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1.
J Transl Med ; 22(1): 419, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702818

RESUMEN

BACKGROUND: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. METHODS: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. RESULTS: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. CONCLUSIONS: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.


Asunto(s)
Apoptosis , Proliferación Celular , Glioblastoma , Mitocondrias , Biogénesis de Organelos , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Humanos , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/tratamiento farmacológico , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proliferación Celular/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos
2.
Chem Sci ; 15(14): 5211-5217, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38577354

RESUMEN

Indoles are privileged chemical entities in natural products and drug discovery. Indole-fused heterocycles, particularly seven-membered ones, have received increasing attention due to their distinctive chemical characteristics and wide spectrum of bioactivities. However, the synthetic access to these compounds is highly limited. Herein, we report a unique multicomponent reaction (MCR) for modular assembly of indole-fused seven-membered heterocycles. In this process, indole, formaldehyde and amino hydrochloride could assemble rapidly to yield indole-fused oxadiazepines, and another addition of sodium thiosulphate would furnish indole-fused thiadiazepines. The biological evaluation disclosed the promising anticancer activity of these compounds. Furthermore, this MCR could be applicable in the late-stage and selective modifications of peptides. Therefore, this work provides a powerful strategy for indole functionalization and valuable tool for construction of seven-membered heterocycles.

3.
Protein Pept Lett ; 31(1): 43-60, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38058092

RESUMEN

BACKGROUND: Increasing evidence proves that long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of colorectal cancer. However, the function and molecular mechanism of LINC01836 in CRC are still unknown. METHODS: The differentially expressed lncRNAs in colorectal cancer were obtained from the RNA sequencing data. The effects of LINC01836 on colorectal cancer cells were tested in in vitro experiments. The mechanism of LINC01836 action was investigated through western blot, RNA immunoprecipitation assay and luciferase reporter assay. Moreover, the xenograft mouse model was conducted to examine the effects of LINC01836 in vivo. RESULTS: In this study, we showed that LINC01836 was significantly elevated in colorectal cancer tissues and cells. Elevated LINC01836 expression significantly correlated with larger tumor size, positive lymph node metastasis, distant metastasis, advanced tumor-node-metastasis (TNM) stage, and poor prognosis. Furthermore, decreased expression of LINC01836 repressed proliferation, migration, and invasion in vitro and vivo, and high LINC01836 expression displayed the opposite effect. Further analysis revealed that LINC01836 could regulate the expression of SLC17A9 by competing with miR---1226-3p. Furthermore, down-regulation of LINC01836 or increased expression of miR-1226-3p markedly reversed the effects of SLC17A9 overexpression on colorectal cancer cells. CONCLUSION: This study showed that LINC01836 regulated the expression of SLC17A9 through sponge miR-1226-3p by acting as a competitive endogenous RNA (ceRNA), promoted the progression of colorectal cancer, and suggested a new prognostic biomarker and potential cancer treatment target for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , ARN Endógeno Competitivo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
4.
Indian J Orthop ; 57(9): 1452-1460, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37609008

RESUMEN

Background: Regarding trochanteric hip fractures, one type of posterior coronal fragments was described as the "banana-shaped fragment", while the impact of the banana-shaped fragment on mechanical stability has not been further studied. The current study investigated the association between the banana-shaped fragment and mechanical complications after surgery. Methods: This retrospective cohort study included 273 patients treated by proximal femoral nail antirotation (PFNA) in the full analysis. The age, the sex, the fracture side, the follow-up time, the American Society of Anesthesiologists classification, the operators, the fracture classification, the tip-apex distance, the blade positions, the reduction quality and the bone mineral density were analyzed in relation to mechanical complications, through univariate and multivariate approaches. Results: Mechanical complications happened in 33 patients. The banana-shaped fragment (adjusted odds ratio 5.240, 95% CI 2.172 to 12.641; p < 0.001), the tip-apex distance and the reduction quality showed significant association with mechanical complications in both univariate and multivariate analysis. Moreover, for 118 patients with the banana-shaped fragment, we found that the use of wire cerclage couldn't significantly lower the rates of mechanical complications (p = 0.648). Conclusions: The banana-shaped fragment had a negative impact on mechanical stability of trochanteric hip fractures treated by PFNA. In the perioperative period, the BSF should be carefully evaluated, and its specific handling deserves further study.

