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1.
Food Chem ; 434: 137420, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37696154

RESUMO

Steviol glycosides possess Bola-form amphiphilic structure, which can solubilize hydrophobic phytochemicals and exert physical modification to the hydrophilic matrix. However, the effect of steviol glycosides on the starch hydrogel is still unclear. Herein, the physicochemical properties, in vitro digestibility, and release behavior of starch hydrogel in the presence of steviol glycosides were investigated. The results showed that the addition of steviol glycosides promoted the gelatinization and gelation of starch, and endowed the starch hydrogel with softer texture, larger volume, and higher water holding capacity. The hydrophobic curcumin was well integrated into hydrogel by steviol glycosides, providing the gel with improved colour brilliance. The introduction of steviol glycosides hardly affected the digestibility of starch gel, but it promoted the release rate of curcumin. Notably, this release behavior was pH dependent, which tended to target the alkaline intestine. This work provided some theoretical supports for the development of sugar-free starchy foods.


Assuntos
Curcumina , Diterpenos do Tipo Caurano , Stevia , Glicosídeos/química , Amido , Stevia/química , Hidrogéis , Diterpenos do Tipo Caurano/química , Concentração de Íons de Hidrogênio
2.
Food Chem ; 437(Pt 1): 137673, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37913708

RESUMO

Chitosan-based food packaging film was prepared by incorporating zein-tannic acid nanoparticles (ZTNPs) into chitosan and was evaluated in terms of structure, physical, mechanical and functional properties. Results showed that there were hydrogen bonding interactions between ZTNPs and chitosan matrix, which is conductive to mechanical enhancements of chitosan films. Compared with the pure chitosan film, the composite films with 10% ZTNPs at pH 4 showed the increased tensile strength by 196.58%, increased elongation at break by 161.37%, decreased water vapor permeability by 70.76% and decreased oxygen permeability by 40.68%. The highest inhibition rates of this composite film-forming fluid against Escherichia coli and Staphylococcus aureus reached 83.32% and 72.35%, respectively. The composite film forming solution formed by adding 10% ZTNPs was used for sugar orange preservation. The weight loss rate of oranges was reduced and the nutrient retention rate was improved. This study expanded the application of chitosan-based packaging materials in fruit preservation.


Assuntos
Quitosana , Nanopartículas , Zeína , Quitosana/química , Zeína/química , Açúcares , Permeabilidade , Embalagem de Alimentos/métodos , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química
3.
Patient Educ Couns ; 118: 108031, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37924743

RESUMO

OBJECTIVE: To comprehensively analyze and further enhance the established E4 communication model for online medical counseling in Chinese settings, by proposing the novel E5 model. Additionally, it aims to evaluate the performance of Chinese doctors in fulfilling the E5 model. METHODS: Through thematic analysis and grounded theory of 500 online medical consultations in China, we developed the extended E5 model from the E4 model. We identified four dimensions of patient attitudes and behaviors using Stanford Topic Modeling Toolbox, then employed Chi-square analysis to investigate their influence on doctors' performance of E5 model. RESULTS: Our study illustrates that the extended E5 model, with its operable strategies, accurately mirrors the nuanced dynamics of online medical counseling in China, significantly varying in doctors' execution in response to the four identified dimensions of patient attitudes and behaviors. CONCLUSION: The extended E5 model, coupled with insights into patient attitudes and behaviors, provides a comprehensive framework for understanding and enhancing communication in China's online healthcare context. PRACTICE IMPLICATIONS: The findings highlight the necessity for doctor training in the E5 model for effective online communication. Furthermore, fostering conducive relationship between patients and doctors could potentially boost doctors' E5 performance.


Assuntos
Relações Médico-Paciente , Médicos , Humanos , População do Leste Asiático , Médicos/psicologia , Comunicação , Encaminhamento e Consulta
4.
Front Plant Sci ; 14: 1280126, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38046615

