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1.
Int J Biol Macromol ; 270(Pt 1): 132026, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38704074

RESUMEN

Multiple phenolic substances have been shown to promote SIRT3 expression, however, few studies have focused on the effects of these phenolics on SIRT3 enzyme activity. This study constructed a variety of reaction systems to elucidate the mechanisms by which different polyphenols affect SIRT3 enzyme activity. The results showed that acP53317-320 was the most suitable substrate among the five acetylated peptide substrates (Kcat/Km = 74.85 ± 1.86 M-1•s-1). All the phenolic compounds involved in the experiment inhibited the enzymatic activity of SIRT3, and the lowest IC50 among them was quercetin (0.12 ± 0.01 mM) and the highest was piceatannol (1.29 ± 0.08 mM). Their inhibition types were mainly competitive and mixed. In addition, piceatannol was found to be a natural SIRT3 agonist by enzyme kinetic analysis and validation of deacetylation efficiency. This study will provide a useful reference for polyphenol modulation of SIRT3 dosage, as well as the development and application of polyphenol-based SIRT3 activators and agonists.

2.
Mol Nutr Food Res ; : e2300917, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778506

RESUMEN

SCOPE: High-fat diet induced circadian rhythm disorders (CRD) are associated with metabolic diseases. As the main functional bioactive component in oat, ß-glucan (GLU) can improve metabolic disorders, however its regulatory effect on CRD remains unclear. In this research, the effects of GLU on high-fat diet induced insulin resistance and its mechanisms are investigated, especially focusing on circadian rhythm-related process. METHODS AND RESULTS: Male C57BL/6 mice are fed a low fat diet, a high-fat diet (HFD), and HFD supplemented 3% GLU for 13 weeks. The results show that GLU treatment alleviates HFD-induced insulin resistance and intestinal barrier dysfunction in obese mice. The rhythmic expressions of circadian clock genes (Bmal1, Clock, and Cry1) in the colon impaired by HFD diet are also restored by GLU. Further analysis shows that GLU treatment restores the oscillatory nature of gut microbiome, which can enhance glucagon-like peptide (GLP-1) secretion via short-chain fatty acids (SCFAs) mediated activation of G protein-coupled receptors (GPCRs). Meanwhile, GLU consumption significantly relieves colonic inflammation and insulin resistance through modulating HDAC3/NF-κB signaling pathway. CONCLUSION: GLU can ameliorate insulin resistance due to its regulation of colonic circadian clock and gut microbiome.

3.
J Diabetes Res ; 2024: 2431441, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577301

RESUMEN

Background: Diabetes mellitus is often accompanied by dyslipidemia. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM), have been reported to exert effects on lipid, while the results remain controversial. This study is aimed at exploring the effect of SGLT2 inhibitor canagliflozin on lipid profile. Methods: This study was a single-center, open-label, nonrandomized, prospective study. Metformin (500 mg three times per day) or canagliflozin (100 mg, once daily) was administered for 12 weeks. Fasting blood samples were collected before and 12 weeks after treatment. Serum lipid profile levels and angiopoietin-like protein 3 (ANGPTL3) were determined. In animal experiment, C57BL/6 J mice were divided into three groups including control, STZ + HFD, and STZ + HFD + canagliflozin. Lipid profile and plasma ANGPTL3 level were measured after 12 week's treatment. Moreover, the expression of ANGPTL3 was detected in the liver tissues. Results: There was a decreased trend in low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) after canagliflozin treatment, while canagliflozin significantly increased high-density lipoprotein cholesterol (HDL-c) level and decreased plasma ANGPTL3 level. In addition, the expression of ANGPTL3 in liver tissues decreased obviously in diabetic mice with canagliflozin treatment. Conclusions: Canagliflozin increases HDL-c level and suppresses ANGPTL3 expression in patients with T2DM and diabetic mice. The reduction of ANGPTL3 may contribute to the increase of HDL-c. However, the specific mechanism needs further research. This trial is registered with ChiCTR1900021231.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Humanos , Ratones , Animales , Canagliflozina/farmacología , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Proteína 3 Similar a la Angiopoyetina , HDL-Colesterol , Diabetes Mellitus Experimental/tratamiento farmacológico , Estudios Prospectivos , Ratones Endogámicos C57BL , Triglicéridos , Proteínas Similares a la Angiopoyetina
4.
J Pathol ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38606616

