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BACKGROUND AND PURPOSE: The detection and characterization of functional activities in the gray matter of schizophrenia (SZ) have been widely explored. However, the relationship between resting-state functional signals in the white matter of first-episode SZ and short-term treatment response remains unclear. METHODS: Thirty-six patients with first-episode SZ and 44 matched healthy controls were recruited in this study. Patients were classified as nonresponders and responders based on response to antipsychotic medication during a single hospitalization. The fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) of white matter were calculated. The relationships between functional changes and clinical features were analyzed. In addition, voxel-based morphometry was performed to analyze the white matter volume. RESULTS: One-way analysis of variance showed significant differences of fALFF and ReHo in the left posterior thalamic radiation and left cingulum (hippocampus) in the patient group, and the areas were regarded as seeds. The FC was calculated between seeds and other white matter networks. Compared with responders, nonresponders showed significantly increased FC between the left cingulum (hippocampus) and left posterior thalamic radiation, splenium of corpus callosum, and left tapetum, and were associated with the changes of clinical assessment. However, there was no difference in white matter volume between groups. CONCLUSION: Our work provides a novel insight that psycho-neuroimaging-based white matter function holds promise for influencing the clinical diagnosis and treatment of SZ.
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Esquizofrenia , Sustancia Blanca , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Sustancia Blanca/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Corteza Cerebral , Imagen por Resonancia Magnética/métodos , EncéfaloRESUMEN
Diabetes has been regarded as an independent risk factor for Alzheimer's disease (AD). Our previous study found that diabetes activated autophagy, but lysosome function was impaired. Autophagy-lysosome dysfunction may be involved in Aß deposition in diabetic cognitive impairment. In the present study, we used STZ-induced diabetic rats and SH-SY5Y cells to investigate whether diabetes inhibits autophagosome fusion with lysosomes. We found that in the in vivo study, STZ-induced diabetic rats exhibited cognitive dysfunction, and the lysosome function-related factors CTSL, CTSD, and Rab7 were decreased (P < 0.05). In an in vitro study, the mRFP-GFP-LC3 assay showed that the fusion of autophagosomes with lysosomes was partly blocked in SH-SY5Y cells. High glucose treatment downregulated the number of autophagolysosomes, downregulated CTSD, CTSL, and Rab7 expression (P < 0.05), and then influenced the function of ACP2 to partly block the fusion of autophagosomes and lysosomes to inhibit Aß clearance. These findings indicate that high glucose treatment affected lysosome function, interfered with the fusion of autophagosomes with lysosomes, and partly blocked autophagic flux to influence Aß clearance.
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Diabetes Mellitus Experimental , Neuroblastoma , Ratas , Humanos , Animales , Autofagosomas/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Neuroblastoma/metabolismo , Autofagia , Lisosomas/metabolismo , Glucosa/metabolismoRESUMEN
BACKGROUND AND PURPOSE: We used the voxel-mirrored homotopic connectivity (VMHC) method to investigate brain interhemispheric functional connectivity changes in patients with optic neuritis (ON). METHODS: A total of 22 ON patients and 22 healthy controls (HCs) closely matched in age, sex, and weight were enrolled. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). Functional interaction between the hemispheres was assessed with the VMHC method. Correlation analysis was applied to explore the association between altered VMHC values in different brain areas and cognitive features. Receiver operating characteristic (ROC) curve analysis was applied to distinguish ON patients from HCs. RESULTS: Compared with HCs, ON patients had obviously reduced VMHC values in the right superior temporal gyrus, left margin superior gyrus, right superior motor cortex, and left middle cingulate gyrus. a negative relationship between best-corrected visual acuity and VMHC values in left margin superior gyrus was found, besides, the VMHC values within the right superior motor cortex and the right superior temporal gyrus were also anti-correlated with the Hamilton Depression Scales. The ROC curve displayed high diagnostic values in those altered regions. CONCLUSION: Abnormal VMHC values may reflect the underlying neuropathologic mechanism of ON.
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Imagen por Resonancia Magnética , Neuritis Óptica , Humanos , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Corteza Prefrontal , Neuritis Óptica/diagnóstico por imagenRESUMEN
Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.
