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PURPOSE: Postoperative delirium (POD) commonly occurs after major abdominal surgery and is associated with increased morbidity and mortality. There have been many studies on the relationship between POD and various surgeries, but research on POD after pancreatic cancer surgery is limited. The aim of this study was to identify the incidence and risk factors of POD after pancreatic cancer surgery. METHODS: The subjects of this retrospective analysis were 196 patients who were transferred for postoperative care after pancreatic cancer surgery, to a 12-bed critical care medicine ward at Shandong Provincial Hospital, affiliated with Shandong First Medical University, between January 2015 and December 2019. The patients were divided according to whether they suffered POD into a delirium group and a non-delirium group. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit and two independent medical practitioners analyzed all the data. Univariate and multiple logistic regression analyses were performed. RESULTS: The overall delirium incidence was 20.41%, which increased to 29.03% for patients aged ≥ 70 years. POD was associated with age, smoking, the American Society of Anesthesiologists classification, the Acute Physiology and Chronic Health Evaluation II score, and the TNM stage of the cancer. The variables concerning sex, drinking, hypertension, a history of cerebral disease, surgery type, operation time, amount of bleeding, and the intraoperative use of dexmedetomidine did not differ significantly between the two groups. There was no significant difference in the length of ICU stay, with the exclusion of long-term stay for complications, between the groups, but POD tended to prolong the postoperative hospital stay and increase the risk of mortality. There was also a gradual decline in the incidence of POD between 2015 and 2019, especially from 2015 to 2018, after preventive measures were implemented. CONCLUSION: POD is related to many risk factors and worthy of attention. Appropriate management can reduce its incidence or at least shorten its duration.
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Delirio del Despertar , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Incidencia , Factores de Riesgo , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/complicaciones , Neoplasias PancreáticasRESUMEN
BACKGROUND: Cyanobacteria are of special concern because they proliferate in eutrophic water bodies worldwide and affect water quality. As an ancient photosynthetic microorganism, cyanobacteria can survive in ecologically diverse habitats because of their capacity to rapidly respond to environmental changes through a web of complex signaling networks, including using second messengers to regulate physiology or metabolism. A ubiquitous second messenger, bis-(3',5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP), has been found to regulate essential behaviors in a few cyanobacteria but not Microcystis, which are the most dominant species in cyanobacterial blooms. In this study, comparative genomics analysis was performed to explore the genomic basis of c-di-GMP signaling in Microcystis aeruginosa. RESULTS: Proteins involved in c-di-GMP metabolism and regulation, such as diguanylate cyclases, phosphodiesterases, and PilZ-containing proteins, were encoded in M. aeruginosa genomes. However, the number of identified protein domains involved in c-di-GMP signaling was not proportional to the size of M. aeruginosa genomes (4.97 Mb in average). Pan-genome analysis showed that genes involved in c-di-GMP metabolism and regulation are conservative in M. aeruginosa strains. Phylogenetic analysis showed good congruence between the two types of phylogenetic trees based on 31 highly conserved protein-coding genes and sensor domain-coding genes. Propensity for gene loss analysis revealed that most of genes involved in c-di-GMP signaling are stable in M. aeruginosa strains. Moreover, bioinformatics and structure analysis of c-di-GMP signal-related GGDEF and EAL domains revealed that they all possess essential conserved amino acid residues that bind the substrate. In addition, it was also found that all selected M. aeruginosa genomes encode PilZ domain containing proteins. CONCLUSIONS: Comparative genomics analysis of c-di-GMP metabolism and regulation in M. aeruginosa strains helped elucidating the genetic basis of c-di-GMP signaling pathways in M. aeruginosa. Knowledge of c-di-GMP metabolism and relevant signal regulatory processes in cyanobacteria can enhance our understanding of their adaptability to various environments and bloom-forming mechanism.
