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1.
J Neuroinflammation ; 21(1): 29, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38246987

RESUMO

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.


Assuntos
Encefalomielite Autoimune Experimental , Exossomos , MicroRNAs , Bainha de Mielina , Animais , Camundongos , Exossomos/metabolismo , Microglia/metabolismo , MicroRNAs/genética
2.
Am J Gastroenterol ; 118(4): 627-634, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729890

RESUMO

INTRODUCTION: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. METHODS: A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. RESULTS: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). CONCLUSIONS: The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/uso terapêutico , Bismuto/uso terapêutico , Antibacterianos , Quimioterapia Combinada , Claritromicina/uso terapêutico , Resultado do Tratamento , Inibidores da Bomba de Prótons/efeitos adversos
3.
Biochem Biophys Res Commun ; 550: 134-141, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33691199

RESUMO

Tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, has been reported to participate in many human cancers. However, the underlying role of TRIM32 in glioma remains largely unknown. Here, we aimed to explore the function of TRIM32 in glioma cells and the clinical implications and found that TRIM32 was upregulated in glioma tissues. Consistently, overexpression of TRIM32 promoted glioma U87 and U251 cell proliferation and conferred cell resistance to temozolomide (TMZ). Conversely, knockdown of TRIM32 inhibited glioma cells proliferation in vitro and in vivo and sensitized glioma cells to the treatment of TMZ in a p53-dependent and -independent manner. Mechanistically, knockdown of TRIM32 induced apoptosis of U87 an U251 cells. In addition, TRIM32 interacted with the antiapoptotic proteins BCL-xL and BCL-w, which antagonized the inhibitory effect of TRIM32 knockdown in U87 cells. Together, our study uncovered the role of TRIM32 in glioma and TRIM32 may be a potential therapeutic target for gliomas.


Assuntos
Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Glioma/tratamento farmacológico , Glioma/patologia , Temozolomida/uso terapêutico , Fatores de Transcrição/deficiência , Proteínas com Motivo Tripartido/deficiência , Proteína Supressora de Tumor p53 , Ubiquitina-Proteína Ligases/deficiência , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/genética , Humanos , Camundongos , Terapia de Alvo Molecular , Gradação de Tumores , Temozolomida/farmacologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/biossíntese , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/biossíntese , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Inorg Chem ; 59(19): 14085-14092, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32926625

RESUMO

In recent years, two-dimensional (2D) hybrid lead halide perovskites based on corner-shared [PbX6] octahedrons have received extensive attention with important potentials in single-component white-light emitting diodes (WLEDs) due to the soft and distorted crystal lattices. However, limited research focused on the one-dimensional (1D) perovskites although they possess similar structural superiorities to achieve this performance. Herein, by using different types of organic amine cations as structural direction reagents, we report one new type of hybrid 1D perovskites of APbCl3 (A = (DTHPE)0.5, DMTHP, DBN) based on the same 1D face-shared octahedral [PbCl3]- chains. Upon UV light excitation, these 1D APbCl3 perovskites exhibit intrinsic broad-band bluish white-light emissions covering entire visible light spectra with the highest photoluminescence quantum yield (PLQY) of 6.99%, which catches up with the values of previously reported 2D perovskites. Through the systematical studies of time-resolved, temperature-dependent PL emissions, theoretical calculations, and so on, these broad-band light emissions can be ascribed to the radiative transition within conjugated organic cations. The facile assembly process, intrinsic broad-band light emissions, and high PLQYs enable these 1D APbCl3 perovskites as new types of promising candidates in fabricating single-component WLEDs.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 31-36, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948521

RESUMO

OBJECTIVE: To study the clinical effect and complications of continuous blood purification (CBP) in the treatment of multiple organ dysfunction syndrome (MODS) in neonates. METHODS: A retrospective analysis was performed for the clinical data of 21 neonates with MODS who were admitted to the neonatal intensive care unit from November 2015 to April 2019 and were treated with CBP. Clinical indices were observed before treatment, at 6, 12, 24, and 36 hours of CBP treatment, and at the end of treatment to evaluate the clinical effect and safety of CBP treatment. RESULTS: Among the 21 neonates with MODS undergoing CBP, 17 (81%) had response to treatment. The neonates with response to CBP treatment had a significant improvement in oxygenation index at 6 hours of treatment, a significant increase in urine volume at 24 hours of treatment, a stable blood pressure within the normal range at 24 hours of treatment, and significant reductions in the doses of the vasoactive agents epinephrine and dopamine at 6 hours of treatment (P<0.05), as well as a significant reduction in serum K+ level at 6 hours of treatment, a significant improvement in blood pH at 12 hours of treatment, and significant reductions in blood lactic acid, blood creatinine, and blood urea nitrogen at 12 hours of treatment (P<0.05). Among the 21 neonates during CBP treatment, 6 experienced thrombocytopenia, 1 had membrane occlusion, and 1 experienced bleeding, and no hypothermia, hypotension, or infection was observed. CONCLUSIONS: CBP is a safe, feasible, and effective method for the treatment of MODS in neonates, with few complications.


