Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 154
Filtrar
1.
J Photochem Photobiol B ; 253: 112875, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430681

RESUMO

Candida albicans (C. albicans), a major opportunistic pathogenic fungus, is known to cause superficial skin infections. Unfortunately, the misuse of antibiotics has led to the emergence of drug resistance in fungi. Antimicrobial photodynamic therapy (aPDT), a non-antibiotic alternative, has shown potential in treating drug-resistant fungal infections. Curcumin is a photodynamically active phytochemical whose photodynamic fungicidal efficacy is largely dependent on its intracellular accumulation. However, curcumin faces challenges in penetrating the cytoplasm due to its poor water solubility and the fungal cell wall. Borneol, another monoterpenoid phytochemical, is known for its ability to enhance drug absorption. In this study, we showed that borneol improved the cellular uptake of curcumin, thereby enhancing its photodynamic fungicidal efficacy against C. albicans. This effect was attributed to borneol's ability to increase cell permeability. Transcriptomic analysis further confirmed that borneol disrupted the normal structure and function of the C. albicans cell wall and membrane, resulting in dysregulated mRNA expression of related genes and ultimately increased cell permeability. As a result, the excessive accumulation of curcumin in C. albicans triggered the overproduction of intracellular ROS upon exposure to blue light. These excessive intracellular ROS disrupted various cellular structures, interfered with essential cellular processes, inhibited biofilm formation and reduced virulence. Remarkably, borneol was also found to enhance curcumin uptake by C. albicans within biofilms, further enhancing the anti-biofilm efficacy of curcumin-mediated aPDT (Cur-aPDT). In conclusion, the results of this study strongly support the potential of borneol as an adjuvant agent to Cur-aPDT in treating superficial cutaneous fungal infections.


Assuntos
Anti-Infecciosos , Canfanos , Curcumina , Micoses , Fotoquimioterapia , Humanos , Candida albicans , Curcumina/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Fotoquimioterapia/métodos , Anti-Infecciosos/farmacologia , Adjuvantes Imunológicos/farmacologia , Compostos Fitoquímicos , Biofilmes , Fármacos Fotossensibilizantes/farmacologia
2.
J Agric Food Chem ; 72(13): 6871-6888, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38526460

RESUMO

Sesquiterpenes comprise a diverse group of natural products with a wide range of applications in cosmetics, food, medicine, agriculture, and biofuels. Heterologous biosynthesis is increasingly employed for sesquiterpene production, aiming to overcome the limitations associated with chemical synthesis and natural extraction. Sesquiterpene synthases (STSs) play a crucial role in the heterologous biosynthesis of sesquiterpene. Under the catalysis of STSs, over 300 skeletons are produced through various cyclization processes (C1-C10 closure, C1-C11 closure, C1-C6 closure, and C1-C7 closure), which are responsible for the diversity of sesquiterpenes. According to the cyclization types, we gave an overview of advances in understanding the mechanism of STSs cyclization from the aspects of protein crystal structures and site-directed mutagenesis. We also summarized the applications of engineering STSs in the heterologous biosynthesis of sesquiterpene. Finally, the bottlenecks and potential research directions related to the STSs cyclization mechanism and application of modified STSs were presented.


Assuntos
Alquil e Aril Transferases , Sesquiterpenos , Sesquiterpenos/metabolismo , Ciclização , Catálise , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo
3.
J Ovarian Res ; 17(1): 38, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347589

RESUMO

PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.


Assuntos
Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Transcriptoma , Reconhecimento Automatizado de Padrão , Células da Granulosa/metabolismo
4.
Sensors (Basel) ; 24(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38400272

RESUMO

Real-time and high-precision land cover classification is the foundation for efficient and quantitative research on grassland degradation using remote sensing techniques. In view of the shortcomings of manual surveying and satellite remote sensing, this study focuses on the identification and classification of grass species indicating grassland degradation. We constructed a UAV-based hyperspectral remote sensing system and collected field data in grassland areas. By applying artificial intelligence technology, we developed a 3D_RNet-O model based on convolutional neural networks, effectively addressing technical challenges in hyperspectral remote sensing identification and classification of grassland degradation indicators, such as low reflectance of vegetation, flat spectral curves, and sparse distribution. The results showed that the model achieved a classification accuracy of 99.05% by optimizing hyperparameter combinations based on improving residual block structures. The establishment of the UAV-based hyperspectral remote sensing system and the proposed 3D_RNet-O classification model provide possibilities for further research on low-altitude hyperspectral remote sensing in grassland ecology.

