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1.
Clin Psychol Psychother ; 31(2): e2990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659274

RESUMO

BACKGROUND: The prevalence of suicide is high among major depressive adolescents. Poor sleep quality has been documented as a significant risk factor for suicide, influencing perceived social support. Enhanced social support acts as a buffer against suicidal ideation and positively impacts resilience, reducing the prevalence of suicidal ideation. This reciprocal relationship between sleep quality, social support and resilience forms the basis for understanding the mechanisms contributing to suicidal ideation in major depressive adolescents. METHODS: A total of 585 major depressive adolescents aged 11 to 24 years was conducted to explore these associations. Assessments included the Pittsburgh Sleep Quality Index, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale and Beck Scale for Suicide Ideation. Pearson correlation and Model 6 in the SPSS program were employed for chain mediating tests. RESULTS: Better sleep quality positively predicted decreased suicide ideation (ß = 0.207, p < 0.01) and predicted lower perceived social support (ß = -0.226, p < 0.01) and resilience (ß = -0.355, p < 0.01). Perceived social support positively predicted increased resilience (ß = 0.422, p < 0.01) and negatively predicted suicide ideation (ß = -0.288, p < 0.01). Resilience negatively predicted suicide ideation (ß = -0.187, p < 0.01). Sleep quality indirectly predicted suicide ideation through perceived social support and resilience, with a mediation value of 0.0678 (95% CI [0.0359, 0.1060]), constituting 10.65% of the total effect. CONCLUSIONS: This study establishes that sleep quality indirectly predicts suicide ideation in major depressive adolescents, mediated independently by perceived social support and resilience.


Assuntos
Transtorno Depressivo Maior , Resiliência Psicológica , Qualidade do Sono , Apoio Social , Ideação Suicida , Humanos , Adolescente , Feminino , Masculino , Transtorno Depressivo Maior/psicologia , Criança , Adulto Jovem , Fatores de Risco
3.
Cancer Med ; 13(3): e6799, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38239049

RESUMO

Allogeneic hematopoietic stem cell transplantation is one of the most effective treatment strategies for leukemia, lymphoma, and other hematologic malignancies. However, graft-versus-host disease (GVHD) can significantly reduce the survival rate and quality of life of patients after transplantation, and is therefore the greatest obstacle to transplantation. The recent development of new technologies, including high-throughput sequencing, metabolomics, and others, has facilitated great progress in understanding the complex interactions between gut microbiota, microbiota-derived metabolites, and the host. Of these interactions, the relationship between gut microbiota, microbial-associated metabolites, and GVHD has been most intensively researched. Studies have shown that GVHD patients often suffer from gut microbiota dysbiosis, which mainly manifests as decreased microbial diversity and changes in microbial composition and microbiota-derived metabolites, both of which are significant predictors of poor prognosis in GVHD patients. Therefore, the purpose of this review is to summarize what is known regarding changes in gut microbiota and microbiota-derived metabolites in GVHD, their relationship to GVHD prognosis, and corresponding clinical strategies designed to prevent microbial dysregulation and facilitate treatment of GVHD.


Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Microbiota , Humanos , Qualidade de Vida , Doença Enxerto-Hospedeiro/etiologia , Disbiose
4.
Nat Commun ; 15(1): 226, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172511

RESUMO

Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish. Mechanistically, nlrc3 activates the Notch pathway and the downstream gene of Notch hey1. Furthermore, NF-kB signaling acts upstream of nlrc3 to enhance its transcriptional activity. Finally, we find that Nlrc3 signaling is conserved in the regulation of murine embryonic hematopoiesis. Taken together, our findings uncover an indispensable role of Nlrc3 signaling in hematopoietic stem and progenitor cell emergence and provide insights into inflammation-related hematopoietic ontogeny and the in vitro expansion of hematopoietic stem and progenitor cells.


