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Honeycomb sandwich structures have been widely used in the field of engineering owing to their outstanding mechanical properties. However, for a honeycomb sandwich structure with large spatial periodicity, there is a low-frequency sound insulation valley. Here, the sound transmission across locally resonant honeycomb sandwich meta-structures was investigated to overcome this sound-insulation valley. An analytical model was developed based on the space-harmonic approach and the low-frequency sound insulation valley was determined analytically and numerically. The results indicate that the resonator distributed at the center of the face panel has a significant impact on the sound transmission performance of the honeycomb sandwich structure, whereas the resonator distributed on the wall of the honeycomb core does not contribute to overcoming this sound-insulation valley. Based on the research results, a design strategy for overcoming this sound-insulation valley was determined by tuning the damping parameter and constructing graded resonators. Moreover, sound transmission under the excitation of oblique incidence sound waves was also investigated. Compared with the method of filling porous materials, the proposed design method is more effective, and more importantly, the mass of the resonator is only 1.23% of that of the porous materials.
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Atrial fibrillation (AF) is a rapid supraventricular arrhythmia. However, the pathogenesis of atrial fibrillation remains controversial. We obtained transcriptome expression profiles GSE41177, GSE115574 and GSE79768 from GEO database. WGCNA was performed, DEGs were screened, PPI network was constructed using STRING database. CTD database was used to identify the reference score of hub genes associated with cardiovascular diseases. Prediction of miRNAs of hub genes was performed by TargetScan. DIANA-miRPath v3.0 was applied to make functional annotation of miRNA. The animal model of atrial fibrillation was constructed, RT-PCR was used to verify the expression of hub genes. Immunofluorescence assay for THBS2 and VCAN was made to identify molecular. Design of BP neural network was made to explore the prediction relationship of CXCR4 and TYROBP on AF. The merged datasets contained 104 up-regulated and 34 down-regulated genes. GO and KEGG enrichment analysis results of DEGs showed they were mainly enriched in 'regulation of release of sequestered calcium ion into cytosol', 'actin cytoskeleton organization' and 'focal adhesion'. The hub genes were CXCR4, SNAI2, S100A4, IGFBP3, CSNK2A1, CHGB, VCAN, APOE, C1QC and TYROBP, which were up-regulated expression in the AF compared with control tissues. There was strong correlation among the CXCR4, TYROBP and AF based on the BP neural network. Through training, best training performance is 9.6474e-05 at epoch 14, and the relativity was 0.99998. CXCR4 and TYROBP might be involved in the development of atrial fibrillation by affecting inflammation-related signalling pathways and may serve as targets for early diagnosis and preventive treatment.
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Fibrilación Atrial , MicroARNs , Proteínas Adaptadoras Transductoras de Señales/genética , Fibrilación Atrial/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Humanos , Inflamación/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , TranscriptomaRESUMEN
AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto â¼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRPâmPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRPâmPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.
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Proteína Relacionada con Agouti/fisiología , Conducta Materna/fisiología , Red Nerviosa/fisiología , Comportamiento de Nidificación/fisiología , Neuronas/fisiología , Área Preóptica/fisiología , Proteína Relacionada con Agouti/genética , Animales , Frío , Femenino , Privación de Alimentos , Área Hipotalámica Lateral/fisiología , Masculino , Ratones , Ratones Transgénicos , Optogenética , Núcleo Hipotalámico Paraventricular/fisiología , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismoRESUMEN
In mammals, parental care is essential for the survival of the young; therefore, it is vitally important to the propagation of the species. These behaviors, differing between the two sexes, are innate, stereotyped, and are also modified by an individual's reproductive experience. These characteristics suggest that neural mechanisms underlying parental behaviors are genetically hardwired, evolutionarily conserved as well as sexually differentiated and malleable to experiential changes. Classical lesion studies on neural control of parental behaviors, mostly done in rats, date back to the 1950s. Recent developments of new methods and tools in neuroscience, which allow precise targeting and activation/inhibition of specific populations of neurons and their projections to different brain structures, have afforded fresh opportunities to dissect and delineate the detailed neural circuit mechanisms that govern distinct components of parental behaviors in the genetically tractably organism, the laboratory mouse (Mus musculus). In this review, we summarize recent discoveries using modern neurobiological tools within the context of traditional lesion studies. In addition, we discuss interesting cross talk between neural circuits that govern parent care with those that regulate other innate behaviors such as feeding and mating.
