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Correction to: European Review for Medical and Pharmacological Sciences 2023; 27 (4): 1553-1564. DOI: 10.26355/eurrev_202302_31398-PMID: 36876711-published online on February 15, 2023. After publication, the authors applied some corrections to the galley proof: - The order of Table I and II has been inverted. - The scale bar of Figure 9A has been inserted in the Legend. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31398.
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OBJECTIVE: Surgery and radioactive iodine therapy are the main treatments for papillary thyroid carcinoma (PTC), and effective drugs are lacking. As a promising natural product, nobiletin (NOB) has a wealth of pharmacological activities like anti-tumor, antivirus, and other effects. In this research, bioinformatics methods and cellular assays were combined to explore how NOB inhibited PTC. MATERIALS AND METHODS: Our NOB targets were derived from three databases, including the SwissTargetPrediction database, Traditional Chinese Medicine System Pharmacology Database, and the TargetNet server. Four databases were used to identify disease-related targets: GeneCards, PharmGkb, Online Mendelian Inheritance in Man, and DisGeNET. Finally, cross-targets of disease and drug were deemed as pharmacological targets, and they were used for GO and KEGG enrichment analysis. STRING and Cytoscape were applied for PPI Network and core Targets Ranking. Molecular docking analysis validated binding affinity values for NOB and core targets. By using cell proliferation and migration assays, NOB was assessed for its effects on PTC proliferation and migration phenotype. Western blot validated the downregulation of the PI3K/Akt pathway. RESULTS: (1) Preliminarily, 85 NOB targets were predicted for NOB intervention in PTC. (2) Our core target screening identified TNF, TP53, and EGFR, and our molecular docking results confirmed good binding between NOB and protein receptors. (3) NOB inhibited proliferation and migration of PTC cells. PI3K/AKT pathway target proteins were downregulated. CONCLUSIONS: (1) Bioinformatics analyses revealed that NOB may inhibit PTC by regulating TNF, TP53, EGFR and PI3K/AKT signalling pathway. (2) As evidenced by cell experiments, there was an inhibition of proliferating and migrating PTCs by NOB via the PI3K/AKT signalling pathway.
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Flavonas , Farmacología en Red , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Bases de Datos Genéticas , Receptores ErbB , Radioisótopos de Yodo , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Cáncer Papilar Tiroideo/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Flavonas/farmacologíaRESUMEN
This study describes a surgical technique for secondary unilateral cleft rhinoplasty using autologous costal cartilage grafts. The grafts were designed preoperatively and analysed three-dimensionally in 15 Asian patients using a photogrammetric camera. Detailed measurements of the nasal anatomy were taken both preoperatively and postoperatively; the same measurements were also taken from the pre-planned images of the anticipated result. When compared to the preoperative measurements, the postoperative three-dimensional outcome analysis revealed several statistically significant improvements in the nasal appearance: nasal dorsal length (P < 0.001), nasal column height (P = 0.001), nasal column width (P = 0.002), nasal lobule height (P = 0.008), cleft side nostril height (P < 0.001) and width (P < 0.001), columella-labial angle (P = 0.001), and nasal tip projection to nasal dorsum length ratio (NTP/NDL) (P = 0.001). Conversely, the comparison of the postoperative and preoperative design measurements showed mostly no statistically significant differences. Thus, utilizing autologous costal cartilage is a reliable approach with predictable and consistent results in secondary cleft rhinoplasty.
