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1.
Development ; 151(20)2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38646855

RESUMO

Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.


Assuntos
Metamorfose Biológica , Ovário , Reprodução , Animais , Feminino , Reprodução/genética , Metamorfose Biológica/genética , Ovário/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Vitelogênese/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética
2.
Opt Lett ; 49(17): 5011-5014, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39208021

RESUMO

The fluorescence collection from single atoms and emitters has been extensively utilized in quantum information and quantum optics research. Here, we investigated the collection efficiency of an objective lens by drawing an analogy between the free-space beam (FSB) and a waveguide mode. We explored how efficiency is influenced by their thermal motion within a dipole trap. Furthermore, we introduce an effective energy fraction ratio to quantify potential imperfections in the focusing of the objective lens. Our results provide valuable insights for optimizing the fluorescence collection in single-atom experiments and highlight the importance of considering realistic experimental conditions when estimating achievable efficiencies.

3.
Angew Chem Int Ed Engl ; : e202406386, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052016

RESUMO

An unprecedented chemodivergent strategy for parallel kinetic resolution (PKR) is disclosed through which two planar chiral products bearing different structures were simultaneously afforded with opposite stereoselectivities. Two achiral esters are activated by one single chiral N-heterocyclic carbene (NHC) catalyst to react with the different enantiomers of the racemic imine substrate in a parallel fashion. Two products bearing distinct structures and opposite stereoselectivities are respectively afforded from the same reaction system in good to excellent yields, enantio- and diastereoselectivities. Control experiments and kinetic studies are carried out to probe the kinetic and dynamic properties during the reaction progress. The planar chiral pyridine and lactam products show interesting applications in both asymmetric synthesis and pesticide development.

4.
Plant J ; 112(1): 135-150, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35942607

RESUMO

Red leaves are common in trees but rare in cereal crops. Red leaves can be used as raw materials for anthocyanin extraction and may have some adaptive significance for plants. In this study, we discovered a red leaf phenotype in the F1 hybrids derived from a cross between two sorghum accessions with green leaf. Histological analysis of red leaves and green leaves showed that red compounds accumulate in mesophyll cells and gradually spreads to the entire leaf blade. In addition, we found chloroplasts degraded more quickly in red leaves than in green leaves based on transmission electron microscopy. Metabolic analysis revealed that flavonoids including six anthocyanins are more abundant in red leaves. Moreover, transcriptome analysis revealed that expression of flavonoid biosynthesis genes was upregulated in red leaves. These observations indicate that flavonoids and anthocyanins in particular, are ideal candidates for the red compounds accumulating in red leaves. Segregation analysis of the red leaf phenotype suggested a genetic architecture consisting of three dominant genes, one (RL1 for RED LEAF1) of which we mapped to a 55-kb region on chromosome 7 containing seven genes. Sequencing, reverse transcription-polymerase chain reaction, and transcriptome analysis suggested Sobic.007G214300, encoding a wall-associated kinase, as the most likely candidate for RL1. Fine mapping the red leaf gene and identifying the metabolites that cause red leaf in sorghum provide us with a better understanding of the red leaf phenotype in the natural population of sorghum.


Assuntos
Antocianinas , Sorghum , Antocianinas/metabolismo , Grão Comestível/metabolismo , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Pigmentação/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sorghum/genética , Sorghum/metabolismo , Transcriptoma
5.
J Neurosci Res ; 101(8): 1205-1223, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37001980

RESUMO

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have explored abnormal regional spontaneous brain activity in migraine. However, these results are inconsistent. To identify the consistent regions with abnormal neural activity, we meta-analyzed these studies. We gathered whole-brain rs-fMRI studies measuring differences in the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), or regional homogeneity (ReHo) methods. Then, we performed a voxel-wise meta-analysis to identify consistent abnormal neural activity in migraine by anisotropic effect size seed-based d mapping (AES-SDM). To confirm the AES-SDM meta-analysis results, we conducted two meta-analyses: activation likelihood estimation (ALE) and multi-level kernel density analysis (MKDA). We found that migraine showed increased regional neural activities in the bilateral postcentral gyrus (PoCG), left hippocampus (HIP.L), right pons, left superior frontal gyrus (SFG.L), triangular part of right inferior frontal gyrus (IFGtriang.R), right middle frontal gyrus (MFG.R), and left precentral gyrus (PreCG.L) and decreased regional intrinsic brain activities were exhibited in the right angular gyrus (ANG.R), left superior occipital gyrus (SOG.L), right lingual gyrus (LING.R). Moreover, the meta-analysis of ALE further validated the abnormal neural activities in the PoCG, right pons, ANG.R, and HIP. Meta-regression demonstrated that headache intensity was positively associated with the abnormal activities in the HIP.L, ANG.R, and LING.R. These findings suggest that migraine is associated with abnormal spontaneous brain activities of some pain-related regions, which may contribute to a deeper understanding of the neural mechanism of migraine.


