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1.
World J Clin Cases ; 12(20): 4357-4364, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015924

RESUMO

BACKGROUND: Lithium carbonate is used to manage various mood disorders, but it can cause thyroid abnormalities, including goiter, hypothyroidism, and hyperthyroidism. In rare cases, it can lead to giant goiter and subclinical hyperthyroidism, which may require surgical intervention in severe cases. CASE SUMMARY: This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment. The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve, which led to respiratory distress, hoarseness, and dysphagia. The immediate danger of suffocation required urgent surgical intervention. In this report, we describe the case of a 41-year-old Chinese woman. This sheds light on the etiology and challenges associated with managing a giant goiter. The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion. Prior to the procedure, the patient was given iodine to prepare. Concurrently, changes were made to the psychiatric medication regimen. Following surgery, the patient's respiratory function and vocal cord functionality improved significantly, and her mental state remained stable. CONCLUSION: It is essential to monitor thyroid function, test thyroid antibody levels, and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment. This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.

2.
Cell Discov ; 9(1): 74, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37460462

RESUMO

Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy.

3.
Oncogene ; 42(14): 1101-1116, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36792757

RESUMO

Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Processamento Alternativo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Isoformas de Proteínas/genética , Regulação Neoplásica da Expressão Gênica , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo
4.
Arq Bras Cardiol ; 109(5): 466-474, 2017 Nov.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29267627

RESUMO

BACKGROUND: Data are scarce regarding disparities in cardiovascular risk factor management between patients treated with percutaneous coronary intervention (PCI) and those treated with coronary artery bypass grafting (CABG). OBJECTIVE: Whether the goal achievement rates of cardiovascular risk factors were different between PCI and CABG patients. METHODS: We retrospectively reviewed the data retrieved from a clinical record database of patients admitted to Beijing Anzhen Hospital between January 1, 2014, and December 31, 2014, who underwent PCI or CABG. RESULTS: Compared with the CABG group, low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (28.6% vs. 24.7%; p < 0.01), LDL-C < 2.07 mmol/L (43.5% vs. 39.4%; p < 0.01) and blood pressure (BP) < 140/90 mm Hg (85.6% vs. 77.7%; p < 0.01) goal achievement rates were significantly higher in the PCI group. Compared with patients ≥ 60 years old: patients < 60 years old had better BP < 140/90 mm Hg goal achievement rates (87.7% vs. 84.4%; p < 0.01) in the PCI group, and better fasting blood-glucose (FBG) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) and HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) goal achievement rates in the CABG group. Compared with females: males had better LDL-C < 2.07 mmol/L (24.7% vs. 28.5%; p < 0.01), FBG < 7 mmol/L (71.8% vs.75.2%; p < 0.01) and HbA1c < 7% (70.4% vs. 74.1%; p < 0.01) goal achievement rates in the PCI group. CONCLUSION: Patients in the PCI group were generally more likely than those in the CABG group to achieve LDL-C < 1.8 mmol/L and BP goals. The control of cardiovascular risk factors differed between patients ≥ 60 years old and < 60 years old. Female patients were less likely to achieve LDL-C, FBG and HbA1c goals.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea , Prevenção Secundária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Arq. bras. cardiol ; 109(5): 466-474, Nov. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-887966

RESUMO

Abstract Background: Data are scarce regarding disparities in cardiovascular risk factor management between patients treated with percutaneous coronary intervention (PCI) and those treated with coronary artery bypass grafting (CABG). Objective: Whether the goal achievement rates of cardiovascular risk factors were different between PCI and CABG patients. Methods: We retrospectively reviewed the data retrieved from a clinical record database of patients admitted to Beijing Anzhen Hospital between January 1, 2014, and December 31, 2014, who underwent PCI or CABG. Results: Compared with the CABG group, low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (28.6% vs. 24.7%; p < 0.01), LDL-C < 2.07 mmol/L (43.5% vs. 39.4%; p < 0.01) and blood pressure (BP) < 140/90 mm Hg (85.6% vs. 77.7%; p < 0.01) goal achievement rates were significantly higher in the PCI group. Compared with patients ≥ 60 years old: patients < 60 years old had better BP < 140/90 mm Hg goal achievement rates (87.7% vs. 84.4%; p < 0.01) in the PCI group, and better fasting blood-glucose (FBG) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) and HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) goal achievement rates in the CABG group. Compared with females: males had better LDL-C < 2.07 mmol/L (24.7% vs. 28.5%; p < 0.01), FBG < 7 mmol/L (71.8% vs.75.2%; p < 0.01) and HbA1c < 7% (70.4% vs. 74.1%; p < 0.01) goal achievement rates in the PCI group. Conclusion: Patients in the PCI group were generally more likely than those in the CABG group to achieve LDL-C < 1.8 mmol/L and BP goals. The control of cardiovascular risk factors differed between patients ≥ 60 years old and < 60 years old. Female patients were less likely to achieve LDL-C, FBG and HbA1c goals.


