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1.
Proc Natl Acad Sci U S A ; 119(25): e2026733119, 2022 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-35709320

RESUMEN

Safeguarding Earth's tree diversity is a conservation priority due to the importance of trees for biodiversity and ecosystem functions and services such as carbon sequestration. Here, we improve the foundation for effective conservation of global tree diversity by analyzing a recently developed database of tree species covering 46,752 species. We quantify range protection and anthropogenic pressures for each species and develop conservation priorities across taxonomic, phylogenetic, and functional diversity dimensions. We also assess the effectiveness of several influential proposed conservation prioritization frameworks to protect the top 17% and top 50% of tree priority areas. We find that an average of 50.2% of a tree species' range occurs in 110-km grid cells without any protected areas (PAs), with 6,377 small-range tree species fully unprotected, and that 83% of tree species experience nonnegligible human pressure across their range on average. Protecting high-priority areas for the top 17% and 50% priority thresholds would increase the average protected proportion of each tree species' range to 65.5% and 82.6%, respectively, leaving many fewer species (2,151 and 2,010) completely unprotected. The priority areas identified for trees match well to the Global 200 Ecoregions framework, revealing that priority areas for trees would in large part also optimize protection for terrestrial biodiversity overall. Based on range estimates for >46,000 tree species, our findings show that a large proportion of tree species receive limited protection by current PAs and are under substantial human pressure. Improved protection of biodiversity overall would also strongly benefit global tree diversity.


Asunto(s)
Efectos Antropogénicos , Biodiversidad , Conservación de los Recursos Naturales , Ecosistema , Árboles , Conservación de los Recursos Naturales/métodos , Humanos , Filogenia , Árboles/clasificación
2.
Lancet ; 402(10400): 451-463, 2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37423228

RESUMEN

BACKGROUND: Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. METHODS: This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786. FINDINGS: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2]; stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3-4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). INTERPRETATION: First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. FUNDING: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Calidad de Vida , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
3.
Environ Res ; : 119487, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38917932

RESUMEN

The nutraceutical value, and physicochemical profile as well as anti-inflammatory activity potential of Odonthalia floccose and Odonthalia dentata (red macroalgae) dry biomass were investigated in this study. Proximate composition study results revealed that the dry biomass of O. floccose and O. dentae were found to be as ash: 9.11 & 8.7 g 100 g-1, moisture: 8.24 & 8.1 g 100 g-1, total fat: 6.9 & 7.2 g 100 g-1, protein: 24.52 & 25.6 g 100 g-1, and total carbohydrate/polysaccharides: 53.84 & 48.85 g 100 g-1 of dry weight biomass respectively. Both algae biomass contain considerable quantity of minerals (Fe, Cu, Mg, and Zn). Furthermore, the major saturated fatty acids (6.24 & 5.82 g FAME 100 g-1 of total fat of O. floccose and O. dentate) (ΣFAs) present in the test algae were stearic acid, palmitic acid, and margaric acids. O. floccose and O. dentata also contain remarkable protein composition profile that compiled with considerable quantity of essential and non-essential amino acids. The vitamins such as vitamin A, B1, B2, B3, B6, B9, C, and E of O. floccose and O. dentate biomass were also identified at sufficient quantity level. The swelling capacity (SWC), water holding capacity (WHC), and oil holding capacity (OHC) properties of O. floccose and O. dentate at various temperature conditions (25 and 37 ᵒC) were found to be 8.11 & 7.02 mL g-1 and 8.95 & 7.55 mL g-1, 5.1 & 4.87 and 4.8 & 4.1 mL g-1, as well as 2.11 & 1.81 and 1.96 & 1.89 mL g-1 respectively. Among these two marine red macroalgae samples, the O. dentate showed better anti-inflammatory activity than O. floccose at 150 µg mL-1 dosage. Thus, this O. floccose and O. dentate biomass can be considerable as nutritional supplement and pharmaceutical product development related research.