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Background: Using resting-state functional connectivity (rsFC), we investigated alternations in spontaneous brain activities reflected by functional connectivity density (FCD) in patients with optic neuritis (ON). Methods: We enrolled 28 patients with ON (18 males, 10 females) and 24 healthy controls (HCs; 16 males, 8 females). All subjects underwent functional magnetic resonance imaging (fMRI) in a quiet state to determine the values of rsFC, long-range FCD (longFCD), and short-range FCD (IFCD). Receiver operating characteristic (ROC) curves were generated to distinguish patients from HCs. Results: The ON group exhibited obviously lower longFCD values in the left inferior frontal gyrus triangle, the right precuneus and the right anterior cingulate, and paracingulate gyri/median cingulate and paracingulate gyri. The left median cingulate and paracingulate gyri and supplementary motor area (SMA) were also significantly lower. Obviously reduced IFCD values were observed in the left middle temporal gyrus/angular gyrus/SMA and right cuneus/SMA compared with HCs. Conclusion: Abnormal neural activities were found in specific brain regions in patients with ON. Specifically, they showed significant changes in rsFC, longFCD, and IFCD values. These may be useful to identify the specific mechanism of change in brain function in ON.
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Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.
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Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Síndrome Metabólico/tratamiento farmacológico , Saponinas/uso terapéutico , Animales , Línea Celular , Trasplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiología , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Ratones , Ratones Endogámicos C57BL , Saponinas/farmacologíaRESUMEN
OBJECTIVE: Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3ßHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. METHODS: To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). RESULTS: Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. CONCLUSION: The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.
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Antagonistas de Andrógenos/administración & dosificación , Complejos Multienzimáticos/genética , Progesterona Reductasa/genética , Neoplasias de la Próstata/tratamiento farmacológico , Esteroide Isomerasas/genética , Alelos , Antagonistas de Andrógenos/farmacología , Resistencia a Antineoplásicos , Humanos , Masculino , Mutación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
Metabolic syndrome (MetS) is a health disorder characterized by metabolic abnormalities that predict an increased risk to develop cardiovascular disease (CVD) and type 2 diabetes. Biomarkers can provide an insight into the novel mechanism for MetS and can be potentially used for personalized response to therapies. We exploited a targeted HPLC-MS/MS method to characterize plasma amino acids and carnitine metabolic profile in MetS patients. A training set (40 cases and 40 controls) and validation set (80 MetS patients and 80 healthy controls) were carried out to find the metabolic profiles. We discovered two carnitine metabolites including hydroxydecanoyl carnitine and methylglutarylcarnitine. Our results indicated that the decreased level of hydroxydecanoyl carnitine and methylglutarylcarnitine may be associated with the risk of MetS. These biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.
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Aminoácidos/sangre , Carnitina/sangre , Síndrome Metabólico/sangre , Metabolómica/métodos , Biomarcadores/sangre , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.
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Infecciones por Citomegalovirus/complicaciones , Neoplasias Gastrointestinales/etiología , Anciano , Anticuerpos Antivirales/sangre , Estudios Transversales , Citomegalovirus/genética , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/epidemiología , ADN Viral/análisis , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2⯵M) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5â¯mg/kg/d), Cur (25, 15â¯mg/kg/d) for 10â¯weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.
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Aterosclerosis/tratamiento farmacológico , Curcumina/farmacología , Citomegalovirus/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerosis/metabolismo , Curcuma/metabolismo , Curcumina/metabolismo , Citocinas/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Ratones Transgénicos , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Placa Aterosclerótica/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Diabetic rats display cognition impairments accompanied by activation of NF-κB signalling and increased Aß expression. Ghrelin has been suggested to improve cognition in diabetic rats. In this study, we investigated the role of ghrelin on cognition and NF-κB mediated Aß production in diabetic rats. A diabetic rat model was established with streptozotocin (STZ) injection, and diabetic rats were intracerebroventricularly administered with ghrelin or (D-lys3)-GHRP-6 (DG). Our results showed that diabetic rats had cognition impairment in the Morris water maze test, accompanied by the higher expression of Aß in the hippocampus. Western blot analysis showed that diabetic rats exhibited significantly decreased levels of GHSR-1a and protein phosphatase 1 (PP1) in the hippocampus and increased activation of the IKK/NF-κB/BACE1 pathway. Chronic ghrelin administration upregulated hippocampal PP1 expression, suppressed IKK/NF-κB/BACE1 mediated Aß production, and improved cognition in STZ-induced diabetic rats. These effects were reversed by DG. Then, primary rat hippocampal neurons were isolated and treated with high glucose, followed by Ghrelin and DG, PP1 or IKK. Similar to the in vivo results, high glucose suppressed the expression levels of GHSR-1a and PP1, activated the IKK/NF-κB/BACE1 pathway, increased Aß production. Ghrelin suppressed IKK/NF-κB/BACE1 induced Aß production. This improvement was reversed by DG and a PP1 antagonist and was enhanced by the IKK antagonist. Our findings indicated that chronic ghrelin administration can suppress IKK/NF-κB/BACE1 mediated Aß production in primary neurons with high glucose treatment and improve the cognition via PP1 upregulation in diabetic rats.
