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Asymmetric PCR is widely used to produce single-stranded amplicons (ss-amplicons) for various downstream applications. However, conventional asymmetric PCR schemes are susceptible to events that affect primer availability, which can be exacerbated by multiplex amplification. In this study, a new multiplex asymmetric PCR approach that combines the amplification refractory mutation system (ARMS) with the homo-Tag-assisted nondimer system (HANDS) is described. ARMS-HANDS (A-H) PCR utilizes equimolar-tailed forward and reverse primers and an excess Tag primer. The tailed primer pairs initiate exponential symmetric amplification, whereas the Tag primer drives linear asymmetric amplification along fully matched strands but not one-nucleotide mismatched strands, thereby generating excess ss-amplicons. The production of ss-amplicons is validated using agarose gel electrophoresis, sequencing, and melting curve analysis. Primer dimer alleviation is confirmed by both the reduced Loss function value and a 20-fold higher sensitivity in an 11-plex A-H PCR assay than in an 11-plex conventional asymmetric PCR assay. Moreover, A-H PCR demonstrates unbiased amplification by its allele quantitative ability in correct identification of all 31 trisomy 21 samples among 342 clinical samples. A-H PCR is a new generation of multiplex asymmetric amplification approach with various applications, especially when sensitive and quantitative detection is required.
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Reacción en Cadena de la Polimerasa Multiplex , Mutación , Humanos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Cartilla de ADN/química , Síndrome de Down/genética , Síndrome de Down/diagnósticoRESUMEN
BACKGROUND: Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown. METHODS: Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs. RESULTS: The expression levels of inflammation-related markers (diamine oxidase, D-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1ß) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs. CONCLUSIONS: S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.
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Pólipos Adenomatosos , Firmicutes , Humanos , Animales , Ratones , ARN Ribosómico 16S/genética , Inflamación/complicaciones , Pólipos Adenomatosos/complicacionesRESUMEN
Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20â¯g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16â¯S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16â¯S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).
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Microbioma Gastrointestinal , Hiperlipidemias , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Método Doble Ciego , Masculino , Persona de Mediana Edad , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre , Hiperlipidemias/microbiología , Femenino , Adulto , Lípidos/sangre , Almidón Resistente , Almidón , Hipolipemiantes/uso terapéutico , Hipolipemiantes/farmacología , AncianoRESUMEN
Myocardial hypertrophy is a pathological thickening of the myocardium which ultimately results in heart failure. We previously reported that zonisamide, an antiepileptic drug, attenuated pressure overload-caused myocardial hypertrophy and diabetic cardiomyopathy in murine models. In addition, we have found that the inhibition of proteasome activates glycogen synthesis kinase 3 (GSK-3) thus alleviates myocardial hypertrophy, which is an important anti-hypertrophic strategy. In this study, we investigated whether zonisamide prevented pressure overload-caused myocardial hypertrophy through suppressing proteasome. Pressure overload-caused myocardial hypertrophy was induced in mice by trans-aortic constriction (TAC) surgery. Two days after the surgery, the mice were administered zonisamide (10, 20, 40 mg·kg-1·d-1, i.g.) for four weeks. We showed that zonisamide administration significantly mitigated impaired cardiac function. Furthermore, zonisamide administration significantly inhibited proteasome activity as well as the expression levels of proteasome subunit beta types (PSMB) of the 20 S proteasome (PSMB1, PSMB2 and PSMB5) and proteasome-regulated particles (RPT) of the 19 S proteasome (RPT1, RPT4) in heart tissues of TAC mice. In primary neonatal rat cardiomyocytes (NRCMs), zonisamide (0.3 µM) prevented myocardial hypertrophy triggered by angiotensin II (Ang II), and significantly inhibited proteasome activity, proteasome subunits and proteasome-regulated particles. In Ang II-treated NRCMs, we found that 18α-glycyrrhetinic acid (18α-GA, 2 mg/ml), a proteasome inducer, eliminated the protective effects of zonisamide against myocardial hypertrophy and proteasome. Moreover, zonisamide treatment activated GSK-3 through inhibiting the phosphorylated AKT (protein kinase B, PKB) and phosphorylated liver kinase B1/AMP-activated protein kinase (LKB1/AMPKα), the upstream of GSK-3. Zonisamide treatment also inhibited GSK-3's downstream signaling proteins, including extracellular signal-regulated kinase (ERK) and GATA binding protein 4 (GATA4), both being the hypertrophic factors. Collectively, this study highlights the potential of zonisamide as a new therapeutic agent for myocardial hypertrophy, as it shows potent anti-hypertrophic potential through the suppression of proteasome.