RESUMO

Changes in tree species composition are one of the key aspects of forest succession. In recent decades, significant changes have occurred in the tree species composition of subtropical forests in China, with a decrease in coniferous trees and an increase in broad-leaved trees. This study focuses on Zhejiang Province, located in the subtropical region of China, and utilizes seven inventories from the National Continuous Forest Inventory (NCFI) System spanning 30 years (1989-2019) for modeling and analysis. We categorized tree species into three groups: pine, fir, and broadleaf. We used the proportion of biomass in a sample plot as a measure of the relative abundance of each tree species group. A novel nonlinear difference equation system (NDES) model was proposed. A NDES model was established based on two consecutive survey datasets. A total of six models were established in this study. The results indicated that during the first two re-examination periods (1989-1994, 1994-1999), there was significant fluctuation in the trend of tree species abundance, with no consistent pattern of change. During the latter four re-examination periods (1999-2004, 2004-2009, 2009-2014, 2014-2019), a consistent trend was observed, whereby the abundance of the pine group and the fir group decreased while the abundance of the broad-leaved group increased. Moreover, over time, this pattern became increasingly stable. Although the abundances of the pine group and the fir group have been steadily declining, neither group is expected to become extinct. The NDES model not only facilitates short-term, medium-term, and even long-term predictions but also employs limit analysis to reveal currently obscure changing trends in tree species composition.

5.
Calcif Tissue Int ; 2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38043102

RESUMO

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13 years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10 months to 2 years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

6.
J Agric Food Chem ; 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38044624

RESUMO

Methoxyeugenol is a phenylpropene compound derived from plants and has various bioactivities. The chemical synthesis of methoxyeugenol is accompanied by pollution issues, whereas extraction from plants is associated with problems such as low yield and high cost. The production of methoxyeugenol can be effectively addressed through an enzymatic approach. In this study, the acyltransferase genes of Euphorbia lathyris L. were screened by homologous alignment of the transcriptome data of E. lathyris in the late growth stage and the acyltransferase genes of the closely related plant species. The results showed that ElBAHD10 had the closest relationship with earlier reported ScCFAT and PhCFAT, which were found to catalyze the reaction of coniferyl alcohol to generate coniferyl acetate. The ElBAHD10 gene was successfully cloned from E. lathyris and subsequently expressed in Escherichia coli. The purified protein ElBAHD10 catalyzed the reaction of sinapyl alcohol with acetyl CoA and cinnamoyl CoA to form sinapyl acetate and sinapyl cinnamate, respectively. In contrast, the crude ElBAHD10 protein could catalyze sinapyl alcohol to directly generate methoxyeugenol. The recombinant E. coli strain expressing ElBAHD10 produced methoxyeugenol through whole-cell transformation. This study provides insights and lays the foundation for methoxyeugenol production through biosynthetic approaches.

7.
Yeast ; 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041528

RESUMO

Genetic targeting (e.g., gene knockout and tagging) based on polymerase chain reaction (PCR) is a simple yet powerful approach for studying gene functions. Although originally developed in classic budding and fission yeast models, the same principle applies to other eukaryotic systems with efficient homologous recombination. One-step PCR-based genetic targeting is conventionally used but the sizes of the homologous arms that it generates for recombination-mediated genetic targeting are usually limited. Alternatively, gene targeting can also be performed via fusion PCR, which can create homologous arms that are orders of magnitude larger, therefore substantially increasing the efficiency of recombination-mediated genetic targeting. Here, we present GetPrimers (https://www.evomicslab.org/app/getprimers/), a generalized computational framework and web tool to assist automatic targeting and verification primer design for both one-step PCR-based and fusion PCR-based genetic targeting experiments. Moreover, GetPrimers by design runs for any given genetic background of any species with full genome scalability. Therefore, GetPrimers is capable of empowering high-throughput functional genomic assays at multipopulation and multispecies levels. Comprehensive experimental validations have been performed for targeting and verification primers designed by GetPrimers across multiple organism systems and experimental setups. We anticipate GetPrimers to become a highly useful and popular tool to facilitate easy and standardized gene modification across multiple systems.

8.
Sci Rep ; 13(1): 19004, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923817

RESUMO

Although a myriad of studies have been conducted on player behavior in football, in-depth studies with structured theory are rare due to the difficulty in quantifying individual player skills and team strategies. We propose a physics-based mathematical model that describes football players' movements during dribbling situations, parameterized by the attacker aggressiveness, the defender hesitance and the top speed of both players. These player- and situation-specific parameters are extracted by fitting the model to real player trajectories from Major League Soccer games, and enable the quantification of player dribbling attributes and decisions beyond classical statistics. We show that the model captures the essential dribbling dynamics, and analyze how differences between parameters in varying game situations provide valuable insights into players' behavior. Lastly, we quantitatively study how changes in the player's parameters impact dribbling performance, enabling the model to provide scientific guidance to player training, scouting and game strategy development.


