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1.
Ann Vasc Surg ; 108: 419-425, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39025210

RESUMEN

BACKGROUND: Kasabach-Merritt phenomenon (KMP) is characterized by profound thrombocytopenia and consumptive coagulopathy associated with vascular tumors, such as Kaposiform hemangioendothelioma (KHE). The pathogenesis of KMP remains unclear and its treatment is challenging. In this study, we tried to establish an animal model of KMP, which may facilitate the research on the etiology and new treatment. METHODS: A fresh sample of KHE from a one-month-old female infant with KMP was scissored into pieces and transplanted subcutaneously into the back of the nude mice. Blood routine examination was performed before the transplantation and 2, 4, 8, 12, and 16 weeks after the transplantation. Transplanted tumors were harvested 2, 4, 8, 12, and 16 weeks after the transplantation. H-E staining, immunohistochemistry staining of cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), and ultrastructural observation were performed on the plugs. RESULTS: Blood test showed a significant decrease in the number of platelets 2 weeks after transplantation. The number of platelets showed an overall trend of recovery from 2 weeks despite a slight decrease at 12 weeks after transplantation. There was no significant difference in the platelet count at 16 weeks after transplantation compared with the original state. H-E staining showed abundant irregular blood sinuses in the transplanted tumors with plenty of blood cells 2 weeks after the transplantation. 4, 8, and 12 weeks after transplantation, the density of blood sinuses decreased progressively. 16 weeks after transplantation, the plugs involuted into fibrous tissue. Immunohistochemistry staining showed the positive expression of CD31 in the endothelial cells and α-SMA in the perivascular cells. Ultrastructural observation also showed the features of KHE and progressive evolution of the tumors. CONCLUSIONS: We successfully established an experimental model of KMP by the xenograft of KHE in nude mice, which manifested profound thrombocytopenia and typical pathological structure.


Asunto(s)
Actinas , Modelos Animales de Enfermedad , Hemangioendotelioma , Síndrome de Kasabach-Merritt , Ratones Desnudos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , Sarcoma de Kaposi , Animales , Síndrome de Kasabach-Merritt/patología , Hemangioendotelioma/patología , Femenino , Sarcoma de Kaposi/patología , Factores de Tiempo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Actinas/metabolismo , Humanos , Recuento de Plaquetas , Xenoinjertos , Ratones Endogámicos BALB C
2.
Chem Biodivers ; 21(4): e202400135, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38425248

RESUMEN

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.


Asunto(s)
Tiadiazoles , Humanos , Tiadiazoles/farmacología , Antifúngicos/farmacología , Antibacterianos/farmacología , Hongos , Piridinas/farmacología , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 124-130, 2024 Feb 15.
Artículo en Zh | MEDLINE | ID: mdl-38436308

RESUMEN

OBJECTIVES: To study the intervention effect of narrative therapy on non-suicidal self-injury (NSSI), as well as anxiety and depression symptoms in adolescents with depressive disorder. METHODS: Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping. The control group received conventional psychological support, while the intervention group received individual narrative therapy in addition to the conventional psychological support (twice a week, 60 minutes per session, for a total of 3 weeks). Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire, Children's Depression Inventory, and Children's Anxiety and Mood Scale before the intervention, at the end of the intervention, and one month after the intervention for both groups. RESULTS: A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study. At the end of the intervention and one month after the intervention, the intervention group showed a significant reduction in the NSSI frequency score, NSSI level, anxiety score, and depression score compared to before the intervention (P<0.017). Moreover, at the end of the intervention and one month after the intervention, the intervention group exhibited significantly lower NSSI frequency score, NSSI severity score, NSSI level, anxiety score and depression score compared to the control group (P<0.05). CONCLUSIONS: Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity, as well as anxiety and depression symptoms in adolescents with depressive disorder.


Asunto(s)
Trastorno Depresivo , Terapia Narrativa , Conducta Autodestructiva , Niño , Adolescente , Humanos , Estudios Prospectivos , Conducta Autodestructiva/terapia , Ansiedad
4.
Sensors (Basel) ; 23(3)2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36772761

RESUMEN

In this paper, a variety of 2D materials on the surface plasmon resonance sensor based on Al-Ni bimetallic layer are compared. Simulation results indicate that lateral position shift, which is calculated according to the real and imaginary parts of the refractive index of material, can be used as an effective parameter to optimize the sensitivity. By using the parameters for optimizing the SPR structures, the results show that the multiple layer models of Al(40 nm)-Ni(22 nm)-black phosphorus (BP)(1 L) and Al(40 nm)-Ni(22 nm)-blue phosphorus (BlueP)/WS2(1 L) exhibit average angular sensitivities of 507.0 °/RIU and 466 °/RIU in the refractive index range of 1.330-1.335, and maximum sensitivity of 542 °/RIU and 489 °/RIU at the refractive index of 1.333, respectively. We expect more applications can be explored based on the highly sensitive SPR sensor in different fields of optical sensing.