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Anticonvulsivantes , Bloqueadores de los Canales de Calcio , Cardiomegalia , Glucógeno Sintasa Quinasa 3 , Complejo de la Endopetidasa Proteasomal , Zonisamida , Animales , Ratones , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Cardiomegalia/tratamiento farmacológico , Glucógeno Sintasa Quinasa 3/farmacología , Ratones Endogámicos C57BL , Miocitos Cardíacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Zonisamida/farmacología , Zonisamida/uso terapéutico , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéuticoRESUMEN
Autism spectrum disorder is a neurodevelopmental disorder whose core deficit is social dysfunction. Previous studies have indicated that structural changes in white matter are associated with autism spectrum disorder. However, few studies have explored the alteration of the large-scale white-matter functional networks in autism spectrum disorder. Here, we identified ten white-matter functional networks on resting-state functional magnetic resonance imaging data using the K-means clustering algorithm. Compared with the white matter and white-matter functional network connectivity of the healthy controls group, we found significantly decreased white matter and white-matter functional network connectivity mainly located within the Occipital network, Middle temporo-frontal network, and Deep network in autism spectrum disorder. Compared with healthy controls, findings from white-matter gray-matter functional network connectivity showed the decreased white-matter gray-matter functional network connectivity mainly distributing in the Occipital network and Deep network. Moreover, we compared the spontaneous activity of white-matter functional networks between the two groups. We found that the spontaneous activity of Middle temporo-frontal and Deep network was significantly decreased in autism spectrum disorder. Finally, the correlation analysis showed that the white matter and white-matter functional network connectivity between the Middle temporo-frontal network and others networks and the spontaneous activity of the Deep network were significantly correlated with the Social Responsiveness Scale scores of autism spectrum disorder. Together, our findings indicate that changes in the white-matter functional networks are associated behavioral deficits in autism spectrum disorder.
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Trastorno del Espectro Autista , Sustancia Blanca , Humanos , Sustancia Blanca/patología , Imagen por Resonancia Magnética/métodos , Sustancia Gris/patología , Análisis por Conglomerados , EncéfaloRESUMEN
Improper disposal of waste oils containing hazardous components damages the environment and the ecosystem, posing a significant threat to human life and health. Here, we present a method of discharge-assisted laser-induced breakdown spectroscopy combined with filter paper sampling (DA-LIBS-FPS) to detect hazardous components and trace the source of polluting elements. DA-LIBS-FPS significantly enhances spectral intensity by 1-2 orders of magnitude due to the discharge energy deposition into the laser-induced plasma and the highly efficient laser-sample interaction on the filter paper, when compared to single-pulse LIBS with silica wafer sampling (SP-LIBS-SWS). Additionally, the signal-to-noise ratio and the signal-to-background ratio are both significantly increased. Resultantly, indiscernible lines, such as CN and Cr I, are well distinguished. In contrast with DA-LIBS combined with silica wafer sampling (DA-LIBS-SWS), the spectral signal fluctuations in DA-LIBS-FPS are reduced by up to 33%, because of the homogeneous distribution of the oil layer on the filter paper in FPS. Further examination indicates that the limit of detection for Ba is reduced from a several parts per million level in SP-LIBS-SWS to a dozens of parts per billion level in DA-LIBS-FPS, i.e., nearly 2 orders of magnitude enhancement in analysis sensitivity. This improvement is attributed to the extended plasma lifespan in DA-LIBS and the increasing electron density and plasma temperature in FPS. DA-LIBS-FPS provides a low-cost, handy, rapid, and highly sensitive avenue to analyze the hazardous components in waste oils with great potential in environmental and ecological monitoring.
