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1.
Artigo em Inglês | MEDLINE | ID: mdl-39226170

RESUMO

Aims Arterial stiffness, a hallmark of vascular aging, significantly contributes to hypertension and impaired organ perfusion. Vascular smooth muscle cell (VSMC) dysfunction, particularly VSMC senescence and its interaction with stiffness, is crucial in the pathogenesis of arterial stiffness. Although hydrogen sulfide (H2S) and its key enzyme cystathionine γ-lyase (CSE) are known to play roles in cardiovascular diseases, their effects on arterial stiffness are not well understood. Methods & Results First, we observed a downregulation of CSE/H2S in the aortic media during biological aging and Angiotensin II (AngII)-induced aging. The VSMC-specific CSE knockout mice were created by loxp-cre (Tagln-cre) system, and which exacerbated AngII-induced aortic aging and stiffness in vivo and VSMC senescence and stiffness in vitro. Conversely, the CSE agonist norswertianolin mitigated these effects. Next, we identified growth arrest-specific 1 (Gas1) as a crucial target of CSE/H2S and found it to be a downstream target gene of forkhead box protein M1 (Foxm1). siRNA knockdown Foxm1 increased Gas1 transcription and reduced the protective effects of H2S on VSMC senescence and stiffness. Finally, we demonstrated that CSE/H2S sulfhydrates Foxm1 at the C210 site, regulating its nuclear translocation and activity, thus reducing VSMC senescence and stiffness. Innovation Our findings highlight the protective role of CSE/H2S in arterial stiffness, emphasizing the novel contributions of CSE, Gas1, and Foxm1 to VSMC senescence and stiffness. Conclusion Endogenous CSE/H2S in VSMCs reduces VSMC senescence and stiffness, thereby attenuating arterial stiffness and aging, partly through sulfhydration-mediated activation of Foxm1 and subsequent inhibition of Gas1 signaling pathways.

2.
Stem Cell Res Ther ; 15(1): 279, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227906

RESUMO

Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.


Assuntos
Tecido Adiposo , Pé Diabético , Secretoma , Cicatrização , Humanos , Pé Diabético/terapia , Pé Diabético/metabolismo , Pé Diabético/patologia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Secretoma/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Animais
3.
Heliyon ; 10(17): e36327, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39263082

RESUMO

Objective: This study utilized network meta-analysis (NMA) to compare the efficacy of five commonly used traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models. Methods: Relevant literature up to January 2024 was systematically retrieved from seven major databases. The intima-to-media (I/M) ratio was chosen as the primary outcome measure. The risk of bias in animal studies was assessed using the SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Statistical analysis was conducted using Stata 17 software. Results: A total of 43 studies were included in this meta-analysis. NMA results showed that in the rat model, compared to the control group, GS (SMD: 0.99, 95%CI: 1.25 to -0.73), ASIV (SMD: 1.16, 95%CI: 1.65 to -0.67), TMP (SMD: 0.68, 95%CI: 1.31 to -0.05), and TPNS (SMD: 1.36, 95%CI: 1.91 to -0.80) exhibited inhibitory effects on postoperative intimal hyperproliferation, reducing the I/M ratio. In the rabbit model, compared to the control group, TPNS (SMD: 1.23, 95%CI: 1.97 to -0.49) inhibited postoperative intimal hyperproliferation and reduced the I/M ratio. Superiority ranking analysis suggested that total Panax notoginseng saponin (TPNS) might be the most effective traditional Chinese medicine monomer in reducing intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio. Conclusion: NMA indicates that traditional Chinese medicine monomers can effectively reduce postoperative intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio, with TPNS showing optimal efficacy. However, the research on TIIA is insufficient, and the limited sample size may affect the robustness of the results. Furthermore, the majority of research on traditional Chinese medicine monomers is currently limited to the experimental stage, lacking further clinical validation. Conducting standardized animal experiments and reporting their findings can enhance the quality of evidence from animal studies, laying the foundation for future clinical trials.