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Encéfalo/citología , Encéfalo/fisiología , Conducta Materna/fisiología , Vías Nerviosas/fisiología , Neuronas/fisiología , Conducta Paterna/fisiología , Animales , Ratones , Modelos AnimalesRESUMEN
Fibroblast growth factor 21 (FGF21) is known as a potent metabolic regulator but its protective mechanisms against lipotoxicity-induced ß-cell dysfunction and apoptosis remain elusive. Here, we aimed to examine the regulatory pathways whereby FGF21 mediates islet lipid metabolism in lipotoxicity-treated cells and animal models. Rat ß-cell line (INS-1E cells) and islets isolated from C57/BL6J mice were exposed to palmitic acid (PA) with/without FGF21, mimicking lipotoxic conditions. Resultant insulin secretion and intracellular signaling were analyzed with Western blotting and RNA-seq. C57/BL6J and global FGF21 knockout (KO) mice were fed with a high-fat diet (HFD) to induce lipotoxicity and given with a long-acting mimetic of FGF21. Insulin resistance and ß-cell function were then assessed using homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index. FGF21 ameliorated PA-induced lipid accumulation, reversed cell apoptosis, and enhanced glucose-stimulated insulin secretion (GSIS) as impaired by lipotoxicity in islet ß-cells. Mechanistically, FGF21 exerted its beneficial effects through activation of AMPK-ACC (acetyl-CoA carboxylase) pathway and peroxisome proliferation-activated receptors (PPARs) δ/γ signaling, thus increasing the levels of carnitine palmitoyltransferase-1A (CPT1A) and leading to increased fatty acid (FA) oxidation and reduced lipid deposition in ß-cells. Interestingly, FGF21 reduced PA-induced cell death via restoration of the expression of apoptosis inhibitor Birc3. In vivo studies further showed that FGF21 is critical for islet insulinogenic capacity and normal function in the context of HFD-treated animals. FGF21 down-regulates islet cell lipid accumulation, probably via activation of AMPK-ACC and PPARδ/γ signaling, and reduces cell death under lipotoxicity, indicating that FGF21 is protective against lipotoxicity-induced ß-cell dysfunction and apoptosis.
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Proteínas Quinasas Activadas por AMP/metabolismo , Anticuerpos Monoclonales Humanizados/farmacología , Apoptosis/efectos de los fármacos , Diabetes Mellitus Tipo 2/prevención & control , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/farmacología , Resistencia a la Insulina , Células Secretoras de Insulina/efectos de los fármacos , Obesidad/tratamiento farmacológico , Ácido Palmítico/toxicidad , Acetil-CoA Carboxilasa/metabolismo , Animales , Línea Celular Tumoral , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Factores de Crecimiento de Fibroblastos/deficiencia , Factores de Crecimiento de Fibroblastos/genética , Insulina/metabolismo , Células Secretoras de Insulina/enzimología , Células Secretoras de Insulina/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , PPAR gamma/metabolismo , Ratas , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de SeñalRESUMEN
The aggregate morphologies of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) main chain supramolecular polymer amphiphiles (SPA) are tunable by a fine balance of different non-covalent interactions. When the BODIPY segments and sodium cholate are mixed in aqueous solution, they form SPA by electrostatic attraction and hydrogen-bonds. This SPA displays helical nanowires' morphology. After the third component dimeric ß-cyclodextrin (ß-CD-C) is added, the hydrogen bonds between the cholate are substituted by the host-guest interaction between cholate and ß-CD-C. Therefore, these SPA transform their aggregate morphologies into nanosheets' architecture. Therefore, a simple and effective way to regulate self-assembly by non-covalent forces is developed. This supramolecular method may provide an effective way to prepare various nanostructures in aqueous solution and show promising application in the future.
