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BACKGROUND: Individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and stroke risk through the triglyceride-glucose index (TyG) seems plausible but has not been investigated. This study aims to examine whether TyG mediates associations of BMI with stroke risk and the extent of interaction or joint relations of TyG and BMI with stroke outcome. METHODS: The China Health and Retirement Longitudinal Study, initiated in 2011, is a nationally representative, ongoing prospective cohort study involving 8 231 middle-aged and older Chinese adults without a stroke history at baseline. Exposures examined include BMI and the TyG, the latter being the logarithmized product of fasting triglyceride and glucose concentrations. The primary study outcome is stroke incidence, as determined through self-reports, with a follow-up period extending from June 1, 2011, to June 30, 2018. RESULTS: Of the 8 231 participants, 3 815 (46.3%) were men; mean (SD) age was 59.23 (9.32) years. During a median follow-up of 7.1 years, 585 (7.1%) participants developed stroke. The TyG was found to mediate the association between BMI and incident stroke, proportions mediated were 16.3% for BMI in the 24.0-27.9 kg/m2 group and 53.8% for BMI ≥ 28.0 kg/m2 group. No significant multiplicative and additive interactions were found between BMI and TyG on incident stroke (Additive: RERI = 1.78, 95% CI - 1.29-4.86; Multiplicative, HR = 1.40, 95% CI 0.86-2.27). HRs for individuals with BMI ≥ 28.0 kg/m2 and quartile 4 of TyG compared with those with BMI < 24.0 kg/m2 and quartile 1 of TyG were 2.05 (95% CI 1.37-3.06) for incident stroke. Combining BMI and TyG enhanced predictive performance for stroke when compared to their individual (AUCBMI+TyG vs AUCBMI vs AUCTyG, 0.602 vs 0.581 vs 0.583). CONCLUSIONS: TyG appeared to be associated with stroke risk and mediates more than 50% of the total association between BMI and stroke in middle-aged and older Chinese adults. Public health efforts aiming at the reduction of body weight might decrease the stroke risk due to insulin resistance and the burden of stroke.
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Resistencia a la Insulina , Accidente Cerebrovascular , Adulto , Masculino , Persona de Mediana Edad , Humanos , Anciano , Femenino , Índice de Masa Corporal , Estudios Longitudinales , Estudios Prospectivos , China/epidemiología , Glucosa , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Triglicéridos , Glucemia , Factores de Riesgo , BiomarcadoresRESUMEN
Nucleolus was an important cellular organelle. The abnormal morphology and number of the nucleolus have been considered as diagnostic biomarkers for some human diseases. However, the imaging agent based on nucleolus was limited. In this manuscript, a series of nucleolar fluorescent probes based on naphthalimide derivatives (NI-1 â¼ NI-5) had been designed and synthesized. NI-1 â¼ NI-5 could penetrate cell membranes and nuclear membranes, achieve clear nucleolar staining in living cells. These results suggested that the presence of amino groups on the side chains of naphthalimide backbone could enhance the targeting to the cell nucleolus. In addition, the molecular docking results showed that NI-1 â¼ NI-5 formed hydrogen bonds and hydrophobic interactions with RNA, and exhibited enhanced fluorescence upon binding with RNA. These results will provide favorable support for the diagnosis and treatment of nucleolus-related diseases in the future.