Assuntos
Insuficiência de Múltiplos Órgãos , Gasometria , Nitrogênio da Ureia Sanguínea , Hemofiltração , Humanos , Recém-Nascido , Estudos Retrospectivos
6.
Langmuir ; 32(37): 9437-44, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27605160

RESUMO

Structural evolution of polymer (NTZ12) interface films during the process of annealing is revealed at the domain and single molecular levels using the statistical data measured from scanning tunneling microscopy images and through theoretical calculations. First, common features of the interface films are examined. Then, mean values of surface-occupied ratio, size and density of the domain are used to reveal the intrinsic derivation of the respective stages. Formation of new domains is triggered at 70 °C, but domain ripening is not activated. At 110 °C, the speed of formation of new domains is almost balanced by the consumption due to the ripening process. However, formation of new domains is reduced heavily at 150 °C but restarted at 190 °C. At the single molecular level, the ratio of the average length of linear to curved backbones is increased during annealing, whereas the ratios of the total length and the total number of linear to curved skeletons reaches a peak value at 150 °C. The two major conformations of curved backbones for all samples are 120° and 180° bending, but the ripening at 150 °C reduces 180° folding dramatically. Molecular dynamic simulations disclose the fast relaxing process of curved skeletons at high temperature.

7.
Proc Natl Acad Sci U S A ; 110(21): 8375-80, 2013 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-23671096

RESUMO

Synthetic nitrogen (N) fertilizer has played a key role in enhancing food production and keeping half of the world's population adequately fed. However, decades of N fertilizer overuse in many parts of the world have contributed to soil, water, and air pollution; reducing excessive N losses and emissions is a central environmental challenge in the 21st century. China's participation is essential to global efforts in reducing N-related greenhouse gas (GHG) emissions because China is the largest producer and consumer of fertilizer N. To evaluate the impact of China's use of N fertilizer, we quantify the carbon footprint of China's N fertilizer production and consumption chain using life cycle analysis. For every ton of N fertilizer manufactured and used, 13.5 tons of CO2-equivalent (eq) (t CO2-eq) is emitted, compared with 9.7 t CO2-eq in Europe. Emissions in China tripled from 1980 [131 terrogram (Tg) of CO2-eq (Tg CO2-eq)] to 2010 (452 Tg CO2-eq). N fertilizer-related emissions constitute about 7% of GHG emissions from the entire Chinese economy and exceed soil carbon gain resulting from N fertilizer use by several-fold. We identified potential emission reductions by comparing prevailing technologies and management practices in China with more advanced options worldwide. Mitigation opportunities include improving methane recovery during coal mining, enhancing energy efficiency in fertilizer manufacture, and minimizing N overuse in field-level crop production. We find that use of advanced technologies could cut N fertilizer-related emissions by 20-63%, amounting to 102-357 Tg CO2-eq annually. Such reduction would decrease China's total GHG emissions by 2-6%, which is significant on a global scale.


Assuntos
Pegada de Carbono , Indústria Química/métodos , Indústria Química/tendências , Conservação dos Recursos Naturais/métodos , Fertilizantes , Efeito Estufa/prevenção & controle , Nitrogênio , Indústria Química/economia , Indústria Química/legislação & jurisprudência , China , Conservação dos Recursos Naturais/economia , Conservação dos Recursos Naturais/tendências
8.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(7): 867-874, 2016 07.
Artigo em Chinês | MEDLINE | ID: mdl-30634217

