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1.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38801700

RESUMEN

irGSEA is an R package designed to assess the outcomes of various gene set scoring methods when applied to single-cell RNA sequencing data. This package incorporates six distinct scoring methods that rely on the expression ranks of genes, emphasizing relative expression levels over absolute values. The implemented methods include AUCell, UCell, singscore, ssGSEA, JASMINE and Viper. Previous studies have demonstrated the robustness of these methods to variations in dataset size and composition, generating enrichment scores based solely on the relative gene expression of individual cells. By employing the robust rank aggregation algorithm, irGSEA amalgamates results from all six methods to ascertain the statistical significance of target gene sets across diverse scoring methods. The package prioritizes user-friendliness, allowing direct input of expression matrices or seamless interaction with Seurat objects. Furthermore, it facilitates a comprehensive visualization of results. The irGSEA package and its accompanying documentation are accessible on GitHub (https://github.com/chuiqin/irGSEA).


Asunto(s)
Algoritmos , Análisis de la Célula Individual , Programas Informáticos , Análisis de la Célula Individual/métodos , Humanos , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos
2.
FASEB J ; 38(2): e23444, 2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38252081

RESUMEN

Metabolic reprogramming is a hallmark of cancer. The nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway maintains sufficient cellular NAD levels and is required for tumorigenesis and development. However, the molecular mechanism by which NAMPT contributes to HBV-associated hepatocellular carcinoma (HCC) remains not fully understood. In the present study, our results showed that NAMPT protein was obviously upregulated in HBV-positive HCC tissues compared with HBV-negative HCC tissues. NAMPT was positively associated with aggressive HCC phenotypes and poor prognosis in HBV-positive HCC patients. NAMPT overexpression strengthened the proliferative, migratory, and invasive capacities of HBV-associated HCC cells, while NAMPT-insufficient HCC cells exhibited decreased growth and mobility. Mechanistically, we demonstrated that NAMPT activated SREBP1 (sterol regulatory element-binding protein 1) by increasing the expression and nuclear translocation of SREBP1, leading to the transcription of SREBP1 downstream lipogenesis-related genes and the production of intracellular lipids and cholesterol. Altogether, our data uncovered an important molecular mechanism by which NAMPT promoted HBV-induced HCC progression through the activation of SREBP1-triggered lipid metabolism reprogramming and suggested NAMPT as a promising prognostic biomarker and therapeutic target for HBV-associated HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nicotinamida Fosforribosiltransferasa , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Virus de la Hepatitis B , Lipogénesis , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Nicotinamida Fosforribosiltransferasa/genética
3.
FASEB J ; 37(7): e22985, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37249350

RESUMEN

Osteoporosis is one of the chronic complications of type 1 diabetes with high risk of fracture. The prevention of diabetic osteoporosis is of particular importance. Static magnetic fields (SMFs) exhibit advantages on improvement of diabetic complications. The biological effects and mechanism of SMFs on bone health of type 1 diabetic mice and functions of bone cells under high glucose have not been clearly clarified. In animal experiment, six-week-old male C57BL/6J mice were induced to type 1 diabetes and exposed to SMF of 0.4-0.7 T for 4 h/day lasting for 6 weeks. Bone mass, biomechanical strength, microarchitecture and metabolism were determined by DXA, three-point bending assay, micro-CT, histochemical and biochemical methods. Exposure to SMF increased BMD and BMC of femur, improved biomechanical strength with higher ultimate stress, stiffness and elastic modulus, and ameliorated the impaired bone microarchitecture in type 1 diabetic mice by decreasing Tb.Pf, Ct.Po and increasing Ct.Th. SMF enhanced bone turnover by increasing the level of markers for bone formation (OCN and Collagen I) as well as bone resorption (CTSK and NFAT2). In cellular experiment, MC3T3-E1 cells or primary osteoblasts and RAW264.7 cells were cultured in 25 mM high glucose-stimulated diabetic marrow microenvironment under differentiation induction and exposed to SMF. SMF promoted osteogenesis with higher ALP level and mineralization deposition in osteoblasts, and it also enhanced osteoclastogenesis with higher TRAP activity and bone resorption in osteoclasts under high glucose condition. Further, SMF increased iron content with higher FTH1 expression and regulated the redox level through activating HO-1/Nrf2 in tibial tissues, and lowered hepatic iron accumulation by BMP6-mediated regulation of hepcidin and lipid peroxidation in mice with type 1 diabetes. Thus, SMF may act as a potential therapy for improving bone health in type 1 diabetes with regulation on iron homeostasis metabolism and redox status.