Assuntos
Transtornos de Enxaqueca , Córtex Motor , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Transtornos de Enxaqueca/diagnóstico por imagem , Lobo Parietal , Imageamento por Ressonância Magnética/métodos
6.
J Transl Med ; 21(1): 293, 2023 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-37121999

RESUMO

BACKGROUND: Acute lung injury (ALI) is a common and serious complication of sepsis with high mortality. Ferroptosis, categorized as programmed cell death, contributes to the development of lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is an endogenous lipid mediator that exerts protective effects against multiorgan injury. However, the role of PCTR1 in the ferroptosis of sepsis-related ALI remains unknown. METHODS: A pulmonary epithelial cell line and a mouse model of ALI stimulated with lipopolysaccharide (LPS) were established in vitro and in vivo. Ferroptosis biomarkers, including ferrous (Fe2+), glutathione (GSH), malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE), were assessed by relevant assay kits. Glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) protein levels were determined by western blotting. Lipid peroxides were examined by fluorescence microscopy and flow cytometry. Cell viability was determined by a CCK-8 assay kit. The ultrastructure of mitochondria was observed with transmission electron microscopy. Morphology and inflammatory cytokine levels predicted the severity of lung injury. Afterward, related inhibitors were used to explore the potential mechanism by which PCTR1 regulates ferroptosis. RESULTS: PCTR1 treatment protected mice from LPS-induced lung injury, which was consistent with the effect of the ferroptosis inhibitor ferrostatin-1. PCTR1 treatment decreased Fe2+, PTGS2 and lipid reactive oxygen species (ROS) contents, increased GSH and GPX4 levels and ameliorated mitochondrial ultrastructural injury. Administration of LPS or the ferroptosis agonist RSL3 resulted in reduced cell viability, which was rescued by PCTR1. Mechanistically, inhibition of the PCTR1 receptor lipoxin A4 (ALX), protein kinase A (PKA) and transcription factor cAMP-response element binding protein (CREB) partly decreased PCTR1 upregulated GPX4 expression and a CREB inhibitor blocked the effects ofPCTR1 on ferroptosis inhibition and lung protection. CONCLUSION: This study suggests that PCTR1 suppresses LPS-induced ferroptosis via the ALX/PKA/CREB signaling pathway, which may offer promising therapeutic prospects in sepsis-related ALI.


Assuntos
Lesão Pulmonar Aguda , Ferroptose , Sepse , Animais , Camundongos , Antígenos CD59 , Ciclo-Oxigenase 2 , Lipopolissacarídeos/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Sepse/complicações , Fator 2 Ativador da Transcrição
7.
Mol Reprod Dev ; 90(6): 397-405, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37243981

RESUMO

Herein we aimed at exploring mitochondrial energy metabolism status in patients with repeated implantation failure (RIF) and whether key regulatory factor PGC-1α of energy metabolism is involved in the decidualization of endometrial stromal cells. Mitochondrial oxidative phosphorylation level and ATP synthesis were compared in primary endometrial stromal cells from RIF and control group. At the same time, as one of key transcription regulators of mitochondrial energy metabolism, the expression level and acetylation level of PGC-1α were compared with two groups. Then, we downregulated the acetylation levels of PGC-1α, and the expression of decidual markers (PRL and IGFBP1) was observed further. Mitochondrial energy metabolism, showing by mitochondrial oxidative phosphorylation level and ATP synthesis, was decreased in the endometrial stromal cells of the RIF group (RIF-hEnSCs). Meanwhile, PGC-1α acetylation levels were significantly higher in RIF-hEnSCs. When we reduced the acetylation levels of PGC-1α in RIF-hEnSCs, the basal O2 consumption rate and maximal respiration were increased, and also the PRL and IGFBP1. Overall, our data indicated that the endometrial stromal cells of the RIF patients had low level of mitochondrial energy metabolism. Reducing acetylation level of key energy metabolism regulator PGC-1α can increase the decidualization level of RIF-hEnSCs. These findings may inspire new ideas about the treatment of RIF.


