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1.
BMC Pregnancy Childbirth ; 24(1): 13, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166871

RESUMO

BACKGROUND: Healthy parturients may experience pulmonary edema and disturbed cardiac function during labor. We aimed to evaluate the extravascular lung water (EVLW), intravascular volume, and cardiac function of normal parturients during spontaneous vaginal delivery by bedside ultrasound. And to explore the correlation between EVLW and intravascular volume, cardiac function. METHODS: This was a prospective observational study including 30 singleton-term pregnant women undergoing spontaneous vaginal delivery. Bedside ultrasound was performed at the early labor, the end of the second stage of labor, 2 and 24 h postpartum, and 120 scanning results were recorded. EVLW was evaluated by the echo comet score (ECS) obtained by the 28-rib interspaces technique. Inferior vena cava collapsibility index (IVC-CI), left ventricle ejection fraction, right ventricle fractional area change, left and right ventricular E/A ratio, and left and right ventricular index of myocardial performance (LIMP and RIMP) were measured. Measurements among different time points were compared, and the correlations between ECS and other measurements were analyzed. RESULTS: During the spontaneous vaginal delivery of healthy pregnant women, 2 had a mild EVLW increase at the early labor, 8 at the end of the second stage of labor, 13 at 2 h postpartum, and 4 at 24 h postpartum (P < 0.001). From the early labor to 24 h postpartum, ECS first increased and then decreased, reaching its peak at 2 h postpartum (P < 0.001). IVC-CI first decreased and then increased, reaching its minimum at the end of the second stage of labor (P < 0.001). RIMP exceeded the cut-off value of 0.43 at the end of the second stage of labor. ECS was weakly correlated with IVC-CI (r=-0.373, P < 0.001), LIMP (r = 0.298, P = 0.022) and RIMP (r = 0.211, P = 0.021). CONCLUSIONS: During spontaneous vaginal delivery, the most vital period of perinatal care is between the end of the second stage of labor and 2 h postpartum, because the risk of pulmonary edema is higher and the right ventricle function may decline. IVC-CI can be used to evaluate maternal intravascular volume. The increase in EVLW may be related to the increase in intravascular volume and the decrease in ventricular function.


Assuntos
Água Extravascular Pulmonar , Edema Pulmonar , Feminino , Humanos , Gravidez , Parto Obstétrico , Água Extravascular Pulmonar/diagnóstico por imagem , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Volume Sistólico , Ultrassonografia , Estudos Prospectivos
2.
J Nanobiotechnology ; 21(1): 194, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37322478

RESUMO

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.


Assuntos
Exossomos , MicroRNAs , Traumatismo por Reperfusão , Camundongos , Animais , Microglia/metabolismo , MicroRNAs/metabolismo , Exossomos/metabolismo , Traumatismo por Reperfusão/metabolismo , Células da Medula Óssea/metabolismo
3.
Ecotoxicol Environ Saf ; 249: 114392, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508811

RESUMO

Epithelial-mesenchymal transdifferentiation of alveolar type Ⅱ epithelial cells is a vital source of pulmonary myofibroblasts, and myofibroblasts formation is recognized as an important phase in the pathological process of silicosis. miR-30c-5p has been determined to be relevant in the activation of the epithelial-mesenchymal transition (EMT) in numerous disease processes. However, elucidating the role played by miR-30c-5p in the silicosis-associated EMT process remains a great challenge. In this work, based on the establishment of mouse silicosis and A549 cells EMT models, miR-30c-5p was interfered with in vivo and in vitro models to reveal its effects on EMT and autophagy. Moreover, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), connective tissue growth factor (CTGF), autophagy-related gene 5 (ATG5), and autophagy were further interfered with in the A549 cells models to uncover the possible molecular mechanism through which miR-30c-5p inhibits silicosis associated EMT. The results demonstrated the targeted binding of miR-30c-5p to CTGF, ATG5, and MALAT1, and showed that miR-30c-5p could prevent EMT in lung epithelial cells by acting on CTGF and ATG5-associated autophagy, thereby inhibiting the silicosis fibrosis process. Furthermore, we also found that lncRNA MALAT1 might competitively absorb miR-30c-5p and affect the EMT of lung epithelial cells. In a word, interfering with miR-30c-5p and its related molecules (MALAT1, CTGF, and ATG5-associated autophagy) may provide a reference point for the application of silicosis intervention-related targets.


