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1.
Medicine (Baltimore) ; 101(34): e30176, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36042678

RESUMO

BACKGROUND: The yes-associated protein (YAP) gene plays an important role in many malignant tumors, but its clinical significance in breast cancer remains unclear. This study aimed to explore the significance of YAP expression in breast cancer using meta-analysis. METHODS: Seven databases will be searched to collect the case-control studies published on the association between YAP expression and clinical pathogenic features in breast cancer until December 2021: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wan Fang Database, and the Chinese Biomedical Literature Database. To perform meta-analysis, STATA 14.0 and RevMan5 software were used with odds ratio (OR) and 95% confidence interval (95% CI) as the effect index, and publication bias and sensitivity analysis were subsequently tested. RESULTS: Form a total of 10 articles used in this study, 8 studies consisted of nontriple negative breast cancer (non-TNBC) and the other 2 of TNBC. Meta-analysis indicated a positive expression rate of YAP in non-TNBC tissues that was lower than in normal breast tissue (OR = 0.15, 95% CI = 0.10-0.21, P < .001). In contrast, the positive rate of YAP expression in TNBC was significantly higher than that in normal breast tissue (OR = 18.23, 95% CI = 8.20-40.52, P < .001). Furthermore, the positive expression rate was higher in the patients with lymph node metastasis, higher tumor node metastasis stage and histologic grade, and larger diameter in TNBC. However, there was no statistical difference in the positive expression rate of YAP between non-TNBC patients and lymph node metastasis, tumor node metastasis stage, histologic grade, and tumor size. CONCLUSIONS: YAP may participate in the occurrence and development of non-TNBC as a tumor suppressor gene; however, it may also be a carcinogenic factor in TNBC and may be a potential therapeutic target for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas de Sinalização YAP , Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Metástase Linfática , Neoplasias de Mama Triplo Negativas/patologia , Proteínas de Sinalização YAP/genética
2.
Front Vet Sci ; 8: 687923, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621805

RESUMO

Superovulation and embryo transfer techniques are important methods in cattle breeding. Combined with traditional superovulation protocols, immunization against inhibin can further improve follicular development and embryo yield. The aim of this study is to determine the efficacy of immunization against inhibin in improving the fertility of cattle through meta-analysis and to provide better clinical veterinary practice guidance. Three English databases (PubMed, EMBASE, Web of Science) were searched for research articles of immunizations against inhibin influence on cattle fertility. Literature screening, data extraction, and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In addition, the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias (RoB) tool was used to assess the risk of bias of the included animal studies. Potentially relevant studies (317) were identified, and finally 14 eligible studies (all in English) were included. The results of meta-analysis revealed that immunization against inhibin has significant effects on improving the number of ovulations [mean difference (MD) = 0.44, 95% confidence interval (CI) = (0.31, 0.56)], embryos and unfertilized ova [MD = 4.51, 95% CI = (2.28, 6.74)], follicles of the three size categories, the incidence of multiple ovulations [OR = 22.50, 95% CI = (8.13, 62.27)], and the conception rate [OR = 2.36, 95% CI = (1.26, 4.40)]. Moreover, it improved the production of embryos [grades 1 embryos: MD = 3.84, (3.54, 4.15); grade 2 embryos: MD = -0.73, (-0.89, -0.57); grade 3 embryos: MD = -0.50, (-0.75, -0.25); degenerated embryos: MD = 1.16, (-0.51, 2.82); transferable embryos: MD = 2.67, (2.03, 3.31)] and the number of corpora lutea [MD = 1.25, 95% CI = (0.79, 1.71)]. In the above indicators, the differences between the two groups were statistically significant (all p < 0.0001). Additionally, according to the quality evaluation results, the risk of bias in the included studies is relatively high. The quality evaluation of the results of the included studies showed that the risk of bias mainly concentrated in the selective, performance, detection, and reporting of bias aspects.