Assuntos
Mitocôndrias , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Acetilação , Mitocôndrias/metabolismo , Metabolismo Energético , Trifosfato de Adenosina/metabolismo
8.
BMC Cancer ; 23(1): 1220, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082377

RESUMO

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.


Assuntos
Neoplasias da Mama , Proteínas de Repetição de Anquirina Projetadas , Humanos , Camundongos , Animais , Feminino , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Técnicas de Transferência de Genes , Terapia Genética/métodos , Vetores Genéticos/genética , Dependovirus/genética , Dependovirus/metabolismo
9.
J Nanobiotechnology ; 20(1): 20, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991596

RESUMO

BACKGROUND: Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment. RESULTS: In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner. CONCLUSIONS: This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.


Assuntos
Cobre , Corantes Fluorescentes , Nanopartículas , Fotoquimioterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio
10.
J Ultrasound Med ; 41(1): 41-50, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33656184

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the diagnostic efficacy of transvaginal two-dimensional fundamental sonosalpingography (2D-FS) combined with saline infusion pelvic sonosalpingography (SIPS) for assessing fimbrial part's morphology and function of the fallopian tubes. METHODS: One hundred and sixty-nine cases underwent 2D-FS combined with SIPS. Among them, 18 cases received laparoscopy and dye test (LDT) within 3 months after the examination and the results were regarded as reference standard. RESULTS: Excluding proximal or middle segment obstructed tubes, the remaining fimbrial parts' display rate by using 2D-FS combined with SIPS was 75.1%. According to the ultrasonic appearance, the fimbrial parts were classified into 4 types: normal, abnormal, suspected abnormal, and unclassifiable. Normal fimbrial parts accounted for 73.8% when the tubes were patent; abnormal fimbrial parts accounted for 74.1% when the tubes were partial obstructed; all became abnormal when the tubes were distal complete obstructed. The fimbrial parts which had been classified by 2D-FS combined with SIPS were compared with LDT further. This combination's accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Youden's index (YI) were 86.4, 87.5, 85.7, 77.8, 92.3, and 0.73%, respectively. The result of consistency analysis showed the combination was essentially consistent with LDT result (Kappa = 0.713). CONCLUSION: 2D-FS combined with SIPS can be a preferred method for assessment of the fimbrial part's morphology and function, with its advantages of non-invasive, intuition, and accuracy. This combination could provide an objective imaging basis for choosing clinical treatment strategies and predicting prognosis.


Assuntos
Tubas Uterinas , Laparoscopia , Tubas Uterinas/diagnóstico por imagem , Feminino , Humanos , Histerossalpingografia , Pelve
11.
Ren Fail ; 44(1): 1769-1779, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36263441

RESUMO

Renal injury is a fatal complication in critically ill patients with sepsis. As an ultrashort-acting synthetic opioid derivative, remifentanil has been reported to mitigate renal injury and sepsis. Nevertheless, whether remifentanil also suppresses sepsis-triggered renal injury is uncertain. The aim of this study was to investigate the effect of remifentanil on endoplasmic reticulum stress (ERS) and inflammatory response in an in vitro lipopolysaccharide (LPS)-stimulated renal tubular epithelial cell (HK-2) model and its mechanism. The viability of HK-2 cells with the absence or presence of LPS treatment was surveyed by cell counting kit-8 assay. Under the condition of LPS treatment, apoptosis was appraised by TUNEL assay and western blot. Levels of inflammatory factors were estimated though corresponding kits. Western blot tested the expression of toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) signaling-associated proteins. Also, the expression of ERS-related proteins was detected by western blot. Further, ERS inducer tunicamycin (TM) was added and the aforementioned experiments were conducted again. The results underlined the protective effects of remifentanil on LPS-evoked viability injury, inflammation, activation of TLR4/NF-κB signaling and ERS in HK-2 cells. Moreover, the impacts of remifentanil on the biological events of LPS-insulted HK-2 cells were all reversed by TM administration. To conclude, remifentanil might have a remarkable ameliorative effect on sepsis-induced renal injury, which implied the potential of remifentanil-based drug therapy in sepsis-induced renal injury.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Lipopolissacarídeos , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Remifentanil/efeitos adversos , Estresse do Retículo Endoplasmático , Tunicamicina/efeitos adversos , Analgésicos Opioides/farmacologia , Linhagem Celular , Sepse/complicações , Sepse/tratamento farmacológico , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Apoptose
12.
Opt Express ; 29(2): 2466-2477, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33726441

