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1.
J Nanobiotechnology ; 22(1): 138, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555444

RESUMEN

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aß11 and Tween 80 (Aß11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aß11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Humanos , Tigeciclina/farmacología , Tigeciclina/uso terapéutico , Minociclina/farmacología , Infecciones por Acinetobacter/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Agua
2.
Molecules ; 28(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37687199

RESUMEN

Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.


Asunto(s)
Nanopartículas , Plantas Medicinales , Humanos , Medicina de Hierbas , Disponibilidad Biológica , Extractos Vegetales
3.
Saudi Pharm J ; 31(12): 101845, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38028216

RESUMEN

Objectives: This study aimed to evaluate the efficiency of a 14-year refined management system for the reduction of dispensing errors in a large-scale hospital outpatient pharmacy and to determine the effects of person-related and environment-related factors on the occurrence of dispensing errors. Methods: A retrospective study was performed. Data on dispensing errors, inventory and account management from 2008 to 2021 were collected from the electronic system and evaluated using the direct observation method and the Plan-Do-Check-Act (PDCA) cycle. Results: The consistency of the inventory and accounts increased substantially (from 86.93 % to 99.75 %) with the implementation of the refined management program. From 2008 to 2021, the total number of dispensing errors was reduced by approximately 96.1 %. The number of dispensing errors in quantity and name was reduced by approximately 98.2 % and 95.07 %, respectively. A remarkable reduction in the error rate was achieved (from 0.014 % to 0.00002 %), and the rate of dispensing errors was significantly reduced (0.019 % vs. 0.0003 %, p < 0.001). Across all medication dispensing errors, human-related errors decreased substantially (208 vs. 7, p < 0.05), as did non-human-related errors also (202 vs. 9, p < 0.05). There was a correlation between the occurrence of errors and pharmacists' sex (females generally made fewer errors than males), age (more errors were made by those aged 31-40 years), and working years (more errors were made by those with more than 11 years of work experience) from 2016 to 2021. The technicians improved during this procedure. Conclusions: Refined management using the PDCA cycle was helpful in preventing dispensing errors and improving medication safety for patients.

4.
Environ Sci Technol ; 55(9): 6076-6086, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33856783

RESUMEN

Despite the popularity of smartphones worldwide, persistent toxic substances (PTSs) in protective cases of mobile phones (PCMPs) and their health risks via direct skin contact have been ignored. This study investigated PTSs in PCMPs made in China with different materials and sales territory and their potential harm to human health. Polybrominated diphenyl ethers (PBDEs, 6.40 ng/g), new brominated flame retardants (NBFRs, 144 ng/g), organophosphate esters (OPEs, 10.1 µg/g), short-chain chlorinated paraffins (SCCPs, 3.58 µg/g), medium-chain chlorinated paraffins (MCCPs, 3.17 µg/g), and heavy metals (HMs, 72.3 µg/g) were detected. It was found that the different concentrations and compositions depend on the material, region, and use. Moreover, the raw materials used to fabricate PCMPs are of variable quality and may include recycled plastic waste. There are no standard quality specifications for PCMPs, and different materials have different properties, including specific surface area and adsorption ability. The risk assessment performed by Monte Carlo simulations indicated that the PTSs evaluated pose no health risks to the general population and may have adverse effects on individual high-exposure populations. According to the results of this work, it is suggested that more stringent global specifications for the selection of raw materials should be established, including the content and structural characteristics of PTSs, limitations on the use of additives in the production process, and the handling after use.


