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Carcinoma Hepatocelular , Transición Epitelial-Mesenquimal , Factor I del Crecimiento Similar a la Insulina , Neoplasias Hepáticas , Factor de Transcripción STAT5 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Factor de Transcripción STAT5/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Transducción de Señal , AnimalesRESUMEN
The brain microenvironment is tightly regulated, and the blood-brain barrier (BBB) plays a pivotal role in maintaining the homeostasis of the central nervous system. It effectively safeguards brain tissue from harmful substances in peripheral blood. However, both acute pathological factors and age-related biodegradation have the potential to compromise the integrity of the BBB and are associated with chronic neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as Epilepsy (EP). This association arises due to infiltration of peripheral foreign bodies including microorganisms, immune-inflammatory mediators, and plasma proteins into the central nervous system when the BBB is compromised. Nevertheless, these partial and generalized understandings do not prompt a shift from passive to active treatment approaches. Therefore, it is imperative to acquire a comprehensive and in-depth understanding of the intricate molecular mechanisms underlying vascular disease alterations associated with the onset and progression of chronic neurodegenerative disorders, as well as the subsequent homeostatic changes triggered by BBB impairment. The present article aims to systematically summarize and review recent scientific work with a specific focus on elucidating the fundamental mechanisms underlying BBB damage in AD, PD, and EP as well as their consequential impact on disease progression. These findings not only offer guidance for optimizing the physiological function of the BBB, but also provide valuable insights for developing intervention strategies aimed at early restoration of BBB structural integrity, thereby laying a solid foundation for designing drug delivery strategies centered around the BBB.
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Fermentation of pulses as a clean processing technique has been reported to have a favorable impact on the functional and nutritional quality of the starting materials. Compared to commonly fermented pulses such as peas and chickpeas, limited information is available on the effect of fermentation on lentils, especially when using a high protein isolate (>80% protein) as compared to seeds or flours. Therefore, in the present work, lentil protein isolate was used as a feedstock for submerged fermentation with Aspergillus niger, Aspergillus oryzae, or Lactobacillus plantarum. After 48 h, the samples showed increased protein content with enhanced solubility and oil-holding capacity. Controlled fermentation, as opposed to spontaneous fermentation, maintained the high foaming capacity; however, all fermented samples had lower foam and emulsion stabilizing properties and reduced water-holding capacity compared to the control. The fermented proteins were also less digestible, possibly due to an increase in phenolics and saponins. New volatile compounds were identified in fermented samples that show promise for improved sensory attributes. Significant differences were observed in specific quality attributes depending on the microbial strain used. Further research is required to better understand the fermentative metabolism of microbial communities when provided high-protein lentil ingredients as growth substrates. PRACTICAL APPLICATION: Fermented lentil protein isolate has promising flavor profiles that may improve its sensory properties for food application.
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Aspergillus niger , Fermentación , Lactobacillus plantarum , Lens (Planta) , Valor Nutritivo , Compuestos Orgánicos Volátiles , Lens (Planta)/microbiología , Lens (Planta)/química , Lactobacillus plantarum/metabolismo , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo , Aspergillus niger/metabolismo , Proteínas de Plantas/metabolismo , Aspergillus oryzae/metabolismo , Semillas/química , Semillas/microbiología , Gusto , Manipulación de Alimentos/métodosRESUMEN
Grain size is a quantitative trait with a complex genetic mechanism, characterized by the combination of grain length (GL), grain width (GW), length to width ration (LWR), and grain thickness (GT). In this study, we conducted quantitative trait loci (QTL) analysis to investigate the genetic basis of grain size using BC1F2 and BC1F2:3 populations derived from two indica lines, Guangzhan 63-4S (GZ63-4S) and TGMS29 (core germplasm number W240). A total of twenty-four QTLs for grain size were identified, among which, three QTLs (qGW1, qGW7, and qGW12) controlling GL and two QTLs (qGW5 and qGL9) controlling GW were validated and subsequently fine mapped to regions ranging from 128 kb to 624 kb. Scanning electron microscopic (SEM) analysis and expression analysis revealed that qGW7 influences cell expansion, while qGL9 affects cell division. Conversely, qGW1, qGW5, and qGW12 promoted both cell division and expansion. Furthermore, negative correlations were observed between grain yield and quality for both qGW7 and qGW12. Nevertheless, qGW5 exhibited the potential to enhance quality without compromising yield. Importantly, we identified two promising QTLs, qGW1 and qGL9, which simultaneously improved both grain yield and quality. In summary, our results laid the foundation for cloning these five QTLs and provided valuable resources for breeding rice varieties with high yield and superior quality.