Asunto(s)
Resorción Ósea , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Osteoporosis , Ratones , Masculino , Animales , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Experimental/terapia , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Osteogénesis , Hierro/metabolismo , Oxidación-Reducción , Campos Magnéticos , Glucosa
4.
Int J Equity Health ; 23(1): 122, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877457

RESUMEN

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.


Asunto(s)
Accesibilidad a los Servicios de Salud , Profilaxis Posexposición , Rabia , Humanos , Rabia/prevención & control , Rabia/epidemiología , China/epidemiología , Profilaxis Posexposición/estadística & datos numéricos , Profilaxis Posexposición/métodos , Incidencia , Análisis Espacial , Disparidades en Atención de Salud/estadística & datos numéricos , Animales
5.
Cell Mol Life Sci ; 79(9): 501, 2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36036324

RESUMEN

BACKGROUND: Poly-GA, a dipeptide repeat protein unconventionally translated from GGGGCC (G4C2) repeat expansions in C9orf72, is abundant in C9orf72-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9orf72-ALS/FTD). Although the poly-GA aggregates have been identified in C9orf72-ALS/FTD neurons, the effects on UPS (ubiquitin-proteasome system) and autophagy and their exact molecular mechanisms have not been fully elucidated. RESULTS: Herein, our in vivo experiments indicate that the mice expressing ploy-GA with 150 repeats instead of 30 repeats exhibit significant aggregates in cells. Mice expressing 150 repeats ploy-GA shows behavioral deficits and activates autophagy in the brain. In vitro findings suggest that the poly-GA aggregates influence proteasomal by directly binding proteasome subunit PSMD2. Subsequently, the poly-GA aggregates activate phosphorylation and ubiquitination of p62 to recruit autophagosomes. Ultimately, the poly-GA aggregates lead to compensatory activation of autophagy. In vivo studies further reveal that rapamycin (autophagy activator) treatment significantly improves the degenerative symptoms and alleviates neuronal injury in mice expressing 150 repeats poly-GA. Meanwhile, rapamycin administration to mice expressing 150 repeats poly-GA reduces neuroinflammation and aggregates in the brain. CONCLUSION: In summary, we elucidate the relationship between poly-GA in the proteasome and autophagy: when poly-GA forms complexes with the proteasome, it recruits autophagosomes and affects proteasome function. Our study provides support for further promoting the comprehension of the pathogenesis of C9orf72, which may bring a hint for the exploration of rapamycin for the treatment of ALS/FTD.


Asunto(s)
Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Animales , Autofagia , Proteína C9orf72 , Ratones , Complejo de la Endopetidasa Proteasomal , Sirolimus
6.
Ecotoxicol Environ Saf ; 230: 113125, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34971997

