RESUMO
BACKGROUND: His bundle pacing (HBP) is a physiological pacing strategy to preserve the electrical synchrony of ventricular conduction and left ventricular (LV) function. Left bundle branch pacing (LBBP) has emerged as an alternative physiological pacing technique. OBJECTIVE: To evaluate cardiac electrical and mechanical synchrony comparing LBBP and HBP in patients with permanent atrial fibrillation (AF). METHODS: Consecutive patients with symptomatic bradycardia and AF were enrolled from January to June of 2019. The cardiac electrical and mechanical synchrony in different pacing mode were evaluated at baseline and after implantation. RESULTS: Both HBP and LBBP were performed in 20 patients. LBBP significantly widened the QRS duration compared with the intrinsic conduction (113.2 ± 14.5 vs. 96.5 ± 16.2 ms; p = .01), while HBP did not (104.5 ± 22.3 vs. 96.5 ± 16.2 ms; p = .12). Both LBBP and HBP patients had similar LV myocardial strain measurements for the mechanical synchrony evaluation without significant change compared with baseline. There was no significant difference in right ventricular synchrony measurement between LBBP and HBP. Compared to HBP, LBBP had less interventricular synchrony (IMVD, 14.7 ± 9.2 vs. 3.1 ± 12.7 ms, p < .01; Ts-LV-RV, 37.9 ± 10.7 vs. 18.5 ± 10.8 ms, p < .001). CONCLUSIONS: Although LBBP's a physiological pacing mode can achieve a similar cardiac electrical and mechanical synchronization when compared to HBP, LBBP results in modest delay in RV activation, and the clinical implication remains to be studied.
Assuntos
Fibrilação Atrial/terapia , Bradicardia/terapia , Bloqueio de Ramo/terapia , Estimulação Cardíaca Artificial/métodos , Idoso , Fibrilação Atrial/fisiopatologia , Bradicardia/fisiopatologia , Fascículo Atrioventricular/fisiopatologia , Bloqueio de Ramo/fisiopatologia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Recent reports have characterized virological and clinical features of the novel reassortant avian-origin influenza A (H7N9) virus. However, cardiovascular involvement during H7N9 infection is still unclear. In this study, we evaluate cardiac injury among H7N9-infected patients. MATERIALS AND METHODS: A total of 40 patients who were laboratory-confirmed with H7N9 infection were retrospectively included and grouped by Acute Physiology and Chronic Health Evaluation II (APACHE II) score into four subgroups I(0-10), II(11-20), III(21-30) and IV(31-71). Cardiovascular complications and markers of cardiac injury including creatinine kinase (CK), CK iso-enzyme (CK-MB), cardiac troponin I (cTNI) and brain natriuretic peptide (BNP) were assessed. Electrocardiogram (ECG) and echocardiography (ECHO) were also performed. RESULTS: Half of patients manifested with cardiovascular complications, with hypotension (47.5%) and heart failure (40.0%) the most prevalent. CK, CK-MB and cTNI showed marked increase with H7N9 virus infection but significantly decreased after H7N9 viral tests turned negative. More than half of patients presented with an abnormal ECG, but most of them are benign changes. ECHO examination showed different degree of impairment of cardiac function. Pulmonary artery systolic pressure was increased in all groups. Cardiac damage was more evident in patients with higher APACHE II score. CONCLUSIONS: H7N9 virus exerts a transient impairment on the cardiovascular system. Patients with a higher APACHE II score are more susceptible to cardiac damage.
Assuntos
Cardiopatias/virologia , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Creatina Quinase/metabolismo , Ecocardiografia , Eletrocardiografia , Feminino , Cardiopatias/sangue , Humanos , Hipertensão/sangue , Hipertensão/virologia , Influenza Humana/sangue , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Oxigênio/sangue , Pressão Parcial , Estudos Retrospectivos , Troponina I/metabolismo , Adulto JovemRESUMO
Linalool, as a major volatile compound, is widely distributed in natural plant essential oil. In addition, it can also be artificially synthesized. Linalool is used frequently as an important ingredient of perfumes and household detergents. It is still employed in food flavor and industries. Besides, linalool has some positive effect on healthcare. Many studies have showed that linalool exhibited a variety of pharmacological activities, including analgesic, anxiolytic, sedative, anti-inflammatory, anti-tumor and anti-bacterial effects. Therefore, linalool will be a promising agent for clinical application. This article reviews the pharmacological effects and formulation studies of linalool so as to provide a theoretical basis for its further development and utilization.