Asunto(s)
Teléfono Celular , Retardadores de Llama , China , Monitoreo del Ambiente , Retardadores de Llama/análisis , Éteres Difenilos Halogenados/análisis , Humanos
5.
Small ; 16(45): e2005039, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33078579

RESUMEN

The current state of chemotherapy is far from satisfaction, restricted by the inefficient drug delivery and the off-target toxicity. Prodrug nanoassemblies are emerging as efficient platforms for chemotherapy. Herein, three docetaxel dimeric prodrugs are designed using diselenide bond, disulfide bond, or dicarbide bond as linkages. Interestingly, diselenide bond-bridged dimeric prodrug can self-assemble into stable nanoparticles with impressive high drug loading (≈70%, w/w). Compared with disulfide bond and dicarbide bond, diselenide bond greatly facilitates the self-assembly of dimeric prodrug, and then improves the colloidal stability, blood circulation time, and antitumor efficacy of prodrug nanoassemblies. Furthermore, the redox-sensitive diselenide bond can specifically respond to the overexpressed reactive oxygen species and glutathione in tumor cells, leading to tumor-specific drug release. Therefore, diselenide bond bridged prodrug nanoassemblies exhibit discriminating cytotoxicity between tumor cells and normal cells, significantly alleviating the systemic toxicity of docetaxel. The present work gains in-depth insight into the impact of diselenide bond on the dimeric prodrug nanoassemblies, and provides promising strategies for the rational design of the high efficiency-low toxicity chemotherapeutical nanomedicines.


Asunto(s)
Antineoplásicos , Nanopartículas , Profármacos , Línea Celular Tumoral , Docetaxel , Liberación de Fármacos , Nanomedicina
6.
Pharmacol Res ; 157: 104796, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32278048

RESUMEN

Hypertension is an important cardiovascular disease, which need long-term medication. Thus, oral drug delivery system is a preferred route for hypertension patients due to the convenience and compliance. Val-Leu-Pro-Val-Pro (VLPVP, VP5) is an angiotensin converting enzyme inhibitory peptide with antihypertensive effects. However, the oral peptide delivery is faced with obstacles, such as gastric acid, enzyme degradation and intestine barriers. Herein, we developed a controlled release system consisting of a PLGA core encapsulated with VP5 and a folate-decorated lipid shell (FA-VP5-LNPs) for the oral delivery of antihypertensive peptide. The results found that FA-VP5-LNPs exhibited high stability and possessed a controlled release behavior. Besides, FA-VP5-LNPs improved the cellular uptake both in Caco-2 and HT29 cells and enhanced in situ intestinal absorption in SD rats. The in vivo bioavailability study showed a superior oral absorption of FA-VP5-LNPs, and the AUC0-72 h of FA-VP5-LNPs was 30.71-fold higher than that of free VP5. The pharmacodynamics study exhibited that FA-VP5-LNPs maintained strong antihypertensive effect for six days compared with free VP5, which may reduce the frequency of administration and improve patient compliance. In addition, the nano-formulations showed no toxicity to cells and tissues. These promising results suggested that FA-VP5-LNPs could overcome the intestinal barrier and provide a potential strategy for enhancing peptide delivery and improve the antihypertensive effects.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Portadores de Fármacos , Ácido Fólico/metabolismo , Hipertensión/prevención & control , Lípidos/química , Nanopartículas , Oligopéptidos/administración & dosificación , Administración Oral , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Animales , Antihipertensivos/química , Antihipertensivos/farmacocinética , Células CACO-2 , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Ácido Fólico/química , Células HT29 , Humanos , Hipertensión/fisiopatología , Absorción Intestinal , Masculino , Oligopéptidos/química , Oligopéptidos/farmacocinética , Ratas Endogámicas SHR , Ratas Sprague-Dawley
7.
Harm Reduct J ; 17(1): 65, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-32948187