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Multi-targets detection has obtained much attention because this sensing mode can realize the detection of multi-targets simultaneously, which is helpful for biomedical analysis. Carbon nanoparticles have attracted extensive attention due to their superior optical and chemical properties, but there are few reports about red emission carbon nanoparticles for simultaneous detection of multi-targets. In this paper, a red emission fluorescent carbon nanoparticles were prepared by 1, 2, 4-triaminobenzene dihydrochloride at room temperature. The as-prepared red emission fluorescent carbon nanoparticles exhibited strong emission peak located at 635 nm with an absolute quantum yield up to 24%. They showed excellent solubility, high photostability and good biocompatibility. Furthermore, it could sensitively and selectively response to hypochlorite and pH, thus simultaneous detection of hypochlorite and pH was achieved by combining the red emission fluorescent carbon nanoparticles with computational chemistry. The formation mechanisms of red emission fluorescent carbon nanoparticles and their response to hypochlorite and pH were investigated, respectively.
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INTRODUCTION: Luteolin is a flavonoid polyphenolic compound exerting broad pharmacological and medicinal properties. Diabetes-related obesity increases the total blood volume and cardiac output and may increase the myocardial hypertrophy progression. However, the mechanism of luteolin in diabetic myocardial hypertrophy remains uncertain. Therefore, this study aimed to evaluate whether luteolin improved diabetic cardiomyopathy (DCM) by inhibiting the proteasome activity. METHODS: Cardiomyopathy was induced in streptozotocin-treated diabetes mellitus (DM) and db/db mice. Luteolin (20 mg kg-1·day-1) was administrated via gavage for 12 weeks. In vitro, high glucose and high insulin (HGI, glucose at 25.5 mM and insulin at 0.1 µM) inducing primary neonatal rat cardiomyocytes (NRCMs) were treated with or without luteolin for 48 h. Echocardiography, reverse transcription quantitative polymerase chain reaction, histology, immunofluorescence, and Western blotting were conducted. Proteasome activities were also detected using a fluorescent peptide substrate. RESULTS: Luteolin administration significantly prevented the onset of cardiac hypertrophy, fibrosis, and dysfunction in type 1 DM (T1DM) and type 2 DM (T2DM). Compared with DCM mice, luteolin groups showed lower serum triglyceride and total cholesterol levels. Furthermore, luteolin attenuated HGI-induced myocardial hypertrophy and reduced atrial natriuretic factor mRNA level in NRCMs. Proteasome activities were inhibited by luteolin in vitro. Luteolin also reduces the proteasome subunit levels (PSMB) 1, PSMB2, and PSMB5 of the 20S proteasome, as well as proteasome-regulated particles (Rpt) 1 and Rpt4 levels of 19S proteasome. Furthermore, luteolin treatment increased protein kinase B (AKT) and GSK-3α/ß (inactivation of GSK-3) phosphorylation. The phosphorylation level of AMPK activity was also reversed after the treatment with luteolin in comparison with the HGI-treated group. CONCLUSION: This study indicates that luteolin protected against DCM in mice, including T1DM and T2DM, by upregulating phosphorylated protein AMPK and AKT/GSK-3 pathways while decreasing the proteasome activity. These findings suggest that luteolin may be a potential therapeutic agent for DCM.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Insulinas , Ratas , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3/efectos adversos , Glucógeno Sintasa Quinasa 3/metabolismo , Luteolina/farmacología , Luteolina/uso terapéutico , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/uso terapéutico , Transducción de Señal , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucosa , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/prevención & control , Insulinas/efectos adversosRESUMEN
The genetically modified (GM) maize GG2 contains gr79-epsps and gat genes, conferring glyphosate tolerance. The present study aimed to investigate potential effects of maize GG2 in a 90-day subchronic feeding study on Wistar Han RCC rats. Maize grains from GG2 or non-GM maize were incorporated into diets at concentrations of 25% and 50% and administered to Wistar Han RCC rats (n = 10/sex/group) for 90 days. The basal-diet group of rats (n = 10/sex/group) were fed with common commercialized rodent diet. Compared with rats fed with the corresponding non-GM maize and the basal-diet, no biologically relevant diï¬erences were observed in rats fed with the maize GG2, according to the results of body weight/gain, feed consumption/utilization, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, serum chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, these results indicated that maize GG2 is as safe as the non-GM maize in this 90-day feeding study.
