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1.
J Org Chem ; 88(23): 16424-16434, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37943255

RESUMO

A new efficient synthesis of indolo[2,1-b]quinazolin-6(12H)-ones via a sequential Ugi/iodine-promoted cyclization/Staudinger/aza-Wittig reaction was developed. The acid catalyzed three-component reactions of 2-azidobenzaldehydes, 2-[2-(trimethylsilyl)ethynyl]benzenamines (or o-aminoacetophenones), and isocyanides gave Ugi-3CR intermediates, which reacted subsequently with I2/DMSO and triphenylphosphine to produce indolo[2,1-b]quinazolin-6(12H)-ones in good overall yields. The obtained indolo[2,1-b]quinazolin-6(12H)-ones were all colored in bright red or orange. Their luminescent property was studied preliminarily and some of them showed high molar absorption coefficients, strong fluorescence emission intensity, and good absolute light quantum yields.

2.
J Org Chem ; 88(3): 1898-1906, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36649062

RESUMO

A new efficient and stereoselective synthesis of 12-tetrazolyl substituted (E)-5H-quinazolino[3,2-a]quinazolines via sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag(I)-catalyzed cyclization was developed. The four-component reactions of 2-azidobenzaldehyde, 2-(alkynyl)benzenamine, isocyanide, and trimethylsilyl azide gave Ugi-azide intermediates, which were subsequently treated with triphenylphosphine and isocyanate to produce 12-tetrazolyl substituted (E)-5H-quinazolino[3,2-a]quinazolines in the presence of Ag(I) catalyst and K2CO3.

3.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4231-4236, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37802791

RESUMO

Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Estudos Prospectivos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , China
4.
J Environ Manage ; 324: 116323, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36166869

RESUMO

With the increase of the azo pigment wastewater, it is necessary to seek an efficient and sustainable treatment method to address issues of damaging water ecosystems and human health. In this work, organic representing azo dye Acid Orange 7 (AO7), heavy metal representing hexavalent chromium (Cr(VI)), and inorganic representing ammonia nitrogen (NH4+-N) were selected to roughly simulate the azo pigment wastewater. The simultaneous decontamination of multi-target pollutants by 700 °C pyrolyzed peanut shell biochar (BC) with persulfate (PDS) was evaluated. The results showed that AO7, Cr(VI) and NH4+-N could finally reach 100%, 85% and 30% removal ratios separately in the BC/PDS/mixed pollutants system under certain basic conditions. Functional groups (hydroxyl groups (C-OH) and carboxylic ester/lactone groups (O-C=O)) were found by XPS as competing sites for adsorption and activation and were gradually consumed as the reaction proceeded. Combining a series of experiments results and EPR analysis, it was found that AO7 removal worked best and it relied on both the radical pathway (including SO4•-, •OH, O2-•, but not 1O2) and adsorption. Cr(VI) was mainly adsorbed and reduced by BC surface to form Cr(OH)3 and Cr2O3, and the remaining part could be reduced by O2-•, followed by •OH. NH4+-N was removed primarily by the radical same as AO7. Meanwhile, the three target pollutants have a co-competitive mechanism. Specifically, they competed for radicals and adsorption sites simultaneously, while the presence of AO7 and NH4+-N would consume the generated oxidizing radicals and further promote the removal of Cr(VI). The fixed-bed reactor simulated the continuous treatment of wastewater. Various anions (chloride (Cl-), nitrate (NO3-), carbonate (CO32-), and hydrogen phosphate (HPO42-)) interfered differently with the pollutant removal. These findings demonstrate a new dimension of BC potential for decontamination of azo pigment wastewater.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Humanos , Ecossistema , Poluentes Químicos da Água/análise , Carvão Vegetal , Cromo , Adsorção , Cloretos
5.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4256-4260, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046916

RESUMO

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations' safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Prescrições , Controle de Qualidade , Síndrome
6.
Beilstein J Org Chem ; 18: 286-292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35330780

RESUMO

A new efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reaction has been developed. The three-component Passerini reactions of 2-azidobenzaldehydes 1, benzoic acid (2), and isocyanides 3 produced the azide intermediates 4, which were treated sequentially with triphenylphosphine, isocyanates (or CS2), and secondary amines to give polysubstituted 3,4-dihydroquinazolines 8 and 4H-3,1-benzothiazines 11 in good overall yields through consecutive Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reactions.