Assuntos
Células Epiteliais Alveolares , Proteína 5 Relacionada à Autofagia , Fator de Crescimento do Tecido Conjuntivo , Transição Epitelial-Mesenquimal , MicroRNAs , RNA Longo não Codificante , Silicose , Animais , Camundongos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Proteína 5 Relacionada à Autofagia/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Dióxido de Silício/toxicidade , Silicose/genética , Silicose/metabolismo
5.
Yi Chuan ; 44(6): 531-542, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35729101

RESUMO

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. It can inhibit the proliferation of myoblasts and serve as an important candidate gene for animal breed improvement. Mutations of the MSTN gene can cause extensive skeletal muscle hyperplasia and hypertrophy, resulting in "double muscle" symptoms. This leads to reduction of animal fat differentiation and increase of muscle content, thereby meeting the demand for quality consumption of animal meat in the market. In order to obtain a double-muscle phenotype using mutant MSTN gene in cloned goat, the goat MSTN gene was target-modified by TALENs. In this study, the TALENs expression vector was designed and constructed in the first exon sequence of the goat MSTN gene, which was then transfected into the goat fetal fibroblasts. The resistant cell lines were obtained by puromycin selection, and the cell lines with the MSTN gene mutations were analyzed by PCR and gene sequencing, thereby identifying the mutation type(s). The MSTN gene mutant cell lines were used as the nuclear donor cells in somatic cell nuclear transfer procedures in goats, and The morphological structure of the muscle tissue of the goats with MSTN gene mutations was analyzed by tissue section. The body weight of the cloned goats were monitored at different months of age, which provided the growth trend of their weight at different developmental stages. The results show that a total of 109 MSTN gene mutant cell lines were obtained. The mutation efficiency was 79.0% (109/138), of which 46 were biallelic mutations, accounting for 33.3% (46/138) of the total cell lines. Four MSTN gene mutant cell lines (1 biallelic homozygous mutation, 3 non-homozygous mutations) with good growth status were selected for somatic cell nuclear transfer in 12 recipients, of which 4 were pregnant by B-ultrasound at 30 days, indicating the a 33.3% (4/12) pregnancy rate. Two cloned goats were born at the end of the pregnancy. Sequencing analysis showed that there was no mutation in one allele of the M-1 cloned lamb, and the other allele harbored a 3 bp-deletion. The M-2 cloned lamb harbored a 1 bp base insertion in one allele of the MSTN gene, and a deletion of 13 bp in the other allele, resulting in mutations in both alleles and the loss of the protein-coding sequence of MSTN after the mutation site. In addition, the muscle fibers of cloned M-1 goats are tightly arranged and thick, and their monthly body weight is higher than that of normal wild-type goats. However, it is still consistent with the growth trend of normal wild-type goats and the M-1 goats can develop into healthy adults. In summary, this study showed that goat fetal fibroblasts with the multiple MSTN gene mutations were successfully obtained by TALENs technology, and cloned goats with mutant MSTN genes could be generated by somatic cell nuclear transfer method, thereby providing a technical foundation for the cultivation of the "double muscle" phenotype goats, and serving as a reference method for the preparation of other transgenic animals in the future.