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Carcinoma de Células Renales , Alimentos Modificados Genéticamente , Neoplasias Renales , Ratas , Animales , Ratas Wistar , Ratas Sprague-Dawley , Plantas Modificadas Genéticamente/genética , Zea mays/genética , Alimentación Animal/análisis , GlifosatoRESUMEN
Regenerative medicine aims to restore normal tissue architecture and function. However, the basis of tissue regeneration in mammalian solid organs remains undefined. Remarkably, mice lacking p21 fully regenerate injured ears without discernable scarring. Here we show that, in wild-type mice following tissue injury, stromal-derived factor-1 (Sdf1) is up-regulated in the wound epidermis and recruits Cxcr4-expressing leukocytes to the injury site. In p21-deficient mice, Sdf1 up-regulation and the subsequent recruitment of Cxcr4-expressing leukocytes are significantly diminished, thereby permitting scarless appendage regeneration. Lineage tracing demonstrates that this regeneration derives from fate-restricted progenitor cells. Pharmacological or genetic disruption of Sdf1-Cxcr4 signaling enhances tissue repair, including full reconstitution of tissue architecture and all cell types. Our findings identify signaling and cellular mechanisms underlying appendage regeneration in mice and suggest new therapeutic approaches for regenerative medicine.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Extremidades/fisiología , Compuestos Heterocíclicos/farmacología , Receptores CXCR4/antagonistas & inhibidores , Regeneración/efectos de los fármacos , Regeneración/fisiología , Cicatrización de Heridas/fisiología , Animales , Bencilaminas , Linaje de la Célula/genética , Quimiocina CXCL12/metabolismo , Ciclamas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Oído/lesiones , Oído/fisiología , Células Epidérmicas , Epidermis/lesiones , Epidermis/fisiología , Extremidades/lesiones , Queratinocitos/citología , Queratinocitos/metabolismo , Leucocitos/metabolismo , Ratones , Transporte de Proteínas/efectos de los fármacos , Receptores CXCR4/metabolismo , Regeneración/genética , Transducción de Señal/efectos de los fármacos , Cicatrización de Heridas/genéticaRESUMEN
There appears a steep increase in the prevalence of food allergy worldwide in the past few decades. It is believed that, rather than genetic factors, the recently altered dietary and environmental factors are the driving forces behind the rapid increase of this disease. Accumulating evidence has implied that external exposures that occurred in prenatal and postnatal periods could affect the development of oral tolerance in later life. Understanding the potential risk factors for food allergy would greatly benefit the progress of intervention and therapy. In this review, we present updated knowledge on the dietary and environmental risk factors in early life that have been shown to impact the development of food allergy. These predominantly include dietary habits, microbial exposures, allergen exposure routes, environmental pollutants, and so on. The key evidence, conflicts, and potential research topics of each theory are discussed, and associated interventional strategies to prevent the disease development and ameliorate treatment burden are included. Accumulating evidence has supported the causative role of certain dietary and environmental factors in the establishment of oral tolerance in early life, especially the time of introducing allergenic foods, skin barrier function, and microbial exposures. In addition to certain immunomodulatory factors, increasing interest is raised toward modern dietary patterns, where adequately powered studies are required to identify contributions of those modifiable risk factors. This review broadens our understanding of the connections between diet, environment, and early-life immunity, thus benefiting the progress of intervention and therapy of food allergy.
