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1.
Cell Immunol ; 403-404: 104857, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39032210

RESUMEN

The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising anti-tumor cytokine, induces apoptosis in tumor cells with low toxicity to normal cells. However, its off-target toxicity and limited stability have limited its clinical progress. Here, we engineered macrophages with Mono-TRAIL and Tri-TRAIL and found that Tri-TRAIL had higher cytotoxic activity against tumor cells than Mono-TRAIL in vitro. To target the tumor microenvironment (TME), we generated macrophages secreting trimeric TRAIL (Tri-TRAIL-iM) induced by the TME-specific promoter Arg1. The Tri-TRAIL-iM cells displayed high specific activatable activity in cell-based co-culture assay and tumor-baring mice models. In addition, we demonstrated that compared to macrophages over-expressing TRAIL under a non-inducible promoter, Tri-TRAIL-iM could more effectively induce apoptosis in cancer cells, inhibit tumor growth, and reduce systemic side effects. This strategy of inducing TRAIL delivery holds great potential for cancer therapy. It is promising to be combined with other engineering methods to maximize the therapeutic effects of solid tumors.


Asunto(s)
Apoptosis , Macrófagos , Ligando Inductor de Apoptosis Relacionado con TNF , Microambiente Tumoral , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Animales , Macrófagos/metabolismo , Macrófagos/inmunología , Ratones , Humanos , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/inmunología , Ratones Endogámicos C57BL , Femenino , Técnicas de Cocultivo
2.
BMC Psychiatry ; 24(1): 5, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166946

RESUMEN

INTRODUCTION: 'Let's Talk About Children' is a brief family focused intervention developed to improve mental health outcomes of children of parents with mental illness (COPMI). This study aims to assess the efficacy of LTC in improving mental health of children of parents with schizophrenia or bipolar disorder in China. METHODS: The planned study is a multicentre parallel group randomized wait-list controlled trial. A total of 400 eligible families with children aged 8 to 18 years will be recruited, 200 each for families with parental schizophrenia or bipolar disorder. The intervention group will receive Let's Talk About Children delivered by a trained therapist, while the control group will receive treatment as usual. The primary outcomes are child mental health measured by the strengths and difficulties questionnaire and parent-child communication measured using the parent-adolescent communication scale. Parental mental health and family functioning are secondary outcomes. This study also plans to explore mediating factors for the effect of Let's Talk About Children on child mental health, as well as conduct a cost-effectiveness analysis on using Let's Talk About Children in China. CONCLUSION: The present study will provide evidence for the efficacy of Let's Talk About Children in families with parental schizophrenia and bipolar disorder in China. In addition, it will evaluate potential mechanisms of action and cost-effectiveness of Let's Talk About Children, providing a basis for future implementation. TRIAL REGISTRATION: ChiCTR2300073904.


Asunto(s)
Trastorno Bipolar , Trastornos del Neurodesarrollo , Esquizofrenia , Adolescente , Humanos , Trastorno Bipolar/terapia , Esquizofrenia/terapia , Padres/psicología , Salud Mental , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
3.
Psychiatry Clin Neurosci ; 78(2): 123-130, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37984442

RESUMEN

AIM: Blunted niacin response (BNR) was an endophenotype of schizophrenia, but the underlying mechanism remains unclarified. The objective of this study was to verify whether genes associated with BNR pathway constitute the genetic basis and the pathological mechanism of BNR phenotypic psychiatric patients. METHODS: Two independent sample sets consisting of 971 subjects were enrolled in this study. A total of 62 variants were genotyped in the discovery set, then the related variants were verified in the verification set. The published PGC GWAS data were used to validate the associations between the variants and psychiatry disorders. RT-PCR analysis, eQTL data, and Dual-Luciferase Reporter experiment were used to investigate the potential molecular mechanisms of the variants underlying BNR. RESULTS: The results showed that two SNPs, rs56959712 in HCAR2 and rs2454721 in HCAR3 were significantly associated with niacin response. The risk allele T of rs2454721 could affect the niacin responses of psychiatric patients through elevated HCAR3 gene expression. These two genes, especially HCAR3, were significantly associated with the risk of schizophrenia, as identified in this study and verified using the published GWAS data. CONCLUSION: HCAR3 is a novel schizophrenia susceptibility gene which is significantly associated with blunted niacin response in schizophrenia. In-depth investigation of HCAR3 is of great significance for uncovering the pathogenesis and propose new therapeutic targets for psychiatric disorders, especially for the BNR subgroup patients.