Assuntos
Química Farmacêutica , Medicamentos de Ervas Chinesas/química , Monoterpenos/química , Monoterpenos Acíclicos , Animais , Ansiolíticos/química , Ansiolíticos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacologia , Monoterpenos/farmacologiaRESUMO
BACKGROUND: Increasing evidence has revealed that microRNAs (miRNA) played a pivotal role in regulating cancer cell proliferation and metastasis. The deregulation of miR-182 has been identified in colorectal cancer (CRC). However, the role and mechanism of miR-182 in CRC have not been completely understood yet. METHODS: The expression levels of miR-182 in CRC tissues and CRC cell lines were examined by performing stem-loop quantitative RT-PCR. The stable over-expression miR-182 cell lines and control cell lines were constructed by lentivirus infection. Subsequently, CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models were performed to detect the biological functions of miR-182 in vitro and in vivo. A luciferase reporter assay was conducted to confirm target associations. Western blot and immunohistochemical analysis were performed to examine the expression changes of molecular markers that are regulated by miR-182. RESULTS: We found that miR-182 expression is increased in CRC cells that originated from metastatic foci and human primary CRC tissues with lymph node metastases. The ectopic expression of miR-182 enhanced cell proliferation, invasion, and migration in vitro. Stable overexpression of miR-182 also facilitated tumor growth and metastasis in vivo too. Further research showed that miR-182 could directly target the 3'untranslated region (3'UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2, which we identified in previous studies as a CRC metastasis-associated protein. Restoring SATB2 expression could reverse the effects of miR-182 on CRC cell proliferation and migration. Investigations of possible mechanisms underlying these behaviors induced by miR-182 revealed that miR-182 induced epithelial-mesenchymal transition (EMT) by modulating the expression of key cellular molecules in EMT. CONCLUSIONS: Our results illustrated that the up-regulation of miR-182 played a pivotal role in CRC tumorigenesis and metastasis, which suggesting a potential implication of miR-182 in the molecular therapy for CRC.
Assuntos
Proliferação de Células , Neoplasias Colorretais/patologia , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , MicroRNAs/metabolismo , Metástase Neoplásica , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genéticaRESUMO
The ENO1 gene encodes a multifunctional enzyme that has been identified as a key component of the glycolytic pathway. Our previous studies demonstrated that ENO1 gene expression was higher in the ovaries of laying geese compared with prelaying geese. However, the molecular characterisation and expression profiling of the ENO1 gene in geese tissues and ovarian follicles remain to be determined. In this study, ENO1 cDNA (1,445 bp long) of the Sichuan white goose was cloned and characterised. The ORF of ENO1 cDNA is 1,305 bp in length and encodes a 434 amino acid protein with a molecular weight of 47.27 kDa. ENO1 expression in all of the examined tissues was the highest in spleen and the lowest in breast muscle. High expression of ENO1 appeared in the kidney, liver, adrenal gland, and retina. With increasing follicle growth, ENO1 gene expression began to decrease from the small white follicle to F5, which was followed by a sharp increase in expression in F4 and then a gradual decrease in expression from F3 to F1. Furthermore, in the postovulatory follicles (POF), the levels of ENO1 gene expression decreased gradually from POF1 to POF4. In conclusion, the ENO1 transcript was widely distributed in various tissues of the Sichuan white goose, but ENO1 expression was tissue-specific. Furthermore, the results of the ENO1 expression profiling of ovarian follicles suggest that ENO1 may play an important dual role in the progress of follicular development, where ENO1 acts as a glycolytic enzyme and also mediates apoptosis.
Assuntos
Gansos/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Folículo Ovariano/metabolismo , Fosfopiruvato Hidratase/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , Feminino , Gansos/classificação , Dados de Sequência Molecular , Especificidade de Órgãos , Fosfopiruvato Hidratase/química , Filogenia , RNA Mensageiro/genética , Alinhamento de SequênciaRESUMO
The objective of this work was to elucidate the gene expression profiles of luteinizing hormone (LH), prolactin (PRL) and their receptors during the developmental and egg laying stage. The expression of genes encoding pituitary LH and PRL, as well as those for the ovarian LH receptor (LHR) and PRL receptor (PRLR), was determined by quantitative real-time PCR in Zi geese on day 1 and at 1, 2, 3, 4, 5, 6, 7 and 8 months of age, respectively. The expression of LH and LHR fluctuated and increased as the geese aged. The expression of LH was significantly higher at 5 to 8 months of age than in 1 day old geese (P < 0.05). The expression of LHR was higher at 8 months than at 1 day, at 1 to 4 months and at 6 months (P < 0.05). The expression of PRL decreased from day 1, followed by an increase from 3 months, and reached the highest values at 8 months of age in the study. The difference in PRL expression between 7 and 8 months of age was significant (P < 0.05). The expression of PRLR decreased initially and this was followed by a fluctuating increase from 5 months until 8 months of age. The expression of PRLR in 1 to 8 month old geese was significantly lower than at day 1 (P < 0.05). These results suggest that LH and PRLR may play an important role in ovarian development and the egg-laying process in Zi geese.
