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1.
Proc Natl Acad Sci U S A ; 120(6): e2221637120, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36716376

RESUMEN

Lipids establish the specialized thylakoid membrane of chloroplast in eukaryotic photosynthetic organisms, while the molecular basis of lipid transfer from other organelles to chloroplast remains further elucidation. Here we revealed the structural basis of Arabidopsis Sec14 homology proteins AtSFH5 and AtSFH7 in transferring phosphatidic acid (PA) from endoplasmic reticulum (ER) to chloroplast, and whose function in regulating the lipid composition of chloroplast and thylakoid development. AtSFH5 and AtSFH7 localize at both ER and chloroplast, whose deficiency resulted in an abnormal chloroplast structure and a decreased thickness of stacked thylakoid membranes. We demonstrated that AtSFH5, but not yeast and human Sec14 proteins, could specifically recognize and transfer PA in vitro. Crystal structures of the AtSFH5-Sec14 domain in complex with L-α-phosphatidic acid (L-α-PA) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) revealed that two PA ligands nestled in the central cavity with different configurations, elucidating the specific binding mode of PA to AtSFH5, different from the reported phosphatidylethanolamine (PE)/phosphatidylcholine (PC)/phosphatidylinositol (PI) binding modes. Quantitative lipidomic analysis of chloroplast lipids showed that PA and monogalactosyldiacylglycerol (MGDG), particularly the C18 fatty acids at sn-2 position in MGDG were significantly decreased, indicating a disrupted ER-to-plastid (chloroplast) lipid transfer, under deficiency of AtSFH5 and AtSFH7. Our studies identified the role and elucidated the structural basis of plant SFH proteins in transferring PA between organelles, and suggested a model for ER-chloroplast interorganelle phospholipid transport from inherent ER to chloroplast derived from endosymbiosis of a cyanobacteriumproviding a mechanism involved in the adaptive evolution of cellular plastids.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Cloroplastos , Ácidos Fosfatidicos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/metabolismo , Ácidos Fosfatidicos/metabolismo , Tilacoides/metabolismo
2.
J Immunol ; 210(1): 72-81, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36426999

RESUMEN

Fish possess a powerful IFN system to defend against aquatic virus infections. Nevertheless, spring viremia of carp virus (SVCV) causes large-scale mortality in common carp and significant economic losses to aquaculture. Therefore, it is necessary to investigate the strategies used by SVCV to escape the IFN response. In this study, we show that the SVCV nucleoprotein (N protein) negatively regulates cellular IFN production by degrading stimulator of IFN genes (STING) via the autophagy-lysosome-dependent pathway. First, overexpression of N protein inhibited the IFN promoter activation induced by polyinosinic-polycytidylic acid and STING. Second, the N protein associated with STING and experiments using a dominant-negative STING mutant demonstrated that the N-terminal transmembrane domains of STING were indispensable for this interaction. Then, the N protein degraded STING in a dose-dependent and autophagy-lysosome-dependent manner. Intriguingly, in the absence of STING, individual N proteins could not elicit host autophagic flow. Furthermore, the autophagy factor Beclin1 was found to interact with the N protein to attenuate N protein-mediated STING degradation after beclin1 knockdown. Finally, the N protein remarkably weakened STING-enhanced cellular antiviral responses. These findings reveal that SVCV uses the host autophagic process to achieve immune escape, thus broadening our understanding of aquatic virus pathogenesis.


