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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 287(Pt 2): 122084, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379087

RESUMO

Nanozymes have potential applications in many fields, and a novel copper-containing nanozyme with highly dispersity and uniformity was self-assembled for efficient degradation of various organic dyes in this work. In the nanozyme, histidine was used to coordinate with copper ions, and hydrogen peroxide was prone to Fenton-like reaction to generate hydroxylated copper oxide intermediates. The nanozyme showed good peroxidase-like activity, and also had the ability to catalyze the degradation of various organic dyes efficiently with good storage and recycling ability. Furthermore, the degradation kinetics and mechanism of nanozyme had been further studied, and found that hydroxyl radical and singlet oxygen play vital roles in the catalytic degradation process. Meanwhile, this nanozyme can efficiently degrade two organic compounds at the same time, and this system is capable of dealing with complex practical application scenarios where wastewater contains a variety of organic pollutants.


Assuntos
Cobre , Peróxido de Hidrogênio , Histidina , Corantes , Águas Residuárias
2.
J Ethnopharmacol ; 302(Pt B): 115934, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36414216

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-zi-chi decoction (ZZCD), from "Treatise on Febrile Diseases", is a typical traditional Chinese medicine herb pair, which consists of Gardeniae Fructus (GF) and Semen Sojae Praeparatu (SSP). In clinical research, ZZCD was widely used to fight depression, remove annoyance. Many studies have reported that gut microbiota is critical target for the influence of depress through gut-brain axis, and our previously studies have found that ZZCD exhibiting antidepressant effect was through the gut-brain axis. However, the specific mechanism by which gut microbiota mediates the pharmacokinetics parameters of active compounds from ZZCD during the process of depression treatment has not yet been studied. AIM OF THE STUDY: To explore the differences in pharmacokinetics characters of bioactive iridoids from ZZCD and study the changes of gut microbiota at different stages of depression with the personalized medicine of ZZCD. MATERIALS AND METHODS: A new strategy exploring the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as "DIET" was established. Firstly, a fast, selective and sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometer (UPLC-MS/MS) was established and validated to quality the main bioactive compounds from ZZCD and compare the pharmacokinetics and bioavailability of different iridoids prototypes and metabolites from ZZCD between normal and chronic unpredictable mild stress rats. Subsequently, the activity of corresponding metabolic enzymes of anti-depressive compounds, ß-glucosidases and sulfotransferases, were analyzed by ρ-nitrophenyl-ß -D-glucopyranoside and sulfotransferases ELISA kits, respectively. Finally, 16S rRNA gene sequencing was adopt to analyze intestinal bacteria composition for the treatment of depression by ZZCD. RESULTS: The antidepressant effect of ZZCD was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide and genipin 1-gentiobioside, under the depression state. With the ZZCD treatment, the depression was improved, but the exposures of anti-depressive compounds from ZZCD gradually decreased. Meanwhile, there were the corresponding decreased trends on the activity of ß-glucosidases and sulfotransferases. With the consumption of ZZDC and the improvement of depression, the exposures of anti-depressive iridoid glycosides decreased and the activity of metabolism enzymes restored. Meanwhile, the dysbiosis of pathogenic bacteria (Bacteroidota) induced by depression was ameliorated and the probiotics (Firmicutes) at the phylum and genus level raised, the two phyla are closely related to the production of ß-glucosidase and sulfotransferases. CONCLUSIONS: It is the first proposed that ZZCD could personalized to treat depression at different stages targeting gut microbiota and gut microbiome could emerged as a potential diagnostic and therapeutic biomarker in depression.


