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BACKGROUND: Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. METHODS: The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3-), NK (NK1.1-CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. RESULTS: Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice. CONCLUSIONS: Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology.
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Schistosoma japonicum , Animais , Camundongos , Schistosoma japonicum/metabolismo , Receptor 3 Toll-Like/metabolismo , Camundongos Endogâmicos C57BL , Imunoglobulina G , Imunoglobulina MRESUMO
Theory questions the persistence of nonreciprocal interactions in which one plant has a positive net effect on a neighbor that, in return, has a negative net impact on its benefactor - a phenomenon known as antagonistic facilitation. We develop a spatially explicit consumer-resource model for belowground plant competition between ecosystem engineers, plants able to mine resources and make them available for any other plant in the community, and exploiters. We use the model to determine in what environmental conditions antagonistic facilitation via soil-resource engineering emerges as an optimal strategy. Antagonistic facilitation emerges in stressful environments where ecosystem engineers' self-benefits from mining resources outweigh the competition with opportunistic neighbors. Among all potential causes of stress considered in the model, the key environmental parameter driving changes in the interaction between plants is the proportion of the resource that becomes readily available for plant consumption in the absence of any mining activity. Our results align with theories of primary succession and the stress gradient hypothesis. However, we find that the total root biomass and its spatial allocation through the root system, often used to measure the sign of the interaction between plants, do not predict facilitation reliably.
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Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.
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The modern concept of 'family' in the United States recognizes many types of social groups as families, a conceptual shift which was largely helped along by advancements in assisted reproductive technologies enabling those formerly unable to biologically reproduce to have children, as well as by social movements aimed at garnering recognition for these emergent nonbiologically related social groups spearheaded by LGBTQ+ and adoption activists. That these social groups are now recognized as types of families is unquestionably an improvement to the concept, though there are still defects in the concept that preclude these nonnuclear families from achieving the same social-ontological status as nuclear families. Drawing from the nascent philosophical field of conceptual engineering, I analyze our current conception of 'family' and argue that it is tacitly exclusionary of nonnuclear families, which can be attributed to a combination of widespread genetic essentialism and linguistic practices that unduly cast the nuclear family as a more desirable type of family by emphasizing genetic relatedness as a valuable quality. I then offer proposals to ameliorate these defects, such as educational interventions to reduce genetic essentialism and the introduction of new terminology that does not connote one type of family as being superior to another. In doing so, my hope is to reveal and begin to resolve an overlooked defect in the concept of 'family' in order to bolster the movement to view all families as equal.
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Família , Humanos , Estados Unidos , Minorias Sexuais e de Gênero , Núcleo Familiar , Técnicas de Reprodução Assistida/ética , FemininoRESUMO
Fly ash (FA) is a very alkaline, hazardous waste with a potential to be recycled in amelioration of master pedovariables, notably: i) pH, drives soil biogeochemistry, ii) electrical conductivity (EC), reflects soil salinity level and overall soil health, iii) water holding capacity (WHC), determines soil hydraulic functions and iv) bulk denisity (BD), indicates soil compaction and water-air relations. We performed a multilevel meta-analysis, encompassing 30 out of 1325 screend studies, using a random effect model and non-aggregated data sets. By moderating; experimental type, FA application rate, soil type and land use, two distinct meta-analytical approaches on observed pedovariables were performed: i) uni-moderator, considering moderators separately, and ii) multi-moderator, considering moderators combined. It was found that FA application: increased soil pH by 15.4% (Hedge's g = 8.07), EC by 51.7% (Hedge's g = 8.07), WHC by 22.6% (Hedge's g = 7.79), and reduced BD by 13.5% (Hedge's g = -5.03). However, the uni-moderator meta-analytical model revealed a significant increase in pH and EC only with relatively lower FA dosage (up to 20%). In addition, the impact of FA on pH and EC was significantly positive in acid (pHH2O < 6.5), negative in alkaline (pHH2O > 7.2), and not significant in neutral (pHH2O = 6.6-7.2) soil types. The same uni-moderator approach revealed that FA dosages above 5% significantly increased WHC, but reduced BD. Moreover, the multi-moderator model identified two significant interactions: i) between varying FA dosage and land use, and ii) between varying FA dosage and soil type. Confirmed positive implications of FA on key soil properties underscore its strong potential as a valuable resource for sustainable soil management, mitigating widespread soil constraints and contributing waste reduction. However, careful consideration of FA dosage, soil type, and land use is imperative to optimize FA application and prevent potential adverse environmental implications.