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Compuestos de Boro/química , Nanoestructuras/química , Polímeros/química , Tensoactivos/química , Sustancias Macromoleculares/química , Estructura Molecular , Tamaño de la PartículaRESUMEN
Pancreatic progenitor cells (PPCs) are the primary source for all pancreatic cells, including beta-cells, and thus the proliferation and differentiation of PPCs into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Meanwhile, mesenchymal stem cells (MSCs) can enhance the development and function of different cell types of interest, but their role on PPCs remains unknown. We aimed to explore the mechanism-of-action whereby MSCs induce the in vitro and in vivo PPC/ICC development by means of our established co-culture system of human PPCs with human fetal bone marrow-derived MSCs. We examined the effect of MSC-conditioned medium on PPC proliferation and survival. Meanwhile, we studied the effect of MSC co-culture enhanced PPC/ICC function in vitro and in vivo co-/transplantation. Furthermore, we identified IGF1 as a critical factor responsible for the MSC effects on PPC differentiation and proliferation via IGF1-PI3K/Akt and IGF1-MEK/ERK1/2, respectively. In conclusion, our data indicate that MSCs stimulated the differentiation and proliferation of human PPCs via IGF1 signaling, and more importantly, promoted the in vivo engraftment function of ICCs. Taken together, our protocol may provide a mechanism-driven basis for the proliferation and differentiation of PPCs into clinically transplantable islets.
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Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/fisiología , Páncreas/citología , Células Madre/citología , Células Madre/fisiología , Apoptosis/fisiología , Células Cultivadas , Técnicas de Cocultivo , Humanos , Células Madre Mesenquimatosas/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Células Madre/metabolismoRESUMEN
Novel dye sensitizers are highly expected in the development of dye-sensitized solar cells (DSSCs) because dye sensitizers can significantly affect the power conversion efficiency (PCE). Here, the molecular docking strategy is applied to design panchromatic dye sensitizers for DSSCs to improve light-harvesting efficiency covering the full solar spectrum. Considering the broad absorption bands of tetraanthracenylporphyrins (TAnPs) and tetraazuleneporphyrins (TAzPs), based upon porphyrin dye sensitizer YD2-o-C8, the panchromatic dye sensitizers coded as H2(TAnP)-α, H2(TAzP)-γ, H2(TAzP)-ε, and H2(TAzP)-δ are designed by the substitution of the porphyrin-ring in YD2-o-C8 with TAnPs and TAzPs moieties at different positions. The geometries, electronic structures, and excitation properties of the designed dye sensitizers are investigated using density functional theory (DFT) and time-dependent DFT methods. The analysis of geometries, conjugation lengths, electronic structures, absorption spectra, transition configurations, exciton binding energies, and free energy variations for electron injection and dye regeneration supports that the designed molecules are effective to be applied as potential candidates of dye sensitizers for DSSCs. Among the designed dye sensitizers, H2(TAzP)-γ and H2(TAnP)-α must have the better performance in DSSCs.
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BACKGROUND: Toll-like receptor 3 (TLR3) plays a key role in innate immunity. In the present study, we analyzed tissues of patients with human hepatocellular carcinoma (HCC) to determine the significance of the relationship between TLR3 expression and cell proliferation, apoptosis, hepatitis B virus infections, angiogenesis and prognosis. METHODS: We collected paraffin-embedded tissues from 85 patients with HCC who had complete histories and were followed for >5 years. The expression and intracellular localization of TLR3 and downstream proteins (TRIF, NF-κB, and IRF3) were detected using immunohistochemistry. Further, we determined the expression of proteins that mediate cell proliferation (Ki67, cyclin D1), apoptosis (survivin, bcl-2, caspases 3, 8, and 9), and angiogenesis (CD34, MMP-2) as well as the HBV proteins HBsAg and HBcAg. Apoptosis in HCC tissues was detected using TUNEL. We conducted dual-labeling immunohistochemical analyses of TLR3 expression and TUNEL activity. RESULTS: TLR3 expression was significantly lower in HCC tissues compared with adjacent tissues. TRIF, NF-κB, and IRF3 correlated positively with TLR3 expression. Survivin and Bcl-2 expression correlated negatively with TLR3. The frequencies of caspases 3, 8, and 9 expression correlated positively with TLR3 signaling proteins. Cytoplasmic TLR3 and serum levels of HBsAg correlated positively. The apoptotic index determined using the TUNEL method and correlated positively with TLR3 expression. TLR3 expression in the cytoplasm correlated positively with TUNEL-positive cells and HBsAg. Ki67 and cyclin D1 correlated negatively with TLR3 expression. MMP-2 expression, microvessel density (CD34(+)) and endothelial progenitor cells (EPCs) correlated negatively with TLR3 expression. Kaplan-Meier survival analysis shows that TLR3 expression correlated with longer survival. CONCLUSIONS: The expression of TLR3 in HCC tissues may exert a synergistic effect on apoptosis and inhibit the proliferation of HCC cells, MMP-2 expression, generation of EPCs, and angiogenesis. Moreover, TLR3 expression may serve as a prognostic marker of HCC.
