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1.
J Virol ; 97(1): e0143122, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36541801

RESUMEN

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,500 human infections and the culling of millions of poultry. Despite large-scale poultry vaccination, H7N9 AIVs continue to circulate among poultry in China and pose a threat to human health. Previously, we isolated and generated four monoclonal antibodies (mAbs) derived from humans naturally infected with H7N9 AIV. Here, we investigated the hemagglutinin (HA) epitopes of H7N9 AIV targeted by these mAbs (L3A-44, K9B-122, L4A-14, and L4B-18) using immune escape studies. Our results revealed four key antigenic epitopes at HA amino acid positions 125, 133, 149, and 217. The mutant H7N9 viruses representing escape mutations containing an alanine-to-threonine substitution at residue 125 (A125T), a glycine-to-glutamic acid substitution at residue 133 (G133E), an asparagine-to-aspartic acid substitution at residue 149 (N149D), or a leucine-to-glutamine substitution at residue 217 (L217Q) showed reduced or completely abolished cross-reactivity with the mAbs, as measured by a hemagglutination inhibition (HI) assay. We further assessed the potential risk of these mutants to humans should they emerge following mAb treatment by measuring the impact of these HA mutations on virus fitness and evasion of host adaptive immunity. Here, we showed that the L4A-14 mAb had broad neutralizing capabilities, and its escape mutant N149D had reduced viral stability and human receptor binding and could be neutralized by both postinfection and antigen-induced sera. Therefore, the L4A-14 mAb could be a therapeutic candidate for H7N9 AIV infection in humans and warrants further investigation for therapeutic applications. IMPORTANCE Avian influenza virus (AIV) H7N9 continues to circulate and evolve in birds, posing a credible threat to humans. Antiviral drugs have proven useful for the treatment of severe influenza infections in humans; however, concerns have been raised as antiviral-resistant mutants have emerged. Monoclonal antibodies (mAbs) have been studied for both prophylactic and therapeutic applications in infectious disease control and have demonstrated great potential. For example, mAb treatment has significantly reduced the risk of people developing severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition to the protection efficiency, we should also consider the potential risk of the escape mutants generated by mAb treatment to public health by assessing their viral fitness and potential to compromise host adaptive immunity. Considering these parameters, we assessed four human mAbs derived from humans naturally infected with H7N9 AIV and showed that the mAb L4A-14 displayed potential as a therapeutic candidate.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Gripe Humana , Animales , Humanos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Epítopos , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H7N9 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/terapia , Evasión Inmune/genética , Mutación
2.
Zhonghua Yi Xue Za Zhi ; 104(10): 715-720, 2024 Mar 12.
Artículo en Zh | MEDLINE | ID: mdl-38462350

RESUMEN

Endometrial cancer is rising in incidence, especially in young women. This rise in incidence has implications for both primary prevention and screening in high-risk population. In the past several years, our understanding of the integration of clinically related genomic and pathologic data optimized the management of endometrial cancer. The updated 2023 FIGO staging includes the histological and molecular classification to better reflect the improved understanding of the heterogenous nature of endometrial carcinoma. Standard primary treatment is quite essential, however, selection of patients for adjuvant radiation or chemotherapy remains in controversy. Molecular characterization of endometrial cancer is becoming critical in directing treatment for advanced and recurrent disease, and the addition of immunotherapy to frontline chemotherapy is becoming the standard of care. More attention should be given to increase awareness of survivorship issues and improve patient quality-of-life.


Asunto(s)
Neoplasias Endometriales , Humanos , Femenino , Estadificación de Neoplasias , Neoplasias Endometriales/terapia , Neoplasias Endometriales/patología , Radioterapia Adyuvante , Quimioterapia Adyuvante , Histerectomía
3.
J Neuroophthalmol ; 43(1): 69-75, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36166787