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Nucléolo Celular , Naftalimidas , Humanos , Nucléolo Celular/metabolismo , Simulación del Acoplamiento Molecular , ARN/metabolismoRESUMEN
OBJECTIVE: To assess the independent and combined associations of tumor-related psychiatric symptoms (TRPS) with dynamic health-related quality of life (HRQL) in patients with hepatocellular carcinoma (HCC) after hepatectomy and to identify related patterns of health behaviors. METHODS: This prospective study included patients with HCC who underwent hepatectomy between September 2021 and May 2022. Independent and combined associations between TRPS and HRQL were identified by generalized linear model and weighted quantile sum model, respectively. Trajectories of HRQL were identified by latent class mixed model. RESULTS: Among the 205 patients, 174 (84.9%) were male. For the outcome of HRQL at 6 months: Anxiety, depression, fatigue, and sleep disorder were independently associated with a decrease of HRQL (all P < 0.05). A negative combined effect of TRPS was also found (ß = - 5.07, 95% CI, - 10.01 to - 0.13), with depression emerged as the predominant contributor (49%). The health behaviors of body mass index, smoking, drinking, or physical exercise were not significantly modified the associations between combined TRPS and HRQL (all P > 0.05 for interaction). Similar results were also found for the HRQL at baseline and at 1 and 3 months. Three HRQL trajectory groups were identified: recover (44.9%), poor (44.4%), and deteriorating (10.7%). Deteriorating group was associated with higher incidence of TRPS (all P < 0.05). CONCLUSIONS: TRPS were associated with a decrease of HRQL regardless of healthy behaviors in HCC patients. Therefore, healthy behaviors promotion alone might not substantially increase HRQL associated with TRPS, and other measures tackling TRPS are warranted.
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Carcinoma Hepatocelular , Conductas Relacionadas con la Salud , Hepatectomía , Neoplasias Hepáticas , Calidad de Vida , Humanos , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/psicología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/psicología , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Hepatectomía/psicología , Hepatectomía/métodos , Anciano , Depresión/etiología , Depresión/epidemiología , AdultoRESUMEN
BACKGROUND: Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015-2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI. RESULTS: Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65-1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11-2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01-2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530). CONCLUSIONS: Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.
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Glucemia , Índice de Masa Corporal , Pueblos del Este de Asia , Accidente Cerebrovascular , Triglicéridos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucosa/análisis , Estudios Longitudinales , Estudios Prospectivos , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Glucemia/análisis , RiesgoRESUMEN
Synthetic glycoconjugates as chemical probes have been widely developed for the detection of glycosidase enzymes. However, the binding interactions between iminosugar derivatives and glycosidases were limited, especially for the binding interactions between multivalent glycosidase inhibitors and α-glycosidases. In this paper, three naphthalimide-DNJ conjugates were synthesized. Furthermore, the binding interactions and glycosidase inhibition effects of them were investigated. It was found that the strong binding interactions of multivalent glycosidase inhibitors with enzymes were related to the efficient inhibitory activity against glycosidase. Moreover, the lengths of the chain between DNJ moieties and the triazole ring for the naphthalimide-DNJ conjugates influenced the self-assembly properties, binding interactions and glycosidase inhibition activities with multisource glycosidases. Compound 13 with six carbons between the DNJ moiety and triazole ring showed the stronger binding interactions and better glycosidase inhibition activities against α-mannosidase (jack bean) and α-glucosidase (aspergillus niger). In addition, compound 13 showed an effective PBG inhibition effect in mice with 51.18 % decrease in blood glucose at 30 min. This result opens a way for detection of multivalent glycosidase inhibition effect by a fluorescent sensing method.
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Inhibidores Enzimáticos , Glicósido Hidrolasas , Ratones , Animales , Inhibidores Enzimáticos/química , Glicósido Hidrolasas/metabolismo , Naftalimidas/farmacología , Fluorescencia , alfa-ManosidasaRESUMEN
Upper-room ultraviolet germicidal irradiation (UVGI) technology can potentially inhibit the transmission of airborne disease pathogens. There is a lack of quantitative evaluation of the performance of the upper-room UVGI for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) airborne transmission under the combined effects of ventilation and UV irradiation. Therefore, this study aimed to explore the performance of the upper-room UVGI system for reducing SARS-CoV-2 virus transmission in a hospital isolation environment. Computational fluid dynamics and virological data on SARS-CoV-2 were integrated to obtain virus aerosol exposure in the hospital isolation environment containing buffer rooms, wards and bathrooms. The UV inactivation model was applied to investigate the effects of ventilation rate, irradiation flux and irradiation height on the upper-room UVGI performance. The results showed that increasing ventilation rate from 8 to 16 air changes per hour (ACH) without UVGI obtained 54.32% and 45.63% virus reduction in the wards and bathrooms, respectively. However, the upper-room UVGI could achieve 90.43% and 99.09% virus disinfection, respectively, with the ventilation rate of 8 ACH and the irradiation flux of 10 µW cm-2. Higher percentage of virus could be inactivated by the upper-room UVGI at a lower ventilation rate; the rate of improvement of UVGI elimination effect slowed down with the increase of irradiation flux. Increase irradiation height at lower ventilation rate was more effective in improving the UVGI performance than the increase in irradiation flux at smaller irradiation height. These results could provide theoretical support for the practical application of UVGI in hospital isolation environments.