5.
J Leukoc Biol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334307

RESUMO

Poly (ADP ribose) polymerase family member 11(PARP11) has important immune regulatory functions in viral infection and tumor immune response. Particularly, PARP11 showed protumor activities in multiple preclinical murine models. However, no systematic pan-cancer analysis has been conducted to explore PARP11 function. In this study we used multiple databases to assess PARP11 expression, which associations with clinical outcomes, immune checkpoint factors, prognostic significance, genomic characteristics, and immunological aspects. The analysis revealed varying expression levels of PARP11 across different cancer types and a significant correlation between its expression and immune cell infiltration. Insights from the CellMiner database suggest a strong link between PARP11 expression and sensitivity to anticancer drugs, highlighting its potential as a therapeutic target. Moreover, PARP11 expression correlates with patient survival during anti-PD1 and anti-CTLA4 treatments, suggested that PARP11 would be a predictor of immune checkpoint inhibitor (ICI) treatment. In summary, PARP11 would be a potential immunoregulatory target and a diagnosis and prognosis marker for certain types of cancers. The detailed mechanisms of PARP11 in tumor immune responses need to be further investigated.

6.
Sci Total Environ ; 920: 170959, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38365035

RESUMO

Immobilization stands as the most widely adopted remediation technology for addressing heavy metal(loid) contamination in soil. However, it is crucial to acknowledge that this process does not eliminate pollutants; instead, it confines them, potentially leaving room for future mobilization. Presently, our comprehension of the temporal variations in the efficacy of immobilization, particularly in the context of its applicability to arid farmland, remains severely limited. To address this knowledge gap, our research delves deep into the roles of iron-oxidizing bacteria (FeOB) and organic fertilizer (OF) in the simultaneous immobilization of arsenic (As) and cadmium (Cd) in soils. We conducted laboratory incubation and field experiments to investigate these phenomena. When OF was combined with FeOB, a noteworthy transformation of available As and Cd into stable species, such as the residual state and combinations with Fe-Mn/Al oxides, was observed. This transformation coincided with changes in soil properties, including pH, Eh, soluble Fe, and dissolved organic carbon (DOC). Furthermore, we observed synergistic effects between available As and Cd when treated with bacteria and OF individually. The stabilization efficiency of As and Cd, as determined by the Toxicity Characteristic Leaching Procedure, reached its highest values at 33.39 % and 24.67 %, respectively, after 120 days. Nevertheless, the formation of iron­calcium complexes was disrupted due to pH fluctuations. Hence, long-term monitoring and model development are essential to enhance our understanding of the remediation process. The application of organic fertilizer and the use of FeOB in calcareous soil hold promise for the restoration of polluted soil and the maintenance of soil health by mitigating the instability of heavy metals(loid).


Assuntos
Arsênio , Metais Pesados , Poluentes do Solo , Cádmio/análise , Arsênio/análise , Solo/química , Fertilizantes , Metais Pesados/análise , Ferro , Bactérias/metabolismo , Oxirredução , Poluentes do Solo/análise
7.
Sci Total Environ ; 917: 170594, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38309366