4.
Food Chem X ; 23: 101757, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39257497

RESUMO

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

5.
J Cancer Surviv ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141310

RESUMO

PURPOSE: The interplay between sleep quality, anxiety, and depression among breast cancer patients remains poorly understood. This study aimed to investigate and compare the symptoms relationships among these three factors in Chinese breast cancer patients, utilizing two sleep assessments. METHODS: Our study encompassed 288 participants diagnosed with breast cancer, from whom we collected demographic information through questionnaires. Sleep quality symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy, while anxiety and depression symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Network analyses were conducted using R to calculate the centrality (strength) and further identify central symptoms and bridge symptoms in two networks that differed by sleep assessments. Central symptoms are closely related to other symptoms, whereas bridge symptoms indicate that symptoms may increase spread risk between different conditions. RESULTS: In the network using PSQI data, "I have lost interest in my appearance" had the highest strength centrality (rs = 2.417), followed by "sleep duration" (rs = 1.068) and "sleep efficiency" (rs = 0.955). In the network using wrist actigraphy data, "wake after sleep onset" had the highest strength value (rs = 2.437), followed by "sleep efficiency" (rs = 2.397) and "sleep latency" (rs = 1.506). Two bridge symptoms were identified: "I feel cheerful" and "I look forward with enjoyment to things" in both networks. CONCLUSIONS: Depressive symptoms played a leading role in the sleep-anxiety-depression network, underscoring the need for targeted intervention tailored to survivors' specific needs. IMPLICATIONS FOR CANCER SURVIVORS: Health workers can give priority to symptom-specific screening and therapies, incorporating psychological support into standard cancer care.

6.
Eur J Neurol ; : e16422, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096086

RESUMO

BACKGROUND AND PURPOSE: Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. METHODS: Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. RESULTS: A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). CONCLUSIONS: Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

7.
Medicine (Baltimore) ; 103(34): e39392, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39183433

RESUMO

Alzheimer disease is an irreversible neurodegenerative disease, and its pathogenesis involves various mechanisms such as neuroinflammation and ß-amyloid deposition. Erjing Pills can inhibit neuroinflammation by inhibiting toll-like receptor 4/nuclear factor kappa-B/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3; however, qualitative analysis of the material basis is lacking. Therefore, it is necessary to analyze and explore the material basis of network pharmacology research. This study employed a multifaceted approach, including drug-like screening, molecular docking, and bioinformatic analysis. Preliminary screening identified 59 drug ingredients in Erjing Pills that met the Absorption, Distribution, Metabolism, Excretion and Toxicity screening criteria. Among these, 7 ingredients, including diosgenin, exhibited superior binding properties compared with the positive drugs in molecular docking. Gene ontology annotation and pathway analysis revealed their involvement in crucial biological processes, such as hormone response, insulin resistance, and steroid hormone biosynthesis signaling pathways, which are known for their anti-inflammatory and cognitive enhancement effects. A meta-analysis of relevant literature corroborated the anti-inflammatory activities of diosgenin and 5 other ingredients. These 5 ingredients, with diosgenin as a prominent candidate, exert anti-inflammatory effects by targeting key components of the toll-like receptor 4/nuclear factor kappa-B/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3 inflammatory pathway, thereby presenting potential efficacy in the treatment of Alzheimer disease.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Farmacologia em Rede , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , NF-kappa B/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Farmacologia em Rede/métodos , Transdução de Sinais/efeitos dos fármacos , Anti-Inflamatórios/farmacologia
8.
Micromachines (Basel) ; 15(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39203659

RESUMO

In order to solve the performance prediction and design optimization of power amplifiers (PAs), the performance parameters of Gallium Nitride high-electron-mobility transistor (GaN HEMT) PAs at different temperatures are modeled based on the particle swarm optimization-extreme learning machine (PSO-ELM) and extreme learning machine (ELM) in this paper. Then, it can be seen that the prediction accuracy of the PSO-ELM model is superior to that of ELM with a minimum mean square error (MSE) of 0.0006, which indicates the PSO-ELM model has a stronger generalization ability when dealing with the nonlinear relationship between temperature and PA performance. Therefore, this investigation can provide vital theoretical support for the performance optimization of PA design.

