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1.
Plant Physiol ; 194(2): 1181-1203, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-37930306

RESUMEN

Drought stress is a key environmental factor limiting the productivity, quality, and geographic distribution of crops worldwide. Abscisic acid (ABA) plays an important role in plant drought stress responses, but the molecular mechanisms remain unclear. Here, we report an ABA-responsive bHLH transcription factor, MdbHLH160, which promotes drought tolerance in Arabidopsis (Arabidopsis thaliana) and apple (Malus domestica). Under drought conditions, MdbHLH160 is directly bound to the MdSOD1 (superoxide dismutase 1) promoter and activated its transcription, thereby triggering reactive oxygen species (ROS) scavenging and enhancing apple drought tolerance. MdbHLH160 also promoted MdSOD1 enzyme activity and accumulation in the nucleus through direct protein interactions, thus inhibiting excessive nuclear ROS levels. Moreover, MdbHLH160 directly upregulated the expression of MdDREB2A-like, a DREB (dehydration-responsive element binding factor) family gene that promotes apple drought tolerance. Protein degradation and ubiquitination assays showed that drought and ABA treatment stabilized MdbHLH160. The BTB protein MdBT2 was identified as an MdbHLH160-interacting protein that promoted MdbHLH160 ubiquitination and degradation, and ABA treatment substantially inhibited this process. Overall, our findings provide insights into the molecular mechanisms of ABA-modulated drought tolerance at both the transcriptional and post-translational levels via the ABA-MdBT2-MdbHLH160-MdSOD1/MdDREB2A-like cascade.


Asunto(s)
Arabidopsis , Malus , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Resistencia a la Sequía , Especies Reactivas de Oxígeno/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Sequías , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico/genética
2.
Plant J ; 116(3): 669-689, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37471682

RESUMEN

Salt stress adversely affects the yield and quality of crops and limits their geographical distribution. Studying the functions and regulatory mechanisms of key genes in the salt stress response is important for breeding crops with enhanced stress resistance. Autophagy plays an important role in modulating the tolerance of plants to various types of abiotic stressors. However, the mechanisms underlying salt-induced autophagy are largely unknown. Cation/Ca2+ exchanger proteins enhance apple salt tolerance by inhibiting Na+ accumulation but the mechanism underlying the response to salt stress remains unclear. Here, we show that the autophagy-related gene MdATG18a modulated apple salt tolerance. Under salt stress, the autophagic activity, proline content, and antioxidant enzyme activities were higher and Na+ accumulation was lower in MdATG18a-overexpressing transgenic plants than in control plants. The use of an autophagy inhibitor during the salt treatment demonstrated that the regulatory function of MdATG18a depended on autophagy. The yeast-one-hybrid assay revealed that the homeodomain-leucine zipper (HD-Zip) transcription factor MdHB7-like directly bound to the MdATG18a promoter. Transcriptional regulation and genetic analyses showed that MdHB7-like enhanced salt-induced autophagic activity by promoting MdATG18a expression. The analysis of Na+ efflux rate in transgenic yeast indicated that MdCCX1 expression significantly promoted Na+ efflux. Promoter binding, transcriptional regulation, and genetic analyses showed that MdHB7-like promoted Na+ efflux and apple salt tolerance by directly promoting MdCCX1 expression, which was independent of the autophagy pathway. Overall, our findings provide insight into the mechanism underlying MdHB7-like-mediated salt tolerance in apple through the MdHB7-like-MdATG18a and MdHB7-like-MdCCX1 modules. These results will aid future studies on the mechanisms underlying stress-induced autophagy and the regulation of stress tolerance in plants.


Asunto(s)
Malus , Malus/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae/genética , Fitomejoramiento , Plantas Modificadas Genéticamente/genética , Autofagia/genética , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética
3.
Langmuir ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39039962

RESUMEN

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.