4.
Environ Res ; 251(Pt 2): 118729, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38492832

RESUMEN

The study was carried out to evaluate the effectiveness of the Aristolochia bracteolata water flower extract-mediated AgNPs synthesis and assess their antimicrobial potential. According to the experimental and analytical results, A. bracteolata flower extract can produce valuable AgNPs. The characteristic features of these AgNPs were assessed with UV-visible spectrophotometer, Fourier transform-infrared spectroscopy, Transmission Electron Microscope, Scanning Electron Microscopy, as well as. Under UV-vis. spectrum results, showed major peak at 430 nm and recorded essential functional groups responsible for reducing, capping, and stabilizing AgNPs by FT-IR analysis. In addition, the size and shape of the synthesized AgNPs were found as 21.11-25.17 nm and spherical/octahedral shape. The A. bracteolata fabricated NPs showed remarkable antimicrobial activity against fish bacterial pathogens (V. parahaemolytics, Serratia sp., B. subtilis, and E. coli) as well as common fungal pathogens (A. niger, C. albicans, A. flavus, and A. terreus) at the quantity of 100 µg mL-1 than positive controls. Nevertheless, it was not effective against human bacterial pathogens. It concludes that AgNPs synthesized from A. bracteolata aqueous flower extract have excellent antimicrobial activity and may have a variety of biomedical applications.


Asunto(s)
Antiinfecciosos , Antioxidantes , Aristolochia , Flores , Nanopartículas del Metal , Extractos Vegetales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Flores/química , Nanopartículas del Metal/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Aristolochia/química , Plata/química , Plata/farmacología , Bacterias/efectos de los fármacos
5.
Phys Rev Lett ; 131(5): 050802, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37595240

RESUMEN

We develop an iterative, adaptive frequency sensing protocol based on Ramsey interferometry of a two-level system. Our scheme allows one to estimate unknown frequencies with a high precision from short, finite signals consisting of only a small number of Ramsey fringes. It avoids several issues related to processing of decaying signals and reduces the experimental overhead related to sampling. High precision is achieved by enhancing the Ramsey sequence to prepare with high fidelity both the sensing and readout state and by using an iterative procedure built to mitigate systematic errors when estimating frequencies from Fourier transforms. A comparison with state-of-the-art dynamical decoupling techniques reveals a significant speedup of the frequency estimation without loss of precision.

6.
Phys Chem Chem Phys ; 25(26): 17496-17507, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37357726

RESUMEN

Taking advantage of metal-semiconductor junctions, functional nanocomposites have been designed and developed as active substrates for surface-enhanced Raman scattering (SERS) sensing systems. In this work, we prepared three types of nanocomposites based on manganese oxide (MnO2) nanostructures and electrochemically synthesized silver nanoparticles (e-AgNPs), which differed according to the morphologies of MnO2. The SERS performance of MnO2 nanosheet/e-Ag (MnO2-s/e-Ag), MnO2 nanorod/e-Ag (MnO2-r/e-Ag), and MnO2 nanowire/e-Ag (MnO2-w/e-Ag) was then evaluated using tricyclazole (TCZ), a commonly used pesticide, as an analyte. Compared to the others, MnO2-s/e-Ag exhibited the most remarkable SERS enhancement. Thanks to its large surface area and ability to accept/donate the electrons of the semiconductor, MnO2-s acted as a bridge to improve the charge transfer efficiency from e-Ag to TCZ. In addition, the MnO2 content of the nanocomposites was also considered to optimize the SERS sensing performance. With the optimal MnO2 content of 25 wt%, MnO2-s/e-Ag could achieve the best SERS performance, allowing the detection of TCZ at concentrations down to 6 × 10-12 M in standard solutions and 10-11 M in real rice samples.

7.
Langmuir ; 37(41): 12059-12070, 2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34617771

RESUMEN

MoS2-GO composites were fabricated by an ultrasonication method at room temperature. Raman spectra, emission scanning electron microscopy (SEM), and transmission electron microscopy (TEM) images were used to study the structural characteristics, morphologies, and sizes of the synthesized materials. An MoS2-GO/SPE (screen-printed electrode) was prepared by a facile dropping method and acted as an effective electrochemical sensor toward clenbuterol (CLB) and 4-nitrophenol (4-NP) detection. Based on the obtained results, the influence of analyte molecular structure on the adsorption ability and electronic interoperability between the targeted analyte and electrode surface were investigated in detail and discussed as well, through some electrochemical kinetic parameters (electron/proton-transfer number, electron transfer rate constant (ks), charge transfer coefficient, and adsorption capacity (Γ)). In particular, it should be stressed that 4-NP molecules possess a simple molecular structure with many positive effects (electronic, conjugation, and small steric effects) and flexible functional groups, resulting in fast electron transport/charge diffusion and effective adsorption process as well as strong interactions with the electrode surface. Therefore, 4-NP molecules have been facilitated better in electrochemical reactions at the electrode surface and electrode-electrolyte interfaces, leading to improved current response and electrochemical sensing performance, compared with those of CLB.


