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1.
Mol Ther ; 32(3): 572-579, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38327048

ABSTRACT

Metabolic reprogramming is an essential hallmark of tumors, and metabolic abnormalities are strongly associated with the malignant phenotype of tumor cells. This is closely related to transcriptional dysregulation. Super-enhancers are extremely active cis-regulatory regions in the genome, and can amalgamate a complex set of transcriptional regulatory components that are crucial for establishing tumor cell identity, promoting tumorigenesis, and enhancing aggressiveness. In addition, alterations in metabolic signaling pathways are often accompanied by changes in super-enhancers. Presently, there is a surge in interest in the potential pathogenesis of various tumors through the transcriptional regulation of super-enhancers and oncogenic mutations in super-enhancers. In this review, we summarize the functions of super-enhancers, oncogenic signaling pathways, and tumor metabolic reprogramming. In particular, we focus on the role of the super-enhancer in tumor metabolism and its impact on metabolic reprogramming. This review also discusses the prospects and directions in the field of super-enhancer and metabolic reprogramming.


Subject(s)
Metabolic Reprogramming , Neoplasms , Humans , Enhancer Elements, Genetic , Neoplasms/genetics , Neoplasms/therapy , Gene Expression Regulation , Super Enhancers
2.
Nucleic Acids Res ; 51(D1): D571-D582, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36305834

ABSTRACT

Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.


Subject(s)
Ferroptosis , Ferroptosis/genetics , Data Accuracy , Databases, Factual , Lipid Peroxidation , Pseudogenes
3.
Mol Ther ; 31(6): 1756-1774, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-36461633

ABSTRACT

Super-enhancer (SE) plays a vital role in the determination of cell identity and fate. Up-regulated expression of coding genes is frequently associated with SE. However, the transcription dysregulation driven by SE, from the viewpoint of long non-coding RNA (lncRNA), remains unclear. Here, SE-associated lncRNAs in HCC are comprehensively outlined for the first time. This study integrally screens and identifies several novel SE-associated lncRNAs that are highly abundant and sensitive to JQ1. Especially, HSAL3 is identified as an uncharacterized SE-driven oncogenic lncRNA, which is activated by transcription factors HCFC1 and HSF1 via its super-enhancer. HSAL3 interference negatively regulates NOTCH signaling, implying the potential mechanism of its tumor-promoting role. The expression of HSAL3 is increased in HCC samples, and higher HSAL3 expression indicates an inferior overall survival of HCC patients. Furthermore, siHSAL3 loaded nanoparticles exert anti-tumor effect on HCC in vitro and in vivo. In conclusion, this is the first comprehensive survey of SE-associated lncRNAs in HCC. HSAL3 is a novel SE-driven oncogenic lncRNA, and siHSAL3 loaded nanoparticles are therapeutic candidates for HCC. This work sheds lights on the merit of anchoring SE-driven oncogenic lncRNAs for HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Liver Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Transcription Factors/genetics
4.
Molecules ; 28(13)2023 Jul 02.
Article in English | MEDLINE | ID: mdl-37446828

ABSTRACT

Xanthohumol (XN), a natural prenylated flavonoid extracted and isolated from the hop plant (Humulus lupulus), possesses diverse pharmacological activities. Although the metabolites of XN have been investigated in the previous study, a comprehensive metabolic profile has been insufficient in vivo or in vitro until now. The current study was aimed at systematically elucidating the metabolic pathways of XN after oral administration to rats. Herein, a UHPLC-Q-Exactive Orbitrap MS was adopted for the potential metabolites detection. A stepwise targeted matching strategy for the overall identification of XN metabolites was proposed. A metabolic net (53 metabolites included) on XN in vivo and in vitro, as well as the metabolic profile investigation, were designed, preferably characterizing XN metabolites in rat plasma, urine, liver, liver microsomes, and feces. On the basis of a stepwise targeted matching strategy, the net showed that major in vivo metabolic pathways of XN in rats include glucuronidation, sulfation, methylation, demethylation, hydrogenation, dehydrogenation, hydroxylation, and so on. The proposed metabolic pathways in this research will provide essential data for further pharmaceutical studies of prenylated flavonoids and lay the foundation for further toxicity and safety studies.


