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1.
Glob Chang Biol ; 30(1): e16995, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37916642

RESUMO

Wildfires are increasing in frequency, intensity, and extent globally due to climate change and they can alter forest composition, structure, and function. The destruction and subsequent regrowth of young vegetation can modify the ecosystem evapotranspiration and downstream water availability. However, the response of forest recovery on hydrology is not well known with even the sign of evapotranspiration and water yield changes following forest fires being uncertain across the globe. Here, we quantify the effects of forest regrowth after catastrophic wildfires on evapotranspiration and runoff in the world's tallest angiosperm forest (Eucalyptus regnans) in Australia. We combine eddy covariance measurements including pre- and post-fire periods, mechanistic ecohydrological modeling and then extend the analysis spatially to multiple fires in eucalypt-dominated forests in south-eastern Australia by utilizing remote sensing. We find a fast recovery of evapotranspiration which reaches and exceeds pre-fire values within 2 years after the bushfire, a result confirmed by eddy covariance data, remote sensing, and modeling. Such a fast evapotranspiration recovery is likely generalizable to tall eucalypt forests in south-eastern Australia as shown by remote sensing. Once climate variability is discounted, ecohydrological modeling shows evapotranspiration rates from the recovering forest which reach peak values of +20% evapotranspiration 3 years post-fire. As a result, modeled runoff decreases substantially. Contrary to previous research, we find that the increase in modeled evapotranspiration is largely caused by the aerodynamic effects of a much shorter forest height leading to higher surface temperature, higher humidity gradients and therefore increased transpiration. However, increases in evapotranspiration as well as decreases in runoff caused by the young forest are constrained by energy and water limitations. Our result of an increase in evapotranspiration due to aerodynamic warming in a shorter forest after wildfires could occur in many parts of the world experiencing forest disturbances.


Assuntos
Incêndios , Incêndios Florestais , Ecossistema , Água , Florestas
2.
Opt Express ; 31(25): 41428-41444, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087542

RESUMO

This work proposes an optimization algorithm in optical design based on the concepts of ergodic and stochastic processes in statistical mechanics. In mixed-variable optimization problems, pseudo-random number and discrete-to-continuous variable conversion dramatically increase the speed at which the system solves for the optimal solution. Pseudo-random numbers are mainly applied in two important steps in the optimization algorithm: determining the combination of glasses involved and the order in which the successive glass parameters are replaced by real glasses. After two series of stochastic processes, the merit function value decreases rapidly along the steepest descent path, and thus the optical system approaches the optimal solution within a very short duration of time. By using the method proposed in this paper, a plan apochromatic objective with a long working distance was optimized, and finally, a high-quality optical system was obtained.

3.
Glob Chang Biol ; 29(11): 3085-3097, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36876991

RESUMO

Tree planting is a prevalent strategy to mitigate urban heat. Tree cooling efficiency (TCE), defined as the temperature reduction for a 1% tree cover increase, plays an important role in urban climate as it regulates the capacity of trees to alter the surface energy and water budget. However, the spatial variation and more importantly, temporal heterogeneity of TCE in global cities are not fully explored. Here, we used Landsat-based tree cover and land surface temperature (LST) to compare TCEs at a reference air temperature and tree cover level across 806 global cities and to explore their potential drivers with a boosted regression tree (BRT) machine learning model. From the results, we found that TCE is spatially regulated by not only leaf area index (LAI) but climate variables and anthropogenic factors especially city albedo, without a specific variable dominating the others. However, such spatial difference is attenuated by the decrease of TCE with tree cover, most pronounced in midlatitude cities. During the period 2000-2015, more than 90% of analyzed cities showed an increasing trend in TCE, which is likely explained by a combined result of the increase in LAI, intensified solar radiation due to decreased aerosol content, increase in urban vapor pressure deficit (VPD) and decrease of city albedo. Concurrently, significant urban afforestation occurred across many cities showing a global city-scale mean tree cover increase of 5.3 ± 3.8% from 2000 to 2015. Over the growing season, such increases combined with an increasing TCE were estimated to on average yield a midday surface cooling of 1.5 ± 1.3°C in tree-covered urban areas. These results are offering new insights into the use of urban afforestation as an adaptation to global warming and urban planners may leverage them to provide more cooling benefits if trees are primarily planted for this purpose.