RESUMEN

BACKGROUND: Episodic high-altitude exposure leads to optic disc edema and retinopathy. It is uncertain whether high-altitude exposure is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: We performed a single-center, retrospective, cross-sectional case study of 5 patients with high-altitude-associated NAION (HA-NAION) from April 2014 to April 2019. Main study parameters included known vascular risk factors for NAION, evolution of visual acuity, visual field, optic disc, and macula measurements. RESULTS: We studied 5 eyes of 5 patients with HA-NAION that occurred at 7,000-9,000 ft above sea level, 28 patients with classic NAION that developed at sea level (normal altitude NAION or NA-NAION), and 40 controls. All 5 patients with HA-NAION had clinically confirmed NAION by a neuro-ophthalmologist within 3-21 days of onset and comprehensive follow-up evaluations (average follow-up of 23 months). Other than high-altitude exposure, 4 of 5 patients had undiagnosed obstructive sleep apnea (OSA, apnea-hypopnea index 5.4-22.2) and 1 had systemic vascular risk factors. All patients had disc-at-risk in the contralateral eye. The best-corrected distance visual acuity was 20/20 to 20/70 (median logMAR 0) at presentation and 20/70 to counting finger (median logMAR 0) at ≥6 months. Automated static perimetry revealed average mean deviation of -18.6 dB at presentation and -22.1 dB at ≥6 months. The average retinal nerve fiber layer was 244 µm (80-348 µm) at onset and 59 µm (55-80 µm) at ≥6 months. The average ganglion cell complex thickness was 50 µm (43-54 µm) at onset and 52 µm (50-55 µm) at ≥6 months. The patients with OSA were started on home continuous positive airway pressure treatment. Visual outcomes were similar in patients with HA-NAION and NA-NAION. - After addressing all NAION risk factors, no new events occurred in the HA-NAION group within 2-8 years with or without repeat high-altitude exposure. CONCLUSIONS: NAION can occur under high-altitude conditions. HA-NAION is associated with relatively younger age at onset, disc-at-risk, and OSA. These patients exhibit a relatively progressive course of vision loss after initial onset and severe thinning of optic nerves on optical coherence tomography. Treatment for OSA is recommended, especially with repeated high-altitude exposure.


Asunto(s)
Neuropatía Óptica Isquémica , Humanos , Neuropatía Óptica Isquémica/diagnóstico , Neuropatía Óptica Isquémica/etiología , Células Ganglionares de la Retina , Estudios Retrospectivos , Estudios Transversales , Altitud , Tomografía de Coherencia Óptica/métodos
4.
Clin Exp Immunol ; 203(3): 433-447, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33232517

RESUMEN

Sepsis is an intractable clinical syndrome characterized by organ dysfunction when the body over-responds to an infection. Sepsis has a high fatality rate and lacks effective treatment. Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved protein with high expression in the immune system and is related to cytosolic iron assembly and tumour suppression; however, research has been rarely conducted on its immune functions. Our study found that Fam96a-/- mice significantly resisted lesions during sepsis simulated by caecal ligation and puncture (CLP) or endotoxicosis models. After a challenge with lipopolysaccharide (LPS) or infection, Fam96a-/- mice exhibited less organ damage, longer survival and better bacterial clearance with decreased levels of proinflammatory cytokines. While screening several subsets of immune cells, FAM96A-expressing macrophages as the key cell type inhibited sepsis development. In-vivo macrophage depletion or adoptive transfer experiments abrogated significant differences in the survival of sepsis between Fam96a-/- and wild-type mice. Results of the bone marrow-derived macrophage (BMDM) polarization experiment indicated that FAM96A deficiency promotes the transformation of uncommitted monocytes/macrophages (M0) into M2 macrophages, secreting fewer proinflammatory cytokines. FAM96A may mediate an immunometabolism shift - from oxidative phosphorylation (OXPHOS) to glycolysis - in macrophages during sepsis, mirrored by reactive oxygen species (ROS) and glucose uptake. These data demonstrate that FAM96A regulates inflammatory response and provide a novel genomic insight for sepsis treatment.


Asunto(s)
Proteínas Portadoras/genética , Activación de Macrófagos/genética , Macrófagos/metabolismo , Sepsis/genética , Animales , Proteínas Portadoras/metabolismo , Línea Celular , Citocinas/metabolismo , Endotoxemia/inducido químicamente , Endotoxemia/genética , Endotoxemia/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Ratones Endogámicos C57BL , Ratones Noqueados , Insuficiencia Multiorgánica/genética , Insuficiencia Multiorgánica/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sepsis/metabolismo , Análisis de Supervivencia
5.
BJOG ; 128(2): 448-457, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32363759