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GMP Cíclico/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Microcystis/metabolismo , Biología Computacional , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Genómica , Microcystis/clasificación , Microcystis/genética , Liasas de Fósforo-Oxígeno/genética , Liasas de Fósforo-Oxígeno/metabolismo , Filogenia , Dominios Proteicos , Transducción de SeñalRESUMEN
MicroRNAs (miRNAs), a subgroup of small noncoding RNAs, play critical roles in tumor growth and metastasis. Accumulating evidence shows that the dysregulation of miRNAs is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism by which miR-942-3p contributes to HCC remains undocumented. The association between miR-942-3p expression and the clinicopathological characteristics in HCC patients was analyzed by The Cancer Genome Atlas data set. The targets of miR-942-3p were identified by bioinformatic analysis and dual luciferase report assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays were performed to assess the functional role of miR-942-3p in HCC cells. Consequently, we found that miR-942-3p expression level was elevated in HCC tissues and cell lines as compared with the normal tissues and was associated with the pathological stage and tumor node metastasis (TNM) stage, acting as an independent prognostic factor of poor survival in patients with HCC. Ectopic expression of miR-942-3p enhanced the proliferation and invasive potential of HCC cells, but inhibition of miR-942-3p expression had the opposite effects. Mannose-binding lectin 2 (MBL2) was further identified as a direct target of miR-942-3p and possessed a negative correlation with miR-942-3p expression and unfavorable survival in patients with HCC. Restoration of MBL2 inhibited the progression of HCC cells and attenuated the tumor-promoting effects induced by miR-942-3p. In conclusion, miR-942-3p may act as an oncogenic factor in HCC cells by targeting MBL2 and provide a potential marker for patients with HCC.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Lectina de Unión a Manosa/genética , MicroARNs/genética , Carcinoma Hepatocelular/mortalidad , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Resultado del TratamientoRESUMEN
Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1-5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3in vitro.
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Cornus/química , Frutas/química , Inhibidores de Glicósido Hidrolasas/química , Glicósidos/química , Sesquiterpenos/química , Dicroismo Circular , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Glicósidos/aislamiento & purificación , Naftalenos/química , Naftalenos/aislamiento & purificación , Sesquiterpenos/aislamiento & purificaciónRESUMEN
The neurodegenerative disorder known as Parkinson's disease (PD) affects many people. The objective of this investigation was to examine the relationship between immune system infiltration, ATP-binding cassette transporter subfamily A member 7 (ABCA7) and TBL2 as well as potential therapeutic targets for the identification of PD associated to endoplasmic reticulum (ER) stress. First, we obtained PD data through GEO and divided it into two sets: a training set (GSE8397) plus a set for validation (GSE7621). Functional enrichment analysis was performed on a set of DEGs that overlapped with genes involved in endoplasmic reticulum stress. To identify genes of PD linked with endoplasmic reticulum stress, we employed random forest (RF) along with the least absolute shrinkage and selection operator (LASSO) logistic regression. Spearman's rank correlation analysis was then used to find associations among diagnostic markers with immune cell penetration. A grand total of 2 stress-related endoplasmic reticulum signature transcripts were identified. ABCA7 and TBL2 were shown to have diagnostic potential for PD and immune infiltrating cells have a role in the etiology of the disease. Additionally, resting CD4 memory, plasma cells, and NK cells overall exhibited positive associations with ABCA7, whereas triggered macrophages, T cells with active CD4 memory, activating NK cells, T cells with activated CD4 naive, engaged NK cells, and neutrophils all had adverse interactions with ABCA7. Overall, ABCA7 together with TBL2 have diagnostic utility for PD, and several types of immune cells, especially macrophages, may be involved in the development and progression of the disease.
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Biomarcadores , Estrés del Retículo Endoplásmico , Aprendizaje Automático , Enfermedad de Parkinson , Estrés del Retículo Endoplásmico/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/inmunología , Enfermedad de Parkinson/patología , Humanos , Biomarcadores/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/genéticaRESUMEN
With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6â¯J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders.
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Proteínas Quinasas Activadas por AMP , Microbioma Gastrointestinal , Hipoglucemiantes , Hígado , Ratones Endogámicos C57BL , PPAR gamma , Transducción de Señal , Estilbenos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Humanos , PPAR gamma/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones , Masculino , Estilbenos/farmacología , Transducción de Señal/efectos de los fármacos , Células Hep G2 , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucemia/efectos de los fármacos , Glucemia/metabolismoRESUMEN
OBJECTIVE: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. RESULTS: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008). CONCLUSION: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.
