Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Study on the role of nano antibacterial materials in orthodontics (a review)

Abstract Nanoparticles (NPs) are insoluble particles with a diameter of fewer than 100 nanometers. Two main methods have been utilized in orthodontic therapy to avoid microbial adherence or enamel demineralization. Certain NPs are included in orthodontic adhesives or acrylic resins (fluorohydroxyapatite, fluorapatite, hydroxyapatite, SiO2, TiO2, silver, nanofillers), and NPs (i.e., a thin layer of nitrogen-doped TiO2 on the bracket surfaces) are coated on the surfaces of orthodontic equipment. Although using NPs in orthodontics may open up modern facilities, prior research looked at antibacterial or physical characteristics for a limited period of time, ranging from one day to several weeks, and the limits of in vitro studies must be understood. The long-term effectiveness of nanotechnology-based orthodontic materials has not yet been conclusively confirmed and needs further study, as well as potential safety concerns (toxic effects) associated with NP size.

Resumo Nanopartículas (NPs) são partículas insolúveis com diâmetro inferior a 100 nanômetros. Dois métodos principais têm sido utilizados na terapia ortodôntica para evitar a aderência microbiana ou a desmineralização do esmalte: NPs são incluídas em adesivos ortodônticos ou resinas acrílicas (fluoro-hidroxiapatita, fluorapatita, hidroxiapatita, SiO2, TiO2, prata, nanopreenchimentos) e NPs são revestidas nas superfícies de equipamentos ortodônticos, ou seja, uma camada fina de TiO2 dopado com nitrogênio nas superfícies do braquete. Embora o uso de NPs em ortodontia possa tornar acessível modernos recursos, pesquisas anteriores analisaram as características antibacterianas ou físicas por um período limitado de tempo, variando de 24 horas a várias semanas, por isso devem ser compreendidos os limites dos estudos in vitro. A eficácia de longo prazo de materiais ortodônticos com base em nanotecnologia ainda não foi confirmada de forma conclusiva, o que exige mais estudos, bem como potenciais preocupações de segurança (efeitos tóxicos) associadas ao tamanho da NP.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Study on the role of nano antibacterial materials in orthodontics (a review) / Estudo sobre o papel dos materiais nanoantibacterianos na ortodontia

Nanoparticles (NPs) are insoluble particles with a diameter of fewer than 100 nanometers. Two main methods have been utilized in orthodontic therapy to avoid microbial adherence or enamel demineralization. Certain NPs are included in orthodontic adhesives or acrylic resins (fluorohydroxyapatite, fluorapatite, hydroxyapatite, SiO2, TiO2, silver, nanofillers), and NPs (i.e., a thin layer of nitrogen-doped TiO2 on the bracket surfaces) are coated on the surfaces of orthodontic equipment. Although using NPs in orthodontics may open up modern facilities, prior research looked at antibacterial or physical characteristics for a limited period of time, ranging from one day to several weeks, and the limits of in vitro studies must be understood. The long-term effectiveness of nanotechnology-based orthodontic materials has not yet been conclusively confirmed and needs further study, as well as potential safety concerns (toxic effects) associated with NP size.

Nanopartículas (NPs) são partículas insolúveis com diâmetro inferior a 100 nanômetros. Dois métodos principais têm sido utilizados na terapia ortodôntica para evitar a aderência microbiana ou a desmineralização do esmalte: NPs são incluídas em adesivos ortodônticos ou resinas acrílicas (fluoro-hidroxiapatita, fluorapatita, hidroxiapatita, SiO2, TiO2, prata, nanopreenchimentos) e NPs são revestidas nas superfícies de equipamentos ortodônticos, ou seja, uma camada fina de TiO2 dopado com nitrogênio nas superfícies do braquete. Embora o uso de NPs em ortodontia possa tornar acessível modernos recursos, pesquisas anteriores analisaram as características antibacterianas ou físicas por um período limitado de tempo, variando de 24 horas a várias semanas, por isso devem ser compreendidos os limites dos estudos in vitro. A eficácia de longo prazo de materiais ortodônticos com base em nanotecnologia ainda não foi confirmada de forma conclusiva, o que exige mais estudos, bem como potenciais preocupações de segurança (efeitos tóxicos) associadas ao tamanho da NP.

