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1.
J Biomed Sci ; 31(1): 24, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395904

RESUMEN

BACKGROUND: Mutations in CHCHD2 have been linked to Parkinson's disease, however, their exact pathophysiologic roles are unclear. The p32 protein has been suggested to interact with CHCHD2, however, the physiological functions of such interaction in the context of PD have not been clarified. METHODS: Interaction between CHCHD2 and p32 was confirmed by co-immunoprecipitation experiments. We studied the effect of p32-knockdown in the transgenic Drosophila and Hela cells expressing the wild type and the pathogenic variants of hCHCHD2. We further investigated the rescue ability of a custom generated p32-inhibitor in these models as well as in the human fibroblast derived neural precursor cells and the dopaminergic neurons harboring hCHCHD2-Arg145Gln. RESULTS: Our results showed that wildtype and mutant hCHCHD2 could bind to p32 in vitro, supported by in vivo interaction between human CHCHD2 and Drosophila p32. Knockdown of p32 reduced mutant hCHCHD2 levels in Drosophila and in vitro. In Drosophila hCHCHD2 models, inhibition of p32 through genetic knockdown and pharmacological treatment using a customized p32-inhibitor restored dopaminergic neuron numbers and improved mitochondrial morphology. These were correlated with improved locomotor function, reduced oxidative stress and decreased mortality. Consistently, Hela cells expressing mutant hCHCHD2 showed improved mitochondrial morphology and function after treatment with the p32-inhibitor. As compared to the isogenic control cells, large percentage of the mutant neural precursor cells and dopaminergic neurons harboring hCHCHD2-Arg145Gln contained fragmented mitochondria which was accompanied by lower ATP production and cell viability. The NPCs harboring hCHCHD2-Arg145Gln also had a marked increase in α-synuclein expression. The p32-inhibitor was able to ameliorate the mitochondrial fragmentation, restored ATP levels, increased cell viability and reduced α-synuclein level in these cells. CONCLUSIONS: Our study identified p32 as a modulator of CHCHD2, possibly exerting its effects by reducing the toxic mutant hCHCHD2 expression and/or mitigating the downstream effects. Inhibition of the p32 pathway can be a potential therapeutic intervention for CHCHD2-linked PD and diseases involving mitochondrial dysfunction.


Asunto(s)
Células-Madre Neurales , Enfermedad de Parkinson , Animales , Humanos , Adenosina Trifosfato/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Neuronas Dopaminérgicas/metabolismo , Drosophila/genética , Drosophila/metabolismo , Células HeLa , Células-Madre Neurales/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Fenotipo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
2.
J Insect Sci ; 23(2)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37052365

RESUMEN

Endosymbionts live symbiotically with insect hosts and play important roles in the evolution, growth, development, reproduction, and environmental fitness of hosts. Weevils are one of the most abundant insect groups that can be infected by various endosymbionts, such as Sodalis, Nardonella, and Wolbachia. The sweet potato weevil, Cylas formicarius (Coleoptera: Brentidae), is a notorious pest in sweet potato (Ipomoea batatas L.) cultivation. Currently, little is known about the presence of endosymbionts in C. formicarius. Herein, we assessed the endosymbiont load of a single geographic population of C. formicarius. The results showed that Nardonella and Rickettsia could infect C. formicarius at different rates, which also varied according to the developmental stages of C. formicarius. The relative titer of Nardonella was significantly related to C. formicarius developmental stages. The Nardonella-infecting sweet potato weevils were most closely related to the Nardonella in Sphenophorus levis (Coleoptera, Curculionidae). The Rickettsia be identified in bellii group. These results preliminarily revealed the endosymbionts in C. formicarius and helped to explore the diversity of endosymbionts in weevils and uncover the physiological roles of endosymbionts in weevils.