Asunto(s)
Niacina , Receptores Nicotínicos , Esquizofrenia , Humanos , Niacina/farmacología , Niacina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Endofenotipos , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Receptores Nicotínicos/genética , Receptores Nicotínicos/uso terapéutico , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/uso terapéutico
4.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000180

RESUMEN

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 µg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.


Asunto(s)
Péptidos Antimicrobianos , Pruebas de Sensibilidad Microbiana , Animales , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Bacterias Gramnegativas/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/genética , Humanos
5.
Molecules ; 29(18)2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39339396

RESUMEN

The prevalence of antimicrobial resistance reduces the effectiveness of antimicrobial drugs in the prevention and treatment of infectious diseases caused by pathogens such as bacteria, fungi, and viruses. Microbial secondary metabolites have been recognized as important sources for new drug discovery and development, yielding a wide range of structurally novel and functionally diverse antimicrobial drugs for the treatment of a variety of diseases that are considered good producers of novel antimicrobial drugs. Bacteria produce a wide variety of antimicrobial compounds, and thus, antibiotics derived from natural products still dominate over purely synthetic antibiotics among the antimicrobial drugs developed and introduced over the last four decades. Among them, Pseudomonas aeruginosa secondary metabolites constitute a richly diverse source of antimicrobial substances with good antimicrobial activity. Therefore, they are regarded as an outstanding resource for finding novel bioactive compounds. The exploration of antimicrobial compounds among Pseudomonas aeruginosa metabolites plays an important role in drug development and biomedical research. Reports on the secondary metabolites of Pseudomonas aeruginosa, many of which are of pharmacological importance, hold great promise for the development of effective antimicrobial drugs against microbial infections by drug-resistant pathogens. In this review, we attempt to summarize published articles from the last twenty-five years (2000-2024) on antimicrobial secondary metabolites from Pseudomonas aeruginosa.


Asunto(s)
Productos Biológicos , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/química , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Humanos , Pruebas de Sensibilidad Microbiana
6.
Acta Neuropsychiatr ; 36(1): 44-50, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37642170

RESUMEN

INTRODUCTION: Depression is a common mental disorder that endangers physical and mental health. In our study, we aimed to explore whether B vitamins are associated with depression and cognitive dysfunction. METHODS: We enrolled a total of 220 patients with depression and selected 100 controls at the same time. We determined depression and cognitive impairment by assessments. We recorded the basic parameters of the participants and collected blood samples. In addition, we measured serum levels of B vitamins and brain-derived neurotrophic factor (BDNF). RESULTS: We found significant differences in the duration of depression, education, and Hamilton Depression Rating Scale scores between the D-NCI and D-CI groups. We also identified the independent risk factors for patients with depression and cognitive dysfunction. Compared with the healthy controls, serum folate, vitamin B6, and vitamin B12 positively correlated with cognitive dysfunction. The patients with depression and cognitive dysfunction had the lowest levels of B vitamins compared with the other two groups. Our results also showed that the levels of serum folate, vitamin B6, and vitamin B12 in the patients with depression had a positive correlation with each other. CONCLUSION: Our results indicate that vitamin B is associated with depression and cognitive dysfunction and is positively associated with cognitive dysfunction.