Assuntos
Células-Tronco Hematopoéticas , Peixe-Zebra , Animais , Camundongos , Diferenciação Celular/genética , Células-Tronco Hematopoéticas/metabolismo , Hematopoese/genética , Transdução de Sinais , Receptores Notch/metabolismo
5.
J Sci Food Agric ; 104(3): 1531-1538, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37824792

RESUMO

BACKGROUND: Excessive sugar consumption has been linked to type 2 diabetes, obesity and other diseases. Therefore, it is indispensable to reduce sugar of food. However, the sensory characteristics of food are affected after sugar reduction (SR). Currently, SR has been reported in drinks, jams, candies, and other fruit related or sweet foods; but salty or protein related foods have not been explored, therefore there is a big gap that needs to be filled. RESULTS: Sensory scores of initial sweetness and sweetness reduced by 0.26 and 0.12 in 10% SR dried fish mince product compared with control, and there was a small difference between 25% SR (3.33) and 40% SR (3.09) samples. It also showed that 10% SR sample had a small reduction in sweetness value and free sugar content by 3.5% (0.42/11.9) and 7.8% (2.12/27.06) compared with control; while values in 25% SR sample decreased sharply but were not much different from 40% SR sample. Electronic nose results showed that SR had a small effect on odor. Texture analysis showed that texture properties of 25% SR sample were significantly different from control. CONCLUSIONS: Dried fish mince product with below 10% SR had a small difference on the sensory characteristics and there was a big change when SR was more than 20%. Dried fish mince product with 25% SR and 40% SR had no significant difference. SR had a small effect on odor, but had a great effect on texture properties, especially over 20% SR. © 2023 Society of Chemical Industry.


Assuntos
Diabetes Mellitus Tipo 2 , Açúcares , Animais , Açúcares/análise , Produtos Pesqueiros , Manipulação de Alimentos/métodos , Frutas/química
6.
J Mol Graph Model ; 126: 108658, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37871454

RESUMO

In this paper, the first-principle calculations of the lateral heterojunction model synthesized by hBN-Graphene were carried out, and it was found that the bandgap of graphene varied with the change in the proportion of hBN, and the bandgap was best regulated with a bandgap of 1.177 eV when the proportion of hBN was 66.67 %. At this time, the adsorption structures of HCN, CO, NH3, and Cl2 were established and energy band calculations were performed on the hBN and Graphene portions of the hBN-Graphene lateral heterojunctions, respectively, and it was found that the adsorption of Cl2 resulted in a significant change in the band gap, which showed a very high electrical sensitivity. To further investigate the adsorption mechanism of Cl2 on the surface of hBN-Graphene lateral heterojunction, the energy band structure, PDOS, charge transfer, adsorption energy, and recovery time of each stabilized adsorption site of Cl2 on the surface of hBN-Graphene lateral heterojunction were calculated. The results show that the adsorption of Cl2 on the surface of hBN-Graphene lateral heterojunction is a stable chemisorption, and the band gap of C-Top1 increases to 1.274 eV, and the band gaps of C-Top3, N-Top1, and N-Top2 decrease to 0.684 eV, 0.376 eV, and 0.398 eV, respectively, and the changes of band gaps are significant and easy to be electrically detection. The recovery time of Cl2 on the surface of hBN-Graphene lateral heterojunction was 7.36 s-2.59 s in visible light and in the temperature interval of 273 K-283 K. The recovery time of Cl2 on the surface of hBN-Graphene lateral heterojunction was 7.36 s-2.59 s in visible light and in the temperature interval of 273 K-283 K. These findings have implications for the research and application of graphene-based Cl2 gas sensors.