Niobium oxyhydroxide as a bioactive agent and reinforcement to a high-viscosity bulk-fill resin composite

Abstract Objective The present in vitro study incorporated niobium oxyhydroxide fillers into an experimental high-viscosity bulk-fill resin composite to improve its mechanical performance and provide it a bioactive potential. Methodology Scanning electron microscopy synthesized and characterized 0.5% niobium oxyhydroxide fillers, demonstrating a homogeneous morphology that represented a reinforcement for the feature. Fillers were weighed, gradually added to the experimental resin composite, and homogenized for one minute, forming three groups: BF (experimental high-viscosity bulk-fill resin composite; control), BF0.5 (experimental high-viscosity bulk-fill resin composite modified with 0.5% niobium oxyhydroxide fillers), and BFC (commercial bulk-fill resin composite Beautifil Bulk U, Shofu; positive control). In total, 10 specimens/groups (8 × 2 × 2 mm) underwent flexural strength (FS) tests in a universal testing machine (Instron) (500N). Resin composites were also assessed for Knoop hardness (KH), depth of cure (DoC), degree of conversion (DC), elastic modulus (E), and degree of color change (ΔE). The bioactive potential of the developed resin composite was evaluated after immersing the specimens into a simulated body fluid in vitro solution and assessing them using a Fourier-transformed infrared spectroscope with an attenuated total reflectance accessory. One-way ANOVA, followed by the Tukey's test (p<0.05), determined FS, DC, KH, and ΔE. For DoC, ANOVA was performed, which demonstrated no significant difference between groups (p<0.05). Conclusions The high-viscosity bulk-fill resin composite with 0.5% niobium oxyhydroxide fillers showed promising outcomes as reinforcement agents and performed well for bioactive potential, although less predictable than the commercial resin composite with Giomer technology.

Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

Abstract We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studies.

Influence of the addition of nanohydroxyapatite to scaffolds on proliferation and differentiation of human mesenchymal stem cells: a systematic review of in vitro studies

One of the main challenges of tissue engineering in dentistry is to replace bone and dental tissues with strategies or techniques that simulate physiological tissue repair conditions. This systematic review of in vitro studies aimed to evaluate the influence of the addition of nanohydroxyapatite (NHap) to scaffolds on cell proliferation and osteogenic and odontogenic differentiation of human mesenchymal stem cells. In vitro studies on human stem cells that proliferated and differentiated into odontogenic and osteogenic cells in scaffolds containing NHap were included in this study. Searches in PubMed/MEDLINE, Scopus, Web of Science, OpenGrey, ProQuest, and Cochrane Library electronic databases were performed. The total of 333 articles was found across all databases. After reading and analyzing titles and abstracts, 8 articles were selected for full reading and extraction of qualitative data. Results showed that despite the large variability in scaffold composition, NHap-containing scaffolds promoted high rates of cell proliferation, increased alkaline phosphatase (ALP) activity during short culture periods, and induced differentiation, as evidenced by the high expression of genes involved in osteogenesis and odontogenesis. However, further studies with greater standardization regarding NHap concentration, type of scaffolds, and evaluation period are needed to observe possible interference of these criteria in the action of NHap on the proliferation and differentiation of human stem cells.