RESUMEN

BACKGROUND: Electronic cigarettes (e-cigarettes) have been characterised as significantly less harmful than cigarettes by many health agencies and regulators globally. In this study, we examined to what extent perceived relative harms of e-cigarettes compared to cigarettes have changed in the USA. METHODS: We analysed the data from the longitudinal and nationally representative, Population Assessment of Tobacco and Health Study to assess the relative perceived harm of e-cigarettes amongst US adults between 2013 and 2016. RESULTS: The proportion of US adults who correctly perceived e-cigarettes as less harmful than cigarettes decreased each year from 41.1% (CI 40.1-42.1%) in 2013-2014, 31.5% (CI 30.8-32.2%) in 2014-2015 and 25.3% (CI 24.6-26.0%) in 2015-2016. Concurrently, the proportion of US adults who perceived e-cigarettes as equally, or more, harmful than cigarettes increased from 53.7% (CI 52.3-55.1%), 64.9% (CI 63.6-66.2%) to 72.7% (CI 71.5-73.9%) respectively. The proportion of US adults who held negative relative harm perceptions of e-cigarettes increased regardless of current smoking or vaping status by 24.6% and 29.6% respectively within 3 years. In Wave 3, the proportion of current smokers who perceived the relative harm of e-cigarettes as less harmful was lower at 29.3% (CI 28.2-30.4%) compared to current e-cigarette users at 43.5% (CI 40.3-46.7%). Former smokers who used e-cigarettes and believed that they were equally, or more, harmful than cigarettes in 2014-2015 had significantly higher rates of smoking relapse in the following year, 29% and 37% (p < 2.2e-16), respectively, compared to those with positive relative harm perceptions who reported relapse rates of 19%. CONCLUSIONS: In this study, the proportion of US adults who incorrectly perceived e-cigarettes as equal to, or more, harmful than cigarettes increased steadily regardless of smoking or vaping status. Current adult smokers appear to be poorly informed about the relative risks of e-cigarettes yet have potentially the most to gain from transitioning to these products. The findings of this study emphasise the urgent need to accurately communicate the reduced relative risk of e-cigarettes compared to continued cigarette smoking and clearly differentiate absolute and relative harms. Further research is required to elucidate why the relative harm of e-cigarettes is misunderstood and continues to deteriorate.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Reducción del Daño , Productos de Tabaco , Vapeo , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Percepción , Salud Pública , Fumar/epidemiología , Nicotiana , Adulto Joven
8.
Sensors (Basel) ; 20(18)2020 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-32932621

RESUMEN

Here we propose a novel high Q ultra-narrow-band filter in the optical regime. Multiple high Q resonances are achieved in ultra-thin metallic nanoslit arrays on stacked low index-high index dielectric (LID-HID) substrate. Based on the cooperative effect of suppressed modes and transmission modes, the high spectral resolution of transmission peaks is obtained. The number and Q factor of transmission peaks can be freely manipulated by a simple combination of the stacked LID-HID. It is demonstrated that the linewidths of the transmission peaks can be reduced down to the extreme limit of 1 nm and the Q factor is up to 700 by optimizing the structure parameter of the three-layer LID-HID. The results provide a theoretical basis to design a multi-band nanophotonic device with a high Q factor and have potential applications in the next generation of high-resolution plasmonic biosensing and filtering.

9.
Acta Chim Slov ; 63(4): 891-989, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-28004103

RESUMEN

Four metal complexes based on quinoline carboxylate ligand from 2-(pyridin-4-yl)quinoline-4-carboxylic acid (HL), [ML2(H2O)2] · 2H2On (M = MnII, 1; M = CoII, 2; M = CdII, 3) and [Ag2L2(H2O)2] · 3H2On (4) have been synthesized under hydrothermal conditions. Their structures were determined by elemental analyses, IR spectra, and further characterized by single-crystal X-ray diffraction analysis. Complexes 1-3 feature a 1D chain structure which is further linked together to construct the 3D supramolecular network through hydrogen bonds. Complex 4 exhibits a 3D configuration. The fluorescent behavior and antibacterial activities of these compounds have been investigated.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Metales/química , Quinolinas/química , Quinolinas/farmacología , Antibacterianos/síntesis química , Cristalografía por Rayos X , Enlace de Hidrógeno , Luminiscencia , Estructura Molecular , Espectrofotometría Infrarroja
10.
Water Res ; 256: 121577, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38593605