RESUMEN

OBJECTIVE: To evaluate the clinical feasibility of noninvasive prenatal diagnosis (NIPD) for ß-thalassaemia using circulating single molecule amplification and re-sequencing technology (cSMART). DESIGN: Through carrier screening, 102 pregnant Chinese couples carrying pathogenic HBB gene variants were recruited to the study. Pregnancies were managed using traditional invasive prenatal diagnosis (IPD). Retrospectively, we evaluated the archived pregnancy plasma DNA by NIPD to evaluate the performance of our cSMART assay for fetal genotyping. SETTING: Chinese prenatal diagnostic centres specialising in thalassaemia testing. POPULATION: Chinese carrier couples at high genetic risk for ß-thalassaemia. METHODS: Fetal cell sampling was performed by amniocentesis and HBB genotypes were determined by reverse dot blot. NIPD was performed by a newly designed HBB cSMART assay and fetal genotypes were called by measuring the allelic ratios in the maternal cell-free DNA. MAIN OUTCOME MEASURES: Concordance of HBB fetal genotyping between IPD and NIPD and the sensitivity and specificity of NIPD. RESULTS: Invasive prenatal diagnosis identified 29 affected homozygotes or compound heterozygotes, 54 heterozygotes and 19 normal homozygotes. Compared with IPD results, 99 of 102 fetuses (97%) were correctly genotyped by our NIPD assay. Two of three discordant samples were false positives and the other sample involved an incorrect call of a heterozygote carrier as a homozygote normal. Overall, the sensitivity and specificity of our NIPD assay was 100% (95% CI 88.06-100.00%) and 97.26% (95% CI 90.45-99.67%), respectively. CONCLUSIONS: This study demonstrates that our cSMART-based NIPD assay for ß-thalassaemia has potential clinical utility as an alternative to IPD for pregnant HBB carrier couples. TWEETABLE ABSTRACT: A new noninvasive test for pregnancies at risk for ß-thalassaemia.


Asunto(s)
Enfermedades Fetales/diagnóstico , Enfermedades Fetales/genética , Pruebas Prenatales no Invasivas , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genética , China , Estudios de Factibilidad , Femenino , Tamización de Portadores Genéticos , Genotipo , Humanos , Técnicas de Diagnóstico Molecular , Embarazo , Estudios Retrospectivos
6.
Epidemiol Infect ; 148: e26, 2020 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-32046804

RESUMEN

Studies in countries with high immunisation coverage suggest that the re-emergence of pertussis may be caused by a decreased duration of protection resulting from the replacement of whole-cell pertussis vaccine (WPV) with the acellular pertussis vaccine (APV). In China, WPV was introduced in 1978. The pertussis vaccination schedule advanced from an all-WPV schedule (1978-2007), to a mixed WPV/APV schedule (2008-2009), then to an all-APV schedule (2010-2016). Increases in the incidence of pertussis have been reported in recent years in Jinan and other cities in China. However, there have been few Chinese-population-based studies focused on the impact of schedule changes. We obtained annual pertussis incidences from 1956 to 2016 from the Jinan Notifiable Conditions Database. We used interrupted time series and segmented regression analyses to assess changes in pertussis incidence at the beginning of each year, and average annual changes during the intervention. Pertussis incidence decreased by 1.11 cases per 100 000 population (P = 0.743) immediately following WPV introduction in 1978 and declined significantly by 1.21 cases per 100 000 population per year (P < 0.0001) between 1978 and 2001. Immediately after APV replaced the fourth dose of WPV in 2008, the second and third doses in 2009, then replaced all four doses in 2010, pertussis incidence declined by 1.98, 1.98 and 1.08 cases per 100 000 population, respectively. However, the results were not statistically significant. There were significant increasing trends in pertussis incidence after APV replacements: 1.63, 1.77 and 1.78 cases/year in 2008-2016, 2009-2016 and 2010-2016, respectively. Our study shows that the impact of an all-WPV schedule may be less than the impacts of the sequential WPV/APV schedules. The short-term impact of APV was better than that of WPV; however, the duration of APV-induced protection was not ideal. The impact and duration of protective immunity resulting from APVs produced in China need further evaluation. Further research on the effectiveness of pertussis vaccination programme in Jinan, China is also necessary.