Assuntos
Desempenho Atlético , Futebol , Movimento
9.
Heliyon ; 9(11): e20951, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37920522

RESUMO

Background: This research was designed to investigate Algorithm Guided Treatment (AGT) and clinical traits for the prediction of antidepressant treatment outcomes in Chinese patients with major depressive disorder (MDD). Methods: This study included 581 patients who had reached treatment response and 406 patients remained non-responded observed after three months of treatment. Sociodemographic factors, clinical traits, and psychiatric rating scales for evaluating therapeutic responses between the two groups were compared. Logistic regression analysis was adopted to determine the risk factors of unresponsive to antidepressant (URA) in MDD. Kaplan-Meier survival analysis was utilized to compare the therapeutic response between AGT and treatment as usual (TAU). Results: Compared to the MDD responsive to antidepressant (RA) group, the URA group had significantly lower rates of the following clinical traits: married status, anxious distress, moderate to severe depressive symptoms, and higher rates of comorbidity (p-value < 0.05). Logistic Regression Analysis showed that eight clinical traits from psychiatric rating scales, such as anxious characteristics, were correlated positively with URA, while the other eight symptoms, such as autonomic symptoms, were negatively correlated. Time to symptomatic remission was longer in TAU without statistically significant (p-value = 0.11) by log-rank testing. Conclusions: The factors may affect the therapeutic responses and compliance of patients, increasing the non-response risk for antidepressants. Therapeutic responses might be improved by increasing the clarification and elucidation of different symptom clusters of patients. Benefits on treatment response to AGT were not found in our study, indicating a one-size-fits-all approach may not work.Trial Registration: We registered as a clinical trial at the International Clinical Trials Registry Platform (No. NCT01764867) and obtained ethical approval 2012-42 from SMHC.

10.
Artigo em Inglês | MEDLINE | ID: mdl-37924409

RESUMO

The accumulation of antibiotics in the environment can be harmful to human health, and research on their disposal technologies is of increasing interest. In this study, WO3/α-Fe2O3/zeolite (WFZ) type II heterojunction composites with core-shell structures were prepared by coupling WO3 semiconductors with visible-light photocatalytic activity with α-Fe2O3 via hydrothermal synthesis using zeolite as a carrier for the adsorption of synergistic photocatalytic degradation of antibiotics in wastewater. X-ray diffraction, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), specific surface, and porosity measurements were used to characterize the structure of WFZ type II heterojunction. The performance of WFZ heterojunction for the visible photocatalytic degradation of antibiotics (tetracycline hydrochloride (TCH), ciprofloxacin (CIP), and levofloxacin hydrochloride (LVF)) was investigated. Through four photocatalytic cycles, the catalyst exhibited excellent durability and stability. This was attributed to the core-shell structure and type II heterojunction promoting the effective separation of photogenerated carriers and the extended visible light response range, which resulted in the best photocatalytic activity of the catalyst under visible light irradiation. Radical trapping experiments showed that superoxide radicals (•O2-) and hydroxyl radical (•OH) were the main active species that played a major role in the photocatalytic degradation. These findings show that the synthesized WFZ type-II heterojunction can be used as a reliable visible-light-responsive photocatalyst for the treatment of antibiotics in wastewater.

11.
Int J Surg ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924501

RESUMO

AIM: This paper aimed to explore the application of Three-dimensional (3D) printing in cardiovascular diseases, to reach an insight in this field and prospect the future trend. METHODS: The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.16, and CiteSpace 6.1.R6 were used to analyze the information. RESULTS: A total of 467 papers of 3D printing in cardiovascular diseases were identified, and the first included literature appeared in 2000. A total of 692 institutions from 52 countries participated in the relevant research, while the United States of America contributed to 160 articles and were in a leading position. The most productive institution was Curtin University , and Zhonghua Sun who has posted the most articles (n=8) was also from there. The Frontiers in Cardiovascular Medicine published most papers (n=25). The Journal of Thoracic and Cardiovascular Surgery coveted the most citations (n=520). Related topics of frontiers will still focus on congenital heart disease, valvular heart disease, and left atrial appendage closure. CONCLUSIONS: We summarized the publication information of the application of 3D printing in cardiovascular diseases related literature from 2000 to 2023, including country and institution of origin, authors, and publication journal. This study can reflect the current hotspots and novel directions for the application of 3D printing in cardiovascular diseases.

