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1.
J Chem Ecol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372833

RESUMO

The melon fly, Zeugodacus cucurbitae (Coquillett), is a major invasive pest, widely distributed in the Asia-Pacific region and some parts of Africa. Melon fly attractants could improve the effectiveness of current pest management measures. Previous studies have shown that some host fruits are attractive to melon flies but few have investigated the chemical compounds responsible for their attraction. In this study, we aimed to identify the volatile compounds from Luffa acutangula L that attract Z. cucurbitae. In headspace trapping, chemical profiling identified 19 compounds from ridge gourds, with 1-pentadecene being the major component. EAG results revealed that seven compounds elicited antennal responses in Z. cucurbitae, and significant differences in antennal responses between male and female Z. cucurbitae adults were recorded to p-xylene, alpha-pinene, and 1-octadecene. Behavioral experiments demonstrated that the EAG-active compounds methyl isovalerate and methyl myristate had either attractive or repellent effects on Z. cucurbitae at different concentrations, and 1-octadecene attracted Z. cucurbitae. Our findings provide a theoretical basis producing repellents or attractants for effective Integrated Pest Management of Z. cucurbitae.

2.
Surg Innov ; 31(1): 111-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050944

RESUMO

BACKGROUND: In recent years, numerous innovative yet challenging surgeries, such as minimally invasive procedures, have introduced an overwhelming amount of new technologies, increasing the cognitive load for surgeons and potentially diluting their attention. Cognitive support technologies (CSTs) have been in development to reduce surgeons' cognitive load and minimize errors. Despite its huge demands, it still lacks a systematic review. METHODS: Literature was searched up until May 21st, 2021. Pubmed, Web of Science, and IEEExplore. Studies that aimed at reducing the cognitive load of surgeons were included. Additionally, studies that contained an experimental trial with real patients and real surgeons were prioritized, although phantom and animal studies were also included. Major outcomes that were assessed included surgical error, anatomical localization accuracy, total procedural time, and patient outcome. RESULTS: A total of 37 studies were included. Overall, the implementation of CSTs had better surgical performance than the traditional methods. Most studies reported decreased error rate and increased efficiency. In terms of accuracy, most CSTs had over 90% accuracy in identifying anatomical markers with an error margin below 5 mm. Most studies reported a decrease in surgical time, although some were statistically insignificant. DISCUSSION: CSTs have been shown to reduce the mental workload of surgeons. However, the limited ergonomic design of current CSTs has hindered their widespread use in the clinical setting. Overall, more clinical data on actual patients is needed to provide concrete evidence before the ubiquitous implementation of CSTs.


Assuntos
Salas Cirúrgicas , Cirurgiões , Humanos , Carga de Trabalho/psicologia , Cirurgiões/psicologia , Cognição
3.
J Ultrasound Med ; 42(5): 1015-1022, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36217560

RESUMO

OBJECTIVE: To evaluate the location and characterization value of contrast-enhanced ultrasound (CEUS) in the detection of sentinel lymph nodes (SLNs) in malignant melanoma. METHODS: SLNs and the lymph node network were tracked by subcutaneous injection of ultrasonic contrast agent around the tumor and preoperative localization, and qualitative analyses were performed. The SLNs were also detected by the intraoperative subcutaneous injection of carbon nanoparticles, and the findings were compared with lymph nodes located by CEUS. The accuracy of the preoperative lymph node identification was evaluated by the results of postoperative pathology, which served as the gold standard of detection. RESULTS: In 47 patients with malignant melanoma, the mean number of SLNs detected by CEUS was 1.72 ± 0.10, while that by carbon nanoparticle administration it was 1.79 ± 1.07 (P = .371 > .05). Seven cases of lymph node metastasis were detected by CEUS, with a sensitivity of 70.0%, specificity of 97.3%, positive predictive value of 87.5%, negative predictive value of 92.3%, and accuracy of 91.5%. There was high consistency between the findings of CEUS and pathology in differentiating benign and malignant lymph nodes (kappa = 0.726, χ2  = 25.243, P < .001). CONCLUSIONS: CEUS can localize and differentiate SLNs in malignant melanoma, and thus, may potentially guide clinical treatment in the future.