4.
BMC Gastroenterol ; 24(1): 227, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039452

RESUMEN

BACKGROUND: Sepsis is triggered by pathogenic microorganisms, resulting in a systemic inflammatory response. Liver cirrhosis and sepsis create a vicious cycle: cirrhosis weakens immune function, raising infection risk and hindering pathogen clearance. Optimal treatment outcomes depend on understanding liver cirrhosis patients' sepsis risk factors. Thus, preventing sepsis involves addressing these risk factors. Therefore, early identification and understanding of clinical characteristics in liver cirrhosis patients with sepsis are crucial for selecting appropriate antibiotics. A case-control study using logistic regression was conducted to examine the prognostic value of amyloid A/lactate level monitoring in identifying sepsis risk factors in liver cirrhosis patients. METHODS: From March 2020 to March 2022, 136 liver cirrhosis patients treated at our hospital were divided into a sepsis group (n = 35) and a non-sepsis group (n = 101) based on sepsis complications. General clinical data were collected. Univariate analysis screened for liver cirrhosis patients' sepsis risk factors. Multivariate logistic analysis was subsequently employed to evaluate the risk factors. Sepsis patients were followed up for a month. Based on prognosis, patients were categorized into a poor prognosis group (n = 16) and a good prognosis group (n = 19). Serum amyloid A (SAA) and blood lactic acid (BLA) levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of both individual and combined SAA/BLA monitoring. RESULTS: Patient data, including age, diabetes history, liver cancer, hepatic artery embolization, recent antibiotic use, invasive procedures within two weeks, APACHE II Scoring, ALB and SAA and BLA levels, were compared between the sepsis and non-sepsis groups, showing significant differences (P < 0.05). Logistic regression identified factors such as age ≥ 70, recent antibiotic use, recent invasive procedures, history of liver cancer, hepatic artery embolization history, high APACHE II scores, decreased albumin, and elevated SAA and BLA levels as independent sepsis risk factors in liver cirrhosis patients (P < 0.05). Among the 35 sepsis patients, 16 had a poor prognosis, representing an incidence rate of 45.71%. Serum SAA and BLA levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). The AUC for serum SAA and BLA was 0.831 (95%CI: 0.738-0.924), 0.720 (95%CI: 0.600-0.840), and 0.909 (95%CI: 0.847-0.972), respectively. The combined diagnostic AUC was significantly higher than that of single factor predictions (P < 0.05). The predictive value ranked as follows: joint detection > SAA > BLA. CONCLUSION: In treating liver cirrhosis, prioritize patients with advanced age, a history of hepatic artery embolization, recent invasive operations, history of liver cancer, recent antibiotic exposure, high APACHE II scores and low albumin. Closely monitoring serum SAA and BLA levels in these patients can offer valuable insights for early clinical prevention and treatment.


Asunto(s)
Ácido Láctico , Cirrosis Hepática , Sepsis , Proteína Amiloide A Sérica , Humanos , Sepsis/sangre , Sepsis/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Proteína Amiloide A Sérica/análisis , Proteína Amiloide A Sérica/metabolismo , Estudios de Casos y Controles , Ácido Láctico/sangre , Pronóstico , Factores de Riesgo , Anciano , Curva ROC , Biomarcadores/sangre , Modelos Logísticos
5.
J Pediatr Hematol Oncol ; 46(6): e406-e411, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38934602

RESUMEN

OBJECTIVES: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. STUDY DESIGN: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. RESULTS: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). CONCLUSIONS: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Heparina , Trombosis , Humanos , Heparina/administración & dosificación , Heparina/uso terapéutico , Masculino , Femenino , Lactante , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Trombosis/prevención & control , Trombosis/etiología , Recién Nacido , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Alta del Paciente , Infusiones Intravenosas , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Catéteres Venosos Centrales/efectos adversos
6.
Small ; 19(35): e2301148, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37118853

