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1.
Cardiovasc Diabetol ; 22(1): 321, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993858

RESUMEN

BACKGROUND: This study aimed to investigate the association between the triglyceride-glucose (TyG) index and left ventricular global longitudinal strain (GLS) in patients with coronary heart disease and to examine the role of left ventricular GLS in detecting early changes in cardiac function in patients with coronary heart disease in the subclinical stage. METHODS: A cross-sectional study involving 178 participants with symptomatic coronary artery disease excluding myocardial infarction or left ventricular dysfunction was conducted in Jilin Province, China. Basic clinical, biochemical, and echocardiographic data were obtained from all participants. Myocardial strain parameters were compared between patients with higher TyG index and those with lower TyG index, and the association between the gradually elevated TyG index and on subclinical cardiac function in patients with coronary heart disease was evaluated. RESULTS: The GLS of left ventricle was lower in the higher TyG index group than in the lower TyG index group. As the TyG index increases, the GLS progressively decreases. The results remained stable after adjusting for confounding factors. CONCLUSIONS: A higher TyG index maybe independently associated with subclinical left ventricular dysfunction in patients with coronary heart disease.


Asunto(s)
Enfermedad de la Arteria Coronaria , Disfunción Ventricular Izquierda , Humanos , Glucosa , Estudios Transversales , Triglicéridos , Tensión Longitudinal Global , Glucemia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etiología , Factores de Riesgo , Biomarcadores
2.
BMC Cardiovasc Disord ; 20(1): 139, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-32183703

RESUMEN

BACKGROUND: The incidence of CHD is the highest among birth defects and is increasing year to year. CHD seriously harms the health of infants and young children and presents a large economic burden to families and society. The pathogenesis of CHD and preventive measures are the focus of current research. Our research aimed to explore the intervention effect of folic acid on heart abnormalities resulting from sodium arsenic (NaAsO2) exposure during the periconception period. METHODS: Sixty 35-day-old female SD rats were randomly divided into 5 groups with 12 rats in each group. Group A was the control group. The rats were given distilled water and ordinary chow. The rats in group B were given distilled water containing 75 mg/L NaAsO2 and ordinary chow. The rats in groups C, D, and E were given distilled water containing 75 mg/L NaAsO2 and chow containing 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg folic acid, respectively. The general condition of the embryos and the histopathology of the embryonic hearts were examined. The acetylation levels of histone H3K9 in heart tissues and the expression levels of Mef2C (which is related to heart development) were observed. RESULTS: The embryo weight and placental weight of groups B-E were significantly lower than those of group A (P < 0.05). The heart malformation rate of the fetal rats in groups B-E was significantly higher than that of the fetal rats in group A (P < 0.05). We found that the level of H3K9 acetylation in fetal rat cardiomyocytes in groups B-E was significantly higher than that in group A (P < 0.05) and that the level of H3K9 acetylation in groups C-E was lower than that in group B (P < 0.05). The mRNA level of Mef2C in fetal rat cardiomyocytes in group B-E was significantly higher than that in group A (P < 0.05), and the mRNA level of Mef2C in groups C-E was significantly lower than that in group B (P < 0.05). CONCLUSION: Supplementation with folic acid during the periconception period can interfere with the toxic effects of arsenic on the heart. The mechanism may be that lowering the acetylation levels of histone H3K9 in heart tissues leads to decreased expression levels of Mef2C, which may play a protective role in heart development in fetal rats.


Asunto(s)
Arsenitos , Corazón Fetal/efectos de los fármacos , Ácido Fólico/farmacología , Cardiopatías Congénitas/prevención & control , Compuestos de Sodio , Acetilación , Animales , Cardiotoxicidad , Femenino , Corazón Fetal/anomalías , Corazón Fetal/metabolismo , Regulación del Desarrollo de la Expresión Génica , Edad Gestacional , Cardiopatías Congénitas/inducido químicamente , Cardiopatías Congénitas/embriología , Cardiopatías Congénitas/metabolismo , Histonas/metabolismo , Factores de Transcripción MEF2/genética , Factores de Transcripción MEF2/metabolismo , Exposición Materna , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Embarazo , Ratas Sprague-Dawley
3.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4129-4139, 2020 Sep.
Artículo en Zh | MEDLINE | ID: mdl-33164397

