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SCOPE: Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system. METHODS AND RESULTS: In a case-control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high-fat and -cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2-arachidoniylglycerol (2-AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2-AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0-ceramide contents, resulting in down-regulation of de novo fatty acid synthesis and up-regulation of fatty acid ß-oxidation related protein expression levels. CONCLUSIONS: This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/metabolismo , Endocannabinoides/metabolismo , Estudios de Casos y Controles , Hígado/metabolismo , Ácido Eicosapentaenoico/farmacología , Ceramidas/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
As our ongoing searching for the bioactive natural terpenoids, nine ent-kauranoids (1-9), including three previously undescribed ones (1, 2, and 9), were isolated from the aerial parts of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic data analysis, including NMR, MS, and ECD. Compounds 1 and 2 were a pair of tautomeric compounds, which was confirmed by the HPLC analysis and low temperature NMR testing. The underlying mechanism of the tautomer was proposed as an intramolecular SN2 reaction, which was explained by quantum chemical calculation. The HOMO-LUMO gap and the free energy revealed the spontaneous of the tautomeric of the 1 and 2. Additionally, the similar phenomena were also found in the two groups of known compounds 3 and 4 and 6 and 7, respectively. Apart from the tautomer, compounds 3 and 4 can be hydrolyzed into 5 through ester hydrolysis in CDCl3, while compounds 6, 7 can be hydrolyzed into 8 through ester hydrolysis. These phenomena were also confirmed through HPLC analysis and low temperature nuclear magnetic resonance tests and the mechanism was studied using quantum chemical calculation.
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Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon , Estructura Molecular , Isodon/química , Componentes Aéreos de las Plantas/química , Ésteres , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
n-3 polyunsaturated fatty acids (PUFA) have shown to exert beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Supplements of n-3 PUFA occur in either phospholipid or triacylglycerol form. The present study aimed to compare whether the different n-3 PUFA of marine-origin, namely krill oil, DHA/EPA-phospholipid (PL), and EPA/DHA-triacylglycerol (TAG) forms had differential abilities to ameliorate NAFLD. The NAFLD model was established in mice fed a high-fat and high-cholesterol diet (HFD). The mice showed evidence of weight gain, dyslipidemia, insulin resistance and hepatic steatosis after 9 weeks of HFD, while the three forms of the n-3 PUFA reduced hepatic TAG accumulation, fatty liver and improved insulin instance, and hepatic biomarkers after 9 weeks of intervention. Of these, krill oil intervention significantly reduced adipocyte hypertrophy and hepatic steatosis in comparison with DHA/EPA-PL and EPA/DHA-TAG groups. Importantly, only krill oil intervention significantly reduced serum alanine transaminase, aspartate transaminase concentrations and low-density lipoprotein-cholesterol, compared with the HFD group. Supplemental n-3 PUFA lowered circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) concentrations, compared with the HFD group, which was associated with down-regulating CB1 and upregulating adiponectin expressions in adipose tissue. Besides, targeted lipidomic analyses indicated that the increased adiponectin levels were accompanied by reductions in hepatic ceramide levels. The reduced ceramide levels were associated with inhibiting lipid synthesis and increasing fatty acid ß-oxidation, finally inhibiting TAG accumulation in the liver. Through mediating CB1/adiponectin/ceramide pathway, the present study suggested that administration of krill oil had superior health effects in the therapy of NAFLD in comparison with DHA/EPA-PL and EPA/DHA-TAG.
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Ácidos Grasos Omega-3 , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Omega-3/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fosfolípidos/metabolismo , Adiponectina/metabolismo , Triglicéridos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Hígado/metabolismo , Ácidos Grasos Insaturados/metabolismo , Colesterol/metabolismo , Receptores de Cannabinoides/metabolismo , Ácidos Grasos/metabolismoRESUMEN
Eleven previously unreported compounds (1-11), including five diterpenoids (1-5) and six sesquiterpenoids (6-11), together with two known diterpenoids (12-13), have been isolated from the roots of Salvia prattii. Their structures were comprehensively elucidated through spectroscopic methods, and their configurations were established using computational 13C nuclear magnetic resonance and electronic circular dichroism. Compound 1 was found to be an abietane-type diterpenoid with a novel rearrangement generated from the cleavage of the C-4/5 chemical bond, 20-methyl shift, and the rearrangement of the C-10 side chain. Compounds 2-3 were the third and fourth examples of arrangement seco-norabietanes with a spiro-lactone ring. We evaluated all compounds for their protective effects against alcoholic liver diseases (ALD). Compound 2 exhibited potential protective activity and hence can be used as a novel anti-ALD candidate.