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Mapeo Cromosómico , Grano Comestible , Oryza , Sitios de Carácter Cuantitativo , Oryza/genética , Oryza/crecimiento & desarrollo , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Fenotipo , Cromosomas de las Plantas/genética , Semillas/genética , Semillas/crecimiento & desarrolloRESUMEN
The quality of rice, evaluated using multiple quality-related traits, is the main determinant of its market competitiveness. In this study, two japonica rice varieties with significant differences in quality-related traits were used as parents to construct two populations, BC3F2 and BC3F2:3, with Kongyu131 (KY131) as the recurrent parent. A genetic linkage map was constructed using the BC3F2 population based on 151 pairs of SSR/InDel polymorphic markers selected between the parents. Grain-shape-related traits (grain length GL, grain width GW, and length-to-width ratio LWR), chalkiness-related traits (white-core rate WCR, white-belly rate WBR, white-back rate BR, and chalkiness rate CR), and amylose content (AC) were investigated in the two populations in 2017 and 2018. Except for BR and CR, the traits showed similar characteristics with a normal distribution in both populations. Genetic linkage analysis was conducted for these quality-related traits, and a total of 37 QTLs were detected in the two populations. Further validation was performed on the newly identified QTLs with larger effects, and three grain shape QTLs and four chalkiness QTLs were successfully validated in different environments. One repeatedly validated QTL, qWCR3, was selected for fine mapping and was successfully narrowed down to a 100 kb region in which only two genes, LOC_0s03g45210 and LOC_0s03g45320, exhibited sequence variations between the parents. Furthermore, the variation of LOC_Os03g45210 leads to a frameshift mutation and premature protein termination. The results of this study provide a theoretical basis for positional cloning of the qWCR3 gene, thus offering new genetic resources for rice quality improvement.
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Mapeo Cromosómico , Ligamiento Genético , Oryza , Fenotipo , Sitios de Carácter Cuantitativo , Oryza/genética , Mapeo Cromosómico/métodos , Grano Comestible/genética , Cromosomas de las Plantas/genética , Genes de PlantasRESUMEN
The widespread occurrence of organic antibiotic pollution in the environment and the associated harmful effects necessitate effective treatment method. Heterogeneous electro-Fenton (hetero-EF) has been regarded as one of the most promising techniques towards organic pollutant removal. However, the preparation of efficient cathode still remains challenging. Herein, a novel metal-organic framework (MOF)-derived Fe/Ni@C marigold-like nanosheets were fabricated successfully for the degradation of oxytetracycline (OTC) by serving as the hetero-EF cathode. The FeNi3@C (Fe/Ni molar ratio of 1:3) based hetero-EF system exhibited 8.2 times faster OTC removal rate than that of anodic oxidation and possessed many advantages such as excellent OTC degradation efficiency (95.4% within 90 min), broad environmental adaptability (satisfactory treatment performance for multiple antibiotics under various actual water matrixes), good stability and reusability, and significant toxicity reduction. The superior hetero-EF catalytic performance was mainly attributed to: 1) porous carbon and Ni existence were both conducive to the in-situ generation of H2O2 from dissolved O2; 2) the synergistic effects of bimetals together with electron transfer from the cathode promoted the regeneration of ≡ FeII/NiII, thereby accelerating the production of reactive oxygen species; 3) the unique nanosheet structure derived from the precursor two-dimensional Fe-Ni MOFs enhanced the accessibility of active sites. This work presented a promising hetero-EF cathode for the electrocatalytic treatment of antibiotic-containing wastewaters.