Surface Analysis of a Universal Resin Composite and Effect of Preheating on its Physicochemical Properties

Abstract This study was aimed at analyzing the surface properties of a universal resin composite and evaluating the effect of preheating on its physicochemical properties. Two commercial resin composites were used under two conditions: Filtek Universal Restorative (UR); UR preheated (URH); Filtek Supreme (FS) and FS preheated (FSH). The film thickness (FT) test (n = 10) was done using two glass slabs under compression. Flexural strength (FLS) and modulus (FLM) were evaluated using a three-point flexion test (n = 10). Polymerization shrinkage stress (PSS) was evaluated in a universal testing machine (n = 5). Gap width (GW) between composite and mold was measured in internally polished metallic molds (n = 10). The degree of conversion (DC) was evaluated by Fourier Transform Infrared spectroscopy (n = 3). The morphology of the filler particles was checked by scanning electron microscope (SEM) and EDX analysis. Surface gloss (SG) and surface roughness (SR) were evaluated before and after mechanical brushing (n = 10). The outcomes were submitted to 2-way ANOVA and Tukey's test (α = 0.05). Lower mean values of FT were observed for the preheated groups when compared to the non-preheated groups. URH and FSH showed higher mean values of FLS and FLM when compared with UR and FS. No differences were observed between groups in the PSS test. The GW was higher for the UR and FS groups when compared with URH and FSH. The DC was higher for preheated resin composites when compared to the non-preheated groups. The SR of the UR composite was higher than the FS after mechanical brushing, while the SG was higher for the FS groups. In conclusion, the universal resin composite tested generally presented similar physicochemical properties compared with the nanofilled resin composite and either similar or slightly inferior surface properties. The preheating improved or maintained all properties evaluated.

Resumo Neste estudo avaliou-se propriedades físico-químicas e de superfície de um compósito universal pré-aquecido e comparado a um compósito convencional. Foram utilizados dois compósitos comerciais: Filtek Universal Restorative (UR); UR pré-aquecido (URH); Filtek Supreme (FS) e FS pré-aquecido (FSH). O teste de espessura de película (EP) (n = 10) foi feito usando duas placas de vidro sob compressão. A resistência à flexão (RF) e o módulo flexural (MF) foram avaliados por meio do teste de flexão de três pontos (n = 10). A tensão de contração de polimerização (TCP) foi avaliada em uma máquina de teste universal (n = 8). A largura da fenda (LF) entre o compósito e o molde foi medida em moldes metálicos polidos internamente (n = 10). O grau de conversão (GC) foi avaliado por espectroscopia de infravermelho com transformada de Fourier (n = 3). A morfologia das partículas de carga foi observada em microscopia eletrônica de varredura (MEV) e sua composição em EDX. Brilho superficial (BS) e rugosidade superficial (RS) foram avaliados antes e após escovação mecânica (n=10). Os resultados foram submetidos à ANOVA 2-fatores e as médias comparadas pelo teste de Tukey (α = 0,05). Menores valores médios de EP foram observados para os grupos pré-aquecidos quando comparados aos grupos não pré-aquecidos. URH e FSH apresentaram maiores valores médios de RF e MF quando comparados com UR e FS. Não foram observadas diferenças entre os grupos no teste TCP. A LF foi maior para os grupos UR e FS quando comparados com URH e FSH. O GC foi maior para os compósitos pré-aquecidos quando comparados aos não pré-aquecidos. A RS do compósito UR foi maior que o FS após a escovação mecânica, enquanto o BS foi maior para os grupos FS. Em conclusão, o compósito universal testado geralmente apresentou propriedades físico-químicas semelhantes em comparação ao compósito nanoparticulado e propriedades de superfície semelhantes ou ligeiramente inferiores. O pré-aquecimento melhorou ou manteve todas as propriedades avaliadas.