9.
Diabetol Metab Syndr ; 16(1): 208, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39198854

RESUMO

BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists have been shown to reduce major cardiovascular events in diabetic patients, but their role in heart failure (HF) remains controversial. Recent evidence implies their potential benefits on cardiometabolism such as lipid metabolism, which may contribute to lowering the risk of HF. Consequently, we designed a Mendelian randomization (MR) study to investigate the causal relationships of circulating lipids mediating GLP1R agonists in HF. METHODS: The available cis-eQTLs for GLP1R target gene were selected as instrumental variables (IVs) of GLP1R agonism. Positive control analyses of type 2 diabetes mellitus (T2DM) and body mass index (BMI) were conducted to validate the enrolled IVs. Two-sample MR was performed to evaluate the associations between GLP1R agonism and HF as well as left ventricular ejection fraction (LVEF). Summary data for HF and LVEF were obtained from two genome-wide association studies (GWASs), which included 977,323 and 40,000 individuals of European ancestry, respectively. The primary method employed was the random-effects inverse variance weighted, with several other methods used for sensitivity analyses, including MR-Egger, MR PRESSO, and weighted median. Additionally, multivariable MR and mediation MR were applied to identify potentially causal lipid as mediator. RESULTS: A total of 18 independent IVs were included. The positive control analyses showed that GLP1R agonism significantly reduced the risk of T2DM (OR = 0.79, 95% CI = 0.75-0.85, p < 0.0001) and decreased BMI (OR = 0.95, 95% CI = 0.93-0.96, p < 0.0001), ensuring the effectiveness of selected IVs. We found favorable evidence to support the protective effect of GLP1R agonism on HF (OR = 0.75, 95% CI = 0.71-0.79, p < 0.0001), but there was no obvious correlation with increased LVEF (OR = 1.01, 95% CI = 0.95-1.06, p = 0.8332). Among the six blood lipids, only low-density lipoprotein cholesterol (LDL-C) was both associated with GLP1R agonism and HF. The causal effect of GLP1R agonism on HF was partially mediated through LDL-C by 4.23% of the total effect (95% CI = 1.04-7.42%, p = 0.0093). CONCLUSIONS: This study supported the causal relationships of GLP1R agonists with a reduced risk of HF. LDL-C might be the mediator in this association, highlighting the cardiometabolic benefit of GLP1R agonists on HF.

10.
Food Chem ; 460(Pt 2): 140641, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39094343

RESUMO

Insoluble dietary fiber (IDF) isolated through co-fermented bran from probiotics may improve starch gel-based foods. This work aimed to elucidate the comprehensive impact of different IDF samples (CK, unfermented; NF, natively fermented; YF, yeast fermented; LF, Lactobacillus plantarum fermented; and MF, mix-fermented) and their addition ratios (0.3-0.9%) on gel structure-property function. Results indicated that IDF introduction altered the starch pasting behavior (decreased the viscosity and advanced the pasting time). Also, YF, LF, and MF showed less effect on gel multiscale morphology (SEM and CLSM); however, their excessively high ratio resulted in network structure deterioration. Moreover, FT-IR, XRD, and Raman characterization identified the composite gels interaction mechanisms mainly by hydrogen bonding forces, van der Waals forces, water competition, and physical entanglement. This modulation improved the composite gel water distribution, rheological/stress-strain behavior, textural properties, color, stability, and digestive characteristics. The obtained findings may shed light on the construction and development of whole-grain gel-based food products with new perspectives.