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Estructuras Metalorgánicas , Oxitetraciclina , Contaminantes Químicos del Agua , Antibacterianos , Peróxido de Hidrógeno/química , Oxidación-Reducción , Electrodos , Contaminantes Químicos del Agua/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Serotonina/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Hipocampo , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Modelos Animales de Enfermedad , Conducta AnimalRESUMEN
Bioretention has been considered as an effective management practice for urban stormwater in the removal of pollutants including polycyclic aromatic hydrocarbons (PAHs). However, the accumulation of high-molecular-weight (HMW) PAHs in bioretention systems and their potential impact on the pollutants removal performance and microbial ecology are still not fully understood. In this study, comparisons of treatment effectiveness, enzyme activity and microbial community in bioretention systems with different types of media amendments were carried out at different spiking levels of pyrene (PYR). The results showed that the removal efficiencies of chemical oxygen demand (COD) and total nitrogen in the bioretention systems were negatively impacted by the PYR levels. The relative activities of soil dehydrogenase and urease were increasingly inhibited by the elevated PYR level, indicating the declining microbial activity regarding organic matter decomposition. The spiking of PYR negatively affected microbial diversity, and distinct time- and influent-dependent changes in microbial communities were observed. The relative abundance of PAH-degrading microorganisms increased in PYR-spiked systems, while the abundance of nitrifiers decreased. The addition of media amendments was beneficial for the enrichment of microorganisms that are more resistant to PYR-related stress, therefore elevating the COD concentration removal rate by â¼50%. This study gives new insight into the multifaceted impacts of HMW PAH accumulation on microbial fingerprinting and enzyme activities, which may provide guidance on better stormwater management practices via bioretention in terms of improved system longevity and performance.
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Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Análisis de la Demanda Biológica de Oxígeno , Nitrógeno/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , SueloRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) are key organic pollutants in the environment that pose threats to the ecosystem and human health. The degradation of high molecular weight (HMW) PAHs by enriched bacterial consortia has been previously studied, while the involved metabolisms and microbial communities are still unclear and warrant further investigations. In this study, five bacterial consortia capable of utilizing different PAHs (naphthalene, anthracene, and pyrene) as the sole carbon and energy sources were enriched from PAH-contaminated soil samples. Among the five consortia, consortium TC exhibited the highest pyrene degradation efficiency (91%) after 19 d of incubation. The degradation efficiency was further enhanced up to 99% by supplementing yeast extract. Besides, consortium TC showed tolerances to high concentrations of pyrene (up to 1000â mg/L) and different heavy metal stresses (including Zn2+, Cd2+, and Pb2+). The dominant genus in consortium TC, GS, and PL showing relatively higher degradation efficiency for anthracene and pyrene was Pseudomonas, whereas consortium PG and GD were predominated by genus Achromobacter and class Enterobacteriaceae, respectively. Consortium TC, as a highly efficient HMW PAH-degrading consortium, could be applied for synergistic biodegradation of HMW PAHs and in situ bioremediation of the sites contaminated with both PAHs and heavy metals.
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Metales Pesados , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Humanos , Biodegradación Ambiental , Hidrocarburos Policíclicos Aromáticos/metabolismo , Ecosistema , Peso Molecular , Contaminantes del Suelo/metabolismo , Bacterias/metabolismo , Pirenos , Metales Pesados/metabolismo , Antracenos/metabolismo , Microbiología del SueloRESUMEN
BACKGROUND Diabetes is related to higher risk of multiple cancers. This study aimed to explore the effect and mechanism of diabetes on liver metastasis of CRC. MATERIAL AND METHODS Overall and liver metastasis-free survival in diabetic and non-diabetic CRC patients were compared by Kaplan-Meier analysis. Expression of alphavß6 was detected by immunohistochemistry in clinical specimens. Effects of hyperglycemia on alphavß6 expression in colon cancer cells were assessed by western blot, real-time PCR, and flowcytometry. Effects of hyperglycemia on migration and invasion were demonstrated by Transwell assay. Expression and activity of MMP-9 and MMP-2 were determined by real-time PCR and gelatin zymography. Liver metastatic nodules were counted and b6 expression was detected by western blot in a liver metastasis mouse model. RESULTS CRC patients with diabetes had poorer overall and liver metastasis-free survival, and diabetes was associated with higher alphavß6 expression in CRC specimens. Hyperglycemia promoted the invasion and migration of colon cancer cells, and upregulated the expression and activity of MMP-9, which were attenuated by inhibition of alphavß6. Hyperglycemia upregulated the expression of ß6 and cell surface expression of avb6, which was reduced by ERK inhibitor. The in vitro results were confirmed in vivo in the mouse model. CONCLUSIONS Our study demonstrated the enhancing effect of hyperglycemia on liver metastasis of CRC, and showed that alphavß6 was involved in this process, suggesting that control of glucose levels and inhibition of alphavß6 can reduce the risk of liver metastasis in diabetic CRC patients.
