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1.
Mol Cell ; 82(4): 785-802.e10, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35104452

RESUMO

p53, master transcriptional regulator of the genotoxic stress response, controls cell-cycle arrest and apoptosis following DNA damage. Here, we identify a p53-induced lncRNA suicidal PARP-1 cleavage enhancer (SPARCLE) adjacent to miR-34b/c required for p53-mediated apoptosis. SPARCLE is a ∼770-nt, nuclear lncRNA induced 1 day after DNA damage. Despite low expression (<16 copies/cell), SPARCLE deletion increases DNA repair and reduces DNA-damage-induced apoptosis as much as p53 deficiency, while its overexpression restores apoptosis in p53-deficient cells. SPARCLE does not alter gene expression. SPARCLE binds to PARP-1 with nanomolar affinity and causes apoptosis by acting as a caspase-3 cofactor for PARP-1 cleavage, which separates PARP-1's N-terminal (NT) DNA-binding domain from its catalytic domains. NT-PARP-1 inhibits DNA repair. Expressing NT-PARP-1 in SPARCLE-deficient cells increases unrepaired DNA damage and restores apoptosis after DNA damage. Thus, SPARCLE enhances p53-induced apoptosis by promoting PARP-1 cleavage, which interferes with DNA-damage repair.


Assuntos
Apoptose , Caspase 3/metabolismo , Neoplasias Colorretais/enzimologia , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , Poli(ADP-Ribose) Polimerase-1/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Células A549 , Animais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo do DNA , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HEK293 , Células Hep G2 , Humanos , Masculino , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Proteína Supressora de Tumor p53/genética
2.
Genes Dev ; 35(1-2): 102-116, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33334821

RESUMO

p53 is an intensely studied tumor-suppressive transcription factor. Recent studies suggest that the RNA-binding protein (RBP) ZMAT3 is important in mediating the tumor-suppressive effects of p53. Here, we globally identify ZMAT3-regulated RNAs and their binding sites at nucleotide resolution in intact colorectal cancer (CRC) cells. ZMAT3 binds to thousands of mRNA precursors, mainly at intronic uridine-rich sequences and affects their splicing. The strongest alternatively spliced ZMAT3 target was CD44, a cell adhesion gene and stem cell marker that controls tumorigenesis. Silencing ZMAT3 increased inclusion of CD44 variant exons, resulting in significant up-regulation of oncogenic CD44 isoforms (CD44v) and increased CRC cell growth that was rescued by concurrent knockdown of CD44v Silencing p53 phenocopied the loss of ZMAT3 with respect to CD44 alternative splicing, suggesting that ZMAT3-mediated regulation of CD44 splicing is vital for p53 function. Collectively, our findings uncover a p53-ZMAT3-CD44 axis in growth suppression in CRC cells.


Assuntos
Processamento Alternativo/genética , Receptores de Hialuronatos/genética , Splicing de RNA/genética , Proteínas de Ligação a RNA/metabolismo , Carcinogênese/genética , Neoplasias Colorretais/genética , Técnicas de Silenciamento de Genes , Inativação Gênica , Células HCT116 , Células HEK293 , Humanos , Receptores de Hialuronatos/metabolismo , Ligação Proteica/genética , Precursores de RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteína Supressora de Tumor p53/metabolismo
3.
J Cell Mol Med ; 28(10): e18445, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38801403

RESUMO

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.


Assuntos
Doenças Autoimunes , Quimiocina CCL20 , Quimiotaxia , Interleucina-17 , Prostatite , Células Th17 , Masculino , Prostatite/imunologia , Prostatite/patologia , Prostatite/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Animais , Interleucina-17/metabolismo , Interleucina-17/imunologia , Camundongos , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Macrófagos/metabolismo , Macrófagos/imunologia , Modelos Animais de Doenças , NF-kappa B/metabolismo , Transdução de Sinais , Humanos , Camundongos Endogâmicos C57BL , Próstata/patologia , Próstata/metabolismo , Próstata/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Autoimunidade
4.
J Asthma ; 60(3): 600-608, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35608065

RESUMO

OBJECTIVE: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. METHODS: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. RESULTS: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. CONCLUSIONS: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.