RESUMEN

This paper aims to explore the potential of Qingyan Formula(QYF) in the treatment of perimenopausal anxiety disorder(PAD) by network pharmacological method, and verify the pharmacodynamics and mechanism by using animal experiments. First, Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) was used to retrieve the active components of QYF. Then the potential drug targets were screened with use of Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine(TCMIP) v2.0 and Swiss Target Prediction database. Targets related to PAD were retrieved and screened from the OMIM database and GeneCards database. The intersection targets of QYF and PAD were screened out, and then the enrichment analysis of the signal pathways was conducted. Open field experiments and the O maze experiment were used to verify the pharmacodynamic effect of QYF in the treatment of PAD rats, and the serum neurotransmitter level was detected. The results showed that QYF may be have the function of regulating steroid hormone signaling pathways such as steroid hormone synthesis, ovarian steroidogenesis and estrogen signaling pathways, regulating central neurotransmitters signaling pathways including tryptophan metabolism pathways, Toll-like receptor signaling pathways, TGF-ß signaling pathway and regulating inflammatory response pathways including NF-κB signaling pathway, Apelin signaling pathway, MAPK signaling pathway, TNF signaling pathway, and FOXO signaling pathway. All of the signaling pathways were related to PAD, which indicated that QYF may have the role of treating PAD. Qingyan Formula 70% ethanol extract(QYFE) revealed anxiolytic effects by extending the activity time and distance of anxious ovariectomized(OVX) rats in the central field of open field experiments, and increasing the duration and activity distance of anxious OVX rats in the open arm area in O maze experiments. QYFE increased serum serotonin/5-hydroxytryptamine(5-HT), and gamma aminobutyric acid(GABA) levels in anxious OVX rats, significantly reduced glutamate(Glu) and norepinephrine(NA) levels, and reversed the disturbance of excitatory/suppressive transmitter balance caused by OVX, which may be related to its effect on alleviating anxiety disorder in OVX rats.


Asunto(s)
Medicamentos Herbarios Chinos , Perimenopausia , Animales , Trastornos de Ansiedad/tratamiento farmacológico , Medicina Tradicional China , Ratas , Serotonina
4.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4712-4718, 2020 Oct.
Artículo en Zh | MEDLINE | ID: mdl-33164437

RESUMEN

To observe the effect of shikonin on the proliferation, migration, adhesion and invasion of rheumatoid arthritis(RA) fibroblast like synoviocytes induced by tumor necrosis factor-α(TNF-α), and to explore its mechanism of action from aspects of protein kinase B(Akt) and mitogen activated protein kinase(MAPK) signaling pathways. TNF-α(20 ng·mL~(-1)) was used in this experiment to induce human RA fibroblast like synovial cell line(MH7 A). After addition of different concentrations of shikonin(0.025, 0.05, 0.1 pmol·L~(-1)), the proliferation, migration, adhesion and invasion ability of MH7 A cells were detected by MTT test, scratch test, adhesion test, Transwell invasion test, respectively. Protein expression of Akt and MAPK signaling pathway molecules in MH7 A cells was detected by Western blot. The results showed that as compared with the control group, TNF-α could significantly induce the proliferation, migration, adhesion and invasion of MH7 A cells, and increase the phosphorylation level of Akt, JNK, p38 and extracellular regulatory protein kinase(ERK). As compared with the TNF-α group, shikonin had no significant effect on TNF-α-induced proliferation of MH7 A cells after 24 h treatment, and it could reduce the TNF-α-induced proliferation of MH7 A cells in a concentration dependent manner after 48 h treatment. Shikonin also significantly reduced the TNF-α-induced migration, adhesion, invasion and phosphorylation levels of Akt, JNK, p38, ERK in MH7 A cells within 24 h. These results suggested that shikonin could reduce the proliferation, migration, adhesion and invasion ability of MH7 A cells induced by TNF-α, and its mechanism may be related to the down-regulation of Akt and MAPK signaling pathway activation.


