RESUMO
The application of nano fertilizers is one of the hotspots in current agricultural production. In this study, nano silicon materials were mixed with compound fertilizers to make nano silicon fertilizer. The effects of different amounts of nano silicon application on the breaking-resistance strength, lodging-resistance index, lignin accumulation, lignin synthesis related enzymes, and the relative expression of lignin synthesis related genes in the second stem node of wheat were mainly studied. Four treatments were set up: CK (750 kg·ha-1 compound fertilizer), T1 (750 kg·ha-1 compound fertilizer + 0.9 kg·ha-1 nano silicon), T2 (750 kg·ha-1 compound fertilizer + 1.8 kg·ha-1 nano silicon), T3 (750 kg·ha-1 compound fertilizer + 2.7 kg·ha-1 nano silicon). The results of the two-year experiment showed that the breaking-resistance strength, lodging-resistance index, lignin accumulation in the second stem node of wheat treated with nano silicon fertilizer were higher than CK. In the first year of the experiment, the lignin accumulation of T2 was 130.73%, 5.14% and 7.25% higher than that of CK, T1 and T3 respectively at the maturity stage. In the second year of the experiment, the lignin accumulation of T2 was 20.33%, 11.19% and 9.89% higher than that of CK, T1 and T3 respectively at the maturity stage. And the activities of PAL, 4CL, CAD, and related gene expression levels were also higher than CK. And among them, T2 performed the best, indicating that the application of nano silicon fertilizer is beneficial for improving the lodging resistance of wheat stems and is of great significance for improving the quality of wheat.
Assuntos
Fertilizantes , Lignina , Lignina/metabolismo , Triticum/metabolismo , Silício/farmacologia , Silício/metabolismo , Agricultura/métodos , SoloRESUMO
Cuproptosis is an emerging programmed cell death, displaying great potential in cancer treatment. However, intracellular copper content to induce cuproptosis is unmet, which mainly ascribes to the intracellular pumping out equilibrium mechanism by copper exporter ATP7A and ATP7B. Therefore, it is necessary to break such export balance mechanisms for desired cuproptosis. Mediated by diethyldithiocarbamate (DTC) coordination, herein a strategy to efficiently assemble copper ions into polydopamine nanostructure (PDA-DTC/Cu) for reprogramming copper metabolism of tumor is developed. The deposited Cu2+ can effectively trigger the aggregation of lipoylated proteins to induce cuproptosis of tumor cells. Beyond elevating intracellular copper accumulation, PDA-DTC/Cu enables to break the balance of copper metabolism by disrupting mitochondrial function and restricting the adenosine triphosphate (ATP) energy supply, thus catalytically inhibiting the expressions of ATP7A and ATP7B of tumor cells to enhance cuproptosis. Meanwhile, the killed tumor cells can induce immunogenic cell death (ICD) to stimulate the immune response. Besides, PDA-DTC/Cu NPs can promote the repolarization of tumor-associated macrophages (TAMs ) to relieve the tumor immunosuppressive microenvironment (TIME). Collectively, PDA-DTC/Cu presented a promising "one stone two birds" strategy to realize copper accumulation and inhibit copper export simultaneously to enhance cuproptosis for 4T1 murine breast cancer immunotherapy.
Assuntos
Cobre , Imunoterapia , Indóis , Nanoestruturas , Polímeros , Cobre/química , Polímeros/química , Animais , Imunoterapia/métodos , Indóis/química , Indóis/farmacologia , Camundongos , Nanoestruturas/química , Linhagem Celular Tumoral , Humanos , Catálise , Feminino , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
BACKGROUND: The elastomechanical properties of nanocarriers have recently been discussed as important for the efficient delivery of various therapeutics. Some data indicate that optimal nanocarriers' elasticity can modulate in vivo nanocarrier stability, interaction with phagocytes, and uptake by target cells. Here, we presented a study to extensively analyze the in vivo behavior of LIP-SS liposomes that were modified by forming the silicone network within the lipid bilayers to improve their elastomechanical properties. We verified liposome pharmacokinetic profiles and biodistribution, including retention in tumors on a mouse model of breast cancer, while biocompatibility was analyzed on healthy mice. RESULTS: We showed that fluorescently labeled LIP-SS and control LIP-CAT liposomes had similar pharmacokinetic profiles, biodistribution, and retention in tumors, indicating that modified elasticity did not improve nanocarrier in vivo performance. Interestingly, biocompatibility studies revealed no changes in blood morphology, liver, spleen, and kidney function but indicated prolonged activation of immune response manifesting in increased concentration of proinflammatory cytokines in sera of animals exposed to all tested liposomes. CONCLUSION: Incorporating the silicone layer into the liposome structure did not change nanocarriers' characteristics in vivo. Further modification of the LIP-SS surface, including decoration with hydrophilic stealth polymers, should be performed to improve their pharmacokinetics and retention in tumors significantly. Activation of the immune response by LIP-SS and LIP-CAT, resulting in elevated inflammatory cytokine production, requires detailed studies to elucidate its mechanism.