Assuntos
Melanoma , Linfonodo Sentinela , Humanos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Ultrassonografia/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Meios de Contraste , Melanoma/diagnóstico por imagem , Melanoma Maligno Cutâneo
4.
Int J Mol Sci ; 24(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38069395

RESUMO

Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.


Assuntos
Histonas , Zinco , Filogenia , Zinco/metabolismo , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo
5.
Biochem Biophys Res Commun ; 587: 99-106, 2022 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-34872005

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system, and Chinese herbal medicine plays an important role in tumor treatment. The in-depth study of auriculasin isolated from Flemingia philippinensis showed that auriculasin promoted reactive oxygen species (ROS) generation in a concentration-dependent manner; when ROS scavenger NAC was added, the effects of auriculasin in promoting ROS generation and inhibiting cell viability were blocked. Auriculasin induced CRC cell apoptosis, led to mitochondrial shrinkage, and increased the intracellular accumulation of Fe2+ and MDA. When auriculasin and NAC were added simultaneously, the levels of apoptosis, Fe2+ and MDA returned to the control group levels, indicating that auriculasin activated apoptosis and ferroptosis by inducing ROS generation. In addition, auriculasin promoted the expression of Keap1 and AIFM1, but significantly reduced the phosphorylation level of AIFM1, while NAC significantly blocked the regulation of Keap1 and AIFM1 by auriculasin, which indicates that auriculasin can also induce oxeiptosis through ROS. When Z-VAD-FMK, Ferrostatin-1, Keap1 siRNA, PGAM5 siRNA and AIFM1 siRNA were added respectively, the inhibitory effect of auriculasin on cell viability was significantly weakened, indicating that auriculasin inhibits cell viability by inducing apoptosis, ferroptosis and oxeiptosis. Auriculasin also inhibited the invasion and clone forming ability of CRC cells, while NAC blocked the above effects of auriculasin. Therefore, auriculasin can promote CRC cell apoptosis, ferroptosis and oxeiptosis by inducing ROS generation, thereby inhibiting cell viability, invasion and clone formation, indicating that auriculasin has a significant antitumor effect.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Isoflavonas/farmacologia , Espécies Reativas de Oxigênio/agonistas , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/genética , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fabaceae/química , Ferroptose/genética , Células HCT116 , Humanos , Ferro/agonistas , Ferro/metabolismo , Isoflavonas/isolamento & purificação , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Malondialdeído/agonistas , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Modelos Biológicos , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo
6.
J Transl Med ; 20(1): 144, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351133

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown. METHODS: Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments. RESULTS: Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients. CONCLUSION: Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.


Assuntos
Células Progenitoras Endoteliais , Síndromes Mielodisplásicas , Apoptose , Medula Óssea , Células-Tronco Hematopoéticas , Humanos , Síndromes Mielodisplásicas/genética
7.
Haematologica ; 107(10): 2365-2380, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35354250

RESUMO

Bone marrow (BM) endothelial progenitor cell (EPC) damage of unknown mechanism delays the repair of endothelial cells (EC) and recovery of hematopoiesis after chemo-radiotherapy. We found increased levels of the glycolytic enzyme PFKFB3 in the damaged BM EPC of patients with poor graft function, a clinical model of EPC damage-associated poor hematopoiesis after allogeneic hematopoietic stem cell transplantation. Moreover, in vitro the glycolysis inhibitor 3-(3-pyridinyl)- 1-(4-pyridinyl)-2-propen-1-one (3PO) alleviated the damaged BM EPC from patients with poor graft function. Consistently, PFKFB3 overexpression triggered BM EPC damage after 5-fluorouracil treatment and impaired hematopoiesis-supporting ability in vitro. Mechanistically, PFKFB3 facilitated pro-apoptotic transcription factor FOXO3A and expression of its downstream genes, including p21, p27, and FAS, after 5-fluorouracil treatment in vitro. Moreover, PFKFB3 induced activation of NF-κB and expression of its downstream adhesion molecule E-selectin, while it reduced hematopoietic factor SDF-1 expression, which could be rescued by FOXO3A silencing. High expression of PFKFB3 was found in damaged BM EC of murine models of chemo-radiotherapy-induced myelosuppression. Furthermore, a murine model of BM EC-specific PFKFB3 overexpression demonstrated that PFKFB3 aggravated BM EC damage, and impaired the recovery of hematopoiesis after chemotherapy in vivo, effects which could be mitigated by 3PO, indicating a critical role of PFKFB3 in regulating BM EC damage. Clinically, PFKFB3-induced FOXO3A expression and NF-κB activation were confirmed to contribute to the damaged BM EPC of patients with acute leukemia after chemotherapy. 3PO repaired the damaged BM EPC by reducing FOXO3A expression and phospho-NF-κB p65 in patients after chemotherapy. In summary, our results reveal a critical role of PFKFB3 in triggering BM EPC damage and indicate that endothelial-PFKFB3 may be a potential therapeutic target for myelosuppressive injury.


