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1.
Plant Cell ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801741

RESUMEN

The phytohormone jasmonate (JA) plays a central role in plant defenses against biotic stressors. However, our knowledge of the JA signaling pathway in rice (Oryza sativa) remains incomplete. Here, we integrated multi-omic data from three tissues to characterize the functional modules involved in organizing JA-responsive genes. In the core regulatory sector, MYC2 transcription factor transcriptional cascades are conserved. in different species but with distinct regulators (e.g. bHLH6 in rice)., in which genes are early expressed across all tissues. In the feedback sector, MYC2 also regulates the expression of JA repressor and catabolic genes, providing negative feedback that truncates the duration of JA responses. For example, the MYC2-regulated NAC (NAM, ATAF1/2 and CUC2) transcription factor genes NAC1, NAC3, and NAC4 encode proteins that repress JA signaling and herbivore resistance. In the tissue-specific sector, many late-expressed genes are associated with the biosynthesis of specialized metabolites that mediate particular defensive functions. For example, the terpene synthase gene TPS35 is specifically induced in the leaf sheath and TPS35 functions in defense against oviposition by brown planthoppers and the attraction of this herbivore's natural enemies. Thus, by characterizing core, tissue-specific, and feedback sectors of JA-elicited defense responses, this work provides a valuable resource for future discoveries of key JA components in this important crop.

2.
Proc Natl Acad Sci U S A ; 120(13): e2211102120, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36952381

RESUMEN

Receptor-like kinases (RLKs) may initiate signaling pathways by perceiving and transmitting environmental signals to cellular machinery and play diverse roles in plant development and stress responses. The rice genome encodes more than one thousand RLKs, but only a small number have been characterized as receptors for phytohormones, polypeptides, elicitors, and effectors. Here, we screened the function of 11 RLKs in rice resistance to the blast fungus Magnaporthe oryzae (M. oryzae) and identified a negative regulator named BDR1 (Blast Disease Resistance 1). The expression of BDR1 was rapidly increased under M. oryzae infection, while silencing or knockout of BDR1 significantly enhanced M. oryzae resistance in two rice varieties. Protein interaction and kinase activity assays indicated that BDR1 directly interacted with and phosphorylated mitogen-activated kinase 3 (MPK3). Knockout of BDR1 compromised M. oryzae-induced MPK3 phosphorylation levels. Moreover, transcriptome analysis revealed that M. oryzae-elicited jasmonate (JA) signaling and terpenoid biosynthesis pathway were negatively regulated by BDR1 and MPK3. Mutation of JA biosynthetic (allene oxide cyclase (AOC)/signaling (MYC2) genes decreased rice resistance to M. oryzae. Besides diterpenoid, the monoterpene linalool and the sesquiterpene caryophyllene were identified as unique defensive compounds against M. oryzae, and their biosynthesis genes (TPS3 and TPS29) were transcriptionally regulated by JA signaling and suppressed by BDR1 and MPK3. These findings demonstrate the existence of a BDR1-MPK3 cascade that negatively mediates rice blast resistance by affecting JA-related defense responses.


Asunto(s)
Magnaporthe , Oryza , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Transducción de Señal , Reguladores del Crecimiento de las Plantas/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genética , Magnaporthe/fisiología
3.
J Gen Virol ; 105(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38809251

