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1.
Pestic Biochem Physiol ; 204: 106059, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277375

RESUMO

Heat shock proteins (Hsps) are stress response proteins. In a previous study, host larval Hsp70s were identified as the structural proteins of virions of Heliothis virescens ascovirus 3h (HvAV-3h), an insect virus that mainly infects noctuid larvae. To investigate the response of hsp70s of healthy Mythimna separata, Spodoptera exigua, Spodoptera frugiperda, and Spodoptera litura larvae to various abiotic or entomopathogenic stresses, quantitative PCR was used to detect larval hsp70s expression patterns. Results showed distinct expression patterns of hsp70s in response to different abiotic stresses. Notably, Mshsp70 expression pattern resembled Slhsp70 under most treatments. In healthy larvae, no tissue tropism was observed concerning the relative expression of Mshsp70, Sfhsp70, and Slhsp70. After infection with HvAV-3h, the expression of hsp70s in all dissected tissues of all tested larval species increased. Significant differences were found in the fat bodies of M. separata, S. exigua, and S. litura as well as in the hemolymph of S. exigua and S. litura. Subsequent silencing of Slhsp70, resulted in a significant decrease in DNA replication levels of HvAV-3h in S. litura larvae at 24 and 72 h post RNA interference, indicating that Slhsp70 is necessary for DNA replication in HvAV-3h. These data can provide references for the studying on the stress response of noctuid larvae to different environmental factors.


Assuntos
Proteínas de Choque Térmico HSP70 , Larva , Estresse Fisiológico , Animais , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Larva/genética , Larva/metabolismo , Estresse Fisiológico/genética , Spodoptera/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Mariposas/genética , Ascoviridae/genética , Ascoviridae/metabolismo
2.
Clin Lab ; 68(5)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536067

RESUMO

BACKGROUND: Amniocentesis was performed on a pregnant woman with a deletion of exon 45 of the Duchenne Muscular Dystrophy (DMD) gene. METHODS: Fetal Xp21.1 (31944831-32030363) x 0 was found by chromosome microarray analysis (CMA), i.e., 0.086 Mb hemizygote deletion was detected in the Xp21.1 region of the fetal X chromosome, which contained exon 45 of the DMD gene. RESULTS: The results verified by MLPA were consistent with those of CMA, which indicated that CMA was accurate in a single exon deletion in this fetus. This case suggests that CMA may become an essential method for the prenatal diagnosis of a fetus with DMD gene deletion/duplication. CONCLUSIONS: It can routinely detect chromosome copy number variation and analyze DMD diseases caused by exon duplication or deletion, which is enormously significant for new DMD exon deletion or duplication.


Assuntos
Distrofia Muscular de Duchenne , Cromossomos , Variações do Número de Cópias de DNA , Distrofina/genética , Éxons/genética , Feminino , Feto , Deleção de Genes , Humanos , Análise em Microsséries , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Gravidez
3.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4609-4617, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164866

RESUMO

Saposhnikovia divaricata is a commonly used bulk medicinal plant. To explore the key enzyme genes and their expression in the biosynthesis of chromone and coumarin, the key active components, we carried out transcriptome sequencing(Illumina HiSeq) and bioinformatics analysis for the 1-year-old(S1) and 2-year-old(S2) plants of S. divaricata. A total of 40.8 Gb data was obtained. After the sequence assembly via Trinity, 110 732 transcripts and 86 233 unigenes were obtained, which were aligned and annotated with NR, Swiss-Prot, GO, KEGG, and PFAM. Daucus carota and S. divaricata had the highest sequence homology. KEGG pathway enrichment showed that the differentially expressed genes were mainly enriched in plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis pathways. A total of 27 differentially expressed unigenes, including 13 enzyme genes, were identified in the pathways related to the synthesis of active ingredients in S. divaricata. Compared with S1 plant, S2 plant showed up-regulated expression of PAL, BGL, C4H, 4CL, CYP98A, CSE, REF, and CCoAOMT and down-regulated expression of CHS, CAD, and COMT. HCT and POD had both up-regulated and down-regulated unigenes. Among them, PAL, C4H, 4CL, BGL, and CHS can be used as candidate genes for the synthesis of the active ingredients in S. divaricata. The four key enzyme genes were verified by RT-qPCR, which showed the results consistent with transcriptome sequencing. This study enriches the genetic information of S. divaricata and provides support for the identification of candidate genes in the biosynthesis of secondary metabolites.