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Cinza de Carvão , Solo , Solo/química , Concentração de Íons de HidrogênioRESUMO
Liming, as a common amelioration practice worldwide, has the potential to alleviate soil acidification and ensure crop production. However, the impacts of long-term liming on the temperature sensitivity (Q10) of soil organic carbon (SOC) mineralization and its response to labile C input remain unclear. To fill the knowledge gap, soil samples were collected from a long-term (â¼10 years) field trial with unlimed and limed (CaO) plots. These soil samples were incubated at 15 °C and 25 °C for 42 days, amended without and with 13C-labeled glucose. Results showed that compared to the unlimed soil (3.6-8.6 mg C g-1 SOC), liming increased SOC mineralization (6.1-11.2 mg C g-1 SOC). However, liming significantly mitigated the positive response of SOC mineralization to warming, resulting in a lower Q10. Long-term liming increased bacterial richness and Shannon diversity as well as their response to warming which were associated with the decreased Q10. Furthermore, the decreased Q10 due to liming was attributed to the decreased response of bacterial oligotrophs/copiotrophs ratio, ß-glucosidase and xylosidase activities to warming. Labile C addition had a strong impact on Q10 in the unlimed soil, but only a marginal influence in the limed soil. Overall, our research highlights that acidification amelioration by long-term liming has the potential to alleviate the positive response of SOC mineralization to warming and labile C input, thereby facilitating SOC stability in agroecosystems, especially for acidic soils in subtropical regions.
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Compostos de Cálcio , Carbono , Solo , Microbiologia do Solo , ÓxidosRESUMO
BACKGROUND: Poly-γ-glutamic acid (γ-PGA) is employed extensively in agriculture to enhance soil water retention; however, the underlying mechanism by which γ-PGA improves soil structure and soybean productivity in arid regions remains poorly understood. A micro-scale field experiment was conducted in the arid region of northwest China, employing five concentrations of γ-PGA to investigate its impacts on soybean yield, photosynthesis, and water-use efficiency, as well as soil aggregates and water distribution. The five levels of γ-PGA were 0 (CK), 10 (P1), 20 (P2), 40 (P3), and 80 kg ha-1 (P4). RESULTS: The results demonstrated that the application of γ-PGA significantly improved soybean yield, photosynthesis, and chlorophyll content. It resulted in a decrease in soil aggregate content with a maximum diameter of less than 0.053 mm and an increase in the stability of soil aggregates in the uppermost layer of the soil (0-30 cm). The application of γ-PGA significantly increased soil water content, particularly in the uppermost layer of the soil, and effectively reduced water consumption and improving water use efficiency in soybeans. Overall, the P3 treatment exhibited the most pronounced improvement of soybean yield, photosynthesis, water-use efficiency, as well as distribution of soil aggregates and water. The correlation matrix heatmap also revealed a strong correlation between improvement of soybean yield or photosynthesis at various γ-PGA application levels and the enhancement of soil stability or soil water content. CONCLUSION: The multivariate regression analysis revealed that an optimal application level of 46 kg ha-1 γ-PGA could enhance effectively both yield and water use efficiency of soybean in the arid region of northwest China. © 2024 Society of Chemical Industry.