Assuntos
Asma , COVID-19 , Doença Pulmonar Obstrutiva Crônica , Estado Asmático , Adulto , Humanos , Asma/tratamento farmacológico , Nebulizadores e Vaporizadores , Administração por Inalação , Inaladores Dosimetrados , Broncodilatadores/uso terapêutico , Estado Asmático/tratamento farmacológico , Atitude do Pessoal de Saúde , Pessoal de Saúde , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Albuterol/uso terapêutico
5.
Biochem Genet ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910330

RESUMO

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case-control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185-8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187-9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results.

6.
BMC Cardiovasc Disord ; 22(1): 458, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324069

RESUMO

BACKGROUND: Bilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients. METHODS: After identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels. RESULTS: Forty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: - 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD - 0.30 [95%CI: - 0.56, - 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = - 0.17 [95% CI: - 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: - 8.164 [- 14.531, - 1.769]; p = 0.016) in MI patients. CONCLUSION: Prognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Feminino , Doença da Artéria Coronariana/diagnóstico , Bilirrubina , Prognóstico , Razão de Chances , Fatores de Risco
7.
PLoS Genet ; 14(11): e1007802, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30496290

RESUMO

The human genome encodes thousands of long noncoding RNA (lncRNA) genes; the function of majority of them is poorly understood. Aberrant expression of a significant number of lncRNAs is observed in various diseases, including cancer. To gain insights into the role of lncRNAs in breast cancer progression, we performed genome-wide transcriptome analyses in an isogenic, triple negative breast cancer (TNBC/basal-like) progression cell lines using a 3D cell culture model. We identified significantly altered expression of 1853 lncRNAs, including ~500 natural antisense transcript (NATs) lncRNAs. A significant number of breast cancer-deregulated NATs displayed co-regulated expression with oncogenic and tumor suppressor protein-coding genes in cis. Further studies on one such NAT, PDCD4-AS1 lncRNA reveal that it positively regulates the expression and activity of the tumor suppressor PDCD4 in mammary epithelial cells. Both PDCD4-AS1 and PDCD4 show reduced expression in TNBC cell lines and in patients, and depletion of PDCD4-AS1 compromised the cellular levels and activity of PDCD4. Further, tumorigenic properties of PDCD4-AS1-depleted TNBC cells were rescued by exogenous expression of PDCD4, implying that PDCD4-AS1 acts upstream of PDCD4. Mechanistically, PDCD4-AS1 stabilizes PDCD4 RNA by forming RNA duplex and controls the interaction between PDCD4 RNA and RNA decay promoting factors such as HuR. Our studies demonstrate crucial roles played by NAT lncRNAs in regulating post-transcriptional gene expression of key oncogenic or tumor suppressor genes, thereby contributing to TNBC progression.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Estabilidade de RNA , RNA Antissenso/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Proteínas de Ligação a RNA/genética , Neoplasias de Mama Triplo Negativas/genética , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Ligação Proteica , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
8.
Hu Li Za Zhi ; 68(1): 43-53, 2021 Feb.
Artigo em Zh | MEDLINE | ID: mdl-33521918

RESUMO

BACKGROUND: Because of the COVID-19 epidemic, people are mostly isolated at home and must seek medical advice over the internet. In addition, government authorities are currently investing greater efforts in developing internet hospitals. PURPOSE: The purpose of this essay was to assess how outpatients feel about online outpatient clinics and to analyze the factors that affect their satisfaction and willingness to return to these clinics. The results provide advice regarding how to more effectively encourage patients to use online outpatient clinics. METHODS: A self-developed questionnaire was used to survey 191 patients who had visited the online outpatient clinic of a tertiary hospital in Sichuan Province from January to July 2019. A descriptive analysis was conducted on the collected data, and factors influencing satisfaction were identified. RESULTS: The majority of the surveyed patients were young or middle-aged (92.7%) and 42.9% held a college degree or higher. Nearly three-quarters (72.2%) expressed feeling satisfied or better with the online outpatient clinic, with 31.4% of these expressing feeling very satisfied. Nearly all (91.1%) expressed the opinion that the online outpatient clinic had improved their awareness of health self-management . Furthermore, 176 (92.1%) were willing to use the online outpatient clinic again. The results of univariate analysis showed that the main factors negatively influencing re-use of the online outpatient clinic were: failure to solve the problem in a timely manner (χ2 = 8.603, p = .045), the complicated process of online registration (χ2 = 8.322, p = .016), the failure of the online physical examination (χ2 = 8.958, p = .015), and unreliable quality (χ2 = 15.373, p = .004). CONCLUSIONS: The participants surveyed in this study reported a lower satisfaction for their online outpatient clinic experience than reported in similar surveys of traditional outpatient services. However, many reported that their health-related self-management awareness had improved after use, indicating that they feel better about the online outpatient clinic. The factors that affected willingness to reuse to the online outpatient clinic related mainly to imperfections related to the clinic and its inability to adequately meet patient needs. Online outpatient clinics should simplify the process of registration, improve functions, and increase service functions such as online examination appointments and follow-up visits to improve patient satisfaction.