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Péptidos beta-Amiloides/metabolismo , Cognición/fisiología , Diabetes Mellitus Experimental/metabolismo , Ghrelina/metabolismo , Neuronas/metabolismo , Proteína Fosfatasa 1/metabolismo , Transducción de Señal , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Ácido Aspártico Endopeptidasas/metabolismo , Células Cultivadas , Cognición/efectos de los fármacos , Diabetes Mellitus Experimental/psicología , Ghrelina/administración & dosificación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/ultraestructura , Quinasa I-kappa B/metabolismo , Masculino , FN-kappa B/metabolismo , Neuronas/efectos de los fármacos , Neuronas/ultraestructura , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Estreptozocina/administración & dosificación , Sinapsis/efectos de los fármacos , Sinapsis/ultraestructura , Regulación hacia ArribaRESUMEN
Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.
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Metabolismo de los Lípidos , Lipidómica/métodos , Síndrome Metabólico/diagnóstico , Fosfatidilcolinas/sangre , Adulto , Biomarcadores/sangre , Biomarcadores/metabolismo , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Fosfatidilcolinas/metabolismo , Medición de Riesgo/métodos , Espectrometría de Masas en TándemRESUMEN
BACKGROUND AND AIMS: Akebia Saponin D (ASD) is a major bioactive triterpenoid saponin compound isolated from the Chinese herb Dipsacus asper wall (DSW). DSW has been long used as an anti-Alzheimer disease and anti-osteoporosis agent in clinics. However, anti-atherosclerotic effects of ASD have not been fully investigated. The objective of this study is to further investigate the anti-atherosclerotic activities and mechanisms of ASD in vivo and in vitro. METHODS: In in vitro experiments, ASD (50, 100, and 200⯵M) was used to explore the effects of preventing H2O2-induced endothelial cell apoptosis and the possible mechanism involved. In in vivo experiments, ApoE-/- mice were fed a high fat diet (HFD) and treated with atorvastatin (10â¯mg/kg/d), ASD (50, 150, 450â¯mg/kg/d), or the combination therapy (atorvastatin 10â¯mg/kg/d and ASD 150â¯mg/kg/d) for 14 weeks. RESULTS: We found that ASD reduced the generation of reactive oxygen species, inhibited mitochondrial membrane potential (MMP) impairment, diminished the expression of Bax and Caspase-3, increased Bcl-2 expression, and inhibited apoptosis in endothelial cells. ASD significantly increased the expression of anti-oxidant enzymes (GSH, SOD, and CAT) in both liver and vascular tissue, reduced blood lipid levels (TG, TC, and LDL-C), and decreased lipid deposition in the liver and atherosclerotic lesion size in ApoE-/- mice. CONCLUSIONS: Our study revealed that ASD inhibited atherosclerosis development in ApoE-/- mice by inhibiting oxidative stress-induced endothelial cell apoptosis signaling pathway, and suggested that ASD might be a potential therapeutic drug in the prevention of atherosclerosis.