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Diterpenos , Salvia , Terpenos/farmacología , Estructura Molecular , Salvia/química , Diterpenos/farmacología , Diterpenos/química , Abietanos/farmacología , Abietanos/químicaRESUMEN
OBJECTIVE: To investigate the related factors of invasive transformation and prognosis for follicular lymphoma. METHODS: A total of 168 patients with follicular lymphoma at First Affiliated Hospital of Zhengzhou University from August 2015 to January 2021 were collected, and the significance of each index in histological transformation (HT) and prognosis were analyzed. RESULTS: Pathology grade3, Ki-67 index ≥40%, ß2MGï¼3 mg/L, LDHï¼245 U/L, POD24 and non-invasion of bone marrow were associated with HT. Univariate analysis showed that the high risk of FLIPI-2, pathological grade 3, Ki-67≥40%, anemia, ß2MGï¼3 mg/L, LDHï¼245 U/L and HT had significant adverse effects on PFS; ß2MGï¼3 mg/L, LDHï¼245 U/L, POD24 and HT had significant adverse effects on OS. Cox multivariate analysis showed that the ß2MG >3 mg/L and HT were independent risk factors of PFS, HT was independent risk factor of OS. CONCLUSION: The pathological grade, Ki-67, ß2MG, LDH, POD24 and bone marrow invasion of FL can predict the risk of HT. Meanwhile, ß2MG >3 mg/L and HT are significantly related to poor prognosis of FL.
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BACKGROUND: Intravenous thrombolysis (IVT) is one of the most important means of therapy for patients with acute ischemic stroke (AIS). After cerebral infarction, the inflammatory response fulfills an essential role in the pathobiology of stroke, affecting the process of recanalization. Hence, we evaluated the usefulness of the systemic inflammatory response index (SIRI) for the prognosis of patients with AIS. METHODS: A total of 161 patients suffering from AIS were retrospectively analyzed. SIRI was introduced and calculated using the absolute neutrophil, monocyte, and lymphocyte numbers from the admission blood work. The study outcomes were determined using a modified Rankin Scale (mRS) at the 3-month timepoint, and a favorable clinical outcome was calculated in the mRS score range of 0 to 2. The analysis of receiver operating characteristic (ROC) curves was performed to determine the values of the optimal cutoff of SIRI for the prediction of clinical outcomes. In addition, multivariate analyses were performed to investigate the association between clinical outcomes and SIRI. RESULTS: The ROC curve analysis revealed that the ideal SIRI cutoff was at 2.54 [area under the curve, 78.85%; 95% CI, 71.70% to 86.00%; sensitivity, 70.89%; and specificity, 84.14%]. Multivariate analysis indicated that SIRI ≤2.54 (odds ratio, 1.557, 95% CI, 1.269 to 1.840; P =0.021) was an independent predictor of favorable clinical outcomes in patients suffering from AIS after treatment with IVT. CONCLUSIONS: We preliminary speculate that SIRI may serve as an independent predictor of clinical outcomes with AIS following IVT.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Resultado del Tratamiento , Estudios Retrospectivos , Terapia Trombolítica/efectos adversos , Accidente Cerebrovascular/etiología , Inflamación/tratamiento farmacológicoRESUMEN
In this study, we investigated Bartonella infection and its genetic diversity in rodents in Beitun, Xinjiang Uygur Autonomous Region, China. Small mammals were captured using snap traps at four sampling sites in 2018. Spleen and liver tissues were collected and cultured to isolate Bartonella strains. Whole-genome sequencing was performed on the strains identified as Bartonella by gltA gene PCR, and the average nucleotide identity (ANI) of the genomes was calculated by using FastANI v1.33. Phylogenetic trees were constructed for the samples positive for Bartonella spp. by the gltA PCR assay based on 1,290-bp gltA genes, 2,903-bp rpoB genes, and core-genome single nucleotide polymorphisms (SNPs). Among 66 rodents, 11 were positive for Bartonella, with an infection rate of 16.67%. The rodent infection rates in different tissues (χ2 = 2.133; P = 0.242), species (χ2 = 9.631; P = 0.141), and habitats (χ2 = 4.309; P = 0.312) did not show