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Terapia por Acupuntura , Migraña sin Aura , Humanos , Femenino , Imagen por Resonancia Magnética/métodos , Lóbulo Occipital/diagnóstico por imagen , DolorRESUMEN
Phytoplankton community characteristics, diversity, and functional group analysis can respond to the environmental quality status of water bodies. To investigate the influence of urban river black odors on the phytoplankton community, from November 2020 to March 2021, 16 urban rivers in the Sichuan Basin were surveyed for water quality with 38 sampling points, and the degree of urban river black odor was evaluated based on the improved fuzzy mathematical model method and the k-mean principal color extraction method. The rivers were classified into four types:non-black and non-odorous, black and non-odorous, black and odorous, and black and odorous. The results showed that, with black and odorous water, the phytoplankton abundance increased from 1.329×105 cells·L-1 to 6.627×105 cells·L-1, and the dominant phytoplankton phylum decreased from Cyanophyta-Chlorophyta-Bacillariophyta to Cyanophyta. The phytoplankton biomass increased from 64.056 µg·L-1 to 120.465 µg·L-1, and the dominant phytoplankton phylum changed from Chlorophyta-Bacillariophyta type, adapted to a nutrient environment, to Pyrrophyta-Bacillariophyta-Cryptophyta type, adapted to an organic matter environment. The Shannon-Weaver diversity index decreased from 2.45 to 1.98, and Simpson's index decreased from 0.84 to 0.73. Twenty nine functional groups of phytoplankton were observed in the study area, and the growth strategy was reduced from S, R, C, CR, and CS to R with black and odorous water. In summary, phytoplankton indicators can better reflect the state of river black odor, and phytoplankton monitoring is a promising tool for urban river black odor management.
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Diatomeas , Dinoflagelados , Fitoplancton , Odorantes , RíosRESUMEN
Excess accumulation of white adipose tissue (WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke, heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige (brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue (BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products (alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes (T2DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.
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Tejido Adiposo Pardo/fisiología , Tejido Adiposo Blanco/fisiología , Productos Biológicos/farmacología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Descubrimiento de Drogas , Metabolismo Energético , Humanos , Obesidad/tratamiento farmacológico , Fitoquímicos/farmacología , TermogénesisRESUMEN
Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in HepG2 cells was assayed along with the qPCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program LibDock of Discovery Studio 2018 software. The results showed that puerarin improved HepG2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.
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Proteínas Quinasas Activadas por AMP/metabolismo , Hipoglucemiantes/farmacología , Isoflavonas/farmacología , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Glucemia/metabolismo , Células Hep G2 , Humanos , Hiperglucemia , Masculino , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , FosforilaciónRESUMEN
Microcystis, the dominant species among cyanobacterial blooms, normally forms colonies under natural conditions but exists as single cells or paired cells in axenic laboratory cultures after long-term cultivation. Here, a bloom-forming Microcystis aeruginosa strain CHAOHU 1326 was studied because it presents a colonial morphology and grows on the water surface during axenic laboratory culturing. We first examined the morphological features of strain CHAOHU 1326 and three other unicellular M. aeruginosa strains FACHB-925, FACHB-940, and FACHB-975 cultured under the same conditions by scanning and transmission electron microscopy. Then, we compared the extracellular polysaccharide (EPS)-producing ability of colonial strain CHAOHU 1326 to that of the three unicellular M. aeruginosa strains, and found that strain CHAOHU 1326 produced a higher amount of EPS than the other strains during growth. Moreover, based on genome sequencing, multiple gene clusters implicated in EPS biosynthesis and a cluster of 12 genes predicted to be involved in gas vesicle synthesis in strain CHAOHU 1326 were detected. These predicted genes were all functional and expressed in M. aeruginosa CHAOHU 1326 as determined by reverse transcription PCR. These findings provide a physiological and genetic basis to better understand colony formation and buoyancy control during M. aeruginosa blooming.