Assuntos
Miostatina , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição , Animais , Animais Geneticamente Modificados , Peso Corporal , Feminino , Cabras/genética , Miostatina/genética , Gravidez , Ovinos
6.
Phys Chem Chem Phys ; 22(14): 7348-7364, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32211648

RESUMO

The first-principles kinetic Monte Carlo (kMC) simulation has been demonstrated as a reliable multiscale modeling approach in silico to disclose the interplay among all the elementary steps in a complex reaction network for heterogeneous catalysis. Heterogeneous catalytic systems frequently contain fast surface diffusion processes of some adsorbates while the elementary steps in it would be much slower than those in fast diffusion. Consequently, the kMC simulation for these systems is easily trapped in the sub-basins of a super basin on a potential energy surface due to the continuous and repeated sampling of these fast processes, which would significantly increase the total accessible simulation time and even make it impossible to get the reasonable simulation results using the kMC simulation. In this work, we present an improved fast species redistribution (FSR) method for the kMC simulation to overcome the stiffness problem resulting from the low-barrier surface diffusion to accelerate the heterogeneous catalytic kMC simulation. Taking CO oxidations on Pt(111) and Pt(100) as examples, we demonstrate that the FSR approach can properly reproduce the results of an equivalent first-principles microkinetic model simulation with more reasonable reaction rates. The improved kMC simulation based on the FSR method can accurately incorporate the effect of the fast diffusion of species on the surface and provide several orders of magnitude of acceleration compared to the standard kMC simulation.

7.
Int J Med Sci ; 17(18): 3174-3189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173437

RESUMO

Prolactinomas are the most common type of functional pituitary adenoma. Although bromocriptine is the preferred first line treatment for prolactinoma, resistance frequently occurs, posing a prominent clinical challenge. Both the prolactin receptor (PRLR) and estrogen receptor α (ERα) serve critical roles in the development and progression of prolactinomas, and whether this interaction between PRLR and ERα contributes to bromocriptine resistance remains to be clarified. In the present study, increased levels of ERα and PRLR protein expression were detected in bromocriptine-resistant prolactinomas and MMQ cells. Prolactin (PRL) and estradiol (E2) were found to exert synergistic effects on prolactinoma cell proliferation. Furthermore, PRL induced the phosphorylation of ERα via the JAK2-PI3K/Akt-MEK/ERK pathway, while estrogen promoted PRLR upregulation via pERα. ERα inhibition abolished E2-induced PRLR upregulation and PRL-induced ERα phosphorylation, and fulvestrant, an ERα inhibitor, restored pituitary adenoma cell sensitivity to bromocriptine by activating JNK-MEK/ERK-p38 MAPK signaling and cyclin D1 downregulation. Collectively, these data suggest that the interaction between the estrogen/ERα and PRL/PRLR pathways may contribute to bromocriptine resistance, and therefore, that combination treatment with fulvestrant and bromocriptine (as opposed to either drug alone) may exert potent antitumor effects on bromocriptine-resistant prolactinomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Receptor alfa de Estrogênio/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Hipofisárias/terapia , Prolactinoma/terapia , Receptores da Prolactina/metabolismo , Adolescente , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bromocriptina/farmacologia , Bromocriptina/uso terapêutico , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estradiol/metabolismo , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/antagonistas & inibidores , Feminino , Fulvestranto/farmacologia , Fulvestranto/uso terapêutico , Humanos , Hipofisectomia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/patologia , Prolactina/metabolismo , Prolactinoma/patologia , Ratos , Receptores da Prolactina/análise , Adulto Jovem
8.
Med Sci Monit ; 26: e923449, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32564053

