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1.
Fish Shellfish Immunol ; 144: 109291, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38104702

RESUMEN

Discus fish (Symphysodon aequifasciatus) exhibit a unique parental care behavior: adult discus produces secretion through their skin, on which the larvae live after birth. The immune components in the skin mucus of parental discus would change during different parental care. C-type lectins (CTLs) could identify and eliminate pathogenic microorganisms and play important roles in innate immunity. Studies on CTLs of discus fish especially during parental care, however, are scarce. Here, we identified 186 CTL genes that distributed in 27 linkage groups based on discus genome. Phylogenetic analysis showed that S. aequifasciatus CTL (SaCTL) members were grouped into 14 subfamilies. A total of 80 gene replication events occurred, of which 15 pairs were subjected to segmental duplication and 65 pairs underwent tandem duplication. Ka/Ks ranged from 0.11 (SaCTL25/SaCTL158) to 0.68 (SaCTL36/SaCTL69), all undergoing purifying selection. RNA-seq analysis revealed that SaCTL members, including duplicated genes, in the skin of parental discus show distinct expression patterns in different care stages and between male and female parents. The SaCTL11 was differentially expressed in most care stages and reached the maximum after eggs spawned, but the expression of its paired SaCTL14 was low in each stage. The SaCTL39 increased first and then decreased, reaching a peak in eggs spawned, while paired SaCTL48 first decreased and then increased, reaching a peak in hatched eggs. The SaCTL50 was differentially expressed only in female fish during care, but not in male fish. These results provide new insights into the evolution and potential functional differentiation of CTLs in discus fish during parental care.


Asunto(s)
Cíclidos , Lectinas Tipo C , Femenino , Masculino , Animales , Filogenia , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Cíclidos/genética , Piel/metabolismo , Larva
2.
Environ Res ; 236(Pt 2): 116772, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37517496

RESUMEN

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.


Asunto(s)
Arsénico , Agua Potable , Nacimiento Prematuro , Efectos Tardíos de la Exposición Prenatal , Embarazo , Lactante , Niño , Femenino , Humanos , Recién Nacido , Peso al Nacer , Arsénico/toxicidad , Arsénico/análisis , Estudios de Cohortes , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/epidemiología , Agua Potable/análisis , Retardo del Crecimiento Fetal , Exposición Materna/efectos adversos
3.
Environ Res ; 197: 111178, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33865818

RESUMEN

The adaptation mechanism of a wild type (WT) and resistant type (Re) strain of the aerobic denitrifier Enterobacter cloacae strain HNR to short-term ZnO nanoparticle (NP) stresses was investigated. The results showed that Re maintained higher nitrite reductase (NIR) and nitrate reductase (NR) activities and showed lower increment of reactive oxygen species (ROS) than WT, under ZnO NP stresses. The affinity constant (KA) of WT to Zn2+ was 5.06 times that of Re, indicating that Re was more repulsive to Zn2+ released by ZnO NPs. Transcriptomic analysis revealed that the up-regulation of the nitrogen metabolism of Re helped maintain NIR and NR activities, that the enhancement of purine metabolism lowered the intracellular ROS increment, and that the up-regulation of cationic antimicrobial peptide resistance contributed to the lower KA of Re to Zn2+. These findings provided new insights into the adaptation mechanism of aerobic denitrifying bacteria to ZnO NPs.


Asunto(s)
Nanopartículas , Óxido de Zinc , Aclimatación , Adaptación Fisiológica , Enterobacter cloacae/genética , Óxido de Zinc/toxicidad
4.
Phytother Res ; 35(6): 3167-3180, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33885189

RESUMEN

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Espirostanos/farmacología , Animales , Línea Celular , Regulación hacia Abajo , Hipocampo/efectos de los fármacos , Humanos , Inflamasomas/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor PAR-1/genética , Receptor PAR-1/metabolismo , Transducción de Señal/efectos de los fármacos , Estreptozocina
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(2): 163-168, 2018 Mar.
Artículo en Zh | MEDLINE | ID: mdl-29737053