Assuntos
COVID-19 , Idoso , Instituições de Assistência Ambulatorial , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Retratamento , SARS-CoV-2 , Inquéritos e Questionários
9.
Nucleic Acids Res ; 46(19): 10405-10416, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30102375

RESUMO

Long non-coding RNAs (lncRNAs) regulate vital biological processes, including cell proliferation, differentiation and development. A subclass of lncRNAs is synthesized from microRNA (miRNA) host genes (MIRHGs) due to pre-miRNA processing, and are categorized as miRNA-host gene lncRNAs (lnc-miRHGs). Presently, the cellular function of most lnc-miRHGs is not well understood. We demonstrate a miRNA-independent role for a nuclear-enriched lnc-miRHG in cell cycle progression. MIR100HG produces spliced and stable lncRNAs that display elevated levels during the G1 phase of the cell cycle. Depletion of MIR100HG-encoded lncRNAs in human cells results in aberrant cell cycle progression without altering the levels of miRNA encoded within MIR100HG. Notably, MIR100HG interacts with HuR/ELAVL1 as well as with several HuR-target mRNAs. Further, MIR100HG-depleted cells show reduced interaction between HuR and three of its target mRNAs, indicating that MIR100HG facilitates interaction between HuR and target mRNAs. Our studies have unearthed novel roles played by a MIRHG-encoded lncRNA in regulating RNA binding protein activity, thereby underscoring the importance of determining the function of several hundreds of lnc-miRHGs that are present in human genome.


Assuntos
Ciclo Celular/genética , Proteína Semelhante a ELAV 1/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Diferenciação Celular/genética , Divisão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética
10.
J Appl Toxicol ; 40(11): 1480-1490, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33020912

RESUMO

As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate-induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKCα) signaling in neuroblastoma SK-N-SH cells. PKCα activators could positively regulate TOCP-induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKCα activation impaired the ubiquitin-proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF-H families in neurodegenerative disorders.


Assuntos
Autofagia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Proteína Quinase C-alfa/metabolismo , Tritolil Fosfatos/toxicidade , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neurônios/enzimologia , Neurônios/ultraestrutura , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , Ubiquitinação , Proteínas tau/metabolismo
11.
J Oral Rehabil ; 47(7): 802-808, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32124452

RESUMO

OBJECTIVE: To translate and cross-culturally adapt the Craniofacial Pain and Disability Inventory (CF-PDI) into Chinese and, to evaluate measurement properties of the web-based version of the CF-PDI. METHODS: The Chinese version (CF-PDI/C) was first produced according the guidelines. Then, the web-based version of CF-PDI/C (eCF-PDI/C) was developed by our team and a third-party survey provider. The eCF-PDI/C was distributed to patients with painful temporomandibular disorders (TMD) with or without headache to evaluate its psychometric properties. The reliability of the eCF-PDI/C was detected by internal consistency and test-retest reliability. The validity of the measure was performed through construct validity and convergent validity. RESULTS: A total of 206 patients were recruited. The Cronbach's α value and the intraclass correlation coefficients (ICC) value of the eCF-PDI/C was .912 and .82, respectively. Following exploratory factor analysis (EFA), three factors were extracted, accounting for 77.153% of the total variation. With regard to the convergent validity, the measure evidenced a good relationship with the global health question. CONCLUSIONS: The eCF-PDI/C displays good reliability and validity through rigorous performance tests. This can be recommended for use among patients with painful TMD with or without headache.