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BACKGROUND: Neuroendocrine neoplasms (NENs) are a group of diseases that show high heterogeneity but have limited treatment options. This phase I study evaluated the safety and efficacy of sintilimab, anti-PD-1 monoclonal antibody, in treating advanced NENs. METHODS: We prospectively enrolled patients pathologically diagnosed with NENs after standard treatment failure. Neuroendocrine neoplasms were classified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine cancers (NECs). Every patient received sintilimab, and response was assessed every 9 weeks. RESULTS: Twenty-four patients with a median age of 57.0 years were enrolled from November 2016 to 2017. The median Ki-67 index was 60%. Five patients had NET, 1 had NET G3, 17 had NEC, and 1 had mixed adenocarcinoma-neuroendocrine carcinoma. The most common primary tumor sites were the pancreas and gastrointestinal tract in 7 and 10 patients, respectively. In phase Ia trial, 2 patients received sintilimab 1 mg/kg every 2 weeks, one received 3 mg/kg every 2 weeks, and 21 patients enrolled in the phase Ib trial received 200 mg every 3 weeks. The objective response rate was 20.8% in all enrolled patients and 27.8% in NEC patients. The median progression-free survival was 2.2 and 2.1 months in patients with NET and NEC, respectively. The median OS was not applicable (NA) and 10.8 months (95% CI, 4.3, NA) with NET and NEC, respectively. The duration of response (DOR) was not reached, with a median follow-up time of 20.7 months. Treatment-related adverse events (TRAE) occurred in 17 (70.8%) patients. The most frequent TRAE was thyroid dysfunction (41.7%), and a grade 3 pulmonary infection occurred in 1 patient. The programmed cell death 1-ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) rate was 18.8% (3 out of 16) and the expression of PD-L1 did not correlate with response. CONCLUSION: Sintilimab was well-tolerated and showed encouraging response in NECs. CLINICALTRIALS.GOV IDENTIFIER: NCT02937116.
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Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Anticuerpos Monoclonales Humanizados/efectos adversos , Antígeno B7-H1 , Carcinoma Neuroendocrino/patología , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIM: Previous smaller meta-analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta-analysis aimed to reliably identify any difference in the HCC incidence between TDF-treated or ETV-treated CHB patients in general or in specific subgroups. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF-treated and ETV-treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random-effects model. RESULTS: Twenty-four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67-0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72-0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71-0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58-1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66-0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65-0.84; 18 studies). CONCLUSION: Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Guanina/análogos & derivados , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Estudios Retrospectivos , Tenofovir/uso terapéutico , Resultado del TratamientoRESUMEN
Suspected and confirmed cases of infectious diseases such as COVID-19 are diagnosed and treated in specific hospital isolation wards, posing a challenge to preventing cross-infection between patients and healthcare workers. In this study, the Euler-Lagrange method was used to simulate the evaporation and dispersion of droplets with full-size distribution produced by fluctuating coughing and breathing activities in an isolation ward. The effects of supply air temperature and relative humidity, ventilation rates and patient postures on droplet distribution were investigated. The numerical models were validated by an aerosol experiment with an artificial saliva solution containing E. coli bacteria conducted in a typical isolation ward. The results showed that the small size group of droplets (initial size ≤87.5 µm) exhibited airborne transmission in the isolation ward, while the large size group (initial size ≥112.5 µm) were rapidly deposited by gravitational effects. The ventilation rate had a greater effect on the diffusion of droplet nuclei than the supply air temperature and relative humidity. As the air changes per hour (ACH) increased from 8 to 16, the number fraction of suspended droplet nuclei reduced by 14.2% and 6.4% in the lying and sitting cases, respectively, while the number fraction of escaped droplet nuclei increased by 16.2% and 14.6%. Regardless of whether the patient was lying or sitting, the amount of droplet nuclei deposited on the ceiling was highest at lower ventilation rates. These results may provide some guidance for routine disinfection and ventilation strategies in hospital isolation wards.