statistical differences. Bartonella spp. isolated from the rodents were phylogenetically divided into six clades (two different Bartonella species were detected in two rodents). By comparing phylogenetic trees based on gltA genes, rpoB genes, and SNPs, we found that the topological structures of several evolutionary trees are different. However, the Bartonella strains isolated in this study were clustered into six clusters in different phylogenetic trees. Broad distributions and high genetic diversity of Bartonella strains were observed among rodents in Beitun, Xinjiang. IMPORTANCE Rodent-borne Bartonella species have been associated with zoonotic diseases. Bartonella species such as Bartonella elizabethae, Bartonella grahamii, and Bartonella tribocorum can cause disease in humans. Humans can be infected by blood-sucking arthropods through the scratches and bites of an infected reservoir host or via contact with infectious rodents. Xinjiang is one of the provinces with the most abundant species of Bartonella in China, but there are few reports about the prevalence of Bartonella in the Beitun area. This research aims to investigate the occurrence and prevalence of Bartonella infection in rodents at these sampling sites and provide a basis for the prevention and control of rodent Bartonella species in Beitun and the surrounding areas of Xinjiang.
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Infecciones por Bartonella , Bartonella , Animales , Humanos , Roedores , Filogenia , Prevalencia , Bartonella/genética , Infecciones por Bartonella/epidemiología , Infecciones por Bartonella/veterinaria , China/epidemiologíaRESUMEN
Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.
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Neoplasias Pulmonares , Nanopartículas , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Polímeros , SialiltransferasasRESUMEN
Organic thermoelectricity is a blooming field of research that employs organic (semi)conductors to recycle waste heat through its partial conversion to electrical power. Such a conversion occurs by means of organic thermoelectric generator (OTEG) devices. The recent process on the synthesis of novel materials and on the understanding of doping mechanisms to increase conductivity has tremendously narrowed the gap between laboratory research and their application in actual applications. This Feature Article intends to highlight the impressive progress in materials and fabrication techniques for OTEGs made in recent years.
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Lymphocyte infiltration is an important feature of cancer. There is a complex network of chemokines that influence the degree and phenotype of lymphocyte infiltration, as well as the growth, survival, migration, and angiogenesis of tumor cells. High heterogeneity metastasis is a major obstacle to the treatment of breast cancer. Herein, we showed that O-GlcNAcylation of B lymphocyte-induced maturation protein-1 (Blimp-1) in lymphocytes inhibited the migration and invasion of breast cancer cells. It was found that Blimp-1 O-GlcNAcylation at Ser448 and Ser472 in lymphocytes promoted its nuclear localization, and blocked the bindings to three regions upstream of the ccl3l1 promoter to inhibit its expression. Decreased expression of CCL3L1 in lymphocytes not only decreased CCR5 expression in breast cancer cells, but also inhibited the membrane localization and activation of CCR5, thus blocking the migration and invasion of breast cancer cells in vitro. Therefore, O-GlcNAcylation of Blimp-1 in lymphocytes may serve as a new target for the treatment of metastatic breast cancer. IMPLICATIONS: This study reveals a new mechanism by which the lymphatic system promotes breast cancer cell metastasis.
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Neoplasias de la Mama , Linfocitos , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Neoplasias de la Mama/patología , Femenino , Humanos , Linfocitos/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Regiones Promotoras GenéticasRESUMEN
O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL)-an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.