RESUMEN

As an emerging cancer treatment strategy, ferroptosis is greatly restricted by excessive glutathione (GSH) in tumor microenvironment (TME) and low reactive oxygen species (ROS) generation efficiency. Here, this work designs self-assembled copper-alanine nanoparticles (CACG) loaded with glucose oxidase (GOx) and cinnamaldehyde (Cin) for in situ glutathione activated and enzymatic cascade-enhanced ferroptosis and immunotherapy. In response to GSH-rich and acidic TME, CACG allows to effectively co-deliver Cu2+ , Cin, and GOx into tumors. Released Cin consumes GSH through Michael addition, accompanying with the reduction of Cu2+ into Cu+ for further GSH depletion. With the cascade of Cu+ -catalyzed Fenton reactions and enzyme-catalyzed reactions by GOx, CACG could get rid of the restriction of insufficient hydrogen peroxide in TME, leading to a robust and constant generation of ROS. With the high efficiency of GSH depletion and ROS production, ferroptosis is significantly enhanced by CACG in vivo. Moreover, elevated oxidative stress triggers robust immune responses by promoting dendritic cells maturation and T cell infiltration. The in vivo results prove that CACG could efficiently inhibit tumor growth in 4T1 tumor-bearing mouse model without causing obvious systemic toxicity, suggesting the great potential of CACG in enhancing ferroptosis and immunotherapy for effective cancer treatment.


Asunto(s)
Ferroptosis , Nanopartículas , Neoplasias , Animales , Ratones , Cobre , Especies Reactivas de Oxígeno , Inmunoterapia , Glucosa Oxidasa , Glutatión , Peróxido de Hidrógeno , Microambiente Tumoral , Línea Celular Tumoral , Neoplasias/terapia
7.
Nano Lett ; 22(13): 5575-5583, 2022 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-35763414

RESUMEN

Synthetic biology has promoted the development of microbial therapy, but the scope of applicable microbial species is limited and transgenic microorganisms also display safety risks for in vivo applications. Interestingly, symbiotic microorganisms in nature can achieve functional updates by metabolic cooperation. Here, we report on a nongenetic method for engineering microorganisms to construct a heavy metal ion reduction system, which was prepared by linking Shewanella oneidensis MR-1 (SO) and Lactobacillus rhamnosus GG (LGG). SO could reduce metal ions but is limited by finite substrates in vivo. LGG could metabolize glucose to lactate as a substrate for SO, promoting extracellular electron transfer by SO and heavy metal ion reduction. Meanwhile, SO could generate electron donor cytochrome C to promote metabolism of LGG, forming metabolic synergy and circulation between these two bacteria. The SO-LGG system shows splendid ability to remove heavy metal ions and inflammatory modulation in acute or chronic heavy metal poisoning.


Asunto(s)
Metales Pesados , Shewanella , Transporte de Electrón , Iones
8.
J Cell Physiol ; 237(12): 4544-4550, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36256845

RESUMEN

Rapeseed is an important source of oilseed crop in the world. Achieving genetic improvement has always been the major goal in rapeseed production. Single nucleotide substitution is the basis of most genetic variation underpinning important agronomic traits. Nowadays, Cas-base editing acts as an efficient tool to mediate single-base substitution at the target site. In this study, four adenine base editors (ABE) were modified to achieve adenosine base editing at different genome sites in allotetraploid Brassica napus. We designed 18 small guide RNAs to target phytoene desaturase (PDS), acetolactate synthase (ALS), CLAVATA3 (CLV3), CLV2, TRANSPARENT TESTA12 (TT12), carotenoid isomerase (CRTISO), designated de-etiolated-2 (DET2), BRANCHED1 (BRC1), zeaxanthin epoxidase (ZEP) genes, respectively. Among the four ABE systems, pBGE17 had the highest base-editing efficiency, with an average editing efficiency of 3.51%. Target sequencing results revealed that the editing window ranged from A5 to A8 of the protospacer-adjacent motif (PAM) sequence. Moreover, the ABEmax-nCas9NG system with NG PAM was developed, with a base-editing efficiency of 1.22%. These results revealed that ABE system developed in this study could efficiently induce A to G substitution and the ABE-nCas9NG system could broaden editing window in oilseed rape.