RESUMEN

Tick-borne orthoflaviviruses (TBFs) are classified into three conventional groups based on genetics and ecology: mammalian, seabird and probable-TBF group. Recently, a fourth basal group has been identified in Rhipicephalus ticks from Africa: Mpulungu flavivirus (MPFV) in Zambia and Ngoye virus (NGOV) in Senegal. Despite attempts, isolating these viruses in vertebrate and invertebrate cell lines or intracerebral injection of newborn mice with virus-containing homogenates has remained unsuccessful. In this study, we report the discovery of Xinyang flavivirus (XiFV) in Haemaphysalis flava ticks from Xìnyáng, Henan Province, China. Phylogenetic analysis shows that XiFV was most closely related to MPFV and NGOV, marking the first identification of this tick orthoflavivirus group in Asia. We developed a reverse transcriptase quantitative PCR assay to screen wild-collected ticks and egg clutches, with absolute infection rates of 20.75 % in adult females and 15.19 % in egg clutches, suggesting that XiFV could be potentially spread through transovarial transmission. To examine potential host range, dinucleotide composition analyses revealed that XiFV, MPFV and NGOV share a closer composition to classical insect-specific orthoflaviviruses than to vertebrate-infecting TBFs, suggesting that XiFV could be a tick-only orthoflavivirus. Additionally, both XiFV and MPFV lack a furin cleavage site in the prM protein, unlike other TBFs, suggesting these viruses might exist towards a biased immature particle state. To examine this, chimeric Binjari virus with XIFV-prME (bXiFV) was generated, purified and analysed by SDS-PAGE and negative-stain transmission electron microscopy, suggesting prototypical orthoflavivirus size (~50 nm) and bias towards uncleaved prM. In silico structural analyses of the 3'-untranslated regions show that XiFV forms up to five pseudo-knot-containing stem-loops and a prototypical orthoflavivirus dumbbell element, suggesting the potential for multiple exoribonuclease-resistant RNA structures.


Asunto(s)
Flavivirus , Ixodidae , Filogenia , Animales , Flavivirus/genética , Flavivirus/clasificación , Flavivirus/aislamiento & purificación , China , Ixodidae/virología , Femenino
4.
J Biomed Inform ; 151: 104607, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38360080

RESUMEN

OBJECTIVES: Hypothesis Generation (HG) is a task that aims to uncover hidden associations between disjoint scientific terms, which influences innovations in prevention, treatment, and overall public health. Several recent studies strive to use Recurrent Neural Network (RNN) to learn evolutional embeddings for HG. However, the complex spatiotemporal dependencies of term-pair relations will be difficult to depict due to the inherent recurrent structure. This paper aims to accurately model the temporal evolution of term-pair relations using only attention mechanisms, for capturing crucial information on inferring the future connectivities. METHODS: This paper proposes a Temporal Attention Networks (TAN) to produce powerful spatiotemporal embeddings for Biomedical Hypothesis Generation. Specifically, we formulate HG problem as a future connectivity prediction task in a temporal attributed graph. Our TAN develops a Temporal Spatial Attention Module (TSAM) to establish temporal dependencies of node-pair (term-pair) embeddings between any two time-steps for smoothing spatiotemporal node-pair embeddings. Meanwhile, a Temporal Difference Attention Module (TDAM) is proposed to sharpen temporal differences of spatiotemporal embeddings for highlighting the historical changes of node-pair relations. As such, TAN can adaptively calibrate spatiotemporal embeddings by considering both continuity and difference of node-pair embeddings. RESULTS: Three real-world biomedical term relationship datasets are constructed from PubMed papers. TAN significantly outperforms the best baseline with 12.03%, 4.59 and 2.34% Micro-F1 Score improvement in Immunotherapy, Virology and Neurology, respectively. Extensive experiments demonstrate that TAN can model complex spatiotemporal dependencies of term-pairs for explicitly capturing the temporal evolution of relation, significantly outperforming existing state-of-the-art methods. CONCLUSION: We proposed a novel TAN to learn spatiotemporal embeddings based on pure attention mechanisms for HG. TAN learns the evolution of relationships by modeling both the continuity and difference of temporal term-pair embeddings. The important spatiotemporal dependencies of term-pair relations are extracted based solely on attention mechanism for generating hypotheses.


Asunto(s)
Inmunoterapia , Neurología , Aprendizaje , Redes Neurales de la Computación , PubMed
5.
Acta Neurochir (Wien) ; 166(1): 79, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38349572

RESUMEN

As a primitive driving force for biological reproduction, sexual behavior (and its associated mechanisms) is extremely complex, and orgasm plays an essential role. The limbic system plays a very important role in regulating human sexual behavior. However, it is not clear which components of the limbic system are related to orgasm sensation. We studied a rare case of spontaneous orgasmic aura in a male patient with temporal lobe epilepsy. Stereoelectroencephalography (SEEG) revealed that the right amygdala was the origin of orgasmic aura. Surgical removal of the medial temporal lobe, including the right amygdala, completely eliminated the patient's seizures. This study demonstrates the critical role of the amygdala in human male orgasm.