Assuntos
Gansos/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hormônio Luteinizante/metabolismo , Prolactina/metabolismo , Receptores do LH/metabolismo , Receptores da Prolactina/metabolismo , Animais , Feminino , Gansos/metabolismo , Hormônio Luteinizante/genética , Prolactina/genética , Receptores do LH/genética , Receptores da Prolactina/genética , Aumento de PesoRESUMO
Spermidine is a class of biologically active organic small molecules that play an important role in maintaining intestinal homeostasis. The specific objective of this study was to explore the effects of spermidine on intestinal morphology, metabolites, and microbial diversity in mice. We showed that 0.3 mmol/L of spermidine significantly promoted the growth of ileal villi (p < 0.05), and 3.0 mmol/L of spermidine significantly increased the body weight of mice and promoted the growth of jejunum villi (p < 0.05). The 16S rDNA sequencing results indicated that 3.0 mmol/L of spermidine affected the balance of the intestinal flora by increasing the abundance of intestinal Lactic acid bacteria and reducing the abundance of harmful bacteria (Turicibacter and Alistipes). Additionally, spermidine affects the levels of microbial metabolites such as succinic acid and Pantetheine. In summary, spermidine affects intestinal morphology and regulates intestinal flora and metabolites, and this study has provided a new understanding of spermidine's effects on the intestinal tract.
Assuntos
Microbioma Gastrointestinal , Espermidina , Espermidina/farmacologia , Mucosa Intestinal/metabolismo , Íleo , Jejuno , Microbioma Gastrointestinal/fisiologiaRESUMO
BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.
RESUMO
BACKGROUND: The mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expression in mevalonate pathway changes during cardiovascular remodelling in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Hearts and thoracic aortas were removed for the study of cardiovascular remodeling in SHR and Wistar-Kyoto rats (WKY). The protein expression of the enzymes in hearts, aortas and livers was analyzed by western blot. The histological measurements showed that the mass and the size of cardiomyocytes, the media thickness and the media cross-sectional area (MCSA) of the thoracic aorta were all increased in SHR since 3 weeks of age. In the heart, there was overexpression of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FDPS), and geranylgeranyltransferase type I (GGTase-I), and downregulation of squalene synthetase (SQS) in SHR since 3 weeks of age. In the aorta, besides similar expressions of HMGR, SQS, FDPS and GGTase-I as in the heart, there was upregulation of farnesyltransferase α at 16 and 25 weeks of age and of farnesyltransferase ß in 25-weeks-old SHR. Western blot demonstrated overexpression of HMGR and downregulation of SQS in SHR livers at all ages tested. CONCLUSIONS: The cardiovascular remodeling of SHR preceded the development of hypertension, and altered expression of several key enzymes in the mevalonate pathway may play a potential pathophysiological role in cardiovascular remodeling.