Assuntos
Clima , Temperatura Alta , Temperatura , Cidades , Estações do Ano , Monitoramento Ambiental/métodos
4.
Biomacromolecules ; 22(2): 330-339, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33305948

RESUMO

Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.


Assuntos
Incrustação Biológica , Polímeros , Incrustação Biológica/prevenção & controle , Interações Hidrofóbicas e Hidrofílicas , Polimerização , Sulfóxidos , Propriedades de Superfície
5.
Angew Chem Int Ed Engl ; 59(12): 4729-4735, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-31951063

RESUMO

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water-soluble homo-fluoropolymers are reported with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19 F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self-reporting fluoropolymers show outstanding imaging sensitivity and remarkable hydrophilicity, and as such are a new class of low-fouling polymer for bioconjugation and in vivo tracking.


Assuntos
Polietilenoglicóis/síntese química , Sulfóxidos/química , Flúor/química , Halogenação , Interações Hidrofóbicas e Hidrofílicas , Imageamento por Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Polietilenoglicóis/química , Solubilidade , Água/química
6.
Small ; 15(17): e1900212, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30941900

RESUMO

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.


Assuntos
Antineoplásicos/farmacologia , Desoxiglucose/farmacologia , Estresse do Retículo Endoplasmático , Luz , Microambiente Tumoral/efeitos dos fármacos , Apoptose , Terapia Combinada , Humanos , Cinética , Células MCF-7 , Nanomedicina , Necrose , Fagocitose , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio
7.
Biomacromolecules ; 20(4): 1545-1554, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30768256

RESUMO

Drug delivery carriers are now widely established because they can increase the therapeutic efficiency of drugs. In general, the aim in this field is to create effective carriers that have large amounts of drugs loaded to minimize drug carrier material that needs to be disposed of. However, there has been little attention so far in the literature on the effect of the amount of loaded drugs on the biological activity. In this paper, we are trying to answer the question of how the drug-loading content will affect the in vitro activity. We use two methods to load paclitaxel (PTX) into micelles based on the glycopolymer, poly(1- O-methacryloyl-ß-d-fructopyranose)- block-poly(methyl methacylate) (Poly(1- O-MAFru)35- b-PMMA145). In the one-step method, the drug is loaded into the particles during the self-assembly process. However, the size of nanoparticle increased with the PTX content from 26 to 50 nm, triggering enhanced cellular uptake by MCF-7 and MDA-MB-231, which was caused by changes in diameter size and not by changes in drug concentration. To keep the nanoparticle size constant, preformed micelles were loaded with PTX (two-step process). The increasing amount of loaded drug led to decreased cellular uptake and reduced cytotoxicity by the cancer cell lines. Small-angle neutron scattering and small-angle X-ray scattering, supported by transmission electron microscopy and dynamic light scattering, exposed the PTX location in the shell. This caused shrinkage of the shell and lower levels of shell hydration, resulting in lower cellular uptake and lower cytotoxicity. Upon the release of PTX, the shell regained its original level of hydration. We could show that because drug loading causes morphology changes, in either the shell or the size, it is impossible to separate the parameters that will influence the biological activity. Although the same phenomenon may not apply to every drug delivery system, it needs to be considered that except for the well-known parameters that affect cell uptake-size, shape, surface chemistry, type of nanoparticle, and presence of bioactive groups-the amount of loaded drugs might change the physicochemical parameters of the nanoparticle and thus the in vitro and potentially the in vivo outcomes.


Assuntos
Portadores de Fármacos , Glicoconjugados , Micelas , Nanopartículas/química , Paclitaxel , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Glicoconjugados/síntese química , Glicoconjugados/química , Glicoconjugados/farmacocinética , Glicoconjugados/farmacologia , Humanos , Células MCF-7 , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Tamanho da Partícula
8.
Biomacromolecules ; 19(2): 481-489, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29316394