RESUMO

Heavy metal composite pollution is widespread in the surrounding environment of tailings ponds in arid and semi-arid regions, leading to the abandonment of substantial agricultural land. This study investigates the speciation distribution and plant accumulation characteristics of heavy metals in abandoned farmland with different durations of natural aging. The aim is to comprehend the local heavy metal behavior pattern in the soil-plant system and offer insights for environmental remediation. Our findings reveal that Cd stands out as the primary heavy metal pollutant in this area. The mobility ranking of heavy metals is Cd > Pb > Zn > Cu, with Cd and Pb mobility decreasing along the basin. Notably, active Pb exhibits a higher affinity for soil binding compared to other metals. The predominant plant species in the region are primarily small shrubs, herbaceous plants, and semi-shrubs that demonstrate tolerance to drought and salt. Most plant samples showed elevated levels of Cd, Pb, and Zn, surpassing the maximum tolerance levels for dietary minerals in livestock. This elevated metal content poses potential threats to the health of local livestock and wildlife, yet it is also considered a potential for phytoremediation. Selected dominant plant species from the current study include Kalidium foliatum & gracile which shows potential as a Cd accumulator and indicator. Neotrinia splendens and Reaumuria songarica demonstrate potential as Cd excluders, with the latter exhibiting higher tolerance to Cd (62.9 mg/kg). Additionally, our observations indicate that different plant parts exhibit distinct responses to heavy metals, and Zn synergistically influences the aerial part accumulation of Cd. This study holds significant importance in understanding the complex behavior patterns of multi-metal pollutants in the natural environment. The identification of native plants with remediation potential is valuable for phytoremediation of environment pollution in mining area.


Assuntos
Poluentes Ambientais , Metais Pesados , Poluentes do Solo , Solo , Cádmio , Fazendas , Chumbo , Poluentes do Solo/análise , Metais Pesados/análise , Plantas , China , Monitoramento Ambiental
8.
Open Med (Wars) ; 19(1): 20230883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38205152

RESUMO

Kashin-Beck disease (KBD) is an endemic osteochondropathy. A specific gene called SRY-box transcription factor 6 (SOX6) is important for forming cartilage. This study aims to explore the potential correlation between SOX6 single nucleotide polymorphisms (SNPs) and KBD risk for the first time. In the case-control study, 735 unrelated Chinese Han individuals were enrolled. The four mutation sites of the SOX6 gene (rs4539287 G/A, rs3203295 C/A, rs7928675 C/A, and rs10832681 A/G) were screened and genotyped on the Agena MassARRAY platform. The correlation between SOX6 SNPs and KBD risk was explored based on logistic regression analysis. The interaction between SNP and SNP was analyzed based on the multi-factor dimensionality reduction (MDR) method. Overall analysis revealed a remarkable correlation between rs7928675 and rs10832681 and the reduction of KBD risk (p < 0.05). Subgroup analyses further indicated that these two SNPs have a significant protective effect on KBD risk among participants aged ≤65 years, males, and non-smokers (p < 0.05). MDR displayed a marked interaction between rs3203295 and rs10832681. Our study revealed that SOX6 rs7928675 and rs10832681 are markedly correlated with a reduced risk of KBD in the Chinese Han population, providing a new direction for the prevention, diagnosis, and treatment of KBD.

9.
EMBO Mol Med ; 16(1): 10-39, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38177530

RESUMO

Endocrine resistance is a crucial challenge in estrogen receptor alpha (ERα)-positive breast cancer (BCa). Aberrant alteration in modulation of E2/ERα signaling pathway has emerged as the putative contributor for endocrine resistance in BCa. Herein, we demonstrate that MYSM1 as a deubiquitinase participates in modulating ERα action via histone and non-histone deubiquitination. MYSM1 is involved in maintenance of ERα stability via ERα deubiquitination. MYSM1 regulates relevant histone modifications on cis regulatory elements of ERα-regulated genes, facilitating chromatin decondensation. MYSM1 is highly expressed in clinical BCa samples. MYSM1 depletion attenuates BCa-derived cell growth in xenograft models and increases the sensitivity of antiestrogen agents in BCa cells. A virtual screen shows that the small molecule Imatinib could potentially interact with catalytic MPN domain of MYSM1 to inhibit BCa cell growth via MYSM1-ERα axis. These findings clarify the molecular mechanism of MYSM1 as an epigenetic modifier in regulation of ERα action and provide a potential therapeutic target for endocrine resistance in BCa.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Receptor alfa de Estrogênio/genética , Moduladores de Receptor Estrogênico/farmacologia , Moduladores de Receptor Estrogênico/uso terapêutico , Histonas/metabolismo , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Transativadores/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
10.
Sensors (Basel) ; 24(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257706