7.
J Org Chem ; 86(15): 10755-10761, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34251829

RESUMO

A new efficient synthesis of polysubstituted pyrazin-2(1H)-ones via the sequential Ugi/Staudinger/aza-Wittig/isomerization reaction has been developed. The four-component Ugi reactions of arylglyoxals 1, primary amines 2, α-azidovinyl acids 3, and isocyanides 4 produced the azides 5, which were treated with triphenylphosphine to give pyrazin-2(1H)-ones 6 in good yields through domino Staudinger/aza-Wittig/isomerization reactions.


Assuntos
Aminas , Azidas , Cianetos , Isomerismo
8.
Artigo em Chinês | MEDLINE | ID: mdl-38858124

RESUMO

Ectopic pituitary adenoma is rare in clinical practice. This article reports a case of ectopic pituitary adenoma of sphenoid sinus, and summarizes the clinical characteristics, diagnosis and management. A 54-year-old female patient complaining with occasional head distension without dizziness and headache for more than 1 month was admitted due to sinus mass on conventional physical examination. Imaging examination revealed a mass in the occipital slope and bilateral sphenoid sinus. The patient underwent endoscopic resection of the mass under general anesthesia. Postoperative histopathological examination showed "pituitary neuroendocrine tumor". Postoperative recovery was good and no complications occurred. She was followed up for 2 months without relapse.


Assuntos
Neoplasias Hipofisárias , Seio Esfenoidal , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Adenoma/cirurgia , Adenoma/patologia
9.
Anal Chim Acta ; 1304: 342531, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38637047

RESUMO

BACKGROUND: The global release of organic and heavy metal components into natural water bodies is a major concern for the environment and human health. The assessment of water quality relies on analyzing organic and heavy metal components qualitatively and quantitatively. Real-time identification of organic and metal components in water systems requires different analytical techniques due to varying measurement requirements. Thus, on-line detecting both organic compounds and heavy metals in ambient water systems simultaneously using a single instrumentation setup presents a significant challenge. RESULTS: In this study, an analytical technique of nebulization-assisted injection plasma ionization mass spectrometry (NI-PIMS) was developed. This novel method enables the simultaneous detection of heavy metals and organic compounds in water system with high sensitivity, which has been demonstrated by the limit of quantification (LOQ) values below 1.0 µg/L for the three sterols (Enrofloxacin, ciprofloxacin, and clenbuterol) and three heavy metals (Pb, Ba, and Cd). Moreover, the method was successfully applied to rapidly analyze real water samples from urban and rural areas in China. The analytical results are available in less than 0.5 min, and only a few microliters of sample are required for each analysis. SIGNIFICANCE AND NOVELTY: As far as we know, this is the first report of on-line simultaneous analysis of organic compounds and heavy metals in a water system using a single mass spectrometry instrument. Compared to traditional methods, NI-PIMS demonstrates higher efficiency, sensitivity, no or lower sample preparation, and less sample consumption. The advancement and widespread use of this technology are expected to enhance the effectiveness of mass spectrometers, broaden the applications, and play an important role in complex sample analysis in fields such as atmospheric science, environmental science, and earth science.

10.
J Hazard Mater ; 471: 134431, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691936

RESUMO

To promote the environmentally friendly and sustainable development of nuclear energy, it is imperative to address the treatment of wastewater generated by the nuclear industry. This necessitates the enhancement of fission product reclamation efficiency post-treatment. This study aims to combine defect control and confined self-assembly strategies for the precise design of interlayer spacing (14.6 Å to 15.1 Å), leading to the fabrication of conditional natroxalate-functionalized vanadosilicate, and its potential application in the efficient adsorption and reclamation of 90Sr. Na0.03Natroxalate2.47Si1.44Nb0.08V1.92O5·1.2 H2O (Nb4-NxSiVO), with a layer spacing of 14.9 Å, exhibits the highest Sr(II) adsorption capacity (248.76 mg/g), enabling effective separation with Cs+. The natroxalate embedded within the confined interlayers demonstrates excellent stability, offering rapid (within 10 min) and stable adsorption sites for Sr(II). Furthermore, Nb4-NxSiVO exhibits a wide band gap and exceptional thermal stability before and after adsorption, rendering hard desorption of 90Sr. The findings highlight the potential of Nb4-NxSiVO as a promising adsorbent for rapid and selective purification of 90Sr-containing wastewater and further application in nuclear batteries.