Asunto(s)
Esquemas de Inmunización , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Tos Ferina/epidemiología , Tos Ferina/prevención & control , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Ciudades/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Análisis de Series de Tiempo Interrumpido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vacunas Acelulares/administración & dosificación , Vacunas Acelulares/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Adulto Joven
7.
J Biol Regul Homeost Agents ; 32(5): 1231-1237, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30334418

RESUMEN

This study aimed to investigate the relationship between sleep disorders and lymphocyte subsets and cytokines in patients with lung cancer undergoing radiotherapy, and to establish a theoretical foundation for predicting sleep disorders and preventing interventions in radiotherapy in lung cancer patients. Ninety-two patients with lung cancer requiring radiotherapy were selected as the study subjects. The patients' demographic data and disease-related conditions were investigated. Their quality of sleep was measured before radiotherapy, after two and four weeks of radiotherapy, and at the end of radiotherapy. According to the Pittsburgh Sleep Quality Index Number Table (PSQI), patients with PSQI score> 7 points were put into a sleep disorder group, and patients with PSQI score 0-7 were put into a normal sleep group. Lymphocyte subsets were enumerated and cytokine levels (IL-6, IL-1b) were measured during these four periods. The difference in sleep disorders at four weeks between patients with or without synchronous chemotherapy was statistically significant (P less than 0.05). The levels of lymphocyte subsets in the sleep disorder group and the control sleep group showed no difference in the index of lymphocyte subsets before radiotherapy. In the sleep disorder group, CD4+ cells were lower after two weeks of radiotherapy (P less than 0.05). After four weeks of radiotherapy, CD3+, CD4+, and CD16+56+ subsets were lower (P less than 0.05). At the end of radiotherapy, there was no difference in each index. There was no significant difference in IL-6 levels between the two groups before radiotherapy, after two weeks, or after four weeks (P greater than 0.05). At the end of radiotherapy, IL-6 levels in the sleep disorder group were higher than those in the control sleep group (P less than 0.05). There was no significant difference in IL-1b between the two groups (P greater than 0.05). In conclusion, monitoring of T-lymphocyte subsets and IL-6 levels in patients is enhanced during radiotherapy. Clinically effective programs of radiotherapy for lung cancer improve the body's immune status.


Asunto(s)
Citocinas/inmunología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/radioterapia , Subgrupos Linfocitarios/inmunología , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/inmunología , Humanos , Interleucina-6/inmunología , Neoplasias Pulmonares/inmunología , Recuento de Linfocitos , Subgrupos Linfocitarios/citología , Subgrupos Linfocitarios/efectos de la radiación , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/efectos de la radiación
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 52(10): 976-982, 2018 Oct 06.
Artículo en Zh | MEDLINE | ID: mdl-30392313

RESUMEN

Objective: To observe the cellular damage of low-dose combined exposure to Hg, Pb and Cd on hippocampal neurons in rat. Methods: SH-SY5Y cells were randomly divided into 8 groups by 2×2×2 factorial design: control group, Pb exposure group, Hg exposure group, Pb+Hg exposure group, Pb+Cd exposure group, Hg+Cd exposure group and Pb+Cd+Hg exposure group. And the cell viabilities were measured. On this basis, an animal model was established. Twenty eight-week-old SD pregnant rats were randomly divided into four groups by random number table, and five in each group: the control group(distilled water), 1-fold metal mixture exposure group (1×MM, poisoning solution containing mercury chloride 0.15 mg/L, lead acetate trihydrate 25 mg/L, cadmium chloride 7.5 mg/L), 5-fold metal mixture exposure group (5×MM, poisoning solution containing mercury chloride 0.75 mg/L, lead acetate trihydrate 125.00 mg/L, cadmium chloride 37.50 mg/L), 10-fold metal mixture exposure group (10×MM, poisoning solution containing mercury chloride 1.50 mg/L, lead acetate trihydrate 250.00 mg/L, cadmium chloride 75.00 mg/L). Pregnant rats drank water until delivery. Twenty male pups were selected and exposed to these metals through breast milk until weaned. The heavy metals dose of poisoning water was adjusted, and then the weaned rats were exposed to heavy metals via drinking poisoning water until adulthood (postnatal day 83). The blood samples and brain hippocampus samples were collected to observe the ultrastructural changes of hippocampus, and to determine the levels of Hg, Pb and Cd in blood. In addition, apoptosis rate and fluorescence intensity of reactive oxygen species and intracellular free calcium concentration ([Ca(2+)](i)) in hippocampal neurons were measured. Results: Cellular factorial design analysis showed that Hg+Pb+Cd (at no observed adverse effect level, 1.0, 0.5 and 0.1 µmol/L, respectively)had a interaction on cell viability after 48 or 72 hours of combined exposure (P<0.05). The results of ultrastructure showed that mitochondria decreased, ridges and matrixes gradually dissolved in rat hippocampal neurons of 5×MM group; nuclear chromatin aggregated, more ridges and matrixes dissolved and the mitochondria also decreased in rat hippocampal neurons of 10×MM group. The concentration of Hg, Pb and Cd in the blood of 1×MM group, 5×MM group and 10×MM group were higher than those in the control group, and the differences were statistically significant (P<0.001). There was no significant difference in apoptosis rate between the 1×MM group and the control group. The apoptosis rate of 5×MM group and 10×MM group was higher than that in the control group, and the differences were statistically significant (P<0.001). There was no statistically significant difference in the fluorescence intensity of reactive oxygen species in hippocampal neurons of the 1×MM group and the control group. The fluorescence intensity of reactive oxygen species in the 5×MM group and the 10×MM group was higher than that in the control group, the difference was statistically significant (P<0.05). There was no significant difference in the fluorescence intensity of [Ca(2+)](i) between the 1×MM group and the control group. The fluorescence intensity values of [Ca(2+)](i) in the 5×MM group and the 10×MM group were higher than the control group, the differences were statistically significant (P<0.001). Conclusion: Low-level combined exposure to Hg, Pb, and Cd caused synergistic neurotoxic damage, and the process may be related to the changes of neuronal apoptosis, reactive oxide species, and [Ca(2+)](i) levels.