Asunto(s)
Escarabajos , Ipomoea batatas , Gorgojos , Animales , Reproducción
3.
Ecotoxicol Environ Saf ; 211: 111897, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33493719

RESUMEN

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated yet. This study aimed to assess the association between long-term environmental Cd exposure and bone remodeling in women who aged over 50. A total of 278 non-smoking subjects from Cd-polluted group (n = 191) and non-Cd polluted group (n = 87) were investigated. Bone mineral density (BMD), the levels of three bone turnover markers (BTMs), including total procollagen type 1 amino-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (ß-CTX), bone-specific alkaline phosphatase (BALP), together with serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were determined. Early markers of renal dysfunction were measured as well. Urinary Cd concentrations ranged from 0.41 to 87.31 µg/g creatinine, with a median of 4.91 µg/g creatinine. Age, BMD, T-score, and prevalence of osteoporosis showed no statistical differences among the quartiles of urinary Cd concentrations, while serum levels of P1NP, ß-CTX, and OPG were higher in the upper quartiles. Multivariate linear regression models indicated significantly positive associations of urinary Cd concentration with serum levels of P1NP, ß-CTX, BALP, sRANKL, and OPG. A ridge regression analysis with T-score and the three BTMs, sRANKL, and OPG, adjusted for age and body mass index (BMI), indicated that except for age and Cd exposure, ß-CTX was a predictor of T-score. These findings demonstrated that Cd may directly accelerate bone remodeling. Serum ß-CTX might be an appropriate biochemical marker for evaluating and monitoring Cd-related bone loss. Capsule: Cadmium (Cd) may directly accelerate bone remodeling and serum ß-CTX is a valuable biochemical marker for evaluating Cd-related bone loss.


Asunto(s)
Remodelación Ósea , Cadmio/sangre , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/sangre , Adulto , Anciano , Fosfatasa Alcalina , Biomarcadores/sangre , Índice de Masa Corporal , Densidad Ósea , Huesos , Colágeno Tipo I , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis/sangre , Osteoprotegerina , Péptidos , Ligando RANK/sangre
4.
Artículo en Zh | MEDLINE | ID: mdl-22096855

RESUMEN

OBJECTIVE: To evaluate three alternative methods for LD50 test-Fixed Dose Procedure (FDP), the Acute Toxic Class Method (ATC) and Up and Down Procedure (UDP). METHODS: Female SD rats (8-12 weeks of age, 160-200 g) were used. Three alternative methods from OECD were applied to assess 22 chemicals (10 cosmetic raw materials and 12 raw materials of personal and home care products). The toxicity ranking for tested chemicals was established according to Globally Harmonized System (GSH). The results LD50 test were compared for the consistency and correlation between alternative methods and traditional test. RESULTS: For cosmetic raw materials, the concordance rate of the three alternative methods was 80% (8/10); for raw material of personal and home care products, the concordance rates of FDP, ATC and UDP was 91.7% (11/12), 75.0% (9/12) and 83.0% (10/12), respectively. The number of animals required in three alternative methods was significantly lower than that in traditional test (P < 0.05), but the time required in three alternative methods was significantly higher than that in traditional test (P < 0.05). CONCLUSIONS: High consistency and correlation were found between each alternative method and LD50 test. FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials.


Asunto(s)
Cosméticos/toxicidad , Sustancias Peligrosas/toxicidad , Pruebas de Toxicidad Aguda/métodos , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Dosificación Letal Mediana , Ratas , Ratas Sprague-Dawley
5.
Biomed Res Int ; 2020: 7187946, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32695819

RESUMEN

Herbal tea with antioxidant ingredients has gained increasing attention in the field of functional foods due to their amelioration potential in aging-related diseases. Wanglaoji herbal tea (WHT) is a kind of traditional beverage made from herbal materials. This study was performed to investigate its antioxidant activity and identify its protective effect on a H2O2-induced cell damage model. In this study, we identified six kinds of phenolic acids with antioxidant activity in WHT, among which rosmarinic acid had the highest content and the highest contribution ratio to the antioxidant activity of WHT. Moreover, compared with the H2O2-induced damage group, the WHT treatment group can significantly increase the viability of cells and decrease the ratio of senescence-associated ß-galactosidase-positive cells, intracellular malondialdehyde levels, and the percentage of G1 phase. Furthermore, enrichment analysis of differentially expressed genes revealed that heme oxygenase1 (HMOX1) was a key gene for protective effect of WHT on oxidative stress-induced cell damage. Thus, WHT exerted protective effects not only by scavenging reactive oxygen species but also by inducing the expression of cytoprotective genes by activating the HMOX1 pathway, which showed that WHT had a potential of promoting health by reducing oxidative stress-induced cell damage.