RESUMEN

Steroid 5α reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and is crucial for prostatic development. 5α reductase inhibitors (5ARI) reduce prostate size in benign prostate hyperplasia (BPH) and ameliorate lower urinary tract symptoms secondary to BPH. However, the mechanisms of 5ARI functioning are still not fully understood. Here, we used a Srd5a2-/- mouse model and employed single-cell RNA sequencing to explore the impact of SRD5A2 absence on prostate cellular heterogeneity. Significant alterations in luminal epithelial cell (LE) populations were observed, alongside an increased proportion and proliferative phenotype of estrogen receptor 1 (ESR1)+ LE2 cells, following an SRD5A2-independent ESR1 differentiation trajectory. LE2 cells exhibited enhanced estrogen response gene signatures, suggesting an alternative pathway for prostate growth when SRD5A2 is absent. Human prostate biopsy analysis revealed an inverse correlation between the expressions of SRD5A2 and LE2 markers (ESR1/PKCα), and an inverse correlation between SRD5A2 and the clinical efficiency of 5ARI. These findings provide insights into 5ARI resistance mechanisms and potential alternative therapies for BPH-related lower urinary tract symptoms. © 2024 The Pathological Society of Great Britain and Ireland.

5.
Phytopathology ; 114(4): 770-779, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38598410

RESUMEN

Gray mold caused by Botrytis cinerea is among the 10 most serious fungal diseases worldwide. Fludioxonil is widely used to prevent and control gray mold due to its low toxicity and high efficiency; however, resistance caused by long-term use has become increasingly prominent. Therefore, exploring the resistance mechanism of fungicides provides a theoretical basis for delaying the occurrence of diseases and controlling gray mold. In this study, fludioxonil-resistant strains were obtained through indoor drug domestication, and the mutation sites were determined by sequencing. Strains obtained by site-directed mutagenesis were subjected to biological analysis, and the binding modes of fludioxonil and iprodione to Botrytis cinerea Bos1 BcBos1 were predicted by molecular docking. The results showed that F127S, I365S/N, F127S + I365N, and I376M mutations on the Bos1 protein led to a decrease in the binding energy between the drug and BcBos1. The A1259T mutation did not lead to a decrease in the binding energy, which was not the cause of drug resistance. The biological fitness of the fludioxonil- and point mutation-resistant strains decreased, and their growth rate, sporulation rate, and pathogenicity decreased significantly. The glycerol content of the sensitive strains was significantly lower than that of the resistant strains and increased significantly after treatment with 0.1 µg/ml of fludioxonil, whereas that of the resistant strains decreased. The osmotic sensitivity of the resistant strains was significantly lower than that of the sensitive strains. Positive cross-resistance was observed between fludioxonil and iprodione. These results will help to understand the resistance mechanism of fludioxonil in Botrytis cinerea more deeply.


Asunto(s)
Aminoimidazol Carboxamida/análogos & derivados , Botrytis , Dioxoles , Farmacorresistencia Fúngica , Proteínas Fúngicas , Fungicidas Industriales , Histidina Quinasa , Hidantoínas , Pirroles , Botrytis/genética , Botrytis/efectos de los fármacos , Botrytis/enzimología , Dioxoles/farmacología , Fungicidas Industriales/farmacología , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Hidantoínas/farmacología , Pirroles/farmacología , Pirroles/metabolismo , Histidina Quinasa/genética , Histidina Quinasa/metabolismo , Enfermedades de las Plantas/microbiología , Simulación del Acoplamiento Molecular , Mutación , Mutagénesis Sitio-Dirigida
6.
Mater Horiz ; 11(7): 1779-1786, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38314856