Asunto(s)
Epilepsia del Lóbulo Temporal , Masculino , Humanos , Femenino , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Orgasmo , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/cirugía , Convulsiones , Lóbulo Temporal
6.
BMC Genomics ; 24(1): 21, 2023 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-36641451

RESUMEN

BACKGROUND: Salt-alkali stress represents one of the most stressful events with deleterious consequences for plant growth and crop productivity. Despite studies focusing on the effects of salt-alkali stress on morphology and physiology, its molecular mechanisms remain unclear. Here, we employed RNA-sequencing (RNA-seq) to understand how Na2CO3 stress inhibits rice seedling growth. RESULTS: Na2CO3 stress significantly inhibited the growth of rice seedlings. Through RNA-seq, many differentially expressed genes (DEGs) were shown to be potentially involved in the rice seedling response to salt-alkali stress. After 1-day and 5-day treatments, RNA-seq identified 1780 and 2315 DEGs in the Na2CO3-treated versus -untreated rice seedling shoots, respectively. According to the gene ontology enrichment and the Kyoto Encylopedia of Genes and Genomes annotation of DEGs, the growth-inhibition processes associated with salt-alkali stress involve a myriad of molecular events, including biosynthesis and metabolism, enzyme activity, and binding, etc. CONCLUSION: Collectively, the transcriptome analyses in the present work revealed several potential key regulators of plant response to salt-alkali stress, and might pave a way to improve salt-alkali stress tolerance in rice.


Asunto(s)
Oryza , Plantones , Oryza/metabolismo , Álcalis/farmacología , Estrés Salino/genética , Perfilación de la Expresión Génica , Análisis de Secuencia de ARN , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Transcriptoma
7.
Psychol Med ; 53(15): 7242-7254, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37016788

RESUMEN

BACKGROUND: Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. METHOD: Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. RESULTS: The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = -3.161, p = 0.007] and 16 (LS mean difference = -3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. CONCLUSIONS: Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.


Asunto(s)
Trastorno Depresivo Mayor , Psicoterapia Psicodinámica , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Antidepresivos/uso terapéutico , Resultado del Tratamiento , Terapia Combinada
8.
Epilepsy Behav ; 138: 108981, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36470058

RESUMEN

PURPOSE: To explore the localization value of drug-resistant temporal lobe epilepsy (TLE) aura for preoperative evaluation, based on stereoelectroencephalography (SEEG), and its prognostic value on the surgical outcome. METHODS: The data of patients with drug-resistant TLE who had SEEG electrodes implanted during preoperative evaluation at the First Affiliated Hospital of the University of Science and Technology of China (Hefei, China) were retrospectively analyzed. The patients were divided into aura-positive and aura-negative groups according to the presence of aura in seizures. To explore the clinical features of aura, we evaluated the localizing and prognostic values of aura for the outcome of anterior temporal lobectomy based on SEEG. RESULTS: Among forty patients, twenty-seven patients were in the aura-positive group and ten (25.0%) patients had multiple auras. The most common TLE aura was abdominal aura [thirteen (34.2%) patients]. The postoperative seizure frequency was significantly reduced in the preoperative aura-positive patients compared to the preoperative aura-negative patients (P = 0.011). Patients with abdominal (P = 0.029) and single (P = 0.036) auras had better surgical prognoses than aura-negative patients. In the preoperative evaluation, aura-positive patients had a better surgical outcome if the laterality of positron emission tomography-computed tomography (PET-CT) hypometabolism was concordant with the epileptogenic focus identified with SEEG (P = 0.031). A good postoperative epileptic outcome in aura-positive patients was observed among those with hippocampal sclerotic medial temporal lobe epilepsy (P = 0.025). CONCLUSION: Epileptic aura is valuable for the localization of the epileptogenic focus. Abdominal aura and single aura were good predictors of better surgical outcomes. Among patients with a preoperative diagnosis of hippocampal sclerosis or with laterality of PET-CT hypometabolism concordant with the epileptogenic focus identified using SEEG, those with aura are likely to benefit from surgery.