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Apoptosis , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Neoplasias Hepáticas/metabolismo , Receptor Toll-Like 3/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Antígenos CD34/metabolismo , Antígenos Virales/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Expresión Génica , Hepatitis B/metabolismo , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Metaloproteinasa 2 de la Matriz/metabolismo , FN-kappa B/metabolismo , Neovascularización Patológica , Pronóstico , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , SurvivinRESUMEN
Dye sensitizers can significantly affect power conversion efficiency of dye-sensitized solar cells (DSSCs). Porphyrin-based dyes are promising sensitizers due to their performances in DSSCs. Here, based upon a N-fused carbazole-zinc porphyrin-free-base porphyrin triad containing an ethynyl-linkage (coded as DTBC), the novel porphyrin dyes named DTBC-MP and DTBC-TP were designed by varying the porphyrin-free-base units in the π conjugation of DTBC in order to study the effect of porphyrin-free-base in the modification of electronic structures and related properties. The calculated results indicate that, the extension of the conjugate bridge with the porphyrin-free-base unit results in elevation of the highest occupied molecular orbital (HOMO) energies, decrease of the lowest unoccupied molecular orbital (LUMO) energies, reduction of the HOMO-LUMO gap, red-shift of the absorption bands, and enhancement of the absorbance. The free energy changes demonstrate that introducing more porphyrin-free-base units in the conjugate bridge induces a faster rate of electron injection. The transition properties and molecular orbital characters suggest that the different transition properties might lead to a different electron injection mechanism. In terms of electronic structure, absorption spectra, light harvesting capability, and free energy changes, the designed DTBC-TP is a promising candidate dye sensitizer for DSSCs.
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Carbazoles/química , Metaloporfirinas/química , Modelos Teóricos , Modelos MolecularesRESUMEN
Liver cancer is a severe harmful disease. It is the fifth most frequently diagnosed cancer and second most frequent cause of cancer deaths worldwide. As the most popular histologic subtype of hepatocellular carcinoma (HCC), primary HCC is a heterogeneous disease whose management requires a multidisciplinary approach combining genetics, genomics and environmental toxicology. Although many molecular targeted therapies such as sorafenib have entered clinical application and proven effective, the cytotoxicity and other negative effects cannot be ignored. There is an urgent need to identify new therapeutic targets and drugs, which can kill HCC cells with high efficiency and specificity. Plenty of evidence suggests that occurrence and development of HCC is closely related with epigenetics. DNA methylation, histone modification, aberrant expression of miRNAs and dysregulated expression of many epigenetic regulatory genes are significantly altered in HCC. Epigenetic therapeutic drugs may reverse abnormal gene expression, thus controlling the occurrence and development of HCC. In this review, we summarize the latest research progresses in epigenetics and its therapeutic application in HCC,and the potential treatments to be used in the future.
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Carcinoma Hepatocelular/genética , Epigénesis Genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/terapia , Metilación de ADN , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Neoplasias Hepáticas/terapia , MicroARNs/fisiología , ARN Largo no Codificante/fisiologíaRESUMEN
Bacillus subtilis XF-1 has been used as a biocontrol agent of clubroot disease of crucifers infected by Plasmodiophora brassicae, an obligate pathogen. In order to maximize the growth inhibition of the pathogen, random mutagenesis using N-methyl-N'-nitro-N-nitrosoguanidine was applied to strain XF-1. The efficacy of 226 selected mutants was assessed against the growth of an indicator fungal pathogen: Fusarium solani using agar plate assay and the disruptive effects on the resting spores of P. brassicae. Four mutants exhibited inhibition activity significantly higher than the wild type. The cell extracts of these mutants and the XF-1 were subjected to matrix-assisted laser desorption ionization-time of flight mass spectra analysis, and three families of cyclic lipopeptides (CLPs) fengycin, surfactin and iturin were identified from the parental strain and the screened mutants. However, the relative contents and compound diversity changed after mutagenesis, and there was slight variation in the surfactin and fengycin. Notably, only 5 iturin components were discovered from the wild strain XF-1, but 13 were obtained from the mutant strains, and the relative CLPs contents of all mutant strains increased substantially. The results suggested that CLPs might be one of main biocontrol mechanisms of the clubroot disease by XF-1. The 4 mutants are far more effective than the parental strain, and they would be promising biocontrol candidates not only against P. brassicae but probably other plant diseases caused by fungi.