Asunto(s)
Técnicas Electroquímicas , Molibdeno , Electrodos , Microscopía Electrónica de Transmisión , Estructura Molecular
8.
ScientificWorldJournal ; 2021: 6650303, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33976587

RESUMEN

Evidence of health service use and access across different target groups is essential for policy development, health promotion, and promotion of equity in healthcare. This study aims to look at ethnic variations in health service use and access among residents in mountainous areas of Vietnam. A cross-sectional descriptive study was conducted on 321 adults from two mountainous communes in Bac Kan province. Healthcare service use and access were evaluated by using a structured questionnaire. Zero-inflated Poisson regression was used to examine the ethnic variations in the healthcare service use and access. Of 321 mountainous residents, 63.6% used health services in the previous 12 months, of which 24.9% respondents used inpatient services and 47.9% used outpatient services. The number of outpatient medical services used by the Tay participant was higher than that of the Kinh and other ethnic groups (p < 0.05). Multivariate regression results showed that compared to Kinh people, Tay people had a higher number of outpatient service use (Coef. = 0.25, p=0.04), while people in other ethnicities had a lower number of service use (Coef. = -0.64, p=0.01). Meanwhile, no difference was found among groups regarding the number of inpatient service use (p > 0.05). This study showed the ethnic differences in outpatient use of health services among communities living in the northern mountainous setting of Vietnam.


Asunto(s)
Etnicidad/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios Transversales , Escolaridad , Femenino , Geografía , Estado de Salud , Humanos , Masculino , Estado Civil , Persona de Mediana Edad , Distribución de Poisson , Encuestas y Cuestionarios , Vietnam
9.
AIDS Behav ; 24(8): 2347-2354, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31970581

RESUMEN

Stigma poses considerable challenges to the mental health of people living with HIV who use drugs (PLHWUD). In this study, we explored factors related to different types of stigma (perceived and internalized) attached to layered stigmatizing characters (HIV and drug use) and their mental health influences on PLHWUD. The study used baseline data of an ongoing randomized controlled trial among 241 PLHWUD recruited between March and December 2018 in Vietnam. A structural equation model was used to assess the relationships among different types and layers of stigma and mental health status. Both perceived and internalized drug-related stigma measures were significantly higher than their corresponding HIV-related stigma. HIV-related stigma was negatively associated with mental health status; however, we did not find a significant relationship between drug-related stigma and mental health. Tailored intervention strategies in consideration of types and layers of stigma are needed to address stigma-related challenges faced by PLHWUD.


Asunto(s)
Infecciones por VIH , Trastornos Relacionados con Sustancias , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Salud Mental , Persona de Mediana Edad , Estigma Social , Trastornos Relacionados con Sustancias/epidemiología , Vietnam/epidemiología
10.
Adv Exp Med Biol ; 1292: 37-63, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30838542

RESUMEN

BACKGROUND: The sequence polymorphism of mitochondrial DNA (mtDNA) hypervariable segment 1 (HV1) and hypervariable segment 2 (HV2) is studied and applied to genetic diversity and human evolution assessment, forensic genetics, consanguinity determination, and mitochondrial disease diagnosis. METHODS: The study identified the variations of HV1 and HV2 of 517 unrelated Vietnamese individuals in Kinh, Muong, Cham, and Khmer ethnic. We performed sequencing of two hypervariable segments of mitochondrial DNA: HV1 and HV2. RESULTS: Fifty haplogroups were identified in which F1a haplogroup frequency was highest at 15.7%, followed by B5a (10.8%), M (8.9%), and M7b1 (7.7%). The most frequently encountered SNPs in this study were A263G (100%), A73G (99.6%), 315insC (96%), 309insC (56%), C16223T (41%), and T16189C (39%). The genetic diversity was calculated at 99.83%, and the probability of random match of two individuals sharing the same mtDNA haplotype was 0.37%. CONCLUSION: We have assessed the genetic polymorphism of mtDNA HV1 and HV2 of 517 Kinh, Muong, Cham, and Khmer ethnic samples. The result will help in better understanding of Vietnamese's mitochondrial genome diversity and aid in population as well as forensic science.