Asunto(s)
Cadmio/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Hipocampo/patología , Plomo/toxicidad , Mercurio/toxicidad , Neuronas/patología , Síndromes de Neurotoxicidad/etiología , Animales , Femenino , Humanos , Masculino , Embarazo , Ratas
10.
Zhonghua Fu Chan Ke Za Zhi ; 52(2): 93-97, 2017 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-28253571

RESUMEN

Objective: To develop a new method based on droplet digital PCR (DD-PCR) for detection and quantification of maternal cell contamination in prenatal diagnosis. Methods: Invasive prenatal samples from 40 couples of ß(IVS-Ⅱ-654)/ß(N) thalassemia gene carriers who accepted prenatal diagnosis in Affiliated Women and Children's Hospital of Guangzhou Medical University from October 2015 to December 2016 were analyzed retrospectively. Specific primers and probes were designed. The concentration gradient were 50%, 25%, 12.5%, 6.25%, 3.125%, 1.562 5%. There were 40 groups of prenatal diagnostic samples. Comparing DD-PCR with quantitative fluorescent-PCR (QF-PCR) based on the short tandem repeats for assement of the sensitivity and accuracy of maternal cell contamination, respectively. Results: DD-PCR could quantify the maternal cell contamination as low as 1.562 5%. The result was proportional to the dilution titers. In the 40 prenatal samples, 6 cases (15%, 6/40) of maternal cell contamination were detected by DD-PCR, while the QF-PCR based on short tandem repeat showed 3 cases (7.5%, 3/40) with maternal cell contamination, DD-PCR was more accurate (P=0.002) . Conclusion: DD-PCR is a precise and sensitive method in the detection of maternal cell contamintation. It could be useful in clinical application.


Asunto(s)
ADN/análisis , Pruebas de Detección del Suero Materno/métodos , Diagnóstico Prenatal/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Cartilla de ADN , Femenino , Humanos , Repeticiones de Microsatélite/genética , Embarazo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Talasemia
11.
Zhonghua Gan Zang Bing Za Zhi ; 25(5): 354-359, 2017 May 20.
Artículo en Zh | MEDLINE | ID: mdl-28763842