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Antígenos de Neoplasias/metabolismo , Neoplasias Colorrectales/sangre , Hiperglucemia/metabolismo , Integrinas/metabolismo , Adulto , Animales , Antígenos de Neoplasias/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Femenino , Expresión Génica , Humanos , Hiperglucemia/patología , Integrinas/genética , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Metástasis de la Neoplasia , ARN Largo no Codificante , Regulación hacia ArribaRESUMEN
Rationale: Liver fibrosis is frequently associated with gut barrier dysfunction, and the lipopolysaccharides (LPS) -TLR4 pathway is common to the development of both. Intestinal alkaline phosphatase (IAP) has the ability to detoxify LPS, as well as maintain intestinal tight junction proteins and gut barrier integrity. Therefore, we hypothesized that IAP may function as a novel therapy to prevent liver fibrosis. Methods: Stool IAP activity from cirrhotic patients were determined. Common bile duct ligation (CBDL) and Carbon Tetrachloride-4 (CCl4)-induced liver fibrosis models were used in WT, IAP knockout (KO), and TLR4 KO mice supplemented with or without exogenous IAP in their drinking water. The gut barrier function and liver fibrosis markers were tested. Results: Human stool IAP activity was decreased in the setting of liver cirrhosis. In mice, IAP activity and genes expression decreased after CBDL and CCl4 exposure. Intestinal tight junction related genes and gut barrier function were impaired in both models of liver fibrosis. Oral IAP supplementation attenuated the decrease in small intestine tight junction protein gene expression and gut barrier function. Liver fibrosis markers were significantly higher in IAP KO compared to WT mice in both models, while oral IAP rescued liver fibrosis in both WT and IAP KO mice. In contrast, IAP supplementation did not attenuate fibrosis in TLR4 KO mice in either model. Conclusions: Endogenous IAP is decreased during liver fibrosis, perhaps contributing to the gut barrier dysfunction and worsening fibrosis. Oral IAP protects the gut barrier and further prevents the development of liver fibrosis via a TLR4-mediated mechanism.
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Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Cirrosis Hepática/genética , Receptor Toll-Like 4/genética , Adulto , Animales , Tetracloruro de Carbono/toxicidad , Conducto Colédoco/cirugía , Modelos Animales de Enfermedad , Heces/química , Femenino , Proteínas Ligadas a GPI/metabolismo , Humanos , Íleon/metabolismo , Intestinos , Ligadura , Lipopolisacáridos , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Permeabilidad , Proteínas de Uniones Estrechas/genéticaRESUMEN
NEW FINDINGS: What is the central question of this study? MiR-92b-3p was found to be reduced in a rat model of middle cerebral artery occlusion: what are the functions of miR-92b-3p in oxygen and glucose deprivation-reperfusion (OGD/R)? What is the main finding and its importance? MiR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammation caused by OGD/R via targeting TRAF3, suggesting that miR-92b-3p may serve as a potential therapeutic target in ischaemic stroke treatment. ABSTRACT: Stroke is the most common cause of human neurological disability. MiR-92b-3p has been shown to be decreased in a rat model of middle cerebral artery occlusion, but its effects in cerebral ischaemic insult are unknown. In this study, PC12 cells were exposed to oxygen and glucose deprivation-reperfusion (OGD/R) to establish cerebral ischaemic injury in vitro. Quantitative real time-PCR analysis demonstrated that OGD/R exposure led to down-regulation of miR-92b-3p and increased mRNA and protein levels of tumour necrosis factor receptor-associated factor 3 (TRAF3). Gain of miR-92b-3p expression facilitated cell survival; attenuated lactate dehydrogenase leakage, cell apoptosis, caspase 3 activity and cleaved-caspase 3 (c-caspase 3) expression; and decreased the Bax/Bcl-2 ratio. Furthermore, miR-92b-3p repressed mitochondrial membrane potential depolarization, reactive oxygen species production, cytochrome c protein expression, inflammatory cytokine production and the reduction of ATP content. MiR-92b-3p directly targeted the 3'-untranslated region of TRAF3 and decreased TRAF3 expression. Reinforced expression of TRAF3 partly abrogated the biological activity of miR-92b-3p during OGD/R. Hence, miR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammatory responses induced by OGD/R by targeting TRAF3.