Assuntos
Células Progenitoras Endoteliais , NF-kappa B , Animais , Humanos , Camundongos , Medula Óssea/metabolismo , Selectina E/metabolismo , Células Progenitoras Endoteliais/metabolismo , Fluoruracila/farmacologia , Glicólise , NF-kappa B/metabolismo , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo
8.
Chem Rec ; 22(10): e202200131, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35785467

RESUMO

The monitoring and prediction of the health status and the end of life of batteries during the actual operation plays a key role in the battery safety management. However, although many related studies have achieved exciting results, there are few systematic and comprehensive reviews on these prediction methods. In this paper, the current prediction models of remaining useful life of lithium-ion batteries are divided into mechanism-based models, semi-empirical models and data-driven models. Their advantages, technical obstacles, improvement methods and prediction performance are summarized, and the latest research results are shown by comparison. We highlight that the fusion models of convolution neural network, long short term memory network and so on, which have great practical application prospects because of their outstanding computing efficiency and strong modeling ability. Finally, we look forward to the future work in simplifying the model and improving its interpretability.


Assuntos
Fontes de Energia Elétrica , Lítio , Íons
9.
Eur Arch Otorhinolaryngol ; 278(9): 3193-3202, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32979119

RESUMO

OBJECTIVE: Temporal bone squamous cell carcinoma (TBSCC) is a rare, aggressive tumor. Surgery, alone or combined with radiotherapy, represent the mainstay of treatment. To report our experience in the treatment of TBSCC and evaluate the disease-specific survival, identifying the factors influencing this outcome. MATERIALS AND METHODS: A retrospective study was performed on 66 patients between 1993 and 2018. Patients were staged according to the University of Pittsburgh-modified TNM staging system. Nine cases (13.6%) were Stage I, 7 cases (10.6%) Stage II, 20 cases (30.3%) Stage III and 30 cases (45.5%) Stage IV. Twenty-four patients underwent lateral temporal bone resection (LTBR) and 42 patients underwent subtotal temporal bone resection (STBR). RESULTS: One hundred percent of Stage I and II patients showed no evidence of disease (NED) after a median follow-up of 101 months (range 1-289 months). NED resulted in 88.2% of Stage III (mean follow-up 80.3 months; range 8-257) and 46.4% of stage IV (mean follow-up 50.6 months; range 3-217). Pittsburgh Stage or involvement of mastoid, facial nerve, medial wall of the middle ear, temporomandibular joint and middle fossa dura emerged as negative prognostic factors. The highest mortality rate occurred in the first 2 years after treatment, due to local recurrence. CONCLUSIONS: Prognosis of TBSCC can be excellent in early stage tumors, employing a LTBR. In more advanced cases, prognosis is poor. STBR with adjuvant radiotherapy represents the treatment of choice, offering acceptable survival rates. Given the rarity of the pathology, many controversies still exist concerning optimal management.


Assuntos
Carcinoma de Células Escamosas , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Osso Temporal/patologia , Osso Temporal/cirurgia , Resultado do Tratamento
10.
Immunology ; 159(4): 384-392, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31849039

