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1.
Curr Res Food Sci ; 9: 100823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39253721

RESUMO

Matcha shows promise for diabetes, obesity, and gut microbiota disorders. Studies suggest a significant link between gut microbiota, metabolites, and obesity. Thus, matcha may have a positive impact on obesity by modulating gut microbiota and metabolites. This study used 16S rDNA sequencing and untargeted metabolomics to examine the cecal contents in mice. By correlation analysis, we explored the potential mechanisms responsible for the positive effects of matcha on obesity. The results indicated that matcha had a mitigating effect on the detrimental impacts of a high-fat diet (HFD) on multiple physiological indicators in mice, including body weight, adipose tissue weight, serum total cholesterol (TC), and low-density lipoprotein (LDL) levels, as well as glucose tolerance. Moreover, it was observed that matcha had an impact on the structural composition of gut microbiota and gut metabolites. Specifically, matcha was able to reverse the alterations in the abundance of certain obesity-improving bacteria, such as Alloprevotella, Ileibacterium, and Rikenella, as well as the abundance of obesity-promoting bacteria Romboutsia, induced by a HFD. Furthermore, matcha can influence the levels of metabolites, including formononetin, glutamic acid, pyroglutamic acid, and taurochenodeoxycholate, within the gastrointestinal tract. Additionally, matcha enhances caffeine metabolism and the HIF-1 signaling pathway in the KEGG pathway. The results of the correlation analysis suggest that formononetin, theobromine, 1,3,7-trimethyluric acid, and Vitamin C displayed negative correlation with both the obesity phenotype and microbiota known to exacerbate obesity, while demonstrating positive correlations with microbiota that alleviated obesity. However, glutamic acid, pyroglutamic acid, and taurochenodeoxycholate had the opposite effect. In conclusion, the impact of matcha on gut metabolites may be attributed to its modulation of the abundance of Alloprevotella, Ileibacterium, Rikenella, and Romboutsia within the gastrointestinal tract, thereby potentially contributing to the amelioration of obesity.

2.
Curr Res Food Sci ; 9: 100805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131951

RESUMO

As a multi-factorial disease, obesity has become one of the major health problems in the world, and it is still increasing rapidly. Konjac supplementation, as a convenient dietary therapy, has been shown to be able to regulate gut microbiota and improve obesity. However, the specific mechanism by which konjac improves obesity through gut microbiota remains to be studied. In this study, a high-fat diet (HFD) was used to induce a mouse obesity model, and 16S rDNA sequencing and an untargeted metabolomics were used to investigate the impact of konjac on gut microbiota and gut metabolites in HFD-induced obese mice. The results show that konjac can reduce the body weight, adipose tissue weight, and lipid level of high-fat diet induced obese mice by changing the gut microbiota structure and gut metabolic profile. Association analysis revealed that konjac supplementation induced changes in gut microbiota, resulting in the up-regulation of 7-dehydrocholesterol and trehalose 6-phosphate, as well as the down-regulation of glycocholic acid and ursocholic acid within the Secondary bile acid biosynthesis pathway, ultimately leading to improvements in obesity. Among them, g_Acinetobacter (Greengene ID: 911888) can promote the synthesis of 7-dehydrocholesterol by synthesizing ERG3. g_Allobaculum (Greengene ID: 271516) and g_Allobaculum (Greengene ID: 259370) can promote the breakdown of trehalose 6-phosphate by synthesizing glvA. Additionally, the down-regulation of glycocholic acid and ursocholic acid may be influenced by the up-regulation of Lachnospiraceae_NK4A136_group. In conclusion, konjac exerts an influence on gut metabolites through the regulation of gut microbiota, thereby playing a pivotal role in alleviating obesity induced by a high-fat diet.