3.
Exp Ther Med ; 22(3): 950, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34335892

RESUMO

A broad spectrum of health benefits from intermittent fasting have been reported in studies on animal models and human subjects. However, the underlying mechanisms of these beneficial effects remain largely elusive. The present study aimed to explore the effects and potential mode of action of intermittent fasting in mouse models with a focus on the liver. C57BL/6 mice were subjected to intermittent fasting or ad libitum feeding as controls. It was determined that 12 h of daily intermittent fasting for 30 days significantly reduced the cumulative food intake compared with that in mice with ad libitum feeding. Fasting resulted in a significantly reduced liver mass but only had a minimal effect on bodyweight. The effects on the liver by 30 days of fasting were not reversed by subsequent ad libitum refeeding for 30 days. Among the measured blood biochemical parameters, the levels of blood glucose were decreased, while the levels of alkaline phosphatase were increased in fasting mice. Of note, targeted metabolic profiling revealed global elevation of metabolites in the livers of fasting mice. These metabolic molecules included adenosine triphosphate, nicotinamide adenine dinucleotide phosphate (NADP), reduced NADP and succinate, which are essentially involved in the citric acid cycle and oxidative phosphorylation. Thus, it was concluded that daily 12 h of intermittent fasting for one month significantly reduced the liver weight of mice, which is associated with enhanced liver metabolism.

4.
Front Med (Lausanne) ; 8: 793437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35071273

RESUMO

SARS-CoV-2 is an emerging coronavirus threatening human health and the economy worldwide. As an RNA virus, variants emerge during the pandemic and potentially influence the efficacy of the anti-viral drugs and vaccines. Eight spike variants harboring highly recurrent mutations were selected and introduced into a replication-competent recombinant VSV in place of the original G protein (rVSV-SARS-CoV-2). The resulting mutant viruses displayed similar growth curves in vitro as the wild-type virus and could be neutralized by sera from convalescent COVID-19 patients. Several variants, especially Beta strain, showed resistance to human neutralizing monoclonal antibodies targeting the receptor-binding domain (RBD). A single dose of rVSV-SARS-CoV-2 Beta variant could elicit enhanced and broad-spectrum neutralizing antibody responses in human ACE2 knock-in mice and golden Syrian hamsters, while other mutants generated antibody levels comparable to the wild-type. Therefore, our results will be of value to the development of next-generation vaccines and therapeutic antibodies.

5.
J Phys Chem B ; 124(51): 11699-11710, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33306373

RESUMO

The structure of poly(N-isopropylacrylamide) (PNIPAM) in solution is still an unresolved topic. Here, the PNIPAM structure in water was investigated using a bottom-up approach, involving the monomer, dimer, and trimer, and a combination of infrared (IR) spectroscopies as well as molecular dynamics simulations. The experiments show that the monomer and oligomers exhibit a broad and asymmetric amide I band with two underlying transitions, while PNIPAM presents the same major transitions and a minor one. Analysis of the 2D IR spectra and theoretical modeling of the amide I band indicates that the two transitions of the monomer do not have the same molecular origin as the oligomers and the polymer. In the monomer, the two bands originate from the ultrafast rotation of its ethyl group, which leads to different solvation structures for the various rotational conformers. In the case of the oligomers, the asymmetry and splitting of the amide I band is caused by the vibrational coupling among adjacent amide side chains. Moreover, it is deduced from the simulations that the oligomers have three distinct backbone conformations for neighboring amides. In particular, two of the backbone conformations have a closed and compact structure, while in the third, the backbone is open and elongated. The bottom-up approach allowed us to infer that such backbone conformations exist in PNIPAM as well. Consequently, the two major amide I transitions of the polymer are also assigned to split amide I transitions resulting from the vibrationally coupled nearest-neighboring amides. In contrast, the additional minor transition observed in PNIPAM is assigned to unsolvated amide units of the polymer. The proposed molecular model successfully describes that PNIPAM amide I band changes with temperature in terms of its molecular structure. This new model strongly suggests that PNIPAM does not have a completely random backbone structure, but has distinct backbone conformers between neighboring amides.