Assuntos
Celulases , Depressão , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Animais , Ratos , Cromatografia Líquida , Depressão/tratamento farmacológico , Iridoides , Medicina de Precisão , RNA Ribossômico 16S , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/farmacologia
3.
Food Chem ; 403: 134215, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36179639

RESUMO

The non-volatile compounds in Chinese soy sauce (CSS) and Japanese soy sauce (JSS) were qualitatively and quantitatively identified by amino acid analyser and gas-chromatography mass-spectrometry combined with derivatization method (DER-GC-MS). Forty-nine compounds were identified, including 19 amino acids, 8 sugars, 6 sugar alcohols, 8 organic acids and 8 others. Six groups of taste compounds were added to the water at natural concentration in soy sauce were able to reconstitute taste models of CSS and JSS, with no remarkable differences from the soy sauce taste profiles. Through three different rounds of omission tests, it was clear that the recombination models of 10 and 11 key compounds could simulate the typical taste characteristics of CSS and JSS, respectively, with the shared compounds NaCl, glutamate, lysine, isoleucine, leucine, lactic acid, citric acid, and > 500 Da components. This study provided an important theoretical basis for the in-depth research on the soy sauce flavor.


Assuntos
Alimentos de Soja , Alimentos de Soja/análise , Paladar , Japão , Aminoácidos/análise , China , Recombinação Genética
4.
J Hazard Mater ; 443(Pt A): 130213, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36283219

RESUMO

Pharmaceutical compounds in aquatic environments have been considered as emerging contaminants due to their potential risks to living organisms. Microalgae-based technology showed the feasibility of removing pharmaceutical contaminants. This review summarizes the occurrence, classification, possible emission sources, and environmental risk of frequently detected pharmaceutical compounds in aqueous environments. The efficiency, mechanisms, and influencing factors for the removal of pharmaceutical compounds through microalgae-based technology are further discussed. Pharmaceutical compounds frequently detected in aqueous environments include antibiotics, hormones, analgesic and non-steroidal anti-inflammatory drugs (NSAIDs), cardiovascular agents, central nervous system drugs (CNS), antipsychotics, and antidepressants, with a concentration ranging from ng/L to µg/L. Microalgae-based technology majorly remove the pharmaceutical compounds through bioadsorption, bioaccumulation, biodegradation, photodegradation, and co-metabolism. This review identifies the opportunities and challenges for microalgae-based technology and proposed suggestions for future studies to tackle challenges. The findings of this review advance our understanding of the occurrence and fate of pharmaceutical contaminants in aqueous environments, highlighting the potential of microalgae-based technology for pharmaceutical contaminants removal.


Assuntos
Microalgas , Poluentes Químicos da Água , Microalgas/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Biotecnologia , Preparações Farmacêuticas/metabolismo , Águas Residuárias
5.
Small ; : e2206231, 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464643

RESUMO

The past decades have witnessed the rational design of novel functional nanomaterials and the potential to revolutionize many applications. With the increasing focus on electronic biological processes, novel photovoltaic nanomaterials are highly expectable for empowering new therapeutic strategies such as establishing a link between endogenous electric field (EEF) and electrotherapy. Compared to traditional invasive stimulation, the light-initiating strategy has the advantages of non-invasion, non-power supply, and precise controllability. Whereas, common photoactivated materials require short-wavelength light excitation accompanied by poor tissue penetration and biohazard. Herein, by the construction of p-n heterostructured Bi2 S3 /TiO2 /rGO (BTG) nanoparticles, broadener light absorption and higher light conversion than regular UV excitation are realized. Simultaneously, the photoelectric performance of BTG heterostructure, as well as the synergistic effect of Bi2 S3 morphology, are revealed. Besides, the rationally designed biomimetic hydrogel matrix consisting of collagen and hyaluronic acid provides appropriate bioactivity, interface adhesion, mechanical matching, and electron transfer. Therefore, the photovoltaic BTG-loaded matrix provides a platform of light-driven electrical stimulation, coupling the EEF to modulate the electrophysiological and regeneration microenvironment. The implementation of photoelectric stimulation holds broad prospects for non-drug therapy and electrical-related biological process modulation including osseointegration, nerve regeneration, electronic skin, and wound healing.