Assuntos
Fibras na Dieta , Fermentação , Géis , Reologia , Amido , Amido/química , Amido/metabolismo , Fibras na Dieta/análise , Fibras na Dieta/metabolismo , Géis/química , Viscosidade , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/química , Relação Estrutura-Atividade
11.
J Anim Sci ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177443

RESUMO

Stevia, a perennial shrub from the genus Stevia in the Asteraceae family, contains active ingredients like chlorogenic acid and shows promise as a natural feed additive. Despite this potential, there is limited research on the impact of stevia extract specifically on yellow-feather broilers. The study aimed to evaluate the effects of dietary stevia extract with varying concentrations of chlorogenic acid on the growth performance, serum biochemical indices, and intestinal health of yellow-feathered broilers. A total of 425 one-day-old female yellow-feathered broilers were randomly allocated into five treatment groups with five replicates of 17 broilers each, and the feeding trial lasted 63 days. The groups included a control and those supplemented with stevia extract at concentrations of 100 mg/kg, 200 mg/kg, 300 mg/kg, and 400 mg/kg. Results showed that adding 100 mg/kg of stevia extract to the basal diet significantly increased the daily weight gain (ADG) of the broilers, while reducing the average daily feed intake (ADFI) and feed conversion ratio (F/G). However, supplementation with stevia extract at concentrations up to 300 mg/kg led to decreased final weight and ADG. Conversely, dietary supplementation with 100-200 mg/kg of stevia extract improved serum antioxidant capacity and reduced serum total cholesterol levels compared to the control group. Additionally, the cecum n-butyric acid level was significantly higher in the 200 mg/kg stevia extract group than in the control group. In conclusion, supplementing yellow-feathered broilers' diets with stevia extract can enhance growth performance, antioxidant and immune capacity, and intestinal health. The optimal concentration of stevia extract for these benefits is between 100 mg/kg and 200 mg/kg.

12.
Nutrients ; 16(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39064743

RESUMO

(1) Introduction: Previous studies have found that diet can change gut microbiota, thereby affecting metabolic health. However, research on gestational diabetes mellitus (GDM) is still limited. Our study aimed to explore the mediating role of gut microbiota in the relationship between dietary patterns and GDM. (2) Methods: In this case-control study, 107 women with GDM at 24-28 weeks of gestation and 78 healthy pregnant women were enrolled. A semi-quantitative food frequency questionnaire (FFQ) was used to assess dietary intake over the previous month. Mediation analysis was performed to explore the link between dietary patterns, gut microbiota, and GDM. (3) Results: Among the five dietary patterns extracted, the high group (factor scores ≥ -0.07) of the vegetables-fruits dietary pattern had a 67% lower risk of developing GDM compared to the low group (factor scores < -0.07) (OR: 0.33; 95% CI: 0.15-0.74). In addition, a significant alteration was observed in gut microbiota composition among GDM pregnant women. Mediation analysis showed that the Lachnospiraceae family, Blautia, and Ruminococcus genus partially mediated the effect of vegetables-fruits dietary pattern on GDM, explaining 45.81%, 44.33%, and 31.53% of the association, respectively. (4) Conclusions: Adherence to vegetables-fruits dietary patterns during pregnancy may reduce the risk of GDM by altering gut microbiota composition.


Assuntos
Diabetes Gestacional , Dieta , Frutas , Microbioma Gastrointestinal , Verduras , Humanos , Feminino , Diabetes Gestacional/microbiologia , Gravidez , Adulto , Estudos de Casos e Controles , Dieta/estatística & dados numéricos , Comportamento Alimentar , Fatores de Risco , Padrões Dietéticos
13.
Curr Med Sci ; 44(4): 833-840, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38967889

RESUMO

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.