RESUMO

OBJECTIVE: To explore the effect of peptide extract from scorpion venom (PESV) to multidrug resistance (MDR) of leukemic stem cell (LSC) in vivo. METHODS: K562/A02 cells were cultured and collected in the logarithmic phase. K562/A02 stem cells were screened using immunomagnetic beads for reserve. K562/A02 LSC was injected to 5 of 40 BABL/c nude mice for preparing subcutaneous tumor. The rest 35 nude mice were then randomly divided into 7 groups, i.e., the normal control group, the model group, the Adriamycin (ADM) group, the PESV group, the ADM +high dose PESV group, the ADM + middle dose PESV group, the ADM +low dose PESV group, 5 in each group. Tumor tissue was embedded in all groups except the normal control group. One milliliter normal saline was peritoneally injected to mice in the model group after modeling, once per day. ADM 0. 05 mg was peritoneally injected to mice in the ADM group, once per other day. PESV 2 µg was peritoneally injected to mice in the PESV group, once per day. Mice in 3 ADM + PESV groups were peritoneally injected with ADM 0. 05 mg (once per other day) plus PESV (5, 2, and 1 µg respectively, once per day). All medication lasted for 14 days. P-glycoprotein (P-gp) was detected using flow cytometry. Breast cancer resistance protein (BCRP) and mRNA expression of multidrug resistance 1 (MDR1) were measured using RT-PCR. Aldehyde dehydrogenase 1 (ALDH1) was detected using immunohistochemistry. Phosphoinositide 3-kinase (PI3K) was detected using Western blot. NF-κB content was detected using ELISA. RESULTS: CD34 + CD38-ratio was 31.5% and IC50 was (60.33 ± 10. 68) µg/mL before K562/A02 cells were screened with immunomagnetic beads, while they were 92. 8% and (58. 33 ±9. 72) µg/mL after screen. The tumor formation rate was 100% in modeling mice. Compared with the model group, no statistical difference of each index occurred in the ADM group (P <0. 05). There was statistical difference in BCRP, MDR1 mRNA, or NF-κB factor between the model group and the PESV group (P <0. 05). The expression level of P-gp obviously decreased and the protein expression of P13K was down-regulated in 3 ADM + PESV groups (P <0. 05); mRNA expression of BCRP decreased and mRNA ex- pression of MDR1 obviously increased in the ADM + high dose PESV group and the ADM + middle dose PESV group, with statistical difference (P <0. 05). Protein expression of P13K was down-regulated in the ADM+ high dose PESV group, with statistical difference (P <0. 05). P-gp value, BCRP mRNA expression, MDR1 mRNA expression, PI3K, and NF-κB factor were all obviously down-regulated in the ADM +high dose PESV group, as compared with the ADM group and the PESV group respectively (P <0. 05). There was no statistical difference in ALDH1 positive rate among all groups (P >0. 05). Conclusion PESV combined ADM could down-regulate expression levels of P-gp, BCRP, MDR1, P13K, and NF-κB, strengthen the sensitivity of K562/A02 LSC to ADM in vivo, and reverse MDR of LSC.


Assuntos
Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Leucemia Eritroblástica Aguda , Venenos de Escorpião , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Doxorrubicina , Humanos , Células K562 , Leucemia Eritroblástica Aguda/patologia , Camundongos , Camundongos Nus , Peptídeos , Fosfatidilinositol 3-Quinases , Venenos de Escorpião/farmacologia , Células-Tronco
9.
Neurol Sci ; 36(5): 717-21, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25560534

RESUMO

Glioblastoma multiforme and anaplastic astrocytoma are challenges to clinical biologists at present. The patients with glioblastoma have median survival of less than 12 months, despite advances in radiotherapeutical, chemotherapeutical and conventional surgical modalities. Retinoic acids are known to effect in vitro proliferation, differentiation, and apoptosis in colon, prostate, lung, and leukemia cancers. Retinoids are known to have anti-proliferation, anti-migration, and anti-invasive activity against human malignant gliomas, suggesting that retinoids are suitable anticancer agents to inhibit progression of tumors. Recurrent malignant cerebral gliomas have been treated with ATRA and 13-cis RA. However, the side effects associated with the use of high doses of retinoic acid demand for some more potent derivative free from such effects. The present clinical trials are undertaken to investigate the clinical safety and possible efficacy of administering retinoic acid naphthalene triazole (RANT) to patients with recurrent malignant gliomas. The toxicities observed in the patients during RANT treatment were mild. These preliminary results suggest that RANT is more potent compared to RA against recurrent malignant gliomas.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Isotretinoína/uso terapêutico , Naftalenos/uso terapêutico , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Isotretinoína/química , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Naftalenos/química , Análise de Sobrevida , Resultado do Tratamento
10.
World J Clin Oncol ; 15(2): 317-328, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38455137