Assuntos
Elasticidade , Lipossomos , Silicones , Lipossomos/química , Animais , Camundongos , Feminino , Silicones/química , Distribuição Tecidual , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico , Bicamadas Lipídicas/química , Portadores de Fármacos/químicaRESUMO
Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.
Assuntos
Metabolismo dos Lipídeos , Músculo Esquelético , PPAR gama , Poliestirenos , Animais , PPAR gama/metabolismo , PPAR gama/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Poliestirenos/toxicidade , Camundongos , Masculino , Desenvolvimento Muscular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nanopartículas/toxicidade , Tamanho da Partícula , Linhagem Celular , Diferenciação Celular/efeitos dos fármacosRESUMO
The objective of this study was to investigate the potential of native and invasive plant species for the uptake and accumulation of lithium (Li) and strontium (Sr) along the Sava River, focusing on their bioindication and phytoremediation capabilities. Sampling was carried out in riparian zones exposed to different pollution sources in Slovenia, Croatia, and Serbia. Plant samples of native (Salix alba, Populus alba, Populus nigra, Ulmus glabra, Juglans regia) and invasive (Amorpha fruticosa, Reynoutria japonica, Solidago canadensis, Impatiens glandulifera) species were collected. The content of Li and Sr was analyzed in the soils, roots, and leaves of the selected plants, as well as physical and chemical soil properties. Both Li and Sr content in the soils increased from the source to the mouth of the Sava River. The native species showed significant potential for Li and Sr accumulation based on the metal accumulation index. The highest Sr accumulation was measured in the leaves of Salix alba and the roots of Juglans regia, while the highest Li accumulation was measured in Ulmus glabra. Native species, especially Salix alba, proved to be better bioindicators of Li and Sr. Invasive species, especially Amorpha fruticosa and Impatiens glandulifera, showed a remarkable ability to translocate Sr and Li, respectively, to leaves. These results provide valuable insight into the suitability of plants for biomonitoring soil contamination and potential applications in phytoremediation strategies. In summary, the study shows the importance of native species in the context of the accumulation and bioindication of soil pollution.
Assuntos
Populus , Salix , Poluentes do Solo , Estrôncio , Biodegradação Ambiental , Lítio , Rios , Plantas , Solo/química , Populus/química , Poluentes do Solo/análiseRESUMO
Polystyrene microplastics (MPs) are persistent environmental pollutants commonly encountered in daily human life. Numerous studies have demonstrated their ability to induce liver damage, including oxidative stress, inflammation, and lipid accumulation. However, limited information exists regarding preventive measures against this issue. In our study, we investigated the potential preventive role of selenium nanoparticles (YC-3-SeNPs) derived from Yak-derived Bacillus cereus, a novel nanobiomaterial known for its antioxidant properties and lipid metabolism regulation. Using transcriptomic and metabolomic analyses, we identified key genes and metabolites associated with oxidative stress and lipid metabolism imbalance induced by MPs. Upregulated genes (Scd1, Fasn, Irs2, and Lpin) and elevated levels of arachidonic and palmitic acid accumulation were observed in MP-exposed mice, but not in those exposed to SeNPs. Further experiments confirmed that SeNPs significantly attenuated liver lipid accumulation and degeneration caused by MPs. Histological results and pathway screening validated our findings, revealing that MPs suppressed the Pparα pathway and Nrf2 pathway, whereas SeNPs activated both pathways. These findings suggest that MPs may contribute to the development of nonalcoholic fatty liver disease (NAFLD), while SeNPs hold promise as a future nanobio-product for its prevention.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Selênio , Camundongos , Humanos , Animais , Selênio/farmacologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Plásticos , Microplásticos/toxicidade , Estresse Oxidativo , LipídeosRESUMO