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Background: Hyperlipidemia (HLP) presents a significant challenge to global public health. Mounting evidence suggests that statins, the recommended first-line lipid-lowering agents, have significant adverse effects. Consequently, the quest for natural and efficacious alternative therapies is steadily emerging as a research priority for HLP prevention and treatment. Consumption of tea, which is rich in diverse biologically active compounds with the capacity to regulate lipid metabolism and combat obesity, has emerged as a promising alternative therapy. Sea buckthorn leaves are rich in a multitude of biologically active substances, have a hypolipidemic effect, and can be used as a raw material for tea because of their unique flavor. There is a suggestion that combining Aspergillus cristatus with tea could modify or boost the lipid-lowering active compounds present in tea, thereby increasing its efficacy in regulating lipid metabolism. Results: Sea Buckthorn Leaf Fu Tea (SBLFT) was obtained by fermentation when sea buckthorn leaves contained 42 % moisture, inoculated with Aspergillus cristatus 0.2 mL/g, and incubated for 8 d at constant temperature. Animal experiments demonstrated that SBLFT significantly inhibited body weight gain in HLP rats and reduced lipid content and serum oxidative stress. In addition, liver tissue sections and functional indices showed that SBLFT can improve liver morphology and function abnormalities. Reverse transcription-polymerase chain reaction results indicated that the expression of Liver kinase B1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acetyl CoA carboxylase 1 (ACC1), and sterol-regulatory element binding protein-1 (SREBP1c) gene related to lipid metabolism was altered. Conclusion: SBLFT improved HLP, specifically via promoting the expression of LKB1 in the liver of HLP rats, activating AMPK, and inhibiting ACC1 and SREBP1c expression, resulting in the inhibition of fatty acid and triglyceride synthesis-related enzymes at the transcriptional level.
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Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested.
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Neoplasias de la Mama , Receptores Quiméricos de Antígenos , Humanos , Femenino , Receptores Quiméricos de Antígenos/metabolismo , Neoplasias de la Mama/metabolismo , Linfocitos T , Recurrencia Local de Neoplasia/metabolismo , Inmunoterapia Adoptiva , Microambiente TumoralRESUMEN
Medulloblastoma (MB) is a malignant tumor of the cerebellum that occurs in children and infants. Abnormal neuronal differentiation can lead to brain tumors, and topoisomerase IIß (Top IIß) plays an important role in neuronal differentiation. The aim of this study was to investigate the molecular mechanism of 13-cis retinoic acid (13-cis RA) promoting the expression of Top IIß and inducing neuronal differentiation in human MB Daoy cells. The results showed that 13-cis RA inhibited the cell proliferation and induced cell cycle arrest in G0/G1 phase. The cells differentiated into a neuronal phenotype, with high expression of the neuronal marker microtubule-associated protein 2 (MAP2) and abundant Top IIß, and obvious neurite growth. Chromatin immunoprecipitation (ChIP) assay showed that histone H3 lysine 27 tri-methylation (H3K27me3) modification in Top IIß promoter decreased after 13-cis RA-induced cell differentiation, while jumonji domain-containing protein 3 (JMJD3) binding in Top IIß promoter increased. These results suggest that H3K27me3 and JMJD3 can regulate the expression of Top IIß gene, which is related to inducing neural differentiation. Our results provide new insights into understanding the regulatory mechanisms of Top IIß during neuronal differentiation and imply the potential application of 13-cis RA in the clinical treatment of MB.