Asunto(s)
Pueblo Asiatico/genética , ADN Mitocondrial/genética , Etnicidad/genética , Polimorfismo Genético , Haplotipos , Humanos , Análisis de Secuencia de ADN , Vietnam
11.
J Nanosci Nanotechnol ; 18(8): 5591-5599, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29458614

RESUMEN

In this work, a functional graphene oxide-iron oxide-silver (GO-Fe3O4-Ag) ternary nanocomposite was synthesized by using one-pot hydrothermal treatments of mixture solutions of silver nitrate (AgNO3), ferrous chloride tetrahydrate (FeCl2 4H2O), polyvinylpyrrolidone (PVP), graphene oxide (GO), and ammonium hydroxide solution (NH4OH). The systematic effects of synthesis conditions on the microstructure and formation of binary and ternary composite systems were studied. Importantly, high-crystalline GO-Fe3O4-Ag ternary nanomaterials with average sizes of Fe3O4 particles ~16 nm and of Ag particles ~20 nm were obtained at optimized conditions (125 °C, 2.5 mM of AgNO3 and 5 mL of NH4OH). Magnetic analysis indicated that the saturated magnetization value of Fe3O4-Ag binary composite sample (~73.1 emu/g) was improved as compared with pure Fe3O4 nanoparticles (~60.6 emu/g), while this of GO-Fe3O4-Ag ternary composite sample was about 57.3 emu/g. With exhibited advantages of low-cost, high purity and short synthesis time, the hydrothermal-synthesized GO-Fe3O4-Ag ternary nanocomposite can be a promising candidate for advanced environmental catalyst and biomedical applications.

12.
Pharm Biol ; 55(1): 787-791, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28103726

RESUMEN

CONTEXT: Hedyotis pilulifera (Pit.) T.N. Ninh (Rubiaceae) has been used in Vietnamese ethnomedicine; the methanol extract exhibited antibacterial activity in our preliminary screening. OBJECTIVES: In this study, compounds from H. pilulifera were isolated and their antibacterial activity in vitro was evaluated. MATERIALS AND METHODS: The aerial parts of H. pilulifera (1.4 kg) were extracted with MeOH, suspended in water and ethyl acetate extract was chromatographed on a silica gel column. The structures of isolated compounds were elucidated by the combination analyses of spectroscopy including 1D-, 2D-NMR, HRMS and in comparison with the reported NMR data in the literature. All isolated compounds were evaluated for inhibitory effect using the microdilution method toward Staphylococcus aureus, Bacillus subtilis and Mycobacterium smegmatis, and MIC values were determined. RESULTS: Twenty compounds were isolated, including five triterpenoids, two steroids, two aromatic compounds, three fatty acids, one quinone derivative, one lignan glycoside, one ceramide and five glycolipids. Among these, oleanolic acid showed significant antibacterial activity against M. smegmatis with the MIC value of 2.5 µg/mL. Remarkably, rotungenic acid showed strong activity against S. aureus, B. subtilis, M. smegmatis with MIC values of 2.5, 2.5 and 1.25 µg/mL, respectively. Rotundic acid exhibited significant antibacterial activity against B. subtilis with the MIC value of 5 µg/mL. To the best of our knowledge, the antibacterial activity of rotungenic acid, stigmast-4-ene-3,6-dione and (2S,3S,4R,2'R)-2-(2'-hydroxytetracosanoylamino) octadecane-1,3,4-triol was reported for the first time. CONCLUSIONS: Oleanolic acid, rotungenic acid, and rotundic acid were considered to be useful for developing new antimicrobial therapeutic agents for human.


