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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 789-793, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622594

RESUMO

Objective: To determine the best time for conducting cesarean section for the establishment of an animal model of lung development with specific pathogen free (SPF) preterm Bama minipigs under the condition of not making medical interventions such as hyperoxia, mechanical ventilation, or medication. Methods: SPF Bama sows at gestational day (GD) 113, GD107, GD104, GD101, and GD98 were selected and cesarean sections were performed. Then, the viability of the preterm piglets were observed. Based on their general data, viability, and paraffin sections stained with hematoxylin and eosin, the best time for performing cesarean section in order to build a SPF preterm pig model of lung development was determined. Results: Cesarean sections were performed on a total of 7 sows and 55 piglets were delivered, among which 25 were still alive 3 hours after delivery. Seven piglets of GD104 and all piglets of GD107 and GD113 survived, while piglets of GD98 and GD101 all died. The survival rate of piglets of GD104 was 33.33% (7/21). Piglets of GD98 already possessed fully developed physical appearance and lung shape. Piglets from GD104 had better lung expansion and higher density of thin-walled alveoli. The lungs of GD107 piglets were basically fully expanded, and the density of thin-walled alveoli was almost the same as that of normal full-term piglets. Conclusions: Findings of this study suggest that SPF preterm piglets of GD104 with no specific pathogen exposure and no medical intervention can be used to establish a SPF preterm pig model of lung development.


Assuntos
Cesárea , Pulmão , Animais , Modelos Animais de Doenças , Feminino , Gravidez , Organismos Livres de Patógenos Específicos , Suínos , Porco Miniatura
2.
Toxicol Lett ; 350: 249-260, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34302894

RESUMO

Cisplatin-induced hearing loss is a common side effect of cisplatin chemotherapy, for which clinical therapy remains unavailable. Apoptosis of hair cells is considered the primary cause of cisplatin-induced ototoxicity; however, inhibiting apoptosis can only partially restore cisplatin-induced hearing loss. Therefore, auditory cell death caused by cisplatin damage requires further study. Ferroptosis, a novel form of regulated cell death, has been shown to play a role in the mechanism of cisplatin toxicity. In this study, we observed proferroptotic alterations (lipid peroxidation and impaired antioxidant capacity) in the cochleae of C57BL/6 mice after cisplatin damage, verifying the induction of ferroptosis. Using the HEI-OC1 cell line, we observed that cisplatin induced proferroptotic alterations and activated ferritinophagy (specific autophagy pathway). Employing chloroquine, we confirmed that the blockage of autophagy remarkably alleviated cisplatin-induced ferroptosis in HEI-OC1 cells; therefore, the induction of ferroptosis in cisplatin-treated auditory cells was dependent on the activation of autophagy. In addition, the ferroptosis inhibitor ferrostatin-1 and iron chelator deferoxamine significantly attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells and cochlear explants. Moreover, pharmacologically inhibiting ferroptosis using ferrostatin-1 significantly decreased the auditory cell loss and, notably, attenuated hearing loss in C57BL/6 mice after cisplatin damage. Collectively, these findings indicate that autophagy-dependent ferroptosis plays an integrated role in the mechanism of cisplatin-induced hearing loss.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cisplatino/toxicidade , Ferroptose/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva/induzido quimicamente , Ototoxicidade/etiologia , Animais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais
3.
Clinics (Sao Paulo) ; 76: e2769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34231708

RESUMO

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Medidas de Volume Pulmonar , Dosagem Radioterapêutica , Estudos Retrospectivos
4.
Ecotoxicol Environ Saf ; 221: 112432, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34166937

RESUMO

The intensive and long-term use of atrazine in agriculture has resulted in serious environmental pollution and consequently endangered ecosystem and human health. Soil microorganisms play an important role in atrazine degradation. However, their degradation efficiencies are relatively low due to their slow growth and low abundance, and manure amendment as a practice to improve soil nutrients and microbial activities can solve these problems. This study investigated the roles of goat manure in atrazine degradation performance, metabolites and bacterial community structure. Our results showed that atrazine degradation efficiencies in un-amended soils were 26.9-35.7% and increased to 60.9-84.3% in goat manure amended treatments. Hydroxyatrazine pathway was not significantly altered, whereas deethylatrazine and deisopropylatrazine pathways were remarkably enhanced in treatments amended with manure by encouraging the N-dealkylation of atrazine side chains. In addition, goat manure significantly increased soil pH and contents of organic matters and humus, explaining the change of atrazine metabolic pathway. Nocardioides, Sphingomonas and Massilia were positively correlated with atrazine degradation efficiency and three metabolites, suggesting their preference in atrazine contaminated soils and potential roles in atrazine degradation. Our findings suggested that goat manure acts as both bacterial inoculum and nutrients to improve soil microenvironment, and its amendment is a potential practice in accelerating atrazine degradation at contaminated sites, offering an efficient, cheap, and eco-friendly strategy for herbicide polluted soil remediation.