Asunto(s)
Epilepsia Refractaria , Epilepsias Parciales , Epilepsia del Lóbulo Temporal , Epilepsia , Humanos , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Epilepsia/cirugía , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Convulsiones , Electroencefalografía , Resultado del Tratamiento , Imagen por Resonancia Magnética
9.
Ecotoxicol Environ Saf ; 251: 114515, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36628876

RESUMEN

Rice seedlings were exposed to two CO2 concentrations (400 ± 20 and 800 ± 20 µmol mol-1) and three PbNO3 concentrations (0, 50 and 100 µmol L-1) for 10 days to explore the regulatory mechanisms of elevated CO2 for Pb stress resistance. Electrical conductivity, MDA content, SOD, POD, CAT activities and metabolomics changes were studied. Results showed that: Pb stress damaged cell membrane system, electrical conductivity and MDA content increased 49.34 % and 73.27 %, respectively, and some antioxidant enzymes activities increased. Sugar, polyol, amino acid metabolism and fatty acid ß-oxidation were all enhanced to improve osmotic adjustments, maintain cell membrane stability, supply energy, nitrogen assimilates and antioxidant capacity; Under composite treatments, cell membrane damage was reduced, activities of protective enzymes increased compared with only Pb stress, POD activity increased the most (49.14 %) under severe Pb composite treatment. High CO2 caused the enhance of cells antioxidant capacity, TCA cycle intermediate products contents and fatty acid desaturation under mild Pb stress. Many sugars, polyols and amino acids contents were increased as osmotic regulatory substances by high CO2 under severe Pb stress; Secondary metabolites played an important role under Pb stress and composite treatments. The object of this study is to provide a possible molecular mechanism of rice response to Pb stress under high CO2 in the future.


Asunto(s)
Oryza , Plantones , Plantones/metabolismo , Antioxidantes/metabolismo , Oryza/metabolismo , Dióxido de Carbono/metabolismo , Plomo/metabolismo , Ácidos Grasos/metabolismo
10.
Ecotoxicol Environ Saf ; 254: 114740, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36907094

RESUMEN

This study investigated the growth, SPAD value, chlorophyll fluorescence and transcriptome response of endophyte uninoculated and inoculated rice seedlings under Pb stress after treatment of 1 d and 5 d. Inoculation of endophytes significantly improved the plant height, SPAD value, Fv/F0, Fv/Fm and PIABS by 1.29, 1.73, 0.16, 1.25 and 1.90 times on the 1 d, by 1.07, 2.45, 0.11, 1.59 and 7.90 times on the 5 d, respectively, however, decreased the root length by 1.11 and 1.65 times on the 1 d and 5 d, respectively under Pb stress. Analysis of rice seedlings leaves by RNA-seq, there were 574 down-regulated and 918 up-regulated genes after treatment of 1 d, 205 down-regulated and 127 up-regulated genes after treatment of 5 d, of which 20 genes (11 up-regulated and 9 down-regulated) exhibited the same changing pattern after treatment of 1 d and 5 d. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to annotate these DEGs, and it was found that many of DEGs involved in photosynthesis, oxidative detoxification, hormone synthesis and signal transduction, protein phosphorylation/kinase and transcription factors. These findings provide new insights into the molecular mechanism of interaction between endophyte and plants under heavy metal stress, and contribute to agricultural production in limited environments.