Assuntos
Apiaceae , Apoptose , Proteína 11 Semelhante a Bcl-2 , Proliferação de Células , Neoplasias Colorretais , Humanos , Proteína 11 Semelhante a Bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Animais , Apoptose/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Apiaceae/química , Ensaios Antitumorais Modelo de Xenoenxerto , Células CACO-2 , Extratos Vegetais/farmacologia , Proteólise/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Medicamentos de Ervas Chinesas/farmacologia , Camundongos Nus
14.
Nat Metab ; 6(7): 1347-1366, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961186

RESUMO

PAQR4 is an orphan receptor in the PAQR family with an unknown function in metabolism. Here, we identify a critical role of PAQR4 in maintaining adipose tissue function and whole-body metabolic health. We demonstrate that expression of Paqr4 specifically in adipocytes, in an inducible and reversible fashion, leads to partial lipodystrophy, hyperglycaemia and hyperinsulinaemia, which is ameliorated by wild-type adipose tissue transplants or leptin treatment. By contrast, deletion of Paqr4 in adipocytes improves healthy adipose remodelling and glucose homoeostasis in diet-induced obesity. Mechanistically, PAQR4 regulates ceramide levels by mediating the stability of ceramide synthases (CERS2 and CERS5) and, thus, their activities. Overactivation of the PQAR4-CERS axis causes ceramide accumulation and impairs adipose tissue function through suppressing adipogenesis and triggering adipocyte de-differentiation. Blocking de novo ceramide biosynthesis rescues PAQR4-induced metabolic defects. Collectively, our findings suggest a critical function of PAQR4 in regulating cellular ceramide homoeostasis and targeting PAQR4 offers an approach for the treatment of metabolic disorders.


Assuntos
Adipócitos , Ceramidas , Ceramidas/metabolismo , Adipócitos/metabolismo , Animais , Camundongos , Adipogenia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Humanos
15.
J Cancer ; 15(14): 4759-4776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006072

RESUMO

Background: Papillary Thyroid Carcinoma (PTC), a common type of thyroid cancer, has a pathogenesis that is not fully understood. This study utilizes a range of public databases, sophisticated bioinformatics tools, and empirical approaches to explore the key genetic components and pathways implicated in PTC, particularly concentrating on the Transducin-Like Enhancer of Split 4 (TLE4) gene. Methods: Public databases such as TCGA and GEO were utilized to conduct differential gene expression analysis in PTC. Hub genes were identified using Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning techniques, including Random Forest, LASSO regression, and SVM-RFE, were employed for biomarker identification. The clinical impact of the TLE4 gene was assessed in terms of diagnostic accuracy, prognostic value, and its functional enrichment analysis in PTC. Additionally, the study focused on understanding the role of TLE4 in the dynamics of immune cell infiltration, gene function enhancement, and behaviors of PTC cells like growth, migration, and invasion. To complement these analyses, in vivo studies were performed using a xenograft mouse model. Results: 244 genes with significant differential expression across various databases were identified. WGCNA indicated a strong link between specific gene modules and PTC. Machine learning analysis brought the TLE4 gene into focus as a key biomarker. Bioinformatics studies verified that TLE4 expression is lower in PTC, linking it to immune cell infiltration and the JAK-STAT signaling pathways. Experimental data revealed that decreased TLE4 expression in PTC cell lines leads to enhanced cell growth, migration, invasion, and activates the JAK/STAT pathway. In contrast, TLE4 overexpression in these cells inhibited tumor growth and metastasis. Conclusions: This study sheds light on TLE4's crucial role in PTC pathogenesis, positioning it as a potential biomarker and target for therapy. The integration of multi-omics data and advanced analytical methods provides a robust framework for understanding PTC at a molecular level, potentially guiding personalized treatment strategies.