RESUMEN

Objective: To evaluate the effect of human CCR1 (hCCR1) gene overexpression on the migration of human bone marrow-derived mesenchymal stem cells (hMSCs) towards hepatocellular carcinoma (HCC), and to examine the application prospects of MSCs as gene delivery vectors in the treatment of HCC. Methods: The hCCR1 gene was subcloned into a lentiviral vector to generate the recombinant plasmid pLV-hCCR1. The pLV-hCCR1 plasmid and two other packaging plasmids were co-transfected into 293T cells using calcium phosphate, and the virus-containing supernatant was collected. hMSCs were then infected with the recombinant lentivirus, and the expression of hCCR1 mRNA and protein was analyzed by RT-PCR and Western blot, respectively. The effect of CCR1 gene overexpression on the in vitro migration of hMSCs was examined using the Transwell migration assay. Orthotopic nude mice models of HCC were established using the MHCC-97H-GFP cell line, and the mice were divided into two groups (n = 8 per group). hMSCs were then intravenously injected via the tail vein into the tumor-bearing nude mice to examine the effect of hCCR1 overexpression on the in vivo migration of hMSCs towards HCC. Unpaired Student's t-test was used for two-group comparisons, and one-way ANOVA was used for multi-group comparisons. Results: Restriction enzyme digestion and DNA sequencing demonstrated that the recombinant plasmid pLV-hCCR1 was constructed successfully. The LV-hCCR1 lentivirus packaged by 293T cells has high infection efficiency in hMSCs, and hCCR1 was overexpressed in hMSCs after LV-hCCR1 infection. Transwell migration assay showed that hCCR1-transfected hMSCs had significantly enhanced migration towards HCC cell line-derived condition medium (CM) compared with the control RFP-hMSCs [(134.8±15.7)/LPF vs (83.5±10.9)/LPF, t = 10.40, P < 0.01]. In vivo migration experiment also demonstrated that there was significantly higher number of hCCR1-hMSCs localized within the MHCC-97H-GFP xenografts than hMSCs-RFP on day 14 following intravenous injection of hMSCs in mice [(86.7±14.1)/HPF vs (54.5±9.6)/HPF, t = -7.32, P < 0.01]. Conclusion: Overexpression of CCR1 gene can significantly enhance the migration capacity of hMSCs towards HCC cells in vitro and in vivo. This study provides evidence for potential clinical application of MSCs as more effective delivery vehicles in cancer gene therapy.


Asunto(s)
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Células Madre Mesenquimatosas/metabolismo , Receptores CCR1/genética , Animales , Médula Ósea , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Carcinoma Hepatocelular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Vectores Genéticos , Humanos , Neoplasias Hepáticas/genética , Células Madre Mesenquimatosas/química , Ratones , Ratones Desnudos , Receptores CCR1/metabolismo
13.
Zootaxa ; (3802): 23-34, 2014 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-24870989

RESUMEN

The genus Lasiochira Meyrick, 1931 is reviewed, based on the specimens collected from China, Korea, and Vietnam. Of the eight species involved in this study, six are described as new: L. flavaterminata sp. nov., L. jianfengensis sp. nov., L. jiulongshana sp. nov., L. pallidiptera sp. nov., L. rosataenia sp. nov. and L. taiwanensis sp. nov. Photographs of adults and genital structures as well as the wing venation are provided, along with a key to all the known species.


Asunto(s)
Mariposas Nocturnas/anatomía & histología , Mariposas Nocturnas/clasificación , Animales , Asia Oriental , Femenino , Masculino , Vietnam
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1015-1023, 2024 Jun 20.
Artículo en Zh | MEDLINE | ID: mdl-38977330

RESUMEN

OBJECTIVE: To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale, multicenter carrier screening. METHODS: This study was conducted among a total of 33 104 participants (16 610 females) from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods. RESULTS: The overall combined carrier frequency was 55.58% for 197 autosomal genes and 1.84% for 26 X-linked genes in these participants.Among the 16 669 families, 874 at-risk couples (5.24%) were identified.Specifically, 584 couples (3.50%) were at risk for autosomal genes, 306(1.84%) for X-linked genes, and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A, 393 couples), HBA1/HBA2(α-thalassemia, 36 couples), PAH (phenylketonuria, 14 couples), and SMN1(spinal muscular atrophy, 14 couples).The most frequently detected X-linked at-risk genes were G6PD (G6PD deficiency, 236 couples), DMD (Duchenne muscular dystrophy, 23 couples), and FMR1(fragile X syndrome, 17 couples).After excluding GJB2 c.109G>A, the detection rate of at-risk couples was 3.91%(651/16 669), which was lowered to 1.72%(287/16 669) after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95% of at-risk couples, while screening for the top 54 genes further increased the detection rate to over 99%. CONCLUSION: This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing, genetic counseling for specific genes or gene variants can be challenging, and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.