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with limited treatments. Asia has the highest HCC incidence rates; China accounts for over 50% of all HCC cases worldwide. T-cell receptor (TCR) -engineered T-cell immunotherapies specific for human leukocyte antigen (HLA) -A*02:01-restricted α-fetoprotein (AFP) peptide have shown encouraging results in clinics. HLA-A*24:02 is more common than HLA-A*02:01 in Asian countries, including China. Here we identified a novel HLA-A*24:02-restricted peptide KWVESIFLIF (AFP2-11 ) located in AFP signal peptide domain by mass spectrometric analysis of HLA-bound peptides from HepG2 cells. A TCR (KWV3.1) specific for AFP2-11 -HLA-A*24:02 was isolated from peripheral blood mononuclear cells of a healthy donor. The binding affinity of soluble KWV3.1 to its antigen was determined to be ~55 µm, within the affinity range of native TCRs for self-antigens. KWV3.1-transfected T cells could specifically activate and kill AFP2-11 pulsed T2-A24 cells and AFP+  HLA-A*24:02+ tumor cell lines, demonstrating that AFP2-11 can be naturally presented on the surface of AFP+ tumor cell lines. The newly identified antigenic peptide can provide a novel target for immunotherapeutic strategies for patients with AFP+  HLA-A*24:02+ HCC.


Assuntos
Antígenos de Neoplasias/imunologia , Antígeno HLA-A24/imunologia , Oligopeptídeos/imunologia , Sinais Direcionadores de Proteínas/genética , Receptores de Antígenos de Linfócitos T/imunologia , alfa-Fetoproteínas/imunologia , Sequência de Aminoácidos , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Sítios de Ligação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Técnicas de Cocultura , Expressão Gênica , Antígeno HLA-A24/química , Antígeno HLA-A24/genética , Voluntários Saudáveis , Células Hep G2 , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Oligopeptídeos/química , Oligopeptídeos/genética , Ligação Proteica , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Transfecção , alfa-Fetoproteínas/química , alfa-Fetoproteínas/genética
11.
Arch Insect Biochem Physiol ; 105(1): e21721, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557787

RESUMO

The alligator weed flea beetle, Agasicles hygrophila is a monophagous natural enemy of the invasive alligator weed Alternanthera philoxeroides. Oogenesis plays a vital role in the process of individual development and population continuation of oviparous insects. Sox is an ancient and ubiquitous metazoan gene family that plays a key regulatory role in various physiological processes, including oogenesis, which is closely related to fecundity. In this study, two Sox genes AhDichaete and AhSox3 were cloned and characterized, and then the expression profiles of AhDichaete and AhSox3 were qualified by a quantitative reverse transcription-polymerase chain reaction. The result showed that these two Sox genes were expressed significantly higher in ovary, especially in the adult developmental stage. Furthermore, the functions of AhDichaete and AhSox3 in A. hygrophila females were studied using RNA interference (RNAi). Fewer offsprings were produced when AhDichaete and AhSox3 RNAi females mated with wild-type males. Moreover, dsAhSox3 injection reduced the hatching rate of eggs but injection with dsAhDichaete did not. Further study of the reproductive system of AhDichaete and AhSox3 RNAi females showed that yolk protein deposition reduction in the ovarioles, then the expression of vitellogenin gene AhVg2 in ovaries was decreased. These results indicate that AhDichaete and AhSox3 play an important regulatory role in the process of ovarian development and oogenesis by affecting yolk synthesis in the ovary of A. hygrophila.


Assuntos
Besouros/genética , Proteínas de Insetos/genética , Oogênese/genética , Fatores de Transcrição SOX/genética , Animais , Besouros/crescimento & desenvolvimento , Feminino , Proteínas de Insetos/metabolismo , Ovário/crescimento & desenvolvimento , Fatores de Transcrição SOX/metabolismo , Análise de Sequência de DNA
12.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3631-3641, 2020 Aug.
Artigo em Zh | MEDLINE | ID: mdl-32893552