Subject(s)
Flavonoids , Propiophenones , Rats , Animals , Chromatography, High Pressure Liquid , Flavonoids/metabolism , Mass Spectrometry , Propiophenones/pharmacology
5.
Phys Chem Chem Phys ; 24(18): 11023-11029, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35470357

ABSTRACT

A new ice phase, ice XIX, was discovered in 2018, and is the second hydrogen-ordered polymorph of hydrogen-disordered ice VI. The first hydrogen-ordered polymorph of ice VI is ice XV, and ices XIX, VI, and XV comprise a unique triplet group in the ice family. However, the exact crystal structure of ice XIX has not been confirmed. We constructed four possible conformations of ice XIX using neutron diffraction data obtained by Gasser et al. We then optimized these structures and simulated their Raman scattering spectra using first-principles density functional theory. By comparing these simulated spectra with the experimental Raman scattering spectra, we were able to exclude the existence of a ferroelectric structure with the space group Cc. The other three candidate structures are in good agreement with the experimental Raman scattering data; two of them are ferroelectric structures with the space group P21; and the last one is a weak ferroelectric structure with the space group Cc. We proposed that the partially hydrogen-ordered structure of ice XIX maybe a mixing of several hydrogen-ordered structures.

6.
Sensors (Basel) ; 22(21)2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36366065

ABSTRACT

Wearable robots (WRs) might interact with humans in a similar manner to teammates to accomplish specific tasks together. However, the available data on WR user experience (UX) studies are limited, especially during the prototyping phase. Therefore, this study aims to examine the overall experience of WRs during the prototyping phase based on an exploratory research model. This theoretical model considered usability, hedonic quality, and attitude toward using WRs as key factors in explaining and predicting overall experience. To test the hypotheses inherent in the research model, quantitative empirical research was conducted and the data were analyzed by partial least squares structural equation modeling (PLS-SEM). The results from the PLS-SEM analysis revealed the significance level of correlations between the latent variables in the research model. The exploratory research model was able to explain up to 53.2% of the variance in the overall experience of using WRs, indicating medium predictive power. This research develops a new quantitative empirical research model that can be used to explain and predict the overall experience of interactive products such as WRs. Meanwhile, the model is needed during WR testing in the prototype phase.


Subject(s)
Models, Theoretical , Wearable Electronic Devices , Humans , Least-Squares Analysis
7.
Yi Chuan ; 44(12): 1148-1157, 2022 Dec 20.
Article in English | MEDLINE | ID: mdl-36927560

ABSTRACT

Alstrom syndrome is a rare autosomal recessive disorder disease caused by mutations in the ALMS1 gene, and its typical clinical manifestations include cone-rod retinal dystrophy, sensorineural deafness, obesity, insulin resistance, diabetes mellitus, hypertriglyceridemia, non-alcoholic fatty liver, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. In this report, we followed up a young male patient presenting with diabetes mellitus, who was later diagnosed with blindness, deafness, hyperlipidemia, obesity, fatty liver, and insulin resistance. Genetic testing revealed a compound heterozygous mutation in ALMS1 from the patient, with an exon 8 c.5535delG (p.S1847Lfs*24) mutation inherited from the maternal side and an exon 16 c.10819C>T (p.R3607X) mutation from the paternal side. Neither of these two mutations had been previously recorded in the known ALMS1 genetic mutation database. Hyperinsulinemic-euglycemic clamp test indicated that the insulin sensitivity index was significantly improved in the patient after taking oral dapagliflozin. By summarizing and analyzing this case, we should consider Alstrom syndrome in clinical adolescent-onset diabetes patients with blindness, deafness, severe insulin resistance, and lipid metabolism disorder. These two new mutation sites identified in this case enrich the genetic mutation database of the ALMS1 gene, and the follow-up data of this study provide new evidence for deciding appropriate glucose-lowering regimens in patients with Alstrom syndrome.


Subject(s)
Alstrom Syndrome , Deafness , Diabetes Mellitus , Fatty Liver , Insulin Resistance , Adolescent , Humans , Male , Alstrom Syndrome/genetics , Alstrom Syndrome/diagnosis , Cell Cycle Proteins/genetics , Mutation , Obesity/genetics , Diabetes Mellitus/genetics , Blindness
8.
J Cell Mol Med ; 25(4): 2279-2284, 2021 02.
Article in English | MEDLINE | ID: mdl-33421348