5.
J Med Chem ; 66(15): 10791-10807, 2023 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-37498552

RESUMEN

The development of histone deacetylase (HDAC) inhibitors for treating hematologic malignancies has been widely investigated, while their role in hepatocellular carcinoma (HCC) remains unexplored. In this study, we employed a scaffold-hopping design and a multicomponent synthesis approach to develop a novel series of 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridines as HDAC inhibitors. There were a total of 29 compounds achieved with flexible linkers and zinc-binding groups, wherein compound 12k was identified as a promising candidate with good HDAC inhibitory activity, pharmacokinetic profiles, and potency. It exhibited significant therapeutic efficacy in HCC cell lines (IC50 = 30 nM for Bel-7402) and xenograft models (76% inhibition for Bel-7402 xenografts, P.O. at 20 mg/kg, QOD, for 14 days) and was found to upregulate the acetylation of histone H3 and α-tubulin, leading to apoptosis and autophagy in HCC models. Molecular docking studies indicated a unique T-shaped conformation of 12k with the catalytic domain of HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for HCC.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/química , Neoplasias Hepáticas/patología , Simulación del Acoplamiento Molecular , Apoptosis , Piridinas/farmacología , Piridinas/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Histona Desacetilasa 1/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
6.
Exp Biol Med (Maywood) ; 248(12): 1043-1055, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37095701

RESUMEN

Ovarian cancer is the most lethal gynecological tumor in women worldwide. FAM111B (family with sequence similarity 111 member B) is an oncoprotein associated with multiple cancers, but its biological functions in ovarian cancer remain elusive. In this study, FAM111B was overexpressed in ovarian cancer tissues and cell lines. Functional studies in vitro revealed that silencing of FAM111B inhibited ovarian cancer cell proliferation, invasion, and migration, as well as increased cell apoptosis. Furthermore, FAM111B silencing arrested the ovarian cancer cell cycle at the G1/S phase. Furthermore, western blot assays demonstrated that silencing of FAM111B resulted in downregulation of phospho-AKT (p-AKT) protein expression, as well as upregulation of p53 and caspase-1 protein expression. The xenograft animal model of ovarian cancer demonstrated that FAM111B silencing inhibited tumor growth, enhanced cell apoptosis, and inhibited Ki-67 and proliferating cell nuclear antigen (PCNA) protein expression in vivo. Conversely, the overexpression of FAM111B exhibited opposite effects on the ovarian cancer xenograft. It was previously established that inactivating AKT inhibited ovarian cancer progression. This study found that silencing of FAM111B inhibits tumor growth and promotes apoptosis by decreasing AKT activity in ovarian cancer. Caspase-1 and p53 signaling also influenced the function of FAM111B in SKOV3 cells. Collectively, our results demonstrate that silencing of FAM111B is a potential therapeutic strategy against ovarian cancer.


Asunto(s)
Neoplasias Ováricas , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Femenino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Proteína p53 Supresora de Tumor/genética , Línea Celular Tumoral , Apoptosis/genética , Proliferación Celular/genética , Caspasas/metabolismo , Caspasas/farmacología , Caspasas/uso terapéutico , Movimiento Celular/genética , Proteínas de Ciclo Celular/metabolismo
7.
Chem Sci ; 14(7): 1781-1786, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36819861