RESUMO

Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This study believes that the black organic matter constituting Zha-xun is mainly stored in the rocks. The exudation points of Zha-xun mostly distribute on the cliffs of high mountains, which makes it difficult to evaluate its resource distribution and storage area. This paper was aimed at the exudation environment of Tibetan medicine Zha-xun in Sichuan province and 6 ecological environmental factors of the Zha-xun were determined via the field investigation. Combining with these 6 factors as well as the GIS data of Sichuan province, ArcGIS software was used to extract ideal environmental factors which are suitable for exudation of Zha-xun, including geology types, geomorphological types, altitude, slope, vegetation types, and mean annual temperature. The spatial overlay analyses on the extracted environmental factors were carried out to predict the distribution area of Zha-xun in Sichuan province. Afterwards, field investigation was conducted to verify the prediction. The prediction showed that the exudation spots of Zha-xun in Sichuan province mainly located in 29 counties including 12 in Aba Prefecture, 15 in Ganzi Prefecture, and Muli County and Dechang County in Liangshan Prefecture. The deposit areas of Zha-xun were located in the Triassic, Devonian and Silurian strata and were basically distributed in 9 basins, including Dingqu River, Yalong River, Xianshui River, Dadu River, Suomo River, Minjiang River and Baishui River, characterized by a fragmented patch-like distribution along the mountain ranges, and the exudation spots of Zha-xun were mainly scattered among the rain-free cliffs' concavities of river valleys at a certain altitude. The prediction was consistent with the field investigation results, which suggested that it is possible and feasible to predict distribution of Zha-xun resources based on GIS-analysis. The study may provide a scientific basis for comprehensive investigations into Zha-xun's distribution and formation mechanism, thus promoting rational development and utilization of Zha-xun resources.


Assuntos
Sistemas de Informação Geográfica , Medicina Tradicional Tibetana , China , Geologia , Medicina Tradicional , Temperatura
13.
J Biochem Mol Toxicol ; 33(3): e22264, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30597675

RESUMO

Butylene fipronil (BFPN) is a phenylpyrazole insecticide, acting at the γ-aminobutyric acid (GABA) receptor. Here, we show that BFPN inducedcytotoxicity in PC12 murinenervous cells, which lacks GABA receptor. Treatment with BFPN for 48 hours significantly enhanced G0/G1 arrest and induced apoptosis. BFPN decreased the expression of cyclin-dependent kinase (CDK4 and CDK6) and increased P16 and cyclin D1. Simultaneously, Bcl-2 protein was declined while Bax and cytochrome c were significantly enhanced in BFPN-treated groups. The apoptotic enzymes caspase-8, -9, and -3 were also activated by BFPN. Furthermore, treatment with BFPN significantly stimulated reactive oxygen species (ROS) generation, and pretreatment with antioxidant diphenyleneiodonium, substantially reduced cell death. Overall, these results suggest that BFPN is effective to induce G0/G1-phase arrest and apoptosis in PC12 murine nervous cell. Stimulating ROS generation and activation of P16-CDK4/6-cyclin D1 and mitochondrial apoptotic pathway may participate in the cytotoxicity of BFPN.


Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pirazóis/farmacologia , Animais , Caspases/metabolismo , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Citocromos c/metabolismo , Células PC12 , Ratos
14.
Acta Pharmacol Sin ; 40(6): 762-768, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30487649

RESUMO

Pregnane X receptor (PXR) is a member of nuclear receptor subfamily 1 (NR1I2) that is a transcriptional regulator of several metabolic enzymes involved in clopidogrel metabolism. In this study we identified and evaluated the contributions of single nucleotide polymorphisms (SNPs) in NR1I2 and cytochrome P450 (CYP) 2C19 alleles to clopidogrel resistance (CR) and long-term clinical outcomes in acute ischemic stroke (IS) patients. A total of 634 patients with acute IS were recruited, who received antiplatelet medication (clopidogrel or aspirin) every day and completed a 1-year follow-up. The selected SNPs were genotyped, and platelet function was measured. Modified Rankin Scale (mRS) scores and main adverse cardiovascular and cerebrovascular events (MACCE) were noted to assess the prognosis. We showed that SNPs NR1I2 rs13059232 and CYP2C19 alleles (2*/3*) were related to CR. SNP NR1I2 (rs13059232) was identified as an independent risk factor for the long-term clinical outcomes in the clopidogrel cohorts (P < 0.001), but similar results were not observed in a matched aspirin cohort (P > 0.05). Our results suggest that NR1I2 variant (rs13059232) could serve as biomarker for clopidogrel therapy and individualized antiplatelet medications in the treatment of acute IS patients.