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Labio Leporino , Cartílago Costal , Enfermedades Nasales , Rinoplastia , Labio Leporino/cirugía , Cartílago Costal/trasplante , Humanos , Tabique Nasal/cirugía , Nariz/cirugía , Enfermedades Nasales/cirugía , Estudios Retrospectivos , Rinoplastia/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Previous studies investigating donkey parentage and genetic diversity used horse-specific multiplex systems. However, several mis-allele and null-allele issues were found with some of the horse primers when used in donkeys. In 2017, the International Society for Animal Genetics (ISAG) recommended 13 dinucleotide short tandem repeats (STRs) (AHT4, ASB23, HMS2, HMS3, HMS6, HMS7, HMS18, HTG7, HTG10, TKY297, TKY312, TKY337 and TKY343) as a core panel that should be used to identify individuals and to test for parentage in donkeys. To date, no single multiplex STR typing system containing all 13 donkey STRs recommended by the ISAG has been reported. OBJECTIVES: To establish a novel and donkey-specific multiplex STR typing system containing all 13 recommended STRs. STUDY DESIGN: Assay development and validation in field population. METHODS: Primers for seven of the STRs were redesigned and conditions for polymerase chain reaction (PCR) were optimised. We analysed the allele sequences, sensitivity, species-specificity and stutter ratios of this new system. RESULTS: A 13-plex STR typing system for donkey was established. A full profile could be generated from a single PCR reaction using as little as 5 ng of DNA template with the 13 pairs of primers labelled with fluorescent dyes. An allele ladder, containing 101 alleles from the 13 STRs, was generated. No full genotype profile was generated with these primers if DNA from humans, or 11 other commonly encountered animals, was used. Genotypes could be generated for the horse and horse-donkey hybrids (mule and hinny). Stutter ratios and population genetic parameters were calculated based on samples from 150 donkeys. The combined probabilities of paternity exclusion for this system were 0.988907326 (CPEduo) and 0.999665018 (CPEtrio). MAIN LIMITATIONS: This system cannot detect sex. CONCLUSIONS: Our results indicate that our donkey-specific 13-plex STR typing system is sensitive, species-specific and robust for individual identification, paternity testing and population genetic analysis in donkeys, and has potential forensic applications.
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Equidae , Repeticiones de Microsatélite , Alelos , Animales , Genotipo , Caballos , Humanos , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
Objective: To analyze the infection status and recombination of Norovirus in patients with acute gastroenteritis in Ningxia. Methods: The specimens of 10 sentinel hospitals in Ningxia were collected from 2016 to 2017. Real-time quantitative PCR was used for nucleic acid detection. Gâ ¡-positive samples were amplified by RT-PCR for the RdRp and Capsid regions, then sequenced and genotyped. Evolution analysis was performed using software such as MEGA-X, and recombination analysis was performed using Simplot 3.5.1 and RDP4. Results: The age of the 2 334 cases was 1.42 (0.68, 7.69) years old, 1 133 cases in 2016 and 1 201 cases in 2017, 1 343 and 991 cases for males and females respectively. The positive rate of Norovirus Gâ genogroup was 0.86% (20/2 334), and Gâ ¡ genogroup was 14.82% (346/2 334). A total of 78 recombinant strains were sequenced and 12 recombinant types were found. Gâ ¡.Pe/Gâ ¡.4Sydney_2012 and Gâ ¡.P12/Gâ ¡.3 were the main epidemic strains, accounting for 35.90% (28 strains) and 32.05% (25 strain) respectively, followed by Gâ ¡.P16/Gâ ¡.2 accounting for 12.82% (10 strains). Among them,Gâ ¡.P7/Gâ ¡.6 (2 strains), Gâ ¡.P12/Gâ ¡.3 (6 strains), Gâ ¡.P16/Gâ ¡.1 (2 strains), Gâ ¡.P16/Gâ ¡.2 (5 strains), Gâ ¡.Pe/Gâ ¡.4 (7 strains) were detected for the first time in Ningxia. Recombinant strains were all intergenotype recombination, and the recombination breakpionts were all located within ORF1. Conclusion: Norovirus infection in Ningxia area was mainly in Gâ ¡ genogroup from 2016 to 2017, and most of them were recombinant strains. Gâ ¡.Pe/Gâ ¡.4Sydney_2012 and Gâ ¡.P12/Gâ ¡.3 were the main epidemic strains, followed by Gâ ¡.P16/Gâ ¡. 2.