5.
Opt Express ; 30(24): 42875-42891, 2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36522998

RESUMEN

In this paper, modal interference discrepancy in an all-fiber MZI is theoretically analyzed and experimentally verified. Theoretical analysis demonstrates that ambient refractive index (RI) response of core-cladding modal interference in an all-fiber MZI is blue-shift, while that of cladding-cladding modal interference is red-shift. Temperature response trends of the two kinds of modal interference are uniformly red-shift. The discrepancy is used to fabricate an improved Vernier sensor which is cascaded by two unit MZIs. One MZI is slightly core-offset fused to obtain core-cladding modal interference, and the other is obviously offset fused to get cladding-cladding modal interference. Ambient RI sensitivity of the cascaded sensor is improved with temperature cross-talk restrained. Ambient RI responses of the two unit MZIs are measured to be opposite, which are -54.009 nm/RIU (within RI range of 1.3362∼1.3811) for the slight and 142.581 nm/RIU for the obvious offset unit MZI. While, temperature response trends of them are consistent, which are 0.042 nm/°C for the slight and 0.025 nm/°C for the obvious offset unit MZI, respectively. For the cascaded Vernier sensor ambient RI sensitivity reaches -1788.160 nm/RIU, which is 33.1 and 12.5 folds improved over the two unit MZIs, respectively. Temperature sensitivity of the cascaded sensor is as low as 0.167 nm/°C and only causes a slight RI error of 9.339 × 10-5 RIU/°C. Due to the simple structure, ease of fabrication, and low temperature cross-talk, the modal interference discrepancy-based Vernier sensor is believed to have potential application prospects in biochemical sensing fields.

6.
Acta Pharmacol Sin ; 43(10): 2696-2708, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35352018

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most lethal cancers worldwide. Several basic studies have confirmed that Kirsten rat sarcoma virus (KRAS) is a key driver gene for the occurrence of PDAC, and KRAS mutations have also been found in most patients in clinical studies. In this study, two pan-KRAS inhibitors, BI-2852 and BAY-293, were chosen as chemical probes to investigate their antitumor potency in PDAC. Their inhibitory effects on KRAS activation were validated in vitro and their antiproliferative potency in PDAC cell lines were profiled, with half-maximal inhibitory concentration (IC50) values of approximately 1 µM, demonstrating the therapeutic potential of pan-KRAS inhibitors in the treatment of PDAC. However, feedback regulation in the KRAS pathway weakened inhibitor activity, which was observed by a 50 times difference in BAY-293 from in vitro activity. Furthermore, pan-KRAS inhibitors effectively inhibited cell proliferation in 3D organoids cultured from PDAC patient samples; however, there were some variations between individuals. These results provide a sufficient theoretical foundation for KRAS as a clinical therapeutic target and for the application of pan-KRAS inhibitors in the treatment of PDAC, with important scientific significance in translational medicine.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Retroalimentación , Virus del Sarcoma Murino de Kirsten/metabolismo , Mutación , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Neoplasias Pancreáticas
7.
Mar Drugs ; 20(3)2022 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-35323512

RESUMEN

Four new dimeric sorbicillinoids (1-3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6-11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1-5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED50 of 24.25 ± 1.57 µg/mL. The ED50 values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 µM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.


Asunto(s)
Ascomicetos/efectos de los fármacos , Agentes de Control Biológico , Hypocreales/química , Policétidos , Animales , Ascomicetos/crecimiento & desarrollo , Agentes de Control Biológico/química , Agentes de Control Biológico/aislamiento & purificación , Agentes de Control Biológico/farmacología , Agentes de Control Biológico/toxicidad , Camellia sinensis/microbiología , Embrión no Mamífero , Estructura Molecular , Policétidos/química , Policétidos/aislamiento & purificación , Policétidos/farmacología , Policétidos/toxicidad , Pez Cebra
8.
Small ; 16(46): e2004234, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33107207