Assuntos
Elétrons , Grafite , Adsorção , DNA Topoisomerases Tipo II , Eletricidade
7.
J Colloid Interface Sci ; 659: 31-39, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38157724

RESUMO

Rational construction of efficient carbon-supported rare earth cerium nanoclusters as oxygen reduction reaction (ORR) is of great significance to promote the practical application of zinc-air batteries (ZABs). Herein, N doped conductive carbon black anchored CeO2 nanoclusters (CeO2 Clusters/NC) for the ORR is reported. The volatile cerium species vaporized by CeO2 nanoclusters at high temperatures are captured by nitrogen-rich carbon carriers to form highly dispersed Ce-Nx active sites. Benefiting from the coupling effect between oxygen vacancies-enriched CeO2 nanoclusters and highly dispersed Ce-Nx sites, the prepared 2CeO2 Clusters/NC catalyst possesses an ORR half-wave potential of 0.88 V, superior electrochemical stability, and better methanol tolerance compared to commercial Pt/C catalysts. Moreover, the 2CeO2 Clusters/NC involved liquid ZABs show excellent energy efficiency, superior stability, and a high energy density of 982 Wh kg-1 at 10 mA cm-2.

8.
New Phytol ; 241(4): 1510-1524, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38130037

RESUMO

Brassinosteroids (BRs) are plant hormones that are essential in plant growth and development. BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1 ASSOCIATED RECEPTOR KINASE 1 (BAK1), which are located on the plasma membrane, function as co-receptors that accept and transmit BR signals. PROHIBITIN 3 (PHB3) was identified in both BRI1 and BAK1 complexes by affinity purification and LC-MS/MS analysis. Biochemical data showed that BRI1/BAK1 interacted with PHB3 in vitro and in vivo. BRI1/BAK1 phosphorylated PHB3 in vitro. When the Thr-80 amino acid in PHB3 was mutated to Ala, the mutant protein was not phosphorylated by BRI1 and the mutant protein interaction with BRI1 was abolished in the yeast two-hybrid assay. BAK1 did not phosphorylate the mutant protein PHB3T54A . The loss-of-function phb3 mutant showed a weaker BR signal than the wild-type. Genetic analyses revealed that PHB3 is a BRI1/BAK1 downstream substrate that participates in BR signalling. PHB3 has five homozygous in tomato, and we named the closest to AtPHB3 as SlPHB3.1. Biochemical data showed that SlBRI1/SlSERK3A/SlSERK3B interacted with SlPHB3.1 and SlPHB3.3. The CRISPR-Cas9 method generated slphb3.1 mutant led to a BR signal stunted relatively in tomatoes. PHB3 is a new component of the BR signal pathway in both Arabidopsis and tomato.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Arabidopsis/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Brassinosteroides/metabolismo , Solanum lycopersicum/genética , Proteínas Quinases/metabolismo , Fosforilação , Proteínas de Arabidopsis/metabolismo , Cromatografia Líquida , Proibitinas , Espectrometria de Massas em Tandem , Transdução de Sinais/fisiologia , Proteínas Mutantes
9.
Ann Hematol ; 102(12): 3555-3566, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37770617

RESUMO

Growing evidence suggests that highly intestinal microbiota diversity modulates host inflammation and promotes immune tolerance. Several studies have reported that patients undergoing allo-HSCT have experienced microbiota disruption that is characterized by expansion of potentially pathogenic bacteria and loss of microbiota diversity. Thus, the primary aim of this meta-analysis was to determine the association of intestinal microbiota diversity and outcomes after allo-HSCT, and the secondary aim was to analyze the associations of some specific microbiota abundances with the outcomes of allo-HSCT. Electronic databases of Pubmed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2023, and 17 studies were found eligible. The pooled estimate suggested that higher intestinal microbiota diversity was significantly associated with overall survival (OS) benefit (HR = 0.66, 95% CI: 0.55-0.78), as well as decreased risk of transplant-related mortality (HR = 0.56, 95% CI: 0.41-0.76), and lower incidence of grade II-IV aGVHD (HR = 0.41, 95% CI: 0.27-0.63). Furthermore, higher abundance of Clostridiales was associated with a superior OS (HR = 0.40, 95% CI: 0.18-0.87), while higher abundance of Enterococcus (HR = 2.03, 95% CI: 1.55-2.65), γ-proteobacteria (HR = 2.82, 95% CI: 1.53-5.20), and Candida (HR = 3.80, 95% CI: 1.32-10.94) was an adverse prognostic factor for OS. Overall, this meta-analysis highlights the protective role of higher intestinal microbiota diversity on outcomes after allo-HSCT during both pre-transplant and post-transplant periods. Some specific microbiota can be useful in the identification of patients at risk of mortality, offering new tools for individualized pre-emptive or therapeutic strategies to improve allo-HSCT outcomes.


Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Microbiota , Humanos , Recidiva Local de Neoplasia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Bactérias , Doença Enxerto-Hospedeiro/etiologia
10.
Front Immunol ; 14: 1045009, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529051

RESUMO

During the first waves of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, olfactory dysfunction (OD) was reported as a frequent clinical sign. The nasal epithelium is one of the front-line protections against viral infections, and the immune responses of the nasal mucosa may be associated with OD. Two mechanisms underlying OD occurrence in COVID-19 have been proposed: the infection of sustentacular cells and the inflammatory reaction of the nasal epithelium. The former triggers OD and the latter likely prolongs OD. These two alternative mechanisms may act in parallel; the infection of sustentacular cells is more important for OD occurrence because sustentacular cells are more likely to be the entry point of SARS-CoV-2 than olfactory neurons and more susceptible to early injury. Furthermore, sustentacular cells abundantly express transmembrane protease, serine 2 (TMPRSS2) and play a major role in the olfactory epithelium. OD occurrence in COVID-19 has revealed crucial roles of sustentacular cells. This review aims to elucidate how immune responses of the nasal epithelium contribute to COVID-19-related OD. Understanding the underlying immune mechanisms of the nasal epithelium in OD may aid in the development of improved medical treatments for COVID-19-related OD.


Assuntos
COVID-19 , Transtornos do Olfato , Humanos , COVID-19/complicações , SARS-CoV-2 , Transtornos do Olfato/etiologia , Transtornos do Olfato/epidemiologia , Olfato , Mucosa Nasal
11.
Science ; 379(6635): 892-901, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36862793

RESUMO

We elucidate grapevine evolution and domestication histories with 3525 cultivated and wild accessions worldwide. In the Pleistocene, harsh climate drove the separation of wild grape ecotypes caused by continuous habitat fragmentation. Then, domestication occurred concurrently about 11,000 years ago in Western Asia and the Caucasus to yield table and wine grapevines. The Western Asia domesticates dispersed into Europe with early farmers, introgressed with ancient wild western ecotypes, and subsequently diversified along human migration trails into muscat and unique western wine grape ancestries by the late Neolithic. Analyses of domestication traits also reveal new insights into selection for berry palatability, hermaphroditism, muscat flavor, and berry skin color. These data demonstrate the role of the grapevines in the early inception of agriculture across Eurasia.


Assuntos
Evolução Biológica , Domesticação , Vitis , Humanos , Agricultura , Ásia Ocidental , Ecótipo , Fenótipo , Vitis/genética , Aclimatação
12.
J Ovarian Res ; 16(1): 8, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627652

RESUMO

BACKGROUND: Chemotherapy is among the most common treatment methods for ovarian cancer (OC). However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. We herein investigate the biological effect of forkhead box D3 (FOXD3) in the chemoresistance of OC cells. METHODS: Expression of FOXD3, miR-335 and disheveled-associated activator of morphogenesis 1 (DAAM1) was detected in OC cells and tissues. The regulatory network of FOXD3/miR-335/DAAM1 was validated by dual-luciferase reporter and ChIP assays in vitro. After ectopic expression and depletion experiments in carboplatin/paclitaxel (CP)-resistant (A2780CP) or sensitive (A2780S) OC cells, cell viability, colony formation and apoptosis were tested by CCK-8 assay, colony formation assay and flow cytometry respectively. Effects of FOXD3 on the chemoresistance of OC cells in vivo were evaluated in OC xenografts in nude mice. RESULTS: Overexpression of FOXD3 impaired the proliferation and chemoresistance of OC cells, which was related to the promotion of the miR-335 expression. Functionally, DAAM1 was a putative target of miR-335. Silencing of DAAM1 was responsible for the inhibition of myosin II activation, consequently leading to suppressed OC cell proliferation and chemoresistance. In vivo results further showed that FOXD3 weakened the chemoresistance of OC cells to CP. CONCLUSION: Taken together, we unveil a novel FOXD3/miR-335/DAAM1/myosin II axis that regulates the chemoresistance of OC both in vitro and in vivo.