RESUMEN

Nanoplastics (NPs) in wastewaters may present a potential threat to biological nitrogen removal in constructed wetlands (CWs). Iron ions are pivotal in microbially mediated nitrogen metabolism, however, explicit evidence demonstrating the impact of NPs on nitrogen removal regulated by iron utilization and metabolism remains unclear. Here, we investigated how NPs disturb intracellular iron homeostasis, consequently interfering with the coupling mechanism between iron utilization and nitrogen metabolism in CWs. Results indicated that microorganisms affected by NPs developed a siderophore-mediated iron acquisition mechanism to compensate for iron loss. This deficiency resulted from NPs internalization limited the activity of the electron transport system and key enzymes involved in nitrogen metabolism. Microbial network analysis further suggested that NPs exposure could potentially trigger destabilization in microbial networks and impair effective microbial communication, and ultimately inhibit nitrogen metabolism. These adverse effects, accompanied by the dominance of Fe3+ over certain electron acceptors engaged in nitrogen metabolism under NPs exposure, were potentially responsible for the observed significant deterioration in nitrogen removal (decreased by 30 %). This study sheds light on the potential impact of NPs on intracellular iron utilization and offers a substantial understanding of the iron-nitrogen coupling mechanisms in CWs.


Asunto(s)
Hierro , Nitrógeno , Humedales , Hierro/metabolismo , Nitrógeno/metabolismo , Eliminación de Residuos Líquidos , Aguas Residuales/química , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad
11.
Int J Biol Macromol ; 278(Pt 3): 134621, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217042

RESUMEN

Herein, rice was subjected to different soaking processes on water distribution of rice grains, starch characteristics, and eating quality of fresh wet rice noodles. Results demonstrated that, when soaked at temperatures between 10 °C and 40 °C for 120 min, rice grains reached saturation in water absorption, and the hardness gradually stabilized. However, the moisture continued to penetrate the interior of rice grains after 120 min, leading to an increase in moisture content, higher water permeability, and enlarged water migration channels. With extended soaking time periods, the content of damaged starch in rice flour considerably decreased. Although the gelatinization temperature of rice starch decreased after soaking, the enthalpy required for gelatinization increased. The relative crystallinity of rice starch demonstrated an increasing trend, followed by a decreasing trend, and reached its highest value of 18.18 % after 60 min of soaking. To summarize, the texture indices of fresh rice noodles demonstrated an increasing trend, although stretching and cooking quality demonstrated a trend of initially increasing and then decreasing with no considerable changes observed between 120 and 240 min of soaking. In summary, moderate soaking treatment can enhance the edible quality of fresh wet rice noodles.


Asunto(s)
Oryza , Almidón , Agua , Oryza/química , Almidón/química , Agua/química , Harina/análisis , Grano Comestible/química , Temperatura , Culinaria , Calidad de los Alimentos , Manipulación de Alimentos/métodos
12.
Pharmaceuticals (Basel) ; 17(5)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38794224

RESUMEN

Tilianin (Til), a flavonoid glycoside, is well-known for its therapeutic promise in treating inflammatory disorders. Its poor water solubility and permeability limit its clinical applicability. In order to overcome these restrictions, an antisolvent precipitation and ultrasonication technique was used to prepare amorphous tilianin nanocrystals (Til NCs). We have adjusted the organic solvents, oil-to-water ratio, stabilizer composition, and ultrasonic power and time by combining single-factor and central composite design (CCD) methodologies. The features of Til NCs were characterized using powder X-ray diffraction (PXRD), scanning calorimetry (DSC), and transmission electron microscopy (TEM). Specifically, the optimized Til NCs were needle-like with a particle size ranging from 90 to 130 nm. PVA (0.3%, w/v) and TPGS (0.08%, w/v) stabilized them well. For at least two months, these Til NCs stayed amorphous and showed an impressive stability at 4 °C and 25 °C. Remarkably, Til NCs dissolved almost 20 times faster in simulated intestinal fluid (SIF) than they did in crude Til. In RAW264.7 cells, Til NCs also showed a better cellular absorption as well as safety and protective qualities. Til NCs were shown to drastically lower reactive oxygen species (ROS), TNF-α, IL-1ß, and IL-6 in anti-inflammatory experiments, while increasing IL-10 levels and encouraging M1 macrophages to adopt the anti-inflammatory M2 phenotype. Our results highlight the potential of amorphous Til NCs as a viable approach to improve Til's anti-inflammatory effectiveness, solubility, and dissolving rate.