RESUMO

With the increasing scale of deep-sea oil exploration and drilling platforms, the assessment, maintenance, and optimization of marine structures have become crucial. Traditional detection and manual measurement methods are inadequate for meeting these demands, but three-dimensional laser scanning technology offers a promising solution. However, the complexity of the marine environment, including waves and wind, often leads to problematic point cloud data characterized by noise points and redundancy. To address this challenge, this paper proposes a method that combines K-Nearest-Neighborhood filtering with a hyperbolic function-based weighted hybrid filtering. The experimental results demonstrate the exceptional performance of the algorithm in processing point cloud data from offshore oil and gas platforms. The method improves noise point filtering efficiency by approximately 11% and decreases the total error by 0.6 percentage points compared to existing technologies. Not only does this method accurately process anomalies in high-density areas-it also removes noise while preserving important details. Furthermore, the research method presented in this paper is particularly suited for processing large point cloud data in complex marine environments. It enhances data accuracy and optimizes the three-dimensional reconstruction of offshore oil and gas platforms, providing reliable dimensional information for land-based prefabrication of these platforms.

11.
Biochim Biophys Acta Mol Basis Dis ; 1870(2): 166974, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38042310

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with a poor prognosis. The therapeutic outcomes of HCC patients are urgently needed to be improved, and predictive biomarkers for the optimal treatment selection remains to be further defined. In the present study, our results showed that BPTF-associated protein of 18 KDa (BAP18) was highly expressed in HCC tissues. In cultured HCC cells, BAP18 regulated a subset of down-stream genes involved in different functions, particularly including peroxisome proliferator-activated receptor (PPAR) pathway and lipid metabolism. Furthermore, BAP18 co-activated PPARα-mediated transactivation and facilitated the recruitment of nucleosome acetyltransferase of H4 (NuA4)/tat interacting protein 60 (TIP60) complex, thereby increasing histone H4 acetylation on stearoyl-CoA desaturase 1 (SCD1) loci. In addition, BAP18 promoted HCC cell proliferation, increased intracellular lipid levels and enhanced cell survival under the metabolic stress conditions, such as glucose limitation or tyrosine kinase inhibitors (TKIs) treatment. Importantly, higher BAP18 expression was positively correlated with the postoperative recurrence and the poor disease-free survival in clinical patients receiving sorafenib treatment. Altogether, we discovered that BAP18 plays an oncogenic role in the survival and proliferation of HCC cells, and BAP18 may serve as a predictive biomarker for adjunct TKIs treatment in patients with HCC, and further facilitate the precise treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores , Carcinoma Hepatocelular/patologia , Linhagem Celular , Neoplasias Hepáticas/patologia , PPAR alfa/genética , Sorafenibe/uso terapêutico
12.
Sci Total Environ ; 913: 169547, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38160821

RESUMO

Anthropogenic activities release significant quantities of trace elements into the atmosphere, which can infiltrate ecosystems through both wet and dry deposition, resulting in ecological harm. Although the current study focuses on the emission inventory and deposition of trace elements, their complex interactions remain insufficiently explored. In this study, we employ emission inventories and deposition data for eight TEs (Cr, Mn, Ni, Cu, Zn, As, Cd, Pb) in Lanzhou City to unveil the relationship between these two aspects. Emissions in Lanzhou can be roughly divided into two periods centered around 2017. Preceding 2017, industrial production constituted the primary source of TEs emissions except for As; coal combustion was the primary contributor to Cr, Mn, and As emissions; waste incineration played a significant role in As, Zn, and Cd emissions; biomass combustion influenced Cr and Cd emissions; and transportation sources were the predominant contributors to Pb and Cu emissions. With the establishment of waste-to-energy plants and the implementation of ultra-low emission retrofits, emissions from these sources decreased substantially after 2017. Consequently, emissions from industrial production emerged as the main source of TEs. The deposition concentrations of Cr, Mn, Ni, Cu, and Pb followed a similar trend to the emissions. However, Cd and As exhibited lower emissions and a less pronounced response relationship. Moreover, Zn concentrations fluctuated within a narrow range and showed a weaker response to emissions. The consistent changes in emissions and TEs deposition concentrations signify a shift in deposition pollution in Lanzhou city from Coal-fired pollution to that driven by transportation and industrial activities. Within this transition, the industrial production process offers significant potential for emission reduction. This insight provides a crucial foundation for managing TEs pollution and implementing strategies to prevent ecological risks.