Asunto(s)
Carpas , Enfermedades de los Peces , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Proteínas de la Nucleocápside , Viremia , Beclina-1 , Rhabdoviridae/fisiología , Lisosomas , Autofagia
3.
J Environ Manage ; 366: 121876, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39018855

RESUMEN

Integrated MFC-MBR systems effectively remove antibiotics and control the release of antibiotic resistance genes (ARGs). However, the fouling layers on membranes can potentially act as reservoirs for ARGs. This study aims to elucidate the roles of membrane fouling layers and levels in influencing sulfamethoxazole (SMX) removal and ARGs control within an MFC-MBR system. Our findings demonstrate that low-intensity bioelectricity (400-500 mV) mitigates membrane fouling rates. The membrane fouling layer significantly contributes (39%-47%) to SMX removal compared to the cathode/anode zones. Higher extracellular polymeric substance (EPS) content and a lower protein/polysaccharide (PN/PS) ratio favor SMX removal by the membrane fouling layer. Across different levels of membrane fouling, the PN/PS ratio rather than EPS concentration plays a crucial role in SMX removal efficiency. The MFC-MBR with low fouling achieved superior SMX removal (69.1%) compared to medium (54.3%) and high fouling conditions (46.8%). The presence of ARGs in the membrane fouling layer increases with fouling formation, with intrinsic ARGs prevailing. Dense membrane fouling layers effectively retain ARGs, thereby reducing the risk of extracellular ARGs (eARGs) diffusion in effluents. These results provide insights into controlling ARGs in MFC-MBR systems and underscore the significant role of membrane fouling layers in antibiotics and ARGs removal.

4.
BMC Med Educ ; 23(1): 34, 2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36650532

RESUMEN

OBJECTIVE: To investigate the influence of group counselling on the career planning and career maturity of male nursing students. METHOD: Sixty male nursing students were randomly selected from a specific-level first-class hospital in Hunan Province from July to August 2020 by using the convenience sampling method and were subsequently divided into the control group and the experimental group using the random number table method. The control group received routine pre-job training, including aspects concerning the hospital profile, nurse etiquette, nursing core systems, professional ethics, nursing emergency treatment and career prospects and planning. In the experimental group, career planning group counselling was added after the regular pre-service training (once a week) with each session lasting 2 h for a total of six training sessions. At six weeks and three months after the intervention, the career status evaluation scale and the college students' career maturity scale were used to compare the career planning and career maturity status of the two groups of male nursing students. RESULTS: After six weeks and three months of intervention, all the dimensions and total scores of both the career status evaluation scale and the career maturity scale in the experimental group were superior to those in the control group with statistically significant differences (all P < 0.05). The repeated measures of variance analysis indicated that the differences in the total score for career planning and the four dimensions in terms of intergroup effect, time effect and interaction effect between the two groups were statistically significant (P < 0.05). The intergroup effect, time effect and interaction effect of the total score for vocational maturity, career goal, career confidence, career value, career freedom and career reference of the two groups were statistically significant (P < 0.05), while the time effect of the relative dependency dimension was also statistically significant (P < 0.05). CONCLUSION: Group counselling can significantly improve the career planning and career maturity status of male nursing students and has a certain long-term effect.


Asunto(s)
Selección de Profesión , Consejo , Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , Masculino , Estudiantes de Enfermería/psicología
5.
J Gastroenterol Hepatol ; 37(9): 1654-1665, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35722709

RESUMEN

BACKGROUND AND AIM: The purpose of the present study was to evaluate the effect of direct-acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC). METHODS: We searched multiple electronic databases from database inception to June 14, 2021. Meta-analyses were performed separately for HCC recurrence and overall survival (OS). RESULTS: A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41-0.74, P < 0.001; I2  = 66.6%, P < 0.001) and improving OS (adjusted HR = 0.36, 95% CI 0.16-0.83, P = 0.017; I2  = 90.7%, P < 0.001) of HCV-related HCC patients. Compared with non-responders, patients with sustained virologic response (SVR) had greater benefit from DAAs therapy in reducing recurrence (HR = 0.37, 95% CI 0.16-0.84, P = 0.017; I2  = 58.8%, P = 0.088) and improving OS (HR = 0.17; 95% CI 0.06-0.50; P = 0.001; I2  = 56.4%, P = 0.130). Though DAAs did not show significant advantages over IFN in reducing recurrence (adjusted HR = 0.96, 95% CI 0.72-1.28, P = 0.784; I2  = 0.0%, P = 0.805), there seems to be a trend toward OS benefit from DAAs therapy (adjusted HR = 0.11, 95% CI 0.01-1.19, P = 0.059). CONCLUSION: DAAs therapy can prevent recurrence and improve OS of HCV-related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/efectos adversos , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Respuesta Virológica Sostenida
6.
J Environ Manage ; 301: 113924, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34731947