Asunto(s)
Brassica napus , Edición Génica , Adenina , Brassica napus/genética , Edición Génica/métodos , Genoma de Planta , ARN Guía de Sistemas CRISPR-Cas , Tetraploidía
9.
Theor Appl Genet ; 135(7): 2233-2246, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35532733

RESUMEN

KEY MESSAGE: qFT7.1, a major QTL for flowering time in Brassica rapa was fine-mapped to chromosome A07 in a 56.4-kb interval, in which the most likely candidate gene is BraA07g018240.3C. In Brassica rapa, flowering time (FT) is an important agronomic trait that affects the yield, quality, and adaption. FT is a complicated trait that is regulated by many genes and is affected greatly by the environment. In this study, a chromosome segment substitution line (CSSL), CSSL16, was selected that showed later flowering than the recurrent parent, a rapid-cycling inbred line of B. rapa (RcBr). Using Bulked Segregant RNA sequencing, we identified a late flowering quantitative trait locus (QTL), designated as qFT7.1, on chromosome A07, based on a secondary-F2 population derived from the cross between CSSL16 and RcBr. qFT7.1 was further validated by conventional QTL mapping. This QTL explained 39.9% (logarithm of odds = 32.2) of the phenotypic variations and was fine mapped to a 56.4-kb interval using recombinant analysis. Expression analysis suggested that BraA07g018240.3C, which is homologous to ATC (encoding Arabidopsis thaliana CENTRORADIALIS homologue), a gene for delayed flowering in Arabidopsis, as the most promising candidate gene. Sequence analysis demonstrated that two synonymous mutations existed in the coding region and numerous bases replacements existed in promoter region between BraA07g018240.3C from CSSL16 and RcBr. The results will increase our knowledge related to the molecular mechanism of late flowering in B. rapa and lays a solid foundation for the breeding of late bolting B. rapa.


Asunto(s)
Arabidopsis , Brassica rapa , Arabidopsis/genética , Brassica rapa/genética , Mapeo Cromosómico , Flores/genética , Fitomejoramiento , Sitios de Carácter Cuantitativo
10.
Pediatr Cardiol ; 42(2): 340-348, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33090241

RESUMEN

The current study was to report our initial experiences of fetal pulmonary valvuloplasty (FPV) for fetuses with pulmonary atresia with intact ventricular septum (PA/IVS) and critical pulmonary stenosis (CPS), including case selection, technical feasibility, and the effects of FPV on utero and postnatal outcome. Two fetuses with PA/IVS and three fetuses with CPS were enrolled between September 2016 and April 2018. All fetuses were with concomitant severe right ventricular dysplasia and growth arrest. Parameters of right cardiac development and hemodynamics, including tricuspid/mitral annulus ratio (TV/MV), right ventricle/left ventricle long-axis ratio (RV/LV), tricuspid valve inflow duration/cardiac cycle ratio (TVI/CC), degree of tricuspid regurgitation (TR), and blood flow direction of arterial duct and ductus venosus, were evaluated using echocardiogram. FPV was performed trans-abdominally under ultrasound guidance. Echocardiogram was performed post-FPV and every 2-4 weeks thereafter until delivery. The median gestational age at the time of FPV was 28 weeks. From technical perspective, pulmonary balloon valvuloplasty was successfully performed and the opening of pulmonary valve was improved in all fetuses in 2-4 weeks. However, progressive restenosis was observed in four fetuses with gestation advancing, and re-atresia occurred in two PA/IVS fetuses at 36th and 37th weeks' gestation, respectively. The growth trajectories of TV/MV, RV/LV, and TVI/CC were improved in the 1st week after FPV and then slowed down along with pulmonary valve restenosis. All fetuses were born alive and underwent postnatal interventions, including pulmonary balloon valvuloplasty in three fetuses and surgical procedures in two fetuses. During follow-up, three fetuses turned to be biventricular, one became one and a half ventricular at 1-year old, and one died of neonatal infection. Although pulmonary valve restenosis might occur as gestation advancing, FPV seems to be a safe and feasible procedure to improve the growth trajectories of right heart for fetuses with PA/IVS and CPS.


