RESUMEN
The abuse of 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug, can lead to a variety of disorders in neural system, including the death of retinal neural cells. MDMA at lower doses does not cause obvious cytotoxicity to photoreceptor cells, indicating potential indirect mechanisms which have not yet been elucidated. This study investigated the effect of MDMA at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Using a co-culture system, cytotoxicity was caused by MDMA on 661W cells after co-culturing with RAW264.7 macrophage. Results showed that MDMA induced the macrophages to M1 polarization, releasing more pro-inflammatory cytokines, upregulating the M1-related gene and protein expression. The phenotype, secretion pattern, and cytotoxicity of the macrophages treated by MDMA are comparable to those of the ones stimulated by IFNγ and LPS. Our study demonstrated that MDMA promoted macrophage polarization to M1 and induced inflammatory response, providing the scientific rationale for the photoreceptor cell damage caused by the MDMA abuse.
Asunto(s)
Alucinógenos/toxicidad , Macrófagos/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Citocromos c/metabolismo , Citocinas/genética , Citocinas/metabolismo , Daño del ADN , Macrófagos/fisiología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cerium-doped bismuth oxybromide (1%, 5% and 10% Ce-BiOBr) piezocatalysts were synthesized. The piezocatalytic activity was efficiently regulated by defect and morphology engineering. Among them, the 5% Ce-BiOBr exhibits the highest piezocatalytic hydrogen production property with an evolution rate of 1147.6 µmol g-1 h-1, nearly twice that of the original BiOBr. Additionally, the MO dye degradation efficiency of 5% Ce-BiOBr reaches 91.9% within 60 min, with a higher reaction kinetic constant (0.0376 min-1) that was 6.1 times larger than that of pure BiOBr. These outstanding performances of 5% Ce-BiOBr surpass those of most other piezocatalytic material systems.
RESUMEN
We describe a new stromata-producing Neotyphodium species symbiotic with clonal Calamagrostis epigeios (L.) Roth. Stromata on the grass, 47.5-186 mm long, occurred frequently, but neither perithecium nor mature ascus was observed. Morphology of fungal isolates obtained from symptomatic and asymptomatic tillers were identical to each other and similar to those of epichloë endophytes. In phylogenetic analysis all selected five fungal isolates clustered into a significantly distinct clade based on sequences of beta-tubulin gene (tubB) introns and translation elongation factor 1-alpha gene (tefA) introns with bootstrap values of 99%, supporting erection of a new species. Concerning the production of extremely long stromata on the host plants and absence of sexual spores, we propose the name Neotyphodium stromatolongum Y. Ji, L. Zhan et Z. Wang, sp. nov.
Asunto(s)
Neotyphodium/clasificación , Neotyphodium/fisiología , Poaceae/microbiología , China , Neotyphodium/citología , Neotyphodium/aislamiento & purificación , Filogenia , Poaceae/crecimiento & desarrollo , Especificidad de la Especie , Simbiosis/fisiologíaRESUMEN
By combining the fluorophores of axially chiral 1,1'-binaphthol (BINOL) and 1,4-dihydropyridine derivatives, axially chiral 1,4-dihydropyridine derivatives ((R)-/(S)-2) with aggregation-induced emission (AIE) in exciplexes were designed and synthesized. (R)-/(S)-2 emitted low fluorescence in THF solutions of their locally excited states; however, they emitted red-shifted fluorescence in the aggregate state upon exciplex formation. Moreover, (R)-/(S)-2 showed linear and multi-exponential relationships between their local excited and exciplex fluorescence intensities and the viscosity of the medium, which allowed us to determine the viscosities of different mixed solvents. In addition, as an axially chiral viscosity probe, (R)-/(S)-2 show excellent CD signals and have potential applications in the fields of chiral recognition and fluorescence imaging, which will broaden the new family of AIE fluorophores. To the best of our knowledge, there are few reports of axially chiral intramolecular exciplex-mediated AIE molecules.