Asunto(s)
Disfunción Cognitiva , Complejo Vitamínico B , Humanos , Ácido Fólico , Vitamina B 12 , Vitamina B 6 , Depresión , Homocisteína
7.
J Gastroenterol Hepatol ; 38(12): 2185-2194, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37731216

RESUMEN

BACKGROUND: In recent years, the incidence of alcoholic liver disease (ALD) has gradually increased, the development of ALD is attached great attentions. Nostoc commune Vauch. polysaccharide (NCVP) is beneficial to maintain the gut health, but the protective effect of NCVP on the liver has not been reported yet. PURPOSE: To study the protective effect and the underlying mechanisms of NCVP on ALD, a mouse model of acute ALD was established. STUDY DESIGN AND METHODS: We built an acute ALD mouse model and explored the protective effect of NCVP through the detection of cytokines, histological examination, determination of short chain fatty acids, and 16S rRNA analysis of gut microbiota. RESULTS: NCVP had hepatoprotective effects on acute alcohol-induced mice by improving antioxidant capacity, reducing oxidative stress and the serum cytokine levels (IL-1ß, IL-6, and TNF-α). Simultaneously, histopathological changes in liver indicated that NCVP could inhibit local hepatocyte necrosis, cytoplasmic vacuolation and inflammatory cell infiltration induced by alcohol. NCVP also increased the level of total short-chain fatty acids of acute ALD mice. In addition, NCVP could significantly decrease the Firmicutes/Bacteroidetes ratio and the abundance of Patescibacteria, Helicobacter, and Actinomycetes and increase the abundance of Lachospiraceae, Prevotellaceae-UCG-003, Lactobacillaceae, and Desulfovibrio. CONCLUSION: Our study proved that NCVP had in vivo hepatoprotective effect on acute ALD mice and provided scientific evidences that NCVP might be a promising drug candidate for the prevention and treatment of ALD.


Asunto(s)
Microbioma Gastrointestinal , Hepatopatías Alcohólicas , Nostoc commune , Animales , Ratones , ARN Ribosómico 16S , Hepatopatías Alcohólicas/prevención & control , Polisacáridos/farmacología , Hígado/patología , Etanol/efectos adversos , Citocinas , Ratones Endogámicos C57BL
8.
J Ment Health ; 32(3): 541-550, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35775503

RESUMEN

BACKGROUND: Adverse childhood experiences (ACEs) affect children's development, and their harm to health is pervasive throughout the life course. AIMS: To identify ACEs and their risk factors in Chinese household with or without parental mental illness. METHODS: A controlled study was conducted among 181 young adults with parental mental illness (positive group) and 201 demographically matched individuals without parental mental illness (negative group). Univariate and multivariate analyses were performed to study the correlation between ACEs and their risk factors. RESULTS: The positive group suffered emotional abuse, domestic violence, bullying, and cumulative ACEs more frequently than the negative group. In the positive group, living in rural areas and having a low household economic status during childhood were identified as risk factors for cumulative ACEs, whereas a higher education level of the mother was a protective factor for cumulative ACEs in univariate analyses. Low household economic status remained an independent risk factor for cumulative ACEs in the positive group in multivariate analyses. CONCLUSIONS: Children living with parental mental illness are more vulnerable to ACEs, and our findings highlight the importance of socioeconomic factors in increasing the risk of ACEs. To alleviate the deleterious impact of parental mental illness on offspring, multidimensional supports are needed.


Asunto(s)
Experiencias Adversas de la Infancia , Trastornos Mentales , Niño , Adulto Joven , Humanos , Padres , Proyectos de Investigación , China/epidemiología , Trastornos Mentales/epidemiología
9.
BMC Psychiatry ; 21(1): 589, 2021 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-34814877

RESUMEN

BACKGROUND: Although the experiences of mothers with mental illness are well researched in Western countries, little is known about the experiences of Chinese mothers. This study aims to explore the experiences of family life and parenting of Chinese mothers, in the context of their mental illness. METHODS: Fourteen Chinese mothers with mental illness undertook in-depth, semi-structured interviews. Interpretative Phenomenological Analysis was employed to guide the data analysis. RESULTS: Seven themes were identified: motherhood as a central identity, the stigma associated with being a mother with mental illness, participants' perceptions about the impact of mental illness on parenting and their children, experiences of talking to children about mental illness, how having children impacts mothers' illness and recovery, and support obtained and needed. Similar to Western mothers, Chinese mothers experienced stigma and fluctuating mental illness symptoms which impacted on parenting. Unlike mothers based in Western countries, the mothers interviewed in this study highlighted complicated co-caring relationships with parents-in-law and did not raise child custody concerns. CONCLUSIONS: Mental health professionals need to have the skills to identify and recognize the mothering role of their clients. Culturally sensitive interventions are required to assist Chinese families where mothers have a mental illness. Future research is required to investigate family experiences of parental mental illness from the perspectives of children, partners, and mental health professionals.