RESUMO

BACKGROUND Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) that is particularly prevalent in school-aged children. This study explored the potential involvement of cytokines in children with Mycoplasma pneumoniae pneumonia (MPP) infection. MATERIAL AND METHODS Children aged 3-7 years who were hospitalized due to CAP infection were enrolled and divided into 2 groups: an MPP group (n=33) and a NMPP group (n=38), along with 21 age-matched healthy controls. Clinical characteristics and laboratory data were recorded. Serum levels of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were assessed using Luminex xMAP technology. Correlation analysis and ROC curves analysis were also performed to further explore the role of these detected cytokines in CAP. RESULTS Compared with the healthy controls, the serum expression of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were significantly higher in the MPP and NMPP groups. Furthermore, serum IL-18 expression was found to be significantly correlated with lgE, FeNO, IL-5, IL-8, and IL-13 concentrations. Significant differences were also observed between the MPP group and NMPP group patients in levels of IL-18, IL-5, and IL-6, and further ROC analysis showed that the area under the curve (AUC) of IL-18 and IL-5 were 0.813 (95% CI: 0.710-0.917; P<0.01) and 0.844 (95% CI: 0.756-0.933; P<0.01), respectively. CONCLUSIONS IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 serum levels showed significant differences in children with CAP. IL-18 and IL-5 were much higher in the MPP group compared to the NMPP group patients, whereas IL-6 levels were significantly lower in these 2 groups.


Assuntos
Citocinas/imunologia , Óxido Nítrico/metabolismo , Pneumonia por Mycoplasma/imunologia , Testes Respiratórios , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas , Feminino , Humanos , Imunoglobulina E/imunologia , Interferon gama/imunologia , Interleucina-13/imunologia , Interleucina-18/imunologia , Interleucina-33/imunologia , Interleucina-5/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Masculino , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia por Mycoplasma/metabolismo
9.
Phys Chem Chem Phys ; 21(23): 12555-12565, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31149681

RESUMO

It is of great importance to regulate a catalyst to control its selectivity. In general, the Pt catalyzed hydrogenation of nitrobenzene (PhNO2) would produce aniline. Yet, when KOH is added, the more value-added N-N coupling products such as aromatic azoxy and azo exhibit better selectivity. To identify the key factors governing the selectivity towards aromatic azoxy and azo in a complex reaction network, the reaction mechanisms of PhNO2 hydrogenation over Pt(111) are systematically investigated on the Pt(111) surface and at the KOH/Pt(111) interface utilizing microkinetic simulations based on the PBE-D3 calculated results. It is found that the selectivity strongly depends on the adsorption configuration of PhNO2 rather than on the coverage of the surface H*. In neutral environments, PhNO2 tends to lie flat on the Pt(111) with chemisorption of the phenyl group, which is in favor of the production of aniline. The addition of KOH makes PhNO2 preferentially chemisorb at the KOH/Pt(111) interface via the nitro group without the chemisorption of the phenyl group, which is in favor of the N-N coupling products. The KOH-induced tilted adsorption configuration and extra stabilization could promote the dehydroxylation of PhNOH* to form PhN*, which is the key intermediate for the production of azoxy and azo.

10.
J Cell Biochem ; 119(10): 7971-7981, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29236315

RESUMO

To explore the mechanism of lnc SNHG20 in the regulation of proliferation, invasion, and migration of breast cancer cells. mRNA levels of SNHG20, miR-495, and HER2 were detected by qRT-PCR. Protein level of HER2 was measured by Western blot. Cell proliferation, invasion, and migration were detected by CCK-8 assay, Boyden chamber assay, and Transwell assay. The combination between SNHG20 and miR-495 was confirmed by RNA pull down assay. The combination between miR-495 and HER2 was confirmed by luciferase report assays. We also established breast cancer-bearing mice model and analyzed tumor volumes. Our data showed SNHG20 expression was significantly upregulated, miR-495 expression was significantly downregulated, and HER2 expression was significantly upregulated in breast cancer tissues and cell lines. Besides, SNHG20 promoted the proliferation, invasion, and migration of breast cancer cells. We also found SNHG20 negatively regulated miR-495, and miR-495 could negatively regulate HER2. Moreover, we discovered that SNHG20 regulated HER2 via miR-495. SNHG20 regulated proliferation, invasion, and migration of breast cancer cells via miR-495/HER2. Finally, we confirmed the mechanism of SNHG20 in the regulation of proliferation, invasion, and migration in breast cancer-bearing mice model. SNHG20 regulates HER2 via miR-495 to promote proliferation, invasion, and migration of breast cancer cells.