11.
Adv Sci (Weinh) ; : e2404701, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940403

RESUMO

The development of the electric vehicle industry has spurred demand for secondary batteries capable of rapid-charging and slow-discharging. Among them, sodium-ion batteries (SIBs) with layered oxide as the cathode exhibit competitive advantages due to their comprehensive electrochemical performance. However, to meet the requirements of rapid-charging and slow-discharging scenarios, it is necessary to further enhance the rate performance of the cathode material to achieve symmetrical capacity at different rates. Simultaneously, minimizing lattice strain during asymmetric electrochemical processes is also significant in alleviating strain accumulation. In this study, the ordered distribution of transition metal layers and the diffusion pathway of sodium ions are optimized through targeted K-doping of sodium layers, leading to a reduction of the diffusion barrier and endowment of prominent rate performance. At a 20C rate, the capacity of the cathode can reach 94% of that at a 0.1C rate. Additionally, the rivet effect of the sodium layers resulted in a global volume strain of only 0.03% for the modified cathode during charging at a 10C rate and discharging at a 1C rate. In summary, high-performance SIBs, with promising prospects for rapid-charging and slow-discharging capability, are obtained through the regulation of sodium layers, opening up new avenues for commercial applications.

12.
Front Immunol ; 14: 1224129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771581

RESUMO

Allergic rhinitis is a non-infectious chronic inflammatory disease of the nasal mucosa that affects T cells and their cytokines. T cells play significant roles in the development of allergic inflammatory diseases by orchestrating mechanisms underlying innate and adaptive immunity. Although many studies on allergic rhinitis have focused on helper T cells, molecular makeup, and pathogenesis-related transduction pathways, pathological mechanisms have not yet been completely explored. Recent studies have suggested that T cell status may play an important role in the interaction between T cells and the nasal mucosal barrier in allergic rhinitis. This study aimed to explore the interactions between T cells and nasal mucosal barriers in allergic rhinitis and to review the therapeutic modalities of pertinent biological agents involving T cells.


Assuntos
Rinite Alérgica , Humanos , Mucosa Nasal , Inflamação , Citocinas/metabolismo , Imunidade Adaptativa
13.
Environ Sci Pollut Res Int ; 30(56): 119034-119049, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37919501

RESUMO

The continuous and rapid development of textile industry intensifies rhodamine B dye (RhB) wastewater pollution. Meanwhile, massive red mud (RM) solid waste generated by the industrial alumina production process poses detrimental effects to the environment after leaching. For resource utilization and to reduce the expansion of RhB pollution, RM and peel red mud-biochar composite (RMBC) catalyst were synthesized in activating peroxydisulfate (PDS) for RhB degradation. Firstly, characterization results showed that compared to RM, RMBC had a higher content of catalytically active metals (Fe, Al, Ti) (higher than 0.92-4.18%), smaller pore size, and larger specific surface area (10 times), which verified RMBC had more potential catalytic oxidation activity. Secondly, under optimal dosage (catalyst, PDS), pH 4.6, and 20 mg L-1 RhB, it was found that the RhB degradation ratio of RM was 76.70%, which was reduced to 41% after three cycles, while that of RMBC was 89.98% and 67%, respectively. The results indicated that the performance of RMBC was significantly superior to that of RM. Furthermore, the quenching experiments, electron paramagnetic resonance spectroscopy tests, FTIR, and XPS analysis showed the function of O-H, C=O, C-O, Fe-O, and Fe-OH functional groups, which converted the PDS to the active state and hydrolyzed it to produce free radicals ([Formula: see text], 1O2, [Formula: see text]) for RhB degradation. And, Q Exactive Plus MS test obtained that RhB was degraded to CO2, H2O, and intermediate products. This study aimed to raise a new insight to the resource utilization of RM and the control of dye pollution.