Assuntos
Aorta Torácica/enzimologia , Hipertensão/enzimologia , Ácido Mevalônico/metabolismo , Miocárdio/enzimologia , Remodelação Ventricular , Fatores Etários , Envelhecimento , Alquil e Aril Transferases/metabolismo , Análise de Variância , Animais , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Pressão Sanguínea , Western Blotting , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Modelos Animais de Doenças , Farnesil-Difosfato Farnesiltransferase/metabolismo , Farnesiltranstransferase/metabolismo , Geraniltranstransferase/metabolismo , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Fígado/enzimologia , Masculino , Miocárdio/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
The profile of ERalpha and ERbeta gene expression in the ovaries of Zi geese at 1 day and 1,2, 3, 4, 5 and 8 months of age (n=8, respectively) was examined by quantitative real-time PCR (qRT-PCR). The results showed that the expression of ERalpha and ERbeta mRNA was greater at 1 to 5 and 8 months compared with that observed at 1 day. In particular, the level of expression of ERalpha and ERbeta at 8 months was greater, 2.47 +/- 0.23 fold and 29.07 +/- 1.25 fold, respectively, compared with that at 1 day (P<0.05). The expression of ERalpha mRNA was not significantly different at 1, 2, 3 and 4 months (P>0.05). The level of expression of ERalpha mRNA at 5 months was 1.86 +/- 0.17 fold higher than at 1 day (P<0.05). The level of expression of ERbeta mRNA at 2, 3, 4, 5 and 8 months (1.96 +/- 0.13, 2.58 +/- 0.08, 2.08 +/- 0.05, 3.25 +/- 0.11 and 29.07 +/- 1.25 fold, respectively, P<0.05) was significantly higher than at 1 day. In summary, the expression of ERalpha and ERbeta mRNA in the ovaries of geese was increased between newborn and the laying stage. These results suggest that ERalpha and ERbeta mediate the process of ovarian development and egg laying in geese. In addition, ERbeta may play a more important role in regulating the response of the ovary to estrogen during the developmental and egg-laying stages.
Assuntos
Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Gansos/genética , Perfilação da Expressão Gênica , Ovário/metabolismo , Animais , Sequência de Bases , Primers do DNA , Eletroforese em Gel de Ágar , Feminino , Reação em Cadeia da Polimerase em Tempo RealRESUMO
In order to evaluate the expression profile of follicle-stimulating hormone receptor (FSHR) mRNA in the ovary of Zi geese during developmental and egg laying stages, the expression levels of FSHR mRNA in the ovary of Zi geese at the ages of 1 day, 1, 2, 3, 4, 5 and 8 months (n=8, respectively) were examined by quantitative real-time PCR (qRT-PCR). The results showed that FSHR mRNA expression was greater at the age of 1 to 5 and 8 months compared to expression at day 1 (P < 0.05). Particularly, the expression of FSHR mRNA at 4, 5 and 8 months was much greater, 1.86 +/- 0.14, 3.50 +/- 0.19 and 5.11 +/- 0.27 fold, respectively, compared to expression at day 1 (P < 0.01). The level of FSHR mRNA expression at 1, 2 and 3 months was 1.35 +/- 0.12, 1.31 +/- 0.05 and 1.28 +/- 0.09 fold greater, respectively, compared to day 1 (P < 0.05). The results indicate that the expression of FSHR mRNA remains at a stable level during the early developmental stage, and increases initially from 4 months until the egg laying stage. In addition, these results support the possibility that FSHR plays a pivotal role in mediating the response of the goose ovary to follicle-stimulating hormone during the developmental and egg laying stages, and especially during the latter.
Assuntos
Gansos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Ovário/metabolismo , Oviposição/fisiologia , Receptores do FSH/metabolismo , Animais , Feminino , Gansos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do FSH/genéticaRESUMO
An outbreak of hemorrhagic fever with renal syndrome (HFRS) occurred among students in Shenyang Pharmaceutical University in 2006. We conducted a study to characterize etiologic agents of the outbreaks and clarify the origin of hantaviruses causing infections in humans and laboratory animals. Immunoglobulin (Ig) M or IgG antibodies against Seoul virus (SEOV) were detected in the serum samples of all 8 patients. IgG antibodies against hantavirus were also identified in laboratory rats, which were used by these students for their scientific research. Phylogenetic analysis showed that partial small segment sequences recovered from humans, laboratory rats, and local wild rats belonged to SEOV. Hantavirus sequences recovered from humans and laboratory rats clustered within 1 of 3 lineages of SEOV circulating among local wild rats in Shenyang. These results suggest that the HFRS outbreak in Shenyang was caused by SEOV that was circulating among local wild rats and had also infected the laboratory rats.
Assuntos
Anticorpos Antivirais/sangue , Surtos de Doenças , Febre Hemorrágica com Síndrome Renal/epidemiologia , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/transmissão , Vírus Seoul , Adulto , Animais , Animais de Laboratório/virologia , Animais Selvagens/virologia , China/epidemiologia , Feminino , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Murinae/virologia , Filogenia , Ratos , Ratos Wistar , Doenças dos Roedores/virologia , Vírus Seoul/classificação , Vírus Seoul/genética , Vírus Seoul/imunologia , Vírus Seoul/isolamento & purificação , Análise de Sequência de DNA , Estudantes , Universidades , Adulto Jovem , Zoonoses/epidemiologia , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
Coleus blumei can be infected by several viroids of the genus Coleviroid. One year after detecting a mixed infection of coleus blumei viroid 1 (CbVd-1) and 5 (CbVd-5) in coleus seedlings inoculated with these two viroids, we found an additional viroid-like RNA. Sequence analysis revealed a viroid of 342 nucleotides that contains the central conserved region of coleviroids and is a chimera of the left half of CbVd-3 and the right half of CbVd-5. This new viroid, tentatively referred to as coleus blumei viroid 6 (CbVd-6), appears to have arisen from a natural recombination event or genome shuffling.