RESUMEN

OBJECTIVES: This study evaluated the associated biological effects of radio-frequency (RF) exposure at 16 T magnetic resonance imaging (MRI) on mice health. MATERIAL AND METHODS: A total of 48 healthy 8-week-old male C57BL/6 mice were investigated. A 16 T high static magnetic field (HiSMF) was generated by a superconducting magnet, and a radiofrequency (RF) electromagnetic field for hydrogen resonance at 16 T (700 MHz) was transmitted via a homemade RF system. The mice were exposed inside the 16 T HiSMF with the 700 MHz RF field for 60 min, and the body weight, organ coefficients, histomorphology of major organs, and blood indices were analyzed for the basal state of the mice on day 0 and day 14. The Heat Shock Protein 70 (HSP70), cyclooxygenase 2 (COX2), and interleukin- 6 (IL-6) were used to evaluate the thermal effects on the brain. Locomotor activity, the open field test, tail suspension test, forced swimming test, and grip strength test were used to assess the behavioral characteristics of the mice. RESULTS: The 16 T HiSMF with 700 MHz RF electromagnetic field exposure had no significant effects on body weight, organ coefficients, or histomorphology of major organs in the mice. On day 0, the expressions of HSP70 and COX2 in the brain were increased by 16 T HiSMF with 700 MHz RF electromagnetic field exposure. However, the expression of HSP70, COX2, and IL-6 had no significant difference compared with the sham group on day 14. Compared with the sham groups, the meancorpuscularvolume (MCV) on day 0 and the total protein (TP) on day 14 were increased significantly, whereas the other blood indices did not change significantly. The 16 T HiSMF with 700 MHz RF electromagnetic field exposure caused the mice to briefly circle tightly but had no effect on other behavioral indicators. CONCLUSIONS: In summary, 16 T HiSMF with 700 MHz RF electromagnetic field exposure for 60 min did not have severe effects on mice.

7.
J Cell Mol Med ; 24(13): 7201-7213, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32410294

RESUMEN

Non-alcoholic fatty liver disease is a public health problem worldwide associated with high morbidity and hepatic steatosis, but no effective therapeutic interventions. Magnesium isoglycyrrhizinate (MGIG), a derivative of an active component of Glycyrrhiza glabra, is widely used for the treatment of inflammatory liver diseases due to its potent anti-inflammatory and hepatoprotective activities. Hence, this study aimed to study the effects of MGIG on hepatic steatosis in mice fed a high-fat diet (HFD). Oil Red O staining and transmission electron microscopy revealed a decrease in lipid accumulation in the liver after MGIG treatment along with improved mitochondrial ultramicrostructures. Metabonomic analysis demonstrated that MGIG intervention increased glutamate utilization in mitochondria by promoting the uptake of glutamate into the tricarboxylic acid (TCA) cycle. The NAD+ /NADH ratio and the expression of other lipid-metabolism-related genes were increased in MGIG-treated livers. Transcriptome sequencing showed that the expression of TLR4, an isoform of the innate immunity Toll-like receptors (TLRs), was significantly decreased after MGIG treatment, suggesting a link between the anti-inflammatory effects of MGIG and its suppression of lipidation. Our results reveal the potent effects of MGIG on lipid metabolism and suggest that hepatic TLR4 might be a crucial therapeutic target to regulate energy homeostasis in hepatic steatosis.


Asunto(s)
Metabolismo Energético , Homeostasis , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ciclo del Ácido Cítrico/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/genética , Regulación de la Expresión Génica/efectos de los fármacos , Glutamatos/metabolismo , Homeostasis/efectos de los fármacos , Homeostasis/genética , Gotas Lipídicas/efectos de los fármacos , Gotas Lipídicas/metabolismo , Gotas Lipídicas/ultraestructura , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Hígado/efectos de los fármacos , Hígado/lesiones , Hígado/patología , Hígado/ultraestructura , Masculino , Ratones Endogámicos C57BL , NAD/metabolismo , Saponinas/farmacología , Receptor Toll-Like 4/metabolismo , Triterpenos/farmacología
8.
Br J Cancer ; 123(7): 1154-1163, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32632148