Assuntos
Citrus paradisi , Água , Carvão Vegetal
14.
Urol Oncol ; 41(1): 15-26, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35907706

RESUMO

A nephrometry scoring system is a key standard to evaluate the feasibility of partial nephrectomy (PN). Whether based on two-dimensional or three-dimensional images, simplicity, effectiveness, and practicality are the keys to the nephrometric scoring system. Since the emergence of RENAL score in 2009, numerous scoring systems based on different anatomical parameters are established to seek accurately and few parameters to assess the risk of PN and complications. This study aimed to achieve a three-game winning streak in PN more easily and efficiently (negative resection margin, maximum preservation of normal nephron function, and avoiding short-term and long-term complications). Using PubMed, we counted 28 kinds of nephrometric scoring systems. We considered only English literatures published and excluded editorials, commentaries, and meeting abstracts. To the best of our knowledge, this is to date and most comprehensive summary as well as an outlook of the nephrometric scoring system.


Assuntos
Neoplasias Renais , Humanos , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Néfrons , Rim/cirurgia , Estudos Retrospectivos
15.
Front Oncol ; 12: 916850, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479065

RESUMO

Background: The prognosis of bladder cancer (BC) is poor, and there is no effective personalized management method for BC patients at present. Developing an accurate model is helpful to make treatment plan and prognosis analysis for BC patients. Endogenous fatty acid metabolism causes cancer cells to become hypoxic, and the coexistence of hypoxia and inflammation is often characteristic of cancer. All three together influence the tumor immune microenvironment, treatment, and prognosis of BC. Methods: We used The Cancer Genome Atlas-Bladder Urothelial Carcinoma (TCGA-BLAC) cohorts as a train group to build a risk model based on fatty acid metabolism, hypoxia and inflammation-related gene signatures and performed external validation with GSE13507, GSE31684, and GSE39281 cohorts. We validated the model to correlate with the clinicopathological characteristics of patients, created an accuracy nomogram, and explored the differences in immune microenvironment and enrichment pathways. Results: We found significant differences in overall survival and progression-free survival between high- and low-risk groups, and patients in the low-risk group had a better prognosis than those in the high-risk group. In the train group, the AUCs for predicting overall survival at 1, 3, and 5 years were 0.745, 0.712, and 0.729, respectively. The 1-, 3-, and 5-year overall survival AUCs were 0.589, 0.672, and 0.666 in the external validation group, respectively. The risk score independently predicted the prognosis of BC patients with AUCs of 0.729. In addition, there was a significant correlation between risk scores and BC clinicopathological features and, in the GSE13507 cohort, we observed that BC progression and deeper invasion were associated with higher risk scores. Risk scores were highly correlated with coproptosis, pyroptosis, m7G, immune checkpoint-related genes, and immune microenvironment. In addition, we found that patients in the low-risk group responded better to immunotherapy, whereas patients in the high-risk group were more sensitive to commonly used chemotherapy drugs. Conclusion: Our findings provide new treatment decisions for BC, and can effectively predict the prognosis of BC patients, which is helpful for the management of BC patients.

16.
Front Genet ; 13: 866819, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003341

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. ccRCC has obvious immunological characteristics, and the infiltration of immune cells is related to the prognosis of ccRCC. The effect of immune checkpoint therapy is related to the dynamic changes of the tumor immune microenvironment (TIM). The 7-methylguanosine (m7G) is an additional mRNA modification ability besides m6A, which is closely related to the TIM and affects the occurrence and development of tumors. At present, the correlations between m7G and the immune microenvironment, treatment, and prognosis of ccRCC are not clear. As far as we know, there was no study on the relationship between m7G and the immune microenvironment and survival of clear cell renal cell carcinomas. A comprehensive analysis of the correlations between them and the construction of a prognosis model are helpful to improve the treatment strategy. Two different molecular subtypes were identified in 539 ccRCC samples by describing the differences of 29 m7G-related genes. It was found that the clinical features, TIM, and prognosis of ccRCC patients were correlated with the m7G-related genes. We found that there were significant differences in the expression of PD-1, CTLA4, and PD-L1 between high- and low-risk groups. To sum up, m7G-related genes play a potential role in the TIM, treatment, and prognosis of ccRCC. Our results provide new findings for ccRCC and help to improve the immunotherapy strategies and prognosis of patients.