Assuntos
Coleus/virologia , Recombinação Genética , Viroides/classificação , Viroides/isolamento & purificação , Sequência de Bases , Eletroforese em Gel Bidimensional , Modelos Moleculares , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Análise de Sequência de DNA , Viroides/genéticaRESUMO
Characterization of viroid-derived small RNAs (vd-sRNAs) is important to understand viroid-host interactions; however, vd-sRNAs belonging to the genus Coleviroid are yet to be identified and characterized. Herein, we used coleus plants singly infected with coleus blumei viroid (CbVd)-1, -5, or -6 and doubly infected with CbVd-1 and -5 to identify and analyze their vd-sRNAs. We found sense and antisense vd-sRNAs for CbVd-1, -5 and -6, and 22-nt vd-sRNAs were the most abundant; moreover, the 5'-terminal nucleotides (nts) of CbVd-1, -5, and -6 were biased toward U and C, and sRNAs derived from these three viroids were unevenly distributed along their genomes. We also noted that CbVd-5 and -6 share a fragment that forms the right half of the rod-like secondary structure of these viroids, which implied that they generated almost the same type of vd-sRNAs. This finding indicated that vd-sRNA biogenesis is mainly determined by the primary sequence of their substrates. More importantly, we found two complementary vd-sRNAs (22 nt) that were generated from the central conserved region (CCR) of these three viroids, suggesting an important role of CCR in vd-sRNA biogenesis. In conclusion, our results provide novel insight into the biogenesis of vd-sRNAs and the biological roles of CCR.
Assuntos
Coleus/virologia , Pequeno RNA não Traduzido/genética , RNA Viral/genética , Viroides/genética , Sequência de Bases , Genoma Viral/genética , Conformação de Ácido Nucleico , Pequeno RNA não Traduzido/biossíntese , Viroides/metabolismo , Viroides/fisiologiaRESUMO
Accumulating evidence suggests that long noncoding RNA (lncRNA) plays important regulatory roles in cancer biology. However, the involvement of lncRNA in colorectal carcinoma progression remains largely unknown, especially in colorectal carcinoma metastasis. In this study, we investigated the changes in lncRNA expression in colorectal carcinoma and identified a new lncRNA, the antisense transcript of SATB2 (SATB2-AS1), as a key regulator of colorectal carcinoma progression. SATB2-AS1 was frequently downregulated in colorectal carcinoma cells and tissues, and patients whose tumors expressed SATB2-AS1 at low levels had a shorter overall survival and poorer prognosis. Downregulation of SATB2-AS1 significantly promoted cell proliferation, migration, and invasion in vitro and in vivo, demonstrating that it acts as a tumor suppressor in colorectal carcinoma. SATB2-AS1 suppressed colorectal carcinoma progression by serving as a scaffold to recruit p300, whose acetylation of H3K27 and H3K9 at the SATB2 promoter upregulated expression of SATB2, a suppressor of colorectal carcinoma growth and metastasis. SATB2 subsequently recruited HDAC1 to the Snail promoter, repressing Snail transcription and inhibiting epithelial-to-mesenchymal transition. Taken together, these data reveal SATB2-AS1 as a novel regulator of the SATB2-Snail axis whose loss facilitates progression of colorectal carcinoma. SIGNIFICANCE: These data show that the lncRNA SATB2-AS1 mediates epigenetic regulation of SATB2 and Snail expression to suppress colorectal cancer progression.See related commentary by Li, p. 3536.