Asunto(s)
Antibacterianos/química , Antibacterianos/aislamiento & purificación , Hedyotis/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Extractos Vegetales/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología
13.
Nanotechnology ; 27(15): 155707, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26933975

RESUMEN

A promising nanocomposite material composed of MnFe2O4 (MFO) nanoparticles of ∼17 nm diameter deposited onto graphene oxide (GO) nanosheets was successfully synthesized using a modified co-precipitation method. X-ray diffraction, transmission electron microscopy, and selected area electron diffraction confirmed the quality of the synthesized samples. Fourier transform infrared measurements and analysis evidenced that the MFO nanoparticles were attached to the GO surface. Magnetic measurements and analysis using the modified Langevin model evidenced the superparamagnetic characteristic of both the bare MFO nanoparticles and the MFO-GO nanocomposite at room temperature, and an appreciable increase of the effective anisotropy for the MFO-GO sample. Magnetic hyperthermia experiments performed by both calorimetric and ac magnetometry methods indicated that relative to the bare MFO nanoparticles, the heating efficiency of the MFO-GO nanocomposite was similar at low ac fields (0-300 Oe) but became progressively larger with increasing ac fields (>300 Oe). This has been related to the higher effective anisotropy of the MFO-GO nanocomposite. In comparison with the bare MFO nanoparticles, a smaller reduction in the heating efficiency was observed in the MFO-GO composites when embedded in agar or when their concentration was increased, indicating that the GO helped minimize the physical rotation and aggregation of the MFO nanoparticles. These findings can be of practical importance in exploiting this type of nanocomposite for advanced hyperthermia. Magnetoimpedance-based biodetection studies also indicated that the MFO-GO nanocomposite could be used as a promising magnetic biomarker in biosensing applications.

14.
J Nanosci Nanotechnol ; 16(6): 5902-12, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27427651

RESUMEN

In recent years, outbreaks of infectious diseases caused by pathogenic micro-organisms pose a serious threat to public health. In this work, Fe3O4-Ag hybrid nanoparticles were synthesized by simple chemistry method and these prepared nanoparticles were used to investigate their antibacterial properties and mechanism against methicilline-resistant Staphylococcus aureus (MRSA) pathogen. The formation of dimer-like nanostructure of Fe3O4-Ag hybrid NPs was confirmed by X-ray diffraction and High-resolution Transmission Electron Microscopy. Our biological analysis revealed that the Fe3O4-Ag hybrid NPs showed more noticeable bactericidal activity than that of plain Fe3O4 NPs and Ag-NPs. We suggest that the enhancement in bactericidal activity of Fe3O4-Ag hybrid NPs might be likely from main factors such as: (i) enhanced surface area property of hybrid nanoparticles; (ii) the high catalytic activity of Ag-NPs with good dispersion and aggregation stability due to the iron oxide magnetic carrier, and (iii) large direct physical contacts between the bacterial cell membrane and the hybrid nanoparticles. The superparamagnetic hybrid nanoparticles of iron oxide magnetic nanoparticles decorated with silver nanoparticles can be a potential candidate to effectively treat infectious MRSA pathogen with recyclable capability, targeted bactericidal delivery and minimum release into environment.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Nanopartículas de Magnetita/química , Nanopartículas del Metal/química , Viabilidad Microbiana/efectos de los fármacos , Nanotecnología , Plata/química , Procesos Fotoquímicos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología
15.
Lancet Oncol ; 16(6): 619-29, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25981818