Assuntos
Fatores de Transcrição Forkhead , MicroRNAs , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proteínas dos Microfilamentos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Proteínas rho de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/uso terapêutico
13.
J Environ Sci (China) ; 123: 15-29, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521980

RESUMO

Diesel vehicles have caused serious environmental problems in China. Hence, the Chinese government has launched serious actions against air pollution and imposed more stringent regulations on diesel vehicle emissions in the latest China VI standard. To fulfill this stringent legislation, two major technical routes, including the exhaust gas recirculation (EGR) and high-efficiency selective catalytic reduction (SCR) routes, have been developed for diesel engines. Moreover, complicated aftertreatment technologies have also been developed, including use of a diesel oxidation catalyst (DOC) for controlling carbon monoxide (CO) and hydrocarbon (HC) emissions, diesel particulate filter (DPF) for particle mass (PM) emission control, SCR for the control of NOx emission, and an ammonia slip catalyst (ASC) for the control of unreacted NH3. Due to the stringent requirements of the China VI standard, the aftertreatment system needs to be more deeply integrated with the engine system. In the future, aftertreatment technologies will need further upgrades to fulfill the requirements of the near-zero emission target for diesel vehicles.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Emissões de Veículos/prevenção & controle , Emissões de Veículos/análise , Poluição do Ar/prevenção & controle , Poluição do Ar/análise , Catálise , China , Gasolina , Material Particulado/análise , Veículos Automotores
14.
Int J Mol Sci ; 23(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36232562

RESUMO

Brassinosteroid (BR) signaling is very important in plant developmental processes. Its various components interact to form a signaling cascade. These components are widely studied in Arabidopsis; however, very little information is available on tomatoes. Brassinosteroid Insensitive 2 (BIN2), the downstream suppressor of BR signaling, plays a critical role in BR signal pathway, while FRIGIDA as a key suppressor of Flowering Locus C with overexpression could cause early flowering; however, how the BR signaling regulates FRIGIDA homologous protein to adjust flowering time is still unknown. This study identified 12 FRIGIDA-LIKE proteins with a conserved FRIGIDA domain in tomatoes. Yeast two-hybrid and BiFC confirmed that SlBIN2 interacts with 4 SlFRLs, which are sub-cellularly localized in the nucleus. Tissue-specific expression of SlFRLs was observed highly in young roots and flowers. Biological results revealed that SlFRLs interact with SlBIN2 to regulate early flowering. Further, the mRNA level of SlBIN2 also increased in SlFRL-overexpressed lines. The relative expression of SlCPD increased upon SlFRL silencing, while SlDWF and SlBIN2 were decreased, both of which are important for BR signaling. Our research firstly provides molecular evidence that BRs regulate tomato flowering through the interaction between SlFRLs and SlBIN2. This study will promote the understanding of the specific pathway essential for floral regulation.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Brassinosteroides/metabolismo , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Proteínas Quinases/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia
15.
Front Psychiatry ; 13: 976386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117657