RESUMEN

The engineering of multifunctional structures with special surface wettability is highly desirable for all-weather freshwater production, but relevant research is scarce. In this study, a Janus conical vertical array was designed and fabricated via a magnetically driven spray-coating method for the first time. Benefiting from the special structure and wettability enhancement of the array in terms of solar absorption, fog capture and merging, droplet movement and evaporation area, all-weather freshwater production consisting of high-quality daytime solar vapor generation (water evaporation rate approximately 2.43 kg m-2 h-1, 1 kW m-2) and nighttime fog collection (water collection rate approximately 3.536 g cm-2 h-1) can be realized concurrently. When the designed array is employed for outdoor environments (114°35'E, 30°38'N, average daily temperature 34.9 °C, average daily humidity 64.0%), reliable and efficient daily pure water yields of 19.13 kg m-2-26.09 kg m-2 are obtainable. We believe that the proposed strategy for fabricating a Janus conical vertical array is novel in the integration of solar vapor generation and fog collection, which has great significance for all-weather freshwater production.

7.
J Environ Manage ; 351: 119775, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070425

RESUMEN

Recently, biochar has garnered extensive attention in the remediation of soils contaminated with potentially toxic elements (PTEs) owing to its exceptional adsorption properties and straightforward operation. Most researchers have primarily concentrated on the effects, mechanisms, impact factors, and risks of biochar in remediation of PTEs. However, concerns about the long-term safety and impact of biochar have restricted its application. This review aims to establish a basis for the large-scale popularization of biochar for remediating PTEs-contaminated soil based on a review of interactive mechanisms between soil, PTEs and biochar, as well as the current situation of biochar for remediation in PTEs scenarios. Biochar can directly interact with PTEs or indirectly with soil components, influencing the bioavailability, mobility, and toxicity of PTEs. The efficacy of biochar in remediation varies depending on biomass feedstock, pyrolysis temperature, type of PTEs, and application rate. Compared to pristine biochar, modified biochar offers feasible solutions for tailoring specialized biochar suited to specific PTEs-contaminated soil. Main challenges limiting the applications of biochar are overdose and potential risks. The used biochar is separated from the soil that not only actually removes PTEs, but also mitigates the negative long-term effects of biochar. A sustainable remediation technology is advocated that enables the recovery and regeneration (95.0-95.6%) of biochar from the soil and the removal of PTEs (the removal rate of Cd is more than 20%) from the soil. Finally, future research directions are suggested to augment the environmental safety of biochar and promote its wider application.


Asunto(s)
Restauración y Remediación Ambiental , Metales Pesados , Contaminantes del Suelo , Metales Pesados/análisis , Suelo , Contaminantes del Suelo/análisis , Carbón Orgánico
8.
Histopathology ; 84(5): 753-764, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38114291

RESUMEN

AIM: Primary mucinous adenocarcinoma of the urethra represents an extremely rare entity. We sought to characterise further these tumours' clinicopathological, immunohistochemical and molecular features. METHODS AND RESULTS: Thirty-five cases were identified, occurring in 18 males and 17 females. The mean age at diagnosis was 65 years (28-89 years). The main presentation symptoms were haematuria and urinary outlet obstruction. Microscopic analysis revealed that all 35 tumours have stromal dissection by mucin. Ten tumours showed villoglandular dysplasia, nine showed mucinous metaplasia, two showed adenocarcinoma in situ and four showed signet ring cell features. All tumours were immunopositive for CEA, while immunonegative for nuclear ß-catenin; 19 of 23 (83%) expressed high molecular weight cytokeratin; 19 of 33 (58%) CK7; 28 of 34 (82%) CK20; 32 of 35 (91%) CDX2; 22 of 27 (81%) cadherin-17 (CDH-17); 26 of 29 (90%) SATB2; and one of 31 (3%) GATA3. Mismatch repair gene products, including MLH1, PMS2, MSH2 and MSH6, were immunopositive, suggesting the MSI-low genotype of mucinous adenocarcinoma of the urethra. BRAF V600E and ALK rearrangements were not detected. During the mean follow-up of 20 months, nine patients either developed distant metastasis or succumbed to the illness. CONCLUSION: Our study, encompassing the most extensive series of 35 cases of primary mucinous adenocarcinoma of the urethra, provides crucial insights into its precise diagnosis, management and potential targeted treatments. We found a greater CDX2, SATB2 and CDH17 sensitivity in these urethral tumours for the first time, to our knowledge. We identified characteristics such as an MSI-low profile, non-V600E BRAF mutations and an absence of ALK rearrangements.