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N-Acetilglucosaminiltransferasas , Neoplasias , Acetilglucosamina/metabolismo , Glucosa/metabolismo , Glucógeno/metabolismo , Humanos , N-Acetilglucosaminiltransferasas/genética , Fosforilación , Procesamiento Proteico-PostraduccionalRESUMEN
As a natural disturbance agent, soil erosion could affect secondary distribution and species composition of soil seed bank. The composition, storage and distribution pattern of the soil seed banks in five different vegetation recovery areas, including bare ground (1), pine forest land (2-4) and secondary forest (5) in the typical red soil erosion area, were studied to explore the effects of soil erosion on soil seed bank during vegetation restoration. The results showed that a total of 21 species were recorded in the soil seed bank. Species richness was low, and dominated by herbaceous species. The density of soil seed bank varied from 56.7 to 793.3 seeds·m-2 and differed significantly among the sampling plots. Further, the density of soil seed bank decreased obviously with the increasing soil erosion intensity. The seed bank density of 0-2 cm soil layer increased along uphill, middle slope, and downhill. The soil seed banks of severely eroded and strongly eroded plots were mainly distributed in the 5-10 cm soil layer, with almost no seeds in 0-2 cm soil layer on the middle slope and uphill. Soil erosion made the distribution of soil seed bank to deeper soil layer, the accumulation of which will need a long time after vegetation restoration.
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Banco de Semillas , Suelo , Bosques , SemillasRESUMEN
A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat-egg-milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.
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Servicios de Salud Comunitaria/organización & administración , Detección Precoz del Cáncer/estadística & datos numéricos , Neoplasias Esofágicas/prevención & control , Lesiones Precancerosas/epidemiología , Neoplasias Gástricas/prevención & control , Adulto , Factores de Edad , Anciano , China/epidemiología , Servicios de Salud Comunitaria/estadística & datos numéricos , Endoscopía Gastrointestinal/estadística & datos numéricos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidad , Estudios de Factibilidad , Femenino , Humanos , Incidencia , Renta/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Participación del Paciente/estadística & datos numéricos , Lesiones Precancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Encuestas y Cuestionarios/estadística & datos numéricos , Tasa de Supervivencia , Salud Urbana/estadística & datos numéricosRESUMEN
PURPOSE: To evaluate the prognostic value of pretreatment plasma systemic immune-inflammation index (SII), albumin, and fibrinogen levels in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel and to screen out the patients with the greatest risk for poor prognosis. METHODS: The plasma SII, albumin, and fibrinogen levels were examined before treatment and analyzed with patient clinicopathological parameters and overall survival (OS). The survival analysis was performed using the Kaplan-Meier method, and prognostic factors were assessed using the Cox proportional hazard regression model. RESULTS: The incidences of elevated SII level, hypoproteinemia, and hyperfibrinogenemia were 52.51%, 25.14%, and 27.93%, respectively. SII level was associated with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (P < 0.001). Albumin level was found closely correlated with ECOG PS (P = 0.006), PLR (P = 0.042), and hemoglobin (P = 0.009), but not other parameters. Elevated plasma fibrinogen level was significantly associated with Eastern Cooperative Oncology Group performance status (ECOG PS) (P = 0.009), visceral metastases (P < 0.001), and PLR (P = 0.001). In multivariate Cox regression model, visceral metastases SII (HR 2.133, 95% CI 1.163-3.913; P = 0.014), albumin (HR 0.540, 95% CI 0.307-0.949; P = 0.032), and fibrinogen (HR 1.888, 95% CI 1.069-3.335; P = 0.029) were further confirmed to be the independent prognostic factors for OS. Of the three target parameters, we found that patients with none abnormalities of the three parameters showed the best prognosis, and patients with at least any two abnormalities of them showed markedly worse prognosis than patients with any one abnormalities of the three parameters (P < 0.001). CONCLUSIONS: Pretreatment SII, albumin, and fibrinogen are independent prognostic factors in mCRPC patients treated with first-line docetaxel. Moreover, the combined use of SII, albumin, and fibrinogen levels may help us to identify the high-risk populations for treatment decisions.