RESUMO

Coherent population trapping (CPT) resonance signals have promise in a wide range of applications involving precision sensing. Generally, the CPT phenomenon occurs in a three-level Λ system with a bichromatic phase-coherent light fields. We theoretically and experimentally studied an Rb vapor-cell-based atomic system involving bichromatic CPT optical fields and an external microwave (MW) field simultaneously. In such a mixing scheme, the coherence of the ground states could be controlled either by the Rabi frequency of the microwave field or by the relative phase between the optical fields and the MW field. Moreover, we investigated the Rabi resonance in this mixing scheme. The Rabi frequency of the MW field can be measured SI (International System of Units)-traceably based on the Rabi resonance lineshape, and thus holds the potential to realize intensity stabilization of the optical field in this system. Simple theoretical models and numerical calculations are also presented to explain the experimental results. There is scope to use the proposed technique in future development of SI-traceable optical field strength standards.

13.
J Assist Reprod Genet ; 38(4): 809-824, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33447950

RESUMO

RESEARCH QUESTION: Granulosa cells (GCs) surrounding oocytes are crucial for follicular growth, oocyte development, ovulation, and luteinization under the dynamic co-stimulation of follicle stimulating hormone (FSH) and luteinizing hormone (LH). This study aimed to investigate the effect of LH levels on GCs in preovulatory follicles under gonadotropin releasing hormone antagonist-based ovarian stimulation. In vitro experiments were also conducted to study the direct effect of LH on GCs. METHODS: Twelve infertile women were divided into low (L), medium (M), and high (H) LH groups according to their serum LH levels during ovarian stimulation. RNA-sequencing (RNA-seq) was conducted to examine the transcriptome profiles of GCs obtained from the above patients during the oocyte retrieval. The activity of mitochondrial dehydrogenase was measured under the stimulation of recombinant LH (rLH) concentration gradient combined with recombinant FSH. The ultrastructures of subcellular organelles were observed. RESULTS: Bioinformatic analyses showed that compared with the M group, molecule and pathway changes in the L group and in the H group were similar. In cultured GCs, both insufficient and excessive rLH impaired the activity of mitochondrial dehydrogenase. With the medium rLH concentration, numerous cell connections and abundant mitochondria and liposomes were observed. Compared with the medium concentration, GCs showed smaller and rounder mitochondria, more autophagosomes, and massive organelles damages with excessive rLH, and swollen, circular, or forked mitochondria were observed with inadequate rLH. CONCLUSIONS: RNA-seq provided a novel spectrum of transcriptome characteristics of GCs potentially affected by serum LH levels during ovarian stimulation. In vitro, rLH could directly affect GCs at the subcellular level.


Assuntos
Infertilidade Feminina/tratamento farmacológico , Oócitos/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Transcriptoma/genética , Feminino , Fertilização in vitro , Hormônio Foliculoestimulante/farmacologia , Hormônio Liberador de Gonadotropina/farmacologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Hormônio Luteinizante/farmacologia , Recuperação de Oócitos , Oócitos/crescimento & desenvolvimento , Organelas/efeitos dos fármacos , Folículo Ovariano/patologia , Ovulação/efeitos dos fármacos , Indução da Ovulação , Transcriptoma/efeitos dos fármacos
14.
Pharm Biol ; 59(1): 1533-1539, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34726570