Asunto(s)
Adenocarcinoma Mucinoso , Proteínas Proto-Oncogénicas B-raf , Masculino , Femenino , Humanos , Anciano , Proteínas Proto-Oncogénicas B-raf/genética , Uretra/química , Uretra/patología , Biomarcadores de Tumor/análisis , Adenocarcinoma Mucinoso/patología , Factores de Transcripción , Proteínas Tirosina Quinasas Receptoras
9.
J Colloid Interface Sci ; 656: 466-473, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38007938

RESUMEN

Sorption-based atmospheric water harvesting (SAWH) has been proven to be a promising method to alleviate the impact of the water crisis on human activities. However, the low water-sorption capacity and sluggish ab/desorption kinetics of current SAWH materials make it difficult to achieve high daily water production. In this study, a photothermal porous sodium alginate-tannic acid-5/Fe3+@lithium chloride aerogel (SA-TA-5/Fe3+@LiCl) with macroporous structure (average pore diameter ∼43.67 µm) and high solar absorbance (∼98.4 %) was fabricated via Fe3+-induced crosslinking and blackening methods. When it is employed for SAWH, moisture can enter the inner space of the aerogel and contact highly hygroscopic lithium chloride (LiCl) more easily via macroporous channels, resulting in the water uptake for the SA-TA-5/Fe3+@LiCl aerogel reaching approximately 1.229 g g-1 under dry conditions (relative humidity (RH) âˆ¼ 45 %, 25 °C) after a short time (4 h) moisture absorption, and releasing as much as 97.7 % of the absorbed water under 1 sun irradiation within 2 h. As a proof of concept, it is estimated that the daily water yield of the fabricated SA-TA/Fe3+@LiCl aerogel can reach approximately 4.65 kg kg-1 in conditions close to the real outdoor environment (RH âˆ¼ 45 %, 25 °C), which satisfies the daily minimum water consumption of two adults. This study demonstrates a novel strategy for developing advanced solar-driven SAWH materials with enhanced ab/desorption kinetics and efficient water sorption-desorption properties.

10.
PLoS One ; 18(12): e0295893, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38085734

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0173335.].

11.
J Agric Food Chem ; 71(43): 16125-16136, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37857386

RESUMEN

Wheat alkylresorcinols (ARs) consumption has been evidenced to improve obesity and its associated insulin resistance. However, the effect of ARs on glucagon-like peptide 1 (GLP-1) secretion and the underlying mechanism of action are still unclear. In this study, C57BL/6J mice were fed low-fat diet (LFD), high-fat diet (HFD), and HFD supplemented with 0.4% (w/w) ARs separately for 9 weeks. The results showed that ARs intervention significantly improved glucose homeostasis and restored the serum level of GLP-1 compared with the HFD control group. Moreover, ARs treatment alleviated HFD-induced ileal epithelium damage according to TUNEL staining, immunofluorescence, and transmission electron microscopy observation. The alleviative effect was further verified by apoptosis analysis and mitochondrial function evaluation. Furthermore, palmitic acid (PA) was administered to the intestinal secretin tumor cell line (STC-1) to clarify the protective effect of ARs on GLP-1 secretion in vitro. In consistence with the results of animal studies, ARs treatment could significantly improve GLP-1 secretion in STC-1 cells compared with PA treatment alone in a dose-dependent manner, accompanied by a reduction in apoptosis and mitochondrial dysfunction. In addition, ARs treatment notably enhanced the abundance of SCFA (short-chain fatty acid)-producing bacteria, such as Bacteroides, Bifidobacterium, and Akkermansia. The increased levels of intestinal SCFAs, such as acetic acid, propionic acid, and butyric acid, improved the expression of short-chain fatty acid receptors (FFAR3) and glucagon-like peptide-1 receptor (GLP-1R), enhancing the secretion of the intestinal hormones GLP-1. Thus, this study provides potential clinical implications of whole wheat as a dietary strategy to improve glucose homeostasis for obese populations.