6.
Ann Transl Med ; 8(16): 998, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953798

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer due to insufficient actionable molecules. Radiotherapy (RT) plays a vital role in the treatment of ESCC, while radioresistance is a significant challenge to RT and results in locoregional and distant failure. METHODS: Radioresistance is a complex involving confounding factors, and its genetic mechanism is challenging to study. Postoperative recurrence after RT is more likely to be due to genetic causes than recurrence in unoperated patients. Therefore, two independent cohorts of ESCC patients who had received postoperative radiotherapy (PORT) and had opposite prognoses were set up, and whole-exome sequencing (WES) technology was applied. We compared the differences in the mutant spectra between the two groups. RESULTS: The mutation rate was slightly higher in the relapsed group than in the stable group [average mutation rate, 1.15 vs. 0.73 mutations per megabyte (Mb)], while the mutation types and proportions in the two groups were not significantly different. In particular, three mutated genes (TTN, MUC19, and NPIPA5) and two copy number alterations (CNAs) (1q amplification and 14q deletion) were identified to be associated with poor RT prognosis, while MUC4 was a favorable factor. CONCLUSIONS: These radioresistance biomarkers may supply insight into predicting the radioresponse. Further, these findings offer the first data on the mutational landscape of ESCC radioresistance.

7.
Life Sci ; 259: 118148, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32721465

RESUMO

Pancreatic cancer is a malignant cancer with poor prognosis. This study aimed to explore how O6-methylguanine-DNA methyltransferase (MGMT) affects the gemcitabine resistance of pancreatic cancer cells by the regulatory role of SHH/GLI signaling pathway. MGMT inhibition induced by lomeguatrib (LM) suppressed the proliferation, invasion, migration and autophagy, promoted the apoptosis of PanC-1/GEM cells and up-regulated the GEM inhibition rates for PanC-1/GEM cells. Moreover, MGMT inhibition increased the expression of Caspase-3 and Bax and decreased the expression of Bcl-2, Beclin1 and Atg5 in PanC-1/GEM cells. PVT1 silencing could also produce the similar effects of MGMT inhibition induced by LM on PanC-1/GEM cells. And, PVT1 silencing could inhibit the SHH/GLI signaling pathway in PanC-1/GEM cells by regulating the MGMT expression. miR-409 was demonstrated to be a potential target of PVT1 and SHH was demonstrated to be a potential target of miR-409. Furthermore, GLI overexpression could reverse the effects of PVT1 silencing. In the xenograft model of pancreatic cancer, nude mice were treated with GEM. MGMT inhibition suppressed the tumor growth and autophagy and promoted the apoptosis in tumor tissues. And, PVT1 silencing could inhibit the SHH/GLI signaling pathway in tumor tissues. In conclusion, MGMT inhibition could suppress the proliferation, invasion, migration and autophagy and promote the apoptosis of PanC-1/GEM cells in vitro and in vivo. PVT1 silencing may affect the PanC-1/GEM cells through changing the MGMT expression by inhibiting the SHH/GLI signaling pathway.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Metilases de Modificação do DNA/biossíntese , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/biossíntese , Enzimas Reparadoras do DNA/genética , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética , Animais , Autofagia/efeitos dos fármacos , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/antagonistas & inibidores , Desoxicitidina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Purinas/farmacologia , Purinas/uso terapêutico , Proteínas Supressoras de Tumor/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
8.
Angew Chem Int Ed Engl ; 59(39): 17012-17017, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32559329

RESUMO

Hydrogen bonds (H bonds) play a major role in defining the structure and properties of many substances, as well as phenomena and processes. Traditional H bonds are ubiquitous in nature, yet the demonstration of weak H bonds that occur between a highly polarized C-H group and an electron-rich oxygen atom, has proven elusive. Detailed here are linear and nonlinear IR spectroscopy experiments that reveal the presence of H bonds between the chloroform C-H group and an amide carbonyl oxygen atom in solution at room temperature. Evidence is provided for an amide solvation shell featuring two clearly distinguishable chloroform arrangements that undergo chemical exchange with a time scale of about 2 ps. Furthermore, the enthalpy of breaking the hydrogen bond is found to be 6-20 kJ mol-1 . Ab-initio computations support the findings of two distinct solvation shells formed by three chloroform molecules, where one thermally undergoes hydrogen-bond making and breaking.