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Infecciones por Caliciviridae/epidemiología , Gastroenteritis/virología , Norovirus/genética , Recombinación Genética , Niño , China , Femenino , Gastroenteritis/epidemiología , Genotipo , Humanos , Masculino , FilogeniaRESUMEN
BACKGROUND: Due to the thriving development of the modern horse industry and the occurrence of horse related crimes, the demand for methods of individual horse identification, parentage tests and other genetic analyses is increasing. Previous methods had disadvantages that decreased the accuracy of the results, lacked the inclusion of all commonly used short tandem repeats (STR) or increased the experimental cost and time. OBJECTIVES: We aimed to develop a novel 13-plex STR typing system to resolve the above issues. STUDY DESIGN: Experimental study. METHODS: Twelve autosomal and most commonly used di-nucleotide STRs (AHT4, AHT5, ASB2, ASB17, ASB23, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10 and VHL20), and a Y-chromosomal STR (YJ10) were included. We redesigned the primers of eight STRs to establish a novel multiplex PCR system and tested this system for species specificity, sensitivity and repeatability. RESULTS: Full profiles were easily generated in one fast PCR reaction using a low-cost polymerase, as little as 1 ng of horse DNA template and 13 pairs of primers labelled with fluorescent dyes. No full profile was generated from DNA templates of humans or other commonly encountered animals. We also established an allelic ladder that contained 110 alleles based on 200 horses from 12 breeds and calculated standard population genetic parameters based on 150 Thoroughbreds. Stutter analysis showed that the averages of the stutter ratios were distinctly lower than those of lower allele ratios and the combined probability of paternity exclusion for this system were 0.994659935 (CPEduo ) and 0.999854032 (CPEtrio ). MAIN LIMITATIONS: A nonspecific and relatively low peak at 316 bp was frequently observed in locus HMS2, which is a nonexistent allele in all horses and should be ignored. CONCLUSIONS: Our results indicate that this 13-plex STR genotyping system is sensitive, species-specific, cost-effective and robust for applications in the horse industry and forensic investigation.
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Caballos/genética , Repeticiones de Microsatélite/genética , Reacción en Cadena de la Polimerasa/veterinaria , Alelos , Animales , Reacción en Cadena de la Polimerasa/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Especificidad de la EspecieRESUMEN
The superior colliculus (SC) is a major site of sensorimotor integration in which sensory inputs are processed to initiate appropriate motor responses. Projections from the primary visual cortex (V1) to the SC have been shown to exert a substantial influence on visually induced behavior, including "freezing." However, it is unclear how V1 corticotectal terminals affect SC circuits to mediate these effects. To investigate this, we used anatomical and optogenetic techniques to examine the synaptic properties of V1 corticotectal terminals. Electron microscopy revealed that V1 corticotectal terminals labeled by anterograde transport primarily synapse (93%) on dendrites that do not contain gamma aminobutyric acid (GABA). This preference was confirmed using optogenetic techniques to photoactivate V1 corticotectal terminals in slices of the SC maintained in vitro. In a mouse line in which GABAergic SC interneurons express green fluorescent protein (GFP), few GFP-labeled cells (11%) responded to activation of corticotectal terminals. In contrast, 67% of non-GABAergic cells responded to activation of V1 corticotectal terminals. Biocytin-labeling of recorded neurons revealed that wide-field vertical (WFV) and non-WFV cells were activated by V1 corticotectal inputs. However, WFV cells were activated in the most uniform manner; 85% of these cells responded with excitatory postsynaptic potentials (EPSPs) that maintained stable amplitudes when activated with light trains at 1-20 Hz. In contrast, in the majority of non-WFV cells, the amplitude of evoked EPSPs varied across trials. Our results suggest that V1 corticotectal projections may initiate freezing behavior via uniform activation of the WFV cells, which project to the pulvinar nucleus.