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Apoptosis/efectos de los fármacos , Aterosclerosis/prevención & control , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Saponinas/farmacología , Saponinas/uso terapéutico , Animales , Apolipoproteínas E/deficiencia , Células Cultivadas , Células Endoteliales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Akebia saponin D, which is originates from Dipsacus asper Wall, has been used as a tonic, an analgesic and anti-inflammatory agent for the therapy of low back pain, rheumatic arthritis, traumatic hematoma, habitual abortion and bone fractures in traditional Chinese medicine. However, the anti-nociceptive and anti-inflammatory activity and mechanism of Akebia saponin D has been rarely reported. The aim of this study was to investigate the anti-nociceptive and anti-inflammatory activity of Akebia saponin D and to assess its possible mechanism. The anti-nociceptive effect was measured by formalin test, hot plate, and acetic acid-induced writhing in mice while the anti-inflammatory effect was measured by carrageenan induced paw edema test, xylene-induced ear swelling and acetic acid-induced vascular permeability in mice and rats. Furthermore, anti-inflammatory effect was also measured in vitro using LPS-induced RAW 264.7 cells. Our results demonstrated that Akebia saponin D dose-dependently decreased the licking time in the formalin test, delayed the reaction time of mice to the hot plate, and inhibited acetic acid-induced writhing. Treatment of Akebia saponin D attenuated the carrageenan induced paw edema in rats, inhibited the mouse ear swelling, and decreased Evans blue concentration in acetic acid induced vascular permeability test, revealing its strong anti-inflammatory effect. Akebia saponin D significantly decreased NO production and iNOS expression. Our results indicate that Akebia saponin D has anti-nociceptive and anti-inflammatory effects. It will provide experimental evidences for the use of Akebia saponin D and can be used to develop a therapeutic drug against pain and inflammation related diseases.
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Analgésicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Saponinas/farmacología , Animales , Carragenina/farmacología , Células Cultivadas , Edema/inducido químicamente , Ratones , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Dimensión del Dolor/métodos , Fitoterapia , RatasRESUMEN
Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD.
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Hígado Graso/tratamiento farmacológico , Hígado Graso/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Mitofagia/efectos de los fármacos , Mitofagia/genética , Terapia Molecular Dirigida , Saponinas/farmacología , Animales , Línea Celular , Dipsacaceae/química , Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Fitoterapia , Ratas , Saponinas/uso terapéuticoRESUMEN
BACKGROUND: Human cytomegalovirus (HCMV) infection has been associated with inflammatory bowel disease (IBD). Numerous studies have been conducted to analyze the association between HCMV infection and risk of IBD and steroid-resistant IBD, but no clear consensus had been reached. OBJECTIVES: The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. STUDY DESIGN: We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they 1) evaluated the association between HCMV infection and IBD disease; 2) evaluated the association between HCMV infection and steroid-resistant IBD disease; 3) were case-control studies or nested case-control studies; 4) provided the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. RESULTS AND CONCLUSION: A total of 18 studies including 1,168 patients and 951 health groups was identified, and HCMV infection was distinctly confirmed as a risk factor for the occurrence and development of IBD. When involving 17 studies including 1,306 IBD patients, a total of 52.9% of patients in the cytomegalovirus (CMV)-positive groups were observed to have steroid resistance, compared with 30.2% of patients in the CMV-negative groups. There was a significant difference in the risk of steroid resistance between people exposed to HCMV infection and those not exposed HCMV infection in IBD patients. This meta-analysis suggested that HCMV infection is associated with an increased risk for IBD and steroid-resistant IBD.