Applications of Nanoparticles in Agriculture Improvement- A Review

The field of nanotechnology is quickly developing and emerging since it has enormous potential for various human uses. With their unique, size-based physical and chemical attributes, nonmaterials generated and engineered through nanotechnology have many applications in biomedicine and agriculture. Theranostics is a branch of nanomedicine that uses small, highly surface-area nanoparticles to diagnose and treat diseases. Nanomaterials have a wide range of uses in agriculture, from fertilizers that improve soil nutrient uptake by plants to nano pesticides that control a variety of pests, including fungi, phytophagous insects, and weeds, increasing food output. Agriculture and food security are intimately connected, and many researchers are interested. Agriculture production depends on many difficulties due to the severe effects of climate change, water problems and changing the distribution of insect pests. Meanwhile, it faces tremendous challenges in maintaining food security for a massive population amid declining resources. Research is actively exploring the use of nonmaterial in agriculture due to their tremendous promise. Despite their good qualities, nonmaterial present risks to the environment and human health, necessitating risk assessment studies. Green nonmaterial synthesis may lessen the usage of toxic agrochemicals that pollute the environment and enter biological systems, providing an environmentally safe, environmentally friendly, and economically advantageous option. In this critical evaluation, nanoparticles are used in agriculture.

Las nanoestructuras de ZnO y sus aplicaciones como sensor de gas H2S / The ZnO nanostructures and their applications as a H2S gas sensor

RESUMEN Existe un interés global en la detección de gases tóxicos, para la protección del medio ambiente y los seres humanos. Se han desarrollado múltiples estudios enfocados en el uso de sensores de gases basados en óxidos metálicos, como es el óxido de zinc (ZnO), el cual presenta propiedades electrónicas específicas como sensor de gases por ser un semiconductor tipo n y bajo costo de producción. El objetivo de este trabajo fue analizar el uso de nanoestructuras de ZnO, para la fabricación de sensores del gas ácido sulfhídrico (H2S), así como las técnicas de obtención más comunes de dichas estructuras. Las características de las nanoestructuras de óxido de zinc (NE´s-ZnO) varían por efecto del método de obtención, generando diferentes morfologías y tamaño, que impactan en la capacidad de detección de gas (0.5 ppm a 600 ppm) y en el rango de temperatura que se requiere. Los avances en la generación de diversas NE´s-ZnO facilitarán la posibilidad de generar sensores que puedan ser utilizados en detectores portátiles y operen a temperatura ambiente, lo cual es un reto actual.

ABSTRACT There is a global interest in the detection of toxic gases for the protection of the environment and human beings, using low-cost and easy-to-use sensors. Multiple studies have focused on the use of gas detectors based on metal oxides, such as zinc oxide (ZnO), which has specific electronic properties as a gas detector because it is an n-type semiconductor and it has a low production cost. The objective of this work was to analyze the use of ZnO nanostructures for the manufacturing of hydrogen sulfide (H2S) gas sensors, as well as the most common techniques for obtaining these structures. The characteristics of zinc oxide nanostructures (NE´s-ZnO) vary due to the effect of the obtaining method, generating different morphologies and sizes, which impacts gas detection performance (0.5 ppm up to 600 ppm) and in the temperature range that is required. Advances in the design of various NE's-ZnO will have the possibility of generating sensors that can be used in portable detectors and operate at room temperature, which is a current challenge.

La solidez de la investigación homeopática fundamental / The strength of fundamental homeopathic research

La investigación fundamental en homeopatía ha avanzado considerablemente en los últimos 20 años: desde estudios exploratorios con animales y plantas hasta la caracterización de los efectos sistémicos de los medicamentos homeopáticos y estudios in vitro con sistemas celulares aislados para evaluar los cambios en los mecanismos de adaptación celular y señalización intracelular frente a tratamientos homeopáticos variables. El número de artículos publicados a lo largo del tiempo ha permitido realizar varias revisiones sistemáticas. Recientemente, la demostración de que los medicamentos homeopáticos podrían modificar las funciones celulares a través de mecanismos epigenéticos (metilación y desmetilación de ADN) preparó el camino para un campo de investigación completamente nuevo. En paralelo, el descubrimiento de las nanopartículas y propiedades físicas específicas de las diluciones homeopáticas ha arrojado luz hacia un campo antes poco conocido, dado que se consideraba que las diluciones homeopáticas no consistían más que de agua. Así las cosas, los retos para el futuro conciernen a la demostración, o no, de la interrelación entre ambos fenómenos.