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) has a crucial role in the progression of hepatocellular carcinoma (HCC). Tumour cells must develop anoikis resistance in order to survive before metastasis. This study aimed to investigate the mechanism of IQGAP1 in HBV-mediated anoikis evasion and metastasis in HCC cells. METHODS: IQGAP1 expression was detected by immunohistochemistry, real-time PCR and immunoblot analysis. Lentiviral-mediated stable upregulation or knockdown of IGAQP1, immunoprecipitation, etc. were used in function and mechanism study. RESULTS: IQGAP1 was markedly upregulated in HBV-positive compared with HBV-negative HCC cells and tissues. IQGAP1 was positively correlated to poor prognosis of HBV-associated HCC patients. IQGAP1 overexpression significantly enhanced the anchorage-independent growth and metastasis, whereas IQGAP1-deficient HCC cells are more sensitive to anoikis. Mechanistically, we found that HBV-induced ROS enhanced the association of IQGAP1 and Rac1 that activated Rac1, leading to phosphorylation of Src/FAK pathway. Antioxidants efficiently inhibited IQGAP1-mediated anoikis resistance and metastasis. CONCLUSIONS: Our study indicated an important mechanism by which upregulated IQGAP1 by HBV promoted anoikis resistance, migration and invasion of HCC cells through Rac1-dependent ROS accumulation and activation of Src/FAK signalling, suggesting IQGAP1 as a prognostic indicator and a novel therapeutic target in HCC patients with HBV infection.


Asunto(s)
Carcinoma Hepatocelular/patología , Quinasa 1 de Adhesión Focal/fisiología , Neoplasias Hepáticas/patología , Especies Reactivas de Oxígeno/metabolismo , Proteína de Unión al GTP rac1/fisiología , Proteínas Activadoras de ras GTPasa/fisiología , Familia-src Quinasas/fisiología , Animales , Anoicis , Línea Celular Tumoral , Femenino , Hepatitis B/complicaciones , Humanos , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Transducción de Señal/fisiología
9.
Opt Express ; 28(10): 15601-15610, 2020 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-32403584

RESUMEN

Manipulating circularly polarized (CP) light waves at will are highly important for photonic researches and applications. Recently, while Pancharatnam-Berry (PB) metasurfaces have shown unprecedented capabilities to control CP light, meta-devices constructed so far always suffer from the limitations of low-efficiency and narrow bandwidth. Here, we propose a scheme to construct PB metasurfaces with these two issues well addressed. To verify our idea, two PB meta-devices are designed and fabricated for achieving high-efficiency and broadband photonic spin Hall effect and focusing effect, respectively. Experimental results, in good agreement with full wave simulations, demonstrate the desired functionalities with efficiencies reaching 80% within an ultra-wide frequency band (8.2-17.3GHz). The proposed design scheme is generic and can be extended to high-frequency regimes. Our work can stimulate the realizations of high-performance and broadband PB meta-devices with diversified functionalities.

10.
J Cell Biochem ; 120(6): 9193-9202, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30506723

RESUMEN

Immunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO-296 [2-(6-chlorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO-296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO-296 did not affect the expression of cluster of differentiation (CD)-25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO-296 inhibited interleukin (IL)-6, IL-17, and interferon gamma expression but had no effect on IL-2, IL-4, or IL-10. Yet, importantly, PO-296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mitogen-activated protein kinase pathway. In conclusion, these findings indicate that PO-296 inhibits human activated T-lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO-296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.


Asunto(s)
Benzoxazoles/química , Benzoxazoles/farmacología , Activación de Linfocitos/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Transcripción STAT5/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Humanos , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Linfocitos T/citología
11.
J Phys Chem A ; 123(16): 3435-3440, 2019 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-30951309

RESUMEN

HS2 molecules play an important role in the photochemical processes in combustion, atmosphere, and interstellar medium, yet our knowledge about the electronic excited states in the UV region is limited. In this study, we perform high-level ab initio calculations on electronic states of HS2 using the internally contracted multireference configuration interaction method including the Davidson correction (icMRCI + Q) method. The vertical transition energies, oscillator strengths, electron configurations, and transitions of thirteen electronic states of HS2 with energy up to 8 eV are calculated at the icMRCI + Q/aug-cc-pv(5 + d)Z level. Based on the calculated potential energy curves, we investigate the interaction and photodissociation mechanism of the electronic states, which should shed some light on the decomposition processes of the gas-phase HS2 molecules in the ultraviolet region.