3.
DNA Cell Biol ; 43(9): 474-481, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39049814

RESUMO

The qseC gene is a two-component system that encodes a histidine protein kinase and is highly conserved among different Glaesserella parasuis strains. In this study, we used qRT-PCR and enzyme-linked immunosorbent assay to confirm that Toll-like receptor 4 (TLR4) plays a role in the expression of proinflammatory cytokines interleukin (IL)-1ß and IL-6 by stimulating RAW 264.7 macrophages with QseC. Furthermore, we revealed that blocking the p38 and NF-κB pathways that regulate signaling can significantly reduce the production of proinflammatory cytokines induced by QseC. In summary, our data suggest that QseC is a novel proinflammatory mediator that induces TLR4-dependent proinflammatory activity in RAW 264.7 macrophages through the p38 and NF-κB pathways.


Assuntos
Citocinas , Macrófagos , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Camundongos , NF-kappa B/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Células RAW 264.7 , Citocinas/metabolismo , Citocinas/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Histidina Quinase/metabolismo , Histidina Quinase/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Haemophilus parasuis/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética
4.
PLoS One ; 19(5): e0303469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768153

RESUMO

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.


Assuntos
Aprendizado de Máquina , Sepse , Humanos , Sepse/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hepatopatias/mortalidade , Fatores de Risco , Prognóstico
5.
Front Microbiol ; 15: 1371667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765683

RESUMO

Globally, ~8%-12% of couples confront infertility issues, male-related issues being accountable for 50%. This review focuses on the influence of gut microbiota and their metabolites on the male reproductive system from five perspectives: sperm quality, testicular structure, sex hormones, sexual behavior, and probiotic supplementation. To improve sperm quality, gut microbiota can secrete metabolites by themselves or regulate host metabolites. Endotoxemia is a key factor in testicular structure damage that causes orchitis and disrupts the blood-testis barrier (BTB). In addition, the gut microbiota can regulate sex hormone levels by participating in the synthesis of sex hormone-related enzymes directly and participating in the enterohepatic circulation of sex hormones, and affect the hypothalamic-pituitary-testis (HPT) axis. They can also activate areas of the brain that control sexual arousal and behavior through metabolites. Probiotic supplementation can improve male reproductive function. Therefore, the gut microbiota may affect male reproductive function and behavior; however, further research is needed to better understand the mechanisms underlying microbiota-mediated male infertility.

6.
Microb Pathog ; 192: 106685, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38750774

RESUMO

QseC is a membrane sensor kinase that enables bacteria to perceive autoinducers -3, adrenaline, and norepinephrine to initiate downstream gene transcription. In this study, we found that the QseC protein of Glaesserella parasuis can serve as an effective antigen to activate the host's immune response. Therefore, we investigated the immunogenicity and host protective effect of this protein. ELISA and indirect immunofluorescence results showed that QseC protein can induce high titer levels of humoral immunity in mice and regularly generate specific serum antibodies. We used MTS reagents to detect lymphocyte proliferation levels and found that QseC protein can cause splenic lymphocyte proliferation with memory and specificity. Further immunological analysis of the spleen cell supernatant revealed significant upregulation of levels of IL-1ß, IL-4 and IFN-γ in the QseC + adjuvant group. In the mouse challenge experiment, it was found that QseC + adjuvant can provide effective protection. The results of this study demonstrate that QseC protein provides effective protection in a mouse model and has the potential to serve as a candidate antigen for a novel subunit vaccine for further research.


Assuntos
Anticorpos Antibacterianos , Infecções por Haemophilus , Interferon gama , Interleucina-4 , Animais , Camundongos , Interleucina-4/metabolismo , Interleucina-4/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/prevenção & controle , Infecções por Haemophilus/microbiologia , Interferon gama/metabolismo , Histidina Quinase/genética , Histidina Quinase/metabolismo , Histidina Quinase/imunologia , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Imunidade Humoral , Camundongos Endogâmicos BALB C , Baço/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética , Proliferação de Células , Feminino , Adjuvantes Imunológicos , Haemophilus parasuis/imunologia , Haemophilus parasuis/genética , Citocinas/metabolismo , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Modelos Animais de Doenças , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Linfócitos/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/genética
7.
Front Microbiol ; 15: 1343511, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450171

RESUMO

Introduction: It is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain. Methods: In this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites. Results: After a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.