Assuntos
Apiaceae , Transcriptoma , Apiaceae/genética , Cromonas , Cumarínicos , Flavonoides , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reguladores de Crescimento de Plantas
4.
J Pathol ; 251(4): 365-377, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32418203

RESUMO

The classification of the distinct group of mesenchymal neoplasms, first described as 'Xp11 translocation perivascular epithelioid cell tumor (PEComa)' and for which the term 'melanotic Xp11 neoplasm' or 'Xp11 neoplasm with melanocytic differentiation' has recently been proposed, remains challenging and controversial. We collected 27 melanotic Xp11 neoplasms, the largest series to date, for a comprehensive evaluation. Fourteen of the cases, together with eight alveolar soft part sarcomas (ASPS), nine conventional PEComas and a control group of seven normal tissues were submitted to RNA sequencing. Follow-up available in 22 patients showed 5-year overall survival and 5-year disease-free survival of 47.6 and 35.7%, respectively, which were similar to ASPS and significantly worse than conventional PEComa. Univariate analysis of location (occurring in the kidney versus not kidney), infiltrative growth pattern, nuclear pleomorphism, mitotic activity ≥2/50 high-power fields (HPF), necrosis and lymphovascular invasion were found to be associated with overall survival and/or disease-free survival. Multivariate analysis identified that location was the only factor found to independently correlate with disease-free survival. More importantly, RNA sequencing-based clustering analysis segregated melanotic Xp11 neoplasm and ASPS from other tumors, including conventional PEComa and Xp11 translocation renal cell carcinoma, and formed a compact cluster representative of the largely similar expression signature. Here we clearly define the true biologic nature of melanotic Xp11 neoplasms which are distinctive malignant mesenchymal tumors, rather than simply PEComa variants with occasionally unpredictable behavior. Meanwhile, melanotic Xp11 neoplasm and ASPS more likely represent phenotypic variants of the same entity, which is distinct from conventional PEComa and Xp11 translocation renal cell carcinoma. Based on these important findings, melanotic Xp11 neoplasm might be reclassified into a distinctive entity together with ASPS, independent from PEComa, in future revisions of the current WHO categories of tumors of soft tissue and bone for the improved reclassification. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Carcinoma de Células Renais/classificação , Neoplasias Renais/classificação , Neoplasias de Células Epitelioides Perivasculares/classificação , Sarcoma Alveolar de Partes Moles/classificação , Translocação Genética , Adolescente , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Análise por Conglomerados , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia , Sarcoma Alveolar de Partes Moles/genética , Sarcoma Alveolar de Partes Moles/patologia , Análise de Sequência de RNA , Análise de Sobrevida , Adulto Jovem
5.
Phys Rev Lett ; 125(26): 260603, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33449755

RESUMO

The famous Kibble-Zurek mechanism offers us a significant clue to study quantum phase transitions out of equilibrium. Here, we investigate an intriguing phenomenon of a spin-orbit coupled Bose-Einstein condensate by quenching the Raman coupling strength from a high-symmetry phase (nonmagnetic phase) to a low-symmetry phase (magnetic phase). When crossing the critical point, the fluctuation of momentum distribution leads to delayed bifurcation structures. Simultaneously, the domain information emerges in momentum space. Moreover, the universal scalings of spatiotemporal dynamics are extracted from the fluctuations and domains, which manifests homogeneous and inhomogeneous Kibble-Zurek power laws at different timescales. Our work demonstrates a paradigmatic study on the inhomogeneous Kibble-Zurek mechanism.

6.
Opt Express ; 27(5): 6089-6097, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876202

RESUMO

Sequential weak measurements of non-commuting observables are not only fundamentally interesting in terms of quantum measurement but also show potential in various applications. Previously reported methods, however, can only make limited sequential weak measurements experimentally. In this article, we propose the realization of sequential measurements of non-commuting Pauli observables and experimentally demonstrate for the first time the measurement of sequential weak values of three non-commuting Pauli observables using genuine single photons.