RESUMO

The introduction of a strategy toward polymer/nanodiamond hybrids with high polymer grafting density and accessible polymer structural characterization is of critical importance for nanodiamonds' surface modification and bioagent attachment for their biomedical application. Here, we report a glycopolymer/nanodiamond hybrid drug delivery system, which was prepared by grafting amonafide-conjugated glycopolymers onto the surface of nanodiamonds via oxime ligation. Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-ß-d-fructopyranose)-b-poly(3-vinylbenzaldehyde-co-methyl methacrylate), featuring pendant aldehyde groups, is prepared via RAFT polymerization. The anticancer drug amonafide is conjugated to the polymer chains via imine chemistry, resulting in acid-degradable imine linkages. The obtained amonafide-conjugated glycopolymers are subsequently grafted onto the surface of aminooxy-functionalized nanodiamonds via oxime ligation. The molecular weight of the conjugated polymers is characterized by size-exclusion chromatography (SEC), while the successful conjugation and corresponding grafting density is assessed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric aanalysis (TGA). Our results indicate that the mass percentage of amonafide in the polymer chains is around 17% and the surface density of polymer chains is 0.24 molecules/nm2. The prepared drug delivery system has a hydrodynamic size around 380 nm with low PDI (0.3) and can effectively deliver amonafide into breast cancer cell and significantly inhibit the cancer cell viability. In 2D cell culture models, the IC50 values of ND-Polymer-AMF delivery system (7.19 µM for MCF-7; 4.92 µM for MDA-MB-231) are lower than those of free amonafide (11.23 µM for MCF-7; 13.98 µM for MDA-MB-231). An inhibited cell viability of nanodiamonds/polymer delivery system is also observed in 3D spheroids' models, suggesting that polymer-diamonds hybrid materials can be promising platforms for breast cancer therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Materiais Revestidos Biocompatíveis , Sistemas de Liberação de Medicamentos/métodos , Frutose , Nanodiamantes , Naftalimidas , Adenina , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Feminino , Frutose/química , Frutose/farmacologia , Humanos , Células MCF-7 , Nanodiamantes/química , Nanodiamantes/uso terapêutico , Naftalimidas/química , Naftalimidas/farmacologia , Organofosfonatos
9.
Macromol Rapid Commun ; 39(19): e1800172, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29676024

RESUMO

Multihydroxy-anthraquinone derivatives [i.e., 1,2,4-trihydroxyanthraquinone (124-THAQ), 1,2,7-trihydroxyanthraquinone (127-THAQ), and 1,2,5,8-tetrahydroxyanthraquinone (1258-THAQ)] can interact with various additives [e.g., iodonium salt, tertiary amine, N-vinylcarbazole, and 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine] under household green LED irradiation to generate active species (cations and radicals). The relevant photochemical mechanism is investigated using quantum chemistry, fluorescence, cyclic voltammetry, laser flash photolysis, steady state photolysis, and electron spin resonance spin-trapping techniques. Furthermore, the multihydroxy-anthraquinone derivative-based photoinitiating systems are capable of initiating cationic photopolymerization of epoxides or divinyl ethers under green LED, and the relevant photoinitiation ability is consistent with the photochemical reactivity (i.e., 124-THAQ-based photoinitiating system exhibits highest reactivity and photoinitiation ability). More interestingly, multihydroxy-anthraquinone derivative-based photoinitiating systems can initiate free radical crosslinking or controlled (i.e., reversible addition-fragmentation chain transfer) photopolymerization of methacrylates under green LED. It reveals that multihydroxy-anthraquinone derivatives can be used as versatile photoinitiators for various types of photopolymerization reactions.


Assuntos
Antraquinonas/química , Radicais Livres/química , Luz , Processos Fotoquímicos
10.
Biomacromolecules ; 17(9): 2946-55, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27442218

RESUMO

Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-ß-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 µg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Frutose/química , Nanodiamantes/administração & dosagem , Polímeros/química , Antibióticos Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Liberação Controlada de Fármacos , Feminino , Humanos , Nanodiamantes/química , Polímeros/administração & dosagem , Esferoides Celulares/efeitos dos fármacos , Células Tumorais Cultivadas
11.
Macromol Rapid Commun ; 37(24): 2023-2029, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27813236

RESUMO

Carboxyl end-functionalized poly[poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)] and its block copolymer with gemcitabine substituted poly(N-hydroxysuccinimide methacrylate) [PGem-block-P(PEGMEMA)] are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. Then, two polymers are grafted onto the surface of amine-functionalized nanodiamonds to obtain [P(PEGMEMA)]-grafted nanodiamonds (ND-PEG) and [PGem-block-P(PEGMEMA)]-grafted nanodiamonds (ND-PF). Gemcitabine is physically absorbed to ND-PEG to produce ND-PEG (Gem). Two polymer-grafted nanodiamonds (i.e., with physically absorbed gemcitabine ND-PEG (Gem) and with chemically conjugated gemcitabine ND-PF) are characterized using attenuated total reflectance infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis. The drug release, cytotoxicity (to seed human pancreatic carcinoma AsPC-1 cells), and cellular uptake of ND-PEG (Gem) and ND-PF are also investigated.