RESUMEN

The 21th century is the century of exploring and utilizing the underground space. In the future, more and more people will spend more and more time living or/and working in the underground space. However,we know little about the effect on the health of human caused by the underground environment. Herein,we systematically put forward the strategic conception of the deep-underground medicine,in order to reveal relative effects and mechanism of the potential factors in the deep underground space on human's physiological and psychological healthy,and to work out the corresponding countermeasures. The original deep-underground medicine includes the following items. ①To model different depth of underground environment according to various parameters (such as temperature,radiation,air pressure, rock,microorganism), and to explore their quantitative character and effects on human health and mechanism. ② To study the psychological change, maintenance of homeostasis and biothythm of organism in the deep underground space. ③ To learn the association between psychological healthy of human and the depth, structure, physical environment and working time of underground space. ④ To investigate the effect of different terrane and lithology on healthy of human and to deliberate their contribution on organism growth. ⑤ To research the character and their mechanism of growth,metabolism,exchange of energy,response of growth, aging and adaptation of cells living in deep underground space. ⑥ To explore the physiological feature,growth of microbiome and it's interaction with host in the deep underground space. ⑦ To develop deep-underground simulation space, the biologically medical technology and equipments. As a research basis,a deep-underground medical lab under a rock thickness of about 1 470 m has been built,which aims to operate the research of the effect on living organism caused by different depth of underground environment.


Asunto(s)
Investigación Biomédica/tendencias , Espacios Confinados , Humanos
6.
Tumour Biol ; 36(3): 1395-401, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25744731

RESUMEN

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expressions at posttranscriptional level. Growing evidence points to their significant role in the acquisition of drug resistance in cancers. Studies show that miRNAs are often aberrantly expressed in human cancer cells which are associated with tumorigenesis, metastasis, invasiveness, and drug resistance. Breast cancer is the leading cause of cancer-induced death in women. Over the last decades, increasing attention has been paid to the effects of miRNAs on the development of breast cancer drug resistance. Among them, miR-155 takes part in a sequence of bioprocesses that contribute to the development of such drug resistance, including repression of FOXO3a, enhancement of epithelial-to-mesenchymal transition (EMT) and mitogen-activated protein kinase (MAPK) signaling, reduction of RhoA, and affecting the length of telomeres. In this review, we discuss the role of miR-155 in the acquisition of breast cancer drug resistance. This will provide a new way in antiresistance treatment of drug-resistant breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Resistencia a Antineoplásicos/genética , MicroARNs/genética , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos
7.
Tumour Biol ; 35(7): 6327-34, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24648265

RESUMEN

MicroRNA-452 (miRNA-452) was overexpressed in docetaxel-resistant human breast cancer MCF-7 cells (MCF-7/DOC). However, its role in modulating the sensitivity of breast cancer cells to docetaxel (DOC) remains unclear. The aim of this study is to investigate the role of miRNA-452 in the sensitivity of breast cancer cells to DOC.Real-time quantitative PCR (RT-qPCR) were used to identify the differential expression of miRNA-452 between MCF-7/DOC and MCF-7 cells. MiRNA-452 mimic was transfected into MCF-7 cells and miRNA-452 inhibitor was transfected into MCF-7/DOC cells. The role of miRNA-452 in these transfected cells was evaluated using RT-qPCR, MTT assay, and flow cytometry assay. The relationship of miRNA-452 and its predictive target gene "anaphase-promoting complex 4" (APC4) was analyzed by RT-qPCR and Western blot.MiRNA-452 showed significantly higher expression (78.9-folds) in MCF-7/DOC cells compared to parental MCF-7 cells. The expression of miRNA-452 in the mimic transfected MCF-7 cells was upregulated 212.2-folds (P < 0.05) compared to its negative control (NC), and the half maximal inhibitory concentration (IC50) value of DOC (1.98 ± 0.15 µM) was significantly higher than that in its NC (0.85 ± 0.08 µM, P < 0.05) or blank control (1.01 ± 0.19 µM, P < 0.05). Furthermore, its apoptotic rate (6.3 ± 1.3 %) was distinctly decreased compared with that in its NC (23.8 ± 6.6 %, P < 0.05) or blank control (18.6 ± 4.7 %, P < 0.05). In contrast, the expression of miRNA-452 in the inhibitor-transfected MCF-7/DOC cells was downregulated 0.58-fold (P < 0.05) compared to its NC, the IC50 value of DOC (44.5 ± 3.2 µM) was significantly lower than that in its NC (107.3 ± 6.63 µM, P < 0.05) or blank control (102.22 ± 11.34 µM, P < 0.05), and the apoptotic rate (45.5 ± 10.8 %) was distinctly increased compared with its NC (9.9 ± 2.2 %, P < 0.05) and blank control (9.4 ± 2.5 %, P < 0.05). Further, there was an inverse association between miRNA-452 and APC4 expression in breast cancer cells in vitro.Dysregulation of miRNA-452 involved in the DOC resistance formation of breast cancer cells may be, in part, via targeting APC4.