Asunto(s)
Artritis Reumatoide , Sinoviocitos , Artritis Reumatoide/tratamiento farmacológico , Movimiento Celular , Proliferación Celular , Células Cultivadas , Fibroblastos , Humanos , Naftoquinonas , Membrana Sinovial , Factor de Necrosis Tumoral alfa/genética
5.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4149-4153, 2020 Sep.
Artículo en Zh | MEDLINE | ID: mdl-33164399

RESUMEN

Tripterygium wilfordii Hook.f.(TwHF) is one of the most effective traditional Chinese herbal medicines against rheumatoid arthritis. As the representative agents of TwHF, Tripterygium Glycoside Tablets(TGT) and Tripterygium wilfordii Tablets(TWT) were included as Class A drugs in the 2019 edition of Medicine Catalogue for National Basic Medical Insurance, Injury Insurance and Maternity Insurance, and TGT was also included in 2018 edition of National Essential Drug List and 2015 edition of Chinese Pharmacopoeia. However, it is difficult to grasp the specific clinical applications of TGT and TWT. Side effects occur from time to time. The curative effect is uneven in patients. And the package inserts of TGT and TWT are not described in details. In order to standardize the clinical application of Tripterygium wilfordii preparations, 38 authoritative units and 48 well-known experts in rheumatoid immunology clinical department, drug supervision and management, pharmacy and evidence-based medicine research fields jointly developed Tripterygium Glycoside Tablets and Tripterygium wilfordii Tablets Medication Guide for reference in clinical application, teaching and scientific research. The guideline followed the "evidence-based, consensus-assisted and experience-based" principles to form "recommendations" for the evidence supported ones, and form "consensus suggestions" for those without evidence support by using nominal group method. In this way, the medication recommendations on function, usage and dosage, drug combinations, precautions, efficacy, safety and other aspects of TGT and TWT can be provided. The application of this Guide will help to avoid or reduce the adverse reactions of T. wilfordii preparations, enhance the efficacy and reduce the cost of medicine, with certain demonstration and promotion values to improve the rational use level of traditional Chinese medicine.


Asunto(s)
Artritis Reumatoide , Medicamentos Herbarios Chinos , Tripterygium , Artritis Reumatoide/tratamiento farmacológico , Femenino , Glicósidos , Humanos , Guías de Práctica Clínica como Asunto , Embarazo , Comprimidos
6.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4154-4157, 2020 Sep.
Artículo en Zh | MEDLINE | ID: mdl-33164400

RESUMEN

Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the treatment of rheumatoid arthritis(T/CACM 1337-2020) was approved on June, 2020 by the Standardization Office of Chinese Association of Chinese Medicine. Our group developed this guideline for the clinical application of Tripterygium Glycosides/Tripterygium wilfordii Tablets according to the manual for the clinical experts consensus of Chinese patent medicine from January, 2018, when this project was approved by Chinese Association of Chinese Medicine. In this article, the detailed information on our compilation process was provided, in order to facilitate the understanding and the application of the guideline, as well as provide reference for the development of clinical practice guideline for other Chinese patent medicine.


Asunto(s)
Artritis Reumatoide , Medicamentos Herbarios Chinos , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Glicósidos , Humanos , Comprimidos , Tripterygium
7.
Amino Acids ; 51(10-12): 1657-1666, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31729551

RESUMEN

The effects of methionine restriction on lipid metabolism in the liver and adipose tissue have been well determined, while its effects on the skeletal muscle have not been fully studied. The present study was conducted to explore whether methionine restriction in weanling piglets would affect skeletal muscle lipid content and fiber type and whether such changes would further affect the meat quality of growing-finishing pigs. A total of 28 crossbred healthy barrows weaned at the age of 21 days were randomly allotted to two treatments and fed either a methionine-restricted diet (0.25% methionine) or a control diet (0.48% methionine) for 4 weeks. After this period, the pigs were fed the same basal diet throughout the growing-finishing period. The results showed that methionine restriction during the post-weanling period of piglets enhanced lipid accumulation and promoted the formation of slow-twitch muscle fibers in the skeletal muscle, while it had no effects on growth performance. We hypothesized that such effects might be mediated by AMPK-PGC-1α signaling pathway. Furthermore, the effects of methionine restriction on the skeletal muscle of pigs at the post-weanling period had a subsequent effect on growing-finishing pigs, which showed a higher intramuscular fat content. Our results suggest that dietary methionine restriction in piglets at an early stage might be an alternative method for improving meat quality.