Assuntos
Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Nanodiamantes/química , Neoplasias Pancreáticas/tratamento farmacológico , Polietilenoglicóis/química , Linhagem Celular Tumoral , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desoxicitidina/farmacologia , Humanos , Neoplasias Pancreáticas/metabolismo , Gencitabina , Neoplasias Pancreáticas
12.
Biomacromolecules ; 16(7): 1948-57, 2015 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-26057004

RESUMO

Inspired by upregulated levels of fucosylated proteins on the surfaces of multiple types of cancer cells, micelles carrying ß-l-fucose and ß-d-glucose were prepared. A range of block copolymers were synthesized by reacting a mixture of 2-azidoethyl ß-l-fucopyranoside (FucEtN3) and 2-azideoethyl ß-d-glucopyranoside (GlcEtN3) with poly(propargyl methacrylate)-block-poly(n-butyl acrylate) (PPMA-b-PBA) using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Five block copolymers were obtained ranging from 100 mol % fucose to 100% glucose functionalization. The resulting micelles had hydrodynamic diameters of around 30 nm. In this work, we show that fucosylated micelles reveal an increased uptake by pancreatic, lung, and ovarian carcinoma cell lines, whereas the uptake by the healthy cell lines (CHO) is negligible. This finding suggests that these micelles can be used for targeted drug delivery toward cancer cells.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Polietilenoglicóis/síntese química , Polietilenoglicóis/farmacocinética , Animais , Células CHO , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Reação de Cicloadição , Sistemas de Liberação de Medicamentos , Fucose/química , Humanos , Micelas , Estrutura Molecular , Tamanho da Partícula
13.
Macromol Rapid Commun ; 36(18): 1675-80, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26174706

RESUMO

N-vinylcarbazole (NVK) can act simultaneously as a photoinitiator, an additive, and a mono-mer (photoinaddimer) of photopolymerization upon exposure to the household ultraviolet (UV) light-emitting diode (LED) bulb (emission wavelength centered at 392 nm). Even though the light absorption spectrum of NVK exhibits weak overlapping with the emission spectrum of the UV LED, the active species (i.e., radicals and cations) can be generated from the interaction between NVK and diphenyliodonium hexafluorophosphate (Iod) under irradiation of this LED device, which is investigated by steady state photolysis and electron spin resonance spin-trapping methods. Interestingly, the generated radicals and cations from the NVK/Iod system demonstrate high efficiency to initiate the free radical photopolymerization of (meth)acrylates and the cationic photopolymerization of epoxide and divinyl ether under the UV LED irradiation, and the one-step simultaneous catonic/radical photopolymerization of expoxide/acrylate blend can lead to the formation of tack free polyacrylate/polyether-based interpenetrated polymer network film within 10 min even when the polymerization process is exposed to the atmosphere highlighting the high efficiency of the system to reduce the oxygen inhibition effect. More interestingly, NVK/Iod system can also initiate the photopolymerization of NVK under the UV LED irradiation to produce polyvinylcarbazole, and NVK acts as both a photoinitiator and a monomer in the system.


Assuntos
Radicais Livres/química , Fotoquímica/métodos , Polímeros/química , Polimerização
14.
Biochem Biophys Rep ; 37: 101645, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38304575

RESUMO

Chronic pain usually lasts over three months and commonly occurs in chronic diseases (cancer, arthritis, and diabetes), injuries (herniated discs, torn ligaments), and many major pain disorders (neuropathic pain, fibromyalgia, chronic headaches). Unfortunately, there is currently a lack of effective treatments to help people with chronic pain to achieve complete relief. Therefore,it is particularly important to understand the mechanism of chronic pain and find new therapeutic targets. The exchange protein directly activated by cyclic adenosine monophosphate(cAMP) (EPAC) has been recognized for its functions in nerve regeneration, stimulating insulin release, controlling vascular pressure, and controlling other metabolic activities. In recent years, many studies have found that the subtype of EPAC, EPAC1 is involved in the regulation of neuroinflammation and plays a crucial role in the regulation of pain, which is expected to become a new therapeutic target for chronic pain. This article reviews the major contributions of EPAC1 in chronic pain.