12.
Mini Rev Med Chem ; 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37929738

RESUMO

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. AD patients usually present symptoms, such as cognitive dysfunction, progressive memory loss, and other manifestations. With the increasing number of AD cases worldwide, there is an urgent need to develop effective drug treatments. Currently, drugs targeting AD symptoms may not change or prevent the progression of the disease. Curcumin, a polyphenol extracted from the turmeric herb, has been used for the treatment of AD. In this review, we summarized both cellular and animal studies and described the mechanism of action of curcumin in altering the pathological features of AD. Curcumin attenuates the formation of amyloid-ß plaques and promotes its decomposition, reduces the phosphorylation of tau, improves its clearance rate, and binds with copper to reduce cholesterol. It changes the activity of microglia, suppresses acetylcholinesterase, regulates insulin signal transduction, and exhibits antioxidant properties. Studies have found that curcumin can promote nerve repair and has a significant effect on AD. However, the low bioavailability of curcumin may hinder its use as a therapeutic agent. If this limitation can be overcome, curcumin may emerge as a promising drug for the treatment of AD.

13.
Neurosci Lett ; 818: 137560, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37979715

RESUMO

Plasmalogens (Pls) are considered to play a potential role in the treatment of neurodegenerative diseases. In the present study, an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 was established to investigate whether the marine-derived Pls could alleviate cognitive impairments of AD zebrafish. Behavioral tests were carried out to assess the athletic ability. The transcriptional profiles of zebrafish in the control, AD model and AD_PLS group were compared and analyzed to determine the potential mechanisms of dietary Pls on AD. The study found that Pls could reverse athletic impairment in the AD zebrafish model, and the expression levels of genes related to ferroptosis, synaptic dysfunction and apoptosis were significantly altered between experimental groups. Further analysis showed that all of these genes were associated with oxidative stress (OS). These data suggest that healthy protective role of marine-derived Pls on AD zebrafish may result from inhibition of ferroptosis and neuronal apoptosis, restoring synaptic neurotransmission release, and reducing neuroinflammation. Among them, Oxidative stress is acted as the center to connect different regulation pathways. This study provides evidence to support the essential roles of OS in pathogenesis of AD, and the application of Pls in relieving AD.

14.
Cancer Immunol Res ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37956411

RESUMO

Pancreatic cancer is a deadly disease that is largely resistant to immunotherapy, in part because of the accumulation of immunosuppressive cells in the tumor microenvironment (TME). Much evidence suggests that tumor-derived exosomes contribute to the immunosuppressive activity mediated by myeloid-derived suppressor cells (MDSCs) within the pancreatic cancer TME. However, the underlying mechanisms remain elusive. Herein, we report that macrophage migration inhibitory factor (MIF) in tumor-derived exosomes has a key role in inducing MDSC formation in pancreatic cancer. We identified MIF in both human and murine pancreatic cancer-derived exosomes. Upon specific shRNA-mediated knockdown of MIF, the ability of pancreatic cancer-derived exosomes to promote MDSC differentiation was abrogated. This phenotype was rescued by re-expression of the wildtype form of MIF rather than a tautomerase-null mutant or a thiol-protein oxidoreductase-null mutant, indicating that both MIF enzyme activity sites play a role in exosome-induced MDSC formation in pancreatic cancer. RNA sequencing data indicated that MIF tautomerase regulated the expression of genes required for MDSC differentiation, recruitment, and activation. We therefore developed a MIF tautomerase inhibitor, IPG1576. The inhibitor effectively inhibited exosome-induced MDSC differentiation in vitro and reduced tumor growth in an orthotopic pancreatic cancer model, which was associated with decreased numbers of MDSCs and increased infiltration of CD8+ T cells in the TME. Collectively, our findings highlight a pivotal role for MIF in exosome-induced MDSC differentiation in pancreatic cancer and underscore the potential of MIF tautomerase inhibitors to reverse the immunosuppressive pancreatic cancer microenvironment, thereby augmenting anticancer immune responses.