13.
Nat Nanotechnol ; 19(9): 1386-1398, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38898135

RESUMEN

The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis. BPNSs can effectively scavenge a broad spectrum of ROS and suppress atherosclerosis-associated pro-inflammatory cytokine production in lesional macrophages. We also demonstrate ROS-responsive, targeted-peptide-modified BPNS-based carriers for the delivery of resolvin D1 (an inflammation-resolving lipid mediator) to lesional macrophages, which further boosts the anti-atherosclerotic efficacy. The targeted nanotherapeutics not only reduce plaque areas but also substantially improve plaque stability in high-fat-diet-fed apolipoprotein E-deficient mice. This study presents a therapeutic strategy against atherosclerosis, and highlights the potential of BPNS-based therapeutics to treat other inflammatory diseases.


Asunto(s)
Aterosclerosis , Ácidos Docosahexaenoicos , Macrófagos , Nanoestructuras , Fósforo , Especies Reactivas de Oxígeno , Animales , Humanos , Masculino , Ratones , Apolipoproteínas E/genética , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Aterosclerosis/patología , Dieta Alta en Grasa/efectos adversos , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/administración & dosificación , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Nanoestructuras/química , Fósforo/química , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/patología , Placa Aterosclerótica/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo
14.
Methods Mol Biol ; 2622: 191-196, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36781761

RESUMEN

Liposomes are usually defined as spherically shaped microscopic vesicles that consist of one or more phospholipid bilayer membranes. They are widely used in drug delivery due to their biocompatibility, biodegradability, and stability. In recent years, a growing body of research shows that folic acid (FA)-modified liposomes can be targeted to deliver therapeutics to tumor and inflammation sites via receptor-mediated endocytosis between FA and folate receptor (FR). Taking this advantage, FA-modified liposomes are usually used in the targeted treatment of cancer, atherosclerosis, and arthrosis. In this chapter, we provided a classical thin-film hydration method to prepare FA-modified liposomes. We expect that our strategies would provide new opportunities for the development of FA-modified liposomes for research and clinical uses.


Asunto(s)
Liposomas , Neoplasias , Humanos , Ácido Fólico , Sistemas de Liberación de Medicamentos , Línea Celular Tumoral
15.
Environ Int ; 171: 107690, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36516673

RESUMEN

Complex interactions between plants and microorganisms form the basis of constructed wetlands (CWs) for pollutant removal. In the rhizosphere, radial oxygen loss (ROL) plays a key role in the activity and abundance of functional microorganisms. However, little has been done to explore how ROL would influence the niche differentiation of microbial communities at different vertical spatial scales. We demonstrate that ROL decreases with depth, promoting an oxidation-reduction rhizosphere microecosystem in CWs. The high level of ROL in the upper layer could support the oxygen supply for aerobic bacteria (Haliangium), facilitating the COD (60%) and NH4+-N (50%) removal, whereas the enrichment of denitrifiers (e.g., Hydrogenophaga and Ralstonia) and methanotrophs (Methanobaterium) in the lower layer could stimulate denitrification. The function prediction results further certified that the abundance of genes catalyzing nitrifying and denitrification processes were significantly enhanced in the upper and bottom layers, respectively, which was attributed to the oxygen concentration gradient in the rhizosphere. This study contributes to further unraveling the rhizosphere effect and enables an improved understanding of the decontamination mechanisms of CWs.


Asunto(s)
Desnitrificación , Microbiota , Humedales , Rizosfera , Oxígeno , Nitrógeno , Eliminación de Residuos Líquidos/métodos
16.
Front Oncol ; 13: 1070343, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923428

RESUMEN

Background: PARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event. Methods: A pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS). Results: 725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib. Conclusion: Recognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.