15.
Ambio ; 53(2): 324-338, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37819442

RESUMO

Private sector plays an increasingly vital role in nature conservation globally. This study explores the concept of political embeddedness, which suggests that governments and environmental nongovernmental organizations (ENGOs) can leverage each other's strengths to achieve both formal and informal goals. Using the case of Laohegou Nature Reserve in China, this study illustrated how the complementary advantages of the government and ENGOs form the foundation of a land trust reserve. Within the case, the study found that power and interest balance between the government and ENGOs during project implementation supported their formal cooperation in nature conservation. This study proposed a political perspective to elaborate power and interest in the formal and informal dimensions of nature conservation public-private partnership (PPP) project. Moreover, it noted that a balance of power between the government and ENGOs is essential in building partnership networks with inclusive interests.


Assuntos
Conservação dos Recursos Naturais , Parcerias Público-Privadas , Organizações , Governo , China
16.
Cytojournal ; 21: 28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39391210

RESUMO

Objective: Studies have shown that chemokines can stimulate the migration and activation of microglia to cause chronic post-surgical pain (CPSP). However, the involvement of C-X-C motif chemokine receptor 2 (CXCR2) as a new chemotactic factor in regulating CPSP and its underlying mechanism remains unclear. This study is to investigate the role of CXCR2 in the development of CPSP and reveal the underlying mechanism. Material and Methods: A rat model of skin/muscle incision and retraction was established, and treated with or without SB225002 (a selective inhibitor of CXCR2). In addition, the primary microglia cells induced by lipopolysaccharide were applied as an in vitro model for CPSP and treated individually with si-negative control (NC), si-CXCR2, si-CXCR2+Interleukin (IL)-6 (an agonist of the janus kinase (JAK)/signal transducers and activators of transcription (STAT)3 signaling pathway), si-CXCR2+IL-6+si-NC, or si-CXCR2+IL-6+si-exchange protein 1 directly activated by cAMP (EPAC1). Results: Results from the database analysis showed that CXCR2 and JAK/STAT3 signaling pathway-related genes, including JAK1, STAT3, and EPAC1, were mainly involved in the development of CPSP. Inhibition of CXCR2 expression not only inhibited the reduction of foot pain threshold in CPSP models but also led to a decreased expression of CXCR2 and the phosphorylation levels of JAK and STAT3 in both animal and cell models. Furthermore, inhibition of EPAC1 expression can hinder the regulatory function of CXCR2. Conclusion: This study indicated that the high expression of CXCR2 activates the JAK1/STAT3 signaling pathway, enhances EPAC1 activation in microglial cells, and exacerbates CPSP.

17.
Microbiol Res ; 289: 127918, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39342747

RESUMO

Ketoconazole is a classical antifungal drug commonly used in the clinic. With the increased use of ketoconazole in recent years, an increasing number of drug-resistant strains have emerged during clinical treatment. It is well known that fungi acquire drug resistance in multiple ways, while the molecular mechanisms underlying ketoconazole resistance remain for comprehensive exploration. In this study, we found that the expression of the small plasma membrane protein-encoding gene PMP3 was significantly down-regulated in several clinically isolated ketoconazole-resistant strains, indicating the relationship between PMP3 expression and ketoconazole resistance. By knocking out the PMP3, we found that the absence of the Pmp3 resulted in a significant increase in resistance of Candida albicans to ketoconazole, which was also confirmed in a systemic infection model in mice. We further demonstrated that various physiological properties, such as cell membrane fluidity, plasma membrane potential, permeability and ergosterol distribution were altered in the pmp3Δ/Δ mutant, which is associated with the enhanced cellular resistance to ketoconazole. In addition, overexpression rather than deletion of PMP3 alters the hyphal development and biofilm formation capacity in C. albicans. This study reveals the contribution of Pmp3 to alteration of drug resistance in fungal pathogens, which may guide the development of novel antifungal strategies.