Asunto(s)
Dieta Alta en Grasa , Hormonas Gastrointestinales , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Péptido 1 Similar al Glucagón/metabolismo , Ratones Obesos , Triticum/metabolismo , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/etiología , Ácidos Grasos Volátiles/metabolismo , Ácido Palmítico/farmacología , Glucosa/metabolismo , Homeostasis
12.
Nutrients ; 15(13)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37447299

RESUMEN

Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H2O2)-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H2O2-induced PC-12 cell death. Furthermore, piceatannol effectively improved mitochondrial content and mitochondrial function, including enhancing mitochondrial reactive oxygen species (ROS) elimination capacity and increasing mitochondrial transcription factor (TFAM), peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria Complex IV expression. Meanwhile, piceatannol treatment inhibited mitochondria-mediated autophagy as demonstrated by restoring mitochondrial membrane potential, reducing autophagosome formation and light chain 3B II/I (LC3B II/I) and autophagy-related protein 5 (ATG5) expression level. The protein expression level of SIRT3 was significantly increased by piceatannol in a concentration-dependent manner. However, the cytoprotective effect of piceatannol was dramatically abolished by sirtuin 3 (SIRT3) inhibitor, 3-(1H-1,2,3-Triazol-4-yl) pyridine (3-TYP), which led to an exacerbated mitochondrial dysfunction and autophagy in PC-12 cells under oxidative stress. In addition, the autophagy activator (rapamycin) abrogated the protective effects of piceatannol on PC-12 cell death. These findings demonstrated that piceatannol could alleviate PC-12 cell oxidative damage and mitochondrial dysfunction by inhibiting autophagy via the SIRT3 pathway.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Sirtuina 3 , Humanos , Sirtuina 3/genética , Sirtuina 3/metabolismo , Peróxido de Hidrógeno/metabolismo , Feocromocitoma/metabolismo , Estrés Oxidativo , Mitocondrias/metabolismo , Autofagia , Neoplasias de las Glándulas Suprarrenales/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo
14.
Food Funct ; 14(11): 5001-5011, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37199511

RESUMEN

The whitening and loss of brown adipose tissue (BAT) during obesity and aging are associated with a higher risk of metabolic syndrome and chronic diseases. 5-Heptadecylresorcinol (AR-C17), the specific biomarker of whole-grain wheat and rye intake, has been proved to have notable health promoting effects, whereas whether AR-C17 could modulate BAT function and the potential mechanism of action remains unclear. In this study, we found that AR-C17 could significantly inhibit body weight gain and insulin resistance in high-fat diet (HFD) induced obese mice. Moreover, AR-C17 treatment improved whole body energy metabolism and alleviated the whitening and loss of BAT compared with the HFD group. RNA sequencing and western-blot analysis indicated that expression of genes and proteins related to BAT energy metabolism was upregulated by AR-C17 administration, including AMPK, UCP-1, ACSL1, CPT1A, and SIRT3. These results suggested that brown adipose tissue might be the target of AR-C17 to prevent obesity and its associated insulin resistance.