Asunto(s)
Tejido Adiposo/química , Metionina/metabolismo , Fibras Musculares Esqueléticas/química , Carne de Cerdo/análisis , Sus scrofa/fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo/metabolismo , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Proteínas en la Dieta/análisis , Proteínas en la Dieta/metabolismo , Metabolismo de los Lípidos/genética , Metionina/análisis , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Transducción de Señal , Sus scrofa/crecimiento & desarrollo , Sus scrofa/metabolismo , Destete
8.
BMC Cancer ; 18(1): 1170, 2018 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-30477458

RESUMEN

BACKGROUND: Increasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018. METHODS: A comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET. RESULTS: This meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1-5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01-4.25) and rash (OR = 16.91; CI = 3.20-89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90-5.88), disease control rate (OR = 2.92; CI = 1.49-5.71) and 2-year overall survival (OR = 2.78; CI = 1.20-6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14-14.14). No significant differences in other adverse effects were found between the two groups. CONCLUSIONS: Our findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Antineoplásicos Inmunológicos/farmacología , Cetuximab/farmacología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Humanos , Oportunidad Relativa , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Resultado del Tratamiento
9.
Proc Natl Acad Sci U S A ; 112(15): 4702-6, 2015 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-25825755

RESUMEN

The fossil record offers unique insights into the environmental and geographic partitioning of biodiversity during global diversifications. We explored biodiversity patterns during the Cambrian radiation, the most dramatic radiation in Earth history. We assessed how the overall increase in global diversity was partitioned between within-community (alpha) and between-community (beta) components and how beta diversity was partitioned among environments and geographic regions. Changes in gamma diversity in the Cambrian were chiefly driven by changes in beta diversity. The combined trajectories of alpha and beta diversity during the initial diversification suggest low competition and high predation within communities. Beta diversity has similar trajectories both among environments and geographic regions, but turnover between adjacent paleocontinents was probably the main driver of diversification. Our study elucidates that global biodiversity during the Cambrian radiation was driven by niche contraction at local scales and vicariance at continental scales. The latter supports previous arguments for the importance of plate tectonics in the Cambrian radiation, namely the breakup of Pannotia.


Asunto(s)
Biodiversidad , Evolución Biológica , Fósiles , Paleontología/métodos , Animales , Bases de Datos Factuales , Modelos Teóricos , Dinámica Poblacional , Especificidad de la Especie , Factores de Tiempo
10.
Cancer Cell Int ; 15: 77, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26236156

RESUMEN

BACKGROUND: Colon carcinoma is one of the commonly tumors that threaten human beings as its highly morbidity and mortality. Recent evidences suggested that microRNA-21 (miR-21) played an important role in the development of colon carcinoma and might be a potential biological marker for the diagnosis and prognosis of colon carcinoma. However, the potential effect of miR-21 based therapeutic studies in colon carcinoma remains to be fully elucidated. METHODS: In present study, we constructed an eukaryotic expression vector encoding antisense oligonucleotides against miR-21 (termed as p-miR-21-ASO) and the expression of miRNA-21 in human colon cancer was detected by Real-time PCR. To assess its possible effect on the proliferation and migration capacity of human colon carcinoma cells in vitro, CCK-8 assay, colony formation assay and cell invasion, as well as migration assay, were performed respectively. Moreover, PTEN, one of target molecules of miRNA-21, was analyzed by Western blot and Fluorescence activated cell sorter assay. Finally, the transduction of AKT and ERK pathways in human colon carcinoma cells was determined by Western blot. RESULTS: We found that transiently transfection of p-miR-21-ASO could efficiently decrease the relative expression of miR-21 in human colon carcinoma HCT116 cells, accompanied by impaired proliferation and clone formation. Furthermore, we found that down-regulation of miR-21 also could significantly abrogate the invasion and migration capacity in vitro, as well as the expression of vascular endothelial growth factor which is critical for the metastatic capacity of colon carcinoma cells. Mechanistic evidence showed that down-regulation of miR-21 increased the expression of its target molecule PTEN in HCT116 cells. Finally, we revealed that the expression level of both phosphor-ERK1/2 and phosphor-AKT also were altered. CONCLUSIONS: Therefore, our data suggested miR-21 ASO against miR-21 might be a useful strategy to alter the expression of miR-21 in colon carcinoma cells, which was helpful for the development of miR-21-based therapeutic strategies against clinical colon carcinoma.