9.
Talanta ; 210: 120652, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987200

RESUMO

Here, the novel petal-shaped ionic liquids modified covalent organic frameworks (PS-IL-COFs) particles have been synthesized by using ionic liquids as modifying agent, which could be beneficial to avoid the aggregation of COFs during the preparation and improve its dispersing performance. The novel PS-IL-COFs particles have been used and evaluated in the one step cleanup and extraction (OSCE) procedure for human plasma prior to the analysis of 3 general anesthetics by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). In the OSCE procedure, human plasma samples are directly mixed with extraction solvent and PS-IL-COFs particles, and the extraction and cleanup procedure have been carried out simultaneously. Compared with the Oasis PRiME HLB cartridge method, the OSCE procedure using PS-IL-COFs particles as sorbents is much more effective for the minimization of ion suppression resulted from blood phospholipids. Under optimal conditions, the PS-IL-COFs particles show higher cleanup efficiency of 3 general anesthetics with recoveries in the range of 82.5%-115%. The limits of quantification (LOQs) for propofol, ketamine and etomidate are 0.18 µg/L, 0.15 µg/L and 0.016 µg/L, respectively. Validation results on linearity, specificity, precision and trueness, as well as on the application to analysis of general anesthetics in a case of a 54-year-old female suffered gallstone demonstrate the applicability to clinical studies.


Assuntos
Anestésicos/sangue , Etomidato/sangue , Líquidos Iônicos/química , Ketamina/sangue , Compostos Orgânicos/química , Propofol/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Pessoa de Meia-Idade , Tamanho da Partícula , Propriedades de Superfície , Espectrometria de Massas em Tandem
10.
Int J Infect Dis ; 92: 208-213, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978583

RESUMO

OBJECTIVE: The risk factors and the impact of NAI treatments in patients with severe influenza A-associated pneumonia remain unclear. METHODS: A multicenter, retrospective, observational study was conducted in Zhejiang, China during a severe influenza epidemic in August 2017-May 2018. Clinical records of patients (>14 y) hospitalized with laboratory-confirmed influenza A virus infection and who developed severe pneumonia were compared to those with mild-to-moderate pneumonia. Risk factors related to pneumonia severity and effects of NAI treatments (monotherapy and combination of peramivir and oseltamivir) were analyzed. RESULTS: 202 patients with influenza A-associated severe pneumonia were enrolled, of whom 84 (41.6%) had died. Male gender (OR = 1.782; 95% CI: 1.089-2.917; P = 0.022), chronic pulmonary disease (OR = 2.581; 95% CI: 1.447-4.603; P = 0.001) and diabetes mellitus (OR = 2.042; 95% CI: 1.135-3.673; P = 0.017) were risk factors related to influenza A pneumonia severity. In cox proportional hazards model, severe pneumonia patients treated with double dose oseltamivir (300mg/d) had a better survival rate compared to those receiving a single dose (150 mg/d) (HR = 0.475; 95%CI: 0.254-0.887; P = 0.019). However, different doses of peramivir (300 mg/d vs. 600 mg/d) and combination therapy (oseltamivir-peramivir vs. monotherapy) showed no differences in 60-day mortality (P = 0.392 and P = 0.658, respectively). CONCLUSIONS: Patients with male gender, chronic pulmonary disease, or diabetes mellitus were at high risk of developing severe pneumonia after influenza A infection. Double dose oseltamivir might be considered in treating influenza A-associated severe pneumonia.