OBJECTIVES: Chewing gums containing antiseptics or other antimicrobial substances may be effective in reducing plaque and gingivitis. Therefore, the aim of this randomized placebo-controlled clinical trial was to investigate the efficacy of a novel antimicrobial chewing gum containing essential oils (cinnamon, lemon, peppermint) and extracts on reduction of dental plaque and gingivitis as well as on oral health-related quality of life (OHRQoL) in adolescent orthodontic patients. MATERIALS: 52 patients (11-22 years of age) were randomly assigned to use a test chewing gum (COVIDGUM, Clevergum) or a commercially available control chewing gum over a period of 10 days. Approximal plaque index (API), papillary bleeding index (PBI) and an OHRQoL questionnaire for children (COHIP-G19) were assessed at baseline (BL), after 10 days (10d) and 30 days (30d). In addition, oral health and oral hygiene related questions of the COHIP-G19 questionnaire were evaluated separately in subscales at each timepoint. Data were analyzed using non-parametrical statistical procedures (α = 0.05). RESULTS: API and PBI decreased significantly over time from BL to 10d and from BL to 30d in both groups, without significant differences between the groups. In both groups, the COHIP-G19 score, oral health subscale and oral hygiene subscale decreased significantly over time. Regarding the oral hygiene subscale, the test group showed significantly better scores at 30d (p = 0.011). CONCLUSION: Both chewing gums performed similarly effective in terms of reducing plaque accumulation and gingival inflammation and improving OHRQoL. CLINICAL RELEVANCE: Chewing gums without antimicrobial ingredients may be sufficient to decrease plaque accumulation and gingival inflammation.
Assuntos
Goma de Mascar , Placa Dentária , Gengivite , Qualidade de Vida , Humanos , Gengivite/prevenção & controle , Adolescente , Feminino , Masculino , Placa Dentária/prevenção & controle , Criança , Adulto Jovem , Inquéritos e Questionários , Anti-Infecciosos/uso terapêutico , Resultado do Tratamento , Óleos Voláteis/uso terapêutico , Índice de Placa Dentária , Índice PeriodontalRESUMO
The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/ß-Tricalcium phosphate (E-rhBMP-2/ß-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/ß-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/ß-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/ß-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.
Assuntos
Proteína Morfogenética Óssea 2 , Fosfatos de Cálcio , Modelos Animais de Doenças , Osteócitos , Proteínas Recombinantes , Animais , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/metabolismo , Osteócitos/efeitos dos fármacos , Fosfatos de Cálcio/farmacologia , Camundongos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/administração & dosagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Humanos , Regeneração Óssea/efeitos dos fármacos , Masculino , Extração Dentária/efeitos adversos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologiaRESUMO
The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different molar composition (98:2:2, 95:5: 2 and 98:2:5) and their monomer composition, absolute molecular masses and hydrodynamic radii in aqueous media were determined. Using the MTT test, these terpolymers were established to be low toxic for non-tumor Vero cells and HeLa tumor cells. Polymer compositions of hydrophobic dye methyl pheophorbide a (MPP) based on studied terpolymers and linear polyvinylpyrrolidone (PVP) were obtained and characterized in water solution. Quantum-chemical modeling of the MPP-copolymer structures was conducted, and the possibility of hydrogen bond formation between terpolymer units and the MPP molecule was shown. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied, and an increase in the accumulation of MPP with both types of particles was found.