13.
J Environ Manage ; 350: 119587, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38000273

RESUMO

The accurate pollutant prediction by Machine Learning (ML) is significant to efficient environmental monitoring and risk assessment. However, application of ML in soil is under studied. In this study, a Positive Matrix Factorization (PMF) assisted prediction method was developed with Support Vector Machine (SVM) and Random Forest (RF) for heavy metals (HMs) prediction in mining farmland. Principal Component Analysis (PCA) and Redundancy Analysis (RDA) were selected to pretreat data. Experiment results illustrated Cd was the main pollutant with heavy risks in the study area and Pb was easy to migrate. The method effects of HMs total concentration predicting were PMF > Simple > PCA > PCA - PMF, and RF predicted better than SVM. Data pretreatment by RDA prior inspection improved the model results. Characteristic HMs Tessier fractions prediction received good effects with average R value as 0.86. Risk classification prediction performed good in Cd, Cu, Ni and Zn, however, Pb showed weak effect by simple model. The best classifier method for Pb was PMF - RF method with relatively good effect (Area under ROC Curve = 0.896). Overall, our study suggested the combination between PMF and ML can assist the prediction of HMs in soil. Spatial weighted attribute of HMs can be provided by PMF.


Assuntos
Poluentes Ambientais , Metais Pesados , Poluentes do Solo , Fazendas , Cádmio , Chumbo , Poluentes do Solo/análise , Metais Pesados/análise , Solo , Monitoramento Ambiental/métodos , Aprendizado de Máquina , Medição de Risco , China
14.
J Fungi (Basel) ; 9(10)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37888273

RESUMO

Sesquiterpenes are a type of abundant natural product with widespread applications in several industries. They are biosynthesized by sesquiterpene synthases (STSs). As valuable and abundant biological resources, mushroom-forming fungi are rich in new sesquiterpenes and STSs, which remain largely unexploited. In the present study, we collected information on 172 STSs from mushroom-forming fungi with experimentally characterized products from the literature and sorted them to develop a dataset. Furthermore, we analyzed and discussed the phylogenetic tree, catalytic products, and conserved motifs of STSs. Phylogenetic analysis revealed that the STSs were clustered into four clades. Furthermore, their cyclization reaction mechanism was divided into four corresponding categories. This database was used to predict 12 putative STS genes from the edible fungi Flammulina velutipes. Finally, three FvSTSs were selected to experimentally characterize their functions. FvSTS03 predominantly produced Δ-cadinol and FvSTS08 synthesized ß-barbatene as the main product; these findings were consistent with those of the functional prediction analysis. A product titer of 78.8 mg/L ß-barbatene was achieved in Saccharomyces cerevisiae via metabolic engineering. Our study findings will help screen or design STSs from fungi with specific product profiles as functional elements for applications in synthetic biology.

15.
Sensors (Basel) ; 23(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37687939

RESUMO

The utilization of multibeam sonar systems has significantly facilitated the acquisition of underwater bathymetric data. However, efficiently processing vast amounts of multibeam point cloud data remains a challenge, particularly in terms of rejecting massive outliers. This paper proposes a novel solution by implementing a cone model filtering method for multibeam bathymetric point cloud data filtering. Initially, statistical analysis is employed to remove large-scale outliers from the raw point cloud data in order to enhance its resistance to variance for subsequent processing. Subsequently, virtual grids and voxel down-sampling are introduced to determine the angles and vertices of the model within each grid. Finally, the point cloud data was inverted, and the custom parameters were redefined to facilitate bi-directional data filtering. Experimental results demonstrate that compared to the commonly used filtering method the proposed method in this paper effectively removes outliers while minimizing excessive filtering, with minimal differences in standard deviations from human-computer interactive filtering. Furthermore, it yields a 3.57% improvement in accuracy compared to the Combined Uncertainty and Bathymetry Estimator method. These findings suggest that the newly proposed method is comparatively more effective and stable, exhibiting great potential for mitigating excessive filtering in areas with complex terrain.