7.
Fish Shellfish Immunol ; 91: 275-283, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125663

RESUMO

Glycogen phosphorylase (GP, EC 2.4.1.1) catalyze the rate-limiting step in glycogenolysis in animals, forming glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Therefore, GP plays a crucial role in carbohydrate metabolism. In the present study, the full-length cDNA sequence of GP (LvGP) was cloned from shrimp, Litopenaeus vannamei. The obtained 3242-bp LvGP cDNA sequence included a 5'-terminal untranslated region (UTR) of 48 bp, an open reading frame (ORF) of 2559 bp encoding a polypeptide of 852 amino acids (aa) and a 3'-UTR of 635 bp. The predicted LvGP protein sequence contained a typical phosphorylase domain (113-829 aa) and shared 72%-97% identities with GP from other species. Phylogenetic analysis revealed that LvGP showed the closest relationship with GP from Marsupenaeus japonicus. Tissue expression profiles showed that LvGP existed in most examined tissues, with the most predominant expression in the brain, followed by the muscles and stomach. LvGP transcripts in hepatopancreas and hemocytes were up regulated after the WSSV challenge. Furthermore, the role of LvGP in shrimp defending against WSSV infection was investigated by RNA interference (RNAi). Our findings showed that WSSV proliferation and shrimp accumulative mortality increased significantly after LvGP RNAi (P < 0.01). The glycogen, glucose, and pyruvate content decreased in GP RNAi shrimp after WSSV injection, however, the lactate and ATP concentration enhanced. Moreover, lectin and anti-lipopolysaccharide factor2 (ALF2) were induced in LvGP silencing shrimp after WSSV infection, whereas the expression levels of crustin, ALF1 and ALF3 decreased. Our results suggested that the LvGP might play a crucial role in shrimp defending against WSSV infection by regulating metabolism and affecting the anti-infectious gene expression.


Assuntos
Regulação da Expressão Gênica/imunologia , Glicogênio Fosforilase/genética , Glicogênio Fosforilase/imunologia , Imunidade Inata/genética , Penaeidae/genética , Penaeidae/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Perfilação da Expressão Gênica , Glicogênio Fosforilase/química , Filogenia , Interferência de RNA , Regulação para Cima , Vírus da Síndrome da Mancha Branca 1/fisiologia
8.
Fish Shellfish Immunol ; 93: 144-152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326584

RESUMO

Phosphoglycerate kinase (EC 2.7.2.3, PGK) catalyses the reversible transfer of a phosphate group from 1,3-diphosphoglyceric acid and ADP to produce 3-phosphoglyceric acid and ATP, which represents the initial production of ATP during glycolysis; therefore, PGK is a key enzyme in the energy metabolism. To study the role of PGK in the resistance to WSSV infection in shrimp, the full-length cDNA of the PGK gene (LvPGK) from Litopenaeus vannamei was obtained by using homology cloning and RACE amplification. The tissue distribution of LvPGK and its expression changes in the main immune tissues after WSSV stimulation were obtained by quantitative real-time PCR. Furthermore, RNA interference (RNAi) was used to study the role of LvPGK in shrimp defending against WSSV infection. The results showed that the full-length cDNA sequence of LvPGK was 1855 bp, contained a 1248 bp open reading frame (ORF) encoding 415 amino acids, and included a conserved PGK domain. LvPGK presented ubiquitous expression in most examined tissues, with the most predominant expression in the muscle and the weakest expression in the intestine. LvPGK transcripts could be induced in the hemocytes and hepatopancreas by injection with WSSV. Both the replication of WSSV and the shrimp cumulative mortality decreased significantly after LvPGK knockdown (P < 0.01). After challenging LvPGK RNAi shrimp with WSSV, the concentration of glucose in the hepatopancreas and muscle tissue did not show significant change; however, the content of pyruvate and lactate decreased significantly (P < 0.05). Moreover, significant decreases in the expression levels of crustin, ALF1, ALF2 and ALF3 were also detected. The results suggested that LvPGK might be involved in WSSV replication by increasing host aerobic and anaerobic metabolism.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Penaeidae/genética , Penaeidae/imunologia , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Perfilação da Expressão Gênica , Penaeidae/enzimologia , Fosfoglicerato Quinase/química , Filogenia , Alinhamento de Sequência , Vírus da Síndrome da Mancha Branca 1/fisiologia
9.
J Comput Assist Tomogr ; 43(2): 235-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30475249