12.
J Chem Phys ; 150(22): 224305, 2019 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-31202252

RESUMEN

The possibility of laser cooling of bismuth hydride (BiH) molecules has been investigated based on high-level ab initio calculations by considering the core-valence and the spin-orbit coupling (SOC) effects. The potential energy curves of the 12 Λ-S states as well as the 25 Ω states that split from them via SOC are obtained by multireference configuration interaction plus the Davidson correction. The properties of b-X transition are investigated. Based on our calculations, we show that the transition between Ω states b0+-X10+ of BiH is a possible candidate for laser cooling, with consideration of the intermediate Ω state X21. An optical cycling scheme is proposed by utilizing four lasers at wavelengths around 471 and 601 nm with 5400 cycles for photon absorption/emission and a sub-microkelvin temperature. Our study should shed some light on searching for possible molecular candidates for laser cooling with the existence of an intermediate electronic state.

13.
J Cell Biochem ; 119(7): 5382-5390, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29345351

RESUMEN

Benzoxazole and its derivatives have been widely studied in recent years due to their various biological properties. A previous study has demonstrated that K313 (1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole derivative, inhibits T cell proliferation to yield immunosuppressive effects. However, there are no related reports about its anti-inflammatory effects. In the present study, we investigated the anti-inflammatory properties and the underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. K313 dose-dependently (5, 10, and 20 µM) inhibited LPS-stimulated nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 3-nitrotyrosine (3-NT) production and significantly decreased the gene transcription levels of inducible nitric oxide (iNOS), IL-6, and TNF-α. In addition, the results showed that the inflammatory cytokines suppressed by K313 were not regulated by p65 NF-κB, ERK1/2, AKT, or p38 MAPK. Instead, K313 increased phosphorylation of glycogen synthase kinase-3 beta (GSK-3ß) (Ser9) resulting in GSK-3ß deactivation. Moreover, in LPS-stimulated RAW264.7 macrophages, K313 and lithium chloride (LiCl) had a synergistic effect on the anti-inflammatory response. These results indicated that K313 exhibited anti-inflammatory properties and revealed the potential mechanism. K313 can increase GSK-3ß (Ser9) phosphorylation to decrease GSK-3ß activation in LPS-induced RAW264.7 macrophages.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Benzoxazoles/farmacología , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/química , Benzoxazoles/química , Células Cultivadas , Citocinas/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
14.
J Med Virol ; 89(12): 2075-2083, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28786502

RESUMEN

With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Inmunoensayo/métodos , Poliovirus/genética , Poliovirus/inmunología , Animales , Salud Global , Células HEK293 , Humanos , Poliomielitis/inmunología , Poliovirus/aislamiento & purificación , Poliovirus/fisiología , Vacuna Antipolio Oral , Ratas , Replicación Viral
17.
Mol Carcinog ; 55(1): 77-89, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25557841

RESUMEN

Glioblastoma multiforme (GBM) cancer stem cells (GSCs) are responsible for the progression and recurrence of GBM after conventional therapy. Morusin possesses anti-cancer activity in vitro. The purpose of this study is to confirm the growth inhibition effect of morusin on human GSCs growth in vitro and in vivo and to explore the possible mechanism of its activity. Human GSCs were enriched under nonadhesive culture system, and characterized through neurosphere formation, toluidine blue staining, immunofluorescence staining, Western blotting analysis of stemness markers of CD133, nestin, Sox2 and Oct4, and tumorigenecity in vivo; the growth inhibition effect of morusin on human GSCs in vitro and in vivo were tested by cell cytotoxicity, neurosphere formation inhibition, adipogenic differentiation, apoptosis induction, and tumor growth inhibition in vivo assays. The potential molecular mechanisms underlying the growth inhibition effect of morusin on GSCs in vitro and in vivo were investigated with Western blotting evaluation of stemness, adipogenic, and apoptotic proteins in morusin treated GSCs and tumor tissues. GSCs enriched under nonadhesive culture system possess stemness characterstics; Morusin inhibited GSCs growth in vitro and in vivo, it reduced stemness of GSCs, induced them adipocyte-like transdifferention and apoptosis. Morusin has the potential to inhibit human GSCs growth in vitro and in vivo through stemness attenuation, adipocyte transdifferentiation, and apoptosis induction.