16.
J Agric Food Chem ; 71(33): 12452-12461, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37574876

RESUMO

α-Farnesene, a type of acyclic sesquiterpene, is an important raw material in agriculture, aircraft fuel, and the chemical industry. In this study, we constructed an efficient α-farnesene-producing yeast cell factory by combining enzyme and metabolic engineering strategies. First, we screened different plants for α-farnesene synthase (AFS) with the best activity and found that AFS from Camellia sinensis (CsAFS) exhibited the most efficient α-farnesene production in Saccharomyces cerevisiae 4741. Second, the metabolic flux of the mevalonate pathway was increased to improve the supply of the precursor farnesyl pyrophosphate. Third, inducing site-directed mutagenesis in CsAFS, the CsAFSW281C variant was obtained, which considerably increased α-farnesene production. Fourth, the N-terminal serine-lysine-isoleucine-lysine (SKIK) tag was introduced to construct the SKIK∼CsAFSW281C variant, which further increased α-farnesene production to 2.8 g/L in shake-flask cultures. Finally, the α-farnesene titer of 28.3 g/L in S. cerevisiae was obtained by fed-batch fermentation in a 5 L bioreactor.


Assuntos
Saccharomyces cerevisiae , Engenharia Metabólica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Filogenia , Pirofosfatases/genética , Pirofosfatases/metabolismo , Mutagênese Sítio-Dirigida
17.
Arch Immunol Ther Exp (Warsz) ; 71(1): 20, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37632545

RESUMO

Fibroblast growth factor 2 (FGF-2) is not only an angiogenic factor, but also a mitogen for epidermal keratinocytes. FGF-2 has been shown to be positively immunoreactive in the basal layer of psoriatic lesions. In previous work, we used the Escherichia coli (E. coli) expression system to biosynthesize a biologically active anti-FGF-2 nanobody (Nb) screened by phage display technology, but the low yield limited its clinical application. In this study, we aimed to increase the yield of anti-FGF-2 Nb, and evaluate its therapeutic potential for psoriasis by inhibiting FGF-2-mediated mitogenic signaling in psoriatic epidermal keratinocytes. We demonstrated a 16-fold improvement in the yield of anti-FGF-2 Nb produced in the Pichia pastoris (P. pastoris) compared to the  E. coli expression system. In vitro, the FGF-2-induced HaCaT cell model (FHCM) was established to mimic the key feature of keratinocyte overproliferation in psoriasis. Anti-FGF-2 Nb was able to effectively inhibit the proliferation and migration of FHCM. In vivo, anti-FGF-2 Nb attenuated the severity of imiquimod (IMQ)-induced psoriatic lesions in mice, and also improved the inflammatory microenvironment by inhibiting the secretion of inflammatory cytokines (IL-1ß, IL-6, IL-23, and TNF-α), chemokines (CXCL1 and CCL20), and neutrophil infiltration in skin lesions. These were mainly related to the suppression of FGF-2-mediated mitogenic signaling in psoriatic keratinocytes. In conclusion, we have improved the production of anti-FGF-2 Nb and demonstrated the modality of attenuating the abnormal proliferative behavior of psoriatic keratinocytes by inhibiting FGF-2-mediated mitogenic signaling, which offers the possibility of treating psoriasis.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Psoríase , Animais , Camundongos , Escherichia coli , Queratinócitos , Psoríase/tratamento farmacológico , Humanos
18.
Polymers (Basel) ; 15(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37376254