Asunto(s)
Obesidad , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Masculino , Animales , Ratones , Resistencia a la Insulina , Adipocitos Marrones/metabolismo , Metabolismo Energético
15.
Food Funct ; 13(17): 9091-9107, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-35943408

RESUMEN

Alkylresorcinols (ARs) are phenolic lipids present in the bran part of whole grain wheat and rye, which possess antioxidant, anti-inflammatory, anti-cancer and anti-tumor properties. The physiological activities of ARs have been proven to be diverse; however, the specific molecular mechanisms are still unclear. In this study, reverse virtual screening and network pharmacology were used to explore the potential molecular mechanisms of the physiological function of ARs and their endogenous metabolites. The Metascape database was used for GO enrichment and KEGG pathway analysis. Furthermore, molecular docking was used to investigate the interactions between active compounds and potential targets. The results showed that the bioavailability of most ARs and their endogenous metabolites was 0.55 and 0.56, while the bioavailability of certain endogenous metabolites was only 0.11. Multiplex analysis was used to screen 73 important targets and 4 core targets (namely, HSP90AA1, EP300, HSP90AB1 and ERBB2) out of the 163 initial targets. The important targets involved in the key KEGG pathway were pathways in cancer (hsa05200), lipid and atherosclerosis (hsa05417), Th17 cell differentiation (hsa04659), chemical carcinogenesis-receptor activation (hsa05207), and prostate cancer (hsa05215). The compounds involved in the core targets were AR-C21, AR-C19, AR-C17, 3,5-DHPHTA-S, 3,5-DHPHTA-G, 3,5-DHPPTA, 3,5-DHPPTA-S, 3,5-DHPPTA-G, 3,5-DHPPTA-Gly and 3,5-DHPPA-G. The interaction force between them was mainly related to hydrogen bonds and van der Waals. Overall, the physiological activities of ARs are not only related to their multiple targets, but may also be related to the synergistic effect of their endogenous metabolites.


Asunto(s)
Medicamentos Herbarios Chinos , Secale , Biomarcadores , Humanos , Imidazoles , Masculino , Simulación del Acoplamiento Molecular , Farmacología en Red , Resorcinoles/química , Resorcinoles/farmacología , Secale/química , Sulfonamidas , Tiofenos , Triticum/química
16.
J Ethnopharmacol ; 298: 115576, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-35963421

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Wenxin Formula (WXF) is a well-known prescription with a significant curative effect in the treatment of cardiac disease. However, the lack of quality control standards caused by unclear quality control components limits the development of new drugs. AIM OF THE STUDY: The aims of this research were to discover the effective materials and screen the quality markers of WXF through a chinmedomics strategy to aid in efficacy evaluation. MATERIAL AND METHODS: The therapeutic effect of WXF against myocardial ischaemia (MI) was evaluated by serum metabolic profiling combined with routine electrocardiography; analyses of the serum biochemical indices CK, CK-MB and α-HBDH; and histopathological tests involving TTC staining and HE staining. The raw data of serum samples were obtained by UPLC-HDMS, and multivariate statistical analysis was performed with Progenesis QI software. PCMS software was used to sift the quality markers of WXF. RESULTS: A total of 25 metabolites were characterized as biomarkers for myocardial ischaemia, and Wenxin Formula reversed the levels of 23 of them that were involved in arachidonic acid metabolism, glycerophospholipid metabolism, lysine degradation, and tyrosine metabolism. Eight constituents absorbed into blood were considered to form the effective material basis of Wenxin Formula for treating myocardial ischaemia, and the Q-markers selected through PCMS were ginsenoside Rb1, cinnamic acid, paeoniflorin and berberine. CONCLUSIONS: WXF significantly ameliorated the clinical symptoms, pathological changes and metabolic abnormalities of myocardial ischaemia. This study shows that chinmedomics is a powerful strategy to filter Q-markers from effective constituents to rationally evaluate the efficacy and safety of TCMs.