11.
Int J Hypertens ; 2024: 8040917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737523

RESUMEN

Yogurt consumption is a significant factor in reducing the risk of hypertension and preventing cardiovascular diseases. Although increasing evidence has emerged regarding the potential benefits of probiotics in hypertension, there is a lack of large, cross-sectional studies assessing the association between yogurt intake and blood pressure parameters. We aimed to evaluate the association between yogurt intake frequency and blood pressure. A cross-sectional study was designed using data from the National Health and Nutrition Examination Survey from 2003 to 2004 and 2005 to 2006. We included 3, 068 adults with blood pressure data and yogurt intake data. Multivariate regression analyses revealed significant inverse associations between yogurt and systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and mean arterial pressure (P < 0.05) in nonhypertensive participants (n = 1 822) but not in hypertensive participants (n = 1 246). Furthermore, a high frequency of yogurt intake prevented hypertension; however, no additional antihypertensive effects were observed in patients already diagnosed with hypertension.

12.
Front Cardiovasc Med ; 10: 1193971, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441700

RESUMEN

Aims: Using speckle tracking technology to investigate the effect of hypertriglyceridemia on the global longitudinal strain(GLS) of the left ventricle in patients with coronary heart disease in the early stage, and to explore the value of myocardial strain in early identification of cardiac dysfunction in patients with coronary heart disease in the pre-heart failure stage. Methods: A cross-sectional study of 138 participants was conducted in Jilin Province, China. Basic clinical, biochemical, and echocardiographic data were obtained for all patients. Myocardial strain parameters were compared between the hypertriglyceridemia and normal triglyceride level groups and the effect of hypertriglyceridemia on early left ventricular global longitudinal strain impairment in coronary heart disease patients was evaluated. Results: The overall longitudinal strain of the left ventricle was smaller in the hypertriglyceridemia group than in the normal triglyceride group. After the multivariate Logistic regression model adjusting for the influence of confounding factors, the results remained stable. Conclusions: The risk of impairment of global longitudinal strain of the left ventricle in patients with coronary heart disease is positively correlated with triglyceride levels, and hypertriglyceridemia maybe an independent risk factor affecting early cardiac dysfunction in the pre-heart failure stage of patients with coronary heart disease.

13.
Anticancer Res ; 43(5): 1925-1932, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37097647

RESUMEN

BACKGROUND/AIM: Gallbladder cancer (GBC) is a refractory cancer with poor prognosis. Recently, therapy targeting the tumor microenvironment (TME) has gained attention. Cancer hypoxia is a significant factor in the tumor microenvironment (TME). Our research has shown that hypoxia activates several molecules and signaling pathways that contribute to the development of various types of cancer. Our analysis indicated that C4orf47 expression was up-regulated in a hypoxic environment and had a role in the dormancy of pancreatic cancer. There are no other reports on the biological significance of C4orf47 in cancer and its mechanism is still unknown. This study analyzed how C4orf47 affects refractory GBC to develop a new effective therapy for GBC. MATERIALS AND METHODS: Two human gallbladder carcinomas were used to examine how C4orf47 affects proliferation, migration, and invasion. C4orf47 was silenced using C4orf47 siRNA. RESULTS: C4orf47 was over-expressed in gallbladder carcinomas under hypoxic conditions. C4orf47 inhibition increased the anchor-dependent proliferation and decreased the anchor-independent colony formation of GBC cells. C4orf47 inhibition reduced epithelial-mesenchymal transition and suppressed migration and invasiveness of GBC cells. C4orf47 inhibition decreased CD44, Fbxw-7, and p27 expression and increased C-myc expression. CONCLUSION: C4orf47 enhanced invasiveness and CD44 expression, and reduced anchor-independent colony formation, suggesting that C4orf47 is involved in plasticity and the acquisition of the stem-like phenotype of GBC. This information is useful for the development of new therapeutic strategies for GBC.