RESUMO

OBJECTIVE: To compare the diagnostic performance of standard and ultrahigh b-value Diffusion-weighted Imaging (DWI) using volumetric histogram analysis in differentiating transition zone (TZ) cancer from benign prostatic hyperplasia (BPH). METHODS: 57 TZ cancer and 61 BPH patients received standard (1000 s/mm) and ultrahigh b-value (2000 s/mm) DWI. The diagnostic ability of ADC histogram parameters derived from two DWI for differentiating TZ cancer from BPH was determined by receiver operating characteristic curve. RESULTS: Median, minimum, the 10th, 25th percentile ADC in both ADC1000 and ADC2000 and skewness in ADC2000 had significant differences between TZ cancer and BPH (for all, P < 0.05).The 10th percentile ADC showed highest area under the ROC curve (AUC) in both ADC1000 and ADC2000.The 10th percentile ADC of ADC2000 showed significantly higher AUC than did ADC1000 (P = 0.0385). CONCLUSIONS: The 10th percentile ADC obtained from ultrahigh b-value DWI performed better for differentiating TZ cancer from BPH.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Hiperplasia Prostática/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes
10.
Reprod Fertil Dev ; 30(9): 1161-1168, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29505743

RESUMO

The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene on the Y chromosome have not been completely elucidated, due, in part, to difficulties in gene targeting analysis of the Y chromosome. The zinc finger protein, Y-linked (ZFY) gene was first proposed to be a sex determination factor, although its function in spermatogenesis has recently been elucidated. Nevertheless, ZFY gene targeting analysis has not been performed to date. In the present study, RNA interference (RNAi) was used to generate ZFY-interrupted Hu sheep by injecting short hairpin RNA (shRNA) into round spermatids. The resulting spermatozoa exhibited abnormal sperm morphology, including spermatozoa without tails and others with head and tail abnormalities. Quantitative real-time polymerase chain reaction analysis showed that ZFY mRNA expression was decreased significantly in Hu sheep with interrupted ZFY compared with wild-type Hu sheep. The sex ratio of lambs also exhibited a bias towards females. Together, the experimental strategy and findings of the present study reveal that ZFY also functions in spermatogenesis in Hu sheep and facilitate the use of RNAi in the control of sex in Hu sheep.


Assuntos
Fatores de Transcrição Kruppel-Like/genética , Análise para Determinação do Sexo/métodos , Espermatogênese/genética , Cromossomo Y , Dedos de Zinco/genética , Animais , Forma Celular/genética , Masculino , Interferência de RNA , Razão de Masculinidade , Ovinos , Espermatozoides/citologia
11.
Zhongguo Zhong Yao Za Zhi ; 43(16): 3391-3396, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30200746

RESUMO

Clinical characteristics of Yinhua Miyanling Pian user group were analyzed based on real world hospital information system (HIS)database. The information was collected from the HIS in sixteen hospitals of grade Ⅲ-A. Normalizing the data and descriptive analysis was performed. Among the 5 312 cases, female patients(63.67%) were more than male patients (36.33%). The median age was 49 years old. The age of 18-65 accounted for 74.52%.The patient was admitted to the hospital's department of obstetrics and gynecology(28.71%) and urology(28.43%). The median single dose is 2 g, accounted for 49.55%. The median daily dose is 6 g. 88.80% of patients were treated for less than 7 d. The median hospitalization were 12 d, most were 7-14 d accounted for 41.70%. Most hospitalization expenses payment by medicare, accounted for 80.22%. The median hospitalization expenses was 12 211.47 RMB. Most patients with benign tumor(27.36%) and malignant tumor(15.56%), next is the obstruction of urinary tract(15.49%) and urinary calculi(10.52%). The most common syndromes were damp heat syndrome(32.46%), liver and kidney deficiency syndrome(15.33%) and splenasthenic fluid-retention syndrome(15.01%). Clinical use is combined with antibiotics, as well as traditional Chinese medicine heat clearing agents, tonic drugs and so on. Finally, 44.22% were cured and 51.05% were better. Most of the drug users were adults, and mostly were female. Most with the tumor, urinary tract obstruction or stones. TCM syndrome is mainly characterized by dampness and heat, deficiency of liver and kidney, and dampness of spleen. In clinical practice, it was mainly combined with Western medicines, and Chinese medicines were also a-vailable. And most are combined with antibiotics.The medication basically conforms to the drug instruction. Based on the results of the real world HIS,Yinhua Miyanling Pian could provide theidea and reference for regulating the medication in adolescent patients.