Assuntos
Dor Facial , Internet , Humanos , Medição da Dor , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
12.
Cancer Sci ; 110(7): 2180-2188, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31046163

RESUMO

Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real-time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/genética , RNA/genética , Regulação para Cima , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Neoplasias Bucais/sangue , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , RNA Circular , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Sequenciamento do Exoma
13.
J Clin Lab Anal ; 33(1): e22650, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30101436

RESUMO

BACKGROUND: The main risk factors for atherosclerosis patients are not fully explicated. The aim of this study was to analyze the levels of blood lipid and glycosylated lipoprotein in patients with coronary artery atherosclerosis and healthy individuals and to study the relationship between the glycosylated lipoprotein and atherosclerosis. METHODS: The study involved 200 patients diagnosed with myocardial infarction caused by coronary atherosclerosis as case group and 230 healthy individuals as control group. We analyzed and contrasted the levels of blood lipid and glycosylated lipoprotein between the different groups. In addition, we investigated the correlation between glycosylated low-density lipoprotein (G-LDL) and glucose levels. RESULTS: There is no statistical difference between the level of TG in case group and control group. The level of CHOL, HDL-C, and LDL-C in case group is significantly lower than that in control group (3.90 [3.23, 4.42] vs 5.16 [4.86, 5.77] [mmol/L]; 1.09 [0.83, 1.38] vs 1.46 [1.15, 1.80] [mmol/L]; 2.22 [1.68, 2.81] vs 2.95 [2.60, 3.27] [mmol/L]) (P < 0.05). The level of GLU, HbA1c, G-HDL, and G-LDL in case group is significantly higher than that in control group (7.10 [5.68, 9.27] vs 4.84 [4.68, 5.07] [mmol/L]; 6.8 [6.3, 7.4] vs 5.9 [5.6, 6.1] [%]; 30.08 [25.04, 40.17] vs 22.95 [18.14, 27.06] [ng/mL], 6.26 [4.95, 7.50] vs 3.61 [2.66, 5.15] [ng/mL]) (p < 0.05). The level of G-LDL in patients with coronary atherosclerosis was relevant with the level of GLU and HbA1c (r = 0.625, 0.706, P < 0.05), and there was no relevance with LDL-C (r = 0.331, P > 0.05). CONCLUSION: Hyperlipidemia is not an important cause of coronary atherosclerosis. High glucose levels and glycosylated lipoprotein are of high importance in the development and progression of coronary atherosclerosis.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Idoso , Aterosclerose/sangue , Aterosclerose/epidemiologia , Glicemia/análise , Estudos de Casos e Controles , Feminino , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio
14.
Mol Cancer ; 17(1): 168, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477520

RESUMO

Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy.


Assuntos
Neoplasias/metabolismo , Neoplasias/patologia , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Linfócitos T Reguladores/patologia
15.
Immunol Invest ; 47(7): 689-699, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29873573

RESUMO

OBJECTIVE: The etiology of cardiovascular disease (CVD) is complex owing to the interactions of genetic variance with environmental factors. Inflammatory processes are now being increasingly implicated in the pathogenesis of CVD. This meta-analysis investigated the potential role of interleukin-6 (IL-6) as a risk factor for CVD development in healthy individuals. METHODS: Literature search was carried out in multiple electronic databases, and study selection followed a priori eligibility criteria. Meta-analyses of standardized mean differences were carried out to determine an overall effect size of the difference in IL-6 levels between CVD cases and non-CVD matched controls. Meta-regression analyses were performed to examine the relationship between the IL-6 levels in CVD cases and several explanatory variables. RESULTS: Seventeen studies enrolling 288738 healthy individuals with an average follow-up duration of 7.4 ± 4.1 years were found eligible. Overall, data of 5400 CVD cases and 14607 matched non-CVD controls are used in the present meta-analysis. Baseline IL-6 levels were significantly higher in CVD cases than in non-CVD controls (standardized mean difference [95% confidence interval]) of 0.14 [0.09, 0.20]/mean difference of 0.36 [0.28, 0.44] picogram per milliliter). Total cholesterol, LDL-cholesterol, and triglyceride levels were also significantly higher, and HDL-cholesterol levels were significantly lower in CVD cases in comparison with the controls. Systolic blood pressure and total cholesterol levels had a significantly positive relationship, whereas triglyceride levels had a significantly inverse relationship with the levels of IL-6. CONCLUSION: Higher IL-6 levels in healthy individuals are associated with CVD risk, which is co-associated with hypertension and hypercholesterolemia.