Assuntos
Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/genética , Clopidogrel/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X/genética , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Infarto Encefálico/diagnóstico , Estudos de Coortes , Citocromo P-450 CYP2C19/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/genética , Prognóstico , Fatores de Risco
15.
Acta Pharmacol Sin ; 40(4): 492-499, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29950617

RESUMO

Myotoxicity is a significant factor contributing to the poor adherence and reduced effectiveness in the treatment of statins. Genetic variations and high drug plasma exposure are considered as critique causes for statin-induced myopathy (SIM). This study aims to explore the sequential influences of rosuvastatin (RST) pharmacokinetic and myopathy-related single-nucleotide polymorphisms (SNPs) on the plasma exposure to RST and its metabolites: rosuvastatin lactone (RSTL) and N-desmethyl rosuvastatin (DM-RST), and further on RST-induced myopathy. A total of 758 Chinese patients with coronary artery disease were enrolled and followed up SIM incidents for 2 years. The plasma concentrations of RST and its metabolites were determined through a validated ultra-performance liquid chromatography mass spectrometry method. Nine SNPs in six genes were genotyped by using the Sequenom MassArray iPlex platform. Results revealed that ABCG2 rs2231142 variations were highly associated with the plasma concentrations of RST, RSTL, and DM-RST (Padj < 0.01, FDR < 0.05). CYP2C9 rs1057910 significantly affected the DM-RST concentration (Padj < 0.01, FDR < 0.05). SLCO1B1 rs4149056 variant allele was significantly associated with high SIM risk (OR: 1.741, 95% CI: 1.180-2.568, P = 0.0052, FDR = 0.0468). Glycine amidinotransferase (GATM) rs9806699 was marginally associated with SIM incidents (OR: 0.617, 95% CI: 0.406-0.939, P = 0.0240, FDR = 0.0960). The plasma concentrations of RST and its metabolites were not significantly different between the SIM (n = 51) and control groups (n = 707) (all P > 0.05). In conclusion, SLCO1B1 and GATM genetic variants are potential biomarkers for predicting RST-induced myopathy, and their effects on SIM are unrelated to the high plasma exposure of RST and its metabolites.


Assuntos
Amidinotransferases/genética , Doença da Artéria Coronariana/tratamento farmacológico , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Doenças Musculares/induzido quimicamente , Rosuvastatina Cálcica/sangue , Amidinotransferases/sangue , Amidinotransferases/metabolismo , China , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/metabolismo , Variação Genética , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/sangue , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Doenças Musculares/genética , Polimorfismo de Nucleotídeo Único/genética , Rosuvastatina Cálcica/metabolismo , Rosuvastatina Cálcica/farmacocinética
16.
Acta Pharmacol Sin ; 40(2): 208-215, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29891858

RESUMO

MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.


Assuntos
Biomarcadores/sangue , Cardiopatias/diagnóstico , Hemorragia/diagnóstico , MicroRNAs/sangue , Doenças Vasculares/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Estudos Prospectivos
17.
J Ultrasound Med ; 38(5): 1191-1200, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30208234

RESUMO

OBJECTIVES: The changes in the viscoelasticity of the Achilles tendon are related to tendinopathy. Therefore, constructing a data model in the healthy population is essential to understanding the key factors affecting the viscoelasticity of the Achilles tendon. The purpose of our research was to obtain large sample data, construct a data model, and determine parameters that affect the elastic modulus of the Achilles tendon in healthy Chinese adults. METHODS: We designed a prospective multicenter clinical trial to evaluate the viscoelasticity of the Achilles tendon by using shear wave elastography. A total of 1165 healthy adult participants from 17 Chinese hospitals were recruited for the assessment. The necessary parameters (age, height, weight, and body mass index) were recorded. The elastic modulus (Young modulus) was obtained from the middle of the Achilles tendon and calculated with feet in naturally relaxed, dorsal, and plantar positions. The thickness and perimeter of the Achilles tendon were measured via cross section on the same site. A multiple linear regression was performed to find the key factors affecting the Young modulus of the Achilles tendon. RESULTS: The Young modulus of the left Achilles tendon in the natural relaxed position followed a normal distribution (P > .05) with a mean ± SD of 374.24 ± 106.12 kPa. The regression equations showed a positive correlation between the Young modulus and weight and a negative correlation between the Young modulus and the circumference or thickness of the left Achilles tendon (P < .05). CONCLUSIONS: The Young modulus of the Achilles tendon as measured by shear wave elastography is related to body weight as well as the perimeter or thickness of the tendon.