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

Effects and mechanism of Curcumin solid lipid nanoparticles loaded with flower-shaped lactose for inhalation on pulmonary inflammation in COPD model mice / 中国药房

OBJECTIVE To investigate the effects and mechanism of curcumin （Cur） solid lipid nanoparticles （SLN） loaded with flower-shaped lactose （Cur-SLN-FL） for lung inhalation on lung inflammation in chronic obstructive pulmonary disease （COPD） model mice. METHODS Firstly， the irritation of Cur-SLN-FL to lung tissue was investigated， and the local safety of inhalation materials was determined. Then， 10 mice were randomly selected and injected with normal saline through the trachea， and the other 50 mice were all injected with porcine trypsin solution （concentration of 33.3 mg/mL， dosage of 1.0 mL/kg） to induce the COPD model. After normal feeding for 28 days， the mice were divided into sham operation group， model group， budesonide group （20 mg/kg）， Cur-SLN-FL high-dose and low-dose groups （100， 50 mg/kg）， with 10 mice in each group. The corresponding drugs were given to each group， once a day， for 14 consecutive days. Twenty-four hours after the last administration， the bronchoalveolar lavage fluid （BALF） of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin （HE） staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 （NLRP3）， caspase-1 and interleukin-1β （IL-1β） in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3， caspase-1 and nuclear factor of kappa B（NF-κB） in lung tissue. RESULTS Cur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group， the total number of white blood cells， neutrophils and eosinophils in BALF of the model group increased significantly， while the number of lymphocytes decreased significantly （P＜0.05）； ciliated columnar epithelium proliferated， thickened and exfoliated in the trachea， mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue；the deposition of collagen fibers in lung tissue increased significantly， the positive expressions of NLRP3， caspase-1 and IL-1β in lung tissue increased significantly， and the expressions of NLRP3， caspase-1 and NF-κB protein in lung tissue all increased significantly （P＜0.05）. After giving Cur-SLN-FL， the above indexes were all improved to certain extent. CONCLUSIONS Cur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice，and its mechanism may be through regulating the NLRP3 signaling pathway， inhibiting the expressions of caspase-1， NF-κB and IL-1β， thus alleviating the process of pulmonary fibrosis in COPD model mice.

Advances in approved nucleic acid drugs and lipid nanoparticle system / 药学学报

Nucleic acids, as a next generation of biotechnology drugs, not only can fundamentally treat diseases, but also own significant platform characteristics in view of technology and production. Therefore, nucleic acid-based drugs have broad clinical applications in biomedical fields. However, nucleic acids are degradable and unstable, and have very low intracellular delivery efficiency in vitro and in vivo, which greatly limits their applications. In recent years, ionizable lipid-based lipid nanoparticles have shown promising application potentials and have been successfully applied to COVID-19 (Coronavirus Disease 2019) vaccines in clinic. Lipid nanoparticles demonstrate high in vivo delivery efficiency and good safety profile due to their unique structural and physicochemical properties, which provides many possibilities for their clinical applications for nucleic acid delivery in the future. This review focused on the characteristics of nucleic acid drugs and their delivery barriers, and discussed the approved nucleic acid drugs to illustrate the key aspects of the success of their delivery carrier system. In addition, problems to be solved in the field were highlighted.

Advances in bioanalysis methods and pharmacokinetics of polymer nanopharmaceuticals / 药学学报

Polymer nanomaterials have been attracted more and more attention because of their advantages such as long circulation, reduced immunogenicity and less side effects, and have become a hot research topic in nanomaterials. However, the number of polymer nanomedicines successfully applied in clinical application is very limited, and the unsatisfactory pharmacokinetic behavior is one of the main reasons for thisresult. After polymer nanoparticles enter the body, they will release free drugs and polymer excipients. Polymer nanoparticles are the loaded drugs and free drugs are the active chemicals for efficacy, while polymer excipients may cause excipient drug interactions. Therefore, the focus of the pharmacokinetics study of polymer nanoparticles should not be only limited to the free drugs themselves, but should also focus on the loaded drugs, free drugs and polymer excipients. The dynamic changes of polymer excipients and their metabolites pose new requirements and challenges for the bioanalysis of polymer nanomedicines. The characteristics and application scope of common analytical methods for detection polymer nanomedicines including chromatographic assay will be discussed in this paper. Moreover, this review will also summarize the absorption, distribution, metabolism and excretion of polymer nanomedicines. We hope this review will provide reference for the pharmacokinetics study, safety and effectiveness evaluation of polymer nanomedicines.