6.
Curr Psychol ; : 1-9, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36471812

RESUMO

Although considerable research has shown that attachment is a protective factor for cyberbullying, little research has investigated the mechanisms underlying this relationship among college students. This study examined whether loneliness mediates the association between parental attachment and cyberbullying and whether this process is moderated by interdependent self. A sample of 1125 college students (Mage = 19.14, SDage = 1.52 years) in China completed a questionnaire measuring parental attachment, cyberbullying, loneliness, and interdependent self. Loneliness partially mediated the relationship between parental attachment and cyberbullying. Moreover, the mediation effect of loneliness was moderated by interdependent self. A moderated mediation analysis further revealed that interdependent-self moderated the predictive effect of loneliness on cyberbullying. Specifically, the predictive effect of loneliness on cyberbullying was only significant among college students with low interdependent self. The study highlights the complex nature of the association between parental attachment and cyberbullying. These findings provide new perspectives for intervention and prevention of cyberbullying among college students.

7.
Biochem Biophys Res Commun ; 637: 276-285, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36410277

RESUMO

Myocardial Ischemic Injury is a serious threat to human health, and DJ-1 is involved in cardioprotection. The research intended to explore the effects and mechanism of DJ-1 to protect myocardium against ischemia injury. DJ-1 overexpression lentivirus vectors were transduced into the myocardium of SD rats and H9c2 cells, and an AMI model in vivo and a hypoxia model in vitro were established, respectively. Results showed that DJ-1 overexpression alleviated myocardial ischemia injury, as demonstrated by reduced the extent of myocardial infarction, improved cell survival, decreased LDH activity and CK-MB release. Furthermore, DJ-1 interacted with RACK1, activated AMPK/mTOR pathway, induced adaptive autophagy and protected the myocardium. However, RACK1 siRNA or compound C (an AMPK inhibitor) could weaken the above effect of DJ-1 on myocardium. In conclusion, DJ-1 could activate adaptive autophagy by the RACK1/AMPK/mTOR pathway and protect the myocardium against ischemia injury.


Assuntos
Proteínas Quinases Ativadas por AMP , Traumatismos Cardíacos , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR , Autofagia , Miocárdio , Hipóxia , Isquemia , Receptores de Quinase C Ativada , Proteínas de Neoplasias
8.
Front Endocrinol (Lausanne) ; 13: 1014431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425469

RESUMO

Objective: This study aimed to explore the associations of genetic variants in the semaphorin 3A (SEMA3A) signaling pathway genes, including SEMA3A, NRP1, PLXNA1, PLXNA2 and PLXNA3 with osteoporosis (OP) risk and bone mineral density (BMD) in a Chinese Han older adult population. Study design and method: A two-stage design was adopted. Total of 47.8kb regions in the 5 genes were sequenced using targeted next-generation sequencing (NGS) technology in the discovery stage, and the discovered OP-related single nucleotide polymorphisms (SNPs) were further genotyped using improved multiple linkage detection reaction technique in the validation stage. Methods of ALP/TRAP staining, real-time fluorescent quantitative PCR, and cell proliferation and apoptosis assays were performed with MC3T3-E1 and RAW 264.7 cell lines to clarify biological effects of observed functional variants in cell lines responsible for bone mass remodeling. Results: Total of 400 postmenopausal women (211 OP cases) were involved in the discovery stage, where 6 common and 4 rare genetic variants were found to be associated with OP risk. In the validation stage among another 859 participants (417 women, 270 OP cases), the PLXNA2 rs2274446 T allele was associated with reduced OP risk and increased femoral neck (FN) BMD compared to the C allele. Moreover, significant associations of NRP1 rs2070296 with FN BMD/OP risk and of NRP1 rs180868035 with lumbar spine and FN BMDs were also observed in the combination dataset analysis. Compared to the osteoblasts/osteoclasts transfected with the wild-type NRP1 rs180868035, those transfected with the mutant-type had reduced mRNA expression of osteoblastic genes (i.e., ALP, RUNX2, SP7 and OCN), while elevated mRNA expression of osteoclastic genes (i.e., TRAP, NFATc1 and CTSK). Furthermore, mutant NRP1 rs180868035 transfection inhibited osteoblast proliferation and osteoclast apoptosis, while promoted osteoclast proliferation and osteoblast apoptosis in corresponding cell lines. Conclusion: Genetic variants located in NRP1 and PLXNA2 genes were associated with OP risk and BMD. The NRP1 rs180868035 affects bone metabolism by influencing osteoblasts and osteoclasts differentiation, proliferation and apoptosis.