RESUMEN

3D incident light confinement by radical electromagnetic fields offers a facile and novel way to break through the performance limit of inorganic perovskite CsPbBr3 quantum dots (QDs). Herein, metallic nanoparticles decorated anodic aluminum oxide (AAO) hybrid plasmonic nanostructures with geometric control are first proposed for cyclic light utilization of perovskite photodetectors, enabled by spatially extended light confinement. The drastic multiple interference induced by plasmonic coupling within AAO matrixes are generated as a function of pore sizes, which can effectively collect the transmitted photons back to the surface. In addition, the self-assembled metallic nanoparticles simultaneously concentrate the incident and reflected light beams into the CsPbBr3 QD layers. The light confinement inherently stems from the metallic nanoparticles due to the variation of the near surface electromagnetic fields. As a result, perovskite photodetectors based on Al nanoparticles/AAO hybrid plasmonic nanostructures with a pore size of 220 nm exhibit enhanced photoresponse behavior with remarkably increased photocurrent by ≈43× and maintain low dark current under 490 nm light illumination at 1 V.

9.
Small ; 15(28): e1901606, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31140743

RESUMEN

Strong near-surface electromagnetic field formed by collective oscillation of electrons on Cu nanostructure a shows a strong dependence on geometry, offering a promising approach to boost the light absorption of ZnO photoactive layers with enhanced plasmon scattering. Here, a facile way to fabricate UV photodetectors with tunable configuration of the self-assembled Cu nanostructures on ZnO thin films is reported. The incident lights are effectively confined in ZnO photoactive layers with the existence of the uplayer Cu nanostructures, and the interdiffusion of Cu atoms during fabrication of the Cu nanostructures can improve the carrier transfer in ZnO thin films. The optical properties of the hybrid architectures are successfully tailored over a control of the geometric evolution of the Cu nanostructures, resulting in significantly enhanced photocurrent and responsivity of 2.26 mA and 234 A W-1 under a UV light illumination of 0.62 mW cm-2 at 10 V, respectively. The photodetectors also exhibit excellent reproducibility, stability, and UV-visible rejection ratio (R370 nm /R500 nm ) of ≈370, offering an approach of high-performance UV photodetectors for practical applications.

10.
Zhongguo Zhong Yao Za Zhi ; 44(23): 5184-5190, 2019 Dec.
Artículo en Zh | MEDLINE | ID: mdl-32237356

RESUMEN

Traditional Chinese medicine believes that the occurrence and development of tumors is related to the body's Qi deficiency. " Invigorating Qi for consolidation of exterior" has became an effective way to treat tumors by traditional Chinese medicine. This study is based on the " invigorating Qi for consolidation of exterior" to explore the effect of flavonoid components in Qi-invigorating herbs Astragali Radix( AR) on the growth and immune function of mouse Lewis lung cancer xenografts,and further explore its mechanism of action. In the present study,high performance liquid chromatography was performed to analyze the flavonoid components in AR.The Lewis lung cancer model of C57 BL/6 mice was constructed,and the tumor volume of mice was determined by Visual Sonics Vevo2100 high frequency color ultrasound. The levels of IL~(-1)7 and RORγt in serum and tumor tissues were detected by ELISA and immunohistochemistry. The expression of IRE~(-1)/XBP~(-1) pathway-related proteins in tumor tissues was detected by Western blot. The results revealed that treatment of 5 and 10 g·kg~(-1)·d~(-1) of flavonoid components in AR significantly inhibited tumor growth of C57 BL/6 tumorbearing mice. The inhibition rates at the dose of 5 and 10 g·kg~(-1)·d~(-1) of flavonoid components in AR were( 29. 5±4. 4) % and( 43. 4±5. 2) %,respectively. The expression of IL~(-1)7 and RORγt in serum and tumor tissues of Lewis lung cancer mice were decreased,and the spleen index and thymus index were significantly enhanced by the flavonoid components in AR. Flavonoid components in AR could decrease the expression of X-box binding protein 1( XBP1),inositol-requiring enzyme( IRE1) and glucose regulated protein 78 k D( GRP78),and increase the expression of C/EBP homologous protein( CHOP),and the high-dose group is better,suggesting that the anti-lung cancer effect of flavonoid components in AR is related to the regulation of XBP1 mediated ERs. This study provides new evidence that the flavonoid components in AR could inhibit the tumor growth of C57 BL/6 tumor-bearing mice by regulating the body's immune function through " invigorating Qi for consolidation of exterior".