Asunto(s)
Antioxidantes/farmacología , Citoprotección/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Peróxido de Hidrógeno/toxicidad , Estrés Oxidativo/efectos de los fármacos , Tés de Hierbas , Compuestos de Bifenilo/química , Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citoprotección/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hidroxibenzoatos/análisis , Estrés Oxidativo/genética , Picratos/química , Sustancias Protectoras/farmacología , Transcriptoma/genética
6.
Environ Pollut ; 249: 620-628, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30933759

RESUMEN

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated till date. This study aimed to assess the association between rat mesenchymal stem cells (MSCs) and long-term Cd exposure through 38-week intake of CdCl2 at 1 and 2 mg/kg body weight (bw). Increased gene expression of receptor activator of NF-κB ligand (RANKL) and decreased gene expression of osteoprotegerin (OPG) were observed. Fold change of RANKL gene expression (fold change = 1.97) and OPG gene expression (fold change = 1.72) showed statistically significant differences at dose 2 mg/kg bw. Decreased expression of key genes was observed during the early osteogenic differentiation of MSCs. The gene expression of Osterix in 1 mg/kg bw group was decreased by 3.70-fold, and the gene expressions of Osterix, Osteopontin, collagen type I alpha 2 chain (COL1a2) and runt-related transcription factor 2 (RUNX2) in 2 mg/kg bw group were decreased by 1.79, 1.67, 1.45 and 1.35-folds, respectively. Exposure to CdCl2 induced an increase in the renal Cd load, but only an adaptive response was observed, including increased expression of autophagy-related proteins LC3B and Beclin-1, autophagy receptor p62, and heme oxygenase 1 (HO-1), which is an inducible isoform that releases in response to stress. There were no significant changes in the urinary low molecular weight proteins including N-acetyl-b-D-glucosaminidase (NAG), ß2-microglobulin and albumin (U-Alb). Urinary calcium (Ca) excretion showed no increase, and no obvious renal histological changes. Taken together, these results indicated that the chronic CdCl2 exposure directly act on MSCs through RANKL/OPG pathway and downregulate the key genes involved in osteogenic differentiation of MSCs. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity.


Asunto(s)
Cloruro de Cadmio/toxicidad , Cadmio/toxicidad , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/genética , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Animales , Huesos/metabolismo , Proteínas Portadoras/metabolismo , Diferenciación Celular , Colágeno Tipo I/biosíntesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Regulación hacia Abajo , Femenino , Expresión Génica , Humanos , Osteogénesis/efectos de los fármacos , Osteopontina/biosíntesis , Ratas , Ratas Sprague-Dawley , Factores de Transcripción/biosíntesis
7.
Zhong Yao Cai ; 29(1): 16-9, 2006 Jan.
Artículo en Zh | MEDLINE | ID: mdl-16722311