Assuntos
Atrazina/metabolismo , Biodegradação Ambiental , Esterco/microbiologia , Microbiologia do Solo , Animais , Atrazina/análise , Bactérias/metabolismo , Ecossistema , Cabras , Herbicidas/análise , Herbicidas/metabolismo , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/metabolismo
5.
Toxicol Lett ; 349: 115-123, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34089817

RESUMO

Cisplatin, the most widely used platinum-based anticancer drug, often causes progressive and irreversible sensorineural hearing loss in cancer patients. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. Nicotinamide adenine dinucleotide (NAD+), a co-substrate for the sirtuin family and PARPs, has emerged as a potent therapeutic molecular target in various diseases. In our investigates, we observed that NAD+ level was changed in the cochlear explants of mice treated with cisplatin. Supplementation of a specific inhibitor (TES-1025) of α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), a rate-limiting enzyme of NAD+de novo synthesis pathway, promoted SIRT1 activity, increased mtDNA contents and enhanced AMPK expression, thus significantly reducing hair cells loss and deformation. The protection was blocked by EX527, a specific SIRT1 inhibitor. Meanwhile, the use of NMN, a precursor of NAD+ salvage synthesis pathway, had shown beneficial effect on hair cell under cisplatin administration, effectively suppressing PARP1. In vivo experiments confirmed the hair cell protection of NAD+ modulators in cisplatin treated mice and zebrafish. In conclusion, we demonstrated that modulation of NAD+ biosynthesis via the de novo synthesis pathway and the salvage synthesis pathway could both prevent ototoxicity of cisplatin. These results suggested that direct modulation of cellular NAD+ levels could be a promising therapeutic approach for protection of hearing from cisplatin-induced ototoxicity.


Assuntos
Inibidores Enzimáticos/farmacologia , Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva/prevenção & controle , Audição/efeitos dos fármacos , NAD/biossíntese , Ototoxicidade/prevenção & controle , Sirtuína 1/metabolismo , Animais , Animais Geneticamente Modificados , Carboxiliases/antagonistas & inibidores , Carboxiliases/metabolismo , Cisplatino , Modelos Animais de Doenças , Ativação Enzimática , Células Ciliadas Auditivas/enzimologia , Células Ciliadas Auditivas/patologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/enzimologia , Perda Auditiva/fisiopatologia , Sistema da Linha Lateral/efeitos dos fármacos , Sistema da Linha Lateral/enzimologia , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Ototoxicidade/enzimologia , Ototoxicidade/etiologia , Ototoxicidade/fisiopatologia , Peixe-Zebra
6.
Ying Yong Sheng Tai Xue Bao ; 32(5): 1761-1767, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34042371

RESUMO

To explore the effects of arbuscular mycorrhizal fungi (AMF) on the growth of legume crop, pot and field experiments with soybean were conducted. Treatments of inoculation (+AMF) and non-inoculation with AMF (-AMF) were set up for the pot experiment, and AMF mycelium non-limited and limited for the field experiment. Results of the pot experiment showed that inoculation with AMF significantly increased soybean aboveground biomass (16.5%) and root nodules number (131.4%), above-ground plant phosphorus and nitrogen concentrations and uptakes. In the field trial, the above-ground and root biomasses and root nodules number under AMF mycelium non-limited were significantly increased by 123.6%, 61.5%, and 212.5% compared with those under the limited condition, respectively. Plant phosphorus uptake, nitrogen concentration and uptake, and soil available nitrogen and phosphorus concentrations were significantly higher under AMF mycelium non-limited than the limited both in both shoot and root. Our findings provide theoretical reference for further understanding the relationship between legume crop and AMF, as well as the efficient utilization of phosphorus fertilizer.