17.
Chemosphere ; 304: 135308, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35709837

RESUMO

Agricultural waste was characterized by large quantity and low degree of resource utilization. The peanut shell waste was converted into value-added biochar to alleviate the pollution of dyeing wastewater, which caters to the concept of resource recovery and sustainable utilization. In this work, peroxydisulfate (PDS) could be efficiently activated by biochar obtained by pyrolysis at 700 °C (BC) and Acid Orange 7 (AO7) was rapidly eliminated with 96% removal ratio in 10 min. Meanwhile, BC catalyst performed good stability and reusability. In addition, remarkable removal performance within 40 min (>94%) could be achieved in a wide range of pH (3.0-11.0). Through series characterizations, it was found that 700 °C was the critical pyrolysis temperature to prepare material with excellent property mainly attributing to large specific surface area (SSA), followed by high defect structure and rich C-O. It was speculated that radical pathway mainly especially surface-bounded radicals (SO4•-、•OH、O2-•) worked in the degradation of AO7. Specifically, abundant and typical oxygen-containing functional groups (OFGs) and defect structure catalytic sites of BC enhanced PDS activation. In addition, various radicals participated the whole degradation processes, such as the cleavage of azo bond (-NN-), hydroxylation, deamination and desulfurization.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Arachis , Catálise , Carvão Vegetal/química , Sulfatos/química , Poluentes Químicos da Água/análise
18.
Front Genet ; 12: 763590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899848

RESUMO

BACKGROUND: To identify the immune-related genes of bladder cancer (BLCA) based on immunological characteristics and explore their correlation with the prognosis. METHODS: We downloaded the gene and clinical data of BLCA from the Cancer Genome Atlas (TCGA) as the training group, and obtained immune-related genes from the Immport database. We downloaded GSE31684 and GSE39281 from the Gene Expression Omnibus (GEO) as the external validation group. R (version 4.0.5) and Perl were used to analyze all data. RESULT: Univariate Cox regression analysis and Lasso regression analysis revealed that 9 prognosis-related immunity genes (PIMGs) of differentially expressed immune genes (DEIGs) were significantly associated with the survival of BLCA patients (p < 0.01), of which 5 genes, including NPR2, PDGFRA, VIM, RBP1, RBP1 and TNC, increased the risk of the prognosis, while the rest, including CD3D, GNLY, LCK, and ZAP70, decreased the risk of the prognosis. Then, we used these genes to establish a prognostic model. We drew receiver operator characteristic (ROC) curves in the training group, and estimated the area under the curve (AUC) of 1-, 3- and 5-year survival for this model, which were 0.688, 0.719, and 0.706, respectively. The accuracy of the prognostic model was verified by the calibration chart. Combining clinical factors, we established a nomogram. The ROC curve in the external validation group showed that the nomogram had a good predictive ability for the survival rate, with a high accuracy, and the AUC values of 1-, 3-, and 5-year survival were 0.744, 0.770, and 0.782, respectively. The calibration chart indicated that the nomogram performed similarly with the ideal model. CONCLUSION: We had identified nine genes, including PDGFRA, VIM, RBP1, RBP1, TNC, CD3D, GNLY, LCK, and ZAP70, which played important roles in the occurrence and development of BLCA. The prognostic model based on these genes had good accuracy in predicting the OS of patients and might be promising candidates of therapeutic targets. This study may provide a new insight for the diagnosis, treatment and prognosis of BLCA from the perspective of immunology. However, further experimental studies are necessary to reveal the underlying mechanisms by which these genes mediate the progression of BLCA.