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Contaminantes Ambientales , Hipersensibilidad a los Alimentos , Femenino , Embarazo , Humanos , Hipersensibilidad a los Alimentos/prevención & control , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Dieta , Factores de Riesgo , Conducta AlimentariaRESUMEN
Afterglow imaging holds great potential for ultrasensitive biomedical imaging. As it detects photons after the cessation of real-time light excitation, autofluorescence can therefore be effectively eliminated. However, afterglow imaging is still in its infant stage due to the lack of afterglow agents with satisfactory lifetime, biocompatibility, and high luminescence brightness, particularly afterglow in the near-infrared region for in vivo applications. To address these issues, this study for the first time reports chlorin nanoparticles (Ch-NPs) emitting afterglow luminescence peaking at 680 nm with a half-life of up to 1.5 h, which is almost 1 order of magnitude longer than those of other reported organic afterglow probes. In-depth experimental and theoretical studies revealed that the brightness of the afterglow luminescence is strongly correlated with the singlet oxygen (1O2) capacity and the oxidizability of the chlorins. Benefitting from the ultralong half-life and the minimized imaging background, small metastatic tumor foci of 3 mm3 were successfully resected under the guidance of the afterglow luminescence generated upon a single shot of activation prior to the injection, which was impossible for conventional near-infrared fluorescence imaging due to tissue autofluorescence.
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Nanopartículas , Porfirinas , Humanos , Luminiscencia , Imagen ÓpticaRESUMEN
BACKGROUND & AIMS: Elucidating key factors affecting personal responses to food is the first step toward implementing personalized nutrition strategies in for example weight loss programs. Here, we aimed to identify factors of importance for individual weight loss trajectories in a natural setting where participants were provided dietary advice but otherwise asked to self-manage the daily caloric intake and data reporting. METHODS: A 6-month weight-reduction program with longitudinal collection of dietary, physical activity, body weight, and fecal microbiome data as well as single-nucleotide polymorphism genotypes in 83 participants was conducted, followed by integration of the high-dimensional data to define the most determining factors for weight loss in a dietician-guided, smartphone-assisted dieting program. RESULTS: The baseline gut microbiota was found to outperform other factors as a predieting predictor of individual weight loss trajectories. Weight loss was also linked to the magnitude of changes in abundances of certain bacterial species during dieting. Ruminococcus gnavus (MGS0160) was significantly enriched in obese individuals and decreased during weight loss. Akkermansia muciniphila (MGS0120) and Alistipes obesi (MGS0342) were significantly enriched in lean individuals, and their abundance increased during dieting. Finally, Blautia wexlerae (MGS0575) and Bacteroides dorei (MGS0187) were the strongest predictors for weight loss when present in high abundance at baseline. CONCLUSION: Altogether, the baseline gut microbiota was found to excel as a central personal factor in capturing the relationship between dietary factors and weight loss among individuals on a dieting program.
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Trayectoria del Peso Corporal , Dieta Reductora , Microbioma Gastrointestinal , Obesidad/microbiología , Delgadez/microbiología , Pérdida de Peso , Adulto , Akkermansia/aislamiento & purificación , Bacteroides/aislamiento & purificación , Bacteroidetes/aislamiento & purificación , Clostridiales/aislamiento & purificación , Ejercicio Físico , Heces/microbiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Aplicaciones Móviles , Obesidad/tratamiento farmacológico , Obesidad/genética , Polimorfismo de Nucleótido Simple , Programas de Reducción de Peso , Adulto JovenRESUMEN
Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere-derived MCF-7 cells and HMLE-Twist-ER cells, we found that the cells with stem cell-like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl-CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids, and augmented synthesis and utilization of the omega-6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (siRNA) knockdown strikingly limited self-renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self-renewal and growth. Dietary supplementation of nude mice bearing BCSC-derived tumors with omega-3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self-renewal and growth of BCSC, and that omega-3 fatty acids are effective in targeting this pathway to exert their anticancer effect.