Assuntos
Medicina Tradicional Chinesa , Neoplasias/terapia , Doenças Urológicas/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Síndrome , Adulto Jovem
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 37(2): 232-236, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30650279

RESUMO

Objective To observe the effect of Modified Leweiyin Recipe (MLR) on nuclear factor kappa B (NF-κB) and crosstalk between signal transducers and activators of transcription 3 (STAT3) in SGC-7901 human gastric cancer cells. Methods SGC-7901 human gastric cancer cell strain was taken as subjects. The vectors of NF-κB (ReIA/p65)-PECFP and STAT3-PEYFP were constructed and transfected in SGC-7901 human gastric cancer cells. Cells were then intervened by MLR after stimulated by LPS. The crosstalk between NF-κB and STAT3 in cells was detected using fluorescence resonance energy transfer and co-immunoprecipitation. Results After LPS stimulation, the crosstalk between NF-κB and STAT3 was enhanced. But it was significantly weakened after MLR intervention. Conclusion MLR could treat precancerous lesions of gastric cancer and prevent the occurrence of gastric cancer possibly by blocking the crosstalk between NF-κB and STAT3.


Assuntos
Medicamentos de Ervas Chinesas , NF-kappa B , Fator de Transcrição STAT3 , Neoplasias Gástricas , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/farmacologia , Humanos , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico
13.
J Assist Reprod Genet ; 32(1): 107-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25374395

RESUMO

PURPOSE: Patients with a karyotype of 45,X (monosomy X) normally display a female phenotype. However, in some rare cases, monosomy X is associated with maleness. Here we describe a case of a male with a 45,X karyotype and primary infertility, which prompted molecular investigation of the sex-determination gene SRY. METHODS: Karyotyping was performed by GTG-banded chromosome analysis. The presence and location of SRY was investigated using PCR and FISH, respectively. RESULTS: PCR confirmed the presence of the SRY gene while FISH analysis demonstrated its location on the p arm of chromosome 13. These findings demonstrate that autosomal retention of SRY can be sub-microscopic and emphasize the importance of PCR and FISH in the genetic workup of the monosomic X male.


Assuntos
Cromossomos Humanos Par 13/genética , Infertilidade/genética , Proteína da Região Y Determinante do Sexo/genética , Translocação Genética/genética , Síndrome de Turner/genética , Azoospermia/genética , Azoospermia/patologia , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Infertilidade/patologia , Cariotipagem , Masculino , Análise para Determinação do Sexo , Síndrome de Turner/patologia
14.
Angew Chem Int Ed Engl ; 53(26): 6645-9, 2014 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-24839200

RESUMO

A novel rhodium(II)-catalyzed tandem cycloisomerization of methylenecyclopropanes (MCPs) with N-sulfonyl 1,2,3-triazoles is disclosed. The reaction produces a series of highly functionalized polycyclic N heterocycles via a rhodium imino carbene intermediate. A distinct feature of this divergent synthesis is that different types of substrates control the reaction pathways. Moreover, several interesting transformations of these products to construct diazabicyclo[3.2.1]octane derivatives are also reported.