Asunto(s)
Trastornos Mentales , Madres , Niño , China , Femenino , Humanos , Responsabilidad Parental , Padres , Investigación Cualitativa
10.
BMC Public Health ; 21(1): 702, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836705

RESUMEN

BACKGROUND: The current study examined the change in local government staff's emotional distress over 7 years after the 2008 Wenchuan earthquake, and the influence of earthquake exposure and professional quality of life (ProQOL) on emotional distress. METHODS: This longitudinal study assessed 250 participants at 1 year after the earthquake; 162 (64.8%) were followed up at 7 years. Emotional distress was assessed with the Self-Reporting Questionnaire (SRQ) at both time points. We assessed ProQOL, including compassion satisfaction, burnout, and secondary traumatic stress, and earthquake exposure at 1 year. Wilcoxon signed-rank tests were performed to test longitudinal changes in emotional distress. Hierarchical multiple regression was conducted to examine the effect of earthquake exposure and ProQOL. RESULTS: The positive screening rate of emotional distress (SRQ ≥ 8) was 37.6 and 15.4% at one and 7 years, respectively. Emotional distress scores declined over time (p < 0.001). Earthquake exposure and ProQOL predicted one-year (ps < 0.05) but not seven-year emotional distress, whereas burnout predicted both one-year (p = 0.018) and seven-year (p = 0.047) emotional distress. CONCLUSIONS: Although emotional distress can recover over time, it persists even 7 years later. Actions to reduce burnout during the early stage of post-disaster rescue have long-term benefits to staff's psychological outcomes.


Asunto(s)
Terremotos , Distrés Psicológico , Trastornos por Estrés Postraumático , China/epidemiología , Humanos , Gobierno Local , Estudios Longitudinales , Calidad de Vida , Encuestas y Cuestionarios
11.
BMC Health Serv Res ; 21(1): 569, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34107937

RESUMEN

BACKGROUND: Mental disorders impose heavy burdens on patients' families and children. It is imperative to provide family-focused services to avoid adverse effects from mental disorders on patients' families and children. However, implementing such services requires a great deal of involvement of mental health workers. This study investigated the attitudes, knowledge, skills, and practices in respect to family-focused practices (FFP) in a sample of Chinese mental health workers. METHODS: A cross-sectional study design was employed to examine the attitudes, knowledge, skills, and practices of a convenience sample of Chinese mental health workers in respect to FFP, using the Chinese version of the Family-Focused Mental Health Practice Questionnaire (FFMHPQ). RESULTS: In total, 515 mental health workers participated in our study, including 213 psychiatrists, 269 psychiatric nurses, and 34 allied mental health professionals (20 clinical psychologists, 9 mental health social workers, and 4 occupational therapists). Compared with psychiatric nurses, psychiatrists and allied mental health professionals provided more support for families and children of patients with mental illness and were more willing to receive further training in FFP. However, there were no significant differences on knowledge, skills, and confidence across different profession types. After adjusting for demographic and occupational variables, previous training in FFP was positively associated with mental health workers' knowledge, skills, and confidence about FFP, but not actual support to families and children. CONCLUSIONS: Professional differences on FFP exist in Chinese mental health workers. Training is needed to engage psychiatrists and other allied workforce in dissemination and implementation of FFP in China.