Asunto(s)
Oryza , Transcriptoma , Plantones/genética , Plantones/metabolismo , Endófitos/genética , Endófitos/metabolismo , Perfilación de la Expresión Génica , Oryza/metabolismo , Plomo/toxicidad , Plomo/metabolismo , Regulación de la Expresión Génica de las Plantas
11.
Health Promot Int ; 38(5)2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37748868

RESUMEN

Health literacy may constitute a modifiable determinant of smoking behavior and intention to quit. Little is known about the extent to which health literacy affects smoking or quitting smoking. We assessed the nationally representative cross-sectional datasets from the China Health Literacy Surveillance (CHLS) initiated in 2018. Using polytomous logistic regression models, the study investigated the association of health literacy with smoking behavior and the intention to quit smoking among men aged 15-69 in China. After confounding factors were controlled, compared with having below basic health literacy, having adequate health literacy appeared to be an independent protective factor from current smoking [current smoking vs never smoking: adjusted odds ratio [OR], 0.88; 95% confidence interval (CI), 0.81-0.96; p = 0.003; current smoking vs former smoking: adjusted OR, 0.77; 95% CI, 0.64-0.92; p = 0.003], while having intermediate health literacy was associated with current smoking vs never smoking (adjusted OR, 1.09; 95% CI, 1.02-1.17; p = 0.011) or former smoking vs never smoking (adjusted OR, 1.22; 95% CI, 1.06-1.40; p = 0.005). And having adequate health literacy was associated with intending to quit among current smokers (adjusted OR, 1.25; 95% CI, 1.10-1.42; p < 0.001). Findings provide evidence that health literacy may serve as a critical and independent protective factor for reducing poor smoking behavior or enhancing cessation intention among men. Efforts should focus on developing and evaluating intervention to control tobacco use among men with low health literacy level.


Asunto(s)
Alfabetización en Salud , Fumar Tabaco , Humanos , Masculino , Estudios Transversales , Pueblos del Este de Asia , Alfabetización en Salud/estadística & datos numéricos , Fumar/epidemiología , Fumar Tabaco/epidemiología , Conductas de Riesgo para la Salud , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Cese del Uso de Tabaco/estadística & datos numéricos
12.
Invest New Drugs ; 40(4): 690-699, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35404016

RESUMEN

The V-region immunoglobulin-containing suppressor of T cell activation (VISTA), a unique B7 family member, is an attractive immunotherapeutic target for cancer, autoimmune and inflammatory diseases. In 2016, a patent demonstrated V-Set and Immunoglobulin domain containing 8 (VSIG-8) was the putative VISTA receptor. Antagonistic or agonistic agents can conceivably modulate VISTA and its interacting partners, which will greatly benefit the treatment of many diseases. The interaction of VISTA and VSIG-8 were measured by Enzyme-linked Immuno Sorbent Assay (ELISA), Microscale Thermophoresis (MST) and coimmunoprecipitation (Co-IP) experiments. The bioactivity of VSIG-8 inhibitor L557-0155 was evaluated in vitro and in vivo. Kd value of human VISTA binding to human VSIG-8 was 1.58 ± 0.44 µM by MST. When the related amino acid binding site of VISTA was mutated to alanine, the interaction between VISTA and VSIG-8 disappeared. VSIG-8 protein induced an decrease in the level of IL-2 in VISTA-overexpressing cells but a increase in VISTA-/- cells. Furthermore, VSIG-8 inhibitor L557-0155 promoted cytokine production and cell proliferation in PBMCs and suppressed melanoma growth. VSIG-8/VISTA coinhibitory pathway may provide a novel strategy for the treatment of human cancers, and VSIG-8 blockade may increase antitumor immunity. This study was the first time to report that VSIG-8 interacts with VISTA, and inhibited T cell function.


Asunto(s)
Antígenos B7 , Neoplasias , Proliferación Celular , Humanos , Activación de Linfocitos , Linfocitos T
13.
Mol Pharm ; 19(7): 2607-2619, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35485954

RESUMEN

Chlorin e6-C-15-ethyl ester (LS-HB), a newly identified photosensitizer, was isolated from chlorin e6. The mechanism of tumor cell death induced by photodynamic therapy with LS-HB (LS-HB-PDT) is still unknown. Here, we investigated the photophysical properties of LS-HB, evaluated the antitumor effect on melanoma in vitro and in vivo, and explored its possible mechanisms. LS-HB not only has an optimal spectral band of red wavelength (660 nm) for photosensitization but also has favorable photostability. More importantly, LS-HB-PDT elicited a potent dose-dependent phototoxic effect in vitro. We discovered that LS-HB located in the mitochondria of B16F10 cells was able to generate excess reactive oxygen species, which subsequently resulted in mitochondrial membrane potential loss and induced apoptosis via caspase-9 and caspase-3 pathways. Moreover, PDT with LS-HB markedly inhibited the growth of melanoma in vivo. Therefore, LS-HB is expected to be an effective potential photosensitizer in antitumor therapy.