Resumo Fundamento: Há poucos dados referentes às disparidades no manejo de fatores de risco cardiovascular entre pacientes tratados com intervenção coronária percutânea (ICP) e aqueles tratados com cirurgia de revascularização miocárdica (CRM). Objetivo: Avaliar se as taxas de cumprimento de metas de fatores de risco cardiovascular diferiram entre pacientes submetidos a ICP ou a CRM. Métodos: Revisão retrospectiva de banco de dados de prontuários médicos de pacientes admitidos no Hospital Beijing Anzhen entre 1 de janeiro de 2014 e 31 de dezembro de 2014, submetidos a ICP ou a CRM. Resultados: Comparado ao grupo CRM, o grupo ICP apresentou taxas significativamente maiores de cumprimento de meta de colesterol da lipoproteína de baixa densidade (LDL-C) < 1,8 mmol/L (28,6% vs. 24,7%; p < 0,01), LDL-C < 2,07 mmol/L (43,5% vs. 39,4%; p < 0,01) e pressão arterial (PA) <140/90 mmHg (85,6% vs. 77,7%; p < 0,01). Comparados aos pacientes ≥ 60 anos de idade, aqueles < 60 anos de idade apresentaram melhor taxa de cumprimento de meta de PA < 140/90 mmHg (87,7% vs. 84,4%; p < 0,01) no grupo ICP, e melhores taxas de cumprimento de meta de glicemia de jejum (GJ) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) e HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) no grupo CRM. Comparados às mulheres, os homens apresentaram melhores taxas de cumprimento de meta de LDL-C < 2,07 mmol/L (24,7% vs. 28,5%; p < 0,01), GJ < 7 mmol/L (71,8% vs. 75,2%; p < 0,01) e HbA1c < 7% (70,4% vs. 74,1%; p < 0,01) no grupo ICP. Conclusão: Em geral, o grupo ICP apresentou maior probabilidade do que o grupo CRM de cumprir as metas de LDL-C < 1,8 mmol/L e PA. O controle dos fatores de risco cardiovascular diferiu entre pacientes ≥ 60 e < 60 anos de idade. As mulheres apresentaram menor probabilidade de cumprir as metas de LDL-C, GJ e HbA1c.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/cirurgia , Ponte de Artéria Coronária , Prevenção Secundária , Intervenção Coronária Percutânea , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/sangue , Estudos Retrospectivos , Resultado do Tratamento
6.
Drug Des Devel Ther ; 11: 617-627, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28424539

RESUMO

OBJECTIVE: The aim of this study was to explore the effects of ß3-adrenoceptor (ß3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and treated with the ß3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and ß3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol content of the foam cells was also measured, and the cholesterol efflux from the macrophages was examined by determining 3H-labeled cholesterol levels. Expression of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam cells was also assessed. RESULTS: ß3-AR activation increased ApoA-I expression in both the HepG2 cells and the supernatants; PPARγ expression was upregulated, but PPARα expression was not. Treatment with GW9662 abolished the increased expression of ApoA-I induced by the ß3-AR agonist. The HepG2 cell supernatants decreased the lipid accumulation and increased the cholesterol efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1 expression, increased in the macrophage foam cells treated with BRL37344-treated HepG2 cell supernatants. CONCLUSION: Activation of ß3-AR in HepG2 cells upregulates ApoA-I expression, which might further promote cholesterol efflux from macrophage foam cells. PPARγ might be required for the induction of ApoA-I expression.