Assuntos
Doenças Cardiovasculares/epidemiologia , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Interleucina-6/metabolismo , Doenças Cardiovasculares/imunologia , Colesterol/metabolismo , Feminino , Seguimentos , Humanos , Interleucina-6/genética , Masculino , Estudos Prospectivos , Fatores de Risco , Regulação para Cima
16.
Proc Natl Acad Sci U S A ; 112(13): E1550-8, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25775580

RESUMO

The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediators of gene repression and have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in CRC, remain poorly understood. Here, we identified microRNA-215 (miR-215) as a direct transcriptional target of CDX1 by using high-throughput small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines: CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T and LS174T with stable CDX1 knockdown. Validation of candidate miRNAs identified by RNA-seq in a larger cell-line panel revealed miR-215 to be most significantly correlated with CDX1 expression. Quantitative ChIP-PCR and promoter luciferase assays confirmed that CDX1 directly activates miR-215 transcription. miR-215 expression is depleted in FACS-enriched cancer stem cells compared with unsorted samples. Overexpression of miR-215 in poorly differentiated cell lines causes a decrease in clonogenicity, whereas miR-215 knockdown increases clonogenicity and impairs differentiation in CDX1-high cell lines. We identified the genome-wide targets of miR-215 and found that miR-215 mediates the repression of cell cycle and stemness genes downstream of CDX1. In particular, the miR-215 target gene BMI1 has been shown to promote stemness and self-renewal and to vary inversely with CDX1. Our work situates miR-215 as a link between CDX1 expression and BMI1 repression that governs differentiation in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/citologia , Diferenciação Celular , Linhagem Celular Tumoral , Colo/metabolismo , Ilhas de CpG , Perfilação da Expressão Gênica , Células HCT116 , Humanos , Complexo Repressor Polycomb 1/metabolismo , Análise de Sequência de RNA , Transfecção
17.
Methods ; 108: 111-7, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27102625

RESUMO

Gene expression changes in the functional absence of a specific RecQ protein, and how that relates to disease outcomes including cancer predisposition and premature aging in RecQ helicase associated syndromes, are poorly understood. Here we describe detailed experimental strategy for identification of RECQ1-regulated transcriptome that led us to uncover a novel association of RECQ1 in regulation of cancer cell migration and invasion. We initiated a focused study to determine whether RECQ1, the most abundant RecQ protein in humans, alters gene expression and also investigated whether RECQ1 binds with G4 motifs predicted to form G-quadruplex structures in the target gene promoters. Rescue of mRNA expression of select RECQ1-downregulated genes harboring G4 motifs required wild-type RECQ1 helicase. However, some RECQ1-regulated genes are also regulated by BLM and WRN proteins regardless of the presence or absence of G4 motifs. The approach described here is applicable for systematic comparison of gene expression signatures of individual RecQ proteins in isogenic background, and to elucidate their participation in transcription regulation through G-quadruplex recognition and/or resolution. Such strategies might also reveal molecular pathways that drive the pathogenesis of cancer and other diseases in specific RecQ deficiency.


Assuntos
Perfilação da Expressão Gênica/métodos , Neoplasias/genética , RecQ Helicases/genética , Transcriptoma/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(6): 886-890, 2017 Nov.
Artigo em Zh | MEDLINE | ID: mdl-29260526