RESUMEN

Organic-inorganic halide perovskites (OIHPs) are very eye-catching due to their chemical tunability and rich physical properties such as ferroelectricity, magnetism, photovoltaic properties and photoluminescence. However, no nickel-based OIHP ferroelectrics have been reported so far. Here, we designed an ABX3 OIHP ferroelectric (3-pyrrolinium)NiCl3, where the 3-pyrrolinium cations are located on the voids surrounded by one-dimensional chains composed of NiCl6-face-sharing octahedra via hydrogen bonding interactions. Such a unique structure enables the (3-pyrrolinium)NiCl3 with a high spontaneous polarization (P s) of 5.8 µC cm-2 and a high Curie temperature (T c) of 428 K, realizing dramatic enhancement of 112 and 52 K compared to its isostructural (3-pyrrolinium)MCl3 (M = Cd, Mn). To our knowledge, remarkably, (3-pyrrolinium)NiCl3 should be the first case of nickel(ii)-based OIHP ferroelectric to date, and its T c of 428 K (35 K above that of BaTiO3) is the highest among all reported one-dimensional OIHP ferroelectrics. This work offers a new structural building block for enriching the family of OIHP structures and will inspire the further exploration of new nickel(ii)-based OIHP ferroelectrics.

8.
Oncol Lett ; 25(2): 73, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36688111

RESUMEN

Colon cancer associated transcript-1 (CCAT1) is known to play an important role in numerous types of human cancer, including bladder, prostate and ovarian cancer. However, a consistent perspective has not been established in digestive system cancer (DSC). To explore the prognostic value of CCAT1 in patients with DSC, a meta-analysis was performed. A systematic search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Biological Medical Literature database, Cochrane Library and WanFang database was applied to select eligible articles. Pooled odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to estimate the effects of CCAT1 on pathological or clinical features. A total of 1,719 patients from 12 eligible articles were enrolled in the meta-analysis. The results revealed that elevated CCAT1 expression was significantly related to larger tumor size (OR, 1.81; 95% CI, 1.31-2.48), poorer differentiation (OR, 0.45; 95% CI, 0.31-0.64), earlier lymph node metastasis (OR, 3.14; 95% CI, 2.34-4.22) and advanced TNM stage (OR, 3.08; 95% CI, 2.07-4.59). In addition, high CCAT1 expression predicted a poorer outcome for overall survival rate (HR, 2.37; 95% CI, 2.11-2.67) and recurrence-free survival rate (HR, 2.16, 95% CI, 1.31-3.57). High expression levels of CCAT1 were therefore related to unfavorable clinical outcomes of patients with DSC. These results demonstrated that CCAT1 could serve as a prognostic predictor in human DSC.

9.
Histol Histopathol ; 37(12): 1253-1259, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36367373

RESUMEN

AIMS: To investigate the histological and immunohistochemical features of primary ectopic meningiomas (PEMs), especially those of primary ectopic atypical meningiomas (PEAMs). METHODS AND RESULTS: We examined 6 cases of PEM, including 2 PEAM cases, which occurred separately in left nasal cavity, left lower lung, right neck, left orbit, right upper lung, and left upper lung by histological and immunohistochemical analysis. In general, of the 6 PEM cases analyzed, 4 cases exhibited morphology of Grade Ⅰ, including 1 fibrous, 1 meningothelial, and 2 transitional variant. The remaining 2 cases shared similar atypical morphology of Grade Ⅱ. The tumors were distributed in sheet-like patterns with loss of architecture of classic meningiomas. Significant hypercellularity, multi-focal necrosis, and thin-walled blood vessels were identified. The mitotic figures were estimated at 6 per 10 high-power fields in one case, and 8 mitotic figures in another. Immunohistochemically, the 6 PEM cases were all positive for Vimentin and EMA, while none showed immunostaining for CKpan, S-100, CD34, STAT6, SMA, Syn or Bcl-2. 4 PEM cases of Grade Ⅰ were immunoreactive for PR but negative for P53, while the 2 PEAM cases displayed negative staining for PR but positivity for P53. As for Ki-67, the positive staining of 4 Grade Ⅰ cases was no greater than 2%, while the positive rates of the 2 PEAM cases were 10% and 20%. CONCLUSIONS: Our study has expanded cases of PEMs, especially the 2 PEAM cases in rare sites. Our study has also further summarized the pathological features of PEMs, focusing on the histological features of PEAMs, and the immunohistochemical features worthy of further investigations.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Inmunohistoquímica , Proteína p53 Supresora de Tumor , Antígenos CD34
10.
PLoS One ; 17(9): e0272505, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36048751