8.
Environ Sci Pollut Res Int ; 31(1): 1530-1542, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38040889

RESUMO

In industrial applications, Pt-based catalysts for CO oxidation have the dual challenges of CO self-poisoning and SO2 toxicity. This study used synthetic Keggin-type H3PMo12O40 (PMA) as the site of Pt, and the Pt-MoO3 produced by decomposition of PMA was anchored to TiO2 to construct the dual-interface structure of Pt-MoO3 and Pt-TiO2, abbreviated as Pt-P&M/TiO2. Pt-0.125P&M/TiO2 with a molar ratio of Pt to PMA of 8:1 showed both good CO oxidation activity and SO2 tolerance. In the CO activity test, the CO complete conversion temperature T100 of Pt-0.125P&M/TiO2 was 113 ℃ (compared with 135 ℃ for Pt/TiO2). In the SO2 resistance test, the conversion efficiency of Pt-0.125P&M/TiO2 at 170 ℃ remained at 60% after 72 h, while that of Pt/TiO2 was only 13%. H2-TPR and XPS tests revealed that lattice oxygen provided by TiO2 and hydroxyl produced by MoO3 increased the CO reaction rate on Pt. According to the DFT theoretical calculation, the electronegative MoO3 attracted the d-orbital electrons of Pt, which reduced the adsorption energy of CO and SO2 from - 4.15 eV and - 2.54 eV to - 3.56 eV and - 1.52 eV, respectively, and further weakened the influence of strong CO adsorption and SO2 poisoning on the catalyst. This work explored the relationship between catalyst structure and catalyst performance and provided a feasible technical idea for the design of high-performance CO catalysts in industrial applications.


Assuntos
Metais , Oxigênio , Oxirredução , Oxigênio/química , Titânio/química , Catálise , Enxofre
9.
Genomics ; 116(1): 110763, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38110129

RESUMO

Since smallpox was eradicated in 1980, the monkeypox virus (MPXV) has emerged as the most threatening orthopoxvirus in the world. In this study, we conducted a comprehensive analysis of the currently published complete genome sequences of the monkeypox virus. The core/variable regions were identified through core-pan analysis of MPXV. Besides single-nucleotide polymorphisms, our study also revealed that specific genes, multi-copy genes, repeat sequences, and recombination fragments are primarily distributed in the variable region. This result suggests that variable regions are not only more susceptible to single-base mutations, but also to events such as gene loss or gain, as well as recombination. Taken together, our results demonstrate the genomic characteristics of the core/variable regions of MPXV, and contribute to our understanding of the evolution of MPXV.


Assuntos
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Genômica , Mutação , Polimorfismo de Nucleotídeo Único
10.
Front Cell Infect Microbiol ; 13: 1266295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089814

RESUMO

Background: Stenotrophomonas maltophilia is a multidrug-resistant (MDR) opportunistic pathogen with high resistance to most clinically used antimicrobials. The dissemination of MDR S. maltophilia and difficult treatment of its infection in clinical settings are global issues. Methods: To provide more genetic information on S. maltophilia and find a better treatment strategy, we isolated five S. maltophilia, SMYN41-SMYN45, from a Chinese community that were subjected to antibiotic susceptibility testing, biofilm formation assay, and whole-genome sequencing. Whole-genome sequences were compared with other thirty-seven S. maltophilia sequences. Results: The five S. maltophilia strains had similar antibiotic resistance profiles and were resistant to ß-lactams, aminoglycosides, and macrolides. They showed similar antimicrobial resistance (AMR) genes, including various efflux pumps, ß-lactamase resistance genes (blaL1/2), aminoglycoside resistance genes [aac(6'), aph(3'/6)], and macrolide-resistant gene (MacB). Genome sequencing analysis revealed that SMYN41-SMYN45 belonged to sequence type 925 (ST925), ST926, ST926, ST31, and ST928, respectively, and three new STs were identified (ST925, ST926, and ST928). Conclusion: This study provides genetic information by comparing genome sequences of several S. maltophilia isolates from a community of various origins, with the aim of optimizing empirical antibiotic medication and contributing to worldwide efforts to tackle antibiotic resistance.