Asunto(s)
Neoplasias de la Vesícula Biliar , Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Hipoxia/genética , Transducción de Señal , Microambiente Tumoral
14.
Anticancer Res ; 43(7): 2909-2922, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37351966

RESUMEN

BACKGROUND/AIM: Hedgehog (HH) signalling is a potential therapeutic target for gallbladder cancer (GBC), and Mastermind-like 3 (MAML3) is involved in the transcription of Smoothened (SMO), which is a key protein of HH signalling during hypoxia in the cancer microenvironment. MAML3 is a NOTCH signalling activator, and HH and NOTCH are involved in morphogenesis signalling. However, the association between MAML3-NOTCH and HH signalling and its role in regulating GBC cells remain unknown. This study aimed to determine whether NOTCH signalling affects tumour aggressiveness in GBC under hypoxic conditions and if MAML3 could be a new comprehensive therapeutic target that regulates morphogenesis signalling, HH, and NOTCH in GBC. MATERIALS AND METHODS: We used three cell lines (NOZ, TYGBK1, and TGBC2TKB) and 58 resected specimens. These samples were subjected to cell proliferation, RNA interference, invasion, western blot, and immunohistochemical analyses. RESULTS: MAML3 expression was higher under hypoxic conditions than under normoxic conditions and was involved in the activation of HH and NOTCH signalling. It contributed to the proliferation, migration, and invasion of GBC cells through the NOTCH signalling pathway and enhanced gemcitabine sensitivity. Immunohistochemical analysis showed that MAML3 expression was related to lymphatic invasion, lymph node metastasis, stage category, and a poor prognosis. CONCLUSION: MAML3 contributes to the induction of the malignant phenotype of GBC under hypoxia through the HH and NOTCH signalling pathways and may be a comprehensive therapeutic target of morphogenesis signalling in GBC.


Asunto(s)
Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Proteínas Hedgehog/metabolismo , Hipoxia , Fenotipo , Morfogénesis , Microambiente Tumoral , Transactivadores
15.
J Cancer ; 14(2): 306-317, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36741255

RESUMEN

In our comprehensive analysis of pancreatic cancer pathology, we found that the C4orf47 molecule was upregulated in hypoxic environments. C4orf47 is reported to be a centrosome-associated protein, but its biological significance in cancer is completely unknown; therefore, we assessed its role in pancreatic cancer. We found that C4orf47 was a direct target of HIF-1α and is upregulated in hypoxic conditions, in which it suppressed the cell cycle and inhibits cell proliferation through up-regulation of the cell cycle repressors Fbxw-7, P27, and p57; and the down-regulation of the cell cycle promoters c-myc, cyclinD1, and cyclinC. Furthermore, C4orf47 induced epithelial-mesenchymal transition and enhanced their cell plasticity and invasiveness. In addition, the p-Erk/p-p38 ratio was significantly enhanced and down-regulated CD44 expression by C4orf47 suppression, suggesting that C4orf47 is involved in pancreatic cancer dormancy under hypoxic conditions. Furthermore, the potential of C4orf47 expression was a good prognostic biomarker for pancreatic cancer. These results contribute to the elucidation of the pathology of refractory pancreatic cancer and the development of novel therapeutic strategies.

16.
Anticancer Res ; 41(8): 4047-4052, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34281873

RESUMEN

BACKGROUND/AIM: Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells. MATERIALS AND METHODS: Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors. RESULTS: All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells. CONCLUSION: TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptor trkB/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Carbazoles/farmacología , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Alcaloides Indólicos/farmacología , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/genética , Neoplasias Pancreáticas/patología , Inhibidores de Proteínas Quinasas/farmacología , Interferencia de ARN , ARN Interferente Pequeño/genética , Receptor trkB/antagonistas & inhibidores , Receptor trkB/genética , Transducción de Señal/efectos de los fármacos
17.
Mitochondrial DNA B Resour ; 6(9): 2772-2774, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34471700

RESUMEN

Abies forrestii is endemic to southwest China and ecologically important as a major component of the cold temperate forests. This study was the first report complete chloroplast (cp) genome of A. forrestii. The complete chloroplast genome was 120,022 bp in size. In total, 114 genes were identified, including 68 peptide-encoding genes, 35 tRNA genes, four rRNA genes, six open reading frames and one pseudogene. Thirteen genes contain introns. In phylogenetic analysis, A. forrestii was found to be closely related with A. nukiangensis, A. fanjingshanensis and A. delavayi subsp. fansipanensis. Our study will provide potential genetic resources for further evolutionary studies of this ecologically important species.