RESUMEN

In cognitive radio sensor networks, single clustering protocol cannot simultaneously satisfy the various requirements of time-triggered and event-driven traffic, as a result, different kinds of clustering protocols are designed to serve them separately. In addition, for event-driven traffic, the long delay incurred by clustering and searching for available routes after events results in poor timeliness of information transmission. In order to solve above problems, a traffic-driven ions motion optimization-based clustering routing protocol (TD-IMOCRP) is proposed in this paper. For the first time, time-triggered and event-driven traffic can be served by a single clustering protocol. To be specific, ions motion optimization algorithm is leveraged to automatically determine the optimal number of clusters and form basic clustering structure. In this case, time-triggered traffic can be periodically served. Priority-based schedule and corresponding frame structure are designed to ensure priority delivery of event-driven information. The clustering architecture built for time-triggered traffic is leveraged, and there is no cluster construction and route selection after emergent events. Only the CRSNs nodes which discover emergent events and corresponding CHs participate in data transmission, which means that TD-IMOCRP covers fewer nodes, especially when the sink is located at the corner. Therefore, it can help reduce node energy consumption and delay. Simulation results demonstrate that compared with representative event-driven clustering protocols, TD-IMOCRP can decrease the average number of covered nodes and the total energy consumption by more than 66.3% and 25%, respectively. In addition, when serving time-triggered traffic, TD-IMOCRP can achieve almost the same performance as its basic version IMOCRP which is better than majority of current time-triggered clustering protocols. In a word, TD-IMOCRP can guarantee in-time delivery of event-driven information while guaranteeing its performance of serving time-triggered traffic.


Asunto(s)
Redes de Comunicación de Computadores , Tecnología Inalámbrica , Análisis por Conglomerados , Cognición , Iones
11.
Front Surg ; 9: 855851, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35402493

RESUMEN

Purpose: To systematically evaluate the benefits of reducing and fixing displaced lesser trochanter (LT) of trochanteric fractures and when this procedure is worth the effect. Methods: From database establishment through March 2021, four online databases (PubMed, Cochrane, Embase, and Web of Science) were searched for relevant literature that investigated reduction and fixation for displaced LT of trochanteric fractures. The papers were then screened by two reviewers independently and in duplicate according to prior inclusion and exclusion criteria. Demographic data as well as data on fracture types, surgical protocols, and surgical outcomes were recorded, analyzed, and interpreted. Results: Total 10 clinical studies with 928 patients were included, in which 48 cases had intact LT and 880 cases involved the displaced LT, of which 196 (22.27%) cases underwent reduction and fixation for LT while the rest of 684 (77.73%) cases not. In these studies, complications were evaluated as a more applicable predictive parameter for operation than postoperative hip function. Conclusion: It was beneficial to reduce and fix the displaced LT when one of the conditions below occurred: displacement distance of LT ≥2 cm, quantity of comminuted LT fragments ≥2, and range of LT fragments in medial wall ≥75%; the fracture line of LT fragments reaching or exceeding the midline of the posterior wall.