Assuntos
Densidade Óssea , Semaforina-3A , Transdução de Sinais , Idoso , Feminino , Humanos , Apoptose , Densidade Óssea/genética , Osteoclastos , Semaforina-3A/genética , Transdução de Sinais/genética , Animais , Camundongos , Células RAW 264.7 , Pós-Menopausa
9.
Poult Sci ; 102(1): 102302, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36436373

RESUMO

The purpose of this experiment was to determine the effectiveness of compound feed additive (CFA) to replace antibiotics for broiler production. A total of 350 one-day-old Arbor Acres broilers were randomly divided into 7 groups, 5 replications in each group and 10 broilers in each replication. Group A was the control; group B was supplemented with 75 mg/kg chlortetracycline; groups C, D, and E were supplemented with 0.03, 0.06, and 0.09% CFA including glucose oxidase, curcumin, and Lactobacillus acidophilus; group F was supplemented with 0.03% CFA plus 0.50% glucose; group G was supplemented with 0.50% glucose. The feeding period was divided into the early (1-21 d) and later stages (22-42 d). The results showed that average daily gain (ADG) and feed conversion rate (F/G) in group F in later stage were significantly better than those in the control and antibiotic groups; the diarrhea rates in the groups containing CFA in both stages was significantly lower than that in the control and antibiotic groups, indicating that CFA was better than antibiotics to improve growth and decrease diarrhea rate for broilers. Pathogenic E. coli challenge significantly increased diarrhea rates and decreased ADG for broilers; however, CFA addition could alleviate the above negative responses by increasing gut Lactobacillus abundance and decreasing Shigella abundance. It can be concluded that CFA can replace antibiotics to regulate intestinal microbiota, reduce diarrhea rate, and improve broiler growth.

10.
Sci Rep ; 12(1): 20528, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443452

RESUMO

In this article, a modified version of the Sine Cosine algorithm (MSCA) is proposed to solve the optimization problem. Based on the Sine Cosine algorithm (SCA), the position update formula of SCA is redefined to increase the convergence speed, then the Levy random walk mutation strategy is adopted to improve the population diversity. In order to verify the performance of MSCA, 24 well-known classical benchmark problems and IEEE CEC2017 test suites were introduced, and by comparing MSCA with several popular methods, it is demonstrated that MSCA has good convergence and robustness. Finally, MSCA is used to address six complex engineering design problems, demonstrating the engineering utility of the algorithm.

11.
Fam Process ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347126

RESUMO

The integration of the roles of caregivers and interventionists is important in parenting a child with autism spectrum disorder (ASD). However, an instrument to measure dual-role behaviors is unavailable. This study developed and validated the Dual Role Behaviors Scale for parents of autistic children (DRBS-A). Initial items were generated using the interview transcripts of a previous qualitative study. The initial scale was administered to 422 parents. Data were randomly halved to generate Samples 1 and 2. Exploratory factor analysis conducted using Sample 1 (autism spectrum disorder = 216) screened items based on factor loadings and explored the scale's structure. Confirmatory factor analysis (CFA) conducted with Sample 2 (N = 206) examined structural validity. Among the participants, 121 (Sample 3) derived from the two samples were followed up after 1 month to examine the test-retest reliability. Convergent validity was examined with another sample of 105 parents (Sample 4). The formal version of the DRBS-A comprised 20 items across four dimensions: parental acceptance, parental disengagement, persistence in interventions, and punishment in interventions. The four-factor structure with two higher order factors was supported by the CFA results (χ2  = 290.90, df = 165, CFI = 0.94, TLI = 0.93, RMSEA = 0.061, SRMR = 0.063). The subscales' test-retest reliabilities ranged from 0.61 to 0.78. The internal consistencies were satisfactory (Cronbach's αs: 0.67-0.93). Convergent validity was supported by correlations of the DRBS-A dimensions with parental involvement and positive parenting practice. Other factors related to dual-role behaviors were also explored. The DRBS-A has good validity and reliability and can be used to explore the effects of role integration.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36433814

