPU stabilizes the mRNA of c-MYC. We found that the hnRNPU and c-Myc regulatory loop exerts a synergistic effect on the proliferation and self-renewal of HCC, and promotes the HCC progression. Taken together, hnRNPU functions as a novel transcriptional target of c-Myc and promotes HCC progression, which may become a promising target for the treatment of c-Myc-driven HCC.


Asunto(s)
Apoptosis/fisiología , Carcinoma Hepatocelular/patología , Ribonucleoproteína Heterogénea-Nuclear Grupo U/fisiología , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transcripción Genética , Animales , Línea Celular Tumoral , Humanos , Ratones Endogámicos NOD , Ratones SCID , Ensayos Antitumor por Modelo de Xenoinjerto
12.
FEBS Open Bio ; 10(9): 1737-1747, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32662250

RESUMEN

Liver cancer stem cells (L-CSCs) are considered to be an important therapeutic target for hepatocellular carcinoma (HCC). This study provides a new in vitro long-term culture model for a specific subpopulation of L-CSCs enriched by cell surface markers. We combined CD13, CD133 and EpCAM to selectively enrich L-CSCs, which we then cultured in modified chemically defined medium. The enriched L-CSCs exhibited enhanced proliferation, self-renewal and long-term clonal maintenance ability as compared with non-CSCs. Compared with wild-type hepatocellular carcinoma, the expression of stemness surface markers, oncogenes, drug resistance and tumorigenicity in enriched L-CSCs was significantly increased. In summary, the subpopulation of L-CSCs still maintains cancer stem cell-related phenotypes after 14 days of culture.


Asunto(s)
Antígeno AC133/metabolismo , Biomarcadores de Tumor/metabolismo , Antígenos CD13/metabolismo , Carcinoma Hepatocelular/patología , Molécula de Adhesión Celular Epitelial/metabolismo , Neoplasias Hepáticas/patología , Células Madre Neoplásicas/patología , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/metabolismo , Células Tumorales Cultivadas
13.
Cell Death Dis ; 10(6): 453, 2019 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-31186405

RESUMEN

Hepatocellular carcinoma (HCC) has a high mortality rate due to the lack of effective treatments and drugs. Arsenic trioxide (ATO), which has been proved to successfully treat acute promyelocytic leukemia (APL), was recently reported to show therapeutic potential in solid tumors including HCC. However, its anticancer mechanisms in HCC still need further investigation. In this study, we demonstrated that ATO inhibits tumorigenesis and distant metastasis in mouse models, corresponding with a prolonged mice survival time. Also, ATO was found to significantly decrease the cancer stem cell (CSC)-associated traits. Minichromosome maintenance protein (MCM) 7 was further identified to be a potential target suppressed dramatically by ATO, of which protein expression is increased in patients and significantly correlated with tumor size, cellular differentiation, portal venous emboli, and poor patient survival. Moreover, MCM7 knockdown recapitulates the effects of ATO on CSCs and metastasis, while ectopic expression of MCM7 abolishes them. Mechanistically, our results suggested that ATO suppresses MCM7 transcription by targeting serum response factor (SRF)/MCM7 complex, which functions as an important transcriptional regulator modulating MCM7 expression. Taken together, our findings highlight the importance of ATO in the treatment of solid tumors. The identification of SRF/MCM7 complex as a target of ATO provides new insights into ATO's mechanism, which may benefit the appropriate use of this agent in the treatment of HCC.


Asunto(s)
Antineoplásicos/farmacología , Trióxido de Arsénico/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Componente 7 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Células Madre Neoplásicas/metabolismo , Factor de Respuesta Sérica/metabolismo , Animales , Antineoplásicos/uso terapéutico , Trióxido de Arsénico/uso terapéutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Componente 7 del Complejo de Mantenimiento de Minicromosoma/genética , Células Madre Neoplásicas/efectos de los fármacos , Pronóstico , Factor de Respuesta Sérica/antagonistas & inhibidores , Factor de Respuesta Sérica/genética , Trasplante Heterólogo
14.
Zhongguo Zhong Yao Za Zhi ; 43(13): 2784-2788, 2018 Jul.
Artículo en Chino | MEDLINE | ID: mdl-30111032

RESUMEN

To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (P<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (P<0.05), and the ratio of Bcl-2/Bax was decreased (P<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (P<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Animales , Proliferación Celular , Medicamentos Herbarios Chinos , Humanos , Células MCF-7 , Ratas , Proteína X Asociada a bcl-2
15.
Int J Clin Exp Pathol ; 11(9): 4684-4694, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31949869

RESUMEN

To investigate the relationship between a GCKR rs780094 polymorphism and lipid profiles in the Xinjiang Uygur population in China. 980 type 2 diabetes mellitus (T2DM) patients, 1017 hyperuricemia (HUA) and 1185 healthy controls were included in this study. After genotyping of rs780094 by Sequenom Mass ARRAY system, chi-square test and logistic regression analysis were used for association analysis as well as a genotype-phenotype analysis. We found that the serum concentration of TC (P<0.001) was significantly higher and HDL-C (P<0.001) was lower in T2DM than in control participants. Subjects with HUA had a significantly higher TG (P=0.003) and lower HDL-C (P<0.001) than control participants. Additionally, under the recessive model, rs780094 was shown to be associated with the risk of HUA (P=0.015, OR=1.311), particularly in males (P=0.047, OR=1.330). Subsequent interaction analysis between rs780094 and lipid parameters showed that the TG level was positively correlated with HUA in the rs780094- AA+AG carriers (P=0.005). The TC concentrations showed to be associated with T2DM in the rs780094- AA+AG carriers (P<0.001). The association between lipid parameters and gender showed that significantly higher TG levels (P<0.001) and lower HDL-C levels (P<0.001) were observed in female HUA. Higher LDL-C levels were found in male HUA (P=0.015). Moreover, statistically higher TC levels and lower HDL-C levels were found both in male and female T2DM cases (TC: male: P<0.001, female: P=0.014. HDL-C: male: P<0.001, female: P<0.001.).To conclude, our results demonstrated that different genotypes of rs780094 had different effects on blood lipids in HUA and T2DM patients in a Uygur population. Gender was also one of the factors influencing blood lipid levels.