18.
Cancer Biol Ther ; 21(2): 101-107, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31599195

RESUMEN

EGISTs originating outside the gastrointestinal tract share some similarities with the GISTs regarding their immunohistochemical features including the positive expression of CD117 and CD34. The majority of EGISTs carry activating mutations of the C-KIT or PDGFRA genes. However, there is no precedent in the literature where the two mutations occur in one case of EGISTs to date. We describe herein, a 52-year-old female who presented as mesenteric and pelvic regions masses showing positive immunoreactivity for CD117, DOG-1, CD34. Mutation analysis identified two mutations that located in the exon 13 of C-KIT and in the exon 18 of PDGFRA. The patient was treated sequentially with imatinib, sunitinib, sorafenib, and regorafenib. However, the prognosis was undesirable. Previous research has shown that expression of members of Bcl-2 family may be helpful in predicting prognosis, the survival time, and the resistance to chemotherapeutic agents. IHC was performed to detect the expression of BCL-2 family. The results show that high BCL-2 expression and low BAX expression in both specimens. In conclusion, our case may suggest that the presence of both C-KIT and PDGFRA mutations in EGISTs patients may indicate a very poor prognosis; and the expression level of BCL-2 and BAX could predict clinical outcome.


Asunto(s)
Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/secundario , Mesenterio/patología , Recurrencia Local de Neoplasia/patología , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/genética , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Humanos , Mesenterio/efectos de los fármacos , Mesenterio/metabolismo , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Pronóstico
19.
Mitochondrial DNA B Resour ; 5(4): 3821-3822, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-35174281

RESUMEN

Abies yuanbaoshanensis is critically endangered and restricted in the Yuanbao Mountain of China, with no more than 900 surviving individuals. Here, we reported the complete chloroplast (cp) genome of A. yuanbaoshanensis. The complete chloroplast genome is 121,795 bp in size. In total, 114 genes were identified, including 68 peptide-encoding genes, 35 tRNA genes, 4 rRNA genes, 6 open reading frames, and 1 pseudogene. Thirteen genes contain introns. In phylogenetic analysis, both the ML and BI analyses supported the monophyly of the genus Abies. Our study will provide potential genetic resources for further conservation and evolutionary studies of this highly endangered species.

20.
J Immunol Res ; 2019: 1058738, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31772947

RESUMEN

OBJECTIVE: Accumulating evidence indicates that regulatory T cells (Tregs) may be involved in the pathogenesis of ankylosing spondylitis (AS). As different markers have been used to identify Tregs, some studies on the proportions of Tregs in AS patients have generated considerable controversy. To clarify the status of Tregs in such patients, we determine the proportion changes of peripheral Tregs during development of the disease, with different cellular markers. METHODS: We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in AS patients. Using the PRISMA guidelines, we performed a random-effects meta-analysis of the frequencies of peripheral Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I 2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests. RESULTS: A total 29 studies involving 1732 participants were included in the meta-analysis. Their conclusions of using the diversity of Tregs surface markers were inconsistent with each other. No significant difference in the proportions of Tregs was evident regardless of the definitions used [-0.709, (-1.455, 0.037, p = 0.063), I 2 = 97.3%]. Six studies used "single CD25-positive" cells as Tregs, which revealed a significant increase in AS patients compared with healthy blood donors [0.736, (0.138, 1.334), p = 0.016, I 2 = 80.7%]. Notably, the proportions of "CD4+CD25+FOXP3+," "CD4+CD25highCD127low/-," or "CD4+CD25+CD127low" T cells were lower in AS patients [-2.856, (-4.645, -1.066), p = 0.002; -1.812, (-2.648, -0.977), p < 0.001; -1.12, (-1.605, -0.635), p < 0.001]. Tregs defined as "CD25high," "CD25bright," "CD25bright/highCD127low/-," "CD4+FOXP3+," "CD4+CD25highFOXP3+," and "CD4+CD25+CD127-" did not differ in proportion between AS patients and healthy blood donors. CONCLUSIONS: The levels of Tregs varied based on the cellular identification markers used. The proportions of CD4+CD25+FOXP3+Tregs, CD4+CD25highCD127low/-, or CD4+CD25+CD127low in blood of AS patients were significantly decreased as compared with those in healthy blood donors, and our findings lend support to the idea that the Treg status of AS patients is important. And we recommend the above as the best definition of Tregs when evaluating the status of such patients.


Asunto(s)
Susceptibilidad a Enfermedades , Espondilitis Anquilosante/etiología , Espondilitis Anquilosante/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Biomarcadores , Susceptibilidad a Enfermedades/inmunología , Humanos , Inmunofenotipificación , Recuento de Linfocitos , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/diagnóstico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
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