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Neoplasias Cerebelosas , Meduloblastoma , Niño , Humanos , Histonas/genética , Histonas/metabolismo , Isotretinoína/metabolismo , Meduloblastoma/genética , Meduloblastoma/patología , Epigénesis Genética , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Diferenciación Celular , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/patología , Tretinoina/farmacología , Tretinoina/metabolismoRESUMEN
Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae) led to the isolation of a new cucurbitane-type triterpenoid, aquilarolide A (1), along with five known compounds (2-6). The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR) experiments and mass spectrometry (MS) data and theoretical calculations of its electronic circular dichroism (ECD) spectra. Aquilarolide A, cucurbitacin E (3), cucurbitacin B (4), and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one (6) showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1, human lung squamous cell carcinoma NCI-H520, human lung adenocarcinoma A549, and paclitaxel-resistant A549 (A549/Taxol) cell lines. All four active compounds, with IC50 values ranging from 0.002 to 0.91 µM, had better inhibitory activities against A549/Taxol cells than paclitaxel (IC50 = 1.80 µM). Among them, cucurbitacin E (IC50 = 0.002 µM) is the most active. Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms.
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Image-guided tumor ablation eliminates tumor cells by physical or chemical stimulation, which shows less invasive and more precise in local tumor treatment. Tumor ablation provides a treatment option for medically inoperable patients. Currently, clinical ablation techniques are widely used in clinical practice, including cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Previous clinical studies indicated that ablation treatment activated immune responses besides killing tumor cells directly, such as short-term anti-tumor response, immunosuppression reduction, specific and non-specific immune enhancement, and the reduction or disappearance of distant tumor foci. However, tumor ablation transiently induced immune response. The combination of ablation and immunotherapy is expected to achieve better therapeutic results in clinical application. In this paper, we provided a summary of the principle, clinical application status, and immune effects of tumor ablation technologies for tumor treatment. Moreover, we discussed the clinical application of different combination of ablation techniques with immunotherapy and proposed possible solutions for the challenges encountered by combined therapy. It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy.
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Técnicas de Ablación , Ablación por Catéter , Neoplasias , Ablación por Radiofrecuencia , Ablación por Catéter/métodos , Humanos , Inmunoterapia , Neoplasias/terapia , Ablación por Radiofrecuencia/métodosRESUMEN
In order to investigate the pollution characteristics and sources of water-soluble ions in atmospheric PM2.5 in different regions of central China during summer, Wuhan, Suizhou, and Pingdingshan were selected as urban, suburban, and rural monitoring stations, respectively, to collect PM2.5 samples, and the mass concentration of PM2.5 in the atmosphere and the contents of eight water-soluble ions were analyzed. The results showed that ρ(water-soluble ions) at the three sites showed obvious spatial distribution characteristics, with Pingdingshan[(36.29±9.82) µg·m-3] > Wuhan[(32.55±10.05) µg·m-3] > Suizhou[(26.10±6.23) µg·m-3], accounting for 52.47%, 51.32%, and 48.61% of the PM2.5 mass concentration, respectively. In the Pingdingshan station, the proportion of water-soluble ions was the largest due to biomass combustion in the rural area. Additionally, SNA (SO42-, NO3-, and NH4+) were the main ionic components, accounting for 95.65%, 96.12%, and 97.33% of the total water-soluble ions, respectively. The mean values of SOR of the Wuhan (0.64) and Suizhou (0.63) stations were higher than that of the Pingdingshan station (0.50), whereas the NOR values of the Wuhan (0.18) and Pingdingshan (0.19) stations were higher than that of the Suizhou station (0.15). The difference in SOR and NOR among stations was affected by the secondary conversion mechanism, the ammonia-rich environment, and the surrounding traffic sources, respectively. The PM2.5 at the Wuhan and Pingdingshan stations was in general alkaline, whereas at the Suizhou station it was neutral or weakly acidic, which was mainly caused by differences in NH4+. NH4+ mainly existed in the form of (NH4)2SO4 and NH4NO3 at the Wuhan and Pingdingshan stations, whereas at the Suizhou station it mainly existed in the form of (NH4)2SO4 or (NH4)HSO4. PCA-MLR analysis revealed that the Wuhan (89.27%) and Suizhou (67.38%) stations were the most affected by secondary conversion sources, whereas the Wuhan station was also affected by industrial sources (8.54%) and coal sources (2.27%). The pollution sources of the Suizhou station also included biomass combustion (24.42%) and dust sources (8.25%). The Pingdingshan station was most affected by biomass combustion (58.37%), followed by dust and combustion sources (38.05%) and traffic sources (3.58%). The analysis of potential sources of SNA (PSCF) showed that the main potential source areas of Wuhan were the boundary of Hubei, Henan, and Anhui and the southwest area of Anhui. Suizhou and Pingdingshan were affected by long-distance transport, and the main potential source regions were distributed in Shanghai, Jiangsu, and Anhui provinces from the east coast to the west.