RESUMEN

The present paper aimed to investigate the roles of quinones contained in wastewater and the enhanced effects on microbial fuel cells (MFCs) under different redox conditions. The feasibility of using wastewater rich in quinones to act as co-substrate and redox mediators (RMs) library to strengthen the synergistic removal of azo dye in MFCs was evaluated. The results demonstrated that quinones achieved enhanced effects on electricity generation and COD removal of MFC better at higher current intensity. The addition of pure quinone decreased electron transfer resistance (Rct) of MFCs from 4.76 Ω to 2.13 Ω under 1000 Ω resistance and 1.16 Ω-0.75 Ω under 50 Ω resistance. Meanwhile, higher coulombic efficiency was achieved. Compared with sodium acetate, using quinone-rich traditional Chinese medicine (TCM) wastewater as the co-substrate enhanced the synergistic removal of reactive red 2 (RR2) in MFCs from 79.58% to 92.45% during 24 h. RR2 was also degraded more thoroughly due to the accelerated electron transfer process mediated by RMs. Microbial community analysis demonstrated that the presence of quinone in TCM wastewater can enrich different exoelectrogens under varied redox conditions and thus influenced the enhanced effects on MFC. Metagenomic functional prediction results further indicated that the abundance of functional genes involved in carbohydrate metabolism, membrane transport metabolism, biofilm formation, and stress tolerance increased significantly in presence of RMs. Redundancy analyses revealed that RMs addition was the more important factor driving the variation of the microorganism community. This study revealed the potential effect of quinones as redox mediators on the bioelectrochemical system for pollutants removal.


Asunto(s)
Fuentes de Energía Bioeléctrica , Compuestos Azo , Electricidad , Electrodos , Oxidación-Reducción , Quinonas , Aguas Residuales
7.
Chin Med Sci J ; 37(1): 52-59, 2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35256049

RESUMEN

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.


Asunto(s)
Yoduro Peroxidasa/genética , Enfermedad de Kashin-Beck , Estudios de Casos y Controles , Humanos , Enfermedad de Kashin-Beck/genética , Metilación , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Yodotironina Deyodinasa Tipo II
8.
Carcinogenesis ; 42(11): 1305-1313, 2021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34313732

RESUMEN

Circular RNA (circRNA) is a large class of covalently closed circRNA. As a member of competitive endogenous RNA, it participates in the regulation of circRNA-miRNA-mRNA network and plays an important role in the regulation of physiology and pathology. CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA. Studies have shown that circRNA is a ubiquitous molecule, which exceeds the linear mRNA distributed in human cells. Because of its covalent closed-loop structure, circRNA is resistant to RNase R, which is more stable than linear mRNA; circRNA is highly conserved in different species. It was found that circRNA competitively adsorbs miRNA, as a miRNA sponge, to involve in the expression regulation of a variety of genes and plays an important role in tumor development, invasion, metastasis and other processes. These molecules offer new potential opportunities for therapeutic intervention and serve as biomarkers for diagnosis. In this paper, the origin, characteristics and functions of circRNA and its role in tumor development, invasion and metastasis, diagnosis and prognosis are reviewed.


Asunto(s)
Neoplasias/terapia , Medicina de Precisión , ARN Circular , Carcinogénesis/genética , Exones , Humanos , Intrones , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias/diagnóstico , Neoplasias/patología , Neoplasias/virología , Conformación de Ácido Nucleico , Pronóstico , ARN Circular/química , ARN Circular/genética , ARN Circular/fisiología
9.
Carcinogenesis ; 42(5): 762-771, 2021 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-33758932

RESUMEN

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.