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Glycine max , Fotossíntese , Ácido Poliglutâmico , Solo , Água , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismo , Glycine max/química , Solo/química , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/metabolismo , Água/metabolismo , Água/análise , China , Fertilizantes/análise , Clorofila/metabolismoRESUMO
Saline and alkaline soils are a challenge for sustainable crop production. The use of organic and inorganic amendments is a common practice to increase the fertility of salt-affected soils that can trigger faster carbon (C) and nitrogen (N) cycling. We examined the effects of gypsum (Gyps), farm manure (Manure) and rice straw (Straw) on enzyme activities, organic matter mineralization and CO2 emissions in two salt-affected soils [Solonchak (saline); pH: 8, electrical conductivity (EC): 6.5, sodium adsorption ratio (SAR): 2.5, and Solonetz (alkaline sodic); pH: 8.9, EC: 1.6, SAR: 17]. Gypsum addition decreased soil pH up to 0.62 and 0.30 units, SAR 1.2 and 5.2 units, and EC 2.9 and 1.4 units in Solonchak and Solonetz, respectively. Dissolved organic C, microbial biomass C, dissolved organic N, mineral N (NO3- and NH4+), enzyme activities (urease, invertase, catalase, phosphatase, phenol-oxidase), alkali extractable phenols, and available phosphorous increased with the application of all amendments in both soils. Solonetz released more CO2 than Solonchak, whereas maximum CO2 emissions were common after manure application (3140 mg kg-1 in Solonchak, and 3890 mg kg-1 in Solonetz). We conclude that high SAR and low EC increase CO2 emissions through accelerated C and N cycling and manure decomposition in Solonetz soils.
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Oryza , Solo , Solo/química , Sulfato de Cálcio , Esterco , Dióxido de Carbono , Cloreto de Sódio , CarbonoRESUMO
KEY MESSAGE: Extensive crosstalk exists among ABA and different phytohormones that modulate plant tolerance against different abiotic stress. Being sessile, plants are exposed to a wide range of abiotic stress (drought, heat, cold, salinity and metal toxicity) that exert unwarranted threat to plant life and drastically affect growth, development, metabolism, and yield of crops. To cope with such harsh conditions, plants have developed a wide range of protective phytohormones of which abscisic acid plays a pivotal role. It controls various physiological processes of plants such as leaf senescence, seed dormancy, stomatal closure, fruit ripening, and other stress-related functions. Under challenging situations, physiological responses of ABA manifested in the form of morphological, cytological, and anatomical alterations arise as a result of synergistic or antagonistic interaction with multiple phytohormones. This review provides new insight into ABA homeostasis and its perception and signaling crosstalk with other phytohormones at both molecular and physiological level under critical conditions including drought, salinity, heavy metal toxicity, and extreme temperature. The review also reveals the role of ABA in the regulation of various physiological processes via its positive or negative crosstalk with phytohormones, viz., gibberellin, melatonin, cytokinin, auxin, salicylic acid, jasmonic acid, ethylene, brassinosteroids, and strigolactone in response to alteration of environmental conditions. This review forms a basis for designing of plants that will have an enhanced tolerance capability against different abiotic stress.
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Ácido Abscísico , Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Ácido Abscísico/metabolismo , Estresse Fisiológico/fisiologia , Citocininas , Produtos Agrícolas/metabolismoRESUMO
Androgen deprivation therapy is commonly used for the treatment of prostate cancer. Enzalutamide is a next-generation androgen receptor inhibitor, initially approved to treat castration-resistance prostate cancer. Lupeol, a triterpene present in various fruits, vegetables, has anti-oxidant and anti-proliferative activity. The present study aimed to evaluate the Enzalutamide-induced toxicity and its possible amelioration by Lupeol. We performed multiple in vitro and in vivo experiments to conclude our hypothesis. The results revealed that both Enzalutamide and Lupeol interact with DNA through electrostatic interactions. Enzalutamide (5-20 µM) caused cytotoxicity in both normal (PNT2) and cancer cells (LNCaP and 22Rv1). However, Lupeol (10-50 µM) specifically killed the cancer cells while sparing normal cells. The study further revealed that Lupeol could attenuate Enzalutamide-induced cytotoxicity and genotoxicity (chromosomal aberrations and micronucleus formation) to normal cells and potentially induce cytotoxicity to transformed cells. We further observed that Lupeol (40 mg/kg) mediated attenuation of the Enzalutamide (10 mg/kg) induced oxidative and DNA damages. Our study also revealed that Lupeol reverses the Enzalutamide-induced hepatic and renal damages. In conclusion, our study indicates that Lupeol can be used as an adjuvant for reducing the toxic effects and enhancing the effectiveness of Enzalutamide.