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Apoptosis/fisiología , Glucosa/metabolismo , Inflamación/metabolismo , MicroARNs/metabolismo , Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Factor 3 Asociado a Receptor de TNF/metabolismo , Regiones no Traducidas 3'/fisiología , Animales , Isquemia Encefálica/metabolismo , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/fisiología , Regulación hacia Abajo/fisiología , Neuroprotección/fisiología , Células PC12 , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Reperfusión/métodos , Accidente Cerebrovascular/metabolismo , Regulación hacia Arriba/fisiologíaRESUMEN
BACKGROUND: Metabolic reprogramming, in which energetic metabolism changes from oxidative phosphorylation to glycolysis, is well-accepted as a hallmark of cancers including hepatocellular carcinoma (HCC). A growing body of evidence suggests the involvement of oncogenes and tumor suppressor genes in the control of metabolic reprogramming. In this study, we attempt to investigate whether loss of PTEN, a recognized tumor suppressor, drives metabolic reprogramming of HCC. METHODS: Cancerous liver tissues were surgically resected from 128 HCC patients, with 43 adjacent noncancerous liver tissues as control. Aerobic glycolysis (Warburg effect) was reflected by measurements of glucose uptake and lactate production, mitochondrial membrane potential collapse was observed by JC-1 staining, glycolytic rate and mitochondrial respiration were evaluated by determining glycolytic proton efflux rate (glycoPER) and oxygen consumption rate (OCR) in cultured human HHCC cells. RESULTS: Reciprocal expression of PTEN and PI3K was determined in cancer liver tissues. Overexpression of PTEN suppressed the Warburg effect, as evidenced by reductions in glucose uptake and lactate production, maintenance of mitochondrial function, and transformation of energetic metabolism from glycolysis to oxidative phosphorylation in cultured PTEN-negative HHCC cells. Importantly, 740 Y-P, a PI3K agonist that leads to activation of the PI3K pathway, partially abrogated the function of PTEN and reprogramed glucose metabolism in cultured HHCC cells. CONCLUSIONS: The discovery that loss of PTEN allows the tumor metabolic program has been a major advance in understanding the carcinogenesis of HCC. Video abstract Graphic abstract showing that loss of PTEN regulates the tumor metabolic program in hepatocellular carcinoma. Loss of PTEN leads to activation of the PI3K pathway enhances the Warburg effect, thereby promoting the development of hepatocellular carcinoma.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Ácidos/metabolismo , Animales , Apoptosis , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Respiración de la Célula , Regulación hacia Abajo , Espacio Extracelular/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones Desnudos , Persona de Mediana Edad , Mitocondrias/metabolismo , Invasividad Neoplásica , Fenotipo , Pronóstico , Modelos de Riesgos Proporcionales , Efecto Warburg en OncologíaRESUMEN
Thermal-based Zero Liquid Discharge (ZLD) process has been used for managing industrial brine. However, conventional thermal ZLD process is very energy intensive. In view of this, pre-concentration techniques have been applied prior to thermal process to reduce energy consumption of ZLD systems. Capacitive Deionization (CDI) is an emerging desalination technique and has yet to be extensively explored for the treatment of industrial brine especially for ZLD applications. High concentration of total dissolved solids (TDS) and high fouling potential of industrial brine are two major challenges in CDI process. This paper reviews the possible factors for optimizing CDI process in industrial brine treatment, namely, cell architectures, strategies in operation and fouling control. Cell architectures of membrane CDI (MCDI) and flow-electrode CDI (CDI) are preferred options for treating industrial brine compared with classic CDI in terms of energy consumption and fouling propensity. There are other operational strategies that could enhance the feasibility of using CDI process for ZLD application. These include reversed voltage desorption, multi-stage operation, brine recirculation and fouling control. Fouling control methods comprise pretreatment, antifouling modification, antiscalant and chemical cleaning. These methods could be integrated to optimize fouling mitigation. In addition to providing insights on feasibility of using CDI to concentrate industrial brines, this review also proposed guidelines for optimizing CDI process applied to treat industrial brines for ZLD applications.