RESUMO

BACKGROUND: Multiparametric flow cytometry (MFC) has become a powerful tool in minimal residual disease (MRD) detection in B-lymphoblastic leukemia/lymphoma (B-ALL). In the setting of targeted immunotherapy, B-ALL MRD detection often relies on alterative gating strategies, such as the utilization of CD22 and CD24. It is important to depict the full diversity of normal cell populations included in the alternative B-cell gating methods to avoid false-positive results. We describe two CD22-positive non-neoplastic cell populations in the peripheral blood (PB), including one progenitor population of uncertain lineage and one mature B-cell population, which are immunophenotypic mimics of B-ALL. METHODS: Using MFC, we investigated the prevalence and phenotypic profiles of both CD22-positive populations in 278 blood samples from 52 patients with B-ALL; these were obtained pre- and post-treatment with CD19 and/or CD22 CAR-T therapies. We further assessed whether these two populations in the blood were exclusively associated with B-ALL or recent anticancer therapies, by performing the same analysis on patients diagnosed with other hematological malignancies but in long-term MRD remission. RESULTS: The progenitor population and mature B-cell population were detected at low levels in PB of 61.5% and 44.2% of B-ALL patients, respectively. Both cell types showed distinctive and highly consistent antigen expression patterns that are reliably distinguishable from B-ALL. Furthermore, their presence is not restricted solely to B-ALL or recent therapy. CONCLUSIONS: Our findings aid in building a complete immunophenotypic profile of normal cell populations in PB, thereby preventing misdiagnosis of B-ALL MRD and inappropriate management.

13.
Plant Cell Environ ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36358019

RESUMO

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline-alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split-root experiments showed that low Fe-alleviating the salinity-induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X-ray few differences in the root Na+ uptake and vacuolar Na+ sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity-induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe-mediated amelioration of the salinity-induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress.

14.
BMC Health Serv Res ; 22(1): 1367, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397064

RESUMO

BACKGROUND: In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC. METHODS: A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model. RESULTS: Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively. CONCLUSION: Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.


Assuntos
Medicamentos Biossimilares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Bevacizumab/uso terapêutico , Análise Custo-Benefício , Medicamentos Biossimilares/uso terapêutico
15.
Front Public Health ; 10: 1030887, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388375

RESUMO

Background: With the popularization of the Internet, it has become possible to widely disseminate health information via social media. Medical staff's health communication through social media can improve the public's health literacy, and improving the intention of health communication among nursing undergraduates is of great significance for them to actively carry out health communication after entering clinical practice. Objective: To explore the relationship among eHealth literacy, social media self-efficacy, and health communication intention and to determine the mediating role of social media self-efficacy in the relationship between eHealth literacy and health communication intention. Design: A cross-sectional descriptive correlation design was used in this study. Participants: Stratified cluster sampling was used to select 958 nursing students from four nursing colleges in Jiangsu Province, China, from June to July 2021. Methods: Data were collected using the eHealth Literacy Scale, the Social Media Self-efficacy Scale, and the Health Communication Intention Questionnaire. Sociodemographic data were also collected. Correlation analysis and regression analysis were used to determine the relationship between eHealth literacy, social media self-efficacy, and health communication intention. Results: Health communication intention is positively correlated with eHealth literacy and social media self-efficacy. There is a significant positive correlation between eHealth literacy and health communication intention (ß = 0.57, p < 0.001), and social media self-efficacy played a mediating role in the influence of eHealth literacy on health communication intention (the mediating effect accounted for 37.2% of the total effect). Conclusion: The study found that eHealth literacy and social media self-efficacy had an impact on health communication intention. Because there is a correlation between eHealth literacy and social media self-efficacy and health communication intention, in order to promote health communication intention of nursing students, it is also important to cultivate eHealth literacy and social media self-efficacy of nursing students. In view of these results, targeted educational programs must be developed to improve eHealth literacy and social media self-efficacy among nursing undergraduates, thereby promoting their health information transmission.