Asunto(s)
Planta del Astrágalo/química , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/uso terapéutico , Qi , Animales , Chaperón BiP del Retículo Endoplásmico , Ratones , Ratones Endogámicos C57BL , Ensayos Antitumor por Modelo de Xenoinjerto
11.
J Nanosci Nanotechnol ; 18(5): 3466-3477, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29442853

RESUMEN

As a promising candidate for the improved performance, silver nanoparticles (Ag NPs) have been successfully adapted in various applications such as photovoltaics, light emitting diodes (LEDs), sensors and catalysis by taking the advantage of their controllable plasmonic properties. In this paper, the control on the morphologies and optical properties of Ag NPs on c-plane sapphire (0001) is demonstrated by the systematic control of annealing temperature (between 200 and 950 °C) with 20 and 6 nm thick Ag films through the solid state dewetting. With the relatively thicker film of 20 nm, various configuration and size of Ag NPs are fabricated such as irregular, round dome-shaped and tiny Ag NPs depending on the annealing temperature. In a shrill contrast, the 6 nm Ag set exhibits a sharp distinction with the formation of densely packed small NPs and ultra-highly dense tiny Ag NPs due to the higher dewetting rate. While, the surface diffusion assumes the main driving force in the evolution process of Ag NP morphologies up to 550 °C, the sublimation of Ag atoms has played a significant role on top on the surface diffusion between 600 and 950 °C. The reflectance spectra of Ag NPs exhibit the quadrupolar resonance and dipolar resonance peaks, and the evolution of peaks, shift and average reflectance were discussed based on the Ag NPs size and surface coverage. In particular, the dipolar resonance peak in the reflectance spectra red shifts from ~475 to ~570 nm due to the size increment of Ag NPs (38.31 to 74.68 nm). The wide surface coverage of Ag NPs exhibits the highest average reflectance (~27%) and the lowest Raman intensity.

12.
Phys Chem Chem Phys ; 19(23): 15084-15097, 2017 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-28561078

RESUMEN

Metallic nanoparticles (NPs) with tunable physical, optical and catalytic properties have a wide range of applications including various optoelectronics, sensors and fuel cells. In this paper, we demonstrate the evolution of various physical properties, configurations, size and density of palladium (Pd) nanostructures on sapphire(Al2O3) (0001) by the systematic control of deposition amount (DA) at distinct annealing temperatures. The transformation of the deposited thin films into various Pd NPs is achieved by the dewetting of the thin film by means of surface diffusion, nucleation, Volmer-Weber growth and surface energy minimization mechanism. Depending on the evolution of size, density and configuration, five distinctive regimes of Pd nanostructures are demonstrated: (i) nucleation and evolution of small NPs between 1 and 3 nm, (ii) medium NPs with the dominating vertical growth between 5 and 20 nm, (iii) laterally expanded large NPs between 30 and 40 nm, (iv) irregular coalesced Pd NPs between 50 and 80 nm and (v) voids evolution between 100 and 200 nm. Initial film thickness and annealing temperature play major roles on the dewetting process and the resulting Pd nanostructures are notably distinguished. The fabricated Pd nanostructures influence the lattice vibration modes of sapphire(0001) such as gradual decrement in the intensity and left-shift of the peak position with increased surface coverage. In addition, the optical properties are studied by UV-VIS-NIR (300-1100 nm) reflectance spectra, which shows the reflectance, absorption and scattering over the wavelength and are closely related to the morphology evolution of Pd nanostructures.

13.
J Phys Chem Lett ; 15(33): 8427-8433, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39116387

RESUMEN

Infrared solar cells (IRSCs), capable of converting low-energy infrared photons to electron-hole pairs, are promising infrared optoelectronic devices because of their extended utilization region of the solar to short-wavelength infrared region. For PbS QDs IRSCs, charge extraction loss, easily generated at the interfaces, has been one of the dominate obstacles impeding the improvement of device efficiencies due to too many trap states and mismatched energy levels between the photoactive layer and electron transport layer (ETL). Herein, an advanced ZnO ETL was developed to improve the extraction of photogenerated charges from the PbS QD photoactive layer to ETLs. The advanced ETL film exhibited effectively suppressed trap states and better-matched energy levels compared with the QD layer. As a consequence, high-performance PbS QD IRSCs with the highest infrared power conversion efficiencies of 1.26% under 1100 nm filtered solar illumination are achieved, suggesting an effective and facile route for enhancing the charge extraction in infrared photovoltaics.