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Purificación del Agua , Electrodos , Sales (Química)RESUMEN
Gut barrier dysfunction and gut-derived chronic inflammation play crucial roles in human aging. The gut brush border enzyme intestinal alkaline phosphatase (IAP) functions to inhibit inflammatory mediators and also appears to be an important positive regulator of gut barrier function and microbial homeostasis. We hypothesized that this enzyme could play a critical role in regulating the aging process. We tested the role of several IAP functions for prevention of age-dependent alterations in intestinal homeostasis by employing different loss-of-function and supplementation approaches. In mice, there is an age-related increase in gut permeability that is accompanied by increases in gut-derived portal venous and systemic inflammation. All these phenotypes were significantly more pronounced in IAP-deficient animals. Oral IAP supplementation significantly decreased age-related gut permeability and gut-derived systemic inflammation, resulted in less frailty, and extended lifespan. Furthermore, IAP supplementation was associated with preserving the homeostasis of gut microbiota during aging. These effects of IAP were also evident in a second model system, Drosophilae melanogaster. IAP appears to preserve intestinal homeostasis in aging by targeting crucial intestinal alterations, including gut barrier dysfunction, dysbiosis, and endotoxemia. Oral IAP supplementation may represent a novel therapy to counteract the chronic inflammatory state leading to frailty and age-related diseases in humans.
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Envejecimiento/fisiología , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/farmacología , Mucosa Intestinal/enzimología , Envejecimiento/efectos de los fármacos , Animales , Drosophila melanogaster , Microbioma Gastrointestinal/efectos de los fármacos , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Mucosa Intestinal/efectos de los fármacos , Ratones , Permeabilidad/efectos de los fármacosRESUMEN
The presence and molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) among meat products in China were investigated. A total of 110 carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 94 Escherichia coli and 10 Klebsiella pneumoniae isolates, were identified from 105 of 794 (13.2%) samples. The positive rates markedly increased from 2016 (9.4%) to 2018 (22.2%). Only blaNDM genes were detected; 79.1% of blaNDM genes were carried by IncX3 plasmids. Routine monitoring of carbapenemase-producing Enterobacteriaceae in the animal food supply is highly recommended.
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Carbapenémicos/uso terapéutico , Escherichia coli/genética , Klebsiella pneumoniae/genética , Carne/microbiología , Plásmidos/genética , beta-Lactamasas/genética , Animales , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , China , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/metabolismo , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
BACKGROUND: This study aims to determine whether palliative bypass surgery (choledochojejunostomy and gastrojejunostomy), which has a lower incidence of complications and mortality, remains an option for elderly patients with resectable periampullary carcinoma. METHODS: The clinical data of elderly patients with resectable periampullary carcinoma who had been admitted to Qilu Hospital and had undergone palliative bypass surgery in recent years was collected. Factors concerning these patients, including surgical duration, intraoperative haemorrhage, the incidence of complications, mortality, and survival rate, were compared to those in patients who had received radical surgery. RESULTS: Surgical duration, intraoperative haemorrhage, the incidence of complications, pancreatic fistula, abdominal infections, pneumonia, and postoperative hospital stay were found to be more apparent in patients in the radical surgery group than in patients in the palliative bypass surgery group and the difference was statistically significant (P<0.05). However, regarding blood transfusions, deaths, biliary fistula, postoperative haemorrhage, wound infection, delayed gastric emptying, and heart disease, the difference was not statistically significant (P≥0.05). CONCLUSIONS: For elderly patients with periampullary carcinoma, palliative bypass surgery offers safety, low risks, a quick recovery, a shorter surgery duration, less intraoperative haemorrhage, and a lower incidence of complications compared to radical surgery. Although it has a lower long-term survival rate compared to radical surgery, palliative surgery remains an option for elderly patients who prefer not to undergo the invasive procedure of radical surgery.