Asunto(s)
Valvuloplastia con Balón/métodos , Fetoscopía/métodos , Cardiopatías Congénitas/cirugía , Atresia Pulmonar/cirugía , Estenosis de la Válvula Pulmonar/cirugía , China , Ecocardiografía , Ecocardiografía Doppler en Color , Femenino , Edad Gestacional , Cardiopatías Congénitas/embriología , Humanos , Lactante , Embarazo , Atresia Pulmonar/embriología , Estenosis de la Válvula Pulmonar/embriología , Resultado del Tratamiento , Ultrasonografía Intervencional
11.
Theor Appl Genet ; 133(12): 3333-3343, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32816057

RESUMEN

KEY MESSAGE: BnA10.RCO positively regulates the development of leaf lobes in Brassica napus, and cis-regulatory divergences cause the different allele effects. The functional importance of lobed leaves in rapeseed (Brassica napus L.) has been identified with potential advantages for high-density planting and hybrid production. Our previous studies indicated that the tandemly duplicated LMI1-like genes BnA10. RCO and BnA10.LMI1 are candidate genes of an incompletely dominant locus, which is responsible for the lobed-leaf shape in rapeseed. We provided strong evidence that BnA10.LMI1 positively regulates leaf lobe formation. Here, we show that BnA10.RCO is a nucleus-specific protein, encoding an HD-ZIP I transcription factor, which is responsible for the lobed-leaf shape in rapeseed. Sequence analysis of parental alleles revealed that no vital sequence variation was detected in the coding sequence of BnA10.RCO, whereas abundant variations were identified in the regulatory regions. Consistent with this finding, the expression level of BnRCO was substantially elevated in the lobed-leaved parent HY compared with its near-isogenic line. Moreover, the altered expression of BnA10.RCO in transgenic lines showed a positive connection with leaf complexity without a substantial change in BnLMI1 transcript level. Furthermore, CRISPR/Cas9-induced null mutations of BnA10.RCO in the lobed-leaved parent HY were sufficient to produce an unlobed leaf without alteration in BnLMI1 transcript level. Our results indicate that BnA10.RCO functions together with BnA10.LMI1 to positively determine the lobed-leaf development, providing a fundamental basis for crop improvement by targeting leaf shape in rapeseed.


Asunto(s)
Brassica napus/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Genes Homeobox , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Secuencia de Aminoácidos , Brassica napus/genética , Brassica napus/metabolismo , Mapeo Cromosómico , Hojas de la Planta/anatomía & histología , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Homología de Secuencia
12.
Nano Lett ; 19(8): 5568-5576, 2019 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-31262183

RESUMEN

Tumor cells adapt to reactive oxygen species (ROS) attacking by launching DNA damage repairing mechanisms such as nucleotide pool sanitizing enzyme mutt homologue 1 (MTH1) to mitigate the oxidatively induced DNA lesions, which could greatly limit the therapeutic efficiency of current oxidation therapy. Here, an amplified oxidative damage strategy for tumor therapy was proposed that was focused not only on the enhancement of ROS generation but also the inhibition of subsequent MTH1 enzyme activity simultaneously. In our formulation, mesoporous silica-coated Prussian blue nanoplatforms (PB@MSN) with excellent catalase-like activity and drug loading capability were employed to encapsulate MTH1 inhibitor TH287, followed by the modification of tetraphenylporphrin zinc (Zn-Por) via metallo-supramolecular coordination (PMPT), where Zn-Por behaved as photodynamic and fluorescence imaging agents, as well as acid-responsive gatekeepers. The intelligent PMPT nanosystems could induce the decomposition of H2O2 to relieve the hypoxic tumor environment, thus elevating the generation of singlet oxygen for improved oxidative damage. In the meantime, controllable-released TH287 from pores could hinder MTH1-mediated damage repairing process and aggravate oxidative damage, thereby resulting in cellular toxicity as well as tumor growth inhibition.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Enzimas Reparadoras del ADN/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Monoéster Fosfórico Hidrolasas/antagonistas & inhibidores , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Pirimidinas/uso terapéutico , Animales , Neoplasias de la Mama/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Células MCF-7 , Ratones Desnudos , Imagen Óptica , Monoéster Fosfórico Hidrolasas/metabolismo , Fotoquimioterapia , Fármacos Fotosensibilizantes/administración & dosificación , Porfirinas/administración & dosificación , Pirimidinas/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo
13.
Nano Lett ; 19(11): 8049-8058, 2019 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-31558023