RESUMEN

BACKGROUND: In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. METHODS: In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [<18 months vs ≥18 months]) to receive oral regorafenib 160 mg once daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. FINDINGS: Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3-12·2), overall survival was significantly better with regorafenib than it was with placebo (hazard ratio 0·55, 95% CI 0·40-0·77, one-sided p=0·00016; median overall survival 8·8 months [95% CI 7·3-9·8] in the regorafenib group vs 6·3 months [4·8-7·6] in the placebo group). Drug-related adverse events occurred in 132 (97%) of 136 regorafenib recipients and 31 (46%) of 68 placebo recipients. The most frequent grade 3 or higher regorafenib-related adverse events were hand-foot skin reaction (22 [16%] of 136 patients in the regorafenib group vs none in the placebo group), hypertension (15 [11%] vs two [3%] of 68 patients in the placebo group), hyperbilirubinaemia (nine [7%] vs one [1%]), hypophosphataemia (nine [7%] vs none), alanine aminotransferase concentration increases (nine [7%] vs none), aspartate aminotransferase concentration increases (eight [6%] vs none), lipase concentration increases (six [4%] vs one [1%]), and maculopapular rash (six [4%] vs none). Drug-related serious adverse events occurred in 12 (9%) patients in the regorafenib group and three (4%) in the placebo group. INTERPRETATION: This phase 3 trial is the second to show an overall survival benefit with regorafenib compared with placebo in patients with treatment-refractory metastatic colorectal cancer, substantiating the role of regorafenib as an important treatment option for patients whose disease has progressed after standard treatments. In this trial, preceding standard treatments did not necessarily include targeted treatments. Adverse events were generally consistent with the known safety profile of regorafenib in this setting. FUNDING: Bayer HealthCare Pharmaceuticals.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos de Fenilurea/administración & dosificación , Piridinas/administración & dosificación , Anciano , Pueblo Asiatico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos de Fenilurea/efectos adversos , Piridinas/efectos adversos , Resultado del Tratamiento
16.
Bioorg Med Chem Lett ; 25(16): 3246-50, 2015 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-26077495

RESUMEN

A new polyoxygenated cyclohexene, (-)-3-O-debenzoylzeylenone (1), and a new megastigmane glycoside, grandionoside A (2), were isolated from the aerial parts of Uvaria grandiflora collected in Vietnam, together with ten known compounds including polyoxygenated cyclohexenes (3-6), a triterpenoid (7), an alkaloid (8), a long chain alcohol (9), hexenyl glycopyranoside (10), and saponins (11-12). Their chemical structures were elucidated by a combination of extensive NMR spectroscopy with X-ray crystallographic analysis for 1, and chemical conversion for 2. Compound 1 exhibited significant cytotoxicity against the LU-1 and SK-Mel-2 cell lines with IC50 values of 4.68 and 3.63 µM, respectively. Remarkably, the cytotoxicity of 12 against the LU-1, KB, Hep-G2, MKN-7, and SW-480 cell lines was comparable to that of ellipticine, the positive control, with IC50 values ranging from 1.24 to 1.60 µM.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Ciclohexanonas/aislamiento & purificación , Ciclohexanonas/farmacología , Ciclohexenos/aislamiento & purificación , Ciclohexenos/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Norisoprenoides/aislamiento & purificación , Norisoprenoides/farmacología , Uvaria/química , Secuencia de Carbohidratos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Elipticinas/farmacología , Glicósidos , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Datos de Secuencia Molecular , Difracción de Rayos X
17.
J Biomater Sci Polym Ed ; 35(1): 109-125, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37843984

RESUMEN

Similar to most anthraquinone compounds, the pharmacological properties of emodin are limited because of its low water solubility. In this study, the formulation of chitosan and emodin (EMD/CS) was prepared by a bottom-up method with precipitation and sonication steps in order to enhance the solubility of emodin. Thanks to the interactions of oxygen-and nitrogen-containing groups in chitosan with emodin molecules, the solubility of emodin in the formulation was remarkably increased to 0.5 mg/mL. The EMD/CS particles were well dispersed and distributed in a range of sub-micrometer with an average particle size of 342 nm. The EMD/CS formulation exhibited synergic antibacterial activity of emodin and chitosan, against drug-resistant bacterial strains, namely Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli O157:H7 (E. coli O157:H7). When the compositions of emodin and chitosan increased, the antibacterial effectiveness of the EMD/CS formulation increased. The EMD/CS formulation with compositions of 0.5 mg/mL of emodin and 9.0 mg/mL of chitosan could significantly inhibit the proliferation of E. coli O157:H7. Meanwhile, the EMD/CS formulation with a lower concentration of emodin (0.4 mg/mL) and chitosan (7.2 mg/mL) could cause an extermination effect on MRSA. The enhanced solubility of EMD/CS formulation suggests that this formulation can be a potential candidate for the treatment of infectious diseases caused by drug-resistant bacterial pathogens.