Assuntos
Anti-Infecciosos , Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Humanos , Stenotrophomonas maltophilia/genética , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Resistência Microbiana a Medicamentos , Genômica , Testes de Sensibilidade Microbiana
11.
Sci Rep ; 13(1): 20135, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37978247

RESUMO

Colorectal cancer (CRC) is a common and deadly cancer worldwide with a high lethality rate. Disulfidptosis has been found to be an emerging mode of death in cancer, and the purpose of this study was to explore the relationship between disulfidptosis-related lncRNAs (DRLs) and CRC and to develop a prognostic model for CRC and DRLs. The gene expression data and clinicopathologic information of colorectal cancer patients were obtained from The Cancer Genome Atlas (TCGA) and screened for DRLs based on correlation analysis. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to construct the prognostic model, and its validation was carried out by PCA and receiver operating characteristic (ROC) curves. We constructed nomograms combined with the model. Finally, the possible mechanisms by which lncRNAs affect CRC were explored by functional enrichment analysis, immune infiltration and immune escape analysis. In summary, we developed a prognostic marker consisting of lncRNAs associated with disulfidptosis to help clinicians predict the survival of different CRC patients and use different targeted therapies and immunotherapies depending on the condition.


Assuntos
Neoplasias Colorretais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Prognóstico , Nomogramas , Neoplasias Colorretais/genética
12.
Front Oncol ; 13: 1074268, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305583

RESUMO

Gastric cancer is one of the most serious malignant tumor and threatens the health of people worldwide. Its heterogeneity leaves many clinical problems unsolved. To treat it effectively, we need to explore its heterogeneity. Single-cell transcriptome sequencing, or single-cell RNA sequencing (scRNA-seq), reveals the complex biological composition and molecular characteristics of gastric cancer at the level of individual cells, which provides a new perspective for understanding the heterogeneity of gastric cancer. In this review, we first introduce the current procedure of scRNA-seq, and discuss the advantages and limitations of scRNA-seq. We then elaborate on the research carried out with scRNA-seq in gastric cancer in recent years, and describe how it reveals cell heterogeneity, the tumor microenvironment, oncogenesis and metastasis, as well as drug response in to gastric cancer, to facilitate early diagnosis, individualized therapy, and prognosis evaluation.

13.
Molecules ; 28(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375411

RESUMO

Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies.


Assuntos
Glucose , Taninos Hidrolisáveis , Humanos , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/metabolismo
14.
Microb Pathog ; 181: 106215, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37380063

RESUMO

Type II secretion systems (T2SS) are important molecular machines used by bacteria to transport a wide range of proteins across the outer membrane from the periplasm. Vibrio mimicus is an epidemic pathogen threats to both aquatic animals and human health. Our previous study demonstrates that T2SS deletion reduced virulence by 307.26 times in yellow catfish. However, the specific effects of T2SS-mediated extracellular protein secretion in V. mimicus, including its potential role in exotoxin secretion or other mechanisms, require further investigation. Through proteomics and phenotypic analyses, this study observed that the ΔT2SS strain exhibited significant self-aggregation and dynamic deficiency, with a notable negative correlation with subsequent biofilm formation. The proteomics analysis revealed 239 different abundances of extracellular proteins after T2SS deletion, including 19 proteins with higher abundance and 220 proteins with lower and even absent in the ΔT2SS strain. These extracellular proteins are involved in various pathways, such as metabolism, virulence factors expression, and enzymes. Among them, purine, pyruvate, and pyrimidine metabolism, and the Citrate cycle, were the primary pathways affected by T2SS. Our phenotypic analysis is consistent with these findings, suggesting that the decreased virulence of ΔT2SS strains is due to the effect of T2SS on these proteins, which negatively impacts growth, biofilm formation, auto-aggregation, and motility of V. mimicus. These results provide valuable insights for designing deletion targets for attenuated vaccines development against V. mimicus and expand our understanding of the biological functions of T2SS.