Assuntos
Acrilatos , Humanos , Animais , Chlorocebus aethiops , Acrilatos/química , Células Vero , Células HeLa , Sistemas de Liberação de Medicamentos , Pirrolidinonas/química , Metacrilatos/química , Polietilenoglicóis/química , Polímeros/química , Polímeros/síntese química , Sobrevivência Celular/efeitos dos fármacosRESUMO
This comprehensive review delves into the complex issue of plastic pollution, focusing on the emergence of biodegradable plastics (BDPs) as a potential alternative to traditional plastics. While BDPs seem promising, recent findings reveal that a large number of BDPs do not fully degrade in certain natural conditions, and they often break down into microplastics (MPs) even faster than conventional plastics. Surprisingly, research suggests that biodegradable microplastics (BDMPs) could have more significant and long-lasting effects than petroleum-based MPs in certain environments. Thus, it is crucial to carefully assess the ecological consequences of BDPs before widely adopting them commercially. This review thoroughly examines the formation of MPs from prominent BDPs, their impacts on the environment, and adsorption capacities. Additionally, it explores how BDMPs affect different species, such as plants and animals within a particular ecosystem. Overall, these discussions highlight potential ecological threats posed by BDMPs and emphasize the need for further scientific investigation before considering BDPs as a perfect solution to plastic pollution.
Assuntos
Monitoramento Ambiental , Microplásticos , Microplásticos/análise , Plásticos Biodegradáveis , Poluição Ambiental/estatística & dados numéricos , Plásticos/análise , Ecossistema , Biodegradação Ambiental , Poluentes Ambientais/análiseRESUMO
Microplastics merit attention as they can be ingested by lower trophic organisms, transferred to the food web, and pose potential risks to higher trophic levels. This study investigated the accumulation and effects of polyethylene microbeads (PEMBs, 63-75 µm) on adult water flea Moina macrocopa (600-800 µm), an order-magnitude difference in size, as a result of acute exposure. The organisms were exposed to PEMBs in four treatments of 0 (the Control), 5, 50, and 500 mg PEMB/L for examining PEMB accumulation, survival and reproduction of the organisms after the 24- and 48-h exposures. In general, M. macrocopa ingested PEMBs within 24-h exposure and reached the cumulative PEMB accumulation value of 0.17 ± 0.21 beads/adult after 48-h exposure in the 500 mg PEMB/L treatment. Exposure to PEMBs resulted in a statistically significant decrease of the cumulative survival rates, from 93 ± 12% in the Control to 37 ± 21% in the 500 mg/L treatment. Nevertheless, exposure to PEMBs did not significantly reduce the cumulative reproduction (p > 0.05), although a decrease was observed. This study suggests that the relatively large-size PEMBs could be ingested by the relatively small-size M. macrocopa and pose potential risks to these organisms.
Assuntos
Cladocera , Polietileno , Poluentes Químicos da Água , Animais , Cladocera/efeitos dos fármacos , Cladocera/fisiologia , Microplásticos/toxicidade , Microesferas , Polietileno/toxicidade , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidadeRESUMO
OBJECTIVES: To evaluate the most effective method for mechanical inter-dental plaque removal between inter-dental brushes (IDB) and dental floss (DF), in addition to toothbrushing in patients affected by peri-implant mucositis (PIM); to identify possible factors related to the patient or to the single implant-supported element that could influence plaque accumulation and inflammation of peri-implant tissues. METHODS: Forty patients with PIM were recruited. They were randomly assigned to two different groups depending on inter-dental device used (IDB or DF). At baseline (T0), interproximal area (IA), interproximal emergence angle of the implant crown (A°) and manual dexterity (evaluated with Purdue Pegboard) have been recorded. At 14 days (T1), the inter-dental cleaning devices have been inverted between groups. After 14 days (T2), the Plaque Index (PI) and Gingival Index (GI) have been recorded. A questionnaire has been submitted to a patient for the analysis of preferences at T0, T1 and T2. RESULTS: Both inter-dental cleaning devices were effective in reducing PI and GI in the inter-dental area after 14 days of use. GI reduction was influenced by manual dexterity of the dominant hand. No significant differences were found for PI and GI at the variation of IA and A°. CONCLUSION: IDB was the most effective method for inter-dental plaque removal in all subjects regardless of their manual dexterity. DF seems to be more effective than IDB only in subjects with good dexterity.