Asunto(s)
Quitosano , Emodina , Escherichia coli O157 , Staphylococcus aureus Resistente a Meticilina , Quitosano/farmacología , Emodina/farmacología , Solubilidad , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana
18.
Nat Prod Res ; : 1-6, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613430

RESUMEN

This study is focused on investigating the chemical composition and bioactive properties of the essential oil extracted from Psychotria asiatica L., a plant species known for its medicinal properties. Utilising gas chromatography-mass spectrometry (GC-MS) analysis, the essential oil from P. asiatica was found to contain 53 distinct constituents. Major compounds identified include (E)-citral (20.6%), 10-epi-γ-eudesmol (15.9%), (Z)-citral (10.5%), geraniol (7.4%), α-cadinol (6.7%), 7-epi-α-eudesmol (4.4%), linalool (3.7%), and α-muurolol (3.4%). The essential oil did not exhibit antioxidant activity, as indicated by an IC50 value of > 100 µg/mL, whereas the positive control L-Ascorbic acid had an IC50 of 7.37 ± 0.27 µg/mL in the DPPH model. Assessment of its anti-inflammatory potential revealed an inhibitory effect on NO production, with an IC50 value of 29.08 ± 1.54 µg/mL in Lipopolysaccharide-induced RAW264.7 macrophage cells. Furthermore, the essential oil demonstrated significant cytotoxicity against the SK-LU-1 cancer cell line, with an IC50 value of 39.75 ± 1.79 µg/mL according to the sulforhodamine B (SRB) assay.

19.
RSC Adv ; 14(14): 9975-9984, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38528918

RESUMEN

Silver nanoparticles (AgNPs) have been regarded as a highly promising substrate for surface-enhanced Raman scattering (SERS) sensors. In this study, we focused on the electrochemical synthesis method by developing three kinds of AgNPs using three different electrolytes: citrate (e-Ag-C), oleic acid (e-Ag-O) and fish mint (Houttuynia cordata Thunb.) extract (e-Ag-bio). The as-prepared AgNPs were characterized and then employed as SERS substrates to detect the pesticide thiram. The obtained results show that e-Ag-O exhibits the best SERS performance. The effect of the coating agent was explained by chemical and electromagnetic enhancements (CM and EM). Although thiram could absorb onto e-Ag-C at the highest level, allowing its Raman signal to be best enhanced via the CM, the smallest interparticle distance of e-Ag-O could have resulted in the largest improvement in the EM. Using e-Ag-O to develop SERS-based sensors for thiram, we obtain the impressive detection limit of 1.04 × 10-10 M in standard samples and 10-9 M in tea leaves. The linear ranges are from 10-4 M to 10-7 M and from 10-7 M to 10-9 M, covering the maximum residue levels for plant commodities established by the United States Environment Protection Agency and European Food Safety Authority (2-13 ppm ∼7.7 × 10-6 M to 5 × 10-5 M).

20.
Sci Rep ; 14(1): 322, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172521

RESUMEN

Citrus fruit yield is essential for market stability, as it allows businesses to plan for production and distribution. However, yield estimation is a complex and time-consuming process that often requires a large number of field samples to ensure representativeness. To address this challenge, we investigated the optimal altitude for unmanned aerial vehicle (UAV) imaging to estimate the yield of Citrus unshiu fruit. We captured images from five different altitudes (30 m, 50 m, 70 m, 90 m, and 110 m), and determined that a resolution of approximately 5 pixels/cm is necessary for reliable estimation of fruit size based on the average diameter of C. unshiu fruit (46.7 mm). Additionally, we found that histogram equalization of the images improved fruit count estimation compared to using untreated images. At the images from 30 m height, the normal image estimates fruit numbers as 73, 55, and 88. However, the histogram equalized image estimates 88, 71, 105. The actual number of fruits is 124, 88, and 141. Using a Vegetation Index such as IPCA showed a similar estimation value to histogram equalization, but I1 estimation represents a gap to actual yields. Our results provide a valuable database for future UAV field investigations of citrus fruit yield. Using flying platforms like UAVs can provide a step towards adopting this sort of model spanning ever greater regions at a cheap cost, with this system generating accurate results in this manner.


Asunto(s)
Citrus , Dispositivos Aéreos No Tripulados , Diagnóstico por Imagen , Frutas , Altitud
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