Asunto(s)
Melanoma , Fotoquimioterapia , Porfirinas , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Melanoma/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/farmacología , Porfirinas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo
14.
Mol Pharm ; 19(5): 1356-1367, 2022 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-35420039

RESUMEN

Selectively inducing tumor thrombosis and subsequent necrosis is a novel and promising antitumor strategy. We have previously designed a targeting procoagulant protein, called tTF-EG3287, which is a fusion of a truncated tissue factor (tTF) with EG3287, a short peptide against the neuropilin-1 (NRP1) binding site of vascular endothelial growth factor-A 165 (VEGF-A 165). However, off-target effects and high-dose requirements limit the further use of tTF-EG3287 in antitumor therapy. Therefore, we encapsulated tTF-EG3287 into poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (PEOz-DSPE)-modified liposomes to construct pH-responsive liposomes as a novel vascular embolization agent, called tTF-EG3287@Liposomes. The liposomes had an average particle size of about 100 nm and showed considerable drug-loading capacity, encapsulation efficiency, and biocompatibility. Under the stimulation of acidic microenvironments (pH 6.5), the lipid membrane of tTF-EG3287@Liposomes collapsed, and the cumulative drug release rate within 72 h was 83 ± 1.26%. When administered to a mouse model of hepatocellular carcinoma (HCC), tTF-EG3287@Liposomes showed prolonged retention and enhanced accumulation in the tumor as well as a superior antitumor effec, compared with tTF-EG3287. This study demonstrates the potential of tTF-EG3287@Liposomes as a novel embolic agent for solid tumors and provides a new strategy for tumor-targeted infarction therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Concentración de Iones de Hidrógeno , Liposomas/química , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Tromboplastina , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular
15.
Horm Metab Res ; 54(9): 633-640, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35981547

RESUMEN

Preeclampsia (PE) may pose significant adverse effects on pregnant women. Dysregulation of angiogenesis, trophoblast invasion, and proliferation are known to be associated with PE development and progression. Fms related tyrosine kinase 1 (FLT1), an anti-angiogenic factor, is consistently upregulated in PE patients. Recent papers highlight that aberrant miR-30a-3p expression contributes to PE development. More effects are needed to assess the biological function of placental miR-30a-3p in PE. The soluble FLT1 (sFLT1) and FLT1 levels were tested by ELISA assay and Western blotting assay. mRNA levels were measured by RT-qPCR assay. Colony formation and MTT assays were applied to assess the effect of miR-30a-3p on trophoblast cell proliferation. The serum sFLT1 and placental FLT1 levels were substantially high in patients with PE. Using miRNA microarray assay, we identified miR-30a-3p upregulation in PE patients' placenta tissues. We further confirmed that miR-30a-3p binds to the 3'-UTR of FLT1 gene and positively regulate its expression. Forcing miR-30a-3p expression inhibited trophoblast cell proliferation and vice versa. In conclusion, persistent high levels of FLT1 and miR-30a-3p may pose adverse effects on angiogenesis and trophoblast proliferation in placenta of PE patients. Therefore, targeting FLT1 and miR-30a-3p may serve as ideal strategies for managing patients with PE.