RESUMO

Background: The prevalence of adolescent depression in China during the COVID-19 pandemic is increasing. Self-disclosing depressive emotions could help release stress. Self-disclosure, which is a prerequisite for self-efficacy, can directly contribute to people's psychological health, and depression and the choice of coping strategy are determined by the level of self-efficacy perceived. Purpose: We aimed to discuss the relationship between self-efficacy, self-disclosure, and medical coping strategy. Further, we explore the mediation effect of self-efficacy on the influence of self-disclosure on medical coping strategies in adolescents with depression. Methods: A total of 585 patients aged 11-24 years with moderate and major depression were recruited. All the assessments were completed on the second day after admission, including the General Self-Efficacy Scale (GSE), Distress Disclosure Index (DDI), and Medical Coping Modes Questionnaire (MCMQ). Pearson correlation was performed to explore the relationships of these variables. The bootstrap analysis was used to conduct to assess the mediation effects. Results: Both direct and indirect effects of self-disclosure on medical coping strategy were found. As predicted, self-efficacy partially mediated the relationship between self-disclosure and medical coping strategy (b = 0.0385, 95% CI: 0.0244-0.0538 for Confrontation; b = -0.0466, 95%CI: -0.0651 to -0.0296 for Resignation), respectively. The effect size for Confrontation and Resignation was 0.2659 and 0.2485, respectively. Conclusion: Self-efficacy played a partial mediating role in the effect of self-disclosure on medical coping strategies for adolescent depression during the COVID-19 pandemic, and the use of a positive self-disclosure mechanism may be anticipated to promote improved self-efficacy and the use of active coping strategies.

16.
Front Chem ; 10: 933319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873057

RESUMO

When utilized in energy devices, the restacking tendency of MXene Ti3C2T x inhibits its electrochemical performance. Using aerosol jet printing (AJP) technology, hybrid Ti3C2T x /C nanospheres are synthesized with C nanoparticle-bonded MXene nanosheets, and the restacking of MXene nanosheets is blocked efficiently. The formation mechanism for hybrid Ti3C2T x /C nanospheres has been hypothesized, and the Ti3C2T x /C is anticipated to assemble and shape along the droplet surface in tandem with the Marangoni flow within the droplet. The planar microsupercapacitor devices generated from these hybrid spherical nanostructures with increased interlayer spacing exhibit exceptional areal capacitance performance. This concept offers a straightforward and effective method for constructing 3D-structured MXene with suppressed self-stacking for diverse high-performance micro energy storage devices.

17.
J Food Drug Anal ; 30(1): 150-162, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35647726

RESUMO

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances. Eight NA substructures containing susceptible amino sources for N-nitrosation have been identified as screening targets: dimethylamine (DMA), diethylamine, isopropylethylamine, diisopropylamine, N-methyl-2-pyrrolidone, dibutylamine, methylphenylamine, and tetrazoles. Our method detected 192 drug substances with a theoretical possibility of NA impurity, 141 of which had not been reported previously. In addition, the DMA moiety was significantly dominant among the eight NA substructures. The results were validated using data from the literature, and a high detection sensitivity of 0.944 was demonstrated. Furthermore, our approach has the advantage of scalability, owing to which 31 additional drugs with suspected NA-contaminated substructures were identified using the substructures of 1-methyl-4-piperazine in rifampin and 1-cyclopentyl-4-piperazine in rifapentine. In conclusion, the reported substructure-based approach provides an effective and scalable method for the screening and investigation of NA impurities in various pharmaceuticals and might be used as an ancillary technique in the field of pharmaceutical quality control for risk assessments of potential NA impurities.


Assuntos
Contaminação de Medicamentos , Nitrosaminas , Piperazinas , Controle de Qualidade , Medição de Risco
18.
Artigo em Inglês | MEDLINE | ID: mdl-35035506