Assuntos
Fabaceae , Micorrizas , Nitrogênio , Fósforo , Raízes de Plantas
7.
Support Care Cancer ; 29(10): 5967-5972, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33765206

RESUMO

PURPOSE: To explore whether anxiety and depression are prognostic indexes for overall survival in patients with nasopharyngeal carcinoma (NPC) who underwent intensity-modulated radiotherapy (IMRT). METHODS: Clinical data were collected for NPC patients who underwent IMRT. Anxiety and depression were investigated before radiotherapy by using the Hospital Anxiety and Depression Scale (HADS). The survival rate was calculated by the Kaplan-Meier method, and survival curves were compared among patients with different levels of anxiety and depression. The Cox risk regression model was used to screen the factors affecting survival. RESULTS: A total of 390 initially treated NPC patients were included in the study. Among them, 166 patients suffered from anxiety, and 95 patients suffered from depression before radiotherapy. The 5-year overall survival rates for patients with and without anxiety before radiotherapy were 71.6% and 81.8% (χ2 = 5.31, P = 0.021), respectively. The 5-year overall survival rates for patients with and without depression before radiotherapy were 74.3% and 78.1% (χ2 = 0.05, P = 0.82), respectively. Cox regression analysis indicated clinical stages (HR = 3.982, 95% CI: 2.365~6.705), anxiety (HR = 1.832, 95% CI: 1.140~2.944), and gender (HR = 0.555, 95% CI: 0.313~0.984) as independent prognostic factors. CONCLUSION: Anxiety before radiotherapy is associated with poor prognosis in NPC patients.

8.
J Neurophysiol ; 125(4): 1202-1212, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625942

RESUMO

Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Unfortunately, patients are often troubled by serious side effects, especially hearing loss. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We explored the role of autophagy and the efficacy of metformin in cisplatin-induced ototoxicity in cells, zebrafish, and mice. Furthermore, the underlying molecular mechanism of how metformin affects cisplatin-induced ototoxicity was examined. In in vitro experiments, autophagy levels in HEI-OC1 cells were assessed using fluorescence and Western blot analyses. In in vivo experiments, whether metformin had a protective effect against cisplatin ototoxicity was validated in zebrafish and C57BL/6 mice. The results showed that cisplatin induced autophagy activation in HEI-OC1 cells. Metformin exerted antagonistic effects against cisplatin ototoxicity in HEI-OC1 cells, zebrafish, and mice. Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), whereas cells with AMPK silencing displayed otherwise. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.NEW & NOTEWORTHY Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We investigated the protective effect of metformin on cisplatin ototoxicity in vitro and in vivo. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.

9.
J Hazard Mater ; 412: 125212, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33524732

RESUMO

This study explored the change of tetracycline degradation efficiency, metabolic pathway, soil physiochemical properties and degraders in vermiremediation by two earthworm species of epigeic Eisenia fetida and endogeic Amynthas robustus. We found a significant acceleration of tetracycline degradation in both earthworm treatments, and 4-epitetracycline dehydration pathway was remarkably enhanced only by vermiremediation. Tetracycline degraders from soils, earthworm intestines and casts were different. Ralstonia and Sphingomonas were potential tetracycline degraders in soils and metabolized tetracycline through direct dehydration pathway. Degraders in earthworm casts (Comamonas, Acinetobacter and Stenotrophomonas) and intestines (Pseudomonas and Arthrobacter) dehydrated 4-epitetracycline into 4-epianhydrotetracycline. More bacterial lineages resisting tetracycline were found in earthworm treatments, indicating the adaptation of soil and intestinal flora under tetracycline pressure. Earthworm amendment primarily enhanced tetracycline degradation by neutralizing soil pH and consuming organic matters, stimulating both direct dehydration and epimerization-dehydration pathways. Our findings proved that vermicomposting with earthworms is effective to alter soil microenvironment and accelerate tetracycline degradation, behaving as a potential approach in soil remediation at tetracycline contaminated sites.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Bactérias/genética , Solo , Poluentes do Solo/análise , Tetraciclina
10.
Pediatr Res ; 89(6): 1343-1351, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32244247