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Neoplasias da Próstata , Triterpenos , Masculino , Humanos , Triterpenos/farmacologia , Antagonistas de Androgênios/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Triterpenos Pentacíclicos , Nitrilas/farmacologia , Receptores Androgênicos/genética , Linhagem Celular TumoralRESUMO
Bisphenol-A (BPA) is a toxic chemical largely produced and used in polycarbonate plastics worldwide. Majoon Suranjan (MS), a polyherbal formulation, is used as an anti-inflammatory medicine against rheumatoid arthritis. The present study aimed to evaluate BPA-induced toxicity and its possible amelioration by MS. To test our hypothesis, we performed gas chromatography-mass spectrometry (GC-MS) analysis, DNA interaction studies, genotoxicity tests, oxidative stress parameters, and histopathological examinations. GC-MS profiling of MS revealed the presence of various anti-oxidant compounds. DNA interaction studies showed that both chemicals intercalate between DNA base pairs. Next, we observed BPA-induced genotoxicity and oxidative damage. The observed effects might be due to BPA-induced reactive oxygen species production. Further, BPA changed the anti-oxidant enzyme activities, increased the malondialdehyde, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and caused gross damage to the liver and kidney. Interestingly, these effects were significantly reversed by MS. In conclusion, MS shows protective effects against BPA-induced toxicity and could be a potential alternative medicine against BPA toxicity, especially in third-world countries where BPA uses are not strictly regulated.Highlights:Bisphenol-A (BPA) induces multiple toxic effects.BPA induces genotoxicity, oxidative and tissue damage.Majoon Suranjan (MS) ameliorates the BPA induced toxic effects.GC-MS profiling show various active anti-oxidant compounds in MS.MS is anti-genotoxic, anti-oxidant, and hepato-renal protective.
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Antioxidantes , Estresse Oxidativo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , FígadoRESUMO
OBJECTIVE: Almost 80% of the patients responding to the nationwide French patient experience and satisfaction survey (e-Satis) provided free text comments. The objective of this article is to describe an innovative methodology for analysis of this qualitative data. METHODOLOGY: This methodological approach is based on analysis of qualitative data from the comments (verbatims) of respondents to the e-Satis survey. Analysis of the verbatims consists in three main steps: (i) analysis of the meaning of the words, with constitution of a thematic dictionary through exploratory research without preconceived notions; (ii) analysis of the syntax, i.e., the way in which the ideas are articulated, which will enable calculation of a linguistic indicator of speakers' involvement in their speech; (iii) production of statistics and characterisation of the themes, which will include three indicators: occurrence of the themes, the average satisfaction shown in the respondents' discourse, and the positive and negative involvement with which they express themselves. Given these results, a priority matrix of four categories of action is established: strong points, priority areas, good practices, and weak signals. RESULTS: This methodological approach was applied to 5868 e-Satis questionnaires out of a total of 10,061 verbatims by respondents hospitalised at the Hospices Civils de Lyon between 2018 and 2019. The analysis identified 28 major themes with 184 sub-themes. An extract is presented in this article for illustration purposes. DISCUSSION: A methodological approach based on analysis of qualitative data will enable transformation of unstructured data (verbatims) into measurable and comparable data. This methodology is structured to overcome the limitations of closed questions; open questions allow respondents to describe their experiences and perceptions in their own words. Moreover, it is a first step toward comparability of results over time with those of other establishments. This approach is unique in France on account of (a) its exploratory thematic research without preconceived notions and (b) its syntactic analysis of verbatims. CONCLUSIONS: This verbatim analysis methodology should enable precise and operational characterization of Patient Experience and induce prioritized improvement actions in healthcare institutions.