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Terminales Presinápticos/ultraestructura , Corteza Visual/ultraestructura , Vías Visuales/ultraestructura , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , OptogenéticaRESUMEN
Glaucoma can lead to irreversible visual impairment. The pathogenesis of glaucoma is complicated and it is difficult to diagnose early. As an objective and functional examination tool, visual electrophysiology has its own advantages to detect early glaucomatous damage. It can indicate early functional degeneration of retinal ganglion cells and can direct doctors to diagnose and give treatment to glaucoma patients. It has been proved that the pattern electroretinogram, photopic negative response and multifocal electroretinogram can provide most of the information in the early diagnosis of glaucoma. This article overviews the latest application progress of these three visual electrophysiological techniques.(Chin J Ophthalmol, 2018, 54:868-872).
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Diagnóstico Precoz , Potenciales Evocados Visuales , Glaucoma , Electrofisiología , Electrorretinografía , Glaucoma/diagnóstico , HumanosRESUMEN
OBJECTIVES: The objective of this study was to evaluate whether higher reported accuracy estimates are associated with shorter time to publication among imaging diagnostic accuracy studies. METHODS: We included primary imaging diagnostic accuracy studies, included in meta-analyses from systematic reviews published in 2015. For each primary study, we extracted accuracy estimates, participant recruitment periods and publication dates. Our primary outcome was the association between Youden's index (sensitivity + specificity - 1, a single measure of diagnostic accuracy) and time to publication. RESULTS: We included 55 systematic reviews and 781 primary studies. Study completion dates were missing for 238 (30%) studies. The median time from completion to publication in the remaining 543 studies was 20 months (IQR 14-29). Youden's index was negatively correlated with time from completion to publication (rho = -0.11, p = 0.009). This association remained significant in multivariable Cox regression analyses after adjusting for seven study characteristics: hazard ratio of publication was 1.09 (95% CI 1.03-1.16, p = 0.004) per unit increase for logit-transformed estimates of Youden's index. When dichotomizing Youden's index by a median split, time from completion to publication was 20 months (IQR 13-33) for studies with a Youden's index below the median, and 19 months (14-27) for studies with a Youden's index above the median (p = 0.104). CONCLUSION: Imaging diagnostic accuracy studies with higher accuracy estimates were weakly associated with a shorter time to publication. KEY POINTS: ⢠Higher accuracy estimates are weakly associated with shorter time to publication. ⢠Lag in time to publication remained significant in multivariate Cox regression analyses. ⢠No correlation between accuracy and time from submission to publication was identified.
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Diagnóstico por Imagen/normas , Sesgo de Publicación , Edición/estadística & datos numéricos , Bibliometría , Humanos , Metaanálisis como Asunto , Modelos de Riesgos Proporcionales , Proyectos de Investigación , Literatura de Revisión como Asunto , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Objective: To investigate the mental health status in migrant workers in a labor-intensive enterprise and related influencing factors. Methods: Typical sampling was used to perform an investigation in 910 migrant workers in a large foreign-funded labor-intensive enterprise in Shenzhen, China. All the respondents gave informed consent and completed the questionnaire independently and anonymously. The self-reported mental health status was evaluated using the Beck Anxiety Inventory, Beck Depression Inventory, and General Health Questionnaire. Results: Of all the migrant workers in this enterprise, 7.2% had a positive self-reported anxiety symptom, 25.4% had a moderate or severe self-reported depression symptom, and 76.4% had a poor self-reported general health status. Age had significant influence on the self-reported depression symptom (χ2=21.968, P<0.05) ; age did not have significant influence on the self-reported anxiety and general health status (χ2=6.616ã12.498, both P>0.05) . The knowledge of occupational hazards had significant influence on mental health status (χ2Depression=47.289, χ2General health=21.087, both P<0.05) . The feeling of work had significant influence on self-reported depression and general health status (χ2Depression=52.406, χ2General health=17.327, both P<0.05) . Attention to self mental health had significant influence on self-reported depression (χ2=17.714, P<0.05) , and whether the person wanted to learn the knowledge of mental health had significant influence on self-reported anxiety (χ2= 6.145, P<0.05) . Conclusion: The self-reported mental health status in migrant workers is poor and is associated with age, worry about exposure to occupational hazard factors, emphasis on mental health knowledge, and a focus on personal mental health. Therefore, targeted occupational health education and occupational mental health education should be strengthened.