Assuntos
Apolipoproteína A-I/metabolismo , Colesterol/metabolismo , Células Espumosas/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Regulação para Cima , Animais , Sobrevivência Celular , Células Cultivadas , Colesterol/análise , Células Espumosas/citologia , Células Hep G2 , Humanos , Camundongos , Células RAW 264.7
7.
J Geriatr Cardiol ; 13(4): 312-5, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27403140

RESUMO

BACKGROUND: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C). Both oxidized LDL and tissue factor (TF) contributed to the development of prothrombotic state. The present study aims to explore the relationship between plasma level of PCSK9 and that of TF in patient with coronary artery disease (CAD). METHODS: From July 2013 to March 2014, we enrolled 197 consecutive patients who underwent coronary angiography because of suspected CAD at Beijing Anzhen Hospital in this study. All patients had no history of using lipid-lowering medication. Of these 197 patients (131 male and 66 female, mean age 56.9 ± 11.8 years), 81 had angiographically diagnosed CAD. Clinical data were collected. Plasma PCSK9 and TF were measured using enzyme-linked immunosorbent assay (ELISA). Levels of plasma PCSK9 and TF were compared and their correlation analyzed among different patient groups. RESULTS: Both plasma levels of PCSK9 (279.8 ± 60.4 µg/L vs. 216.5 ± 45.3 µg/L, P < 0.01) and TF (156.4 ± 26.6 µg/mL vs. 112.1 ± 38.3 µg/L, P < 0.01) were significantly higher in patients with CAD, as compared with those without CAD. Correlation analysis showed plasma level of PCSK9 was significantly correlated with that of TF in both patients with and without CAD. However, multivariate regression analysis after adjustment for age, gender, smoking, alcohol, hypertension and hyperlipidemia showed that only in CAD patients with type 2 diabetes mellitus, there was significant positive correlation between plasma levels of PCSK9 and TF (ß = 0.353, P < 0.01). CONCLUSIONS: The plasma level of PCSK9 is independently and positively associated with that of TF in CAD patients with diabetes mellitus, but not in those without diabetes mellitus. Further study is needed to investigate the underlying mechanism.

8.
Pulm Pharmacol Ther ; 39: 85-91, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27373439

RESUMO

BACKGROUND: Statins may be beneficial in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), but their application remains controversial. OBJECTIVES: This meta-analysis of published studies investigated their potential benefit in ALI/ARDS treatment. METHODS: PubMed, EMBASE, Google Scholar and Cochrane databases were searched and all randomized controlled trials (RCT) and cohort studies with head-to-head comparison between statin and standard care were included. RESULTS: Three RCTs and six cohort studies were included. Overall, statins treatment had no significant effect on mortality compared with placebo (RCTs: OR = 0.99, 95% CI = 0.72, 1.37; cohorts: OR = 0.99, 95% CI = 0.71, 1.37). In addition, ventilator-free days were comparable between the two groups (RCTs: SMD = 0.08, 95% CI = -0.03, 0.19; cohorts: SMD = 0.06, 95% CI = -0.17, 0.29). The one-way sensitivity analysis confirmed the stability of results. CONCLUSION: The results did not show that statins had effects on mortality and ventilator-free days among ALI/ARDS patients. However, this meta-analysis is limited by the number of RCTs included.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Lesão Pulmonar Aguda/mortalidade , Lesão Pulmonar Aguda/fisiopatologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/fisiopatologia , Resultado do Tratamento
9.
Eur J Pharmacol ; 742: 75-80, 2014 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-25220245