RESUMO

Inflammation is generally considered a key risk factor in the progress of several chronic diseases, such as arthritis, gastritis, and hepatitis. Natural products with anti-inflammatory ability have played a great role in the process of overcoming these inflammatory diseases. In this study, we evaluated the anti-inflammatory activities of ten natural compounds derived from lotus seedpod and discovered (E)-9-octadecenoic acid ethyl ester (E9OAEE) inhibited the production of nitric oxide (NO) optimally in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Furthermore, we explored the effects of E9OAEE on inflammatory responses and the underlying mechanisms in LPS-induced RAW264.7 macrophages. The results indicated that E9OAEE significantly suppressed the production of NO, prostaglandin E2 (PGE2), and tumour necrosis factor-α (TNFα) in a dose-dependent manner. The protein expression and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) were inhibited by pretreatment of E9OAEE. Furthermore, E9OAEE restrained the phosphorylation of mitogen-activated protein kinase (MAPKs) family members, ERK, P38, and JNK stimulated by LPS-treated for 30 min and prevented the nuclear translocation of nuclear factor-kappa B (NF-κB) prompted by LPS-treated for 6 h in RAW264.7 macrophages. Taken together, we discovered an anti-inflammatory component from lotus seedpod and identified E9OAEE attenuated the inflammatory response in LPS-induced RAW264.7 macrophages probably by regulating the activation of MAPKs and NF-κB signalling pathways, which would provide some base for the development of new anti-inflammatory drugs.

19.
Food Nutr Res ; 662022.
Artigo em Inglês | MEDLINE | ID: mdl-36590859

RESUMO

Background: Macrophage plays an important role in innate immune responses by secreting immune molecules and phagocytosis. Camellia oleifera fruit shell, accounting for approximately 60% weight of the single C. oleifera fruit, is rich in polysaccharides and has several biological activities such as anti-oxidation, lipid regulation and anticancer. However, the immunomodulatory activity of the polysaccharide from C. oleifera fruit shells (CPS) has not been reported. Objective: This study aimed to investigate the immunomodulatory activities and mechanisms of CPS in RAW264.7 macrophages. Methods: The Methyl Thiazolyl Tetrazolium (MTT) method was used to evaluate the effect of CPS on the cell viability of RAW264.7 macrophages, and cell morphology was pictured using microscope. The production of immune-related molecules, including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNFα), interleukin (IL)-1ß and IL-6, was detected by Griess assay and enzyme-linked immunosorbent assay (ELISA). The protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) and the phosphorylation level of mitogen-activated protein kinases (MAPKs) were analyzed through western blotting. The mRNA levels of related genes were tested using reverse transcription-polymerase chain reaction (RT-PCR). The nuclear translocation of nuclear factor-kappa B (NF-κB) was detected using immunofluorescence technology. Results: The results indicated that CPS treatment stimulated the production of NO and PGE2 and significantly enhanced the protein expression of iNOS and COX2 with little effect on the cell morphology and viability. Also, the secretion and mRNA levels of TNFα were increased by the treatment of CPS. In addition, CPS treatment markedly upregulated the phosphorylation level of MAPKs including Extracellular Signal Regulated Kinase (ERK), P38, and c-Jun N-terminal Kinase (JNK) at different time points and caused the activation and nuclear translocation of NF-κB. Conclusion: Our data implied that CPS exerts immunomodulatory activities by activating MAPKs and NF-κB signaling pathways in RAW264.7 macrophages.

20.
Nanomaterials (Basel) ; 13(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36616092

RESUMO

Flexible strain sensors with significant extensibility, stability, and durability are essential for public healthcare due to their ability to monitor vital health signals noninvasively. However, thus far, the conductive networks have been plagued by the inconsistent interface states of the conductive components, which hampered the ultimate sensitivity performance. Here, we demonstrate structurally integrated 3D conductive networks-based flexible strain sensors of hybrid Ag nanorods/nanoparticles(AgNRs/NPs) by combining a droplet-based aerosol jet printing(AJP) process and a feasible transfer process. Structurally integrated 3D conductive networks have been intentionally developed by tweaking droplets deposition behaviors at multi-scale for efficient hybridization and ordered assembly of AgNRs/NPs. The hybrid AgNRs/NPs enhance interfacial conduction and mechanical properties during stretching. In a strain range of 25%, the developed sensor demonstrates an ideal gauge factor of 23.18. When real-time monitoring of finger bending, arm bending, squatting, and vocalization, the fabricated sensors revealed effective responses to human movements. Our findings demonstrate the efficient droplet-based AJP process is particularly capable of developing advanced flexible devices for optoelectronics and wearable electronics applications.

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