Research progress on drug combination therapy against Candida albicans / 药学实践杂志

Candida albicans is one of the most common species of Candida, which is an important cause of invasive candidiasis in clinic. Due to the frequently use of classical antifungal agents, there are amounts of drug resistant C. albicans being isolated, causing the significantly decreasing of the efficacy of some antifungal agents in clinical treatment. Besides, the use of some compounds in clinic has been limited because of their toxicities. In such a context, drug combination therapy shows great potential on antifungal because of the synergy of different drugs or therapeutic methods that could bring, which could improve the weaknesses of single drug.

Toxicity evaluation of zinc oxide nanoparticles in vitro and in vivo on cornea / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the toxic effects of zinc oxide nanoparticles(ZnO NPs)on cornea by constructing intoxicated model in vivo and in vitro.METHODS:Human corneal epithelial cells(HCEpiC)were cultured in vitro and exposed to different concentrations(0.5, 5, 12.5, 25, 50, 100, 250 μg/mL)of ZnO NPs for 24h. The cell culture medium without nano-solution was used as the blank control group. The viability of the cells was assessed by MTT assay. Three different concentrations(25, 50 and 100 μg/mL)of ZnONPs dispersions were exposed to the conjunctival sac of anesthetized mice three times a day for 7d consecutively. The phosphate buffered saline(PBS)eye group was the PBS control group. Corneal morphology was observed on 1, 3, 5 and 7d, and the eyes were removed on 8d for various laboratory examinations, including corneal pathological changes and expression levels of inflammatory factors(TNF-α, IL-6).RESULTS:After treatment of HCEpiC cells with different concentrations of ZnO NPs for 24h, the MTT results showed that Zno NPs cause damage to cells at 0.5 μg/mL, and the cell survival rate was about 80%(P&#x003C;0.05). Half of the cells were killed at a dose of 5 μg/mL, the damaging effect on cells in the concentration range of 5～250 μg/mL was concentration-dependent(P&#x003C;0.0001). After 7d of conjunctival capsule spotting in mice, dot-like staining of fluorescein was seen in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups. Localized circular fluorescein stained areas were seen in the corneas of the 100 μg/mL ZnO NPs group. HE staining showed that the corneal epithelial layer, stromal layer thickness and stromal layer immune cell number did not change significantly in the 25 μg/mL and 50 μg/mL ZnO NPs groups(all P&#x003E;0.05), while the corneal epithelial layer thinned, the corneal stromal layer thickened and the stromal layer immune cells increased significantly in the 100 μg/mL ZnO NPs group(all P&#x003C;0.05). Immunohistochemical staining showed that the number of corneal stromal immune cells producing TNF-α and IL-6 and the mean integral optical density(IOD)values of TNF-α and IL-6 were significantly higher in the 100 μg/mL ZnO NPs group than in the PBS control group(P&#x003C;0.05), and the degree of inflammation response was concentration-dependent. Compared with the PBS control group, no significant increase in immune cell count and IOD values in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups(P&#x003E;0.05).CONCLUSION:The toxic damaging effect of ZnO NPs on the cornea was confirmed from both in vitro and in vivo, which provided a theoretical basis for the ocular safety evaluation of ZnO NPs.