Asunto(s)
MicroARNs , Preeclampsia , Trofoblastos/citología , Regiones no Traducidas 3'/genética , Movimiento Celular , Proliferación Celular , Femenino , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Placenta/metabolismo , Preeclampsia/genética , Preeclampsia/metabolismo , Embarazo , Trofoblastos/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
16.
Mol Biol Rep ; 49(10): 9613-9622, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36040546

RESUMEN

BACKGROUND: Biotechnologists seeking to develop marker-free transgenic plants have established co-transformation methods. For co-transformation using mixed Agrobacterium strains, the mix ratio of Agrobacterium strains and selection scheme may influence co-transformation frequency. This study used fluorescent GFP and RFP markers to compose different selection schemes for observation of the selective dynamics of transformed rice cells and to investigate the factors affecting co-transformation efficiency. METHODS AND RESULTS: We utilized GFP and RFP markers in co-transformation and tested the combinations of an antibiotic-selectable vector (pGFP-HPT) and a single RFP vector (pRFP) and of two antibiotic-selectable vectors (pGFP-HPT and pRFP-HPT) in rice. The pGFP-HPT/pRFP combination resulted in 70.9% to 81.2% of co-transformation frequencies while lower frequencies (56.6% on average) were obtained with the pGFP-HPT/pRFP-HPT combination. Based on GFP/RFP segregation patterns, 55% of the pGFP-HPT/pRFP co-transformants contained unlinked T-DNAs and segregated single RFP progeny, which simulated the selection process of marker-free transgenic plants that carry an actual gene of interest. Transgene expression levels in the rice lines varied as revealed by RT-PCR, and tandem-linked T-DNAs were detected in co-transformants, suggesting that transgene expression might be affected by duplicated T-DNA structures. CONCLUSION: Co-transformation via mixed Agrobacterium strains is feasible, and approximately 55% of the pGFP-HPT/pRFP co-transformants contained unlinked T-DNAs and segregated single RFP progeny. The pGFP-HPT/pRFP and the pGFP-HPT/pRFP-HPT vector combinations showed distinctive selective dynamics of transformed rice cells, suggesting that co-transformation efficiency depends on both vector system and selection scheme.


Asunto(s)
Oryza , Agrobacterium/genética , Antibacterianos , ADN Bacteriano/genética , Vectores Genéticos/genética , Proteínas Fluorescentes Verdes/genética , Oryza/genética , Oryza/microbiología , Plantas Modificadas Genéticamente/genética , Transformación Genética
17.
Macromol Rapid Commun ; 43(2): e2100286, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34463397

RESUMEN

Microporous membrane with a hydrophobic surface, high porosity, and narrow pore size distribution is the ideal membrane distillation (MD) membrane. The electrospun membranes for MD are a new type and effective way to seawater desalination. Herein, a novel polyvinylidene fluoride (PVDF)/tetrabutylammonium chloride (TBAC) electrospun nanofiber membrane (ENMs) fabricated apply to for direct contact membrane distillation (DCMD). Combine with the spinning condition, the characteristic and content of TBAC significant effect on the multimorphology structure of nanofiber. Therefore, the porous structure and morphology of PVDF/TBAC ENMs can be well-designed by optimizing relative humidity and TBAC concentration in spinning process, three different structure nanofiber membranes are obtained. Lab-scale setup is used to test membrane separation performance. The result indicates that the ultrafine ENMs with 0.025 mol L-1 TBAC presented a steady water flux of about 20.6 L m-2 h-1 and a high-efficiency salt rejection rate of over 99%. PVDF/TBAC ENMs are expected to provide a solution for development of efficient water treatment membrane.


Asunto(s)
Destilación , Nanofibras , Polímeros de Fluorocarbono , Membranas Artificiales , Polivinilos , Compuestos de Amonio Cuaternario
18.
Clin Immunol ; 223: 108650, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33316373