16.
Mol Med Rep ; 16(6): 8589-8594, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28990107

RESUMEN

Bone marrow stromal cells (BMSCs) can differentiate into osteoblasts. The present study investigated the osteogenic effects of estradiol, as well as the role of the c­Jun N­terminal kinase (JNK) signaling pathway in promoting estradiol­enhanced osteogenesis of rat (r)BMSCs. rBMSCs were treated for 7 days with or without estradiol and further treated with or without the JNK­specific inhibitor SP600125. The role of estrogen during rBMSC osteogenesis was evaluated by alkaline phosphatase activity and mineralized nodule formation using the Gomori method and Alizarin red S staining, respectively. Subsequently, the mRNA expression levels of transforming growth factor-ß1 (TGF­ß1) and core­binding factor α1 (Cbfα1) were evaluated by reverse transcription­quantitative polymerase chain reaction, and TGF­ß1, Cbfα1 and phosphorylated (p)­JNK protein expression was detected by western blotting. All groups treated with SP600125 expressed low levels of TGF­ß1 and Cbfα1 mRNA and protein, and low p­JNK protein expression. Compared with the control cells, rBMSCs cultured with estradiol exhibited a significant upregulation in the expression levels of osteogenic genes and proteins. The present study demonstrated that estradiol enhanced osteogenic differentiation of rBMSCs and that the JNK signaling pathway was involved in this process, providing insights into the molecular mechanisms involved in rBMSC osteogenesis upon estradiol stimulation.


Asunto(s)
Estradiol/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/enzimología , Osteogénesis/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Biomarcadores/metabolismo , Forma de la Célula/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Citometría de Flujo , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Minerales/metabolismo , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo
17.
Anal Biochem ; 537: 50-55, 2017 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-28882747

RESUMEN

A novel method, real-time reverse transcription PCR (real-time RT-PCR) coupled with probe-melting curve analysis, has been established to detect two kinds of samples within one fluorescence channel. Besides a conventional TaqMan probe, this method employs another specially designed melting-probe with a 5' terminus modification which meets the same label with the same fluorescent group. By using an asymmetric PCR method, the melting-probe is able to detect an extra sample in the melting stage effectively while it almost has little influence on the amplification detection. Thus, this method allows the availability of united employment of both amplification stage and melting stage for detecting samples in one reaction. The further demonstration by simultaneous detection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in one channel as a model system is presented in this essay. The sensitivity of detection by real-time RT-PCR coupled with probe-melting analysis was proved to be equal to that detected by conventional real-time RT-PCR. Because real-time RT-PCR coupled with probe-melting analysis can double the detection throughputs within one fluorescence channel, it is expected to be a good solution for the problem of low-throughput in current real-time PCR.


Asunto(s)
ARN Viral/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Secuencia de Bases , Sondas de ADN/química , Sondas de ADN/metabolismo , VIH/genética , Hepacivirus/genética , Humanos , Transición de Fase , ARN Viral/genética , ARN Viral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
18.
Mitochondrial DNA B Resour ; 2(2): 455-456, 2017 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-33490456

RESUMEN

Coelastrum is a genus of green algae that belongs to the Scenedesmaceae family. There is little information available about this genus. A phylogenetic analysis of the ITS2 sequences showed that Coelastrum is a paraphyletic group. To better explore the phylogenetic status of this genus, we report the mitochondrial genome sequence of Coelastrum sp. F187 using next-generation sequencing technology. The complete mitochondrial genome is 52,888 bp in size and encodes 43 conventional mitochondrial genes, including 14 protein-coding genes (PCGs), 24 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. Most of the PCGs (12/14) and all tRNAs were located in the heavy chain and the light chain, respectively. The phylogenetic analysis based on the complete mitochondrial genome sequences indicated that Coelastrum is closely related to Pectinodesmus pectinatus. The sequenced complete mitochondrial genome of Coelastrum sp. F187 provides fundamental molecular data that will be useful for species identification, population genetics, and evolutionary relationships.

19.
Sci Rep ; 6: 34854, 2016 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-27708385

RESUMEN

Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked ß-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape.


Asunto(s)
Candida albicans/patogenicidad , Candidiasis/microbiología , Pared Celular/metabolismo , Inositol/química , Monoéster Fosfórico Hidrolasas/genética , Acilación , Animales , Candida albicans/genética , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Eliminación de Gen , Glicosilfosfatidilinositoles/metabolismo , Ratones , Monoéster Fosfórico Hidrolasas/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 41(4): 619-623, 2016 Feb.
Artículo en Chino | MEDLINE | ID: mdl-28871682

RESUMEN

Terminalia chebula Retz, known as the "king" of Mongolian and Tibetan medicines, is a drug for a wide range of diseases. The main chemical components of myrobalan include triterpene acid, galloyl glucose, anthraquinonoid. The modern pharmacological studies show that myrobalan has multiple biological activities, including antimicrobial, anti-inflammatory, antioxidation as well as anti-tumor. Based on domestic and foreign literatures in recent years, this paper gave a review on the advance of studies for pharmacological activity of T. chebula. and its active components, so as to provide a reference for the in-depth studies on the pharmacological action of myrobalan, and the further development and utilization of myrobalan.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Terminalia/química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Triterpenos/química , Triterpenos/farmacología
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