RESUMEN

OBJECTIVE: To study the antihyperlipidemia effective constituent of Polygala fallax Hemsl. METHOD: Column chromatographic techniques were employed for isolation and purification of chemical constituents of the plant and the structures were elucidated by IR, NMR and MS spectroscopy. RESULT: Four triterpenoid saponins were isolated and determined as 3-O-beta-D-glucopyranosyl-( 1--> 2) -beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4 ) -alpha-L-rhamnopyranosyl-(1-->2 ) -beta-D-fucopyranosyl ester (I), 3-O-beta-D-glucopyranosyl-(1-->2) -beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4) -alpha-L-rhamnopyranosyl-(1-->2) -(3-O-acetyl)-beta-D-fucopyranosyl ester (II), 3-O-beta-D-glucopyranosyl-(1-->2) -beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4) -alpha-L-rhamnopyranosyl-(1-->2) -(4-O-acetyl) -beta-D-fucopyranosyl ester (II) and 3-O-beta-D-glucopyranosyl-(1--2) -beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4 ) -alpha-L-rhamnopyranosyl-(1-->2 ) - (3,4-diacetyl) -beta-D-fucopyranosyl ester (IV). CONCLUSIONS: The effective constituents of Polygala fallax Hemsl. reduced blood lipid especially plasma TG markedly. The authors have studied the chemical constituents of effective constituent systematically for the first time.


Asunto(s)
Hipolipemiantes/farmacología , Plantas Medicinales/química , Polygala/química , Saponinas/farmacología , Cromatografía Líquida de Alta Presión , Hidrólisis , Raíces de Plantas/química , Saponinas/aislamiento & purificación
8.
Int J Environ Res Public Health ; 12(10): 11988-2001, 2015 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-26404328

RESUMEN

OBJECTIVES: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd) and biomarkers of renal dysfunction. METHODS: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years) were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre), ß2-microglobulin (ß2-MG), α1-microglobulin (α1-MG), metallothionein (MT), retinol binding protein (RBP), albumin (AB), N-acetyl-ß-D-glucosaminidase (NAG), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) and kidney injury molecule-1 (KIM-1). Spearman's rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model) were used to model the dose-response relationships between U-Cd and nine urine markers. RESULTS: Spearman's rank correlation showed that NAG, ALP, RBP, ß2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R² of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. CONCLUSIONS: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.


Asunto(s)
Cadmio/orina , Riñón/metabolismo , Acetilglucosaminidasa/orina , Adulto , Anciano , Albuminuria , alfa-Globulinas/orina , Biomarcadores/orina , China , Creatinina/orina , Estudios Transversales , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Glicoproteínas de Membrana/orina , Metalotioneína/orina , Persona de Mediana Edad , Receptores Virales , Proteínas Celulares de Unión al Retinol/orina , Población Rural , Microglobulina beta-2/orina , gamma-Glutamiltransferasa/orina
9.
Arch Pharm Res ; 35(10): 1793-801, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23139131

RESUMEN

Our aims were to investigate the hypoglycemic effects and mechanisms of action of Ganoderma lucidum polysaccharides (GLPs) administered for 7 days in type 2 diabetic mice. The mice were randomly divided into four groups (8 mice/group): normal control group, diabetic control group, low-dose GLP-treated diabetic group (50 mg/kg/d), and high-dose GLP-treated diabetic group (100 mg/kg/d). Diabetes was induced by streptozotocin injection and high-fat dietary feeding. At the end of the study, fasting serum glucose, insulin, body weight (BW) and epididymal white adipose tissue weight were measured. The hepatic mRNA levels of glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes were determined by real-time polymerase chain reaction. Both doses of GLPs significantly decreased fasting serum glucose, insulin and epididymal fat/BW ratio compared with the diabetic control group (p < 0.05). The hepatic mRNA levels of GP, FBPase, PEPCK and G6Pase were significantly lower in both GLP-treated groups compared with the diabetic control group. Taken together, GLPs significantly decrease fasting serum glucose levels in type 2 diabetic mice in a dose-dependent manner. The decreases in fasting serum glucose levels may be associated with decreased mRNA expression levels of several key enzymes involved in gluconeogenesis and/or glycogenolysis.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Polisacáridos Fúngicos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Reishi/química , Tejido Adiposo Blanco/efectos de los fármacos , Animales , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 2/sangre , Polisacáridos Fúngicos/administración & dosificación , Polisacáridos Fúngicos/aislamiento & purificación , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/aislamiento & purificación , Insulina/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Medicina Tradicional China , Ratones , Ratones Endogámicos , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estreptozocina/farmacología
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