RESUMO

CONTEXT: Astragalus polysaccharin (APS), an extract of Astragalus propinquus Schischk, exerts antitumor effects in hepatocellular carcinoma (HCC). OBJECTIVE: This study investigated the mechanism of action of APS in HCC. MATERIALS AND METHODS: Tumour-associated macrophages (TAMs) were treated with APS (0, 8, 16 mg/mL) for 24 h. APS (16 mg/mL)-treated TAMs were co-cultured with MHCC97H/Huh7 cells for 24 h. Finally, BALB/c nude mice were divided into PBS, APS (50 mg/kg), APS (100 mg/kg), APS (200 mg/kg) groups: mice were inoculated with Huh7 cells to construct tumour xenograft model, followed by administration of APS (50, 100, 200 mg/kg) or PBS daily for 30 days. Cell proliferation, migration, invasion, tumour growth, macrophage markers and proportions were measured. RESULTS: APS 16 mg/mL treatment enhanced the expression of M1 macrophage markers (iNOS, IL-1ß and TNF-α) and M1 macrophage proportions, while reducing the expression of M2 macrophage markers (IL-10, Arg-1) and M2 macrophage proportions in TAMs. Moreover, the APS-mediated M1 phenotype of TAMs significantly repressed cell proliferation, migration and invasion of MHCC97H and Huh7 cells. Moreover, APS (50, 100, 200 mg/kg) enhanced M1 macrophage proportions and reduced M2 macrophage proportions in the tumour tissues, and thus inhibited tumour growth of HCC. DISCUSSION AND CONCLUSIONS: APS inhibits HCC-like phenotypes in a murine HCC model through repression of M2 polarization of TAMs. This work provides a novel theoretical basis for the application of APS in the clinical treatment of HCC.


Assuntos
Astragalus propinquus/química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fenótipo , Extratos Vegetais/administração & dosagem , Macrófagos Associados a Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Cell Physiol ; 235(3): 2792-2799, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31541462

RESUMO

C-Jun N-terminal kinase (JNK) is a pivotal MAPK (mitogen-activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK-IN-8 in ischemic stroke and the mechanisms underlying of JNK-IN-8 about neuroprotection are not well understood. In this work, male rats were treated with JNK-IN-8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot-fault test (FFT), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels were assessed. We found that JNK-IN-8-treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK-IN-8 also played anti-inflammatory roles as indicated through decreased activation of microglia and decreased IL-6, IL-1ß, and TNF-α expression. Furthermore, JNK-IN-8 suppressed the activation of JNK and nuclear factor-κB (NF-κB) signaling as indicated by the decreased level of phosphorylated-JNK and p65. All data demonstrate that JNK-IN-8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF-κB and is a promising agent for the prevention of ischemic brain injury.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Hipóxia-Isquemia Encefálica/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Lesões Encefálicas Traumáticas/patologia , Células Cultivadas , Hipóxia-Isquemia Encefálica/patologia , Inflamação/tratamento farmacológico , Interleucina-1beta/análise , Interleucina-6/análise , AVC Isquêmico/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Microglia/metabolismo , Artéria Cerebral Média/patologia , Neuroproteção/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Córtex Sensório-Motor/efeitos dos fármacos , Córtex Sensório-Motor/patologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/análise
16.
J Exp Bot ; 71(18): 5506-5520, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32497182

RESUMO

Biomass and grain yield are key agronomic traits in sorghum (Sorghum bicolor); however, the molecular mechanisms that regulate these traits are not well understood. Here, we characterized the biomass yield 1 (by1) mutant, which displays a dramatically altered phenotype that includes reduced plant height, narrow stems, erect and narrow leaves, and abnormal floral organs. Histological analysis suggested that these phenotypic defects are mainly caused by inhibited cell elongation and abnormal floral organ development. Map-based cloning revealed that BY1 encodes a 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) that catalyses the first step of the shikimate pathway. BY1 was localized in chloroplasts and was ubiquitously distributed in the organs examined, particularly in the roots, stems, leaves, and panicles, which was consistent with its role in biomass production and grain yield. Transcriptome analysis and metabolic profiling revealed that BY1 was involved in primary metabolism and that it affected the biosynthesis of various secondary metabolites, especially flavonoids. Taken together, these findings demonstrate that BY1 affects biomass and grain yield in sorghum by regulating primary and secondary metabolism via the shikimate pathway. Moreover, our results provide important insights into the relationship between plant development and metabolism.


Assuntos
Sorghum , Biomassa , Grão Comestível , Desenvolvimento Vegetal , Folhas de Planta , Sorghum/genética
17.
Neurobiol Learn Mem ; 169: 107155, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31904547