RESUMO

BACKGROUND: Asthma is a common chronic respiratory disease in children. In addition to medications, physical therapy is considered as a treatment strategy for asthma. We conducted this study to investigate the effects of physical therapy on lung function in children with asthma. METHODS: Three databases were searched. We conducted the meta-analysis for the forced expiratory volume in the first second in percent predicted values [FEV1(%pred)], the forced vital capacity in percent predicted values [FVC(%pred)], and the peak expiratory flow in percent predicted values [PEF(%pred)] by using a random effect model. RESULTS: Of the 6474 identified studies, 18 studies (16 in physical training, 2 in breathing exercise or inspiratory muscle training) were included in the systematic review and 11 studies (all in physical training) were included in the meta-analysis. The meta-analysis showed a significantly improved FVC(%pred) in the experimental group. CONCLUSIONS: Physical training improved FVC(%pred) significantly in children with asthma. Further study is needed, especially on the effects of breathing exercise and inspiratory muscle training in children with asthma. IMPACT: Our study reviewed the physical therapies for children with asthma and clarified whether and how these therapies affect them. Our study found that physical training improved the forced vital capacity in percent predicted values [FVC(%pred)] significantly in asthmatic children. Our study provided evidence that physical training could improve lung function in children with asthma, which is not identical to the Global Initiative for Asthma (GINA) guidelines.

11.
Biomed Pharmacother ; 133: 110940, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33227707

RESUMO

Naoxintong Capsule (NXTC), a standardized herbal medicine, has been widely applied in treating cardiovascular and cerebrovascular diseases with remarkable efficacy. However, the efficacy contributing components of NXTC are unclear, and the in vivo absorption and metabolism processes of NXTC remain largely obscured. In this study, using beagle dog as model species, we have identified and tentatively characterized 25 prototype and 15 catabolites of NXTC in beagle dog plasma by ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). We have proposed the in vivo bio-transformation pathways of these absorbed constituents. In addition, for six crucial components, we have developed a quantitative method and conducted plasma pharmacokinetic study of these six components by rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS). In conclude, our study provided comprehensive insights into the understanding of the plasma absorbed components profiling of NXTC as well as their in vivo transformation behaviors, which would be of great value for identifying efficacy contributing critical components as well as mechanism related investigations of NXTC in the future.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Administração Oral , Animais , Biotransformação , Cápsulas , Cromatografia Líquida de Alta Pressão , Cães , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Masculino , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
12.
Sci Total Environ ; 766: 142441, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33097271

RESUMO

Diazotrophs play a critical role in converting air-inactive nitrogen to bio-available nitrogen. Assessing the influences of different fertilization regimes on diazotrophs is essential for a better understanding of their maintenance of soil fertility and agricultural sustainability. In this study, we targeted the nifH gene to investigate the effects of different long-term fertilization on the diazotrophic community in a vertisol, using real-time quantitative polymerase chain reaction (PCR) and MiSeq sequencing. Five fertilization regimes were tested: no fertilizer (CK), chemical nitrogen, phosphorus, and potassium fertilizer (NPK), organic fertilizer (O), chemical NPK plus organic fertilizer with an equivalent application rate of nitrogen (NPKO), and chemical NPK plus organic fertilizer with a high application rate of nitrogen (HNPKO). Our results showed that fertilization significantly affected the diazotrophic activity, abundance and composition. NPK tended to reduce the activity, abundance, operational taxonomic units (OTU)-richness and alpha-diversity of the diazotrophs, while O had the opposite effect. The effects of inorganic and organic fertilization on the diazotrophs depended on the N application rate, showing that the diazotrophic activity, abundance, and alpha-diversity in NPKO were higher than that of HNPKO. For the diazotrophic community structure, CK, O, and NPKO were grouped and separated from NPK and HNPKO. The diazotrophic community structure strongly correlated with the soil pH, electrical conductivity (EC), total carbon content (TC), and total nitrogen content (TN), among which pH was the major factor shaping the diazotrophic community structure. Different network patterns were observed between the long-term organic and non-organic fertilizers, suggesting that the organic amendment resulted in a more complicated diazotrophic community than the non-organic amendments. Rhizobium was the most important hub connecting members in the community. These results indicated that organic amendments are beneficial to diazotrophic activity, abundance, OTU richness, alpha-diversity, and the diazotrophic communities' potential interactions, which may enhance biological nitrogen fixation in vertisols.