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Organelles possess critical biological effects in cellular processes. However, the relationship between organelle targeting and antitumour activity is a challenging issue. In this paper, a number of amide/acylhydrazine modified naphthalimide derivatives were designed and synthesized. Interestingly, amide modified naphthalimide derivatives NI-A-NH and NI-C-NH with (R)-piperdine and (S)-pyrrolidine functionalization exhibited enhanced cytotoxicity compared with acylhydrazine modified derivatives NI-A-2NH and NI-C-2NH. However, acylhydrazine modified derivatives NI-B-2NH and NI-D-2NH with (S)-piperdine and achiral piperdine conjugates possessed better cytotoxicity than NI-B-NH and NI-D-NH with amide modifications. Fluorescence imaging, DNA binding interactions and cell cycle analyses were further completed to clarify that the nucleus-targeting effects showed enhanced cytotoxic activity, strong DNA binding and the blocking of cells in S phase. These results provide a preliminary theoretical basis for the further design of organelle-targeting antitumour drugs.
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Antineoplásicos/química , Antineoplásicos/farmacología , Núcleo Celular/efectos de los fármacos , Naftalimidas/química , Naftalimidas/farmacología , Antineoplásicos/análisis , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patología , Células HeLa , Humanos , Naftalimidas/análisis , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Imagen ÓpticaRESUMEN
The fruit of Citrus medica L. var. sarcodactylis Swingle is not only used as a traditional medicinal plant, but also served as a delicious food. Six new (3'â7â³)-biflavonoids (1-6), and twelve known biflavonoid derivatives (7-18) were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. Their structures were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, and IR spectral data coupled with the data described in the literature. Compounds (1-18) were evaluated for their hypolipidemic activities with Orlistat as the positive control, and assayed for their immunosuppressive activities with Dexamethasone as the positive control, respectively. Among them, compounds (1-3) exhibited moderate inhibition of pancreatic lipase activity by inhibiting 68.56 ± 1.40%, 56.18 ± 1.57%, 53.51 ± 1.59% of pancreatic lipase activities at the concentration of 100 µM, respectively. Compounds (4-6) and 8 showed potent immunosuppressive activities with the IC50 values from 16.83 ± 1.32 to 50.90 ± 1.79 µM. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this study.
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Biflavonoides/farmacología , Citrus/química , Inhibidores Enzimáticos/farmacología , Hipolipemiantes/farmacología , Inmunosupresores/farmacología , Lipasa/antagonistas & inhibidores , Animales , Biflavonoides/química , Biflavonoides/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Concanavalina A/antagonistas & inhibidores , Concanavalina A/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Frutas/química , Células Hep G2 , Humanos , Hipolipemiantes/química , Hipolipemiantes/aislamiento & purificación , Inmunosupresores/química , Inmunosupresores/aislamiento & purificación , Lipasa/metabolismo , Estructura Molecular , Páncreas/enzimología , Bazo/efectos de los fármacos , Relación Estructura-Actividad , PorcinosRESUMEN
The fruit of Citrus medica L. var. sarcodactylis Swingle is a functional food with rich nutrients and medicinal values because of its content of bioactive compounds. A bioactivity-guided chemical investigation from the fruits of C. medica L. var. sarcodactylis Swingle afforded three new benzodioxane neolignans (1-3), three new phenanthrofuran neolignan glycosides (4-6), two new biphenyl-ketone neolignans (7-8), two new 1',7'-bilignan neolignans (9-10), as well as fourteen known neolignan derivatives (11-24), which were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. These neolignan derivatives were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, IR spectral data and compared with the data described in the literature. Among them, compounds 1-3 and 12-13 exhibited moderate hepatoprotective activities to improve the survival rates of HepG2 cells from 46.26 ± 1.90% (APAP, 10 mM) to 67.23 ± 4.25%, 62.87 ± 4.43%, 60.06 ± 6.34%, 56.75 ± 2.30%, 58.35 ± 6.14%, respectively. Additionally, compounds 7-8 and 21-22 displayed moderate neuroprotective activities to raise the survival rates of PC12 cells from 55.30 ± 2.25% to 66.94 ± 3.37%, 70.98 ± 5.05%, 64.64 ± 1.93%, and 62.81 ± 4.11% at 10 µM, respectively. The plausible biogenetic pathway and preliminary structure-activity relationship of the selected compounds were scientifically summarized and discussed in this paper.