15.
ACS Macro Lett ; 12(11): 1576-1582, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37934863

RESUMO

The morphology of materials has a huge impact on their properties and functions; however, the precise control and direct evolution toward specific morphologies remains challenging. Herein, we outline a novel strategy for the morphology modulation of covalent organic frameworks based on COF-300 with the diamond structure, which usually exhibits a three-dimensional shuttle morphology. A monofunctional structural regulator has been designed to break the continuity of the three-dimensional structure. As the proportion of the monofunctional structural regulator increases, the morphology of COF-300 shows a directional evolution from a shuttle morphology to a two-dimensional nanosheet, while still retaining the consistency of the crystal structure. Our study reports the first two-dimensional nanosheet based on a three-dimensional structured COF to date and will inspire future research into the traced morphological evolution in materials by predesign.

16.
Int J Pharm ; : 123629, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37992979

RESUMO

Given that current androgenetic alopecia (AGA) medications have adverse effects such as sexual dysfunction and drug dependence, researchers are actively exploring natural bioactive ingredients and innovative approaches (e.g., transdermal drug delivery systems) to effectively combat hair loss with minimal side effects. Herein, we develop a new transdermal drug delivery system incorporating globefish skin collagen peptides with dissolving microneedles (GSCPs-MNs) for hair regrowth. These microneedles generate skin micro-wounds upon application, which not only improves the efficiency of bioactive ingredients delivery, but also stimulates signals involved in hair follicle (HF) regeneration. Our in vivo study shows that minimally invasive implanted GSCPs-MNs are more effective than topical GSCPs in reducing inflammation and promoting collagen formation. Additionally, the upregulation of vascular markers including VEGF and CD31 alongside the downregulation of TNF-α, IL-1ß, and malondialdehyde (MDA) index indicate that GSCPs-MNs can significantly alleviate inflammation and oxidation, as well as promoting vascularization and HF functionalization. Overall, our findings suggest that GSCPs-MNs can effectively promote hair regrowth in AGA mice, which offer excellent prospects for the development of new therapeutics and cosmetic supplements for hair loss, along with the combined drug delivery optimization, which could alleviate hair loss in patients with AGA.

17.
Aging (Albany NY) ; 152023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37980166

RESUMO

Currently, the roles of ZNF692 have been documented exclusively in lung, colon, and cervical cancers. However, its involvement in pan cancer remains unknown. In this study, we employed bioinformatics analysis and experimental validation to investigate the role of ZNF692 in pan cancer. Our findings revealed aberrant expression of ZNF692 across various types of cancer. High expression of ZNF692 was associated with poor overall survival (OS) in ACC, COAD, KIRC, LAML, and LIHC. ZNF692 exhibited promising diagnostic potential in certain tumor types. A significant correlation was observed between high ZNF692 expression and advanced stages of ACC, BLCA, KICH, KIRC, LIHC, and OV. The expression of ZNF692 exhibited a significant association with microsatellite instability (MSI) in eight types of cancer and tumor mutational burden (TMB) in ten types of cancer. A noteworthy correlation was observed between ZNF692 expression and immune infiltration as well as immune checkpoints. Amplification of ZNF692 emerged as the most frequent alteration in pan cancer. ZNF692 was implicated in various biological processes, cellular components, and molecular functions within the context of pan cancer. It is plausible that ZNF692 may contribute to chemotherapy and potentially be linked to chemoresistance. We constructed a competing endogenous RNA (ceRNA) network involving AC009403.11/miR-126-3p/ZNF692 in hepatocellular carcinoma (HCC). The expression of ZNF692 exhibited a notable upregulation in HCC cell lines. Aberrant expression of ZNF692 was observed across various types of cancer. ZNF692 holds potential as a valuable diagnostic, prognostic, and therapeutic target in the context of pan cancer.