Assuntos
Fertilizantes , Microbiologia do Solo , Fertilização , Fertilizantes/análise , Nitrogênio/análise , Solo
13.
Clinics ; 76: e2769, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1278923

RESUMO

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Radioterapia de Intensidade Modulada , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Dosagem Radioterapêutica , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar
14.
Infect Drug Resist ; 13: 4335-4346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293837

RESUMO

A virus is an infectious particle which generally contains nucleic acid genome (DNA or RNA inside a protein shell), except for human immunodeficiency virus (HIV). Viruses have to reproduce by infecting their host cells. Polyamines are ubiquitous compounds in mammalian cells and play key roles in various cellular processes. The metabolic pathways of polyamines have been well studied. Targeting these metabolic pathways can reduce infections caused by viruses. In the study, we systematically reviewed the association of polyamine metabolic pathways and viruses including coxsackievirus B3 (CVB3), enterovirus 71 (EV71), poliovirus (PV), Zika virus (ZKV), hepatitis C virus (HCV), hepatitis B virus (HBV), dengue virus (DENV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), Ebola virus (EBOV), marburgvirus (MARV), chikungunya virus (CHIKV), sindbis virus (SINV), Semliki Forest virus (SFV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV), human cytomegalovirus (HCMV), vesicular stomatitis virus (VSV), Rabies virus (RABV), Rift Valley fever virus (RVFV), La Crosse virus (LACV), human immunodeficiency virus (HIV), Middle East respiratory syndrome virus (MERS-CoV), and coronavirus disease 2019 (SARS-CoV-2). This review revealed that targeting polyamine metabolic pathways may be a potential approach to control human viral infection.

15.
Biomed Res Int ; 2020: 5891016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33145355

RESUMO

Background: Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC. Methods: The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein-protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. Results: A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease-associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients. Conclusions: This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Quempferóis/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Quinases da Família src/antagonistas & inibidores , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Sítios de Ligação , Medicamentos de Ervas Chinesas , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular/métodos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Farmacogenética , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Mapas de Interação de Proteínas , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Quinases da Família src/química , Quinases da Família src/genética , Quinases da Família src/metabolismo
16.
Cancer Manag Res ; 12: 8221-8227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982418

RESUMO

Purpose: This study aims to explore the applicability of the Nutrition Risk Screening 2002 (NRS2002) tool in screening nutritional risk and the Patient-Generated Subjective Global Assessment (PG-SGA) in determining nutrition status in nasopharyngeal carcinoma (NPC) patients. Materials and Methods: NRS2002 and PG-SGA were simultaneously applied to evaluate the nutritional status of NPC patients before induction chemotherapy, as well as before and after radiotherapy. The PG-SGA results were considered golden standard in evaluating nutrition status, and the ROC curve value and Youden index were applied to analyze NRS2002 effectiveness in screening nutritional risk. Results: A total of 102 NPC patients were included in this study. Patients with an NRS2002 score <3 and PG-SGA score ≥4 accounted for 5.3% (5/95), 19.6% (18/92) and 94.8% (36/38) at the time before induction chemotherapy, before radiotherapy and at the end of radiotherapy, respectively. The cut-off values of NRS2002 scores all <2 corresponded to the maximum Youden index at the three procedural times. And the area under curve (AUC) were 0.598 (P = 0.390), 0.665 (P = 0.015) and 0.940 (P = 0.034), respectively. At the end of radiotherapy, NRS2002 scores of <3 and <2 were used as cut-off values for nutritional risk screening, respectively. Additionally, the malnutrition-missed detection rates were 36.0% and 12.0% (χ 2 = 15.789; P <0.001). Discussion: NRS2002 nutritional risk screening combined with the PG-SGA nutritional assessment has certain applicability in NPC. NRS2002 score ≥2 can be considered as a new cut-off point for nutritional assessment.