ABSTRACT

Obesity increases the morbidity and severity of asthma, with poor sensitivity to corticosteroid treatment. Metformin has potential effects on improving asthma airway inflammation. Regulatory T cells (Tregs) play a key role in suppressing the immunoreaction to allergens. We built an obese asthmatic mouse model by administering a high-fat diet (HFD) and ovalbumin (OVA) sensitization, with daily metformin treatment. We measured the body weight and airway inflammatory status by histological analysis, qRT-PCR, and ELISA. The percentage of Tregs was measured by flow cytometry. Obese asthmatic mice displayed more severe airway inflammation and more significant changes in inflammatory cytokines. Metformin reversed the obese situation and alleviated the airway inflammation and remodelling with increased Tregs and related transcript factors. The anti-inflammatory function of metformin may be mediated by increasing Tregs.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Asthma/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Obesity/drug therapy , T-Lymphocytes, Regulatory/drug effects , Animals , Asthma/immunology , Asthma/pathology , Body Weight/drug effects , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , CD4 Lymphocyte Count , Diet, High-Fat , Disease Models, Animal , Humans , Inflammation , Interleukin-4/antagonists & inhibitors , Interleukin-4/immunology , Interleukin-4/metabolism , Lung/drug effects , Lung/immunology , Lung/pathology , Mice , Obesity/immunology , Obesity/pathology , Ovalbumin/administration & dosage , Spleen/drug effects , Spleen/immunology , Spleen/pathology , T-Lymphocytes, Regulatory/immunology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism
9.
Biol Res ; 54(1): 30, 2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34517910

ABSTRACT

OBJECTIVE: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). METHODS: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. RESULTS: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. CONCLUSION: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.


Subject(s)
Epithelial-Mesenchymal Transition , MicroRNAs , Pre-Eclampsia , Trophoblasts/cytology , Cell Movement , Cell Proliferation , Female , Humans , MicroRNAs/genetics , Placenta , Pregnancy
10.
J Transl Med ; 17(1): 101, 2019 03 28.
Article in English | MEDLINE | ID: mdl-30922329

ABSTRACT

BACKGROUND: SETD2, the single mediator of trimethylation of histone 3 at position lysine 36, has been reported associated with initiation progression and chemotherapy resistance in acute myeloid leukemia (AML). Whether polymorphisms of SETD2 affect prognosis and chemotherapy response of AML remains elusive. METHODS: Three tag single-nucleotide polymorphisms (tagSNPs) of SETD2 were genotyped in 579 AML patients by using Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, overall survival (OS) and relapse-free survival (RFS) were analyzed. RESULT: Survival analysis indicated that SETD2 rs76208147 TT genotype was significantly associated with poor prognosis of AML (TT vs. CC + CT hazard ratio: HR = 1.838, 95% confidence interval (CI) 1.005-3.360, p = 0.048). After adjusting for the known prognostic factors including risk stratification, age, allo-SCT, WBC count and LDH count, rs76208147 TT genotype was still associated with OS in the multivariate analysis (TT vs. CC + CT HR = 1.923, 95% CI 1.007-3.675, p = 0.048). In addition, after adjusting by other clinical features, patients with rs4082155 allele G carries showed higher rate of complete remission which indicated by CR rate (AG + GG vs. AA odd ratio (OR) = 0.544, 95% CI 0.338-0.876, p = 0.012). CONCLUSIONS: SETD2 genetic polymorphism is associated with AML prognosis and chemotherapy outcome, suggesting the possibility for development in AML diagnostics and therapeutics towards SETD2.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Histone-Lysine N-Methyltransferase/genetics , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , China/epidemiology , Cytarabine/administration & dosage , Female , Follow-Up Studies , Genotype , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Prognosis , Remission Induction , Survival Analysis , Treatment Outcome , Young Adult
11.
J Transl Med ; 17(1): 220, 2019 07 10.
Article in English | MEDLINE | ID: mdl-31291961

ABSTRACT

BACKGROUND: The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. METHODS: DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed. RESULTS: DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10-4 and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035). CONCLUSION: Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.


Subject(s)
Alleles , Asian People/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Leukemia, Myeloid, Acute/genetics , Mutation/genetics , Adolescent , Adult , Aged , Anthracyclines/pharmacology , DNA Methyltransferase 3A , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Young Adult
12.
Int J Mol Sci ; 20(7)2019 Apr 04.
Article in English | MEDLINE | ID: mdl-30987314

ABSTRACT

The reversible phase transfer of compounds between two immiscible liquid phases has many applications in a wide range of fields, and ionic liquids have been widely used as potential functional solvents and catalysts. However, photo-triggered reversible phase transfer of ionic liquids between the organic phase and water phase has not been reported so far. In the present work, the reversible phase transfer of six kinds of azobenzene-based ionic liquid surfactants between the organic phase and water phase is investigated by alternative irradiation of UV and visible light. Factors affecting the transfer efficiency, such as chemical structure and concentration of the ionic liquid surfactants, equilibrium photo-isomerization degree, and the aggregation state of ionic liquid surfactants are investigated in detail. It is shown that transfer efficiency greater than 89% was achieved under optimal conditions, equilibrium photo-isomerization degree of the ionic liquid surfactants is the main factor to determine their transfer efficiencies, and the aggregation of cis-isomers is not beneficial for the transfer.