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Neoplasias de la Mama , Ácidos Grasos Omega-3 , Animales , Neoplasias de la Mama/patología , Ácidos Grasos/metabolismo , Ácidos Grasos Monoinsaturados/metabolismo , Ácidos Grasos Omega-3/farmacología , Femenino , Humanos , Lipogénesis , Ratones , Ratones Desnudos , Células Madre Neoplásicas/metabolismo , ARN Interferente Pequeño/metabolismo , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismoRESUMEN
Astroviruses (AstVs) are among the most important viruses causing diarrhea in human infants and many animals, posing a threat to public health safety and a burden on the economy. Five porcine AstV (PAstV) genotypes have been identified in various countries, including China. However, the epidemiology of PAstV in Yunnan province, China, remains unknown. In this study, 489 fecal samples from pigs in all 16 prefectures/cities of Yunnan were collected between April and August of 2020 for epidemiological investigation. The total infection rate of PAstV-2 or PAstV-5 was 39.9%, with suckling piglets having the highest infection rate (62.3%). The ORF2 genes of seven PAstV-2 and 10 PAstV-5 isolates were sequenced and phylogenetically analyzed. In addition to coinfections with PAstV-2 and PAstV-5, coinfections of PAstV with other diarrhea-inducing viruses (e.g., porcine bocavirus) were also discovered. A comparison of ORF2-encoded capsid protein sequences revealed that there were multiple insertions and deletions in the seven Yunnan PAstV-2 sequences, while point mutations, but no deletions or insertions, were found in the 10 Yunnan PAstV-5 sequences, which were very similar to the reference sequences. This is the first epidemiological investigation and genetic characterization of PAstV-2 and PAstV-5 in Yunnan province, China, demonstrating the current PAstV infection situation in Yunnan.
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Infecciones por Astroviridae , Enfermedades de los Porcinos , Animales , Infecciones por Astroviridae/epidemiología , Infecciones por Astroviridae/veterinaria , China/epidemiología , Genotipo , Mamastrovirus , Filogenia , Porcinos , Enfermedades de los Porcinos/epidemiologíaRESUMEN
BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.
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Insuficiencia Cardíaca , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Pronóstico , Factores de RiesgoRESUMEN
The characterization of laser-induced breakdown spectroscopy (LIBS) near the gas-liquid two-phase interface was investigated with the laser acting on the sample along the horizontal direction. Simulation of the laser beam focusing process and observation of laser beam spot images show that difference in focusing positions in the air and the solution results from refraction of the laser beam entering the solution from the air and the change of propagation direction on the container lateral. The peak power and mean irradiance of the focused laser beam spot increase with the distance away from the interface, which is attributed to the fact that the loss of laser energy due to the refraction and reflection of light at the interface decreases with the focusing position moving away from the interface. This variation trend of laser irradiance allows for the growth of the spectral line intensity and lifetime with increasing the distance from the interface. The plasma electron density and temperature decrease with the delay time but increase with the distance away from the interface at the same delay time. Our findings help us to gain more insight into the characteristics and evolution mechanisms of LIBS produced near the gas-liquid two-phase interface, which provides theoretical guidance for the correction of LIBS spectra especially in water pollution monitoring.
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BACKGROUND AND OBJECTIVES: Adverse environmental factors in tunnels increase the occurrence of respiratory and intestinal inflammatory disease, which is seriously harmful to worker health. It is reported that medium-chain triglycerides (MCT) can improve immune status and alter the gut microflora. This study investigates MCT effects on immune status and gut microbiota among tunnel workers. METHODS AND STUDY DESIGN: Forty-five workers were randomly divided into an MCT group (n=30) and control group (n=15), where they ingested MCT-milk or a placebo milk for 12 weeks, respectively. The primary outcome measure was the incidence of respiratory infection and diarrhea. Secondary outcomes were changes in serum immune-related markers and changes in gut microbiota. RESULTS: The incidence of diarrhea in MCT group was significantly decreased after 4 weeks (p<0.01), with no significant differences in the control group. MCT reduced the level of pro-inflammatory cytokines (TNF-α, CRP, and IL-6) and enhanced the anti-inflammatory cytokines (IL-10, C3, C4, IgA, IgG, and IgM), respectively (p<0.01). The Chao index was reduced (p<0.01) and microbiota composition changed significantly after 12 weeks of MCT intervention. MCT reduced the abundance of Bacteroides, Roseburia, Ruminococcus_1, Lachnospira and increased that of Blautia and Fusicatenibacter at the genus level (p<0.01). CONCLUSIONS: The consumption of MCT reduces diarrhea occurrence and improves serum immune profiles together with gut microbiomics in tunnel workers.