The Application and Progress of Carbon Nanoparticles in Colorectal Cancer Surgery / 中山大学学报(医学科学版)

Colorectal cancer is one of the most common cancer types with the highest morbidity and mortality. It is necessary to harvest sufficient lymph nodes to perform an accurate postoperative pathologic assessment. Carbon nanoparticles have been widely used as a new kind of tracer in colorectal cancer due to its lymphotropic property， safety and long effectiveness. Carbon nanoparticles were reported to be able to help locate the primary tumor， trace regional lymph nodes， determine the extent of lymph node excision， reduce surgical difficulty， preserve more intestines， increase the number of postoperative lymph node detection， and reduce the operation time and hospital stay. In this article， the mechanism of carbon nanoparticles will be introduced. The effect in colorectal surgery and further research direction will be reviewed.

Mechanism of rhynchophylline solid lipid nanoparticles inhibiting the proliferation of airway smooth muscle cells in asthmatic model mice / 中国药房

OBJECTIVE To study the inhibitory effect mechanism of rhynchophylline solid lipid nanoparticles （Rhy-SLN） on the proliferation of airway smooth muscle cells （ASMCs） in asthmatic model mice. METHODS Asthma model was prepared by ovalbumin+calmogastrin sensitization. The primary isolation and culture of ASMCs were performed， and morphological observation and identification were also conducted [when α -smooth muscle actin （α -SMA） appeared red and Desmin appeared green in ASMCs， indicating successful cultivation of ASMCs]. The cells were divided into blank group （ASMCs of normal mice）， model group （ASMCs of asthma model mice）， Rhy-SLN group （ASMCs of asthma model mice）， recombinant suppressors of cytokine signaling 1 （SOCS1） overexpression group （ASMCs of asthma model mice transfected with SOCS1 vector）， SOCS1-RNAi group （ASMCs of asthma model mice transfected with SOCS1-RNAi vector） and SB203580 group [p38 mitogen-activated protein kinase （p38 MAPK） inhibitor， ASMCs of asthma model mice]. The cells of each group were added into the corresponding culture medium containing drug （10 μmol/L） or not containing drug for 24 hours. MTT method was used to detect the proliferation of ASMCs in asthmatic mice； Western blot assay was used to detect the protein expressions of α-SMA， interleukin-1β （IL-1β）， SOCS1， p38 MAPK and phosphorylated p38 MAPK （p-p38 MAPK） in ASMCs. RESULTS The primary ASMCs of mice varied in shape and size， presenting irregular， spindle and triangular shapes；α-SMA appeared red and Desmin appeared green， indicating successful cultivation of ASMCs. Compared with model group， ASMCs absorbance values and protein expressions of α -SMA， p38 MAPK， and p-p38 MAPK were reduced significantly in Rhy- SLN group， SOCS1 overexpression group and SB203580 E-mail：wangmeng106@163.com group， while protein expression of SOCS1 （except for group） was increased significantly （P＜0.05）； protein expressions of IL-1β was reduced significantly in ASMCs （P＜ 0.05）. ASMCs absorbance values and protein expressions of α-SMA， SOCS1， p38 MAPK and p-p38 MAPK were increased significantly in SOCS1-RNAi group （P＜0.05）. CONCLUSIONS Rhy-SLN can inhibit the proliferation of ASMCs， the mechanism of which may be associated with overexpression of SOCS1 and inhibiting the protein expressions of IL-1β and p38 MAPK.

Trends in nano-antimicrobial therapy for severe liver disease with infection / 临床肝胆病杂志

Severe liver disease with infection has always been a key and difficult point in clinical treatment. Through continuous exploration of nanomaterials, researchers have found that nanomaterials can achieve targeted antibacterial and immunomodulatory effects due to their special physicochemical properties. With reference to recent articles and advances, this article reviews the possible mechanisms of nano-therapies for severe liver disease with infection from the aspects of targeted antibacterial effect of nanomaterials without antibiotics, targeted antibacterial effect of nano-drug delivery systems, and targeted immunomodulatory therapy, so as to provide new treatment strategies for the prevention and treatment of severe liver disease with infection in clinical practice.

Lipid nanomaterials-based RNA therapy and cancer treatment

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.