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Salud Mental , Enfermedades Profesionales/psicología , Migrantes/psicología , Adulto , Ansiedad , Trastornos de Ansiedad , China , Depresión , Personal de Salud , Estado de Salud , Humanos , Encuestas y CuestionariosRESUMEN
The objective of this study was to evaluate the estrogenic effects and mechanisms of three flavonoid components in Xiaoyao powder: quercetin, kaempferol, and isorhamnetin. The drugs were used to treat estrogen receptor (ER)-positive human breast cancer MCF-7 cells, and proliferation was measured using the MTT method. The expression of proteins and mRNA of the ER subtype were measured using western blotting and real time polymerase chain reaction. The quercetin (10(-2) µM, 10(-3) µM), kaempferol (100 µM, 10(-2) µM), and isorhamnetin (10(-3) µM) promoted the proliferation of MCF-7 cells, and the expression of ERα and ERß proteins and mRNA were all increased significantly (P < 0.05). These effects were reversed by treatment with 0.1 µM estrogen antagonist ICI182780. Three flavonoid components in Xiaoyao powder increased the expression of proteins and mRNA of ERα and ERß and promoted the proliferation of MCF-7 cells. These estrogenic effects were mediated by the ER.
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Medicamentos Herbarios Chinos/química , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Quempferoles/farmacología , Quercetina/análogos & derivados , Quercetina/farmacología , ARN Mensajero/genética , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Receptor alfa de Estrógeno/agonistas , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/agonistas , Receptor beta de Estrógeno/metabolismo , Ácido Fólico/análogos & derivados , Ácido Fólico/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Quempferoles/antagonistas & inhibidores , Células MCF-7 , Polvos/química , Quercetina/antagonistas & inhibidores , ARN Mensajero/agonistas , ARN Mensajero/metabolismo , Transducción de SeñalRESUMEN
Recent studies underscore the importance of crosstalk between tumor-associated macrophages (TAMs) and tumor cells in cancer progression and metastasis. In our study, AdCD68STAT3ß, a recombinant adenovirus containing a STAT3ß gene driven by CD68 macrophage-specific promoter, was used to suppress STAT3 and the downstream signaling pathways in TAMs. The results showed that STAT3ß gene under the control of CD68 macrophage-specific promoter was only expressed in macrophages, which significantly inhibited the motility and invasion of breast cancer cells when co-cultured with 4T1 cells. Moreover, cell-specific STAT3ß expression in TAMs extended survival of tumor-bearing mice and suppressed breast tumor growth, angiogenesis and metastasis, by regulating the crosstalk between tumor cells and TAMs. Therefore, our study provided a novel strategy for the antitumor effects of STAT3ß.