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Microcystis/crecimiento & desarrollo , Polisacáridos Bacterianos/metabolismo , Vías Biosintéticas , Eutrofización , Genoma Bacteriano , Microcystis/genética , Microcystis/metabolismo , Microcystis/ultraestructura , Filogenia , Polisacáridos Bacterianos/genética , Microbiología del AguaRESUMEN
Many drugs with anti-diabetic effects regulate glucose consumption in peripheral tissues. Via cellular glucose consumption assays, we identified that coptisine, a main effective constituent from the plant Coptis chinensis, enhanced hepatic and skeletal muscle glucose consumption. We further explored its effects on glucose metabolism in diabetic animals to elucidate its mechanism of action. Our results showed that coptisine did not show cytotoxicity. Intragastric administration of coptisine for ten days in normal ICR mice markedly decreased fasting blood-glucose levels without significant effects on body weight. In alloxan-induced type 1 diabetic mice, intragastric administration of coptisine for 28 days decreased fasting and non-fasting blood-glucose levels as well. In type 2 diabetic KKAy mice, intragastric administration of coptisine for nine weeks improved glucose tolerance. It decreased fasting/non-fasting blood-glucose and fructosamine levels. Coptisine decreased low-density lipoprotein and total cholesterol levels, however, had no significant effect on triglyceride levels. Coptisine increased AMPK phosphorylation while decreasing Akt phosphorylation in HepG2 hepatic cells and C2C12 myotubes. Coptisine also reduced mitochondrial respiration in isolated and cellular mitochondria, suggesting that coptisine lowered cellular energy levels. In particularly, coptisine administration (10-6â¯M) decreased the mitochondrial oxygen consumption rate (OCR) with a greater extracellular acidification rate (ECAR), resulting in an oxidative-to-glycolysis phosphorylation shifted for cellular energy generation. Our results demonstrate that coptisine acts as an enhancer of peripheral glucose consumption could improve glucose metabolism in diabetic animals. Coptisine may serve as a novel anti-diabetic agent and warrant further evaluation.
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Berberina/análogos & derivados , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Hipoglucemiantes/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Berberina/farmacología , Berberina/uso terapéutico , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Activación Enzimática/efectos de los fármacos , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Células Hep G2 , Humanos , Hipoglucemiantes/uso terapéutico , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , RatasRESUMEN
Urotensin-II (U-II) is an endogenous peptide agonist of a G protein-coupled receptor-urotensin receptor. There are many conflicting findings about the effects of U-II on blood glucose. This study aims to explore the effects of U-II on glucose metabolism in high-fat diet-fed mice. Male C57BL/6J mice were fed a 45% high-fat diet or chow diet and were administered U-II intraperitoneally for in vivo study. Skeletal muscle C2C12 cells were used to determine the effects of U-II on glucose and fatty acid metabolism as well as mitochondrial respiratory function. In this study, we found that chronic U-II administration (more than 7 days) ameliorated glucose tolerance in high-fat diet-fed mice. In addition, chronic U-II administration reduced the weight gain and the adipose tissue weight, including visceral, subcutaneous, and brown adipose tissue, without a significant change in blood lipid levels. These were accompanied by the increased mRNA expression of the mitochondrial thermogenesis gene Ucp3 in skeletal muscle. Furthermore, in vitro treatment with U-II directly enhanced glucose and free fatty acid consumption in C2C12 cells with increased aerobic respiration. Taken together, chronic U-II stimulation leads to improvement on glucose tolerance in high-fat diet-fed mice and this effect maybe closely related to the reduction in adipose tissue weights and enhancement on energy substrate utilization in skeletal muscle.
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Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4+ CD25+ FoxP3+ (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.
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Encefalomielitis Autoinmune Experimental/terapia , Células Madre Mesenquimatosas/metabolismo , Esclerosis Múltiple/terapia , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Cordón Umbilical/metabolismo , Animales , Autoinmunidad/fisiología , Linfocitos T CD4-Positivos/metabolismo , Sistema Nervioso Central/metabolismo , Femenino , Humanos , Células Asesinas Naturales/metabolismo , Ratones , Ratones Endogámicos C57BL , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Transfección/métodosRESUMEN
Stroke is the leading cause of disability and death in the world. Central post-stroke pain (CPSP), a central neuropathic pain syndrome occurring after cerebral stroke, is a serious problem. But on account of the lack of reliable animal models, the mechanisms underlying CPSP remains poorly understood. To better understand of the pathophysiological basis of CPSP, we developed and characterized a new rat model of CPSP. This model is based on a hemorrhagic stroke lesion with intra-thalamic autologous blood (ITAB) injection in the ventral posterolateral nucleus of the thalamus. Behavioral analysis demonstrated that the animals displayed a significant decrease in mechanical allodynia threshold. We found a signiï¬cant increase in P2 × 4 receptor expression in microglia in thalamic peri-lesion tissues post-hemorrhage. The mechanical allodynia in rats with CPSP were reversed by blocking P2 × 4 receptors. A significant alleviation of mechanical allodynia was achieved following the administration of adrenergic antidepressants and antiepileptics. Meanwhile, we found a signiï¬cant decrease in P2 × 4 receptor expression after treatment with these drugs. Taken together, our results suggest that targeting P2 × 4 receptor may be effective in the treatment of CPSP.