Asunto(s)
Medicamentos Herbarios Chinos , Isquemia Miocárdica , Biomarcadores , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Metabolómica , Isquemia Miocárdica/tratamiento farmacológico , Control de Calidad
17.
Int J Biol Macromol ; 216: 75-85, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35792311

RESUMEN

To clarify the effect of quinoa bran soluble dietary fiber (QBSDF) on gut inflammation and homeostasis, ulcerative colitis (UC) mice induced by dextran sodium sulfate (DSS) were fed QBSDF for four weeks. Histological staining, immunofluorescence, western blot and 16S rRNA sequencing analysis were carried out to investigate the action mechanism of QBSDF. Results showed that QBSDF alleviated DSS-induced colitis symptoms accompanied by significant mitigation of colon shortening and colonic epithelial damage. Moreover, QBSDF supplementation downregulated the mRNA and protein expression level of TNF-α and IL-1ß, while elevated the expression of tight junction proteins, and significantly reduced colonic cells apoptosis. In addition, the diversity and abundance of gut microbiota in QBSDF fed mice were significantly increased compared to that of UC mice. Moreover, QBSDF notably increased the abundance of Firmicutes at phylum level, while decreased the abundance of Bacteroidetes and pathogenic Helicobacter. Besides, the levels of short-chain fatty acids, especially acetic acid and butyric acid were significantly increased by QBSDF administration. These findings suggested the promising potential of QBSDF as a functional food ingredient to prevent ulcerative colitis through maintaining intestinal barrier function and modulating gut microbiota.


Asunto(s)
Chenopodium quinoa , Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Animales , Colitis/inducido químicamente , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colon , Sulfato de Dextran/efectos adversos , Fibras de la Dieta/metabolismo , Fibras de la Dieta/farmacología , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Sulfatos
18.
NPJ Precis Oncol ; 6(1): 31, 2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35508696

RESUMEN

Prostate cancer is characterized by a high degree of heterogeneity, which poses a major challenge to precision therapy and drug development. In this review, we discuss how nongenetic factors contribute to heterogeneity of prostate cancer. We also discuss tumor heterogeneity and phenotypic switching related to anticancer therapies. Lastly, we summarize the challenges targeting the tumor environments, and emphasize that continued exploration of tumor heterogeneity is needed in order to offer a personalized therapy for advanced prostate cancer patients.

19.
Can J Urol ; 29(1): 10992-11002, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35150221

RESUMEN

INTRODUCTION: To determine whether marital status combined with race serve as prognostic factors for survival in localized prostate cancer. MATERIALS AND METHODS: Patients with localized prostate cancer were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test was used to investigate the association between marital status combined with race and other variables. Gray's test was used to compare the cumulative incidence function of different variables. Multivariable analysis was conducted to assess prognostic factors after adjusting for other variables. RESULTS: A total of 207,219 patients with localized prostate cancer from the SEER database from 2010 to 2016 were eligible. We found that black or single patients had the highest risk of mortality (p < 0.001). When marital status and race were combined, single black patients had the worst prognosis after adjusting for other variables (hazard ratio = 1.93, 95% confidence interval: 1.58-2.35; p < 0.001). Married status had a prognostic advantage in all races. In the same marital groups, whites and Asians had lower risk of prostate cancer-specific mortality and other-cause mortality than blacks with married and single status (p < 0.001). CONCLUSIONS: Marital status and race serve as prognostic factors for localized prostate cancer. Blacks or single individuals had higher risk of mortality when considered independently, and single black patients had the worst prognosis. Furthermore, married status was an advantage in the same race group, and whites and Asians had lower risk than blacks with married and single status. Accordingly, the interaction between race and marital status on prostate cancer prognosis in clinical practice should be assessed carefully.


Asunto(s)
Neoplasias de la Próstata , Humanos , Masculino , Estado Civil , Pronóstico , Estudios Retrospectivos , Programa de VERF , Tasa de Supervivencia
20.
Diabetol Metab Syndr ; 14(1): 10, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35033179

RESUMEN

BACKGROUND: AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. METHODS: A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student's t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman's correlation. RESULTS: AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501-0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528-0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). CONCLUSION: AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

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