Assuntos
Neoplasias da Mama/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Imunoprecipitação , Camundongos , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Longo não Codificante/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(3): 315-320, 2018 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-29978785

RESUMO

Objective To observe the effect of Gui Zhi Fu Ling Jiao Nang (GZFLJN) on the expressions of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) in uterine vascular smooth muscle cells (VSMC) of rat models with an intrauterine device (IUD) and to determine the thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) levels in peripheral blood. Methods Female Wistar rats were randomly divided into four groups:normal group (n=16,with normal breed without treatment),model group (n=18,drenching 0.9% normal saline after modeling of IUD),GZFLJN group (n=18),and aminocaproic acid tablets group (n=17). Immunohistochemical SP method was used to detect the expressions of α-SMA and PCNA in uterine VSMC.ELISA was served to detect the levels of TXB2 and 6-keto-PGF1α in peripheral blood. Results The positive rate of α-SMA were (50.89±9.41)%,(26.93±6.80)%,(48.92±6.80)%,and (34.63±7.26)%,respectively,in normal group,model group,GZFLJN group,and aminocaproic acid tablets group;obviously,it was significantly higher in normal group (t=14.43,P=0.00) and GZFLJN group (t=11.37,P=0.00) than that in model group and it was significantly lower in aminocaproic acid tablets group than in normal group (t=9.96,P=0.00) and GZFLJN group (t=8.23,P=0.00). The positive rate of PCNA were (25.66±7.24)%,(61.26±9.98)%,(28.36±9.17)%,and (50.23±8.71)%,respectively,in these four groups;obviously,it was significantly lower in the normal group (t=20.86,P=0.00) and GZFLJN group (t=19.12,P=0.00) than in model group and it was significantly higher in aminocaproic acid tablets group than in normal group (t=17.82,P=0.00) and GZFLJN group (t=16.05,P=0.00). Serum TXB2 level in these four groups were (445.86±24.43),(508.78±12.42),(448.11±9.63),and (498.11±13.63)ng/L;obviously,it was significantly higher in model group than in normal group (t=16.55,P=0.00) and aminocaproic acid tablets group (t=-4.12,P=0.00) and it was significantly lower in GZFLJN group than in model group (t=-15.23,P=0.00) and aminocaproic acid tablets group (t=-12.08,P=0.00). Serum 6-keto-PGF1α level in these four groups were (23.17±1.93),(18.09±0.93),(22.70±1.61),and (20.70±1.41)ng/L,respectively;obviously,it was significantly lower in model group than in normal group (t=-13.98,P=0.00) and aminocaproic acid tablets group (t=5.26,P=0.00) and it was significantly higher in GZFLJN group than in model group (t=11.43,P=0.00) and aminocaproic acid tablets group (t=8.76,P=0.00). Conclusion GZFLJN can regulate the expressions of α-SMA and PCNA of VSMC in the endometrium of IUD rats and the concentrations of TXB2 and 6-keto-PGF1α in the serum.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Dispositivos Intrauterinos , Miócitos de Músculo Liso/efeitos dos fármacos , Útero/citologia , Actinas/metabolismo , Animais , Cinnamomum aromaticum/química , Dinoprosta/sangue , Feminino , Hemorreologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Tromboxano B2/sangue , Wolfiporia/química
13.
Basic Res Cardiol ; 112(1): 7, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28004242

RESUMO

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor ß superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16+ cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1+) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.


Assuntos
Envelhecimento/genética , Proteínas Morfogenéticas Ósseas/genética , Fatores de Diferenciação de Crescimento/genética , Coração/fisiologia , Traumatismo por Reperfusão Miocárdica , Animais , Proteínas Morfogenéticas Ósseas/administração & dosagem , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Terapia Genética/métodos , Fatores de Diferenciação de Crescimento/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Microbolhas , Miocárdio , Regeneração , Transcriptoma
14.
Asian-Australas J Anim Sci ; 30(8): 1175-1182, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28002927

RESUMO

OBJECTIVE: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with transcription activator-like effector nucleases. METHODS: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT). RESULTS: The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23%) were confirmed pregnant at 30 d. In second round SCNT, 7 (53%), 4 (31%), and 3 (23%) recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. CONCLUSION: This finding signifies the combined use of TALENs and SCNT can generate bi-allelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.