RESUMO

Diabetic rats display cognition impairments accompanied by activation of NF-κB signalling and increased Aß expression. Ghrelin has been suggested to improve cognition in diabetic rats. In this study, we investigated the role of ghrelin on cognition and NF-κB mediated Aß production in diabetic rats. A diabetic rat model was established with streptozotocin (STZ) injection, and diabetic rats were intracerebroventricularly administered with ghrelin or (D-lys3)-GHRP-6 (DG). Our results showed that diabetic rats had cognition impairment in the Morris water maze test, accompanied by the higher expression of Aß in the hippocampus. Western blot analysis showed that diabetic rats exhibited significantly decreased levels of GHSR-1a and protein phosphatase 1 (PP1) in the hippocampus and increased activation of the IKK/NF-κB/BACE1 pathway. Chronic ghrelin administration upregulated hippocampal PP1 expression, suppressed IKK/NF-κB/BACE1 mediated Aß production, and improved cognition in STZ-induced diabetic rats. These effects were reversed by DG. Then, primary rat hippocampal neurons were isolated and treated with high glucose, followed by Ghrelin and DG, PP1 or IKK. Similar to the in vivo results, high glucose suppressed the expression levels of GHSR-1a and PP1, activated the IKK/NF-κB/BACE1 pathway, increased Aß production. Ghrelin suppressed IKK/NF-κB/BACE1 induced Aß production. This improvement was reversed by DG and a PP1 antagonist and was enhanced by the IKK antagonist. Our findings indicated that chronic ghrelin administration can suppress IKK/NF-κB/BACE1 mediated Aß production in primary neurons with high glucose treatment and improve the cognition via PP1 upregulation in diabetic rats.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Cognição/fisiologia , Diabetes Mellitus Experimental/metabolismo , Grelina/metabolismo , Neurônios/metabolismo , Proteína Fosfatase 1/metabolismo , Transdução de Sinais , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Células Cultivadas , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/psicologia , Grelina/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Quinase I-kappa B/metabolismo , Masculino , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/administração & dosagem , Sinapses/efeitos dos fármacos , Sinapses/ultraestrutura , Regulação para Cima
18.
Intervirology ; 63(1-6): 10-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32772018

RESUMO

BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.


Assuntos
Infecções por Citomegalovirus/complicações , Neoplasias Gastrointestinais/etiologia , Idoso , Anticorpos Antivirais/sangue , Estudos Transversais , Citomegalovirus/genética , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , DNA Viral/análise , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
19.
BMC Bioinformatics ; 20(Suppl 22): 719, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888447

RESUMO

BACKGROUND: Subcellular localization prediction of protein is an important component of bioinformatics, which has great importance for drug design and other applications. A multitude of computational tools for proteins subcellular location have been developed in the recent decades, however, existing methods differ in the protein sequence representation techniques and classification algorithms adopted. RESULTS: In this paper, we firstly introduce two kinds of protein sequences encoding schemes: dipeptide information with space and Gapped k-mer information. Then, the Gapped k-mer calculation method which is based on quad-tree is also introduced. CONCLUSIONS: >From the prediction results, this method not only reduces the dimension, but also improves the prediction precision of protein subcellular localization.


Assuntos
Algoritmos , Biologia Computacional/métodos , Armazenamento e Recuperação da Informação/métodos , Proteínas/química , Frações Subcelulares/metabolismo , Sequência de Aminoácidos , Bases de Dados de Proteínas , Dipeptídeos/química , Máquina de Vetores de Suporte
20.
Plant Cell Physiol ; 60(4): 788-801, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590744

RESUMO

Plant mechanical strength contributes to lodging resistance and grain yield, making it an agronomically important trait in sorghum (Sorghum bicolor). In this study, we isolated the brittle culm 1 (bc1) mutant and identified SbBC1 through map-based cloning. SbBC1, a homolog of rice OsBC1 and Arabidopsis thaliana AtCOBL4, encodes a COBRA-like protein that exhibits typical structural features of a glycosylphosphatidylinositol-anchored protein. A single-nucleotide mutation in SbBC1 led to reduced mechanical strength, decreased cellulose content, and increased lignin content without obviously altering plant morphology. Transmission electron microscopy revealed reduced cell wall thickness in sclerenchyma cells of the bc1 mutant. SbBC1 is primarily expressed in developing sclerenchyma cells and vascular bundles in sorghum. RNA-seq analysis further suggested a possible mechanism by which SbBC1 mediates cellulose biosynthesis and cell wall remodeling. Our results demonstrate that SbBC1 participates in the biosynthesis of cellulose in the secondary cell wall and affects the mechanical strength of sorghum plants, providing additional genetic evidence for the roles of COBRA-like genes in cellulose biosynthesis in grasses.


Assuntos
Parede Celular/metabolismo , Celulose/metabolismo , Sorghum/metabolismo , Autoimunidade/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas Quinases Ativadas por Mitógeno/metabolismo
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