RESUMO

BACKGROUND: Limonin is one of the most abundant active ingredients of Tetradium ruticarpum. It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear. AIM: To evaluate the effects of limonin on CSCs derived from CRC cells. METHODS: CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability. RESULTS: As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and ß-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and ß-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 µmol/L colievlin. CONCLUSION: Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

11.
Aging (Albany NY) ; 16(3): 2774-2788, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38319729

RESUMO

As an inflammatory bowel disease, ulcerative colitis (UC) does not respond well to current treatments. It is of positive clinical significance to further study the pathogenesis of UC and find new therapeutic targets. B lymphocytes play an important role in the pathogenesis of UC. The effect of anti-CD20 therapy on UC also provides new evidence for the involvement of B cells in UC process additionally, suggesting the important role and potential therapeutic value of B cells in UC. In this study, we screened the most critical immune cell-related gene modules associated with UC and found that activated B cells were closely related to the gene modules. Subsequently, key activated B cell-associated gene (BRG) signatures were obtained based on WGCNA and differential expression analysis, and three overlapping BRG-associated genes were obtained by RF and LASSO algorithms as BRG-related diagnostic biomarkers for UC. Nomogram model was further performed to evaluate the diagnostic ability of BRG-related diagnostic biomarkers, subsequently followed by UC molecular subsets identification and immunoinfiltration analysis. We also further verified the expressions of the three screened BRGs in vitro by using an LPS-induced NCM460 cell line model. Our results provide new evidence and potential intervention targets for the role of B cells in UC from a new perspective.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Doenças Inflamatórias Intestinais/complicações , Redes Reguladoras de Genes , Biomarcadores
12.
Int J Med Sci ; 10(10): 1301-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23983589

RESUMO

BACKGROUND: The Nemo-like kinase (NLK) is a serine/threonine-protein kinase that involved in a number of signaling pathways regulating cell fate. Variation of NLK has been shown to be associated with the risk of cancer. However, the function of NLK in oral adenosquamous carcinoma cells line CAL-27 is unknown. METHODS: In this study, we evaluated the function of NLK in CAL-27 cells by using lentivirus-mediated RNA silence. The targeted gene expression, cell proliferation and cell cycle are investigated by RT-PCR, western-blot, MTT method, colony forming assay and flow cytometry analysis respectively. RESULTS: After NLK silencing, the number of colonies was significantly reduced (54 ± 5 colonies/well compared with 262 ± 18 colonies/well in non-infected or 226 ± 4 colonies/well in negative control group (sequence not related to NLK sequence with mismatched bases). Using crystal violet staining, we also found that the cell number per colony was dramatically reduced. The RNA silencing of NLK blocks the G0/G1 phase to S phase progression during the cell cycle. CONCLUSIONS: These results suggest that NLK silencing by lentivirus-mediated RNA interference would be a potential therapeutic method to control oral squamous carcinoma growth.


Assuntos
Carcinoma Adenoescamoso/enzimologia , Fase G1/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lentivirus/genética , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA/fisiologia , Fase de Repouso do Ciclo Celular/fisiologia , Fase S/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Fase G1/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Serina-Treonina Quinases/genética , Fase de Repouso do Ciclo Celular/genética , Fase S/genética
13.
Heliyon ; 9(2): e13185, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36747547

RESUMO

Background: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. Methods: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package "limma". Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. Results: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. Conclusion: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA.

14.
Sci Adv ; 9(16): eabq7105, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37083538

RESUMO

The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer's disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3×Tg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , MicroRNAs , Animais , Camundongos , Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , MicroRNAs/metabolismo , Neurônios/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Humanos
15.
Opt Lett ; 36(19): 3933-5, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21964146

RESUMO

Because of the limited approximation capability of using fixed basis functions, the performance of reflectance estimation obtained by traditional linear models will not be optimal. We propose an approach based on the regularized local linear model. Our approach performs efficiently and knowledge of the spectral power distribution of the illuminant and the spectral sensitivities of the camera is not needed. Experimental results show that the proposed method performs better than some well-known methods in terms of both reflectance error and colorimetric error.