Assuntos
Antivirais/uso terapêutico , Vírus da Influenza A/fisiologia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Neuraminidase/antagonistas & inibidores , Oseltamivir/uso terapêutico , Pneumonia Viral/epidemiologia , Ácidos Carbocíclicos , China , Ciclopentanos/uso terapêutico , Epidemias , Feminino , Guanidinas/uso terapêutico , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
11.
Anesth Analg ; 130(4): 1054-1062, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30346356

RESUMO

BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an α2-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P < .001), and preserved kidney gross morphology and structure and attenuated cell apoptosis after ischemia-reperfusion. Furthermore, Dex also significantly increased acetylcholine release to 135.8 pmol/L (median) when compared to that (84.7 pmol/L) in the sham group (P < .001) and reduced the levels of several inflammatory mediators induced by renal ischemia/reperfusion. All the effects were abolished by vagotomy, splenectomy, or combinative administration of atipamezole, an α2-adrenergic receptor antagonist. CONCLUSIONS: Our findings suggest that Dex provides renoprotection, at least in part, through anti-inflammatory effects of the parasympathetic nervous system activation in addition to its direct actions on α2-adrenergic receptors.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Anti-Inflamatórios/farmacologia , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Nefropatias/prevenção & controle , Sistema Nervoso Parassimpático/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Acetilcolina/sangue , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Apoptose/efeitos dos fármacos , Catecolaminas/sangue , Imidazóis/farmacologia , Mediadores da Inflamação/metabolismo , Rim/patologia , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nervo Vago/fisiopatologia
12.
Gen Physiol Biophys ; 38(6): 485-495, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31829306

RESUMO

Circular RNA-microRNA (circRNA-miR) node has recently been found to modulate cancer process. Here, we investigated whether circCDYL and miR-150-5p exerted biological function in colon cancer cells. Colon cancer tissues were collected and subjected to qRT-PCR assay for circCDYL and miR-150-5p. SW480 and SW620 cells were forced to overexpress circCDYL and miR-150-5p before subjected to viability, colony formation, apoptosis, migration, invasion and protein (associated with proliferation, apoptosis and signaling pathways) assays. To confirm the combined function, the cells were transfected to simultaneously overexpress circCDYL and miR-150-5p. We found circCDYL was generally decreased while miR-150-5p was increased in colon cancer tissues in parallel with the para-carcinoma tissues. In circCDYL-transfected SW480 and SW620 cells, circCDYL decreased viability and promoted apoptosis with down-regulation of c-Myc and cyclin D1, up-regulation of p53, and cleavage of caspase-3 and PARP. Besides, migration and invasion behaviors were impeded. By contrast, miR-150-5p showed a carcinogenesis. However, suppressive role of circCDYL in cellular growth and migration was restrained in the cells simultaneously transfected with circCDYL and miR-150-5p, which was companied by down-regulation of PTEN and phosphorylation of PI3K, AKT, JAK2 and STAT5. circCDYL overexpression repressed cellular growth and migration via repressing miR-150-5p in colon cancer cells.


Assuntos
Proteínas Correpressoras/genética , Neoplasias do Colo , Hidroliases/genética , MicroRNAs/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Humanos
13.
Braz J Med Biol Res ; 52(12): e8834, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31826181

RESUMO

Polydatin (PD), a monocrystalline polyphenolic drug mainly found in the roots of Polygonum cuspidatum, has various pharmacological activities. Long non-coding RNAs (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) was found to participate in the suppression of multiple cancers. Here, we proposed to study the effect of PD on myocardial infarction (MI) by inducing DGCR5. CCK-8 assay was performed to detect the viability of H9c2 cells. Flow cytometry was utilized to test apoptosis of H9c2 cells. These results determined the optimal concentration and effect time of hypoxia as well as PD. Si-DGCR5 was transfected into cells and the expression level was determined by qRT-PCR. Western blot was utilized to evaluate the expression of apoptosis-related proteins, Bcl-2, Bax, and cleaved-caspase-3, as well as autophagy-associated proteins including Beclin-1, p62, and LC3-II/LC3-I. As a result, PD efficiently attenuated hypoxia-induced apoptosis and autophagy in H9c2 cells. The expression of DGCR5 was down-regulated by hypoxia and up-regulated by PD. Besides, knocking-down the expression of DGCR5 inhibited the protection of PD in H9c2 cells. In addition, PD up-regulated the accumulation of DGCR5, DGCR5 decreased the expression of Bcl-2 and p62, raised the expression of Bax and cleaved-caspase-3, and the proportion of LC3-II/LC3-I. PD stimulated the PI3K/AKT/mTOR and MEK/ERK signaling pathways via up-regulating the expression of DGCR5. Our data demonstrated that PD reduced cell apoptosis and autophagy induced by hypoxia in cardiomyocytes. Moreover, PD activated PI3K/AKT/mTOR and MEK/ERK signaling pathways by up-regulating the expression of DGCR5.