Assuntos
Tendão do Calcâneo/fisiologia , Módulo de Elasticidade/fisiologia , Técnicas de Imagem por Elasticidade/métodos , Tendão do Calcâneo/diagnóstico por imagem , Adulto , China , Feminino , Humanos , Masculino , Estudos Prospectivos , Valores de Referência
18.
J Insect Sci ; 19(5)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557289

RESUMO

Glucose-6-phosphatase (G6Pase) and hexokinase (HK) are two key enzymes in the glycolysis and gluconeogenesis pathways, which catalyze the synthesis and degradation of glucose in insects, respectively. G6Pase and HK play an important role in insect growth by regulating the metabolism of glucose, leading to the efficient metabolism of other macromolecules. However, it is unclear whether these genes could be investigated for pest control through their actions on chitin metabolism. We studied the potential functions of G6Pase and HK genes in the regulation of chitin metabolism pathways by RNAi technology. Interference with G6Pase expression did not affect trehalose and chitin metabolism pathways in brown planthopper, Nilaparvata lugens (Stål). However, knockdown of the HK gene resulted in a significant decrease of expression of genes associated with the trehalose metabolic pathway but had no significant effect on trehalase activity, trehalose content, or glucogen content. Additionally, HK knockdown resulting in downregulation of the genes involved in chitin metabolism in the brown planthopper. These insects also showed wing deformities and difficulty in molting to varying degrees. We suggest that the silencing of HK expression directly inhibited the decomposition of glucose, leading to impaired chitin synthesis.


Assuntos
Quitina/biossíntese , Glucose/metabolismo , Hemípteros/metabolismo , Animais , Glucose-6-Fosfatase/genética , Hemípteros/enzimologia , Hemípteros/genética , Hexoquinase/genética , Proteínas de Insetos/genética , Interferência de RNA , Trealose/metabolismo
19.
Clin Anat ; 32(2): 244-252, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30281853

RESUMO

Because of a general lack of knowledge regarding the precise anatomy of the seminal vesicle system, efforts to use transurethral seminal vesiculoscopy (TSV) are currently constrained. We investigated 26 normal adult male specimens. Contrast medium was injected into the seminal vesicle system in 18 specimens and the openings of the ejaculatory ducts were examined with an operating microscope. India ink was injected into the urethra in four specimens to investigate the function of the ejaculatory duct valve. Another four specimens were examined histologically to identify the anatomical relationships of the seminal vesicle system. We found that the openings of the ejaculatory ducts were covered by the ejaculatory duct valve, which could be classified into two types and acted as a one-way valve. The apex of the seminal colliculus together with the right and left openings of the ejaculatory ducts formed a shape resembling an isosceles triangle. This could be used to locate the openings of the ejaculatory ducts during TSV. The ejaculatory ducts can be classified into two types according to their course. During surgery, efforts must be made to protect the ejaculatory duct valve. During inspection or surgery, the second segment and the angles of the ejaculatory ducts, particularly in Type Ib and Type II cases, require particular attention. Clin. Anat. 32:244-252, 2019. © 2018 Wiley Periodicals, Inc.


Assuntos
Ductos Ejaculatórios/anatomia & histologia , Glândulas Seminais/anatomia & histologia , Cadáver , Ductos Ejaculatórios/fisiologia , Humanos , Masculino , Uretra/anatomia & histologia
20.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1781-1788, 2019 May.
Artigo em Zh | MEDLINE | ID: mdl-31342702

RESUMO

The growth parameters,clonal propagation parameters and sexual reproduction parameters of Acanthopanax giraldii population were systematically investigated and analyzed by means of population ecology in this study. The correlation among the above mentioned parameters and the correlation among canopy density,topography and soil fertility factors were analyzed. It is clear that there was a significant correlation among the clonal ramets,the fruit production capacity of the cluster and the new shoot production capacity of the A. giraldii. Sexual reproduction and clonal reproduction played an important role in the continuation of the population. Illumination was the key ecological factor that determined growth type. The increase in canopy density changed the population from " group clonal growth" to " guerrilla clonal growth",and the higher stand closure degree and low-strength herb layer competition was a necessary condition for seed germination and colonization. Under the background of natural forest protection and sustainable development of resources,the reproductive characteristics of wild A. giraldii resulted in the decrease of its recoverable quantity.


Assuntos
Ecossistema , Eleutherococcus/fisiologia , Eleutherococcus/crescimento & desenvolvimento , Florestas , Reprodução , Solo
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