15.
Front Vet Sci ; 11: 1455338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39280835

RESUMO

Understanding the differences in ubiquitination-modified proteins between Duroc pigs and Tibetan fragrant pigs is crucial for comprehending the growth and development of their skeletal muscles. In this study, skeletal muscle samples from 30-day-old Duroc pigs and Tibetan fragrant pigs were collected. Using ubiquitination 4D-Label free quantitative proteomics, we analyzed and identified ubiquitination-modified peptides, screening out 109 differentially expressed ubiquitination-modified peptides. Further enrichment analysis was conducted on the proteins associated with these differential peptides. GO analysis results indicated that the differential genes were primarily enriched in processes such as regulation of protein transport, motor activity, myosin complex, and actin cytoskeleton. KEGG pathway analysis revealed significant enrichment in pathways such as Glycolysis/Gluconeogenesis and Hippo signaling pathway. The differentially expressed key ubiquitinated proteins, including MYL1, MYH3, TNNC2, TNNI1, MYLPF, MYH1, MYH7, TNNT2, TTN, and TNNC1, were further identified. Our analysis demonstrates that these genes play significant roles in skeletal muscle protein synthesis and degradation, providing new insights into the molecular mechanisms of muscle development in Duroc pigs and Tibetan fragrant pigs, and offering theoretical support for breeding improvements in the swine industry.

16.
Molecules ; 17(6): 6832-9, 2012 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-22669039

RESUMO

Celastrol, a quinone methide triterpene isolated from Tripterygium wilfordii Hook F., has various biochemical and pharmacological activities, and is now being developed as a promising anti-tumor agent. Inhibitory activity of compounds towards UDP-glucuronosyltransferase (UGT) is an important cause of clinical drug-drug interactions and herb-drug interactions. The aim of the present study is to investigate the inhibition of celastrol towards two important UDP-glucuronosyltransferase (UGT) isoforms UGT1A6 and UGT2B7. Recombinant UGT isoforms and non-specific substrate 4-methylumbelliferone (4-MU) were used. The results showed that celastrol strongly inhibited the UGT1A6 and 2B7-mediated 4-MU glucuronidation reaction, with 0.9 ± 0.1% and 1.8 ± 0.2% residual 4-MU glucuronidation activity at 100 µM of celastrol, respectively. Furthermore, inhibition kinetic study (Dixon plot and Lineweaver-Burk plot) demonstrated that celastrol noncompetitively inhibited the UGT1A1-mediated 4-MU glucuronidation, and competitively inhibited UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 0.49 µM and 0.045 µM for UGT1A6 and UGT2B7, respectively. At the therapeutic concentration of celastrol for anti-tumor utilization, the possibility of celastrol-drug interaction and celastrol-containing herbs-drug interaction were strongly indicated. However, given the complicated nature of herbs, these results should be viewed with more caution.


Assuntos
Inibidores Enzimáticos/farmacologia , Glucuronosiltransferase/antagonistas & inibidores , Interações Ervas-Drogas , Tripterygium/química , Triterpenos/farmacologia , Inibidores Enzimáticos/química , Humanos , Himecromona/análogos & derivados , Himecromona/metabolismo , Cinética , Triterpenos Pentacíclicos , Triterpenos/química
17.
Molecules ; 17(5): 4896-903, 2012 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-22543504

RESUMO

Gossypol, the polyphenolic constituent isolated from cottonseeds, has been used as a male antifertility drug for a long time, and has been demonstrated to exhibit excellent anti-tumor activity towards multiple cancer types. The toxic effects of gossypol limit its clinical utilization, and enzyme inhibition is an important facet of this. In the present study, in vitro human liver microsomal incubation system supplemented with UDPGA was used to investigate the inhibition of gossypol towards UGT1A1, 1A9 and 2B7-mediated metabolism of xenobiotics and endogenous substances. Estradiol, the probe substrate of UGT1A1, was selected as representative endogenous substance. Propofol (a probe substrate of UGT1A9) and 3'-azido-3'-deoxythimidine (AZT, a probe substrate of UGT2B7) were employed as representative xenobiotics. The results showed that gossypol noncompetitively inhibits UGT-mediated estradiol-3-glucuronidation and propofol O-glucuronidation, and the inhibition kinetic parameters (K(i)) were calculated to be 34.2 and 16.4 µM, respectively. Gossypol was demonstrated to exhibit competitive inhibition towards UGT-mediated AZT glucuronidation, and the inhibition kinetic parameter (K(i)) was determined to be 14.0 µM. All these results indicated that gossypol might induce metabolic disorders of endogenous substances and alteration of metabolic behaviour of co-administered xenobiotics through inhibition of UGTs' activity.