16.
Neurocrit Care ; 14(3): 377-81, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21298359

RESUMO

BACKGROUND: There is limited information on the incidence and effect of acute kidney injury (AKI) in patients with severe traumatic brain injury (TBI), although AKI may affect outcome. Recently, acute kidney injury network (AKIN) classification has been widely accepted as a consensus definition for AKI. The aim of this study is to estimate the frequency and level of severity of AKI in patients with severe TBI by using AKIN criteria and to study whether AKI affects outcome. METHODS: The authors retrospectively identified a total of 136 patients with severe TBI admitted to the neurosurgical center during a 3-year period ending May 2010. Demographic data, severity of TBI, serum creatinine, urine output, outcome at 6 month, and death were collected. Renal function was assessed by using AKIN criteria. RESULTS: Thirty-one patients (23%) were classified as having AKI by using AKIN criteria during their hospitalization. Of them, 21 patients (68%) were stratified as stage 1, 7 patients (22%) as stage 2, and 3 patients (10%) as stage 3. Patients who developed AKI were older, had lower Glasgow coma scale at admission, and had higher level of admission serum creatinine and blood urea nitrogen. Patients with AKI had higher mortality and worse outcome when compared with patients with normal renal function. Furthermore, patients with mild renal dysfunction (stage 1 AKI) are also found having increased mortality and worse long-term outcome, compared with patients without renal dysfunction. CONCLUSION: It is demonstrated using the newly defined AKIN criteria for renal dysfunction that AKI is a relatively common feature in patients with severe TBI, and even seemingly insignificant decrease in renal function may be associated with worse outcome. This study highlights the importance of close surveillance of renal function and stresses the value of renal hygiene in the severe TBI population.


Assuntos
Injúria Renal Aguda/classificação , Injúria Renal Aguda/diagnóstico , Lesões Encefálicas/classificação , Lesões Encefálicas/diagnóstico , Injúria Renal Aguda/mortalidade , Adulto , Idoso , Lesões Encefálicas/mortalidade , Creatinina/sangue , Diurese/fisiologia , Feminino , Seguimentos , Escala de Coma de Glasgow , Mortalidade Hospitalar , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
17.
Zhonghua Zhong Liu Za Zhi ; 33(4): 260-4, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21575495

RESUMO

OBJECTIVE: To investigate the effect of hypoxia inducible factor-1α (HIF-1α) on the proliferation, migration and vasculogenic mimicry(VM) in human esophageal squamous cell carcinoma cell line Eca-109 and gastric adenocarcinoma cell line SGC-7901 in vitro. METHODS: The recombinant plasmid pGCsi-shHIF-1α was transfected into Eca-109 and SGC-7901 cells by Lipofectamine(TM) 2000. The inhibitory effect of HIF-1α was measured at protein level by Western blot under normoxia and hypoxia. The cell proliferation was detected by colony formation and MTT assays. The migration of transfected cells was assayed using Transwell chambers. Whether Eca-109 and SGC-7901 cells could form the capillary tube-like structures (TLSs) was observed by 3-dimensional culture, and the tube formation of transfected cells was detected by tube-like structure formation assay. RESULTS: The expression of HIF-1α protein in each group of transfected cells was significantly suppressed under normoxia and hypoxia (Eca-109: 0.00, 0.74 ± 0.05; 0.00, 1.11 ± 0.06; SGC-7901: 0.00, 0.60 ± 0.05; 0.00, 0.96 ± 0.07, P < 0.01). Colony formation and MTT assays showed that the cell proliferation of the pGCsi-shHIF-1α transfected cells was slower than that of the control groups (104.7 ± 9.6, 151.7 ± 4.5; 88.3 ± 5.1, 128.3 ± 6.7, P < 0.05). The migration of the recombinant plasmid-transfected cells was significantly suppressed compared with that of cells transfected with empty vector (55.5 ± 11.2, 121.9 ± 17.3; 64.7 ± 10.8, 132.3 ± 16.0, P < 0.01). Both the Eca-109 and SGC-7901 cells could form TLSs when cultured on matrigel, and the number of tubules was significantly increased under hypoxia (30.8 ± 3.9, 34.3 ± 3.4; 26.2 ± 3.4, 30.1 ± 4.1, P < 0.05), the tubule-forming ability of transfected groups was significantly inhibited under normoxia and hypoxia (Eca-109: 3.7 ± 2.8, 30.8 ± 3.9; 3.9 ± 2.7, 34.3 ± 3.4; SGC-7901: 4.9 ± 3.5, 26.2 ± 3.4; 5.3 ± 3.6, 30.1 ± 4.1, P < 0.01). CONCLUSIONS: Both the esophageal squamous cell carcinoma cell line Eca-109 and gastric adenocarcinoma cell line SGC-7901 are capable of forming vasculogenic mimicry structures in vitro. The recombinant plasmid pGCsi-shHIF-1α can efficiently suppress their proliferation, migration and vasculogenic mimicry formation.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Interferência de RNA , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Hipóxia Celular , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Patológica/patologia , Plasmídeos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Transfecção
18.
Ying Yong Sheng Tai Xue Bao ; 32(11): 4021-4028, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34898118