Assuntos
Comunicação em Saúde , Mídias Sociais , Estudantes de Enfermagem , Telemedicina , Humanos , Estudos Transversais , Autoeficácia , Intenção , Promoção da Saúde , Telemedicina/métodos
16.
Front Pharmacol ; 13: 1040591, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339629

RESUMO

Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile acids (BAs). Since the intestinal microflora affects physiological functions of the brain through the gut-microbiota-brain axis, herein we investigated whether CSS altered BA levels, gut microflora, and depression-like symptoms in chronic unpredictable mild stress (CUMS) mice, a well-established mouse model of depression. Furthermore, we determined whether BA manipulation and fecal microbiota transplantation altered CSS antidepressant actions. We found that the BA chelator cholestyramine impaired the antidepressant effects of CSS, which was partially rescued by dietary cholic acid. CSS increased the relative abundance of Parabacteroides distasonis in the colon of CUMS mice, and increased serum levels of various BAs including hyocholic acid (HCA) and 7-ketodeoxycholic acid (7-ketoDCA). Furthermore, gut bacteria transplantation from CSS-treated mice into untreated or cholestyramine-treated CUMS mice restored serum levels of HCA and 7-ketoDCA, alleviating depression-like symptoms. In the hippocampus, CSS-treated mice had decreased expression of genes associated with BA transport (Bsep and Fxr) and increased expression of brain-derived neurotrophic factor and its receptor, TrkB. Overall, CSS increases intestinal P. distasonis abundance, leading to elevated levels of secondary BAs in the circulation and altered expression of hippocampal genes implicated in BA transport and neurotrophic signaling. Our data strongly suggest that the gut microbiota-brain axis contributes to the potent antidepressant action of CSS by modulating BA metabolism.

17.
Quant Imaging Med Surg ; 12(11): 5129-5139, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36330180

RESUMO

Background: Mucin 4 (MUC4) overexpression promotes tumorigenesis and increases the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). To date, no study has reported the association between radiomics and MUC4 expression in PDAC. Thus, we aimed to explore the utility of radiomics based on multi-sequence magnetic resonance imaging (MRI) to predict the status of MUC4 expression in PDAC preoperatively. Methods: This retrospective study included 52 patients with PDAC who underwent MRI. The patients were divided into two groups based on MUC4 expression status. Two feature sets were extracted from the arterial and portal phases (PPs) of dynamic contrast-enhanced MRI (DCE-MRI). Univariate analysis, minimum redundancy maximum relevance (MRMR), and principal component analysis (PCA) were performed for the feature selection of each dataset, and features with a cumulative variance of 90% were selected to develop radiomics models. Clinical characteristics were gathered to develop a clinical model. The selected radiomics features and clinical characteristics were modeled by multivariable logistic regression. The combined model integrated radiomics features from different selected data sets and clinical characteristics. The classification metrics were applied to assess the discriminatory power of the models. Results: There were 22 PDACs with a high expression of MUC4 and 30 PDACs with a low expression of MUC4. The area under the receiver operating characteristic (ROC) curve (AUC) values of the arterial phase (AP) model, the PP model, and the combined model were 0.732 (0.591-0.872), 0.709 (0.569-0.849), and 0.861 (0.760-0.961), respectively. The AUC of the clinical model was 0.666 (0.600-0.682). The combined model that was constructed outperformed the AP, the PP, and the clinical models (P<0.05, although no statistical significance was observed in the combined model vs. AP model). Conclusions: Radiomics models based on multi-sequence MRI have the potential to predict MUC4 expression levels in PDAC.