Asunto(s)
Apoptosis/efectos de los fármacos , Autorrenovación de las Células/efectos de los fármacos , Transdiferenciación Celular/efectos de los fármacos , Flavonoides/farmacología , Glioblastoma/metabolismo , Glioblastoma/patología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Animales , Apoptosis/genética , Biomarcadores , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Expresión Génica , Glioblastoma/genética , Humanos , Ratones , Esferoides Celulares , Carga Tumoral , Células Tumorales Cultivadas
18.
Lancet ; 381(9871): 1037-45, 2013 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-23352749

RESUMEN

BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6­36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 6­11 months [infants] and 120 aged 12­36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3­954·3]), followed by those who received the 320 U formulation (497·9 [383·1­647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3­1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9­676·6] in infants and 708·4 [524·1­957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5­457·5] in infants and 498·0 [383·4­646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9­48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12­5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.


Asunto(s)
Enterovirus Humano A/inmunología , Infecciones por Enterovirus/prevención & control , Vacunas Virales/efectos adversos , Anticuerpos Antivirales/sangre , Formación de Anticuerpos/efectos de los fármacos , Preescolar , Método Doble Ciego , Femenino , Humanos , Inmunidad Celular/efectos de los fármacos , Lactante , Masculino , Resultado del Tratamiento , Vacunas Virales/inmunología
19.
Nutr Cancer ; 66(4): 613-24, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24660968

RESUMEN

Lithocarpus polystachyus leaves have been used as tea beverage and folk medicine for healthy care in the Southwest of China. The purpose of this study is to investigate the anticancer activity of Lithocarpus polystachyus Rehd leaf aqueous extract (LPAE) and to explore the possible mechanism of its activity. Growth inhibition effects of LPAE breast cancer were tested in vitro and in vivo. The possible mechanism of its activity was analyzed with cell biological and molecular biological assays. After LPAE treatment, the proliferation and colony formation of cancer cells decreased; apoptotic cells increased; DNA fragmentations were evident; mRNA and protein expressions of PPARγ, Bax, and caspase-3 genes increased and expressions of cyclin D1 and Bcl-2 genes decreased; in vivo experiment, LPAE inhibited human beast cancer growth. The findings in this experimental study suggested that LPAE has potential cytotoxic and apoptotic effects on human breast cancer cells in vitro and inhibits the cancer growth in vivo, and its mechanism of activity might be associated with apoptosis induction of cancer cells through upregulation of the mRNA and protein expressions of PPARγ, Bax, and capase-3 genes and downregulation of the expressions of cyclin D1 and Bcl-2 genes.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Fagaceae/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , China , Ciclina D1/genética , Ciclina D1/metabolismo , Fragmentación del ADN/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , PPAR gamma/genética , PPAR gamma/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125058, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39226669

RESUMEN

In organic solar cells (OSCs), comprehending the charge transfer mechanism at D/A interfaces is crucial for photoinduced charge generation and enhancing power conversion efficiency (PCE). The charge transfer mechanism and photovoltaic performance of the parallel stacking interface configuration of the PTQ10 polymer donor and T2EH non-fullerene acceptor (NFA) are systematically studied at the microscopic scale. The analysis of the electron-hole distribution of the PTQ10/T2EH excited states revealed the presence of multiple charge excitation modes and charge transfer pathways. Using Marcus theory, we examine the charge separation rate (KCS) of PTQ10/T2EH under external electric field (Fext) modulation, and it is clarified that reorganization energy (λ) is the main factor that affects the KCS. Our results show that Fext has a positive impact on the photovoltaic properties of PTQ10/T2EH thin films, as evidenced by the modulation of the open circuit voltage (VOC), voltage loss (VLOSS) and fill factor (FF). Overall, this study provides valuable theoretical insights for Fext to accelerate the charge separation process and enhance photovoltaic efficiency.

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