13.
Laryngoscope Investig Otolaryngol ; 6(5): 1228-1234, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34667869

RESUMEN

OBJECTIVES: We aimed to construct an induction system for polyploid giant cancer cells (PGCCs), as well as to investigate PGCC features and clinical significance. METHODS: A laryngeal neoplasm-PGCC induction system was constructed using paclitaxel liposomes (PTX). We used western blots to compare expression of epithelial-mesenchymal transition-related proteins, stem cell interrelated proteins, and cyclin-associated proteins. We then measured PGCC count in tissue samples of patients with laryngeal neoplasms and analyzed its relationship with prognosis. Statistical significance was determined using t-tests. RESULTS: PTX successfully induced PGCCs. Western blotting showed that CyclinB1, CDC25C, CDK1, E-cadherin, and EIF-4A expression decreased in PGCCs compared with normal cancer cells, whereas vimentin and CD133 expression increased. Number of PGCCs in laryngeal cancer tissues and overall survival time were inversely correlated (P < .05). CONCLUSIONS: PTX successfully induces PGCC formation in laryngeal carcinoma, which may be the cause of poor prognosis in patients with laryngeal cancer.Level of Evidence: 4.

14.
Front Cell Dev Biol ; 9: 710407, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34395438

RESUMEN

Adenomyosis (AM) is a disease in which endometrial tissue invades the myometrium and has a 10-60% prevalence in reproductive-aged women. TSC2 regulates autophagy via mTOR1 signalling in colorectal cancer and endometrial carcinoma. Dysregulation of autophagy is implicated in adenomyosis pathogenesis. However, whether TSC2 participates in adenomyosis via autophagy remains obscure. Here, we found that the expression of TSC2 in adenomyosis was significantly decreased than that in normal endometrium during the secretory phase. Moreover, TSC2 and autophagy marker expression was significantly lower in ectopic lesions than in eutopic samples. TSC2 downregulation inhibited autophagy through mTOR1 signalling pathway activation in endometrial cells, leading to excessive proliferation, migration, and EMT; TSC2 overexpression induced the opposite effects. Rapamycin treatment suppressed cell proliferation, migration and EMT in the absence of TSC2. In parallel, an autophagy-specific inhibitor (SAR-405) restored migration and EMT under rapamycin treatment in TSC2-knockdown Ishikawa cells. Finally, SAR-405 treatment promoted EMT and migration of overexpressing cells. Collectively, our results suggest that TSC2 controls endometrial epithelial cell migration and EMT by regulating mTOR1-autophagy axis activation and that hypo-expression of TSC2 in the endometrium might promote adenomyosis.

15.
Methods Mol Biol ; 2326: 197-201, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34097269

RESUMEN

To assess the toxicities of gas/aerosol, inhalation exposure model is necessary. Especially important is the inhalation exposure early in life. Traditional inhalation exposure method requires specific instruments and may have to imitate the exposure either days before or after birth. Here, a new inhalation exposure method is introduced, which may be performed without any specific instruments and effectively expose late stage chicken embryos to gas/aerosol very early-in-life by inhalation. This method may facilitate the risk assessment and mechanistic studies regarding the early-in-life effects of gas/aerosol exposure.


Asunto(s)
Aerosoles/efectos adversos , Embrión de Pollo/efectos de los fármacos , Gases/efectos adversos , Exposición por Inhalación/efectos adversos , Aerosoles/toxicidad , Animales , Pollos , Gases/toxicidad , Pruebas de Toxicidad/métodos
16.
Cancer Biol Med ; 18(1): 139-154, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33628590

RESUMEN

Objective: Vascular endothelial growth factor (VEGF), apart from its predominant roles in angiogenesis, can enhance cancer cell proliferation, but its mechanisms remain elusive. The purpose of the present study was therefore to identify how VEGF regulates cancer cell proliferation. Methods: VEGF effects on cancer cell proliferation were investigated with the VEGF receptor 2 inhibitor, Ki8751, and the breast cancer cell lines, MCF-7 and MDA-MB-231, using flow cytometry, mass spectrometry, immunoblotting, and confocal microscopy. Data were analyzed using one-way analysis of variance followed by Tukey's multiple comparison test. Results: VEGF blockade by Ki8751 significantly reduced cancer cell proliferation, and enhanced breast cancer cell apoptosis. Mass spectrometric analyses revealed that Ki8751 treatment significantly upregulated the expression of mitochondrial proteins, suggesting the involvement of mitochondrial biogenesis. Confocal microscopy and flow cytometric analyses showed that Ki8751 treatment robustly increased the mitochondrial masses of both cancer cells, induced endomitosis, and arrested cancer cells in the high aneuploid phase. VEGFR2 knockdown by shRNAs showed similar effects to those of Ki8751, confirming the specificity of Ki8751 treatment. Enhanced mitochondrial biogenesis increased mitochondrial oxidative phosphorylation and stimulated reactive oxygen species (ROS) production, which induced cancer cell apoptosis. Furthermore, Ki8751 treatment downregulated the phosphorylation of Akt and PGC1α, and translocated PGC1α into the nucleus. The PGC1α alterations increased mitochondrial transcription factor A (TFAM) expression and subsequently increased mitochondrial biogenesis. Conclusions: VEGF enhances cancer cell proliferation by decreasing Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis, ROS production, and cell apoptosis. These findings suggested the anticancer potential of Ki8751 via increased mitochondrial biogenesis and ROS production.