Assuntos
Sistemas de Secreção Tipo II , Animais , Humanos , Sistemas de Secreção Tipo II/genética , Sistemas de Secreção Tipo II/metabolismo , Vacinas Atenuadas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
15.
Virus Res ; 334: 199163, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37364814

RESUMO

The family Alloherpesviridae contains herpesviruses of fish and amphibians. Due to the significant economic losses to aquaculture that herpesviruses can cause, the primary areas of research interest are concerning their pathogenesis and prevention. Despite alloherpesvirus genomic sequences becoming more widely accessible, methods regarding their genus/species classification are still relatively unexplored. In the present study, the phylogenetic relationships between 40 completely sequenced alloherpesviruses were illustrated by the viral proteomic tree (ViPTree), which was divided into three monophyletic groups, namely Cyprinivirus, Ictalurivirus and Batrachovirus. Additionally, average nucleotide identity (ANI) and average amino acid identity (AAI) analyses were performed across all available sequences and clearly displayed species boundaries with the threshold value of ANI/AAI set at 90%. Subsequently, core-pan analysis uncovered 809 orthogroups and 11 core genes shared by all 40 alloherpesvirus genome sequences. For the former, a 15 percent identity depicts a clear genus boundary; for the latter, 8 of them may be qualified for phylogenetic analysis based on amino acid or nucleic acid sequences after being verified using maximum likelihood (ML) or neighbor-joining (NJ) phylogenetic trees. Finally, although the dot plot analysis was valid for the members within Ictalurivirus, it was unsuccessful for Cyprinivirus and Batrachovirus. Taken together, the comparison of individual methodologies provides a wide range of alternatives for alloherpesviruses classification under various circumstances.


Assuntos
Herpesviridae , Ictalurivirus , Animais , Filogenia , Proteômica , Herpesviridae/genética , Ictalurivirus/genética , Genômica/métodos
16.
Pharm Biol ; 61(1): 696-709, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37092313

RESUMO

CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma. MATERIALS AND METHODS: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 µM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice. RESULTS: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC50 values of 2.378 µM and 2.719 µM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth. CONCLUSIONS: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Antígenos CD/metabolismo , Moléculas de Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos Nus , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
17.
Front Pharmacol ; 13: 1042992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506576

RESUMO

Background: Opicapone, a novel third-generation catechol-O-methyltransferase inhibitor, has demonstrated efficacy in Parkinson's Disease (PD) patients with end-of-dose motor fluctuations. Objective: This study aimed to compare the short-term (<6 months) and long-term (≥6 months) tolerability of opicapone adjuvant treatment in PD patients. Method: Electronic databases including PubMed, Embase, Web of Science and Cochrane library were searched for randomized controlled trials (RCTs) and observational studies. The end points included any treatment-related adverse events (TEAEs), serious TEAEs (SAEs) and treatment discontinuation. A random-effects model was used to generate overall incidences of TEAE. Results: Three RCTs, three RCT extension studies and three open-label studies involving 2177 PD patients were evaluated. In the short-term studies, there were reports of TEAEs with an incidence of ≥5% in individuals treated with opicapone 50 mg, including dyskinesia (14.1%), elevated blood creatine phosphokinase levels (8.0%) and urinary tract infection (6.0%). Any TEAEs, SAEs and treatment discontinuation all occurred at rates of 62.9%, 4.8% and 9.3%, respectively. TEAEs with opicapone 50 mg that were reported by more than 5% of patients in long-term studies included dyskinesia (16.1%), dry mouth (12.1%), medication effect decreased (12.1%), PD exacerbated (7.8%), blood creatine phosphokinase level raised (7.4%), nausea (6.1%) and insomnia (5.1%). The incidence of any TEAEs, SAEs and treatment discontinuation were, correspondingly, 73.2%, 8.7% and 8.4%. Conclusion: These studies demonstrated that opicapone was generally well-tolerated and had a low risk of adverse events, suggesting that it could be a valuable therapeutic choice for people with PD.