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Antineoplásicos/uso terapéutico , Docetaxel/uso terapéutico , Fibrinógeno/análisis , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Albúmina Sérica/análisis , Anciano , Anciano de 80 o más Años , Humanos , Recuento de Leucocitos , Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Recuento de Plaquetas , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
The construction of antibacterial and antitumor coatings could offer effective routes to improve the therapeutic effects of non-vascular stents for unresectable obstructions caused by malignant tumours. Herein, polyelectrolyte multilayers have been explored as bactericidal coatings with controlled antitumor drug release. To solve the challenges of loading and controlled release of small-molecule chemotherapeutic drugs in polyelectrolyte multilayers, the antitumor drug doxorubicin (DOX) was chemically conjugated onto polyethylenimine via cis aconitic anhydride (pH-sensitive linker), thus obtaining the polycation prodrug PEI-CA-DOX. Alginate sodium was oxidized (O-Alg) and mixed with DOX to prepare the O-Alg-DOX complex as a polyanion. QCM-D and contact angle tests were used to monitor and verify the progressive build-up of the PEI-CA-DOX/O-Alg-DOX multilayer films, which show a linear growth. The in vitro antibacterial tests indicated that the PEI-CA-DOX-terminated PEI-CA-DOX/O-Alg-DOX multilayers could kill the bacteria effectively. As-such multilayers also presented a long-term sustained DOX release behaviour in PBS due to the combination of slow release in PEI-CA-DOX and fast release in the O-Alg-DOX complex. The as-designed PEI-CA-DOX/O-Alg-DOX multilayers with combined antibacterial and antitumor properties may have great potential for applications in non-vascular stent coatings for palliative treatment of obstruction caused by malignant tumours.
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Antibacterianos/química , Antineoplásicos/química , Portadores de Fármacos/química , Liberación de Fármacos , Stents , Ácido Aconítico/análogos & derivados , Ácido Aconítico/química , Alginatos/química , Doxorrubicina/química , Concentración de Iones de Hidrógeno , Polietileneimina/químicaRESUMEN
Traditional herb medicine, golden thread (Anoectochilus formosanus Hayata) has been used to treat various diseases. Hyperglycemia induces generation of reactive oxygen species (ROS) and enhancement of oxidative stress which are risk factors for cancer progression and metastasis. In this study, we evaluated hypoglycemic effect of A. formosanus extracts (AFEs) in an inducible hyperglycemia animal model and its capacity of free-radical scavenging to establish hyperglycemia-related carcinogenesis. AFE reduced blood glucose in hyperglycemic mice while there was no change in control group. The incremental area under blood glucose response curve was decreased significantly in hyperglycemic mice treated with AFE in a dose-dependent manner. AFE and metformin at the same administrated dose of 50 mg/kg showed similar effect on intraperitoneal glucose tolerance test in hyperglycemic mice. Free-radical scavenger capacity of AFE was concentration dependent and 200 µg/ml of AFE was able to reduce more than 41% of the free radical. Treatment of cancer cells with AFE inhibited constitutive PD-L1 expression and its protein accumulation. It also induced expression of pro-apoptotic genes but inhibited proliferative and metastatic genes. In addition, it induced anti-proliferation in cancer cells. The results suggested that AFE not only reduced blood glucose concentration as metformin but also showed its potential use in cancer immune chemoprevention/therapy via hypoglycemic effect, ROS scavenging and PD-L1 suppression.
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Six new monoterpenoid indole alkaloids, 19(E)-9-demethoxy-16-dehydroxylchitosenine-17-O- ß-d-glucopyranoside (1), 19(E)-9,10-didemethoxy-16-dehydroxylchitosenine-17-O-ß-d-gluco-pyranoside (2), 19(E)-9,10-didemethoxy-16-dehydroxyl-11-methoxychitosenine (3), 19(E)-9,10-didemethoxy-16-dehydroxyl-11-methoxychitosenine-17-O-ß-d-glucopyranoside (4), 19(Z)-18-carboxylgardneramine (5), and 19(E)-18-demethoxygardneramine-N (4)-oxide (6), along with four known alkaloids, were isolated from Gardneria multiflora, and their structures were elucidated by spectroscopic analysis. Compounds 1, 2 and 4 are the first example of Gardneria alkaloids whose glucose units were attached to C-17. None of the compounds were cytotoxic to any of five human cancer cell lines.