Asunto(s)
Trastornos Mentales , Enfermería Psiquiátrica , Niño , China , Estudios Transversales , Personal de Salud , Humanos , Trastornos Mentales/terapia , Salud Mental
12.
Fish Physiol Biochem ; 46(1): 187-197, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31612298

RESUMEN

Cadmium (Cd) is the most abundant heavy metal in aquatic environments and is easily detected on a global scale. Carassius auratus gibelio is a common aquaculture species. The aim of this study was to explore the toxic effects of 1, 2, and 4 mg/L Cd on the energy metabolism, growth performance, and neurological responses of C. gibelio. After 30 days of exposure, Cd concentrations in the liver and brain were significantly increased in Cd-exposed groups. Low-level Cd exposure (1 mg/L) increased weight and length gains, as well as food intake, in the fish. Acetylcholinesterase activity decreased significantly in the Cd-exposed groups. Energy metabolism levels (as reflected by oxygen consumption, ammonia excretion rate, and swimming activity), as well as serum T3 and T4 levels, increased significantly in the fish exposed to 1 mg/L Cd. However, energy metabolism and serum T3/T4 levels decreased significantly in the 4-mg/L Cd group. Neuropeptide gene expression levels in brain were consistent with the observed changes in food intake. In the Cd-exposed groups, the expression levels of neuropeptide Y (NPY), apelin, and metallothionein (MT) increased significantly, while those of pro-opinmelanocortin (POMC), ghrelin, and corticotrophin-releasing factor (CRF) decreased significantly. Our data suggested that in fish, low doses of Cd might increase food intake, as well as weight and length gains, but high doses of Cd might have the opposite effect. These effects might be a result of neurohumoral regulation. Long-term exposure to low doses of Cd might cause weight gain and affect food intake.


Asunto(s)
Cadmio/toxicidad , Metabolismo Energético/efectos de los fármacos , Carpa Dorada/crecimiento & desarrollo , Neuropéptidos/metabolismo , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Carpa Dorada/metabolismo , Neuropéptidos/genética , Contaminantes Químicos del Agua/toxicidad
13.
Fish Shellfish Immunol ; 89: 141-148, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30926477

RESUMEN

Cadmium (Cd) is the most common heavy metal and is easily detected in aquatic environments worldwide. The genus Bacillus was one of dominant probiotics, which was commonly used in aquaculture. The present study was undertaken to explore the effects of Bacillus cereus (B. cereus) supplementation on hematological parameters and the immune response of Carassius auratus gibelio (C. gibelio) following Cd exposure. Fish were exposed to waterborne Cd (0, 1 and 2 mg/L) and/or treated with dietary B. cereus at 108 cfu/g for four weeks. The hematological disturbances observed after exposure of waterborne Cd included significant decreases in red blood cell (RBC) count, hemoglobin (Hb) concentration and hematocrit (HCT). While significant elevation (P < 0.05) of RBC count, HCT and Hb levels in the 1 and 2 mg/L Cd-B. cereus administration group at 4 weeks, compared with the Cd-only group. Among serum enzymatic activities, aspartate aminotransferase (AST) and alanine transaminase (ALT) activities by Cd exposure were significantly higher than controls, but this increase was effectively inhibited in Cd-B. cereus administration groups. In the Cd-B. cereus administration group, significant down-regulation of Hsp70, Hsp90, IL-1ß, IL-6, IL-10 and TNF-α in conjunction with the up-regulation of IgM and LZM in the spleen indicated that B. cereus alleviated the Cd-induced damage to the immune system to some degree. The results of this study suggested that B. cereus has the potential to countermeasure Cd-induced hematological disturbances and immunosuppression in C. gibelio.


Asunto(s)
Bacillus cereus/química , Cadmio/efectos adversos , Carpa Dorada/inmunología , Tolerancia Inmunológica , Probióticos/farmacología , Contaminantes Químicos del Agua/efectos adversos , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Pruebas Hematológicas/veterinaria , Distribución Aleatoria
14.
Respirology ; 24(12): 1152-1155, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31157493

RESUMEN

Non-invasive positive pressure ventilation (NPPV) is undoubtedly one of the most significant advancements in mechanical ventilation technology in the past 30 years. With accumulating evidence from clinical studies and support from clinical guidelines, NPPV is now widely used in hospitals and increasingly prescribed for home therapy in the Asia-Pacific region. However, in comparison with the developed Western countries, overall use of NPPV in the region is lagging behind. This study reviews this imbalance of NPPV use both in the acute and domiciliary settings in the Asia-Pacific region. Important issues related to NPPV use are also discussed along with speculation around potential strategies that could promote wider implementation of NPPV in the region. We hope this review will stimulate interest in the clinical application and potential research avenues for NPPV in the Asia-Pacific region, and promote education and staff training in the technique.