14.
ACS Appl Mater Interfaces ; 16(19): 24572-24579, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38690767

RESUMEN

Infrared (IR) solar cells, capable of converting low-energy IR photons to electron-hole pairs, are promising optoelectronic devices by broadening the utilization range of the solar spectrum to the short-wavelength IR region. The emerging PbS colloidal quantum dot (QD) IR solar cells attract much attention due to their tunable band gaps in the IR region, potential multiple exciton generation, and facile solution processing. In PbS QD solar cells, ZnO is commonly utilized as an electron transport layer (ETL) to establish a depleted heterostructure with a QD photoactive layer. However, band gap shrinkage of large PbS QDs makes it necessary to tailor the behaviors of the ZnO ETL for efficient carrier extraction in the devices. Herein, the characteristics of ZnO ETL are efficiently and flexibly tailored to match the QD layer by handily adjusting the postannealing process of ZnO ETL. With a suitable temperature, the well-matched energy level alignment and suppressed trap states are simultaneously achieved in the ZnO ETL, effectively reducing the nonradiative recombination and accelerating the electron injection from the QD layer to ETL. As a consequence, a high-performance PbS QD photovoltaic device with power conversion efficiencies (PCEs) of 10.09% and 1.37% is obtained under AM 1.5 and 1100 nm filtered solar illumination, demonstrating a simple and effective approach for achieving high-performance IR photoelectric devices.

15.
Food Chem ; 454: 139732, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38815327

RESUMEN

The spine grapes (Vitis davidii Foëx.) are wild grape species that grow in southern China, and can be used for table grapes, juicing and winemaking. To systematically investigate the flavor profiles of spine grapes, flavonoids and volatile compounds were detected in five spine grape varieties (Seputao, Ziqiu, Miputao, Tianputao and Baiputao) using HPLC-QqQ-MS/MS and GC-MS. The content of flavonoids highly depended on the variety, such as the total concentrations of anthocyanins (91.43-328.85 mg/kg FW) and flavonols (33.90 to 83.16 mg/kg FW). The volatile compounds with higher odor active value were selected to describe the aroma of spine grapes. Hexanal, (E)-2-hexenal and (E, Z)-2,6-nonadienal contributed to the higher herbaceous flavor to Baiputao and Ziqiu. ß-Damascenone and (E)-2-nonenal gave Baiputao a flavor with more floral, fruity and earthy. Their characteristic flavor compounds were subsequently revealed using multivariate statistical analysis. The results helped producers to further develop and utilize the spine grapes.


Asunto(s)
Flavonoides , Aromatizantes , Frutas , Cromatografía de Gases y Espectrometría de Masas , Metabolómica , Vitis , Compuestos Orgánicos Volátiles , Vitis/química , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/análisis , China , Aromatizantes/química , Aromatizantes/análisis , Aromatizantes/metabolismo , Frutas/química , Flavonoides/análisis , Flavonoides/química , Gusto , Odorantes/análisis , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , Humanos
16.
Cancer Commun (Lond) ; 44(6): 670-694, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38734931

RESUMEN

BACKGROUND: Metabolic reprograming and immune escape are two hallmarks of cancer. However, how metabolic disorders drive immune escape in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, the aim of the present study was to investigate the metabolic landscape of HNSCC and its mechanism of driving immune escape. METHODS: Analysis of paired tumor tissues and adjacent normal tissues from 69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing. The tumor-promoting function of kynurenine (Kyn) was explored in vitro and in vivo. The downstream target of Kyn was investigated in CD8+ T cells. The regulation of CD8+ T cells was investigated after Siglec-15 overexpression in vivo. An engineering nanoparticle was established to deliver Siglec-15 small interfering RNA (siS15), and its association with immunotherapy response were investigated. The association between Siglec-15 and CD8+ programmed cell death 1 (PD-1)+ T cells was analyzed in a HNSCC patient cohort. RESULTS: A total of 178 metabolites showed significant dysregulation in HNSCC, including carbohydrates, lipids and lipid-like molecules, and amino acids. Among these, amino acid metabolism was the most significantly altered, especially Kyn, which promoted tumor proliferation and metastasis. In addition, most immune checkpoint molecules were upregulated in Kyn-high patients based on RNA-sequencing. Furthermore, tumor-derived Kyn was transferred into CD8+ T cells and induced T cell functional exhaustion, and blocking Kyn transporters restored its killing activity. Accroding to the results, mechanistically, Kyn transcriptionally regulated the expression of Siglec-15 via aryl hydrocarbon receptor (AhR), and overexpression of Siglec-15 promoted immune escape by suppressing T cell infiltration and activation. Targeting AhR in vivo reduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8+ T cell infiltration and killing capacity. Finally, a NH2-modified mesoporous silica nanoparticle was designed to deliver siS15, which restored CD8+ T cell function status and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 was positively correlated with AhR expression and CD8+PD-1+ T cell infiltration in HNSCC tissues. CONCLUSIONS: The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec-15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias de Cabeza y Cuello , Quinurenina , Carcinoma de Células Escamosas de Cabeza y Cuello , Escape del Tumor , Humanos , Quinurenina/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Animales , Ratones , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Línea Celular Tumoral
17.
Nat Prod Bioprospect ; 14(1): 23, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517590