Asunto(s)
Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Biogénesis de Organelos , Compuestos de Fenilurea/farmacología , Quinolinas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Proteínas Mitocondriales/metabolismo , Neovascularización Patológica/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética
17.
Environ Pollut ; 266(Pt 3): 114961, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32622003

RESUMEN

In this study we systematically reviewed 1203 research papers published between 2008 and 2018 in China and recorded related data on eight kinds of soil heavy metals (Cr, Pb, Cd, Hg, As, Cu, Zn, and Ni). Based on that, the pollution levels, ecological risk and health risk caused by soil heavy metals were evaluated and the pollution hot spots and potential driving factors of different heavy metals in different provinces were also identified. Results indicated accumulation of heavy metals in soils of most provinces in China compared with background values. Consistent with previous findings, the most prevalent polluted heavy metals were Cd and Hg. Polluted regions are mainly located in central, southern and southwestern China. Hunan, Guangxi, Yunnan, and Guangdong provinces were the most polluted provinces. For the potential health risk caused by heavy metals pollution, children are more likely confront with non-carcinogenic risk than adults and seniors. And children in Hunan and Guangxi province were experiencing relatively larger non-carcinogenic risk. In addition, children in part of provinces were undergoing potentially carcinogenic risks due to soil heavy metals exposure. Furthermore, in our study the 31 provinces in mainland China were divided into six subsets according to corresponding potential driving factors for heavy metal accumulation. Our study provide more comprehensive and updated information for contributing to better soil management, soil remediation, and soil contamination control in China.


Asunto(s)
Metales Pesados/análisis , Contaminantes del Suelo/análisis , Adulto , Niño , China , Monitoreo del Ambiente , Humanos , Medición de Riesgo , Suelo
18.
Quant Imaging Med Surg ; 10(3): 657-667, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32269926

RESUMEN

BACKGROUND: Bone age can reflect the true growth and development status of a child; thus, it plays a critical role in evaluating growth and endocrine disorders. This study established and validated an optimized Tanner-Whitehouse 3 artificial intelligence (TW3-AI) bone age assessment (BAA) system based on a convolutional neural network (CNN). METHODS: A data set of 9,059 clinical radiographs of the left hand was obtained from the picture archives and communication systems (PACS) between January 2012 and December 2016. Among these, 8,005/9,059 (88%) samples were treated as the training set for model implementation, 804/9,059 (9%) samples as the validation set for parameters optimization, and the remaining 250/9,059 (3%) samples were used to verify the accuracy and reliability of the model compared to that of 4 experienced endocrinologists and 2 experienced radiologists. The overall variation of TW3-metacarpophalangeal, radius, ulna and short bones (RUS) and TW3-Carpal bone score, as well as each bone (13 RUS + 7 Carpal) between reviewers and the AI, were compared by Bland-Altman (BA) chart and Kappa test, respectively. Furthermore, the time consumption between the model and reviewers was also compared. RESULTS: The performance of TW3-AI model was highly consistent with the reviewers' overall estimation, and the root mean square (RMS) was 0.50 years. The accuracy of the BAA of the TW3-AI model was better than the estimate of the reviewers. Further analysis revealed that human interpretations of the male capitate, hamate, the first distal and fifth middle phalanx and female capitate, the trapezoid, and the third and fifth middle phalanx, were most inconsistent. The average image processing time was 1.5±0.2 s in the TW3-AI model, which was significantly shorter than manual interpretation. CONCLUSIONS: The diagnostic performance of CNN-based TW3 BAA was accurate and timesaving, and possesses better stability compared to diagnostics made by experienced experts.