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Contaminantes Atmosféricos , Material Particulado , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , China , Monitoreo del Ambiente , Tamaño de la Partícula , Material Particulado/análisis , Estaciones del Año , AguaRESUMEN
In order to understand the pollution characteristics, spatial distribution, potential sources, and ecological risk of heavy metals in the sediments of Tangxun Lake, the contents of heavy metals (As, Hg, Cd, Cr, Cu, Pb, Zn, and Ni) in the surface sediments of Tangxun Lake were analyzed, and the pollution status and potential ecological risk degree of heavy metals in the sediments were evaluated using the geo-accumulation index and potential ecological risk index. The potential sources of heavy metal pollutants were analyzed by correlation and principal component analysis. The results showed that except for Cr, the contents of other heavy metals were higher than their background values. The contents of Hg, Cd, Zn, and Cu were higher in the southwest and northeast corners of the lake, which may come from the combined pollution of sewage discharge, fisheries, and surrounding industrial and agricultural activities. The geo-accumulation index and potential ecological risk showed that Hg and Cd were in moderate pollution; Cu, Pb, and Zn were in non-light pollution; and As, Cr, and Ni were in non-pollution. Except for Hg and Cd, there were serious and serious potential ecological risks, and the other elements were at a low risk level. The heavy metals in the surface sediments of Tangxun Lake showed a high ecological risk level.
Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Sedimentos Geológicos , Lagos , Metales Pesados/análisis , Medición de Riesgo , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Rhabdomyosarcoma is the most common soft tissue tumor in children. Rhabdomyosarcoma commonly results in pain and bleeding caused by tumor compression and is prone to early metastasis and recurrence, which can seriously affect the therapeutic outcomes and long-term prognosis. Up to 37.7% of rhabdomyosarcomas may metastasize. Therefore, the molecular mechanisms underlying rhabdomyosarcoma must be explored to identify an effective target for its early diagnosis and specific treatment. METHODS: A dataset of 18 rhabdomyosarcoma tissue samples and 6 healthy skeletal muscle samples was downloaded. Differentially expressed genes between rhabdomyosarcoma and healthy tissue samples were identified by GEO2R. Kyoto Encyclopedia of Genes and Genomes and gene ontology pathway enrichment analyses were performed. A protein-protein interaction network was constructed, and hub genes were identified. Expression and survival analyses of hub genes were performed. Additionally, 30 patients with rhabdomyosarcoma were recruited, and overall survival information and samples were collected. Reverse transcription quantitative real-time polymerase chain reaction assays were performed to verify the expression of MYBPC2 and MYL1 in rhabdomyosarcoma tumor tissues. The Kaplan-Meier method was used to explore overall survival based on our clinical data. RESULTS: In total, 164 genes were up-regulated and 394 were down-regulated in rhabdomyosarcoma tumor tissues. Gene ontology analysis revealed that variations were predominantly enriched in the cell cycle, muscle contraction, muscle system processes, cytoskeleton, nucleotide binding, and cytoskeletal protein binding. The protein-protein interaction network revealed 3274 edges, and 441 nodes were constructed. Ten hub genes were identified; of these, MYBPC2 and MYL1 were significantly up-regulated in rhabdomyosarcoma. Compared with the healthy group, patients with rhabdomyosarcoma exhibiting high expression of MYBPC2 and MYL1 exhibited significantly worse overall survival. CONCLUSIONS: We found differentially expressed genes between rhabdomyosarcoma and healthy tissue samples. MYBPC2 and MYL1 may be involved in the pathogenesis of rhabdomyosarcoma and therefore deserve further exploration.