Assuntos
Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glucosídeos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , RNA Longo não Codificante/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Linhagem Celular , Citoproteção , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos
14.
Biochim Biophys Acta Rev Cancer ; 1871(1): 117-125, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30528647

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has recently been recognized as an important etiology contributing to the increased incidence of hepatocellular carcinoma (HCC). NAFLD, characterized by fat accumulation in the liver, is affecting at least one-third of the global population. The more aggressive form, nonalcoholic steatohepatitis (NASH), is characterized by hepatocyte necrosis and inflammation. The development of effective approaches for disease prevention and/or treatment heavily relies on deep understanding of the mechanisms underlying NAFLD to HCC development. However, this has been largely hampered by the lack of robust experimental models that recapitulate the full disease spectrum. This review will comprehensively describe the current in vitro and mouse models for studying NAFLD/NASH/HCC, and further emphasize their applications and possible future improvement for better understanding the molecular mechanisms involved in the cascade of NAFLD to HCC progression.


Assuntos
Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Progressão da Doença , Humanos , Camundongos , Fatores de Risco
15.
Braz. j. med. biol. res ; 52(12): e8834, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1055472

RESUMO

Polydatin (PD), a monocrystalline polyphenolic drug mainly found in the roots of Polygonum cuspidatum, has various pharmacological activities. Long non-coding RNAs (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) was found to participate in the suppression of multiple cancers. Here, we proposed to study the effect of PD on myocardial infarction (MI) by inducing DGCR5. CCK-8 assay was performed to detect the viability of H9c2 cells. Flow cytometry was utilized to test apoptosis of H9c2 cells. These results determined the optimal concentration and effect time of hypoxia as well as PD. Si-DGCR5 was transfected into cells and the expression level was determined by qRT-PCR. Western blot was utilized to evaluate the expression of apoptosis-related proteins, Bcl-2, Bax, and cleaved-caspase-3, as well as autophagy-associated proteins including Beclin-1, p62, and LC3-II/LC3-I. As a result, PD efficiently attenuated hypoxia-induced apoptosis and autophagy in H9c2 cells. The expression of DGCR5 was down-regulated by hypoxia and up-regulated by PD. Besides, knocking-down the expression of DGCR5 inhibited the protection of PD in H9c2 cells. In addition, PD up-regulated the accumulation of DGCR5, DGCR5 decreased the expression of Bcl-2 and p62, raised the expression of Bax and cleaved-caspase-3, and the proportion of LC3-II/LC3-I. PD stimulated the PI3K/AKT/mTOR and MEK/ERK signaling pathways via up-regulating the expression of DGCR5. Our data demonstrated that PD reduced cell apoptosis and autophagy induced by hypoxia in cardiomyocytes. Moreover, PD activated PI3K/AKT/mTOR and MEK/ERK signaling pathways by up-regulating the expression of DGCR5.


Assuntos
Animais , Ratos , Estilbenos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , RNA Longo não Codificante/efeitos dos fármacos , Glucosídeos/farmacologia , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos , Linhagem Celular , Citoproteção , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia
16.
Oncol Lett ; 16(2): 1885-1891, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30008880