19.
Postgrad Med J ; 96(1135): 286-295, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32054779

RESUMEN

The prognostic value of long intergenic non-protein coding RNA 460 (LINC00460) overexpression in human solid malignant tumours remains unclear. Therefore, we conducted the meta-analysis to systematically review and assess the evidence for the correlation between LINC00460 overexpression and clinicopathological features and overall survival (OS) of patients with solid malignant tumour. An electronic search of PubMed, EMBASE, Web of Science, CNKI, Cochrane Library, Chinese Biological Medical Literature database and WanFang database was applied to select eligible articles. Pooled ORs or HRs with their 95% CIs were calculated to estimate the effects. 9 eligible studies with a total of 935 patients were enrolled in this meta-analysis. The results revealed that high LINC00460 expression was associated with positive lymph node metastasis (positive vs negative: OR=2.97, 95% CI 1.74 to 5.05, p=0.812), advanced tumour-node-metastasis stage (III+IV vs I+II: OR=2.82, 95% CI 1.64 to 4.85, p=0.193) and poorer differentiation (high vs low: OR=0.60, 95% CI 0.36 to 0.99, p=0.569). Additionally, the overexpression of LINC00460 could predict a poorer OS (HR=1.57, 95% CI 1.39 to 1.77) and the shorter disease-free survival (HR=2.32, 95% CI 1.25 to 4.31). Furthermore, according to subgroup analysis and meta-regression results, the heterogeneity of current meta-analysis may be attributed to the differences of cancer type and follow-up months. High expression of LINC00460 could predict poor prognosis in patients with solid malignant tumour. LINC00460 may serve as potential prognostic biomarker for clinical outcomes in various human solid malignant tumours.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias/metabolismo , ARN Largo no Codificante/metabolismo , Factores de Edad , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Neoplasias/patología , Pronóstico , Factores Sexuales , Carga Tumoral
20.
Postgrad Med J ; 96(1131): 43-52, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31444240

RESUMEN

Long intergenic non-coding RNA 01296 (LINC01296) has been reported to play an important role in many human malignancies, but a consistent perspective has not been established now. To explore the prognostic value of LINC01296 in different types of human solid malignant tumours, we performed this meta-analysis.An electronic search of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Cochrane Library, Chinese Biological Medical Literature database and WanFang database was applied to select eligible literatures. Pooled ORs or HRs with their 95% CIs were calculated to estimate the effects.A total of 559 patients from nine eligible studies were enrolled in this meta-analysis. The results revealed that high LINC01296 expression was significantly related to larger tumour size (OR 3.42, 95% CI 2.08 to 5.63), lymph node metastasis (OR 3.03, 95% CI 2.01 to 4.57) and advanced tumor-node-metastasis (TNM) stage (OR 4.41, 95% CI 2.65 to 7.34). Moreover, we found that elevated LINC01296 expression predicted a poor outcome for overall survival (HR 1.78, 95% CI 1.48 to 2.14) and recurrence-free survival (HR 4.00, 95% CI 1.04 to 15.67).High expression levels of LINC01296 were associated with unfavourable clinical outcomes of patients with cancer. Our results indicated that LINC01296 could serve as a prognostic predictor in human solid malignant tumours.


Asunto(s)
Neoplasias , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estadificación de Neoplasias , Neoplasias/genética , Neoplasias/mortalidad , Neoplasias/patología , Pronóstico , Carga Tumoral
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