Asunto(s)
Factor Nuclear 4 del Hepatocito/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Neovascularización Patológica/genética , Proteínas de Unión al ARN/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Xenoinjertos , Humanos , Neoplasias Pulmonares/patología , Masculino , Ratones , Neovascularización Patológica/patología , Transducción de Señal/genética
10.
Plant J ; 102(1): 53-67, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31733118

RESUMEN

Phosphorus (P) is an essential macronutrient required for plant development and production. The mechanisms regulating phosphate (Pi) uptake are well established, but the function of chloroplast Pi homeostasis is poorly understood in Oryza sativa (rice). PHT2;1 is one of the transporters/translocators mediating Pi import into chloroplasts. In this study, to gain insight into the role of OsPHT2;1-mediated stroma Pi, we analyzed OsPHT2;1 function in Pi utilization and photoprotection. Our results showed that OsPHT2;1 was induced by Pi starvation and light exposure. Cell-based assays showed that OsPHT2;1 localized to the chloroplast envelope and functioned as a low-affinity Pi transporter. The ospht2;1 had reduced Pi accumulation, plant growth and photosynthetic rates. Metabolite profiling revealed that 52.6% of the decreased metabolites in ospht2;1 plants were flavonoids, which was further confirmed by 40% lower content of total flavonoids compared with the wild type. As a consequence, ospht2;1 plants were more sensitive to UV-B irradiation. Moreover, the content of phenylalanine, the precursor of flavonoids, was also reduced, and was largely associated with the repressed expression of ADT1/MTR1. Furthermore, the ospht2;1 plants showed decreased grain yields at relatively high levels of UV-B irradiance. In summary, OsPHT2;1 functions as a chloroplast-localized low-affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes.


Asunto(s)
Cloroplastos/metabolismo , Flavonoides/metabolismo , Oryza/metabolismo , Proteínas de Transporte de Fosfato/metabolismo , Proteínas de Plantas/metabolismo , Homeostasis , Oryza/genética , Oryza/fisiología , Oryza/efectos de la radiación , Fenilalanina/metabolismo , Proteínas de Transporte de Fosfato/genética , Fotosíntesis , Proteínas de Plantas/genética , Almidón/metabolismo , Sacarosa/metabolismo , Rayos Ultravioleta/efectos adversos
11.
J Transl Med ; 19(1): 400, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34551785

RESUMEN

BACKGROUND: Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. METHODS: Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. RESULTS: LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. CONCLUSION: Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.


Asunto(s)
MicroARNs , Neoplasias Pancreáticas , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Chaperonas Moleculares , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/genética , ARN Largo no Codificante/genética
12.
Inorg Chem ; 60(5): 3156-3164, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33591741

RESUMEN

A bifunctional ligand strategy for modification of the functional pores is of great significance in the structural design of metal-organic frameworks (MOFs). Herein, a new 2-fold interpenetrated "pillared-layer" 3D Co-MOF, {[Co(HL)(4,4'-bipy)]·DMF·2H2O}n (1), was successfully synthesized by using two kinds of ligands, imidazolecarboxylic acid and pyridine. The metal-carboxylic layers are pillared by the 4,4'-bipy ligand, displaying a 3D framework with rectangular 3D channels (high BET surface of 190.9 m2 g-1 and maximum aperture of 3.9 Å) that are decorated with abundant uncoordinated N and O atoms. 1 shows good water stability and thermal stability (320 °C). The proper pores and active sites endowed 1 with a selective adsorption of Congo red in aqueous solution. In addition, a high CO2 adsorption capacity and an excellent CO2 chemical conversion were observed.