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Macrófagos/inmunología , Macrófagos/metabolismo , Neoplasias Mamarias Experimentales/terapia , Factor de Transcripción STAT3/biosíntesis , Adenoviridae/genética , Adenoviridae/metabolismo , Animales , Antineoplásicos , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Femenino , Expresión Génica , Células HEK293 , Humanos , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/inmunología , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factor de Transcripción STAT3/genética , Transducción de SeñalRESUMEN
Emerging evidence has shown that cancer stem cells (CSCs) are the cellular determinants to promote cancer invasion and metastasis. However, the mechanism underlying CSC invasion remains unknown. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression, and their expressions are often dysregulated in cancers. In the present study, we demonstrated that two functionally related microRNAs, miR-20a and -106a (miR-20a/106a), were capable of enhancing the invasiveness of CD133(+) glioma stem cells (GSCs) isolated from both glioblastoma cell line U87 and primary human glioma specimens. We found that the level of miR-20a/106a in GSCs was significantly higher than that in the committed CD133(-) glioma cells, and correlated with the invasive capability of GSCs. By bioinformatic analysis, we identified tissue inhibitor of metalloproteinases-2 (TIMP-2) as one of the miR-20a/106a-targeted genes. TIMP-2 level correlated inversely with miR-20/106 expression. Directly targeting by miR-20a/106a on 3'-untranslation region (3'-UTR) of TIMP-2 mRNA was confirmed by 3'-UTR dual-luciferase reporter assay. Knockdown of miR-20a/106a in GSCs increased endogenous TIMP-2 protein abundance, thereby inhibiting GSC invasion. We also found that Nordy, a synthetic lipoxygenase inhibitor, inhibited GSC invasiveness by elevating the expression of TIMP-2 via downregulation of miR-20a/106a. Our results indicate that miR-20a/106a has a key role in GSC invasion and may serve as targets for treatment of glioblastoma.
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Neoplasias Encefálicas/patología , Glioblastoma/patología , MicroARNs/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/fisiología , Antígeno AC133 , Animales , Antígenos CD/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/metabolismo , Humanos , Inhibidores de la Lipooxigenasa/farmacología , Masculino , Masoprocol/análogos & derivados , Masoprocol/farmacología , Ratones , Ratones Desnudos , MicroARNs/biosíntesis , MicroARNs/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Trasplante de Neoplasias , Células Madre Neoplásicas , Péptidos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño , Inhibidor Tisular de Metaloproteinasa-2/biosíntesis , Trasplante HeterólogoRESUMEN
Antidepressant treatments enhance synaptic connectivity in stress-sensitive brain regions such as the medial prefrontal cortex (mPFC). The mPFC plays a key role in controlling cognition and emotion. While several signaling pathways are involved in this enhancement process, the exact mechanisms are not fully established. In the present study, we evaluated the role of the glycogen synthase kinase 3ß (GSK3ß)/ß-catenin signaling pathway in the antidepressant effect of citalopram in rats exposed to forced swim stress. The acute stress group received the classic, two-day variant of the forced swimming test (FST), whereas the chronic stress group received swim stress for 14 consecutive days. We found that rats exposed to acute swim stress showed depressive-like behaviors and expressed normal GSK3ß and ß-catenin levels in the mPFC. Chronic swim stress, also induced a significant behavior changes but was associated with decreased levels of phosphorylated GSK3ß and ß-catenin in the rat's mPFC. Chronic citalopram treatment alleviated these behavioral changes in chronically stressed rats and normalized the downregulation of GSK3ß/ß-catenin signaling. Our results suggest that GSK3ß/ß-catenin signaling plays an important role in chronic but not acute stress-related depression and contributes, at least in part, to the antidepressant effects of citalopram in distinct brain regions associated with mood regulation.
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Antidepresivos/farmacología , Citalopram/farmacología , Depresión/tratamiento farmacológico , Glucógeno Sintasa Quinasa 3/metabolismo , Corteza Prefrontal/efectos de los fármacos , beta Catenina/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Western Blotting , Enfermedad Crónica , Depresión/etiología , Depresión/metabolismo , Activación Enzimática/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta , Masculino , Corteza Prefrontal/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Estrés Psicológico/complicacionesRESUMEN
Brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal survival, proliferation, and synaptic remodeling and modulates the function of many other neurotransmitters. Additionally, it likely underlies neurodegenerative and psychiatric disorders, including alcohol dependence-related depression (AD-D). Here, we investigated the possible association between three single nucleotide polymorphisms (SNPs) of the BDNF gene (rs13306221, rs6265, rs16917204) and AD-D. Of 548 patients with alcohol dependence (AD), 166 had AD-D and 312 healthy controls. Response to 8-week sertraline treatment was also assessed. The frequency of the A allele of rs6265 (Val66Met) was significantly higher in AD-D patients than in the healthy controls (p=0.009 after Bonferroni correction). The analysis revealed a strong association between the rs6265 genotype distribution and AD-D (p=0.005 after Bonferroni correction), and the A allele of rs6265 was significantly overrepresented in AD-D patients compared to AD without depression (AD-nD) patients (p=0.001 after Bonferroni correction). Additionally, carriers of the A allele of rs6265 responded better to sertraline treatment (p=0.001). Our results suggested a novel association between BDNF rs6265 and AD-D. These findings might lead to earlier detection of AD-D, perhaps providing better tools for clinical care of these patients in the future.