RESUMEN

In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1-12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish.

18.
Food Chem ; 460(Pt 1): 140508, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39047494

RESUMEN

This study aimed to clarify how microclimate diversity altered volatilomics in Cabernet Sauvignon grapes and wines. Four row-oriented vineyards were selected, and metabolites of grapes and wines were determined from separate canopy sides. Results showed that shaded sides received 59% of the solar radiation and experienced 55% of the high-temperature days compared to the exposed sides on average. Grape primary metabolites were slightly affected by the canopy side. Herbaceous aromas were consistently more abundant in grapes and wines from shaded clusters. Heat-stressed canopy sides accelerated terpenoid loss and increased norisoprenoid levels in grapes, while ß-damascenone in north-side wines was 13%-32% higher than that in south-side wines of the east-west vineyard. The northeast-southwest vineyard showed the most notable variation in taste and aroma sensory scores, with four parameters significantly different. There were 32 aroma series identified in wines, and banana, pineapple, and strawberry odors were highly correlated with aroma sensory score.


Asunto(s)
Frutas , Odorantes , Gusto , Vitis , Compuestos Orgánicos Volátiles , Vino , Vitis/química , Vitis/metabolismo , Vino/análisis , Odorantes/análisis , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/análisis , Frutas/química , Frutas/metabolismo , Frutas/crecimiento & desarrollo , Humanos , Granjas , Aromatizantes/química , Aromatizantes/análisis , Femenino , Masculino
19.
J Nat Med ; 78(4): 849-862, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38724866

RESUMEN

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.


Asunto(s)
Diterpenos , Hipoglucemiantes , Células Secretoras de Insulina , Regeneración , Pez Cebra , Animales , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Estructura Molecular , Regeneración/efectos de los fármacos , Relación Estructura-Actividad , Madera/química , Animales Modificados Genéticamente , Thymelaeaceae/química
20.
Food Res Int ; 191: 114726, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059919

RESUMEN

Vitis amurensis grape, an East Asian Vitis species, has excellent cold and disease resistance and exhibits high winemaking potential. In this study, the aroma compounds in grapes from five V. amurensis cultivars ('Beiguohong', 'Beiguolan', 'Shuangfeng', 'Shuanghong', 'Shuangyou') and three interspecific hybrids ('Beibinghong', 'Xuelanhong', 'Zuoyouhong') from two regions (Zuojia and Ji'an, Jilin, China) were identified via HS-SPME-GC/MS. The results showed that V. amurensis grapes had a greater concentration of aroma compounds than the interspecific hybrid berries. 'Beibinghong' was relatively rich in terpenes, although their concentrations were all lower than the threshold. 'Shuangfeng' contained more concentrations of free C6/C9 compounds, alcohols, aromatics and aldehydes/ketones than the other cultivars. The aroma characteristics of 'Beiguolan' and 'Shuanghong' were relatively similar. The grapes from the lower temperature and more fertile soil of Zuojia contained more C6/C9 compounds, norisoprenoids and alcohols, while aromatics were more abundant in the grapes from Ji'an, which was warmer than the Zuojia region. Herbaceous, floral, fruity and sweet were the main aroma series of V. amurensis grapes. Our study could provide a reference for the development and utilization of V. amurensis grapes and lay a foundation for the development of wild grape cultivars and the production of wines with characteristic styles.


Asunto(s)
Frutas , Cromatografía de Gases y Espectrometría de Masas , Genotipo , Odorantes , Vitis , Compuestos Orgánicos Volátiles , Vino , Vitis/química , Vitis/genética , Vitis/clasificación , Odorantes/análisis , Compuestos Orgánicos Volátiles/análisis , Frutas/química , Vino/análisis , China , Hibridación Genética , Microextracción en Fase Sólida
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