Asunto(s)
Ventilación no Invasiva/métodos , Respiración con Presión Positiva/métodos , Utilización de Procedimientos y Técnicas , Insuficiencia Respiratoria , Asia , Necesidades y Demandas de Servicios de Salud , Humanos , Islas del Pacífico , Utilización de Procedimientos y Técnicas/normas , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/terapia
16.
Respir Res ; 19(1): 225, 2018 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-30458805

RESUMEN

BACKGROUND: Difference between combined inspiratory and expiratory muscle training in same respiratory cycle or different cycles remained unclarified. We explored the difference between both patterns of combined trainings in patients with COPD. METHODS: In this randomized, open-label, controlled trial, stable COPD subjects trained for 48 minutes daily, for 8 weeks, using a monitoring device for quality control. Ninety-two subjects were randomly and equally assigned for sham training, inspiratory muscle training(IMT), combined inspiratory and expiratory muscle training in same cycle(CTSC) or combined inspiratory and expiratory muscle training in different cycles(CTDC). Respiratory muscle strength, as the primary endpoint, was measured before and after training. Registry: ClinicalTrials.gov (identifier: NCT02326181). RESULTS: Respiratory muscle training improved maximal inspiratory pressure(PImax), while no significant difference was found in PImax among IMT, CTSC and CTDC. Maximal expiratory pressure(PEmax) in CTSC and CTDC was greater than IMT(P = 0.026, and P=0.04, respectively) and sham training (P = 0.001). IMT, CTSC, and CTDC shortened inhalation and prolonged exhalation(P < 0.01). Subjects with respiratory muscle weakness in IMT and CTDC exhibited greater increase in PImax than those without. IMT, CTSC and CTDC showed no difference in symptoms and quality of life scales among themselves(P > 0.05). CONCLUSION: Both patterns of CTSC and CTDC improved inspiratory and expiratory muscle strength, while IMT alone only raised PImax. Respiratory muscle training might change the respiratory cycles, and be more beneficial for COPD patients with inspiratory muscle weakness.


Asunto(s)
Ejercicios Respiratorios/métodos , Espiración/fisiología , Inhalación/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Músculos Respiratorios/fisiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología
17.
J Nanobiotechnology ; 16(1): 62, 2018 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-30165861

RESUMEN

BACKGROUND: Epidermal growth factor (EGF) can promote cell proliferation as well as migration, which is feasible in tissue wound healing. Oil bodies have been exploited as an important platform to produce exogenous proteins. The exogenous proteins were expressed in oil bodies from plant seeds. The process can reduce purification steps, thereby significantly reducing the purification cost. Mostly, the diameter of oil body particle ranges between 1.0 and 1.5 µm in the safflower seeds, however, it reduces to 700-1000 nm in the transgenic safflower seeds. The significant reduction of particle size in transgenic seeds is extremely beneficial to skin absorption. RESULTS: The diameter of oil body in the transgenic safflower seeds was recorded in the range of 700-1000 nm. The smaller particle size improved their skin absorption. The expression level of oleosin-hEGF-hEGF in T3 transgenic seeds was highest at 69.32 mg/g of seeds. The oil body expressing oleosin-hEGF-hEGF had significant proliferative activity on NIH/3T3 cells and improved skin regeneration thereby accelerating wound healing in rats. The wound coverage rate exceeded 98% after treatment for 14 days with oil body expressing oleosin-hEGF-hEGF, while the saline without EGF group and wild type oil body group both showed less than 80%. The neonatal fibroblast and collagen were found to be increased in the safflower oil body expressing oleosin-hEGF-hEGF treatment group. TGF-ß1, bFGF and VEGF were noted as important growth factors in the repair of cutaneous wounds. Their expression level increased after 4 and 7 day treatment, but decreased after 14 days. Therefore, it can promote skin regeneration to accelerate wounds healing. CONCLUSIONS: The expression of oleosin-hEGF-hEGF in T3 transgenic seeds was 80.43 ng/µL oil body. It had significant proliferative activity on NIH/3T3 cells and improved skin regeneration to accelerate wound healing in rats. The expression process of TGF-ß1, bFGF and VEGF increased at first and then gradually declined.