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Hemorragia Cerebral/patología , Hiperalgesia/patología , Hemorragias Intracraneales/complicaciones , Receptores Purinérgicos P2X4/metabolismo , Accidente Cerebrovascular/patología , Animales , Modelos Animales de Enfermedad , Hiperalgesia/fisiopatología , Hemorragias Intracraneales/patología , Masculino , Microglía/patología , Ratas Sprague-Dawley , Accidente Cerebrovascular/fisiopatología , Tálamo/patología , Tálamo/fisiopatología , Núcleos Talámicos Ventrales/patología , Núcleos Talámicos Ventrales/fisiopatologíaRESUMEN
The aims of this study were to identify arteriographic manifestations of acute renal hemorrhage and to evaluate the efficacy of emergency embolization. Emergency renal artery angiography was performed on 83 patients with acute renal hemorrhage. As soon as bleeding arteries were identified, emergency embolization was performed using gelatin sponge, polyvinyl alcohol particles, and coils. The arteriographic presentation and the effect of the treatment for acute renal hemorrhage were analyzed retrospectively. Contrast extravasation was observed in 41 patients. Renal arteriovenous fistulas were found in 12 of the 41 patients. In all, 8 other patients had a renal pseudoaneurysm, 5 had pseudoaneurysm rupture complicated by a renal arteriovenous fistula, and 1 had pseudoaneurysm rupture complicated by a renal artery-calyceal fistula. Another 16 patients had tumor vasculature seen on arteriography. Before the procedure, 35 patients underwent renal artery computed tomography angiography (CTA). Following emergency embolization, complete hemostasis was achieved in 80 patients, although persistent hematuria was present in 3 renal trauma patients and 1 patient who had undergone percutaneous nephrolithotomy (justifying surgical removal of the ipsilateral kidney in this patient). Two-year follow-up revealed an overall effective rate of 95.18 % (79/83) for emergency embolization. There were no serious complications. Emergency embolization is a safe, effective, minimally invasive treatment for renal hemorrhage. Because of the diversified arteriographic presentation of acute renal hemorrhage, proper selection of the embolic agent is a key to successful hemostasis. Preoperative renal CTA plays an important role in diagnosing and localizing the bleeding artery.
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Cateterismo , Embolización Terapéutica/métodos , Tratamiento de Urgencia , Hemorragia/terapia , Arteria Renal , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism. METHODS: Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method. RESULTS: The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05). CONCLUSION: Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.
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Alcoholismo/fisiopatología , Quinasa 5 Dependiente de la Ciclina/metabolismo , Glucósidos/farmacología , Hipocampo/efectos de los fármacos , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Estilbenos/farmacología , Animales , Medicamentos Herbarios Chinos/farmacología , Hipocampo/enzimología , RatasRESUMEN
OBJECTIVE: To study the effect of progesterone on matrix metalloproteinase-3 (MMP-3) expression in neonatal rat brain after hypoxic-ischemia. METHODS: Followed the hypoxic-ischemia of neonatal rat brain, Evans blue (EB) staining and transmission electron microscopy were used to detect the blood-brain barrier pathological changes on permeability. MMP-3 protein expression in cerebral cortex was measured with Western blot. RESULTS: Transmission electron microscopy results showed that the blood brain barrier in hypoxic-ischemic group changed significantly compare to progesterone group. EB staining results suggested that the blood-brain barrier permeability of hypoxic-ischemic group was significantly increased compared to sham-operated group (P < 0.01). The blood-brain barrier permeability in progesterone group was also decreased in comparison to that of hypoxic-ischemic group (P < 0.05). Western blot image analysis results indicated that MMP-3 protein expression in the hypoxic-ischemic group increased significantly than that in sham-operated group (P < 0.01), and the progesterone group was decreased significantly than that in hypoxic-ischemic group (P < 0.05). CONCLUSION: Progesterone may reduce the blood-brain barrier damage by reducing MMP-3 expression. This might be one of the protective mechanisms in the hypoxic-ischemic brain injury.
Asunto(s)
Barrera Hematoencefálica/fisiopatología , Hipoxia-Isquemia Encefálica/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Progesterona/farmacología , Animales , Animales Recién Nacidos , Hipoxia-Isquemia Encefálica/patología , Hipoxia-Isquemia Encefálica/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.