Asunto(s)
Neoplasias de la Mama/genética , MicroARNs/genética , Subunidad Apc4 del Ciclosoma-Complejo Promotor de la Anafase/genética , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Docetaxel , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , MicroARNs/biosíntesis , Taxoides/administración & dosificación
8.
Tumour Biol ; 35(10): 9649-59, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24969560

RESUMEN

Breast cancer (BCa) remains chemo-unresponsive by inevitable progression of resistance to first-line treatment with docetaxel (doc). Emerging studies indicate that exosomes act as mediators of intercellular communication between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development. Such modulatory effects have been related to the constant shuttle of biologically active molecules including microRNAs (miRNAs). Here, we aimed to investigate the relevance of exosome-mediated miRNA delivery in resistance transmission of BCa subpopulations. Using microarray and polymerase chain reaction, we found that exosomes from doc-resistant BCa cells (D/exo) loaded cellular miRNAs. Following D/exo transfer to the fluorescent sensitive cells (GFP-S), some miRNAs were significantly increased in recipient GFP-S. Target gene prediction and pathway analysis revealed the involvement of the top 20 most abundant miRNAs of D/exo in pathways implicated in therapy failure. Coculture assays showed that miRNA-containing D/exo increased the overall resistance of GFP-S to doc exposure. Moreover, D/exo was able to alter gene expression in GFP-S. Our results open up an intriguing possibility that drug-resistant BCa cells may spread chemoresistance to sensitive ones by releasing exosomes and that the effects could be partly attributed to the intercellular transfer of specific miRNAs.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos/genética , Exosomas/metabolismo , MicroARNs/genética , Comunicación Celular , Línea Celular Tumoral , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena en Tiempo Real de la Polimerasa
9.
Tumour Biol ; 35(11): 10773-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25077924

RESUMEN

Acquired drug resistance is a major obstacle to chemotherapy of cancers. In this study, we aim to investigate the role of exosomes in drug-resistance transfer between breast cancer cells and detect the probable mechanism. A docetaxel-resistant variant of MCF-7 cell line (MCF-7/DOC) was established and then compared with the drug-sensitive variant (MCF-7/S). Exosomes were expelled from the cell supernatant using ultracentrifugation. Drug resistance was assessed by apoptosis assay and MTT examination. Expressions of P-glycoprotein (P-gp) were analyzed by flow cytometry. Stained exosomes were absorbed by receipt cells. MCF-7/S in the presence of exosomes extracted from the supernatant of MCF-7/DOC (DOC/exo) acquired drug resistance, while MCF-7/S exposed to their own exosomes (S/exo) did not. P-gp expression patterns of exosomes were similar as the originated cells. P-gp expression of MCF-7/S increased after incubation with DOC/exo and was affected by the amount of exosomes. Exosomes are effective in transferring drug resistance as well as P-gp from drug-resistant breast cancer cells to sensitive ones. The delivery of P-gp via exosomes may be a mechanism of exosome-mediated drug resistance transfer.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Exosomas , Taxoides/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Docetaxel , Femenino , Citometría de Flujo , Humanos , Células Tumorales Cultivadas
10.
Sci Total Environ ; 914: 170002, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38220024