Assuntos
Estudos Cross-Over , Dispositivos para o Cuidado Bucal Domiciliar , Índice de Placa Dentária , Placa Dentária , Índice Periodontal , Escovação Dentária , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Placa Dentária/prevenção & controle , Escovação Dentária/instrumentação , Escovação Dentária/métodos , Estomatite/etiologia , Estomatite/prevenção & controle , Idoso , Adulto , Resultado do Tratamento , Mucosite/etiologia , Mucosite/prevenção & controle , Implantes Dentários/efeitos adversos , Peri-Implantite/prevenção & controleRESUMO
This study characterized the occurrence patterns of microplastics (MPs) in the bronchoalveolar lavage fluid (BALF) of children with pulmonary diseases. MPs were detected in 89.6% of BALF samples with an average of 4.31 ± 2.77 items/10 mL, supporting the hypothesis that inhalation is a significant pathway of airborne MP exposure to pediatric lungs. Inhaled MPs were predominantly composed of 10 polymer types [e.g., polypropylene (41.9%), polyethylene (19.4%), and polyester (13.6%)], with the majority being smaller than 20 µm. MP levels in BALF exhibited a negative correlation with children's age, probably owing to the preferential crawling and tumbling actions in indoor environments and underdeveloped immune systems of young children. Participants living in urban areas suffered from higher pulmonary MP exposure, likely due to higher environmental levels, compared with suburban/rural residents (P < 0.05). Although no significant differences were found between MP levels in pediatric lungs with community-acquired pneumonia (CAP) and asthma (P > 0.05), the severe CAP group displayed significantly higher MP contamination than the nonsevere group (P < 0.05), indicating that some yet undiscovered relationship(s) between inhaled MPs and pediatric pulmonary diseases may exist.
Assuntos
Pneumopatias , Poluentes Químicos da Água , Humanos , Criança , Pré-Escolar , Microplásticos , Plásticos , Líquido da Lavagem Broncoalveolar , População do Leste Asiático , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
Various studies have been conducted on the perfluorochemicals (PFCs) family over the years. These compounds have been sought in various industrial aspects involving the synthesis of everyday utilities due to their broad range of applications. As a result, PFCs have built up in the environment, causing concern. The presence of PFCs in various environmental media, such as terrestrial and marine settings, as well as the mechanisms of transport, bioaccumulation, and physio-chemical interactions of PFCs within plants, aquatic organisms, microplastics, and, ultimately, the human body, are discussed in this review, which draws on a variety of research publications. The interaction of PFCs with proteins, translocation, and adsorption by hydrophobic interactions were observed, and this had an impact on the natural functioning of biological processes, resulting in events such as phylogenic clustering, competitive inhibition, and many others, posing potential hazards to human health and other relevant organisms in the ecosystem. However, further research is needed to have a better knowledge of PFCs and their interactions so that low-cost treatments can be developed to eliminate them. It is therefore, future research should focus on the role of soil matrix as a defensive mechanism for PFCs, as well as the impact of PFC chain length rejection.
Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Humanos , Fluorocarbonos/toxicidade , Fluorocarbonos/análise , Ecossistema , Plásticos , Hidrocarbonetos Fluorados , Solo/química , Monitoramento Ambiental , Poluentes Químicos da Água/análiseRESUMO
Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunotherapy, molecular therapy or surface-engineered nanotherapeutics could offer the benefits here owing to drug resistance over tumor heterogenicity. We have developed tumor-sensing phosphorothioate and amino-modified aptamer (AS1411)-conjugated stealth nanoliposomes, encapsulating with apigenin for precise and significant biodistribution of apigenin into the target tumor to exploit maximum bio-therapeutic assistances. The stable aptamer functionalized PEGylated nanoliposomes (Apt-NLCs) had an average vesicle size of 100-150 nm, a smooth surface, and an intact lamellarity, as ensured by DLS, FESEM, AFM, and Cryo-TEM. This study has specified in vitro process of optimum drug (apigenin) extrusion into the cancer cells by nucleolin receptor-mediated cellular internalization when delivered through modified AS1411 functionalized PEGylated nanoliposomes and ensured irreversible DNA damage in HCC. Significant improvement in cancer cell apoptosis in animal models, due to reduced clearance and higher intratumor drug accumulation along with almost nominal toxic effect in liver, strongly supports the therapeutic potential of aptamer-conjugated PEGylated nanoliposomes compared to the nonconjugated formulations in HCC. The study has established a robust superiority of modified AS1411 functionalized PEGylated nanoliposomes as an alternative drug delivery approach with momentous reduction of HCC tumor incidences.