16.
J Agric Food Chem ; 72(29): 16276-16286, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38981046

RESUMO

As primary flavonoids extracted from citrus fruits, hesperidin has been attracting attention widely for its capacity to act as antioxidants that are able to scavenge free radicals and reactive oxygen species (ROS). Many factors have made oxidative stress a risk factor for the occurrence of intestinal barrier injury, which is a serious health threat to human beings. However, little data are available regarding the underlying mechanism of hesperidin alleviating intestinal injury under oxidative stress. Recently, endoplasmic reticulum (ER) mitochondria contact sites (ERMCSs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and Ca2+ transport. In our experiment, 24 piglets were randomly divided into 4 groups. Piglets in the diquat group and hesperidin + diquat group received an intraperitoneal injection of diquat (10 mg/kg), while piglets in the hesperidin group and hesperidin + diquat group received hesperidin (300 mg/kg) with feed. The results indicated that hesperidin alleviated growth restriction and intestinal barrier injury in piglets compared with the diquat group. Hesperidin ameliorated oxidative stress and restored antioxidant capacity under diquat exposure. The mitochondrial dysfunction was markedly alleviated via hesperidin versus diquat group. Meanwhile, hesperidin alleviated ER stress and downregulated the PERK pathway. Furthermore, hesperidin prevented the disorder of ERMCSs by downregulating the level of ERMCS proteins, decreasing the percentage of mitochondria with ERMCSs/total mitochondria and the ratio of ERMCSs length/mitochondrial perimeter. These results suggested hesperidin could alleviate ERMCS disorder and prevent mitochondrial dysfunction, which subsequently decreased ROS production and alleviated intestinal barrier injury of piglets under oxidative stress.


Assuntos
Retículo Endoplasmático , Hesperidina , Mucosa Intestinal , Mitocôndrias , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Estresse Oxidativo/efeitos dos fármacos , Hesperidina/farmacologia , Suínos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/lesões , Masculino , Humanos , Antioxidantes/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos
17.
BMC Plant Biol ; 24(1): 652, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982365

RESUMO

BACKGROUND: Protein phosphatase class 2 C (PP2C) is the largest protein phosphatase family in plants. Members of the PP2C gene family are involved in a variety of physiological pathways in plants, including the abscisic acid signalling pathway, the regulation of plant growth and development, etc., and are capable of responding to a wide range of biotic and abiotic stresses, and play an important role in plant growth, development, and response to stress. Apocynum is a perennial persistent herb, divided into Apocynum venetum and Apocynum hendersonii. It mainly grows in saline soil, deserts and other harsh environments, and is widely used in saline soil improvement, ecological restoration, textiles and medicine. A. hendersonii was found to be more tolerant to adverse conditions. The main purpose of this study was to investigate the PP2C gene family and its expression pattern under salt stress and to identify important candidate genes related to salt tolerance. RESULTS: In this study, 68 AvPP2C genes and 68 AhPP2C genes were identified from the genomes of A. venetum and A. hendersonii, respectively. They were classified into 13 subgroups based on their phylogenetic relationships and were further analyzed for their subcellular locations, gene structures, conserved structural domains, and cis-acting elements. The results of qRT-PCR analyses of seven AvPP2C genes and seven AhPP2C genes proved that they differed significantly in gene expression under salt stress. It has been observed that the PP2C genes in A. venetum and A. hendersonii exhibit different expression patterns. Specifically, AvPP2C2, 6, 24, 27, 41 and AhPP2C2, 6, 24, 27, 42 have shown significant differences in expression under salt stress. This indicates that these genes may play a crucial role in the salt tolerance mechanism of A. venetum and A. hendersonii. CONCLUSIONS: In this study, we conducted a genome-wide analysis of the AvPP2C and AhPP2C gene families in Apocynum, which provided a reference for further understanding the functional characteristics of these genes.