Asunto(s)
Factor de Crecimiento Epidérmico/química , Gotas Lipídicas/química , Proteínas de Plantas/química , Piel/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéutico , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Células 3T3 NIH , Tamaño de la Partícula , Aceites de Plantas/química , Ratas , Ratas Wistar , Regeneración/efectos de los fármacos , Semillas/química , Propiedades de Superficie , Distribución Tisular/efectos de los fármacos , Distribución Tisular/inmunología
18.
Phytother Res ; 32(4): 723-732, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29377296

RESUMEN

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and ß-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.


Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Dieta/efectos adversos , Iridoides/química , Movilización Lipídica/efectos de los fármacos , Obesidad/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Masculino , Ratas
19.
Protein Expr Purif ; 138: 7-12, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26384708

RESUMEN

Fibroblast growth factor 10 (FGF10) is a member of the FGF superfamily. It exhibits diverse biological functions, and is extensively used for fundamental research and clinical applications involving hair growth, tissue repair, and burn wounds. Oil bodies, obtained from oil seeds, have been exploited for a variety of biotechnology applications. The use of oil bodies reduces purification steps and costs associated with the production of heterogonous proteins. Here, recombinant human FGF10 (rhFGF10) was expressed in safflower (Carthamus tinctorius L.) seeds using oilbody-oleosin technology. A plant expression vector, pOTBar-oleosin-rhFGF10, was constructed and introduced into safflower using Agrobacterium tumefaciens transformation, and mature safflower plants were obtained by grafting. Oleosin-rhFGF10 was successfully transformed and expressed in safflower seeds and inherited to the T3 generation. Moreover, MTT assays demonstrated that oil bodies expressed oleosin-FGF10 had a dose-dependent effect on cellular proliferation. In conclusion, this may provide a method of producing oleosin-rhFGF10, and help us meet the increasing pharmacological demands for the protein.


Asunto(s)
Carthamus tinctorius/genética , Factor 10 de Crecimiento de Fibroblastos/genética , Vectores Genéticos/química , Proteínas de Plantas/genética , Semillas/genética , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/metabolismo , Animales , Linfocitos B/citología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Carthamus tinctorius/química , Carthamus tinctorius/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Factor 10 de Crecimiento de Fibroblastos/biosíntesis , Factor 10 de Crecimiento de Fibroblastos/aislamiento & purificación , Factor 10 de Crecimiento de Fibroblastos/farmacología , Expresión Génica , Vectores Genéticos/metabolismo , Humanos , Gotas Lipídicas/química , Gotas Lipídicas/metabolismo , Ratones , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Semillas/química , Semillas/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 41(20): 3727-3732, 2016 Oct.
Artículo en Zh | MEDLINE | ID: mdl-28929648

RESUMEN

The tocopherol cyclase was one of the key enzymes in plant vitamin E biosynthesis pathway. According to the study of Carthamus tinctorius transcriptome data,the Tocopherol cyclase gene was obtained using RT-PCR techniques and named CtTC . Bioinformatics analysis showed theopen reading frame (ORF)of CtTC was 1 524 bp. The putative protein contained 507 amino acids with a predicted molecular mass of 62.9 kDa and theoretically isoelectric point was 5.01.Signal peptide analysis showed that it was a non secretory protein, and there was no signal peptide. The subcellular localization showed that the CtTC protein was located in the chloroplast. The expression of CtTC gene in safflower seeds at different development stages was determined by quantitative real-time PCR, it was found that the highest expression level of CtTC gene was detected in 50 DAF.Quantitative RT-PCR analysis suggested that expression of CtTC is induced and strengthened by drought stresses. This research provided a candidate gene for metabolic engineering of vitamin E and resisting stress.


Asunto(s)
Carthamus tinctorius/enzimología , Transferasas Intramoleculares/genética , Proteínas de Plantas/genética , Proteínas de Unión al ARN/genética , Carthamus tinctorius/genética , Cloroplastos/enzimología , Clonación Molecular , Semillas/enzimología , Vitamina E/biosíntesis
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