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BACKGROUND: The gut is becoming increasingly recognized as the source of various systemic diseases, and recently, it has been linked to bone metabolism via the so-called gut-bone axis. The microbiome and gut-derived mediators are thought to impact upon bone metabolism, and administration of probiotics has been shown to have beneficial effects in bone. The gut brush border enzyme intestinal alkaline phosphatase (IAP) plays an important role in controlling calcium absorption, inhibiting lipopolysaccharides, and other inflammatory mediators responsible for endotoxemia and appears to preserve the normal gut microbiota. Interestingly, IAP-deficient mice (AKP3-/-) also display a significant decrease in fecal Lactobacillus, the genus shown to be beneficial to bone. MATERIALS AND METHODS: IAP mRNA levels in mouse bone were measured using quantitative real-time polymerase chain reaction. Femurs of IAP-knockout (KO) and wild-type (WT) mice were analyzed by microcomputed tomography and histopathology. Serum levels of alkaline phosphatase, calcium, and phosphorus were measured. Target cell response upon exposure to serum from IAP-KO and WT mice was quantified using primary bone marrow macrophages. RESULTS: IAP was not significantly expressed in bones of WT or KO animals. IAP (alkaline phosphatase 3) expression in bone was vanishingly low compared to the duodenum (bone versus duodenum, 56.9 ± 17.7 versus 25,430.3 ± 10,884.5 relative expression, P = 0.01). Bone histology of younger IAP-KO and WT animals was indistinguishable, whereas older IAP-deficient mice showed a distinctly altered phenotype on histology and computed tomography scan. Younger KO mice did not display any abnormal levels in blood chemistry. Older IAP-KO animals showed an isolated increase in serum alkaline phosphatase levels reflecting an environment of active bone formation (IAP-WT versus IAP-KO, 80 ± 27.4 U/I versus 453 ± 107.5 U/I, P = 0.004). There was no significant difference in serum calcium or phosphorus levels between KO and WT mice. Serum from IAP-KO mice induced a significantly higher inflammatory target cell response. CONCLUSIONS: Through its multiple functions, IAP seems to play a crucial role in connecting the gut to the bone. IAP deficiency leads to chronic changes in bone formation, most likely through dysbiosis and systemic dissemination of proinflammatory mediators.
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Fosfatasa Alcalina/deficiencia , Remodelación Ósea/fisiología , Duodeno/metabolismo , Fémur/patología , Mucosa Intestinal/metabolismo , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/genética , Animales , Células Cultivadas , Disbiosis/metabolismo , Femenino , Fémur/diagnóstico por imagen , Fémur/metabolismo , Microbioma Gastrointestinal/fisiología , Macrófagos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales , Cultivo Primario de Células , ARN Mensajero/aislamiento & purificación , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Organismos Libres de Patógenos Específicos , Microtomografía por Rayos XRESUMEN
A facile energy-saving route is developed for fabricating Sb2Te3-Te nanocomposites and nanosized Te powders. The fabrication route not only avoids using organic chemicals, but also keeps the energy consumption to a minimum. The fabrication procedure involves two steps. Energetic precursors of nanosized powders of Sb and Te are produced at room temperature followed by hot pressing at 400°C under 70 MPa for 1 h. The resulting Sb2Te3-Te nanocomposite exhibits enhanced power factor. The dimensionless figure of merit zT value of the Sb2Te3-Te nanocomposite is 0.29 at 475 K.