Assuntos
Apocynum , Filogenia , Apocynum/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Tolerância ao Sal/genética , Genes de Plantas , Perfilação da Expressão Gênica
18.
Int J Biol Macromol ; 274(Pt 2): 133256, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908629

RESUMO

Aiming to investigate the changes and effects of different particle sizes of wheat A/B starch during dough fermentation, the present study reconstituted A/B starch fractions in ratios of 100:0, 75:25, 50:50, 25:75, and 0:100, further blended with gluten and subjected to slight (20 min), medium (30 min), and high (60 min) fermentation processes by yeasts. Results showed that fermentation gas production promoted gluten network extension, inducing starch granule exposure and dough surface roughness. Also, fermentation fractured protein intermolecular disulfide bonds and decreased α-helix and ß-folded structure content, contributing to GMP, LPP, and SPP content decreases. Moreover, moderately increasing the B-starch ratio in the dough can improve gluten network stability, continuity, and air-holding capacity. The 25A-75B steam bread exhibited optimal processing suitability (better morphology, texture, and quality) due to its higher GMP and polymer protein content with lower free sulfhydryl and monomeric protein content. Further, conformational relationships indicated the key indicators influencing dough products' properties were free sulfhydryl content, GMP content, protein molecular weight distribution, and secondary structure. The obtained findings contributed to understanding the effect of wheat starch granule size distribution on dough processing behavior, and future targeted breeding for wheat cultivars with high B-starch content for improved fermentation pasta product qualities.


Assuntos
Pão , Fermentação , Amido , Triticum , Triticum/química , Triticum/metabolismo , Amido/química , Amido/metabolismo , Pão/análise , Farinha/análise , Glutens/química , Tamanho da Partícula , Manipulação de Alimentos/métodos , Estrutura Molecular
19.
J Colloid Interface Sci ; 673: 178-189, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38871625

RESUMO

The activation of peroxymonosulfate (PMS) by carbon-based catalysts is deemed to be a promising method for the degradation of refractory organic contaminants in wastewater. Herein, a Cu-doping strategy in B and N co-doped carbon nanotubes with highly dispersed BOCu sites and graphite nitrogen were successfully synthesized for activating PMS to degradate tetracycline. The best removal rate of tetracycline within 60 min (97.63 %) was obtained by the 1.5 % Cu-BNC and the degradation rate was increased by 17.9 times. The enhanced catalyst activity was attributed to the promoting the cycle of the Cu(I)/Cu(II) redox pair by the formed BOCu sites, and the accelerating the electron transfer process by the adsorption of graphitic N for PMS. The non-free radical pathway including 1O2 and electron transfer played a dominant role in the 1.5 % Cu-BNC/PMS system. The degradation intermediates of TC were identified and three possible degradation pathways were proposed. Further toxicity analysis of the intermediates showed that the 1.5 % Cu-BNC/PMS system had a significant effect on weakening and reducing the biological toxicity and mutagenicity of TC. Moreover, it presented an excellent degradation performance in raw natural water. In general, the proposed regulation of carbon-based catalysts via the coordination-driven effect provides ideas for efficient wastewater treatment.


Assuntos
Cobre , Grafite , Nitrogênio , Tetraciclina , Tetraciclina/química , Grafite/química , Nitrogênio/química , Cobre/química , Catálise , Poluentes Químicos da Água/química , Sulfatos/química , Nanotubos de Carbono/química , Peróxidos/química , Propriedades de Superfície , Tamanho da Partícula
20.
Fundam Res ; 4(1): 43-50, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38933847

RESUMO

Quasi-parametric chirped-pulse amplification (QPCPA), which features a theoretical peak power much higher than those obtained with Ti:sapphire laser or optical parametric chirped-pulse amplification, is promising for future ultra-intense lasers. The doped rare-earth ion used for idler dissipation is critical for effective QPCPA, but is usually not compatible with traditional crystals. Thus far, only one dissipative crystal of Sm3+-doped yttrium calcium oxyborate has been grown and applied. Here we introduce optical means to modify traditional crystals for QPCPA applications. We theoretically demonstrate two dissipation schemes by idler frequency doubling and sum-frequency generation with an additional laser. In contrast to absorption dissipation, the proposed nonlinear dissipations ensure not only high signal efficiency but also high small-signal gain. The demonstrated ability to optically modify crystals will facilitate the wide application of QPCPA.

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