Assuntos
Aptâmeros de Nucleotídeos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Apigenina/farmacologia , Apigenina/uso terapêutico , Distribuição Tecidual , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Sistemas de Liberação de Medicamentos , Oligodesoxirribonucleotídeos , Polietilenoglicóis/uso terapêutico , Linhagem Celular TumoralRESUMO
Microplastics (MPs) increase the effective state of heavy metals (HMs) in soil and seriously threaten the yield and quality of peanuts (Arachis Hypogea L.). Kaolinite (KL) has the potential to ameliorate MP- and HM- contaminated soils, but the mechanism of action between them is not well understood. Therefore, 60-day experiments were conducted, where KL (1 %, 2 %) and MPs (0.1 %, 1 %) were individually or jointly mixed into soils with different cadmium (Cd) concentrations (0.5, 2.5, and 5.0 mg·kg-1) to cultivate peanuts in a greenhouse. Finally, soil-bioavailable Cd, peanut dry weight, peanut Cd concentrations, the pH, cation exchange capacity (CEC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) were determined. It was shown that MPs negatively affected the peanut dry weight and increased the content of soil-bioavailable Cd and Cd concentration in peanut. In the MP- and Cd-contaminated soils, KL mitigated the negative influence of MPs by increasing the dry weight of peanuts by 8.40 %-40.59 %, decreasing the soil-bioavailable Cd by 23.70-35.74 %, and significantly decreasing peanut Cd concentrations by 9.65-30.86 %. The presence of MPs decreased soil pH (7.69-7.87) and the CEC (20.96-23.95 cmol·L-1) and increased the soil DOC (1.84-2.26 mg·kg-1). KL significantly increased soil pH (7.79-8.03) and the CEC (24.96-28.28 cmol·L-1) and mitigated the adverse influence of MPs on the pH and CEC of Cd-contaminated soils. A regression path analysis (RPA) evidenced that KL decreased Cd accumulation in plants by changing the properties of soil contaminated with MPs and Cd. The research results revealed the mechanism of KL on peanut growth and Cd absorption in MP- and Cd-contaminated soil. The results of this study provide a foundation to improve the quality of MP- and HM-contaminated soils and realize safe peanut production.
Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Arachis/química , Solo/química , Microplásticos , Plásticos , Caulim , Poluentes do Solo/análiseRESUMO
Olea europaea L. leaves contain a wide variety of pentacyclic triterpenes (TTPs). TTPs exhibit many pharmacological activities, including antihyperlipidemic effects. Metabolic alterations, such as dyslipidemia, are an established risk factor for hepatocellular carcinoma (HCC). Therefore, the use of TTPs in the adjunctive treatment of HCC has been proposed as a possible method for the management of HCC. However, TTPs are characterized by poor water solubility, permeability, and bioavailability. In this work, a microemulsion (ME) loading a TTP-enriched extract (EXT) was developed, to overcome these limits and obtain a formulation for oral administration. The extract-loaded microemulsion (ME-EXT) was fully characterized, assessing its chemical and physical parameters and release characteristics, and the stability was evaluated for two months of storage at 4 °C and 25 °C. PAMPA (parallel artificial membrane permeability assay) was used to evaluate the influence of the formulation on the intestinal passive permeability of the TTPs across an artificial membrane. Furthermore, human hepatocarcinoma (HepG2) cells were used as a cellular model to evaluate the effect of EXT and ME-EXT on de novo lipogenesis induced by elevated glucose levels. The effect was evaluated by detecting fatty acid synthase expression levels and intracellular lipid accumulation. ME-EXT resulted as homogeneous dispersed-phase droplets, with significantly increased EXT aqueous solubility. Physical and chemical analyses showed the high stability of the formulation over 2 months. The formulation realized a prolonged release of TTPs, and permeation studies demonstrated that the formulation improved their passive permeability. Furthermore, the EXT reduced the lipid accumulation in HepG2 cells by inhibiting de novo lipogenesis, and the ME-EXT formulation enhanced the inhibitory activity of EXT on intracellular lipid accumulation.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Olea , Triterpenos , Humanos , Triterpenos Pentacíclicos , Lipogênese , Células Hep G2 , Carcinoma Hepatocelular/tratamento farmacológico , Emulsões/química , Neoplasias Hepáticas/tratamento farmacológico , Triterpenos/farmacologia , Triterpenos/química , Membranas Artificiais , Folhas de Planta , LipídeosRESUMO