13.
Epilepsy Behav ; 118: 107957, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33872942

RESUMEN

BACKGROUND: Radiofrequency thermocoagulation (RFTC) guided by stereo-electroencephalography (SEEG) has been proved to be a safe method to reduce seizure frequency in patients with drug-resistant epilepsy. However, there are few reports addressing the value and safety of this procedure in hypothalamic hamartoma (HH). OBJECTIVE: To present the results of our experience using SEEG-guided RFTC in HH patients with drug-resistant epilepsy, and identify outcome predictors. METHODS: We retrospectively reviewed the clinical and surgical characteristics of 27 HH-related patients with epilepsy in our center between 2015 and 2019. All patients underwent invasive recordings with SEEG before RFTC was performed. We reported surgical outcome predictors and postoperative follow-up concerning safety and efficacy (mean follow-up, 27.3 months; range, 12-63). Surgical strategy was also analyzed. RESULTS: Nineteen patients (70.4%) achieved Engel's class I outcome, while 4 patients (14.8%) did not show significant improvement. Of all observed seizures, two different onset patterns of intracranial electrophysiology recorded by SEEG were observed. Patients presented with focal low-voltage fast activity were more likely to obtain seizure freedom (p = 0.045), while classification (p = 0.478), volume (p = 0.546), history of resection (p = 0.713), seizure types (p = 0.859), or seizure duration (p = 0.415) showed no significant effect on the outcome. Weight gain was the most common long-term complication (18.5%). CONCLUSION: The SEEG can guide the ablation of HH and serve as an important factor to predict favorable seizure outcomes. Radiofrequency thermocoagulation guided by SEEG can offer a minimally invasive and low-risk surgical approach with excellent outcomes. Disconnecting the attachment of HH should be the appropriate strategy to obtain the best seizure outcome.


Asunto(s)
Hamartoma , Electrocoagulación , Electroencefalografía , Hamartoma/cirugía , Humanos , Enfermedades Hipotalámicas , Imagen por Resonancia Magnética , Pronóstico , Estudios Retrospectivos , Técnicas Estereotáxicas , Resultado del Tratamiento
14.
Int J Neurosci ; 131(8): 755-764, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32271641

RESUMEN

OBJECTIVES: Increasing evidence confirmed that miRNA plays a critical role in the occurrence and development of ischemic stroke. Here, the aim of this study was to examine the function and mechanisms of miR-195 in vascular endothelial cell apoptosis induced by oxygen-glucose deprivation (OGD). METHODS: This study intended to use OGD to simulate ischemia in vitro. The mRNA expression of miR-195, IKKα and NF-κB in human umbilical vein endothelial cells (HUVECs) were detected by RT-qPCR. The proliferation and apoptosis ability of HUVECs were evaluated using MTT assay, colony formation assay and flow cytometry, respectively. Western blot was applied to examine related protein expression. The interaction between miR-195 and IKKα was verified by dual-luciferase reporter gene assay. RESULTS: OGD significantly inhibited cell viability and induced cell apoptosis in HUVECs. Meanwhile, OGD treatment notably decreased the expression of miR-195, as well as enhanced NF-κB expression. Moreover, miR-195 directly interacted with IKKα and suppressed its expression. Mechanically, overexpression of miR-195 exhibited pro-proliferation and anti-apoptotic effect on HUVECs treated with OGD through targeting IKKα-mediated NF-κB pathway. At the molecular level, through suppressing IKKα/NF-κB pathway, miR-195 inhibited the expression of pro-apoptotic protein Bax and active caspase-3, but increased the expression of anti-apoptotic Bcl-2 in HUVECs. CONCLUSIONS: Our finding uncovers the protective effect of miR-195 on the biological behavior of HUVECs via suppression of the NF-κB pathway induced by IKKα, which may provide a new potential strategy for ischemic stroke clinical treatment.


Asunto(s)
Apoptosis/efectos de los fármacos , Isquemia/metabolismo , MicroARNs/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/genética , Hipoxia de la Célula , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Glucosa , Humanos , Quinasa I-kappa B/metabolismo , MicroARNs/administración & dosificación , FN-kappa B/metabolismo
15.
J Cell Biochem ; 121(3): 2467-2477, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31736157