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Instalações de Saúde , Medidas de Resultados Relatados pelo Paciente , Humanos , Inquéritos e Questionários , Satisfação do Paciente , Projetos de PesquisaRESUMO
Soil salinization is a critical environmental issue restricting agricultural production. Inner Mongolia is one of the areas with severe land salinization in China. This study aimed to investigate the effects of conditioning agent (containing marlstone and a range of enzymes) and cultivating Jerusalem artichoke on saline soils in Inner Mongolia. The effects of conditioner (0, 0.06 and 0.18 kg/m2) on soil physical, chemical and biological properties, including soil carbon fractions and microbiota in saline soils planted with Jerusalem artichoke, were characterized. The results showed that soil salinity was reduced significantly after cultivating Jerusalem artichoke and declined also after the conditioner addition. The application of conditioner increased the content of DOC (dissolved organic carbon), HFOC (heavy fraction organic carbon) and the content of aggregates >0.25 mm compared to the soil planted with Jerusalem artichoke alone. The relative abundance of halophilic bacteria such as Thioalkalivibrio and Thiohalobacter was greater in the CK (non-treated control). By contrast, the relative abundance of microorganisms with the carbon assimilation and nitrogen fixation capacities, such as Cyanobacteria and Rhodovulum, was greater in the conditioner-treated and Jerusalem artichoke-planted treatments. The planting of Jerusalem artichoke reduced soil salinity, increased soil organic carbon fractions, improved soil structure, and altered the soil microbial community, with the application of the conditioning agent enhancing these positive changes. The co-occurrence network structure of "Jerusalem artichoke-conditioner-saline soil-soil microorganism" was established, which provided scientific basis for Jerusalem artichoke-conditioner to improve saline soil.
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Helianthus , Solo , Solo/química , Helianthus/microbiologia , Carbono/análise , Agricultura , China , Microbiologia do SoloRESUMO
The wastes generated from the mining and processing of granite and marble stone are generally regarded as useless. However, these waste materials were used as the soil amendments for the first time. The functional groups, crystalline structure and micro-morphology of granite and marble wastes amendments (GMWA) were different from the original wastes demonstrated by X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FT-IR) and Scanning electron microscope-energy dispersive spectrometer (SEM-EDS) analyses. With the addition of the amendments, the cation exchange capacity, electrical conductivity and nutrient availability of the soil increased, and the extractable heavy metals of the soil reduced significantly. Under the condition of the addition of 3% amendments, 7.0%, 99.9%, 99.7% and 70.5% of Cu, Pb, Zn and Cd in exchangeable fractions in soil were transformed to the more stable Fe-Mn oxides- or carbonates-bounded fractions. Tessier method and correlation analysis showed that the reduction of extractable metals in the acidic paddy soil can be attributed to the adsorption of available SiO2, the co-precipitation induced by the elevated pH value, the complexation induced by Fe-Mn oxides and the cation exchange induced by mineral nutrients. This study provides a new strategy for resource recovery of waste stones and remediation of heavy metal-contaminated soil.
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Metais Pesados , Poluentes do Solo , Solo/química , Dióxido de Silício , Poluentes do Solo/análise , Carbonato de Cálcio , Espectroscopia de Infravermelho com Transformada de Fourier , Metais Pesados/análise , ÓxidosRESUMO
In the past decade, plant sterols gained more attention due to their significant therapeutic activity, but their poor solubility and low bioavailability limited their use. Here, we developed and optimized phospholipon® 90H modulated phospholipid (PmP) complex of ethanolic extract of Lagenaria siceraria (EELs) by solvent evaporation using Box-Behnken Design. The optimized PmP complex was then evaluated physico-chemically and functionally by particle size and zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and apparent solubility studies. Phospholipon® 90 H (1-Oleoyl-2-palmitoyl-phosphatidylcholine) consists of 85% stearic acid and about 15% palmitic acid., with N,N,N-trimethylethanolammonium cation (choline) as a polar head attached to phosphate group acting as an anion, which forms a weaker intermolecular hydrogen bonding with the third hydroxyl group of isolated sterols. This interaction causes the sterols to get incorporated into the phospholipid at the molecular level. Thereby it leads to the formation of PmP-complex, which enhanced chemical stability with improved solubility. The apparent solubility study demonstrated more than 26-fold increase in aqueous solubility of EELs after forming PmP-complex. This complex with enhanced solubility may be formulated into various pharmaceutical dosage forms, and further pharmacological studies may solve the biopharmaceutical aspects related to therapeutic efficacy.