Subject(s)
Azo Compounds/chemistry , Ionic Liquids/chemistry , Oils/chemistry , Surface-Active Agents/chemistry , Water/chemistry
13.
Phys Chem Chem Phys ; 20(18): 12808-12816, 2018 May 09.
Article in English | MEDLINE | ID: mdl-29700535

ABSTRACT

Photo-induced conductivity modulation of stimuli-responsive materials is of great importance from the viewpoint of fundamental research and technology. In this work, 5 new kinds of azobenzene-based photo-responsive ionic liquids were synthesized and characterized, and UV/vis light modulation of their conductivity was investigated in an aqueous solution. The factors affecting the conductivity modulation of the photo-responsive fluids, such as photo-isomerization efficiency, photo-regulation aggregation, concentration and chemical structure of the ionic liquids, were examined systematically. It was found that the conductivity of the ionic liquids in water exhibited a significant increase upon UV light irradiation and the ionic liquids with a shorter alkyl spacer in the cation showed a more remarkable photo-induced conductivity enhancement with a maximum increase of 150%. In addition, the solution conductivity was restored (or very close) to the initial value upon an alternative irradiation with visible light. Thus, the solution conductivity can be modulated using alternative irradiation with UV and visible light. Although the reversible photo-isomerization of the azobenzene group under UV/vis irradiation is the origin of the conductivity modulation, the photo-regulated aggregation of the ionic liquid in water is indispensable for the maximum degree of conductivity modulation because UV irradiation can weaken, even break the aggregated cis-isomers of the ionic liquids in an aqueous solution.

14.
J Clin Nurs ; 26(3-4): 369-378, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27647779

ABSTRACT

AIMS AND OBJECTIVES: Our study was conducted to further investigate the model of social support and care for People Living with HIV/AIDS(PLHA), to explore their role in People Living with AIDS's quality of life (QOL) as reference for improving nursing policies for AIDS. BACKGROUND: Social support and care are the most important factors impacting the QOL of People Living with HIV/AIDS, but most studies conducted upon the influence of social support and QOL of People Living with HIV/AIDS are mainly based on cross-sectional design. DESIGN: Our study was a nonrandomised controlled community intervention study. METHODS: The participants diagnosed as People Living with HIV/AIDS at Beijing You An Hospital received a comprehensive social support care from December 2013 to December 2014. To evaluate the impact of social support and care model on People Living with HIV/AIDS, our study analysed the different dimension scores of social support scale and quality of life before and after the intervention. Correlation between the net benefit value of social support and that of QOL from various dimensions were analysed. RESULTS: There were significant differences in the score of objective support and usage of support (all p = 0·02) for social support. Net values of objective support score and usage of support were 0·25 and 0·19, respectively, after intervention. There were significant differences in physiological function, role physical, general health, vitality, social function, mental health, health transition and total score of quality of life (all p < 0·05). The canonical correlation analysis of net values of social support and QOL indicated that the first and second canonical correlation were statistically significant, with correlation coefficients of 0·53 (p = 0·00) and 0·21 (p = 0·04). CONCLUSION: Social support and care intervention model can effectively improve perceived subjective feeling on social support and QOL condition for People Living with HIV/AIDS. And strategies to improve social support and care intervention programmes are strongly encouraged. RELEVANCE TO CLINICAL PRACTICE: The method is simple and cost-effective and could be a way to improve the quality of life condition for People Living with HIV/AIDS.