19.
Neurosci Lett ; 727: 134922, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32205185

RESUMO

Our previous experiments found that a suitable dose of vitamin A (VA) can affect neuronal apoptosis after hypoxic-ischemic brain damage (HIBD) by binding to RARα to activate the PI3K/AKT signaling pathway; however, the other neuroprotective effects of VA after HIBD, for example, whether it promotes neural stem cell (NSC) proliferation, remain unclear. In this study, in vivo and in vitro experiments revealed that VA regulates ß-catenin signaling through RARɑ to affect NSC proliferation after HIBD and to improve neurocognitive outcomes. Because of the accumulation and suspended growth characteristics of NSCs, we performed in vitro experiments with PC12 cells to mimic NSCs. Flow cytometry, CCK8, EdU staining, immunofluorescence and behavioral tests were performed to explore the effects of retinoic acid (RA) on NSC proliferation and post-HIBD function. The expression of RARα and ß-catenin pathway components were measured by real-time PCR and Western blotting. We found that the learning and memory of the VA-deficient (VAD) group was more seriously damaged than that of the VA normal (VAN) group. The proliferation of hippocampal NSCs was significantly decreased in the VAD group compared with the VAN group. The mRNA and protein expression of RARɑ, AKT, GSK-3ß, ß-catenin and Cyclin D1 were significantly lower in the VAD group than in the VAN group. In vitro, too high and too low of an RA intervention resulted in decreased proliferation, while an appropriate RA concentration (1-5 µmol/L) significantly promoted proliferation, S phase cells and high ß-catenin pathway expression. These results suggested that VA can exert a neuroprotective effect by promoting the proliferation of hippocampal NSCs after neonatal HIBD injury at the appropriate concentration. VA activates RARɑ, which regulates the ß-catenin signaling pathway, which in turn upregulates Cyclin D1 expression, promotes NSC proliferation, and finally plays a role in the neuroprotective effect.


Assuntos
Proliferação de Células/fisiologia , Hipóxia-Isquemia Encefálica/metabolismo , Células-Tronco Neurais/metabolismo , Transdução de Sinais/fisiologia , Vitamina A/farmacologia , beta Catenina/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células/efeitos dos fármacos , Feminino , Hipóxia-Isquemia Encefálica/prevenção & controle , Células-Tronco Neurais/efeitos dos fármacos , Células PC12 , Ratos , Ratos Sprague-Dawley , Receptor alfa de Ácido Retinoico , Transdução de Sinais/efeitos dos fármacos , Vitamina A/uso terapêutico
20.
Cancer Manag Res ; 12: 5793-5802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765082

RESUMO

PURPOSE: Eosinophils are proven to play a role in the prognosis of some malignant-tumors. The prognostic value of eosinophils in glioma patients is, however, scarcely reported. The authors of this article have designed a novel prognostic indicator based on eosinophils and the neutrophil-to-lymphocyte ratio (NLR), named ENS, to predict the survival of patients with glioma. METHODS: A retrospective study was conducted on 217 glioma patients. The cut-off values for eosinophil, NLR, and other clinical variables were determined by the receiver operating characteristic (ROC) curve analysis. Patients with both low eosinophil count (<0.08 ×109/L) and high NLR (≥1.70) were given a score of 2. Those with one or neither got a score of 1 or 0, respectively. The nomogram was based on ENS and several other clinical variables, its performance was determined by the concordance index (c-index). RESULTS: Our results showed that ENS is an independent prognostic indicator for overall survival (OS). The three-year OS rates for low-grade glioma patients (LGGs) were 84.0%, 69.0%, and 46.4% for ENS=0, ENS=1, and ENS=2, respectively (P=0.014). The three-year OS incidence for LGGs stratified into eosinophils count ≥0.08×109/L and<0.08×109/L subgroups were 88.1% and 80.0%, respectively (P=0.043). ENS was positively correlated with glioma grade (r=0.311, P<0.001). The c-index for OS prognosis was 0.80 using this nomogram in LGGs. CONCLUSION: Preoperative ENS can predict OS to some extent for LGGs and can increase prognostic accuracy for individual OS in LGGs postoperatively when incorporating other clinical variables compose a nomogram.

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