17.
Environ Int ; 179: 108144, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37586276

RESUMEN

Rhizosphere is a crucial area in comprehending the interaction between plants and microorganisms in constructed wetlands (CWs). However, influence of photoperiod, a key factor that regulates photosynthesis and rhizosphere microbial activity, remains largely unknown. This study investigated the effect of photoperiod (9, 12, 15 h/day) on pollutant removal and underlying mechanisms. Results showed that 15-hour photoperiod treatment exhibited the highest removal efficiencies for COD (87.26%), TN (63.32%), and NO3--N (97.79%). This treatment enhanced photosynthetic pigmentation and root activity, which increased transport of oxygen and soluble organic carbon to rhizosphere, thus promoting microbial nitrification and denitrification. Microbial community analysis revealed a more stable co-occurrence network due to increased complexity and aggregation in the 15-hour photoperiod treatment. Phaselicystis was identified as a key connector, which was responsible for transferring necessary carbon sources, ATP, and electron donors that supported and optimized nitrogen metabolism in the CWs. Structural equation model analysis emphasized the importance of plant-microbe interactions in pollutant removal through increased substance, information, and energy exchange. These findings offer valuable insights for CWs design and operation in various latitudes and rural areas for small-scale decentralized systems.


Asunto(s)
Desnitrificación , Contaminantes Ambientales , Fotoperiodo , Humedales , Rizosfera , Plantas/metabolismo , Carbono , Nitrógeno/análisis , Eliminación de Residuos Líquidos/métodos
18.
Sci Total Environ ; 877: 162883, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36934950

RESUMEN

Combination of constructed wetlands (CWs) and microalgae-based technologies has been proved as effective wastewater treatment option; however, little attention was paid to investigate the optimal combination ways. This study showed that the integrated system (IS) connecting microalgal pond with CWs exhibited improved pollutant-removal efficiencies and preferred carbon reduction effects compared to other alternatives such as coupled system or independent CWs. Microbial analysis demonstrated that core microorganisms (e.g., Acinetobacter and Thermomonas) of the IS were mostly associated with carbon, nitrogen, and energy metabolism. Based on co-occurrence networks, microbial quantity with denitrification function in the IS accounted for 71.01 % of the microorganism related to nitrogen metabolism, which was higher than that of 48.84 % in the independent CWs, indicating that the presence of microalgae in IS played important role in promoting biological denitrification. These findings provide insights into the microbial mechanism and highlights the complementary effects between microalgae and CWs.


Asunto(s)
Carbono , Microalgas , Eliminación de Residuos Líquidos , Desnitrificación , Microalgas/metabolismo , Humedales , Nitrógeno/metabolismo
19.
Bioresour Technol ; 383: 129251, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37268089

RESUMEN

Constructed wetlands (CWs) have emerged as a promising environmentally sustainable technique for wastewater treatment. However, the susceptibility of CWs to disturbances caused by harmful algal blooms (HABs) raises concerns. This study aimed to investigate the impact of HABs on the pollutants' removal performance of CWs and the response of rhizosphere microbial community. Results revealed that CWs possessed an adaptive capacity that enabled them to recover caused by HABs. The rhizosphere was found to stimulate the occurrence of Acinetobacter, which played a critical role to help resist HABs disturbance. This study also observed an increased dissimilatory nitrate reduction metabolic pathway which promoted denitrification and enhanced the nitrogen removal efficiency of CWs. Additionally, the structural equation model further suggested that dissolved oxygen exerted a significant influence on the microbial activities and then affected the pollutants removal performance. Overall, our findings shed light on the mechanism for CW stability maintenance during HABs disturbance.


Asunto(s)
Eliminación de Residuos Líquidos , Humedales , Eliminación de Residuos Líquidos/métodos , Floraciones de Algas Nocivas , Compuestos Orgánicos , Nitrógeno/metabolismo , Desnitrificación
20.
Acta Pharm Sin B ; 13(3): 942-954, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36970209

RESUMEN

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

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