18.
Front Psychol ; 13: 1019898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36570993

RESUMO

Introduction: Social exclusion as well as a sense of belonging and depression have been identified as risk factors for suicide among older adults in pension institutions. In particular, the elderly living in rural pension institutions is more likely to have poor mental health and a higher incidence of suicidal ideation. This study explored the mechanism of social exclusion on suicidal ideation among the elderly in rural pension institutions, and the moderating effect of interpersonal trust. Methods: The social exclusion experience scale, sense of belonging, depression self-rating scale (CES-D), suicidal ideation scale (BSI-CV), and interpersonal trust scale (ITS) were used to investigate the elderly in rural pension institutions. A total of 1,387 samples (53.35% female) were collected, ranging in age from 65 to 95 years (M = 72.8, SD = 6.173). Results: The results of the study found that: (1) social exclusion increases the suicidal ideation of the elderly in rural pension institutions, and the sense of belonging and depression play a significant chain-mediated role in the relationship between social exclusion and suicidal ideation in the elderly. (2) Interpersonal trust moderates the impact of social exclusion on the sense of belonging, depression, and suicidal ideation. Specifically, interpersonal trust can alleviate the promotion effect of social isolation on suicidal ideation and depression, and can also reduce the adverse effect of social exclusion on the sense of belonging. Discussion: This study validates that social exclusion is a risk factor for suicidal ideation in the rural elderly and identifies interpersonal trust as a protective factor against social exclusion and its negative outcomes in the elderly. This study provides a scientific basis for improving the depression status of the elderly in rural China and formulating suicide prevention measures.

19.
Microb Pathog ; 172: 105785, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36150554

RESUMO

The ptsG (hpIIBCGlc) gene, belonging to the glucose-specific phosphotransferase system, encodes the bacterial glucose-specific enzyme IIBC. In this study, the effects of a deletion of the ptsG gene were investigated by metabolome and transcriptome analyses. At the transcriptional level, we identified 970 differentially expressed genes between ΔptsG and sc1401 (Padj<0.05) and 2072 co-expressed genes. Among these genes, those involved in methane metabolism, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, pyruvate metabolism, phosphotransferase system (PTS), biotin metabolism, Two-component system and Terpenoid backbone biosynthesis showed significant changes in the ΔptsG mutant strain. Metabolome analysis revealed that a total of 310 metabolites were identified, including 20 different metabolites (p < 0.05). Among them, 15 metabolites were upregulated and 5 were downregulated in ΔptsG mutant strain. Statistical analysis revealed there were 115 individual metabolites having correlation, of which 89 were positive and 26 negative. These metabolites include amino acids, phosphates, amines, esters, nucleotides, benzoic acid and adenosine, among which amino acids and phosphate metabolites dominate. However, not all of these changes were attributable to changes in mRNA levels and must also be caused by post-transcriptional regulatory processes. The knowledge gained from this lays the foundation for further study on the role of ptsG in the pathogenic process of Glaesserella parasuis (G.parasuis).


Assuntos
Glucose , Pasteurellaceae , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato , Adenosina/metabolismo , Aminas/metabolismo , Aminoácidos/metabolismo , Amino Açúcares/metabolismo , Benzoatos/metabolismo , Biotina/genética , Biotina/metabolismo , Glucose/metabolismo , Metaboloma , Metano , Nucleotídeos/metabolismo , Fosfatos , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/genética , Piruvatos/metabolismo , RNA Mensageiro/metabolismo , Amido/metabolismo , Sacarose/metabolismo , Terpenos , Transcriptoma , Pasteurellaceae/enzimologia
20.
Chem Commun (Camb) ; 58(72): 10036-10039, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-35983883

RESUMO

Here, a novel transformed CdO with low coordination and N doping environment was simply synthesized through the involvement of the target molecule tetracycline (TC). The results showed that the shedding of surface hydroxyl groups led to a low coordination environment, and N doping formed a new doping energy level, which increased the charge density and promoted the migration and separation of photo-generated carriers. Its photocatalytic performance was 4.32 times higher than that of hydroxy-rich CdO and the selectivity coefficient was 4.8. Combined with theoretical calculation and in situ Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) analysis, the significant improvement of selectivity was due to the interaction of the doped N atom with the methyl carbon in TC. This work provided a new idea for the simultaneous construction of low coordination environment and N-doped materials for efficient selective photocatalysis.


Assuntos
Antibacterianos , Tetraciclina , Carbono , Catálise
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