RESUMO

Notch-regulated ankyrin-repeat protein (NRARP) has recently been reported to be involved in a number of malignant cancers; however, its role in non-small lung cancer (NSCLC) remains unclear. The present study aimed to identify whether NRARP could be applied as a novel prognostic marker for NSCLC. A total of 108 NSCLC patients were enrolled in the present study and their lung tissues were collected. Reverse-transcription quantitative polymerase chain reaction and immunohistochemical staining were used to assess the mRNA and protein levels of NRARP. Appropriate statistical tests were performed to evaluate the associations between NRARP protein expression and clinicopathological features and prognosis in NSCLC patients. The results revealed that NRARP expression was significantly associated with tumor differentiation (P=0.001), Tumor-Node-Metastasis stage (P=0.004) and cigarette smoking (P<0.001). Furthermore, patients with higher NRARP protein expression had significantly shorter overall survival times (P<0.001). Multivariate analysis indicated that overexpression of NRARP protein could be applied as an independent prognostic biomarker for NSCLC. In summary, the present study demonstrated that NRARP protein is overexpressed in NSCLC and that high NRARP expression is correlated with tumor progression and overall survival time. These data indicated the potential value of NRARP as a novel therapeutic target for the treatment of NSCLC.

17.
Anal Chim Acta ; 1020: 41-50, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-29655427

RESUMO

An enhanced cleanup efficiency hydroxy functionalized-magnetic graphene oxide (EH-Mag-GO) fully covered porous nano-titania as coating has been designed and synthesized. It has been evaluated in PRiME (process, robustness, improvements, matrix effects, ease of use) pass-through cleanup procedure for human plasma prior to analysis of strychnine and brucine by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). Comparing with the magnetic carboxyl-graphene (Mag-CG), EH-Mag-GO is much more effective for the removal of matrix effect resulted from blood phospholipids. Under optimal conditions, the results show higher cleanup efficiency of EH-Mag-GO with recoveries in the range of 89.4%-118%. The limits of quantification (LOQs) for strychnine and brucine are 0.088 µg/L and 0.092 µg/L, respectively. Especially, the EH-Mag-GO is also evaluated for reuse (20 times) without much sacrifice of the cleanup efficiency. Validation results on linearity, specificity, accuracy and precision, as well as on the application to analysis of strychnine and brucine in six cases of suspected semen strychni poisoning demonstrate the applicability to clinical studies.


Assuntos
Grafite/química , Óxidos/química , Estricnina/análogos & derivados , Estricnina/sangue , Cromatografia Líquida , Humanos , Fenômenos Magnéticos , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície , Espectrometria de Massas em Tandem
20.
RSC Adv ; 8(35): 19437-19448, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35541007

RESUMO

The geometrical structures, electronic structures, optoelectronic properties and phosphorescence efficiencies of four blue-emitting phosphors [Ir(fpmi)2(pyim)] (1), [Ir(pyim)2(fpmi)] (2), [Ir(fpmi)2(fptz)] (3), [Ir(tfmppz)2(pyim)] (4), [fpmi = 1-(4-fluorophenyl)-3-methylimdazolin-2-ylidene-C,C2'; pyim = 2-(1H-imidazol-2-yl)pyridinato; fptz = 5-(trifluoromethyl-2H-1,2,4-triazol-3-yl)pyridine; tfmppz = 1-(4-trifluoromethylphenyl)pyrazolyl] were investigated by DFT and TDDFT methods. We first optimized geometrical structures in the ground and lowest triplet states, and computed the absorption and emission spectra of 1 and 5[Ir(fpmi)2(pypz)] [pypz = 2-(1H-pyrazol-5-yl)pyridinato], which have been synthesized and characterized in a laboratory, using three functionals, B3LYP, CAM-B3LYP, and M062X. The calculation results were compared with relevant experimental data to assess the performance of the functionals. The suitable methods and functionals were then applied to study properties of the three other complexes. The HOMOs of 1-3 are composed of d(Ir) and π(cyclometalated ligands), however, the HOMO of 4 resides on the pyim ligand, while the LUMOs of all four complexes are dominantly localized on the chelating ligands. The calculated absorption results show that the corresponding absorption peaks for the four mainly studied complexes are almost at the same positions, however, the absorption intensities of the bands differ largely from each other. The lowest energy emissions of the four complexes are localized at 507, 512, 468, and 513 nm, respectively. In order to estimate their efficiencies, we carried out simplified radiative rate constant calculations. It turns out that complex 3, which possesses the shortest emission wavelength and the largest radiative rate constant (k r) value, can be considered as a highly efficient blue-emitting iridium(iii) complex.

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