RESUMEN

The triggering receptor expressed on myeloid cells-1 (TREM-1) signal is related to the continuous amplification of inflammatory pathway. However, it is not clear whether and how HBV can regulated the expression of TREM-1 on monocyte participated in the progression of liver disease. Here, we showed that the expression of TREM-1 on monocyte subsets were increased significantly in HBV related liver cirrhosis group compared with chronic infected group and healthy control group. HBsAg and HBeAg could up-regulated TREM-1 on monocyte by NF-KB pathway, and at least last for 72 h. Increased TREM-1 on monocyte might associated with high level of inflammatory cytokine (TNF-a, IL-1ß and IL-6) and the activation of LX-2 cells. Bioinformatics analysis showed that the high expression of TREM-1 was related to the poor prognosis of hepatocellular carcinoma (HCC). The level of TREM-1 might help to predict the progression of HBV infected liver disease and treat target to prevent fibrosis progression.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Virus de la Hepatitis B/fisiología , Hepatitis B/inmunología , Neoplasias Hepáticas/diagnóstico , Monocitos/inmunología , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/mortalidad , Células Cultivadas , Biología Computacional , Citocinas/metabolismo , Progresión de la Enfermedad , Antígenos del Núcleo de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Neoplasias Hepáticas/mortalidad , FN-kappa B/metabolismo , Pronóstico , Transducción de Señal , Análisis de Supervivencia , Receptor Activador Expresado en Células Mieloides 1/genética , Regulación hacia Arriba
19.
Biochem Cell Biol ; 99(6): 735-740, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34734756

RESUMEN

Preeclampsia is a severe pregnancy complication characterized by hypertension and may cause maternal morbidity and mortality. A better understanding of the essential genes involved in preeclampsia pathophysiology is urgently needed. This study investigated the function and molecular mechanisms of pumilio RNA binding family member 1 (PUM1) in extravillous trophoblast cells (EVTs). The interaction between protein and mRNA was verified by RNA pull-down assays, RNA immunoprecipitation assays, and luciferase reporter assays. The mRNA and protein levels of the genes involved were determined by RT-qPCR and western blot assays, respectively. Our results demonstrated that PUM1 could bind to the 3'-untranslated region of low-density lipoprotein receptor-related protein 6 (LRP6) mRNA, resulting in reduced expression of LRP6 mRNA and protein. Repression of PUM1 resulted in enhanced colony formation, cell proliferation, migration, and invasion of EVTs. The PUM1-depletion-mediated promotion effects on EVTs could be abrogated by LRP6 knockdown. PUM1 regulates the growth and mobility of EVTs by modulating LRP6 expression. Developing strategies to balance PUM1 and LRP6 levels may be beneficial for the management of preeclampsia patients.


Asunto(s)
Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad , Trofoblastos , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Embarazo , Proteínas de Unión al ARN , Trofoblastos/metabolismo
20.
Plant Cell Environ ; 44(3): 982-994, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33190219

RESUMEN

Long non-coding RNA (lncRNA) are important regulators of many biological processes in plants, including defence against pathogens; whether lncRNAs mediate defence against herbivore attack is yet to be explored. With wild tobacco, Nicotiana attenuata, and its well-characterized interactions with herbivores, we identified a total of 1,290 significantly up- or down-regulated lncRNAs in response to a precise herbivore elicitation treatment. Of these, long intergenic non-coding RNAs (lincRNAs) were the most abundant. Based on their expression patterns, these up-regulated lincRNAs were classified as early (<1 hr) or late (>3 hr) responders. The early responding lincRNAs had accumulation patterns that tracked the herbivore-elicited burst of bioactive jasmonates (JAs) and the expression of regulator genes in JA signalling which regulate plant defences against herbivores. Silencing two of these early responders in N. attenuata (JAL1 and JAL3) significantly attenuated the accumulation of JAs, JA-mediated defensives and the plant's resistance to M. sexta attack, suggesting roles in regulating JA-mediated plant defence. By lincRNA sequencing of JA-deficient lines, many late responder lincRNAs were found to be transcriptionally regulated by JA signalling. This study uncovers a new role of lncRNAs in JA-mediated herbivore resistance.


Asunto(s)
Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Defensa de la Planta contra la Herbivoria , Reguladores del Crecimiento de las Plantas/metabolismo , ARN Largo no Codificante/metabolismo , ARN de Planta/metabolismo , Animales , Regulación de la Expresión Génica de las Plantas/genética , Manduca , Defensa de la Planta contra la Herbivoria/genética , Defensa de la Planta contra la Herbivoria/fisiología , Reguladores del Crecimiento de las Plantas/fisiología , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , ARN de Planta/genética , ARN de Planta/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/fisiología
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