15.
Cell Physiol Biochem ; 38(2): 763-76, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26871894

RESUMO

BACKGROUND/AIMS: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. METHODS: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF(V600E) mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. RESULTS: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF(V600E) mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF(V600E) mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF(V600E) mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). CONCLUSION: This meta-analysis confirmed significant associations between BRAF(V600E) mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF(V600E) mutation for PTC prognosis.


Assuntos
Carcinoma/genética , Carcinoma/patologia , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/genética , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Fatores Etários , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma Papilar , Feminino , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores Sexuais , Câncer Papilífero da Tireoide , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia
16.
Chemistry ; 22(16): 5698-704, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26934305

RESUMO

Metal-support interactions are desired to optimize the catalytic turnover on metals. Herein, the enhanced interactions by using a Mo2C nanowires support were utilized to modify the charge density of an Ir surface, accomplishing the selective hydrogenation of α,ß-unsaturated aldehydes on negatively charged Ir(δ-) species. The combined experimental and theoretical investigations showed that the Ir(δ-) species derive from the higher work function of Ir (vs. Mo2C) and the consequently electron transfer. In crotonaldehyde hydrogenation, Ir/Mo2C delivered a crotyl alcohol selectivity as high as 80%, outperforming those of counterparts (<30%) on silica. Moreover, such electronic metal-support interactions were also confirmed for Pt and Au, as compared with which, Ir/Mo2C was highlighted by its higher selectivity as well as the better activity. Additionally, the efficacy for various substrates further verified our Ir/Mo2C system to be competitive for chemoselective hydrogenation.

17.
J Chem Inf Model ; 55(12): 2519-27, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26549421

RESUMO

Graph data are becoming increasingly common in machine learning and data mining, and its application field pervades to bioinformatics and cheminformatics. Accordingly, as a method to extract patterns from graph data, graph mining recently has been studied and developed rapidly. Since the number of patterns in graph data is huge, a central issue is how to efficiently collect informative patterns suitable for subsequent tasks such as classification or regression. In this paper, we consider mining discriminative subgraphs from graph data with multiple labels. The resulting task has important applications in cheminformatics, such as finding common functional groups that trigger multiple drug side effects, or identifying ligand functional groups that hit multiple targets. In computational experiments, we first verify the effectiveness of the proposed approach in synthetic data, then we apply it to drug adverse effect prediction problem. In the latter dataset, we compared the proposed method with L1-norm logistic regression in combination with the PubChem/Open Babel fingerprint, in that the proposed method showed superior performance with a much smaller number of subgraph patterns. Software is available from https://github.com/axot/GLP.


Assuntos
Mineração de Dados/métodos , Modelos Teóricos , Relação Quantitativa Estrutura-Atividade , Algoritmos , Mineração de Dados/normas , Descoberta de Drogas , Estrutura Molecular , Análise de Regressão
18.
Prenat Diagn ; 34(12): 1189-97, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25042792

RESUMO

AIM: The aims of this article are to establish three-dimensional ultrasonographic nomograms of normal fetal spleen size and to evaluate the clinical application value. METHODS: An observational, cross-sectional study was performed on 455 women with a normal singleton pregnancy between 18 and 38 weeks' gestational age (GA). Fetal spleen volume was measured using three-dimensional ultrasound equipped with virtual organ computer-aided analysis, and biometric parameters were assessed in multiplanar mode to create reference ranges to GA. Thirty cases were randomly selected to conduct reliability analyses via intraobserver and interobserver ultrasonographic measurement. Moreover, 50 cases of suspected splenic malformations were evaluated by the newly established nomograms and followed up subsequently. RESULTS: Using regression formulas, we found that fetal spleen size increased with GA. We observed strong reliability in intraobserver and interobserver volume measurements with intraclass correlation coefficients of 0.994 and 0.962. Bland-Altman analyses showed narrow limits of agreement [intraobserver: (-3.2 to 3.5)%; interobserver: (-3.2 to 4.3)%]. Of the 50 cases with suspected splenic malformations, six cases of splenomegaly and one case of splenic cyst were diagnosed. CONCLUSION: Three-dimensional ultrasound nomograms of normal fetal spleen size across a range of GA have a strong diagnostic value. Volume measurements with good reliability were optimal in clinical practice.