Subject(s)
Acquired Immunodeficiency Syndrome/psychology , Community Health Services , Delivery of Health Care , HIV Seropositivity/psychology , Quality of Life , Social Support , Adult , Beijing , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nurse's Role , Surveys and Questionnaires
15.
Tumour Biol ; 37(3): 2779-88, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26715267

ABSTRACT

Cervical cancer contributed the second highest number of deaths in female cancers, exceeded only by breast cancer, carrying high risks of morbidity and mortality. There was a great need and urgency in searching novel treatment targets and prognosis biomarkers to improve the survival rate of cervical cancer patients. Many long non-coding RNAs (lncRNAs) were emerging as pivotal regulators in various biological processes and took vitally an effect on the oncogenesis and progression of cervical cancer. In this review, we summarized the origin and overview function of lncRNAs; highlighted the roles of lncRNAs in cervical cancer in terms of prognosis and tumor progression, invasion and metastasis, apoptosis, and radio-resistance; and outlined the molecular mechanisms of lncRNAs in cervical cancer from the aspects of the interaction of lncRNAs with proteins/mRNAs (especially in HPV protein) and miRNAs, as well as RNA N-methyladenosine (m6A) methylation of lncRNAs. Meanwhile, the application of lncRNAs as biomarkers in cervical cancer prognosis and predictors for metastasis was also discussed. An overview of these researches will be valuable for broadening horizons into mechanisms, selection of meritorious biomarkers for diagnosis as well as prognosis, and future targeted therapy of cervical cancer.


Subject(s)
RNA, Long Noncoding/physiology , Uterine Cervical Neoplasms/pathology , Apoptosis , Cell Proliferation , Disease Progression , Female , Humans , Neoplasm Invasiveness , Neoplasm Metastasis , Radiation Tolerance , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/mortality
16.
Diabetes Metab Syndr Obes ; 17: 493-506, 2024.
Article in English | MEDLINE | ID: mdl-38318450

ABSTRACT

Purpose: This study aims to investigate cardiovascular risk factors in nonobese patients with type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) and to determine whether they might be used to predict high-risk individuals effectively. Patients and Methods: This cross-sectional study included 245 nonobese patients with T2DM who underwent FibroTouch in the National Metabolic Management Center of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from January 2021 to December 2022. All individuals were divided into NAFLD and non-NAFLD groups. Patients with NAFLD were further grouped by UAP tertiles (T1, T2 and T3). We created a Cardiovascular Score (total scale: 0-5 points; ≥3 points was defined as high-risk individual) based on baPWV, carotid ultrasound, and urinary microalbumin creatinine ratio (UA/CR) to assess the risk of cardiovascular disease in non-obese T2DM patients with NAFLD. Risk factors were evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic (ROC) curve. Results: Atherogenic index of plasma (AIP), atherosclerosis index (AI), prevalence of hypertension, body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR) were higher in the NAFLD group compared to the non-NAFLD group. In T3 group, AIP, AI, BMI and HOMA-IR were higher than those of T1 group. Multivariate logistic regression showed that age, systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C) and AIP were risk factors for cardiovascular disease among nonobese patients with T2DM and NAFLD. The area under the ROC curve for age, systolic blood pressure, LDL-C and AIP were 0.705, 0.688, 0.738 and 0.642, respectively. The area under the ROC curve was 0.895 when combining them. Conclusion: Age, systolic blood pressure, AIP and LDL-C are all independent risk factors for cardiovascular disease in non-obese individuals with T2DM and NAFLD, which can be combined to identify high-risk populations and carry out intervention.

17.
Front Pharmacol ; 15: 1294755, 2024.
Article in English | MEDLINE | ID: mdl-38515855

ABSTRACT

Hyperuricemia (HUA), a severe metabolic disease derived from purine metabolism disorder, will lead to abnormally increased serum uric acid (SUA) levels in the body. Studies have shown that HUA is highly related to gout, hypertension, diabetes, coronary heart disease, chronic kidney diseases, and so on. Traditional Chinese medicine (TCM) shows excellent results in treating HUA because of its unique advantages of multi-metabolites and multi-targets. This article reports on the use of TCM components for uric acid (UA)-lowering activity with excellent efficacy and low side effects based on established HUA models. This work summarizes the advantages and limitations of various HUA disease models for efficacy evaluation. Applications of TCM in HUA treatment have also been discussed in detail. This paper reveals recent research progress on HUA in constructing evaluation models and systematic TCM interventions. It will provide a scientific reference for establishing the HUA model and suggest future TCM-related HUA studies.