Assuntos
Neoplasias Colorretais/genética , Proteínas de Ligação à Região de Interação com a Matriz , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Epigênese Genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de TranscriçãoRESUMO
BACKGROUND: Higher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce. METHODS: 345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured. RESULTS: T2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients. CONCLUSION: Higher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Obesidade/sangue , alfa-2-Glicoproteína-HS/análise , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Reactive oxygen species (ROS), originating predominantly from vascular smooth muscle cells (VSMCs), lead to vascular damage and endothelial dysfunction in rats with hypertension. The downstream signaling pathways of farnesyl pyrophosphate (FPP) synthase, Ras-related C3 botulinum toxin substrate 1 (Rac1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mediate the generation of ROS. The present study investigated the effect of the FPP synthase inhibitor, ibandronate, on ROS production, the possible beneficial effect on endothelial dysfunction and the underlying mechanisms in spontaneously hypertensive rats (SHRs). The SHRs were treated with ibandronate for 30 days. Endotheliumdependent and independent vasorelaxation were measured in isolated aortic rings. Additionally, VSMCs from the SHRs and WistarKyoto (WKY) rats were cultured. The production of ROS and activation of NADPH oxidase were determined using fluorescence and chemiluminescence, respectively, in vivo and in vitro. Angiotensin II (Ang II) increased ROS production in the cultured VSMCs from the WKY rats and SHRs, in a concentrationdependent manner. The Ang IIinduced responses were more marked in the SHR VSMCs, compare with those in the WKY VSMCs, however, the response decreased significantly following ibandronate pretreatment. Treatment with ibandronate significantly decreased the production of ROS, translocation of NADPH oxidase subunit p47phox, and activities of NADPH oxidase and Rac1 in the aorta and VSMCs, and improved the impaired endotheliumdependent vasodilation in the SHRs. Adding geranylgeraniol, but not farnesol or mevalonate, reversed the inhibitory effects of ibandronate. In addition, inhibiting geranylgeranyl-transferase mimicked the effect of ibandronate on the excess oxidative response. Ibandronate exerted cellular antioxidant effects through the Rac1/NADPH oxidase pathway. These effects may have contributed to the vasoprotective effects on the impaired endothelium in SHRs.
Assuntos
Difosfonatos/farmacologia , Endotélio Vascular/metabolismo , Geraniltranstransferase/antagonistas & inibidores , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Animais , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Ácido Ibandrônico , NADPH Oxidases/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: The higher expression of vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) is associated with the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fetuin-A is shown to have proangiogenic and proinflammatory effects. METHODS: This study included 245 T2DM patients consisting of 95 cases with non-diabetic retinopathy (NDR), 78 cases with non-proliferative diabetic retinopathy (NPDR) and 72 cases with proliferative diabetic retinopathy (PDR), in addition to 65 healthy controls. Serum fetuin-A, VEGF and CRP concentrations and related parameters were measured. RESULTS: Significant positive correlations were found between fetuin-A and VEGF and CRP, and between VEGF and CRP in T2DM patients (all p<0.001). After adjustment for confounders, fetuin-A was correlated independently with VEGF and CRP in NPDR and PDR patients, but not in NDR subjects. In addition, fetuin-A was correlated independently with HOMA-IR (all 4 groups), HbA1c (NDR, NPDR and PDR groups) and duration of diabetes (PDR group). When compared with NDR and control subjects, NPDR and PDR patients had higher HOMA-IR. CONCLUSIONS: Serum fetuin-A concentrations are independently correlated with VEGF and CRP concentrations in T2DM patients with DR, but not in NDR subjects.
Assuntos
Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/complicações , Fator A de Crescimento do Endotélio Vascular/sangue , alfa-2-Glicoproteína-HS/metabolismo , Idoso , Nefropatias Diabéticas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To report a case of Tako-tsubo cardiomyopathy in a blind woman. CASE PRESENTATION: We report a confirmed case of Tako-tsubo cardiomyopathy in a 55-year-old blind woman with past medical history of ocular trauma. The patient suffered from sudden chest pain after a quarrel. Transthoracic echocardiogram (TTE) showed regional wall motion abnormalities. Coronary angiogram showed no significant coronary stenosis, but ventriculogram demonstrated apical ballooning akinesis and hypercontraction in the basal segments. The follow-up TTE revealed a recovery of systolic function 6 weeks later. CONCLUSION: We report a case of Tako-tsubo cardiomyopathy after a quarrel, implicating that severe emotional or physical stress could trigger myocardial stunning.
Assuntos
Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/etiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Cegueira , Angiografia Coronária , Ecocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Cardiomiopatia de Takotsubo/complicações , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Three-dimensional hierarchical Prussian blue composed of ultrathin nanosheets was successfully synthesized by employing a self-aggregation and oriented attachment strategy. The unique structure highly increases the exposure of micropores and metal sites of Prussian blue to guests, thus significantly enhancing its hetero-catalysis and adsorption properties compared to cubic and commercial counterparts.