Assuntos
Baço/diagnóstico por imagem , Esplenopatias/congênito , Ultrassonografia Pré-Natal , Estudos Transversais , Feminino , Humanos , Imageamento Tridimensional , Gravidez , Valores de Referência , Baço/anormalidades , Esplenopatias/diagnóstico por imagem
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(8): 1003-7, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25223189

RESUMO

OBJECTIVE: To observe the effect of Yanggan Yishui Granule (YGYSG) on collagen protein I, III, and IV, as well as fibronection (EN) in spontaneously hypertensive rats (SHR), and to explore its possible renal protective mechanisms. METHODS: Fourty SHR were randomly divided into four groups, i.e., the model group, the Benazepril group, the low dose YGYSG group, and the high dose YGYSG group, 10 in each group. A normal control group was set up with recruited Wistar-Kyoto (WKY) rats. After 6 weeks of treatment, the expression of collagen protein I, III, and IV, as well as FN in the 5.1 image analysis system. RESULTS: In the WKY-control group, there was only a small amount of brown particles in the mesenchymal region, the glomerular basement membrane, or the mesangial region. The expression of collagen I, Ill, and IV, as well as EN significantly increased more in the model group than in the normal control group (P < 0.01). After treatment, the expression of collagen I, III, and IV, as well as FN significantly decreased in each treated group, showing statistical difference when compared with the model group (P < 0.01). Besides, decresed expression of collagen I, III, and IV was shown in the low dose YGYSG group and the Benazepril group (P > 0.05). The expression of collagen I, III, and IV could be further reduced in the high dose YGYSG group, showing statistical difference when compared with the Benazepril group and the low dose YGYSG group (P < 0.05, P < 0.01). CONCLUSION: YGYSG might play an important role in the renal protective effect through reducing the synthesis of renal collagen I, III, and IV, as well as FN, increasing the degradation of renal collagen I, III, and IV, as well as FN, thereby reducing excessive deposition of renal extracellular matrix (ECM).


Assuntos
Colágeno/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fibronectinas/metabolismo , Hipertensão/metabolismo , Animais , Hipertensão/tratamento farmacológico , Rim/metabolismo , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(4): 982-5, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25007613

RESUMO

In order to study the influencing factors on Raman spectroscopy, we research a series of comparative Raman spectroscopy of multi-walled carbon nanotubes (MWCNT) with different tube diameter and length. The results suggest that the G peak and D peak of MWCNT are all red-shifted as compared to that of polycrystalline graphite; In the same conditions, the peak intensity (G peak and D peak) is directly proportional to the diameter of the MWCNT, and inversely proportional to the length of the MWCNT; G peak frequency shift is closely related to the MWCNT diameter and length, which are inversely proportional to the diameter (with identical results of the single-walled carbon nanotube radial breathing modes) and direct proportional to the length. While, the influences of the diameter and length on D peak frequency shift are weak, and future analysis for the reason of this kind of phenomenon is as follows. Subsequently, we investigated the relation between D peak frequency shift and MWCNT aspect ratio, the relationship between G peak frequency shift and aspect ratio is nearly linear increase. Using the same analysis method, we plotted the different graphs of G peak and D peak intensity vs the aspect ratio of MWCNT, respectively. As the expected, the linear degression relation are existent in the two relationships.

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