18.
Pharmacol Biochem Behav ; 233: 173672, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37944671

RESUMO

OBJECTIVE: Ghrelin is physiologically important for maintaining sleep rhythm. Cigarette smoking has been demonstrated to significantly increase the risk of insufficient sleep by regulating ghrelin at the central and peripheral levels. No research has been published to study the relationship between active smoking and sleep via ghrelin level in cerebrospinal fluid (CSF). METHODS: A total of 139 Chinese males were recruited and divided into active smokers (n = 77) and non-smokers (n = 62). The levels of CSF and plasma ghrelin were measured. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep. RESULTS: Non-smokers had lower PSQI scores (1.71 ± 1.93) than active smokers (3.70 ± 1.78). Non-smokers have significantly lower plasma ghrelin levels and lower plasma/CSF ghrelin ratio but higher CSF ghrelin than active smokers. Among non-smokers, plasma ghrelin levels were not correlated with PSQI scores (all p > 0.05), CSF ghrelin levels were positively correlated with PSQI scores (r = 0.309, p = 0.019), and the plasma/CSF ghrelin ratio was negatively correlated with PSQI scores (r = -0.346, p = 0.008). CONCLUSIONS: This study is the first to reveal the relationship between cigarette smoking, high CSF ghrelin levels and insufficient sleep, suggesting that maintaining a normal plasma/CSF ghrelin ratio may be the physiological mechanism of healthy sleep, and the insufficient sleep population must quit smoking.


Assuntos
Fumar Cigarros , Transtornos do Sono-Vigília , Masculino , Humanos , Grelina , Privação do Sono , Sono , Transtornos do Sono-Vigília/epidemiologia , Tabaco
19.
Biomedicines ; 11(11)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-38001963

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is associated with enhanced aerobic glycolysis through elevated glucose uptake and the upregulated expression of genes encoding rate-limiting glycolytic enzymes. However, the direct impact of altered glycolytic pathways on pancreatic tumor progression has not been thoroughly investigated. Here, we utilized two strains of BAC transgenic mice with pancreatic expression of two distinct sets of glycolytic genes each arranged in a polycistronic fashion (PFKFB3-HK2-GLUT1 and LDHA-PDK1, respectively) to investigate the role of altered glycolysis on the development of pancreatic ductal tumor development in the Pdx1-Cre; LSL-KrasG12D mice. The overexpression of the two sets of glycolytic genes exhibited no significant effects on tumor development in the 4-5-month-old mice (the PanIN2 lesions stage). In the 9-10-month-old mice, the overexpression of PFKFB3-HK2-GLUT1 significantly accelerated PanIN3 progression, exhibiting elevated levels of ductal cell marker CK19 and tumor fibrosis. Surprisingly, the overexpression of LDHA-PDK1 significantly attenuated the progression of PanIN3 in the 9-10-month-old mice with significantly downregulated levels of CK19 and fibrosis. Therefore, distinct set of glycolytic enzymes that are involved in different glycolytic routes exhibited contrasting effects on pancreatic ductal tumor development depending on the tumor stages, providing novel insights into the complexity of the glycolytic pathway in the perspective of PDAC development and therapy.

20.
Front Microbiol ; 14: 1279996, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029107

RESUMO

Hypercholesterolemia, a risk factor for cardiovascular disease (CVD), often requires therapeutic agents with varying degrees of side effects. This has created a need for safe and natural alternatives such as medications or functional foods that can improve lipid metabolism and reduce cholesterol levels. In recent years, Next-generation probiotics (NGPs) have recently emerged as a potential solution, offering distinct mechanisms compared to traditional probiotics. Among the NGPs, Bacteroides, a dominant bacterial genus in the human gut, has gained significant attention due to its prevalence, ability to break down plant polysaccharides, and production of short-chain fatty acids (SCFAs). Recent evidence has demonstrated that Bacteroides effectively reduces cholesterol levels, prevents obesity, and lowers the risk of CVD. However, research on Bacteroides is currently limited to a few species, leaving rooms for exploration of the beneficial functions of different species in this genus. In this study, we isolated 66 Bacteroides strains, including 9 distinct species, from healthy adults' fecal samples. By comparing their ability to assimilate cholesterol, we found that the transformation ability was not specific to any particular species. Notably, Bacteroides dorei YGMCC0564 revealed superior cholesterol-lowering capabilities and bile salt hydrolase (BSH) activity in vitro, surpassing that of Lactobacillus GG (LGG). YGMCC0564 exhibited favorable probiotic characteristics, including high survival rate in vitro simulation of gastrointestinal digestion, excellent adhesion ability, susceptibility to antibiotics, absence of hemolysis or virulence genes, and substantial production of SCFAs. The strain also demonstrated remarkable bile salt deconjugation activities and upregulation of the BT_416 gene associated with cholesterol, providing insights into a possible molecular mechanism underlying its cholesterol-reducing activity. These findings establish YGMCC0564 as a promising NPG candidate for improving cardiovascular health.

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