RESUMO

Planting grasses in orchards is important to maintain soil basic fertility, improve the soil ecological environment, and promote sustainable growth of fruit. However, the quantitative effects of grasses on nutrient content of orchard soil in China is unclear, as well as the mechanisms associated with higher fruit yield and quality in orchards. This meta-analysis included 62 literature published between 1990 and 2020 to quantify effects of soil depth, planting years of raw grasses, and raw grasses to the physical and chemical properties and fruit yield and quality of orchards, as well as to explore the impacts of grasses on the sustainable production of Chinese orchards. Between 1990 and 2020, compared with the non-grass orchards, the content of soil organic matter, alkali nitrogen and available phosphorus in orchard with grasses increased by 18%, 11%, and 27% respectively, and the soil bulk density was reduced by 20%. Orchard grass increased soil temperature by 23% when the temperature was below 10 ℃, and reduced soil temperature by about 8% when the temperature was above 10 ℃. Compared with annual grasses, perennial grasses (natural or artificial) significantly improved soil properties, fruit yield and quality. These findings indicated that long-term grass planting in orchards had far-reaching significance on sustainable production.


Assuntos
Malus , Solo , Frutas/química , Nitrogênio/análise , Fósforo
19.
Eur Neurol ; 64(6): 320-4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21071947

RESUMO

The present note provides an overview of the historical development of neurology and its current status in the People's Republic of China, against the backdrop of the current massive transformation of Chinese society. We trace the origins of neurology in China to missionary medicine during the Republican period (1911-1949), and describe how the discipline grows with difficulty throughout the subsequent decades (1950-1976). We then introduce an influential legacy of the post-revolutionary period, the ideal of integrating traditional Chinese medicine (TCM) and Western medicine, and briefly describe recent efforts to modernize medical education and training. Finally, we provide a brief overview of topics in neurology and neuropsychiatry that have a 'Chinese face', last but not least the successful integration of TCM and Western medicine in the treatment of hepatolenticular degeneration/Wilson's disease.


Assuntos
Medicina Tradicional Chinesa/história , Neurologia/educação , Neurologia/história , China , História do Século XX , História do Século XXI , Humanos , Recursos Humanos
20.
J Laparoendosc Adv Surg Tech A ; 30(5): 547-552, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32045316

RESUMO

Objective: This study aimed to investigate the application of nanocarbon in surgical endoscopy in patients with thyroid cancer for the clinical tracing of level VI sentinel lymph nodes (SLNs) and for parathyroid gland protection. Materials and Methods: Ninety-three patients with papillary thyroid carcinoma (PTC) who underwent an endoscopic thyroid cancer operation were included. We randomly divided these patients into a control group (n = 42) and a nanocarbon group (n = 51). For the nanocarbon group, after thyroid exposure, nanocarbon was injected into the thyroid gland, and the SLNs were resected and subjected to frozen sectioning and routine pathological examination. In addition, the postoperative calcium and parathyroid hormone (PTH) levels of both groups were analyzed to compare the features of the nanocarbon application. Results: The number of central lymph (level VI) nodes dissected and the number of metastatic lymph nodes identified were analyzed in both groups. The number of dissected lymph nodes from both unilateral and bilateral thyroid surgeries was significantly larger in the nanocarbon group than in the control group. At the same time, the number of identified metastasis lymph nodes dissected were higher in the nanocarbon group than in the control group. We assessed the postoperative calcium and PTH level to evaluate the parathyroid function. Our results show that the nanocarbon group had a better protective effect on parathyroid function than the control group. Conclusions: As a lymph node trace agent, nanocarbon could better evaluate and permit a more clear lymph dissection for patients with PTC. Nanocarbon contributes to a decrease in the incidence rate of parathyroid damage, which has great clinical value.


Assuntos
Carbono/química , Nanopartículas/química , Glândulas Paratireoides/cirurgia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto , Mama/cirurgia , Dissecação , Endoscopia , Feminino , Secções Congeladas , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/metabolismo , Período Pós-Operatório , Estudos Prospectivos , Linfonodo Sentinela/cirurgia , Adulto Jovem
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