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Citrus/química , Lignanos/química , Sustancias Protectoras/química , Animales , Supervivencia Celular/efectos de los fármacos , Citrus/metabolismo , Frutas/química , Frutas/metabolismo , Células Hep G2 , Humanos , Lignanos/aislamiento & purificación , Lignanos/farmacología , Espectroscopía de Resonancia Magnética , Conformación Molecular , Células PC12 , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
To study phenylpropanoids from Eleocharis dulcis and their hepatoprotective activities. The compounds were separated and purified from ethyl acetate part by conventional column chromatography and preparative liquid chromatography, and their structures were identified by various spectral techniques. The HL-7702 cells damage model of hepatocytes induced by APAP was used to screen and evaluate the hepatoprotective activities of these compounds. Sixteen compounds were isolated from ethyl acetate part of E. dulcis, and their structures were identified as 6'-(4â³-hydroxy-3â³-methoxy-phenylpropenyl)-1-(10-methoxy-phenylacetone)-1'-O-ß-D-glucopy-ranoside(1), susaroyside A(2), clausenaglycoside B(3), clausenaglycoside C(4), clausenaglycoside D(5), emarginone A(6), emarginone B(7), thoreliin B(8), 4-O-(1',3'-dihydroxypropan-2'-yl)-dihydroconiferyl alcohol 9-O-ß-D-glucopyranoside(9), 2-[4-(3-methoxy-1-propenyl)-2-methoxy-phenoxy]-propane-1,3-diol(10), 6'-O-(E-cinnamoyl)-coniferin(11), methyl 3-(2-O-ß-D-glucopyranosyl-3,4,5,6-tetramethoxyphenyl) propanoate(12), clausenaglycoside A(13), 9-O-(E-cinnamoyl)-coniferin(14), 6'-O-(E-cinnamoyl)-syringin(15), 2'-O-(E-cinnamoyl)-syringin(16). Among them, compound 1 was a new compound. Compounds 2-16 were isolated from this plant for the first time. Among them, compounds 2 and 8 showed certain hepatoprotective activities.
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Eleocharis , Cromatografía , Hepatocitos , Extractos VegetalesRESUMEN
The transmission and deposition of pathogenic bioaerosols and the subsequent contamination of the air and surfaces is well recognized as a potential route of hospital cross-infection. A full-scale experiment using Bacillus subtilis and computational fluid dynamics were utilized to model the bioaerosol characteristics in a two-bed hospital ward with a constant air change rate (12 ACH). The results indicated that the bioaerosol removal efficiency of unilateral downward ventilation was 50% higher than that of bilateral downward ventilation. Additionally, health care workers (HCWs) and nearby patients had lower breathing zone concentrations in the ward with unilateral downward ventilation. Furthermore, a partition played a positive role in protecting patients by reducing the amount of bioaerosol exposure. However, no obvious protective effect was observed with respect to the HCWs. Only 10% of the bioaerosol was deposited on the surfaces in the ward with unilateral downward ventilation, while up to 35% of the bioaerosol was deposited on the surfaces in the ward with bilateral downward ventilation during the 900 s. The main deposition locations of the bioaerosols were near the wall on the same side of the room as the patient's head in all cases. This study could provide scientific evidence for controlling cross-infection in hospital wards, as well as several guidelines for the disinfection of hospital wards.