Asunto(s)
Pueblo Asiatico , Tamización de Portadores Genéticos , Humanos , China/epidemiología , Pueblo Asiatico/genética , Femenino , Masculino , Tamización de Portadores Genéticos/métodos , Mutación , Pruebas Genéticas/métodos , Conexinas/genética , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Talasemia alfa/epidemiología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Heterocigoto , Pueblos del Este de Asia , Conexina 26
15.
Neurooncol Pract ; 11(2): 188-198, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38496907

RESUMEN

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods: A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results: A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions: GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

16.
Contact Dermatitis ; 65(6): 329-35, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21831240

RESUMEN

BACKGROUND: Hand eczema is common in the nursing profession, and has been reported widely in various parts of the world. OBJECTIVES: The aim of this study was to determine the prevalence and severity of hand eczema among nurses working in a regional hospital in Hong Kong, as well as its psychosocial impact and any possible associated risk factors. PATIENTS/MATERIALS/METHODS: The study took the form of a self-report questionnaire survey; 1240 nurses in a regional hospital were asked to participate in the survey by completing the questionnaire and returning it anonymously within 2 weeks. RESULTS: Seven hundred and twenty-four nurses returned the questionnaire (a response rate of 59%). The prevalence of hand eczema among the respondents was 22.1% (160/724). More than 90% had moderate to severe hand eczema. Itchiness and dryness were the most common symptoms. Occupational work, housework, mood, social activities and sleep were particularly affected. Multinomial logistic regressions showed that a personal or family history of atopy and a hand washing frequency of >20 times per day were independent risk factors for hand eczema. CONCLUSIONS: Hand eczema is common and severe among Hong Kong nurses. The results of this study suggest that hand eczema is an important problem for nurses and that preventive measures should be emphasized.


Asunto(s)
Dermatitis Profesional/epidemiología , Eccema/epidemiología , Dermatosis de la Mano/epidemiología , Personal de Enfermería en Hospital/estadística & datos numéricos , Adulto , Dermatitis Profesional/psicología , Eccema/complicaciones , Eccema/psicología , Femenino , Dermatosis de la Mano/complicaciones , Dermatosis de la Mano/psicología , Desinfección de las Manos , Hong Kong/epidemiología , Humanos , Hipersensibilidad Inmediata/complicaciones , Hipersensibilidad Inmediata/genética , Modelos Logísticos , Masculino , Prevalencia , Calidad de Vida , Factores de Riesgo , Autoinforme , Índice de Severidad de la Enfermedad
17.
Eur Rev Med Pharmacol Sci ; 24(10): 5292-5302, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32495862

RESUMEN

OBJECTIVE: Ovarian carcinoma (OC) is one prevalent fatal malignancy in gynecology. Currently, there is an imperative need to better investigate the pathogenesis of OC. Accumulating evidence has indicated that microRNAs (miRNAs) play pivotal roles in OC occurrence and development. In this study, we mainly investigated the potential roles of miR-18a in OC progression. PATIENTS AND METHODS: We first examined miR-18a expressions in OC tissue samples and cell lines using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, OC patients involved in current study were assigned into two groups based on the mean miR-18a expression level. Kaplan-Meier analysis was carried out to assess the overall survival rate of miR-18a in OC patients. Next, we investigated whether miR-18a could regulate OC cell proliferation abilities by using MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assays. Next, transwell assay was used to detect the effects of miR-18a on cell invasion and migration. We further performed Luciferase reporter assays by cotransfecting with miR-18a mimics and the Luciferase reporter vector containing CBX7 3'UTR-WT or MUT. We then performed immunohistochemistry (IHC) assays to determine the expression of CBX7 in OC tissues. RESULTS: QRT-PCR results indicated that miR-18a expressions were notably decreased in OC related cell lines and tissues. Moreover, the low miR-18a expression was related to the malignant phenotype and poor prognosis of OC patients. Overexpression of miR-18a in OC cells could prominently suppress the proliferation, migration and invasion abilities via modulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT). Furthermore, CBX7 was confirmed as a functional target of miR-18a, indicating that miR-18a exerted the suppressive functions in OC cells partially via the regulation of CBX7. Additionally, restoration of miR-18a remarkably reduced the OC tumor growth in vivo. CONCLUSIONS: Taken together, our study rationally suggested that miR-18a may serve as an effective diagnostic and therapeutic biomarker for OC.