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Fosfolipídeos , Água , Solubilidade , Fosfolipídeos/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Solventes , Varredura Diferencial de CalorimetriaRESUMO
PURPOSE: Iloperidone (IP) is an antipsychotic drug which belongs to Biopharmaceutical Classification System (BCS) II exhibiting poor aqueous solubility. The current investigation explores the possibility of enhancement of solubility and dissolution characteristics of IP by formulation of liquid self-nano emulsifying drug delivery system (L-SNEDDS) utilizing Box-Behnken Design (BBD) and desirability function. METHODS: The oils, surfactants and co-surfactants used in the study were selected based on solubility of the drug and their emulsification ability. Optimization of the formulation was performed using BBD by employing four response variables such as globule size (nm), percentage transmittance (%), self-emulsification time (sec) and percent drug released in 15min. 2D contour plots and 3D response surface plots were constructed using Design Expert software. RESULTS: The developed optimal L-SNEDDS of IP through BBD approach resulted in improvement of solubility and dissolution rate as compared with the pure drug. Based on desirability function, optimized formulation was prepared and was assessed for response variables (globule size, percentage transmittance, self-emulsification time and percent drug dissolved in 15min). The characterization studies revealed droplet size to be 21.80±2.41nm, 99.584±0.65% transmittance, 24.43±2.12sec emulsification time and 95.31±1.57% cumulative drug release in 15min. CONCLUSION: The results conclude the potentiality of prepared L-SNEDDS in improving solubility and dissolution rate of IP.
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Sistemas de Liberação de Medicamentos , Nanopartículas , Emulsões , Sistemas de Liberação de Medicamentos/métodos , Isoxazóis , Tensoativos , Solubilidade , Tamanho da Partícula , Administração OralRESUMO
Wound healing, tissue regeneration, and organ regrowth are all regeneration phenomena observed in vertebrates after an injury. However, the ability to regenerate differs greatly among species. Mammals can undergo wound healing and tissue regeneration, but cannot regenerate an organ; for example, they cannot regrow an amputated limb. In contrast, amphibians and fish have much higher capabilities for organ-level regeneration. In addition to medical studies and those in conventional mammalian models such as mice, studies in amphibians and fish have revealed essential factors for and mechanisms of regeneration, including the regrowth of a limb, tail, or fin. However, the molecular nature of the cellular memory needed to precisely generate a new appendage from an amputation site is not fully understood. Recent reports have indicated that organ regeneration is closely related to epigenetic regulation. For example, the methylation status of genomic DNA is related to the expression of regeneration-related genes, and histone-modification enzymes are required to control the chromatin dynamics for regeneration. A proposed mechanism of cellular memory involving an inheritable system of epigenetic modification led us to hypothesize that epigenetic regulation forms the basis for cellular memory in organ regeneration. Here we summarize the current understanding of the role of epigenetic regulation in organ regeneration and discuss the relationship between organ regeneration and epigenetic memory.
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Cromatina/metabolismo , Epigênese Genética/genética , Extremidades/crescimento & desenvolvimento , Regeneração/efeitos dos fármacos , Vertebrados/metabolismo , Animais , CamundongosRESUMO
Sorafenib is an FDA-approved chemotherapeutic drug used as standard therapy for advanced-stage cancers. However, Sorafenib-induced multiple adverse effects are a major limitation that directly impacts patients' physical and physiological well-being. Therefore, it is vital to identify agents that can lessen the associated adverse effects and enhance efficacy. Apigenin, a dietary plant flavone, is a bioactive-compound present in fruits and vegetables having anti-oxidant, anti-inflammatory, and anti-cancer properties. Our study aimed to investigate Sorafenib-induced toxic effects at genomic, cellular, and tissue level and the potential protective effects of Apigenin. To achieve our goal, we treated Swiss albino mice with Apigenin (50 mg/kg bw) alone or in combination with Sorafenib (40 mg/kg bw). Next, we performed DNA interaction, genotoxicity, oxidative damages, anti-oxidant activities, liver enzyme levels, and histopathological studies. We demonstrated that Apigenin and Sorafenib bind DNA via electrostatic interaction. Further, Sorafenib induces genetic, oxidative, and tissue damages characterized by an increase in chromosomal aberrations and micronucleus, reactive oxygen species (ROS) and reactive nitrogen species (RNS), oxidative and DNA damage, lipid peroxidation, and hepato-renal damages, and a decrease in antioxidant-enzymes. Interestingly, the Sorafenib-induced adverse effects were ameliorated by Apigenin. Our findings indicate that Apigenin has protective effects against Sorafenib-induced toxicity and could be combined with Sorafenib to lessen its adverse effects and enhance its efficacy. However, further pre-clinical and clinical studies are required to evaluate Apigenin's effectiveness with Sorafenib.