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BACKGROUND: Vitamin D status may influence the risk of Insulin resistance related diseases such as Type 2 diabetes (T2DM), metabolic syndrome (MetS), and polycystic ovarian syndrome (PCOS). Several studies have assessed vitamin D receptor (VDR) gene polymorphism in relationship with these diseases; however, results remain inconsistent. Our study was conducted to elucidate whether VDR Gene polymorphisms could predict insulin resistance on a large scale. METHODS: A meta-analysis using MEDLINE and EMBASE, was performed up to December 16th, 2016. Studies reporting association of vitamin D gene polymorphism with incident T2DM, MetS and PCOS outcomes were included and sub-group analysis by pigment of skin and latitude were performed. RESULTS: A total of 28 articles based on four gene variation, and comprising 9232 participants with 5193 Insulin resistance related diseases patients were included. No significant associations of the VDR ApaI, BsmI, FokI and TaqI variant with Insulin resistance related diseases were found. However, sub-group analysis analysis showed that PCOS in TaqI (OR = 1.47, 95% CI = 1.03-2.09, P = 0.03) for T allele and MetS for G allele (OR = 1.41, 95% CI = 1.07-1.85, P = 0.01) in BsmI was significant association with VDR gene polymorphism. Simultaneously, sub-group analysis showed VDR ApaI rs7975232(G > T)variant was associated with insulin resistance related diseases in Asians (GG/GT + TT) (OR, 1.62; 95% CI, 1.03-2.53; P = 0.04) and population who lived in middle latitude district (30-60°) (GG/GT + TT) (OR, 1.22; 95% CI, 1.04-1.43; P = 0.02), VDR BsmI rs1544410 (A > G)and VDR Taq1rs731236 (T/C) variant were associated with insulin resistance related diseases in Caucasian (dark-pigmented). CONCLUSION: The results suggested that the association between insulin resistance related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasian with white skin.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Resistencia a la Insulina/genética , Síndrome Metabólico/genética , Síndrome del Ovario Poliquístico/genética , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Pueblo Asiatico , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/patología , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Masculino , Síndrome Metabólico/etnología , Síndrome Metabólico/patología , Oportunidad Relativa , Síndrome del Ovario Poliquístico/etnología , Síndrome del Ovario Poliquístico/patología , Pigmentación de la Piel/genética , Población BlancaRESUMEN
Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta-analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non-atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG-based HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17-25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The meta-analysis results showed that HCMV infection is significant connected with an increased risk for AS.
Asunto(s)
Aterosclerosis/etiología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/virología , Citomegalovirus/fisiología , Adulto , Anticuerpos Antivirales/sangre , Aterosclerosis/virología , Citomegalovirus/genética , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/etnología , ADN Viral/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Proteínas de la Matriz Viral/aislamiento & purificaciónRESUMEN
Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-ß (Aß), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aß accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether the expression of RAGE and LRP-1 is related to Aß1-42 deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that diabetic rats had longer escape latency and less frequency of entrance into the target zone than that of the control group (P < 0.05) in the Morris water maze (MWM) test. The Aß1-42 expression in the hippocampus and prefrontal lobe significantly increased in the DM group compared to the control group (P < 0.05). RAGE increased (P < 0.05), while LRP-1 decreased (P < 0.05) in the hippocampus tissue and prefrontal lobe tissue of DM rats. The Aß1-42 deposition was correlated with RAGE positively (P < 0.05), but with LRP-1 negatively (P < 0.05). Further, the expression levels of Aß1-42, RAGE, and LRP-1 were not changed in the amygdala between the diabetic rats and the control group. These findings indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus and the prefrontal lobe contributed to the Aß1-42 accumulation and then further promoted the cognitive impairment of diabetic rats.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Péptidos beta-Amiloides/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/metabolismo , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Corteza Prefrontal/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Péptidos beta-Amiloides/genética , Animales , Cognición , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Masculino , Aprendizaje por Laberinto , Ratas , Ratas Sprague-Dawley , Receptor para Productos Finales de Glicación Avanzada/genéticaRESUMEN
BACKGROUND: Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease. Numbers studies were conducted to analyze the association between HCMV infection and risk of vascular disease, but no clear consensus had been reached. The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. METHODS: We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: (1) evaluating the association between HCMV infection and vascular disease; (2) case-control studies or nested case-control studies; (3) and supply the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. Ultimately, We included data from 68 studies, which altogether enrolled 12027 cases and 15386 controls from 24 countries. RESULTS: HCMV IgG was detected 7376 in 10611 cases, HCMV IgM was detected 153 in 1486 cases and HCMV DNA was detected 654 in 2139 cases. Overall, people exposed to HCMV infection had higher risk than those not exposed for vascular disease (OR 1.70 [95% CI 1.43-2.03] IgG-based HCMV tests, 2.88 [95% CI 1.87-4.43] IgM-based HCMV tests and 2.56 [95% CI 1.46-4.49 PCR-based HCMV tests]). HCMV infection was clearly identified as a risk factor for vascular disease in Asian group, Caucasian group and other group, especially Asian group(OR 1.86 [95% CI 1.33-2.60] IgG-based HCMV tests, 3.57 [95% CI 1.94-6.60] IgM-based HCMV tests and 4.09 [95% CI 3.10-5.40 PCR-based HCMV tests]). CONCLUSION: This meta-analysis suggested that HCMV infection is associated with an increased risk for vascular disease.