Asunto(s)
Transición Epitelial-Mesenquimal , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Complejo Represivo Polycomb 1/metabolismo , Células Cultivadas , Progresión de la Enfermedad , Femenino , Humanos , MicroARNs/genética , Persona de Mediana Edad , Complejo Represivo Polycomb 1/genética
18.
Science ; 255(5052): 1663-70, 1992 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-17749419

RESUMEN

Thermochronologic, sedimentologic, oceanographic, and paleoclimatic studies suggest that rapid uplift and unroofing of southern Tibet began about 20 million years ago and that the present elevation of much of the Tibetan plateau was attained by about 8 million years ago. Hypotheses advanced to explain the tectonic evolution of the India-Asia collision, which began about 40 to 50 million years ago, predict the timing and rates of crustal thickening of the southern margin of Asia. However, these models do not predict the prominently enhanced early Miocene denudation and uplift that are manifested in a variety of geological records. A model involving continental extrusion, development of a crustal-scale thrust ramp of the Main Central Thrust beneath the Gangdese belt, and lithospheric delamination provides a history consistent with these observations.

19.
Cancer Genomics Proteomics ; 5(3-4): 137-49, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18820368

RESUMEN

BACKGROUND: Imatinib mesylate (Gleevec, Novartis, Basel, Switzerland) is a small-molecule tyrosine kinase inhibitor with activity against ABL, BCR-ABL, c-KIT, and PDGFR alpha. Several clinical trials have evaluated the efficacy and safety of imatinib in patients with ovarian carcinoma who have persistent or recurrent disease following front-line platinum/taxane based chemotherapy. However, there is limited pre-clinical and clinical data on the molecular targets and action of imatinib in ovarian cancer. MATERIALS AND METHODS: Human ovarian cancer cells (A2780) were treated with imatinib mesylate for either 6 or 24 h. We employed a 2D (two-dimensional) gel electrophoresis and mass spectrometry-based proteomics approach to identify protein expression patterns and signaling pathways that were altered in response to imatinib. Cells were analyzed for PDGFR alpha and AKT expression, which were then correlated with imatinib sensitivity. RESULTS: Using 2D gel electrophoresis of overlapping pH ranges from pH 4 to 11, about 4,000 protein spots could be analyzed reproducibly. Proteins whose levels changed between twofold to 30 fold were grouped according to whether changes were in the same direction at both time points of treatment with respect to the control, or changed their levels only at one of the time points. CONCLUSION: Differentially regulated proteins following imatinib treatment of A2780 cells involved the regulation of actin cytoskeleton, metabolic pathways, cell cycle, cell proliferation, apoptosis, cell junctions, and signal transduction. Thus, exposure of cells to imatinib produces complex changes in the cell that require further investigation.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Ováricas/metabolismo , Piperazinas/farmacología , Pirimidinas/farmacología , Antineoplásicos/uso terapéutico , Benzamidas , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Femenino , Perfilación de la Expresión Génica , Humanos , Mesilato de Imatinib , Espectrometría de Masas , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirimidinas/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo
20.
Sci Rep ; 8(1): 9184, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29907789

RESUMEN

Primary motor (M1), primary somatosensory (S1) and dorsal premotor (PMd) cortical areas of rhesus monkeys previously have been associated only with sensorimotor control of limb movements. Here we show that a significant number of neurons in these areas also represent body position and orientation in space. Two rhesus monkeys (K and M) used a wheelchair controlled by a brain-machine interface (BMI) to navigate in a room. During this whole-body navigation, the discharge rates of M1, S1, and PMd neurons correlated with the two-dimensional (2D) room position and the direction of the wheelchair and the monkey head. This place cell-like activity was observed in both monkeys, with 44.6% and 33.3% of neurons encoding room position in monkeys K and M, respectively, and the overlapping populations of 41.0% and 16.0% neurons encoding head direction. These observations suggest that primary sensorimotor and premotor cortical areas in primates are likely involved in allocentrically representing body position in space during whole-body navigation, which is an unexpected finding given the classical hierarchical model of cortical processing that attributes functional specialization for spatial processing to the hippocampal formation.


Asunto(s)
Corteza Motora/fisiología , Movimiento/fisiología , Propiocepción/fisiología , Corteza Somatosensorial/fisiología , Navegación Espacial/fisiología , Animales , Interfaces Cerebro-Computador , Macaca mulatta , Neuronas/fisiología
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