18.
Foods ; 13(12)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38928761

ABSTRACT

The efficacy of selenium-chelating polypeptides derived from wheat protein hydrolysate (WPH-Se) includes enhancing antioxidant capacity, increasing bioavailability, promoting nutrient absorption, and improving overall health. This study aimed to enhance the bioavailability and functional benefits of exogenous selenium by chelating with wheat gluten protein peptides, thereby creating bioactive peptides with potentially higher antioxidant capabilities. In this study, WPH-Se was prepared with wheat peptide and selenium at a mass ratio of 2:1, under a reaction system at pH 8.0 and 80 °C. The in vitro antioxidant activity of WPH-Se was evaluated by determining the DPPH, OH, and ABTS radical scavenging rate and reducing capacity under different conditions, and the composition of free amino acids and bioavailability were also investigated at various digestion stages. The results showed that WPH-Se possessed significant antioxidant activities under different conditions, and DPPH, OH, and ABTS radical scavenging rates and reducing capacity remained high at different temperatures and pH values. During gastrointestinal digestion in vitro, both the individual digestate and the final digestate maintained high DPPH, OH, and ABTS radical scavenging rates and reducing capacity, indicating that WPH-Se was able to withstand gastrointestinal digestion and exert antioxidant effects. Post-digestion, there was a marked elevation in tryptophan, cysteine, and essential amino acids, along with the maintenance of high selenium content in the gastrointestinal tract. These findings indicate that WPH-Se, with its enhanced selenium and amino acid profile, serves as a promising ingredient for dietary selenium and antioxidant supplementation, potentially enhancing the nutritional value and functional benefits of wheat gluten peptides.

19.
Sci Total Environ ; 926: 171986, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38552979

ABSTRACT

As a natural adsorbent material, bentonite is widely used in the field of heavy metal adsorption. The heavy metal adsorption capacity of bentonite varies significantly in studies due to the differences in the properties of bentonite, solution, and heavy metal. To achieve accurate predictions of bentonite's heavy metal adsorption capacity, this study employed six machine learning (ML) regression algorithms to investigate the adsorption characteristics of bentonite. Finally, an eXtreme Gradient Boosting Regression (XGB) model with outstanding predictive performance was constructed. Explanation analysis of the XGB model further reveal the importance and influence manner of each input feature in predicting the heavy metal adsorption capacity of bentonite. The feature categories influencing heavy metal adsorption capacity were ranked in order of importance as adsorption conditions > bentonite properties > heavy metal properties. Furthermore, a web-based graphical user interface (GUI) software was developed, facilitating researchers and engineers to conveniently use the XGB model for predicting the heavy metal adsorption capacity of bentonite. This study provides new insights into the adsorption behaviors of bentonite for heavy metals, offering guidance and support for enhancing its application efficiency and addressing heavy metal pollution remediation.

20.
Cardiovasc Toxicol ; 24(3): 291-301, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38369677

ABSTRACT

Polyethylene terephthalate microplastics (PET MPs) are widespread in natural environment, and can enter organisms and accumulate in the body, but its toxicity has not been well studied. Therefore, in order to investigate the toxic effects of PET microplastics on mammals, this study investigated the toxic effects of PET MPs on ICR mice and H9C2 cells by different treatment groups. The results indicated the cardiac tissue of mice in the PET-H (50 µg/mL) group showed significant capillary congestion, myocardial fiber breakage, and even significant fibrosis compared to the PET-C (control) group (P < 0.01). Results of the TUNEL assay demonstrated significant apoptosis in myocardial tissue in the PET-H and PET-M (5 µg/mL) groups (P < 0.01). Meanwhile, Western blotting showed increased expression of the apoptosis-related protein Bax and decreased expression of PARP, caspase-3, and Bcl-2 proteins in both myocardial tissues and H9C2 cells. In addition, flow cytometry confirmed that PET MPs decreased the mitochondrial membrane potential and apoptosis in H9C2 cells; however, this trend was reversed by N-acetylcysteamine application. Moreover, PET MP treatment induced the accumulation of reactive oxygen species (ROS) in H9C2 cells, while the MDA level in the myocardial tissue was elevated, and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were decreased (P < 0.01), indicating a change in the redox environment. In conclusion, PET MPs promoted cardiomyocyte apoptosis by inducing oxidative stress and activating mitochondria-mediated apoptotic processes, ultimately leading to myocardial fibrosis. This study provides ideas for the prevention of PET MP toxicity and promotes thinking about enhancing plastic pollution control.


Subject(s)
Microplastics , Plastics , Mice , Animals , Microplastics/metabolism , Microplastics/pharmacology , Plastics/metabolism , Plastics/pharmacology , Polyethylene Terephthalates/metabolism , Polyethylene Terephthalates/pharmacology , Mice, Inbred ICR , Myocytes, Cardiac , Oxidative Stress , Apoptosis , Mammals/metabolism
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