RESUMO

OBJECTIVE: To explore the association between intake of pickled vegetables and colorectal cancer (CRC),including the interactions between pickled vegetables and other dietary habits. METHODS: A 1:1 matched case-control study was undertaken,involving 400 patients with newly histopathologically diagnosed CRC and 400 healthy residents matched by age and gender. The participants were asked to complete a questionnaire. Conditional logistic regression models were established to identify risk factors of CRC and interactions between these factors. Additive interactions were analyzed using relative excess risk of interaction (RERI),attributable proportion of interaction (AP),and synergy index (S). RESULTS: Excessive intake of pickled vegetables (more than 3 times per week) increased the risk of CRC [odds ratio (OR)=2.703,95% confidence interval (CI): 1.866-3.916]. There was no multiplicative interaction between pickled vegetables and other dietary habits. Additive interactions were detected between pickled vegetables and cured meat,tea and bean products: with a RERI of 3.172 (95%CI: 0.834-5.518),2.131 (95%CI: 0.115-4.417) and 2.503 (95%CI: 0.760-4.246),respectively; an AP of 0.472 (95%CI: 0.245-0.699),0.386 (95%CI: 0.122-0.650) and 0.493 (95%CI: 0.253-0.732),respectively; and a S of 2.244 (95%CI: 1.266-3.978),1.893 (95%CI: 1.050-3.416) and 2.586 (95%CI:1.168-5.723) ,respectively. CONCLUSION: Excessive intake of pickled vegetables may be a risk factor of CRC. Cured meats and pickled vegetables might have a synergistic effect on CRC. However,tea and bean products might be antagonistic to the risk imposed by pickled vegetables on CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Dieta , Alimentos Fermentados , Verduras , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco
19.
Zhongguo Zhong Yao Za Zhi ; 42(20): 3895-3900, 2017 Oct.
Artigo em Zh | MEDLINE | ID: mdl-29243424

RESUMO

Young petiole of Tussilago farfara was used as the material to investigate the plant growth regulators which could influence in vitro culture and plant regeneration and to establish rapid propagation technique. The ideal sterilization method was that young petiole of T. farfara was sterilized with 75% ethanol for 30 s, and then transferred to saturated bleaching power supernatant for 15 min. The suitable medium for callus induction was MS+6-BA 3.0 mg•L⁻¹+2,4-D 2.0 mg•L⁻¹ with 96.2% induction rate. The seedlings had better differentiation with 91% differentiation rate and 8.26 buds on the medium containing MS+ZT 2.0 mg•L⁻¹+NAA 0.3 mg•L⁻¹. The preferred enrichment medium of adventitious bud was MS+KT 1.0 mg•L⁻¹+IBA 0.3 mg•L⁻¹ with 11.81 enrichment times and 4.9 cm seedling height. The rooting medium included 1/2MS+IBA 0.2 mg•L⁻¹ with the average number of rooting was 5.86 and the rooting rate was above 95.22%. The container seedlings can grow well and the survival rate was more than 90% when they were transplanted on the medium added with river sand and organic fertilizer with the ratio of 3∶1. The field experiments indicated that significant differences in increment and yield of pollen grains among the tissue-culture, cultivation and wild type of T. farfara under the same cultivation conditions. The cultivated plants were relatively high on the increment and yield of pollen grains. The active ingredient content of the tissue culture and the wild materials was basically the same.


Assuntos
Plantas Medicinais/crescimento & desenvolvimento , Regeneração , Técnicas de Cultura de Tecidos , Tussilago/crescimento & desenvolvimento , Meios de Cultura , Reguladores de Crescimento de Plantas
20.
Biomed Environ Sci ; 29(6): 457-60, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27470108

RESUMO

To evaluate the effect of acute high-altitude exposure on sensory and short-term memory using interactive software, we transported 30 volunteers in a sport utility vehicle to a 4280 m plateau within 3 h. We measured their memory performance on the plain (initial arrival) and 3 h after arrival on the plateau using six measures. Memory performance was significantly poorer on the plateau by four of the six measures. Furthermore, memory performance was significantly poorer in the acute mountain sickness (AMS) group than in the non-AMS group by five of the six measures. These findings indicate that rapid ascent to 4280 m and remaining at this altitude for 3 h resulted in decreased sensory and short-term memory, particularly among participants who developed AMS.


Assuntos
Doença da Altitude/epidemiologia , Altitude , Transtornos da Memória/epidemiologia , Doença Aguda , Adulto , Doença da Altitude/etiologia , China/epidemiologia , Humanos , Masculino , Transtornos da Memória/etiologia , Memória de Curto Prazo , Fatores de Tempo , Adulto Jovem
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