RESUMEN

Matrine, also known as oxymatrine, is an important active ingredient of traditional Chinese herb Sophora flavescens. Recent studies have found that matrine may inhibit multiple tumors through inhibiting the tumor cell proliferation, inducing cell apoptosis, blocking cell cycle, suppressing cell invasion and migration and assisting in the synergy, and attenuation of radiotherapy and chemotherapy. This study mainly investigated the role of matrine in gastric cancer and its possible mechanism. The real-time fluorescence quantitative polymerase chain reaction technique showed that matrine inhibited the proliferation and migration of gastric tumor cells and significantly suppressed the expression of miR-93-5p. The dual-luciferase reporter gene assay indicated that AHNAK was a target gene of miR-93-5p and regulated by miR-93-5p and matrine. The torsion test demonstrated that matrine exerted its role via miR-93-5p while miR-93-5p played a role by targeting AHNAK. Thus, this study found that matrine affected the progression of gastric cancer by inhibiting the function of gastric cancer cells through the possible mechanism of inhibiting miR-93-5p expression to increase the expression level of the downstream target gene AHNAK.


Asunto(s)
Alcaloides/farmacología , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de la Membrana/genética , MicroARNs/genética , Proteínas de Neoplasias/genética , Quinolizinas/farmacología , Neoplasias Gástricas/patología , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Humanos , Ratones , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Matrinas
16.
Toxicol Ind Health ; 36(12): 1031-1038, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33215568

RESUMEN

To explore the protective mechanism of L-arginine against T-2 toxin-induced apoptosis in mouse Leydig cells, we investigated whether L-arginine can prevent T-2 toxin-induced apoptosis in mouse Leydig cells and explored the underlying mechanisms. Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), L-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) + L-arginine (0.25, 0.5, or 1.0 mM) for 24 h. Cells and supernatants were harvested to examine proliferation of the cells, the apoptosis rate, activity of caspase-3 and mitochondria, and the gene expression levels of Bcl-2, Bax, PARP, and caspase-3. Results showed that proliferation and mitochondrial activity of Leydig cells were inhibited by administration of T-2 toxin. Bcl-2 gene expression levels was decreased, while the gene expression levels of Bax and PARP were increased, which could trigger mitochondria-mediated apoptosis, activate downstream caspase-3, and then increased caspase-3 at both activity and gene expression levels. The expression of the Bcl-2 gene was upregulated and the expression of Bax, caspase-3, and PARP gene were downregulated when L-arginine was added to the cultured cells. The results of this study showed that L-arginine could block T-2 toxin-induced apoptosis in mouse Leydig cells by regulating specific intracellular death-related pathways.


Asunto(s)
Apoptosis/efectos de los fármacos , Arginina/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Sustancias Protectoras/farmacología , Toxina T-2/farmacología , Animales , Caspasa 3/biosíntesis , Proliferación Celular , Células Cultivadas , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Proteínas de Neoplasias , Poli(ADP-Ribosa) Polimerasa-1/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína X Asociada a bcl-2/biosíntesis
17.
Molecules ; 25(4)2020 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-32074994

RESUMEN

Constructed wetlands (CWs) could achieve high removal efficiency of antibiotics, but probably stimulate the spread of antibiotic resistance genes (ARGs). In this study, four CWs were established to treat synthetic wastewater containing sulfamethoxazole (SMX). SMX elimination efficiencies, SMX degradation mechanisms, dynamic fates of ARGs, and bacterial communities were evaluated during the treatment period (360 day). Throughout the whole study, the concentration of SMX in the effluent gradually increased (p < 0.05), but in general, the removal efficiency of SMX remained at a very high level (>98%). In addition, the concentration of SMX in the bottom layer was higher compared with that in the surface layer. The main byproducts of SMX degradation were found to be 4-amino benzene sulfinic acid, 3-amino-5-methylisoxazole, benzenethiol, and 3-hydroxybutan-1-aminium. Temporally speaking, an obvious increase of sul genes was observed, along with the increase of SMX concentration in the bottom and middle layers of CWs. Spatially speaking, the concentration of sul genes increased from the surface layer to the bottom layer.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Sulfametoxazol/farmacología , Aguas Residuales/microbiología , Humedales , Antibacterianos/farmacología , Humanos , Eliminación de Residuos Líquidos
18.
Water Sci Technol ; 82(2): 330-338, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32941174