Assuntos
Inibidores Enzimáticos/farmacologia , Glucuronosiltransferase/antagonistas & inibidores , Gossipol/farmacologia , Microssomos Hepáticos/enzimologia , Estradiol/metabolismo , Glucuronídeos/metabolismo , Glucuronosiltransferase/metabolismo , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Cinética , Microssomos Hepáticos/efeitos dos fármacos , Propofol/metabolismo , Especificidade por Substrato , Uridina Difosfato Ácido Glucurônico/metabolismo , Xenobióticos/metabolismo , Zidovudina/metabolismo
18.
Pharmazie ; 67(8): 715-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22957438

RESUMO

The aim of the present study was to investigate the inhibitory potential of glimepiride towards important UDP-glucuronosyltransferase (UGT) isoforms in human liver, which play a key role in the elimination of drugs. The recombinant UGT enzymes were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 microM of glimepiride inhibited UGT1A1, UGT1A3, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 by 54.7%, 43.1%, 100%, 70.5%, 32.7 and 37.2%, respectively. Given that glimepiride exhibited strong inhibition towards UGT1A6, further inhibitory kinetic behaviour was determined. Glimepiride exerted concentration-dependent inhibition towards UGT1A6. Both Dixon and Lineweaver-Burk plots demonstrated that inhibition of UGT1A6 was best fit for noncompetitive inhibition type, and the inhibition kinetic parameter (Ki) was calculated to be 59.8 microM. Given that UGT1A6 plays a key role in detoxification of many drugs, more attention should be given when glimepiride was co-administered with the drugs mainly undergoing UGT1A6-mediated metabolism.


Assuntos
Glucuronosiltransferase/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Fígado/enzimologia , Compostos de Sulfonilureia/farmacologia , Humanos , Himecromona/análogos & derivados , Himecromona/metabolismo , Isoenzimas/antagonistas & inibidores , Cinética , Fígado/efeitos dos fármacos , Especificidade por Substrato
19.
Free Radic Biol Med ; 184: 208-217, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367342

RESUMO

Acute lung injury (ALI) is the leading cause of bacterial sepsis-related death because of disrupted pulmonary endothelial barrier, resulting in protein-rich pulmonary oedema, an influx of pro-inflammatory cells and refractory hypoxaemia. Several studies have reported that C3a levels are significantly higher in organs with sepsis and their peripheral organs and are closely associated with organ dysfunction and poor prognosis in sepsis. However, the role of the C3a complement in sepsis ALI remains unclear. Therefore, this study aimed to investigate the important role and mechanism of C3a in preventing the occurrence of pyroptosis (a pro-inflammatory form of cell death) to protect the lung endothelial cells (ECs) in sepsis-induced ALI. A septic mouse model was established with cecal ligation and puncture (CLP), which demonstrated that C3a mediated EC pyroptosis through its C3aR receptor. Furthermore, inhibition of the C3a-C3aR axis could block both NLRP3/caspase-1 and caspase-11 pathways, thus preventing pulmonary EC from pyroptosis. These results indicate that inhibition of the C3A-C3AR complement axis can inhibit pulmonary vascular EC pyroptosis, a potential target for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Sepse , Lesão Pulmonar Aguda/metabolismo , Animais , Caspases/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Piroptose , Sepse/complicações , Sepse/metabolismo
20.
Asian J Androl ; 23(2): 188-196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33159025

RESUMO

Transforming growth factor-ß1 (TGF-ß1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-ß1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-ß1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-ß1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-ß1 contributes to the progression of PCa.


Assuntos
Fator de Transcrição E2F3/genética , MicroRNAs/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Neoplasias da Próstata/genética , Fator de Crescimento Transformador beta1/metabolismo , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fator de Transcrição E2F3/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Transplante de Neoplasias , Células PC-3 , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Neoplasias da Próstata/metabolismo
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