RESUMEN

The motility behaviors at the individual-cell level and the collective physiological responsive behaviors of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress were investigated. The results revealed that as salinity increased, electron transport activity and adenosine triphosphate content decreased from 15.75 µg O2/g/min and 593.51 mM/L to 3.27 µg O2/g/min and 5.34 mM/L, respectively, at 40 g/L, leading to a reduction in the rotation velocity and vibration amplitude of strain HNR. High salinity stress (40 g/L) down-regulated genes involved in ABC transporters (amino acids, sugars, metal ions, and inorganic ions) and activated the biofilm-related motility regulation mechanism in strain HNR, resulting in a further decrease in flagellar motility capacity and an increase in extracellular polymeric substances secretion (4.08 mg/g cell of PS and 40.03 mg/g cell of PN at 40 g/L). These responses facilitated biofilm formation and proved effective in countering elevated salt stress in strain HNR. Moreover, the genetic diversity associated with biofilm-related motility regulation in strain HNR enhanced the adaptability and stability of the strain HNR populations to salinity stress. This study enables a deeper understanding of the response mechanism of aerobic denitrifiers to high salt stress.


Asunto(s)
Enterobacter cloacae , Estrés Salino , Enterobacter cloacae/genética , Biopelículas , Matriz Extracelular de Sustancias Poliméricas , Iones , Estrés Fisiológico
11.
Synapse ; 67(12): 865-74, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23813456

RESUMEN

Our previous and other studies have confirmed that a selective M1 and M3 receptor antagonist, Penehyclidine hydrochloride (PHC), has neuroprotection activity in cerebral ischemia. However, the precise mechanisms of protection of PHC are still elusive. In this study we analyzed PHC-mediated neuroprotection on a model of brain ischemia (oxygen and glucose deprivation), named postischemic LTP (i-LTP). We found that the activation of NMDA receptor was required for the induction of i-LTP. Compared with scopolamine, PHC could prevent it due to selectively blocking M1 receptor, not M2 receptor, to decrease NMDAR activation. Our findings further showed that the inhibition of SK2 channels occluded the prevention of PHC on NMDAR activation. Furthermore, we confirmed that PHC exerted its roles through directly disinhibition of SK2 channels by blocking M1 receptor and subsequent restricting PKC activation. Moreover, our studies further revealed the critical roles of SK2 channels in i-LTP. Thus, the mechanisms of PHC in brain protection may be involved in suppression of NMDAR by regulation of SK2 channels. Our results obtained in effects of PHC on i-LTP further provided a better understanding of the therapy strategy during stroke and identified potential therapeutic targets to prevent development of ischemia.


Asunto(s)
Isquemia Encefálica/fisiopatología , Potenciación a Largo Plazo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Quinuclidinas/farmacología , Receptor Muscarínico M1/antagonistas & inhibidores , Receptor Muscarínico M3/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Bloqueadores de los Canales de Potasio/farmacología , Proteína Quinasa C/metabolismo , Ratas , Ratas Sprague-Dawley , Escopolamina/farmacología , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/antagonistas & inhibidores
12.
Gene ; 862: 147260, 2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-36775217

RESUMEN

Discus Symphysodon spp. employs an unusual parental care behavior where fry feed on parental skin mucus after hatching. Studies on discus immunoglobulin superfamily (IgSF) especially during parental care are scarce. Here, a total of 518 IgSF members were identified based on discus genome and clustered into 12 groups, unevenly distributing on 30 linkage groups. A total of 92 pairs of tandem duplication and 40 pairs of segmental duplication that underwent purifying selection were identified. IgSF genes expressed differentially in discus skin during different care stages and between male and female parents. Specifically, the transcription of btn1a1, similar with mammalian lactation, increased after spawning, reached a peak when fry started biting on parents' skin mucus, and then decreased. The expression of btn2a1 and other immune members, e.g., nect4, fcl5 and cd22, were up-regulated when fry stopped biting on mucus. These results suggest the expression differentiation of IgSF genes in skin of discus fish during parental care.