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Loganiaceae/química , Alcaloides de Triptamina Secologanina/química , Línea Celular Tumoral , Humanos , Estructura Molecular , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
The occurrence of proton tunneling in MAPbI3 hybrid organic inorganic perovskites is demonstrated through the effect of isotopic labeling of the methylammonium (MA) component on the dielectric permittivity response. Deuteration of the ammonium group results in the acceleration of proton migration (inverse primary isotope effect), whereas deuteration of the methyl group induces a normal secondary isotope effect. The activation energies for proton migration are calculated to be 50 and 27 meV for the tetragonal and orthorhombic phases, respectively, which decrease upon deuteration of the ammonium group. The low activation barrier and the deviation from unity of the ratio of the pre-exponential factors (AH/AD = 0.3-0.4) are consistent with a tunneling mechanism for proton migration. Deuteration of the PEDOT:PSS hole transport layer results in a behavior that is intermediate between that of the deuterated and undeuterated perovskite, due to extrinsic ion migration between the two materials.
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Overload-exercise (OE) causes myocardial injury through inducing autophagy and apoptosis. In this study we examined whether an autophagy inhibitor 3-methyladenine (3-MA) could alleviate OE-induced cardiac injury. Rats were injected with 3-MA (15 mg/kg, iv) or saline before subjected to various intensities of OE, including no swim (control), 2 h swim (mild-intensity exercise, MIE), 2 h swim with 2.5% body weight overload (moderate OE; MOE), 5% overload (intensive OE; IOE) or 2.5% overload until exhausted (exhaustive OE; EOE). After OE, the hearts were harvested for morphological and biochemiacal analysis. The cardiac morphology, autophagosomes and apoptosis were examined with H&E staining, transmission electron microscopy and TUNEL analysis, respectively. Autophagy-related proteins to (LC3-II/I and Beclin-1) and apoptosis-related proteins (Bcl-2/Bax) were assessed using Western blotting. Our results showed that compared with the control, MIE did not change the morphological structures of the heart tissues that exhibited intact myocardial fibers and neatly arranged cardiomyocytes. However, IOE resulted in irregular arrangement of cardiomyocytes and significantly increased width of cardiomyocytes, whereas EOE caused more swollen and even disrupted cardiomyocytes. In parallel with the increased OE intensity (MOE, IOE, EOE), cardiomyocyte autophagy and apoptosis became more and more prominent, evidenced by the increasing number of autophagosomes and expression levels of LC3-II/I and Beclin-1 as well as the increasing apoptotic cells and decreasing Bcl-2/Bax ratio. 3-MA administration significantly attenuated OE-induced morphological changes of cardiomyocytes as well as all the autophagy- and apoptosis-related abnormalities in MOE, IOE and EOE rats. Thus, the autophagy inhibitor 3-MA could alleviate OE-induced heart injury in rats.
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Adenina/análogos & derivados , Autofagia/efectos de los fármacos , Lesiones Cardíacas/tratamiento farmacológico , Condicionamiento Físico Animal , Adenina/farmacología , Animales , Modelos Animales de Enfermedad , Lesiones Cardíacas/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Accumulating evidence from animal and human research indicate that adult hippocampal neurogenesis plays a key role in cognition. Meanwhile, cognitive decline is well known to associate with ageing-related neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Therefore, prevention of hippocampal neurogenesis reduction should be critical for these diseases. Physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential therapy or an adjunctive therapeutic strategy for cognitive decline. In this review, we discuss the recent findings on hippocampal neurogenesis and the incorporation of new born neurons into the neuronal network in humans and in rodents. By focusing on hippocampal neurogenesis, we illustrate the role and possible mechanisms of physical exercise in cognition preservation.