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Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/genética , Depresión/tratamiento farmacológico , Depresión/genética , Polimorfismo de Nucleótido Simple/genética , Sertralina/uso terapéutico , Adulto , Alcoholismo/complicaciones , Alcoholismo/genética , Distribución de Chi-Cuadrado , China , Depresión/etiología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Vesicular stomatitis virus (VSV) is an oncolytic virus currently being investigated as a promising tool to treat cancer because of its ability to selectively replicate in cancer cells. To enhance the oncolytic property of the nonpathologic laboratory strain of VSV, we generated a recombinant vector [rVSV(MΔ51)-M3] expressing murine gammaherpesvirus M3, a secreted viral chemokine-binding protein that binds to a broad range of mammalian chemokines with high affinity. As previously reported, when rVSV(MΔ51)-M3 was used in an orthotopic model of hepatocellular carcinoma (HCC) in rats, it suppressed inflammatory cell migration to the virus-infected tumor site, which allowed for enhanced intratumoral virus replication leading to increased tumor necrosis and substantially prolonged survival. These encouraging results led to the development of this vector for clinical translation in patients with HCC. However, a scalable current Good Manufacturing Practice (cGMP)-compliant manufacturing process has not been described for this vector. To produce the quantities of high-titer virus required for clinical trials, a process that is amenable to GMP manufacturing and scale-up was developed. We describe here a large-scale (50-liter) vector production process capable of achieving crude titers on the order of 10(9) plaque-forming units (PFU)/ml under cGMP. This process was used to generate a master virus seed stock and a clinical lot of the clinical trial agent under cGMP with an infectious viral titer of approximately 2 × 10(10) PFU/ml (total yield, 1 × 10(13) PFU). The lot has passed all U.S. Food and Drug Administration-mandated release testing and will be used in a phase 1 clinical translational trial in patients with advanced HCC.
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Biotecnología/métodos , Vectores Genéticos , Neoplasias/terapia , Viroterapia Oncolítica , Virus de la Estomatitis Vesicular Indiana , Animales , Técnicas de Cultivo de Célula , Línea Celular , Cromatografía por Intercambio Iónico , Cricetinae , Vectores Genéticos/genética , Vectores Genéticos/ultraestructura , Células HEK293 , Humanos , Ultrafiltración , Virus de la Estomatitis Vesicular Indiana/genética , Virus de la Estomatitis Vesicular Indiana/ultraestructuraRESUMEN
AIM: To investigate the effect of copper on the virulence of Edwardsiella tarda. METHODS AND RESULTS: The pathogenic Edw. tarda strain TX5 was cultured under copper-stressed conditions and examined for any potential alteration in capacities that are associated with pathogenicity. The results showed that compared to untreated TX5, Cu-treated TX5 exhibits reduced planktonic and biofilm growth, an impaired ability to adhere to host mucus, modulation of host immune response, and dissemination in host blood and liver. Consistent with these observations, the overall bacterial virulence of Cu-treated TX5 is significantly attenuated. SDS-PAGE analyses of whole cell protein production showed that Cu-treated TX5 differs from the untreated TX5 in its production of at least one protein. Quantitative real time reverse transcriptase PCR analyses showed that copper treatment decreased the expression of virulence-associated genes encoding components of the type III and type VI secretion systems, the Eth haemolysin system, and the LuxS/AI-2 quorum-sensing system. CONCLUSIONS: Prolonged exposure to copper has multiple effects on TX5 and results in significant attenuation of bacterial virulence. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study demonstrate that copper treatment has a broad and profound effect on the virulence-associated capacities of TX5, which is exerted at least in part at the transcription level. These findings provide new insights to the antimicrobial mechanism of copper.