Serotonin (5-HT), an indoleamine compound, has been known to mediate many physiological responses of plants under environmental stress. The deep-seeding (≥20 cm) of maize seeds is an important cultivation strategy to ensure seedling emergence and survival under drought stress. However, the role of 5-HT in maize deep-seeding tolerance remains unexplored. Understanding the mechanisms and evaluating the optimal concentration of 5-HT in alleviating deep-seeding stress could benefit maize production. In this study, two maize inbred lines were treated with or without 5-HT at both sowing depths of 20 cm and 3 cm, respectively. The effects of different concentrations of 5-HT on the growth phenotypes, physiological metabolism, and gene expression of two maize inbred lines were examined at the sowing depths of 20 cm and 3 cm. Compared to the normal seedling depth of 3 cm, the elongation of the mesocotyl (average elongation 3.70 cm) and coleoptile (average elongation 0.58 cm), secretion of indole-3-acetic acid (IAA; average increased 3.73 and 0.63 ng g-1 FW), and hydrogen peroxide (H2O2; average increased 1.95 and 0.63 µM g-1 FW) in the mesocotyl and coleoptile were increased under 20 cm stress, with a concomitant decrease in lignin synthesis (average decreased 0.48 and 0.53 A280 g-1). Under 20 cm deep-seeding stress, the addition of 5-HT activated the expression of multiple genes of IAA biosynthesis and signal transduction, including Zm00001d049601, Zm00001d039346, Zm00001d026530, and Zm00001d049659, and it also stimulated IAA production in both the mesocotyl and coleoptile of maize seedlings. On the contrary, 5-HT suppressed the expression of genes for lignin biosynthesis (Zm00001d016471, Zm00001d005998, Zm00001d032152, and Zm00001d053554) and retarded the accumulation of H2O2 and lignin, resulting in the elongation of the mesocotyl and coleoptile of maize seedlings. A comprehensive evaluation analysis showed that the optimum concentration of 5-HT in relieving deep-seeding stress was 2.5 mg/L for both inbred lines, and 5-HT therefore could improve the seedling emergence rate and alleviate deep-seeding stress in maize seedlings. These findings could provide a novel strategy for improving maize deep-seeding tolerance, thus enhancing yield potential under drought and water stress.
Assuntos
Cotilédone , Plântula , Plântula/metabolismo , Cotilédone/metabolismo , Zea mays/metabolismo , Serotonina/metabolismo , Lignina/metabolismo , Peróxido de Hidrogênio/metabolismo , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismoRESUMO
Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy is not adequately addressed. This work addresses this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. It is observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. The role of different morphologies on pharmacological performance of drug loaded micelles against triple-negative breast cancer and pancreatic cancer tumor models is further evaluated. Spherical micelles accumulate rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulate more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug-micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.
Assuntos
Antineoplásicos , Micelas , Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanomedicina , Polímeros/químicaRESUMO
The persistence of plastics and its effects in different environments where they accumulate, particularly in coastal areas, is of serious concern. These plastics exhibit signs of degradation, possibly mediated by microorganisms. In this study, we investigated the potential of sediment microbial communities from Manila Bay, Philippines, which has a severe plastics problem, to degrade low-density polyethylene (LDPE). Plastics in selected sites were quantified and sediment samples from sites with the lowest and highest plastic accumulation were collected. These sediments were then introduced and incubated with LDPE in vitro for a period of 91 days. Fourier transform infrared spectroscopy detected the appearance of carbonyl and vinyl products on the plastic surface, indicating structural surface modifications attributed to polymer degradation. Communities attached to the plastics were profiled using high-throughput sequencing of the V4-V5 region of the 16S rRNA gene. Members of the phylum Proteobacteria dominated the plastic surface throughout the experiment. Several bacterial taxa associated with hydrocarbon degradation were also enriched, with some taxa positively correlating with the biodegradation indices, suggesting potential active roles in the partial biodegradation of plastics. Other taxa were also present, which might be consuming by-products or providing nourishment for other groups, indicating synergy in utilizing the plastic as the main carbon source and creation of a microenvironment within the plastics biofilm. This study showed that sediment microbes from Manila Bay may have naturally occurring microbial groups potentially capable of partially degrading plastics, supporting previous studies that the biodegradation potential for plastics is ubiquitously present in marine microbial assemblages.