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Diarrea , Microbioma Gastrointestinal , Enfermedades Intestinales , Triglicéridos , Anticuerpos/sangre , China , Citocinas/sangre , Diarrea/terapia , Humanos , Inflamación/terapia , Enfermedades Intestinales/terapia , Enfermedades Profesionales/terapia , Triglicéridos/administración & dosificaciónRESUMEN
Antiepileptic drug zonisamide has been shown to be curative for Parkinson's disease (PD) through increasing HMG-CoA reductase degradation protein 1 (Hrd1) level and mitigating endoplasmic reticulum (ER) stress. Hrd1 is an ER-transmembrane E3 ubiquitin ligase, which is involved in cardiac dysfunction and cardiac hypertrophy in a mouse model of pressure overload. In this study, we investigated whether zonisamide alleviated cardiac hypertrophy in rats by increasing Hrd1 expression and inhibiting ER stress. The beneficial effects of zonisamide were assessed in two experimental models of cardiac hypertrophy: in rats subjected to abdominal aorta constriction (AAC) and treated with zonisamide (14, 28, 56 mg · kg-1 · d-1, i.g.) for 6 weeks as well as in neonatal rat cardiomyocytes (NRCMs) co-treated with Ang II (10 µM) and zonisamide (0.3 µM). Echocardiography analysis revealed that zonsiamide treatment significantly improved cardiac function in AAC rats. We found that zonsiamide treatment significantly attenuated cardiac hypertrophy and fibrosis, and suppressed apoptosis and ER stress in the hearts of AAC rats and in Ang II-treated NRCMs. Importantly, zonisamide markedly increased the expression of Hrd1 in the hearts of AAC rats and in Ang II-treated NRCMs. Furthermore, we demonstrated that zonisamide accelerated ER-associated protein degradation (ERAD) in Ang II-treated NRCMs; knockdown of Hrd1 abrogated the inhibitory effects of zonisamide on ER stress and cardiac hypertrophy. Taken together, our results demonstrate that zonisamide is effective in preserving heart structure and function in the experimental models of pathological cardiac hypertrophy. Zonisamide increases Hrd1 expression, thus preventing cardiac hypertrophy and improving the cardiac function of AAC rats.
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Cardiomegalia/tratamiento farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Zonisamida/uso terapéutico , Animales , Aorta Abdominal/cirugía , Apoptosis/efectos de los fármacos , Degradación Asociada con el Retículo Endoplásmico/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Masculino , Miocitos Cardíacos/efectos de los fármacos , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Endoplasmic reticulum stress (ER stress) plays a key role in the development of cardiac hypertrophy and diabetic cardiomyopathy (DCM). Zonisamide (ZNS) was originally developed as an antiepileptic drug. Studies have shown that ZNS suppresses ER stress-induced neuronal cell damage in the experimental models of Parkinson's disease. Herein, we investigated whether ZNS improved DCM by attenuating ER stress-induced apoptosis. C57BL/6J mice were fed with high-fat diet (HFD) and intraperitoneally injected with low-dose streptozotocin (STZ) to induce type 2 diabetes mellitus (T2DM), and then treated with ZNS (40 mg·kg-1·d-1, i.g.) for 16 weeks. We showed that ZNS administration slightly ameliorated the blood glucose levels, but significantly alleviated diabetes-induced cardiac dysfunction and hypertrophy. Furthermore, ZNS administration significantly inhibited the Bax and caspase-3 activity, upregulated Bcl-2 activity, and decreased the proportion of TUNEL-positive cells in heart tissues. We analyzed the hallmarks of ER stress in heart tissues, and revealed that ZNS administration significantly decreased the protein levels of GRP78, XBP-1s, ATF6, PERK, ATF4, and CHOP, and elevated Hrd1 protein. In high glucose (HG)-treated primary cardiomyocytes, application of ZNS (3 µM) significantly alleviated HG-induced cardiomyocyte hypertrophy and apoptosis. ZNS application also suppressed activated ER stress in HG-treated cardiomyocytes. Moreover, preapplication of the specific ER stress inducer tunicamycin (10 ng/mL) eliminated the protective effects of ZNS against HG-induced cardiac hypertrophy and ER stress-mediated apoptosis. Our findings suggest that ZNS improves the cardiac diastolic function in diabetic mice and prevents T2DM-induced cardiac hypertrophy by attenuating ER stress-mediated apoptosis.