17.
PeerJ ; 8: e9737, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879802

RESUMO

Background: In our aging society, age-related hearing loss (AHL) is the most common sensory disorder in old people. Much progress has been made in understanding the pathological process of AHL over the past few decades. However, the mechanism of cochlear degeneration during aging is still not fully understood. Methods: Next generation sequencing technique was used to sequence the whole transcriptome of the cochlea of C57BL/6 mice, a mouse model of AHL. Differentially expressed genes (DEGs) were identified using the Cuffdiff software. GO and KEGG pathway enrichment analyses of the DEGs were implemented by using the GOseq R package and KOBAS software, respectively. Results: A total of 731 genes (379 up- and 352 down-regulated) were revealed to be differentially expressed in the cochlea of aged mice compared to the young. Many genes associated with aging, apoptosis, necroptosis and particularly, inflammation were identified as being significantly modulated in the aged cochlea. GO and KEGG analyses of the upregulated DEGs revealed that the most enriched terms were associated with immune responses and inflammatory pathways, whereas many of the downregulated genes are involved in ion channel function and neuronal signaling. Real-time qPCR showed that H2O2 treatment significantly induced the expression of multiple inflammation and necroptosis-related genes in HEI-OC1 cells. Conclusion: Using next generation sequencing, our transcriptomic analysis revealed the differences of gene expression pattern with age in the cochlea of C57BL/6 mice. Our study also revealed multiple immune and inflammatory transcriptomic changes during cochlear aging and provides new insights into the molecular mechanisms underlying cochlear inflammation in AHL.

18.
Pharm Biol ; 58(1): 1006-1022, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32985308

RESUMO

CONTEXT: Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. OBJECTIVE: This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). MATERIALS AND METHODS: Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1ß, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. RESULTS: NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). CONCLUSIONS: The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

19.
Oncol Lett ; 20(4): 66, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32863899

RESUMO

Alkylglycerone phosphate synthase (AGPS) is a key enzyme for ether ester synthesis and acts as an oncogene in malignant tumors. The present study aimed to investigate the effect of AGPS silencing on the expression levels of long non-coding RNAs (lncRNAs) and the co-expression with mRNAs in glioma U251 cells using microarray analysis. Furthermore, the underlying biological functions of crucial lncRNAs identified were investigated. It was discovered that in vitro U251 cell proliferation was suppressed following the genetic silencing of AGPS. Differentially expressed lncRNAs and mRNAs in U251 cells were sequenced following AGPS silencing. The results from the Gene Ontology analysis identified that the co-expressed mRNAs were mainly involved in biological processes, such as 'cellular response to hypoxia', 'extracellular matrix organization' and 'PERK-mediated unfolded protein response'. In addition, Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis revealed that the co-expressed mRNAs were the most enriched in the 'AGE/RAGE signaling pathway in diabetic conditions'. Additionally, the PI3K/Akt and epidermal growth factor receptor signaling pathways serve important roles in tumor processes, for example carcinogenesis and angiogenesis. Furthermore, it was identified that the lncRNA AK093732 served a vital role in the regulatory network and the core pathway in this network regulated by this lncRNA was discovered to be the 'Cytokine-cytokine receptor interaction'. In conclusion, the findings of the present study suggested that AGPS may affect cell proliferation and the degree of malignancy. In addition, the identified lncRNAs and their co-expressed mRNAs screened using microarrays may have significant biological effects in the occurrence, development and metastasis of glioma, and thus may be novel markers of glioma.

20.
Med Sci Monit ; 26: e923664, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32759885

RESUMO

BACKGROUND Gastric cancer (GC) is a worldwide malignancy and the molecular mechanism of the GC carcinogenesis has not been fully elucidated. Our previous study suggested CDCA5 played a role in GC development via regulating cell proliferation, migration, and apoptosis in GC cells. MATERIAL AND METHODS Here, we first carried out bioinformatics analysis and found cyclin-dependent kinase 1 (CDK1) was possibly associated with CDCA5 using STRING. Then, the expression levels of CDK1 and CDCA5 in cancer tissues were estimated through Oncomine and The Cancer Genome Atlas (TCGA) database. After that, functional experiments were exerted to detect the association of CDK1 and CDCA5. Finally, cell proliferation assay, colon formation assay, cell scratch assay, transwell migration and invasion assays were applied to explore the roles of CDK1 and CDCA5 in GC cells MGC-803. RESULTS CDK1 and CDCA5 were both upregulated and co-expressed in GC tissues. The expression of CDK1 and CDCA5 in MGC-803 was positively related. CDK1 or CDCA5 inhibition can suppress the proliferation, colon formation, migration, and invasion abilities of GC cells. CONCLUSIONS Co-expression of CDK1 and CDCA5 might confer cell proliferation, migration, and invasion abilities in GC cells, and this can provide some clues for further therapies of gastric tumors.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica/genética , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , Neoplasias Gástricas/patologia , Transcriptoma , Transfecção , Regulação para Cima/genética
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