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Reasonable equipment layout is essential for creating a healthy and safe environment, especially in a three-level biosafety laboratory with high potential risk factors of infection. Since 2019, COVID-19, an emerging infection has swept the world and caused severe losses. Biosafety laboratories are mandatory sites for detecting high-risk viruses, so related research is urgently needed to prevent further laboratory-acquired infections of operators. This study investigated the effects of obstacles on exposure infection of staff in a biosafety laboratory with related experimental equipment. The numerical simulation results are highly verified by the measured results. The results indicate that although the equipment layout does not affect the bioaerosol removal time, nearly 17% of the pollutant particles in the actual laboratory cannot be discharged effectively compared with the ideal situation. These particles lingered in the lower space under the influence of vortex, which would increase the respiratory risk of operators. In addition, after the experiment a large part of bioaerosol particles would be captured by equipment and floor, and the deposition rate per unit area is 0.45%/m2 and 0.8%/m2, respectively. Although the results show that the equipment layout could reduce the pollution on the floor, the disinfection is still an important link, especially on the surfaces of equipment. Meanwhile, the result also indicates that the action should be light and slow when operating in BSL-3 laboratory, so as to avoid the secondary suspension pollution of bioaerosol particles on the equipment surface and floor.
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Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage ΦX174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.
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OBJECTIVE: To determine whether serum prealbumin levels are associated with long-term survival after hepatectomy in patients with primary hepatocellular carcinoma(HCC). METHODS: A consecutive sample of 526 patients with HCC who underwent potentially curative hepatectomy from August 2007 to August 2010 was retrospectively analyzed. Patients were classified as having normal or reduced serum prealbumin based on cut-off values of 200 or 182 mg/L. RESULTS: Multivariate analysis identified the preoperative level of serum prealbumin as an independent prognostic factor of long-term survival (P < 0.05): Survival was significantly better for those with normal levels than for those with reduced levels, based on either cut-off value. Similar results were observed in subgroup analyses based on the degree of cirrhosis, level of É-fetoprotein and Barcelona Clinic Liver Cancer stage. CONCLUSIONS: Preoperative level of serum prealbumin may be useful for predicting long-term survival in patients with HCC after hepatectomy.
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Carcinoma Hepatocelular/mortalidad , Hepatectomía , Neoplasias Hepáticas/mortalidad , Prealbúmina/análisis , Biomarcadores/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , alfa-Fetoproteínas/análisisRESUMEN
Pancreatic adenocarcinoma is a highly malignant cancer that often involves a deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the regulation of a variety of physiological processes and is involved in early neoplastic development, resulting in poor progression. Hence, suppression of c-Myc overexpression is a potential strategy for pancreatic cancer therapy. CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). It has shown potential efficiency in patients with lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors with c-Myc alterations, but the evidence is lacking for how CUDC-907 regulates c-Myc. In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c-Myc and Ki67 expression in tumor tissue was observed in a human pancreatic cancer Aspc-1 xenograft nude mouse model in vivo. Our results suggest that CUDC-907 can be a valuable therapeutic option for treating pancreatic adenocarcinoma.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Histona Desacetilasa 6/antagonistas & inhibidores , Morfolinas/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-myc/metabolismo , Pirimidinas/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Antígeno Ki-67/metabolismo , Masculino , Ratones Endogámicos BALB C , Morfolinas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias PancreáticasRESUMEN
Four new biphenyl derivatives (1-4), along with six known biphenyl derivatives (5-10) were isolated and elucidated by their detailed analyses of spectroscopic data and references from the aerial parts of Oenanthe javanica for the first time. Compounds (1-10) were assayed for their activities about the inhibition of COX-2 enzyme inâ vitro for the first time. Compounds 1, 2, 4, and 6 showed inhibitory activities against COX-2 with IC50 values ranging from 22.18±0.29 to 108.54±0.42â µm.
Asunto(s)
Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Oenanthe/química , Componentes Aéreos de las Plantas/química , Compuestos de Bifenilo/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Concentración 50 Inhibidora , Estructura Molecular , Análisis Espectral/métodosRESUMEN
In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.