Asunto(s)
Cíclidos , Piel , Animales , Femenino , Masculino , Piel/metabolismo , Cíclidos/genética , Vertebrados , Inmunoglobulinas/metabolismo , Lactancia , Mamíferos
13.
Cancer Biomark ; 38(3): 321-332, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37545219

RESUMEN

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Neoplasias de la Próstata , Masculino , Humanos , Proteínas Proto-Oncogénicas c-akt , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Proliferación Celular
14.
Med Oncol ; 41(1): 32, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38150063

RESUMEN

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.The canonical Wnt/ß-catenin signaling pathway has been shown to be involved in the regulation of tumor proliferation, migration and differentiation. Activation of the canonical Wnt/ß-Catenin signaling pathway in the prostate has oncogenic effects. Drugs targeting the canonical Wnt/ß-catenin signaling pathway have great potential in the treatment of prostate cancer. In this study, we found that Gastrodin could significantly inhibit the proliferation of prostate cancer cell line PC3 and DU145. Oral administration Gastrodin could significantly inhibit the tumor growth of PC3 cells subcutaneously injected. Gastrodin has an inhibitory effect on canonical Wnt/ß-Catenin signaling pathway in Prostate cancer, and this inhibitory effect can be abolished by Wnt/ß-Catenin agonist LiCl. These findings raise the possibility that Gastrodin can be used in the treatment of Prostate cancer by targeting canonical Wnt/ß-Catenin signaling pathway.


Asunto(s)
Carcinoma , Neoplasias de la Próstata , Masculino , Humanos , Vía de Señalización Wnt , Neoplasias de la Próstata/tratamiento farmacológico , Alcoholes Bencílicos/farmacología , Proliferación Celular
15.
Chemosphere ; 309(Pt 1): 136646, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36183890

RESUMEN

The plastisphere refers to biofilm formation on the microplastic (MP) surface, but its subsequent functions, especially driving the nitrogen biogeochemical cycle, are rarely studied. Here, MPs were incubated in the pelagic water and benthic water-sediment interface of an aquaculture pond, and the two corresponding microcosms amended with incubated plastisphere were simulated. The results showed decreased ammonia concentrations and increased nitrification rates in microcosms with either pelagic or benthic plastispheres. To uncover the possible mechanisms, the community structure and function of the plastisphere were investigated. As clarified by 16S rRNA, the community diversity of the pelagic plastisphere was significantly higher than that of the corresponding hydrosphere. Plastisphere communities, especially those incubated in pelagic water, were separated from the hydrosphere. Moreover, the abundance of Proteobacteria increased while the abundance of Cyanobacteria decreased in both plastispheres. Metagenome further revealed that the abundance of amoA and annotated Nitrososphaeraceae_archaeon and hao and affiliated Nitrosomonas_europaea, which contributed to ammonia oxidation to nitrite, was higher in the benthic plastisphere. Comparing the pelagic plastisphere with the corresponding hydrosphere, however, the abundance of nxrA and annotated Nitrobacter hamburgensis and nxrB and the affiliated Nitrospira moscoviensis, which are involved in nitrite oxidation, was more abundant in the plastisphere. These findings suggest that the plastisphere might selectively enrich functional microorganisms and genes in a habitat-dependent manner to promote nitrification in aquaculture ponds.


Asunto(s)
Nitrificación , Plásticos , ARN Ribosómico 16S/genética , Amoníaco , Microplásticos , Nitritos , Estanques , Filogenia , Acuicultura , Nitrógeno , Agua , Oxidación-Reducción
16.
Orthop Surg ; 14(2): 435-442, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34939333