RESUMO

Hyperlipidemia can be harmful to the lung and ß3-adrenoceptor agonist can improve lipid metabolism disorders. In this study, we aim to investigate the effects of ß3-adrenoceptor activation on the interactions of adrenoceptors and angiotensin II receptors in aged apolipoprotein E gene knockout (ApoE(-/-)) mouse lung. Ten wild type C57BL/6J mice were included as normal control, 40 ApoE(-/-) mice were randomly divided into hyperlipidemia model (saline), low dose and high dose ß3-adrenoceptor agonist and ß3-adrenoceptor antagonist groups. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were examined by an automatic biochemical analyzer. Quantitative real-time PCR and Western blot were used to analyze the mRNA and protein expression of α1A-, α1B-, α2A-, ß1-, ß2-, ß3-adrenoceptors and angiotensin II type 1 and type 2 receptors in lung. We found that ß3-adrenoceptor agonist could decrease TG, TC and LDL-C in aged ApoE(-/-) mice (P<0.01) and down-regulate the expressions of α1A-, α2A-adrenoceptors and angiotensin II type 1 receptor which were significantly increased in model mice (P<0.01, P<0.05). Compared with model mice, α1B-, ß1-, ß2-, ß3-adrenoceptors and angiotensin II type 2 receptor expressions were increased in ß3-adrenoceptor agonist-treat mice (P<0.01, P<0.05). These findings suggest that the expressions of adrenoceptors and angiotensin II receptors in lung are regulated towards adverse directions after taking ß3-adrenoceptor agonist, which shows there are interactions between ß3-adrenoceptor and other adrenoceptor subtypes and angiotensin II receptors. These interactions may play a protective role in lung under condition of hyperlipidemia.


Assuntos
Apolipoproteínas E/deficiência , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Receptores de Angiotensina/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Antagonistas de Receptores Adrenérgicos beta 3/farmacologia , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Apolipoproteínas E/genética , Colesterol/sangue , LDL-Colesterol/sangue , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores Adrenérgicos/genética , Receptores Adrenérgicos/metabolismo , Receptores Adrenérgicos beta 3/genética , Receptores de Angiotensina/genética , Triglicerídeos/sangue
10.
Parasitol Res ; 113(10): 3631-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25015050

RESUMO

To seek natural products for the development of environment friendly mosquito control agents, fumigant activity of eleven essential oil compounds and the joint action of the active compounds were evaluated against Culex pipiens pallens adults. Fumigant bioassay demonstrated that carvacrol exhibited the highest fumigant activity followed by thymol and l-perillaldehyde, with LC50 values of 0.26, 0.28, and 0.34 mg/L air, respectively. Among the binary mixtures of four compounds with preferable performance, only the binary mixture of carvacrol and thymol (1:1, w/w) displayed a synergistic effect with the co-toxicity coefficient (CTC) value of 174.1 and LC50 value of 0.16 mg/L air. Furthermore, the actual efficacy of the binary mixture at 300 mg/mat (KT50 = 7.9, 15.8, and 22.0 min after 0, 2, and 4 h of preliminary heating, respectively) was comparable with that of d-allethrin at 30 mg/mat (KT50 = 8.7, 17.9, and 21.2 min after 0, 2, and 4 h of preliminary heating, respectively) tested in vaporizing mats by the glass chamber method (70 × 70 × 70 cm). These results revealed that carvacrol, thymol, and their binary mixture have potential for the development of natural fumigants for adult mosquito control.


Assuntos
Culex/efeitos dos fármacos , Inseticidas/farmacologia , Monoterpenos/farmacologia , Controle de Mosquitos/métodos , Óleos Voláteis/farmacologia , Timol/farmacologia , Animais , Bioensaio , Cimenos , Feminino , Fumigação , Dose Letal Mediana
11.
J Am Mosq Control Assoc ; 30(3): 199-203, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25843095

RESUMO

We studied the knockdown activity and lethal toxicity of 6 essential oil compounds-methyl salicylate, linalool, 2-phenethyl alcohol, eugenol, ß-citronellol, and trans-cinnamaldehyde-as fumigants against adult female Culex pipiens pallens in the laboratory. Of the 6 products tested, trans-cinnamaldehyde was the most toxic (LC50  =  0.26 µl/l air, 24 h) with a slow knockdown time (KT95  =  176.5 min at 0.5 µl/l air). Methyl salicylate displayed a lower toxicity (LC50  =  1.17 µl/l air, 24 h) but the fastest knockdown activity (KT95  =  16.8 min) at the sublethal concentration 0.5 µl/l air. Furthermore, the binary mixture of methyl salicylate and trans-cinnamaldehyde exhibited a combined effect of fast knockdown activity and high toxicity against Cx. p. pallens adults, showing potential for development as natural fumigants for mosquito control.


Assuntos
Acroleína/análogos & derivados , Culex , Fumigação , Inseticidas , Controle de Mosquitos , Óleos Voláteis , Salicilatos , Animais , Feminino
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