18.
Nanoscale ; 16(25): 12095-12106, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38819371

RESUMO

Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p-toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.


Assuntos
Retículo Endoplasmático , Imunoterapia , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Camundongos , Feminino , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Nanopartículas/química , Retículo Endoplasmático/metabolismo , Humanos , Heme Oxigenase-1/metabolismo , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Prata/farmacologia , Porfirinas/química , Porfirinas/farmacologia
19.
Biomater Sci ; 12(11): 2978-2992, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38683548

RESUMO

Inhalable nanomedicines are increasingly being developed to optimise the pharmaceutical treatment of respiratory diseases. Large lipid-based nanosystems at the forefront of the inhalable nanomedicines development pipeline, though, have a number of limitations. The objective of this study was, therefore, to investigate the utility of novel small lipidated sulfoxide polymers based on poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA) as inhalable drug delivery platforms with tuneable membrane permeability imparted by differential albumin binding kinetics. Linear PMSEA (5 kDa) was used as a hydrophilic polymer backbone with excellent anti-fouling and stealth properties compared to poly(ethylene glycol). Terminal lipids comprising single (1C2, 1C12) or double (2C12) chain diglycerides were installed to provide differing affinities for albumin and, by extension, albumin trafficking pathways in the lungs. Albumin binding kinetics, cytotoxicity, lung mucus penetration and cellular uptake and permeability through key cellular barriers in the lungs were examined in vitro. The polymers showed good mucus penetration and no cytotoxicity over 24 h at up to 1 mg ml-1. While 1C2-showed no interaction with albumin, 1C12-PMSEA and 2C12-PMSEA bound albumin with KD values of approximately 76 and 10 µM, respectively. Despite binding to albumin, 2C12-PMSEA showed reduced cell uptake and membrane permeability compared to the smaller polymers and the presence of albumin had little effect on cell uptake and membrane permeability. While PMSEA strongly shielded these lipids from albumin, the data suggest that there is scope to tune the lipid component of these systems to control membrane permeability and cellular interactions in the lungs to tailor drug disposition in the lungs.


Assuntos
Lipídeos , Humanos , Animais , Lipídeos/química , Polímeros/química , Administração por Inalação , Sistemas de Liberação de Medicamentos , Albuminas/química , Albuminas/metabolismo , Pulmão/metabolismo , Ligação Proteica , Portadores de Fármacos/química
20.
Sci Total Environ ; 905: 167203, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730031

RESUMO

To mitigate climate change, the utilization of wind energy has rapidly expanded over the last two decades. However, when producing clean electricity, wind farms (WFs) may in turn alter the local climate by interfering in land surface-atmosphere interactions. Currently, China and the United States have the highest wind energy capacities globally. Thus, quantitatively analyzing the impacts of WFs on land surface temperature (LST) between the two countries is valuable to deeply understand the climate impact of WF. In this study, we use the moderate-resolution imaging spectroradiometer (MODIS) time series from 2001 to 2018 to reveal the impacts of 186 WFs (76 in China and 110 in the US) on local LSTs. The remote sensing observations reveal that WFs generally lead to warming impacts in both countries, with stronger effects in the US compared to China. During the daytime, WFs in the US exhibit a significant warming effect of 0.08 °C (p < 0.05), while the impact in China is nonsignificant (0.06 °C, p = 0.15). At night, the warming impacts in the US are approximately 1.7 times greater than in China (0.19 °C vs. 0.11 °C). Differences in the LST impacts between the two countries are primarily driven by cropland WFs, which cause more significant cooling effects in China (-0.34 °C in the daytime and - 0.19 °C at night, p < 0.01) compared to the US. However, these differences are not significant for grassland WFs. Moreover, the impacts of WFs on croplands' LSTs are strongly correlated with their evapotranspiration impacts, likely influenced by irrigation practices. In addition to evapotranspiration, a machine learning model suggests that background climate and terrain factors can alter the LST impacts. Our observations in the two largest WF-deployment countries provide a new understanding of the climate impacts of WFs, which should be considered in the fields of wind and renewable energy deployment.

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