RESUMEN

Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Decitabina/uso terapéutico , Epigénesis Genética/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Piroptosis/efectos de los fármacos , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Cisplatino/administración & dosificación , Decitabina/administración & dosificación , Sistemas de Liberación de Medicamentos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Liposomas , Ratones , Ratones Endogámicos BALB C , Neoplasias/genética , Receptores de Estrógenos/genética
14.
Int J Legal Med ; 133(3): 699-710, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30610448

RESUMEN

Vaginal fluid and saliva are of great importance in forensic sciences. The identification of vaginal fluid or saliva is especially important in criminal cases. Microbes are considered as a promising marker for the identification of body fluids. In this study, 18 salivary fluids and 18 vaginal fluid samples were collected from 18 healthy women of the Han population in Guangdong province, China. The microbes of the above samples were analyzed by 16S rDNA high-throughput sequencing. The results showed that the microbes whose proportions are over 1% in saliva samples distributed across 12 genera and 57 operational taxonomic units (OTUs), and in vaginal fluid distributed across 4 genera and 9 OTUs. The microbes that dominated in saliva were quite different from those dominated in vaginal fluids. The linear discriminant analysis (LDA) effect size (LEfSe) algorithm was used to screen out the specific microbes of the studied samples, and the results showed that the specific microbes in saliva samples are Haemophilus parainfluenzae, Veillonella parvula, and Aggregatibacter segnis, while in vaginal fluid is Lactobacillus iners.


Asunto(s)
Moco del Cuello Uterino/microbiología , ADN Bacteriano/genética , ADN Ribosómico/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Saliva/microbiología , Análisis de Secuencia de ADN , Adulto , China , Análisis Discriminante , Etnicidad/genética , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S , Adulto Joven
15.
Breed Sci ; 69(1): 47-54, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31086483

RESUMEN

Seed coat color is an important agronomic trait in Brassica rapa. Yellow seeds are a desirable trait for breeding oilseed Brassica crops. To identify quantitative trait loci (QTLs) that condition seed coat color in B. rapa, we used a population of recombinant inbred lines (RILs) derived from crossing 09A001, a standard rapid-cycling (RcBr) inbred line of B. rapa L. ssp. dichotoma with yellow seeds, with 08A061, an inbred line of heading Chinese cabbage with dark brown seeds. Using two phenotypic scoring methods, we detected a total of nine QTLs distributed on four chromosomes (Chrs.), A03, A06, A08, and A09, that explained 3.17 to 55.73% of the phenotypic variation for seed color. To validate the effects of the identified QTLs in the RIL population, chromosome segment substitution lines (CSSLs) harboring the chromosomal segment carrying the candidate QTL region from 08A061 were selected, and two co-localized major QTLs, qSC9.1 and qSCb9.1, and one minor QTL, qSC3.1, were successfully validated. The validated QTL located on Chr. A03 appears to be a new locus underlying seed coat color in B. rapa. These findings provide additional insight that will help explain the complex genetic mechanisms underlying the seed coat color trait in B. rapa.

16.
Molecules ; 21(8)2016 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-27556436

RESUMEN

Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR-irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection.