RESUMEN

Nitrogen removal in osmosis membrane bioreactor (OMBR) is important to its applications but remains a challenge. In this study, a bioelectrochemically-assisted (BEA) operation was integrated into the feed side of OMBRs to enhance nitrogen removal, and sodium acetate was served as a draw solute and supplementary carbon source for the growth of denitrifying bacteria due to reversed-solute. The effects of operation mode and influent ammonium (NH4 +) concentration were systematically examined. Compared to a conventional OMBR, the integrated BEA-OMBR achieved higher total nitrogen removal efficiency of 98.13%, and chemical oxygen demand removal efficiency of 95.83% with the influent NH4 +-N concentration of 39 mg L-1. The sequencing analyses revealed that ammonia-oxidizing bacteria (0-0.04%), nitrite-oxidizing bacteria (0-0.16%), and denitrifying bacteria (1.98-8.65%) were in abundance of the microbial community in the feed/anode side of integrated BEA-OMBR, and thus BEA operation increased the diversity of the microbial community in OMBR. Future research will focus on improving nitrogen removal from a high ammonium strength wastewater by looping anolyte effluent to the cathode. These findings have demonstrated that BEA operation can be an effective approach to improve nitrogen removal in OMBRs toward sustainable wastewater treatment.


Asunto(s)
Desnitrificación , Nitrógeno , Reactores Biológicos , Ósmosis , Aguas Residuales
19.
Zhongguo Zhong Yao Za Zhi ; 45(13): 2993-3000, 2020 Jul.
Artículo en Zh | MEDLINE | ID: mdl-32726003

RESUMEN

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Medicamentos Herbarios Chinos , Pandemias , Neumonía Viral , Adolescente , Adulto , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Medicina Tradicional China , Persona de Mediana Edad , Neumonía Viral/tratamiento farmacológico , Estudios Prospectivos , SARS-CoV-2 , Adulto Joven , Tratamiento Farmacológico de COVID-19
20.
Plant Cell Physiol ; 60(12): 2785-2796, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31424513

RESUMEN

Phosphorus is one of the most important macronutrients required for plant growth and development. The importance of phosphorylation modification in regulating phosphate (Pi) homeostasis in plants is emerging. We performed phosphoproteomic profiling to characterize proteins whose degree of phosphorylation is altered in response to Pi starvation in rice root. A subset of 554 proteins, including 546 down-phosphorylated and eight up-phosphorylated proteins, exhibited differential phosphorylation in response to Pi starvation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the differentially phosphorylated proteins indicated that RNA processing, transport, splicing and translation and carbon metabolism played critical roles in response to Pi starvation in rice. Levels of phosphorylation of four mitogen-activated protein kinases (MAPKs), including OsMAPK6, five calcium-dependent protein kinases (CDPKs) and OsCK2ß3 decreased in response to Pi starvation. The decreased phosphorylation level of OsMAPK6 was confirmed by Western blotting. Mutation of OsMAPK6 led to Pi accumulation under Pi-sufficient conditions. Motif analysis indicated that the putative MAPK, casein kinase 2 (CK2) and CDPK substrates represented about 54.4%, 21.5% and 4.7%, respectively, of the proteins exhibiting differential phosphorylation. Based on the motif analysis, 191, 151 and 46 candidate substrates for MAPK, CK2 and CDPK were identified. These results indicate that modification of phosphorylation profiles provides complementary information on Pi-starvation-induced processes, with CK2, MAPK and CDPK protein kinase families playing key roles in these processes in rice.


Asunto(s)
Quinasa de la Caseína II/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oryza/metabolismo , Fosfatos/metabolismo , Proteínas de Plantas/metabolismo , Quinasa de la Caseína II/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Proteínas Quinasas Activadas por Mitógenos/genética , Oryza/fisiología , Fosfatos/deficiencia , Proteínas de Plantas/genética
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