RESUMEN

This study was designed to analyze the causes of cervical adjacent segment degenerative disease (ASDis), evaluate the surgical outcomes of longitudinal spinous-splitting laminoplasty with coral bone (SLAC) during cervical reoperation, and accumulate data on reoperation with SLAC in a primary hospital. Based on the inclusion and exclusion criteria, we conducted a retrospective study involving 52 patients who underwent cervical reoperation for ASDis using SLAC at the spinal surgery department of the Beijing Jishuitan Hospital from 1998 to 2014. Among them, 39 were treated with anterior cervical fusion and internal fixation during the first operation (anterior cervical corpectomy with fusion [ACCF], n = 24; anterior cervical discectomy and fusion [ACDF], n = 11; and cervical disc arthroplasty [CDA], n = 4). Outcomes were the Japanese Orthopaedic Association (JOA) score, neck disability index (NDI) score, upper limb/neck and shoulder evaluated using a visual analogue scale (VAS), and rates of ASDis. In patients who underwent an anterior cervical approach in the first instance, the incidence of ASDis was significantly higher in the C3/4 gap than in the other gaps. In the ACCF group, the lateral radiograph of the cervical spine revealed that the distance between the anterior cervical plate and the adjacent segment disc was <5 mm in 15 (62.5%) cases and five (12.8%) cases, respectively, the internal fixation screws broke into the annulus of the adjacent segment. After the first SLAC, ASDis developed at C2/3 and C3/4 in four (30.8%) and eight (61.5%) cases, respectively. After reoperation, all cases were followed up for >5 (average, 6.2) years. The pre-reoperation and last follow-up values were as follows: mean Japanese Orthopaedic Association score, 10.2 ± 1.5 vs 15.5 ± 0.7 (P = 0.03); neck disability index, 26.2 vs 13.6 points (P = 0.01); upper-limb visual analog scale (VAS) score, 6.1 vs 2.6 points (P = 0.04); and neck and shoulder VAS score, 6.6 vs 2.1 points (P = 0.03). SLAC is a simple technique in which the local anatomy is clearly visible and satisfactory clinical outcomes are obtained.


Asunto(s)
Antozoos , Degeneración del Disco Intervertebral , Laminoplastia , Fusión Vertebral , Animales , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Discectomía/métodos , Estudios de Seguimiento , Humanos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Estudios Retrospectivos , Fusión Vertebral/métodos , Resultado del Tratamiento
17.
Water Res ; 191: 116800, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33433335

RESUMEN

Compartmentalization can protect cells from the interference of external toxic substances by sequestering toxic products. We hypothesized that proteinaceous nanocompartments may be a feasible candidate material to be added to genetically modified bacteria for the sequestration of toxic environmental products, which would open up a new bioremediation pathway. Here, we showed that the model bacterium (Escherichia coli) with self-assembling nanocompartments can remove silver (Ag) from water. Transmission electron microscopy and energy dispersive X-ray (TEM-EDX) analysis showed that the nanocompartments combined stably with silver in vitro. In addition, when exposed to 30 µM AgNO3, the survival rate of genetically modified bacteria (with nanocompartments) was 86%, while it was just 59% in the wild-type bacteria (without nanocompartments). Label-free quantitative proteomics indicated that the nanocompartments enhanced bacterial activity by inducing the up-regulation of protein processing and secondary metabolites, and decreased their intracellular silver concentration, both of which contributed to their increased resistance to toxic silver. This study on nanocompartments has contributed to a deeper understanding of how bacteria respond to environmental stressors like heavy metal pollutants in water. The technology promises to provide a new strategy for recycling heavy metals from sewage.


Asunto(s)
Nanopartículas del Metal , Plata , Bacterias , Escherichia coli , Microscopía Electrónica de Transmisión , Agua
18.
Phytomedicine ; 91: 153686, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34333330

RESUMEN

BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.