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Antineoplásicos , Neoplasias , Animais , Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Apigenina/farmacologia , Apoptose , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Sorafenibe/toxicidadeRESUMO
The aim of this study was to characterize the effects of cornstalk biomass amendments on microbial communities in bauxite residues (BRs) by phylogenetic analysis. Improvements in soil geochemical, physical, and biological properties were assessed to identify the major factors controlling microbial community development in BRs. After one year of incubation, the salinity and structure of the amended BRs had gradually improved, with pH dropping from 11.39 to 9.89, the exchangeable sodium percentage (ESP) dropping from 86.3% to 35.2%, and the mean weight diameter (MWD) rising from 0.12 mm to 0.38 mm. Further analysis of community level physiological profiles (CLPP) showed that the microbial utilization of different carbohydrates had shifted significantly, in addition to increases in the diversity index H' (0.7-7.34), U (2.16-3.14), and the average well color development (0.059-1.08). Over the one-year outside incubation, the dominant fungal phyla in the BRs had shifted gradually from Ascomycota (85.64%) to Ascomycota (52.07%) and Basidiomycota (35.53%), while the dominant bacterial phyla had shifted from Actinobacteria (38.47%), Proteobacteria (21.39%), and Gemmatimonadetes (12.72%) to Actinobacteria (14.87%), Proteobacteria (23.53%), and Acidobacteria (14.37%). Despite these shifts, microbial diversity remained lower in the amended BRs than in the natural soil. Further redundancy analysis indicated that pH was the major factor driving shifts in the bacterial community, while aggregates were the major factor driving shifts in the fungal community. This study demonstrated that amendment with cornstalk biomass shifted the microbial community in the BRs from halophilic groups to acidogenic groups by improving the soil environmental conditions.
Assuntos
Microbiota , Microbiologia do Solo , Óxido de Alumínio/química , Biomassa , Filogenia , Solo/químicaRESUMO
Soil cadmium (Cd) contamination is a serious problem on agricultural land. Adequate nitrogen (N) may help ameliorate plant fitness under Cd stress. This study examined the role of N application in improving maize tolerance to Cd stress. Two maize genotypes, Zhongke11 (larger root system) and Shengrui999 (smaller root system), were grown in a loessal soil amended with Cd (Cd0, no added Cd; Cd1, 20 mg kg-1 soil as CdCl2·2.5 H2O) and N (N0, no added N; N1, 100 mg kg-1 soil as urea) under greenhouse, and plants were assessed at silking and maturity stages. Maize plants exhibited moderate Cd stress with significantly reduced grain yield, especially under low N (N1). Roots accumulated more Cd than above-ground parts. Grain Cd concentration was the least (0.05-0.06 µg g-1) among all organs which is below the safety threshold. Leaf Cd concentrations (0.24-1.18 mg kg-1) were also under the toxicity threshold. Nitrogen addition significantly improved plant growth, chlorophyll content, photosynthesis traits, and tissue Cd contents, and reduced Cd concentration in soil compared to N0 treatment. Nitrogen promoted Cd bioconcentration and translocation factors in stem and leaves. Cadmium stress reduced N fertilizer agronomic efficiency at maturity. At maturity, root Cd content was positively correlated with root N and calcium accumulation, and stem Cd content was positively correlated with stem N content (both P ≤ 0.05). Genotypes with different root system size differed in response to Cd toxicity and / or N deficit. The small-rooted genotype Shengrui999 was more tolerant to moderate Cd stress than the large-rooted Zhongke11. Addition of N ameliorated Cd stress in both maize genotypes by improving plant growth performance, and regulating Cd translocations among plant organs.