18.
Cell Oncol (Dordr) ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350496

RESUMO

PURPOSE: AKT hyperactivation drives malignant phenotypes in lung cancer via promoting tumor cell proliferation and survival. However, the relationship between dysregulation of cell cycle progression and AKT1 kinase activity is still not clear. METHODS: Following the expression level of PKMYT1 in lung cancer, we performed cell proliferation, migration, invasion, and xenograft assays to determine the function of PKMYT1. We used RNA-seq to explore the anti-tumor mechanism of PKMYT1 and examined the effect of PKMYT1 on AKT1 activity. RESULTS: In this study, we report that PKMYT1 is downregulated in lung adenocarcinoma (LUAD) tissues and its low expression predicts a poor prognosis in LUAD patients. PKMYT1 exerts potent tumor-suppressive functions in LUAD cells by inhibiting AKT1 activation and thereby repressing cell cycle progression, which depends on its tyrosine and threonine protein kinase activity. Interestingly, PKMYT1 could directly bind AKT1 to abrogate AKT1 activation. Moreover, silencing AKT1 and inhibitors targeting the AKT pathway effectively reverse the promoting effects of PKMYT1 knockdown on proliferation, migration and invasion of LUAD cells. CONCLUSION: This work reveals the anti-tumor effect of PKMYT1 in LUAD and provides evidence to clarify the dual roles of PKMYT1 in tumor progression. Moreover, our findings broaden the current understandings on AKT1 activation and identify PKMYT1 as a potential negative regulator of AKT1 kinase activity, providing further insights into targeting the AKT pathway in LUAD.

19.
Life (Basel) ; 12(11)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36362895

RESUMO

BACKGROUND: With the discovery of more and more drug-resistant bacterial strains, there is an urgent need for safer and more effective alternative treatments. In this study, antibacterial peptides and probiotic microcapsules were combined to treat gastrointestinal inflammation caused by Vibrio parahaemolyticus infection. METHODS: To improve the stability of probiotics in the gastrointestinal tract, two types of mixed natural anionic polysaccharides and chitosan were used as carriers to embed the probiotics. Taking Lacticaseibacillus casei CGMCC1.8727 microcapsules with good performance as the research object, the in vitro characteristics of the microcapsules were studied via acid resistance test and intestinal release test. The microcapsules were then tested for in vivo treatment in combination with the antibacterial peptide, bomidin, and the therapeutic effects were compared among microencapsulated probiotics, free probiotics, and probiotics in combination with bomidin. RESULTS: Microencapsulation was successfully manufactured under suitable processing parameters, with the product particle size being 2.04 ± 0.2743 mm. Compared with free probiotics, microencapsulation significantly improved the activity and preservation stability of the probiotics under simulated gastrointestinal conditions. Microencapsulated probiotics showed better therapeutic effects than free probiotics in vivo. Microcapsules combined with antimicrobial peptides accelerated the elimination of bacteria in vivo. This study provides a reference for anti-inflammatory treatment, especially for the treatment of gastrointestinal diseases.

20.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36430962

RESUMO

The GARP genes are plant-specific transcription factors (TFs) and play key roles in regulating plant development and abiotic stress resistance. However, few systematic analyses of GARPs have been reported in allotetraploid rapeseed (Brassica napus L.) yet. In the present study, a total of 146 BnaGARP members were identified from the rapeseed genome based on the sequence signature. The BnaGARP TFs were divided into five subfamilies: ARR, GLK, NIGT1/HRS1/HHO, KAN, and PHL subfamilies, and the members within the same subfamilies shared similar exon-intron structures and conserved motif configuration. Analyses of the Ka/Ks ratios indicated that the GARP family principally underwent purifying selection. Several cis-acting regulatory elements, essential for plant growth and diverse biotic and abiotic stresses, were identified in the promoter regions of BnaGARPs. Further, 29 putative miRNAs were identified to be targeting BnaGARPs. Differential expression of BnaGARPs under low nitrate, ammonium toxicity, limited phosphate, deficient boron, salt stress, and cadmium toxicity conditions indicated their potential involvement in diverse nutrient stress responses. Notably, BnaA9.HHO1 and BnaA1.HHO5 were simultaneously transcriptionally responsive to these nutrient stresses in both hoots and roots, which indicated that BnaA9.HHO1 and BnaA1.HHO5 might play a core role in regulating rapeseed resistance to nutrient stresses. Therefore, this study would enrich our understanding of molecular characteristics of the rapeseed GARPs and will provide valuable candidate genes for further in-depth study of the GARP-mediated nutrient stress resistance in rapeseed.


Assuntos
Brassica napus , Brassica rapa , Brassica napus/genética , Brassica rapa/genética , Nutrientes , Desenvolvimento Vegetal , Família
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