Asunto(s)
Enfermedad de Alzheimer , Encefalopatías/tratamiento farmacológico , Diabetes Mellitus Experimental , Espirostanos/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide , Péptidos beta-Amiloides/metabolismo , Animales , Ácido Aspártico Endopeptidasas , Línea Celular , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucógeno Sintasa Quinasa 3 beta , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , PPAR gamma , Fosforilación , Ratas , Proteínas tau/metabolismo
19.
Sci Total Environ ; 725: 138284, 2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32276046

RESUMEN

The aerobic denitrification process is a promising and cost-effective alternative to the conventional nitrogen removal process. Widely used ZnO nanoparticles (NPs) will inevitably reach wastewater treatment plants, and cause adverse impacts on aerobic denitrification and nitrogen removal. Therefore, a full understanding of the responses and adaption of aerobic denitrifiers to ZnO NPs is essential to develop effective strategies to reduce adverse effects on wastewater treatment. In this study, the responses and adaption to ZnO NPs were investigated of a wild type strain (WT) and a resistant type strain (Re) of aerobic denitrifying bacteria Enterobacter cloacae strain HNR. When exposed to 0.75 mM ZnO NPs, the nitrate removal efficiency of Re was 11.2% higher than that of WT. To prevent ZnO NPs entering cells by adsorption, the production of extracellular polymeric substances (EPS) of WT and Re strains increased 13.2% and 43.9%, respectively. The upregulations of amino sugar and carbohydrate-related metabolism contributed to the increase of EPS production, and the increased nitrogen metabolism contributed to higher activities of nitrate and nitrite reductases. Interestingly, cationic antimicrobial peptide resistance contributed to resist Zn (II) released by ZnO NPs, and many antioxidative stress-related metabolism pathways were upregulated to resist the oxidative stress resulting from ZnO NPs. These findings will guide efforts to improve the aerobic denitrification process in an environment polluted by NPs, and promote the application of aerobic denitrification technologies.


Asunto(s)
Desnitrificación , Óxido de Zinc , Enterobacter cloacae , Nitrógeno/análisis , Aguas Residuales
20.
Biochem Pharmacol ; 175: 113849, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32059841

RESUMEN

Gestational diabetes mellitus (GDM) is associated with an increased risk of progressing to type 2 DM and cardiovascular disease; however, the pathogenesis is still poorly understood. This study was to investigate roles of thrombin and its receptor protease-activated receptor 1 (PAR-1) and NLRP1 inflammasome in endothelial injury in GDM condition. Umbilical cord and plasma of GDM patients and high glucose (HG) cultured human umbilical vein endothelial cells (HUVECs) were used to examine the pathological changes of these pathways. Meanwhile, ameliorative effects and potential mechanisms of a natural product sarsasapogenin (Sar) were investigated in HUVECs. Thrombin/PAR-1 pathway, advanced glycation endproducts (AGEs) and their receptor (RAGE) axis, and the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome were activated in GDM condition and HG-cultured HUVECs, accompanied by endothelial injury (decreased cell viability and increased lactate dehydrogenase release). Nevertheless, thrombin inhibition or PAR-1 antagonism caused decreases in AGEs formation and RAGE expression in HG-cultured HUVECs, while AGEs inhibition or RAGE antagonism declined PAR-1 expression not thrombin activity. Furthermore, thrombin inhibition or PAR-1 antagonism restrained NLRP1 inflammasome activation in HG-cultured HUVECs; meanwhile, NLRP1 expression and interleukin 18 levels were remarkably reduced in HG-cultured HUVECs after PAR-1 knockdown. Interestingly, Sar co-treatment could suppress thrombin/PAR-1 pathway, NLRP1 inflammasome, and AGEs/RAGE axis. Together, endothelial damages in GDM were likely due to enhanced interaction between AGEs/RAGE axis and thrombin/PAR-1 pathway, followed by NLRP1 inflammasome activation. Moreover, Sar may act as a protective agent against endothelial injury in chronic HG condition.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Diabetes Gestacional/patología , Endotelio Vascular/patología , Inflamasomas/metabolismo , Receptor PAR-1/metabolismo , Trombina/metabolismo , Glucemia/análisis , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Medios de Cultivo/química , Diabetes Gestacional/sangre , Diabetes Gestacional/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Glucosa/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Proteínas NLR , Embarazo , Receptor PAR-1/genética , Transducción de Señal , Espirostanos/farmacología , Cordón Umbilical/efectos de los fármacos , Cordón Umbilical/metabolismo
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