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Sulfato de Cobre/farmacología , Edwardsiella tarda/efectos de los fármacos , Edwardsiella tarda/patogenicidad , Infecciones por Enterobacteriaceae/veterinaria , Enfermedades de los Peces/microbiología , Lenguado/microbiología , Animales , Adhesión Bacteriana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , Edwardsiella tarda/genética , Edwardsiella tarda/fisiología , Electroforesis en Gel de Poliacrilamida , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/microbiología , Enfermedades de los Peces/inmunología , Regulación Bacteriana de la Expresión Génica , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Inmunidad Innata , Viabilidad Microbiana , Percepción de Quorum/genética , Transcripción Genética , Virulencia/genética , Factores de Virulencia/genética , Factores de Virulencia/metabolismoRESUMEN
A successful experiment with a physical model requires necessary conditions of similarity. This study presents an experimental method with a semi-scale physical model. The model is used to monitor and verify soil conservation by check dams in a small watershed on the Loess Plateau of China. During experiments, the model-prototype ratio of geomorphic variables was kept constant under each rainfall event. Consequently, experimental data are available for verification of soil erosion processes in the field and for predicting soil loss in a model watershed with check dams. Thus, it can predict the amount of soil loss in a catchment. This study also mentions four criteria: similarities of watershed geometry, grain size and bare land, Froude number (Fr) for rainfall event, and soil erosion in downscaled models. The efficacy of the proposed method was confirmed using these criteria in two different downscaled model experiments. The B-Model, a large scale model, simulates watershed prototype. The two small scale models, D(a) and D(b), have different erosion rates, but are the same size. These two models simulate hydraulic processes in the B-Model. Experiment results show that while soil loss in the small scale models was converted by multiplying the soil loss scale number, it was very close to that of the B-Model. Obviously, with a semi-scale physical model, experiments are available to verify and predict soil loss in a small watershed area with check dam system on the Loess Plateau, China.
Asunto(s)
Monitoreo del Ambiente/métodos , Suelo/análisis , Movimientos del Agua , China , Conservación de los Recursos Naturales , Modelos TeóricosRESUMEN
BACKGROUND: To date, there has been no large-scale survey of geriatric depression (GD) involving both rural and urban areas in China using standardized assessment tools and diagnostic criteria. This study aimed to determine the 12-month and lifetime prevalence rates of GD and sociodemographic correlates in urban and rural regions of Beijing, China.MethodA total of 1601 elderly patients (aged 60 years) were randomly selected and interviewed in Beijing using the Composite International Diagnostic Interview (CIDI 1.0). Basic sociodemographic and clinical data were also collected during the interviews. RESULTS: The overall 12-month prevalence of GD was 4.33%, and the 12-month prevalence rates for men and women were 2.65% and 5.83% respectively. The overall lifetime prevalence of GD was 7.83%, and lifetime prevalence rates for men and women were 4.65% and 10.66% respectively. Female sex, lower educational level, monthly income, rural abode, and the presence of one or more major medical conditions were associated with increased risk of GD. Of the GD subjects interviewed, 25.2% were receiving some type of treatment, with only 4.7% preferring to seek treatment from mental health professionals. CONCLUSIONS: Although still relatively low by international standards, there is an increasing trend in the prevalence of GD in China. The low percentage of subjects treated for GD is a major public health concern that should be addressed urgently.