Asunto(s)
Oro/química , Lisina/química , Nanopartículas del Metal/química , Señales de Localización Nuclear/química , Oligonucleótidos/genética , Endosomas/genética , Células HeLa , Humanos , Luz , Lisosomas/genética , Oligonucleótidos/química , Oxidación-Reducción , Procesos Fotoquímicos , Especies Reactivas de Oxígeno/metabolismo , Transfección
17.
Soft Matter ; 10(7): 947-51, 2014 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-24983102

RESUMEN

A six-residue facial cyclopeptide was designed with the following sequence: c-[D-Leu-L-Lys-D-Ala-L-Lys-D-Leu-L-Gln] (CP). Extensive hydrogen bonding between the cyclopeptide backbones mainly regulated CP to self-assemble into single-walled nanotubes. Simultaneously, the hydrophobic interaction among facial hydrophobic side chains of CP was introduced to stabilize the hydrogen bonding, resulting in the formation of the thick-walled nanotubes with high length­diameter ratios.


Asunto(s)
Nanotubos/química , Péptidos Cíclicos/química , Nanotubos/ultraestructura , Polimerizacion , Conformación Proteica
18.
Proc Natl Acad Sci U S A ; 108(47): 19078-83, 2011 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-22042856

RESUMEN

Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. Here, we report the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity >99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin.


Asunto(s)
Reactores Biológicos , Biotecnología/métodos , Modelos Moleculares , Oryza/metabolismo , Semillas/metabolismo , Albúmina Sérica/biosíntesis , Animales , Humanos , Plantas Modificadas Genéticamente , Ratas , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Albúmina Sérica/química
19.
Surg Radiol Anat ; 36(3): 299-302, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23851942

RESUMEN

PURPOSE: We report an extremely rare case of saccular aneurysm in the left medial type persistent trigeminal artery (PTA) trunk and discuss its clinical importance. MATERIALS AND METHODS: A 77-year-old woman who had symptom suggestive of vertebrobasilar insufficiency underwent cerebral magnetic resonance (MR) imaging and non-contrast three dimensional time-of-flight MR angiography (3D TOF MRA) using a 3 T scanner. RESULTS: 3D TOF MRA images revealed a left medial type PTA originated from the left internal carotid artery C5 portion, through cavernous sinus and connected to the basilar artery with a saccular aneurysm in the mid portion of its trunk. The basilar artery (BA) under the union was hypoplastic. The bilateral posterior communicating arteries were absent. CONCLUSION: To our knowledge, this is the first report of a medial type PTA associated with a saccular aneurysm in the PTA trunk. Being aware of this is crucial in clinical, because they can influence surgical and interventional procedures.


Asunto(s)
Aneurisma/patología , Anciano , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/patología , Angiografía por Resonancia Magnética
20.
J Forensic Leg Med ; 100: 102615, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37995431

RESUMEN

Vaginal fluids are one of the most common biological samples in forensic sexual assault cases, and their characterization is vital to narrow the scope of investigation. Presently, approaches for identifying vaginal fluids in different regions are not only rare but also have certain limitations. However, the microbiome has shown the potential to identify the source of body fluids and reveal the characteristics of individuals. In this study, 16S rRNA gene high-throughput sequencing was used to characterize the vaginal microbial community from three regions, Sichuan, Hainan and Hunan. In addition, data on relative abundance and alpha diversity were used to construct a random forest model. The results revealed that the dominant genera in the three regions were Lactobacillus, followed by Gardnerella. In addition, Ureaplasma, Nitrospira, Nocardiodes, Veillonella and g-norank-f-Vicinamibacteraceae were significantly enriched genera in Sichuan, llumatobacter was enriched in Hainan, and Pseudomonas was enriched in Hunan. The random forest classifier based on combined data on relative abundance and alpha diversity had a good ability to distinguish vaginal fluids with similar dominant microbial compositions in the three regions. The study suggests that combining high-throughput sequencing data with machine learning models has good potential for application in the biogeographic inference of vaginal fluids.


Asunto(s)
Microbiota , Vagina , Femenino , Humanos , ARN Ribosómico 16S/genética , Bacterias/genética , Microbiota/genética , Lactobacillus/genética
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