RESUMO

Polyimide foam (PIF) is a rising star in high-end applications such as aerospace thermal insulation and military sound absorption. However, the basic rule on molecular backbone design and uniform pore formation of PIF still need to be explored. In this work, polyester ammonium salt (PEAS) precursor powders are synthesized between alcoholysis ester of 3, 3', 4, 4'-benzophenone tetracarboxylic dianhydride (BTDE) and aromatic diamines with different chain flexibility and conformation symmetry. Then, a standard "stepwise heating" thermo-foaming approach is used to prepare PIF with comprehensive properties. A rational thermo-foaming program is designed based on in situ observation of pore formation during heating. The fabricated PIFs have uniform pore structure, and PIFBTDA-PDA shows the smallest size (147 µm) and narrow distribution. Interestingly, PIFBTDA-PDA also presents a balanced strain recovery rate (SR = 91%) and mechanical robustness (0.051 MPa at 25% strain) and its pore structure maintains regularity after 10 compression-recovery cycles, mainly due to high rigidity of the chains. Furthermore, all the PIFs possess lightweight feature (15-20 kg∙m-3), good heat resistance (Tg at 270-340 °C), thermal stability (T5% at 480-530 °C), thermal insulation properties (λ = 0.046-0.053 W∙m-1K-1 at 20 °C, λ = 0.078-0.089 W∙m-1K-1 at 200 °C), and excellent flame retardancy (LOI > 40%). The reported monomer-mediated pore-structure control strategy can provide guidelines for the preparation of high-performance PIF and its industrial applications.

19.
J Leukoc Biol ; 114(2): 111-115, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37141382

RESUMO

New strategies targeting STING proteins appear promising for eliciting immunotherapeutic responses. Activation of the STING pathway under the right circumstances can drive dendritic cell maturation, antitumor macrophage differentiation, T-cell initiation and activation, natural killer cell activation, vascular reprogramming, and/or cancer cell death, leading to immune-mediated tumor elimination and generation of antitumor immune memory. However, activation of the STING signaling pathway is complicated in tumor immunity. On one hand, STING signaling was found to promote tumor growth. On the other hand, the cGAS-STING pathway has great potential for regulating antitumor immunity. The development of activators of the cGAS-STING pathway may profoundly change tumor immunotherapy, providing an excellent direction for the development and clinical application of immunotherapeutic strategies for related diseases. This review provides a concise summary of the role of the STING pathway in tumors in recent years.


Assuntos
Memória Imunológica , Transdução de Sinais , Morte Celular , Diferenciação Celular , Nucleotidiltransferases , Humanos
20.
Environ Geochem Health ; 45(10): 7255-7274, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37004580

RESUMO

Understanding the precise sources of heavy metals (HMs) in soil and the contribution of these sources to health risks has positive effects in terms of risk management. This study focused on the HMs in the soil of five land uses in an industrial and mining city. The sources of HMs in soils were identified, and the soil mineralogical characteristics and health risks of HMs were discussed. The results showed that the HMs (Cu, Zn, Ni, Cd, Pb) found in the soil of the five land uses were affected by human activities. For example, the Cu in grassland, gobi beach, woodland, green belt, and farmland is 22.3, 3.5, 22.5, 16.7, and 21.3 times higher than the soil background values in Gansu Province, respectively. The Positive Matrix Factorization model (PMF) results revealed that traffic emissions and industrial and agricultural activities were the primary sources of HMs in the soil, with industrial sources accounting for the largest share at 55.79%. Furthermore, various characteristics proved that the studied HMs were closely related to smelting products. Concentration-oriented health risk assessments showed that HMs in the different soil types held non-carcinogenic and carcinogenic risks for children and adults. Contamination source-oriented health risk assessments of children and adults found that industrial activities controlled non-carcinogenic and carcinogenic risks. This study highlighted the critical effects of smelting on urban soil and the contribution of pollution sources to health risks. Furthermore, this work is significant in respect of the risk control of HMs in urban soils.


Assuntos
Metais Pesados , Poluentes do Solo , Humanos , Carcinógenos , China , População do Leste Asiático , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...