RESUMEN
PURPOSE: Successful treatment of colorectal cancer (CRC) is greatly impeded by metastasis and chemoresistance, particularly to 5-fluoruracil (5-Fu), one of the staples of clinical intervention in advanced CRC. The purpose of this study is to determine whether the gene glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) contributes to CRC cell metastasis and 5-Fu resistance. Ultimately, we evaluated the ability of microRNA 195-5p (miR-195-5p) to reduce GDPD5 expression and thus to enhance CRC cell susceptibility to chemotherapy. METHODS: We obtained human primary CRC and adjacent normal tissues from 15 patients who underwent CRC resection. Quantitative real-time polymerase chain reactions (qRT-PCR), western blot, and immunohistochemistry (IHC) were used to determine GDPD5 expression levels in the human CRC tissues, four CRC cell lines, and two 5-Fu resistant CRC cell lines. To measure the impact of GDPD5 on CRC cell chemoresistance, we silenced GDPD5 using GDPD5 siRNA and measured cell survival and apoptosis using MTT assays and TUNEL staining, respectively. Transwell Matrigel invasion assays were performed to explore whether GDPD5 affects the invasion capabilities of 5-Fu resistant CRC cells. Finally, to assess the effects of miR-195-5p on GDPD5 levels and CRC cell chemoresistance, we generated luciferase reporter plasmids with either the wild-type 3'UTR miR-195-5p potential binding sites or mutant binding sites of GDPD5. RESULTS: We first determined that GDPD5 mRNA and protein are overexpressed in human primary CRC tissues as compared to adjacent normal tissues. GDPD5 overexpression was also evident in four CRC cell lines (Caco-2, HCT8, HCT116 and SW480), as well as in the two 5-Fu resistant CRC cell lines that we generated (HCT116/5-Fu and SW480/5-Fu). Using MTT assays and TUNEL staining of HCT116/5-Fu and SW480/5-Fu cells, we found that GDPD5 silencing sensitizes 5-Fu resistant CRC cells to 5-Fu. Furthermore, GDPD5 silencing in 5-Fu resistant CRC cells reduced the epithelial-to-mesenchymal transition (EMT) and cell invasion, both of which are crucial for CRC metastasis. We then used the bioinformatics algorithm TargetScan to identify the miRNA miR-195-5p, which targets two regions of GDPD5 3'UTR. By generating luciferase reporter plasmids with the 3'UTR miR-195-5p binding sites, we ultimately determined that miR-195-5p increases chemosensitivity and cell apoptosis in 5-Fu resistant CRC cells. CONCLUSION: This study identifies the gene GDPD5 as an effector of chemoresistance and metastasis in CRC. Furthermore, our results demonstrate that miR-195-5p is a potent suppressor of GDPD5 and that, as such, it significantly increases chemosensitivity and apoptosis in chemoresistant CRC cells. This study thus not only identifies potential prognostic biomarkers of CRC, but it also opens the possibility for incorporating miR-195-5p into current therapeutic regimens to overcome barriers to successful CRC treatment.
Asunto(s)
Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , MicroARNs/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Humanos , MicroARNs/genética , Metástasis de la Neoplasia , Hidrolasas Diéster Fosfóricas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and causes a high rate of mortality in affected adults. Many subtypes of ALL exist with disruptions in distinct genetic pathways, including those regulated by miRNAs. Here we identify miR-187-5p as being highly upregulated in B-cell ALL and a driver of cellular proliferation and suppressor of apoptosis. We show that miR-187-5p directly targets the 3'-UTR of DKK2 to mediate these effects. We further determine that inhibition of DKK2 by miR-187-5p in Nalm-6 B cells leads to inappropriate activation of Wnt/ß-catenin signaling. Together, these findings reveal that the miR-187-5p-DKK2 pathway regulates Wnt/ß-catenin signaling, cell growth, and apoptosis. Our findings provide the first evidence of a role for miR-187-5p in promotion of B-cell ALL.
Asunto(s)
Apoptosis/genética , Péptidos y Proteínas de Señalización Intercelular/genética , MicroARNs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Interferencia de ARN , Regiones no Traducidas 3' , Biomarcadores de Tumor , Estudios de Casos y Controles , Línea Celular Tumoral , Proliferación Celular , Niño , Preescolar , Regulación Leucémica de la Expresión Génica , Humanos , Lactante , Recién Nacido , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Regulación hacia Arriba , Vía de Señalización WntRESUMEN
AIM: To investigate the expressions of type I collagen, α2 integrin and ß1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and ß1 integrin. METHODS: After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and ß1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular -7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. RESULTS: The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular -7D lens could decrease the levels of type I collagen, α2 integrin and ß1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION: bFGF can prevent the formation and development of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and ß1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.