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1.
Front Nutr ; 11: 1369594, 2024.
Article in English | MEDLINE | ID: mdl-38840698

ABSTRACT

Background: Although obesity is a recognized risk factor of atrial fibrillation (AF), the mechanisms are not fully understood. Objective: We aimed to identify the potential mediators between body mass index (BMI) and AF. Methods: We conducted a two-sample Mendelian randomization (MR) analysis using publicly available summary-level data from genome-wide association studies. Univariable MR analyses were applied to identify potential mediators, and then the multivariable MR analyses were conducted to explore the mediated roles of circulating biomarkers, metabolic markers and comorbidities in the association between BMI and AF. Results: This MR study found a significant causal association between BMI and AF (OR = 1.41, 95% CI = 1.33-1.50; p < 0.001), which was attenuated to 1.21 (95% CI = 1.03-1.43) after being adjusted for leptin, in which 48.78% excess risk was mediated. After further adjustment for leptin and some cormorbidies, the association was attenuated to null (adjusted for leptin and sleep apnoea: OR=1.05, 95% CI = 0.85-1.30; adjusted for leptin and coronary heart disease: OR = 1.08, 95% CI = 0.90-1.30; adjusted for leptin and systolic blood pressure: OR = 1.11, 95% CI = 0.88-1.41), resulting in 87.80%, 80.49% and 73.17% excess risk being mediated, respectively. Conclusion: These results identified an important mediated role of leptin, particularly for individuals with sleep apnoea, coronary heart disease or hypertension, providing some clues for the underlying mechanisms behind the impact of obesity on AF risk.

2.
Biomed Pharmacother ; 175: 116710, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713942

ABSTRACT

PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40-0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.


Subject(s)
Heart Failure , Hyperlipidemias , Phosphodiesterase 5 Inhibitors , Hyperlipidemias/drug therapy , Hyperlipidemias/blood , Hyperlipidemias/complications , Animals , Heart Failure/drug therapy , Male , Phosphodiesterase 5 Inhibitors/pharmacology , Phosphodiesterase 5 Inhibitors/therapeutic use , Humans , Middle Aged , Female , Sildenafil Citrate/pharmacology , Sildenafil Citrate/therapeutic use , Aged , Disease Models, Animal , Lipid Metabolism/drug effects , Cohort Studies
3.
Atherosclerosis ; 393: 117542, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38652975

ABSTRACT

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDLc) and body mass index (BMI) are not always correlated and their relationship is probably dependent on age, indicating differential age-specific associations of these factors with health outcomes. We aim to discriminate the roles of LDLc and BMI in coronary heart disease (CHD) across different age groups. METHODS: This is a prospective cohort study of 368,274 participants aged 38-73 years and free of CHD at baseline. LDLc and BMI were measured at baseline, and incident CHD was the main outcome. Cox proportional hazards model and restricted cubic spline (RCS) regression were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of exposure on CHD. RESULTS: After a mean of 12 years of follow-up, similar relationships of LDLc and BMI with CHD risk were observed in the overall population but in differential age-specific patterns. Across the age groups of <50, 50-54, 55-59, 60-64 and ≥ 65 years, the LDLc-CHD association diminished with the adjusted HRs decreasing from 1.35, 1.26, 1.19, 1.11 to 1.08; while no declining trend was found in BMI-CHD relationship with the adjusted HRs of 1.15, 1.11, 1.12, 1.13 and 1.15, respectively. The interaction and mediation between LDLc and BMI on CHD risk were more pronounced at young-age groups. LDLc-CHD but not BMI-CHD association was dependent on sex, metabolic syndrome and lipid-lowering drugs use. CONCLUSIONS: There were differential age-specific associations of LDLc and BMI with the risk of developing CHD, calling for future efforts to discriminate the age-different benefits from lipids management or weight control on the primary prevention for CHD.

4.
Int J Cardiol ; 407: 132069, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38642721

ABSTRACT

PURPOSE: The effect of obesity on the development of heart failure (HF) has received attention, and this study intends to further explore the bidirectional association between body size or composition and HF by using Mendelian Randomization (MR) approach. DESIGN: We performed a two-sample bidirectional MR study to investigate the association between body size or composition and the risk of HF using aggregated data from genome-wide association studies. Univariable MR analysis was used to investigate the causal relationship, and multivariable MR analysis was used to explore the mediating role of general and central obesity in the relationship between body size or composition and HF. RESULTS: This forward MR study found that body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), fat mass (FM) and fat-free mass (FFM) were risk factors for the development of HF with the strength of causal association BMI > FM > WC > FFM > WHR. After adjusting for BMI, the observed associations between the remaining indicators and heart failure attenuated to null. After adjusting for WC, only BMI (OR = 1.59, 95%CI: 1.32-1.92, P = 9.53E-07) and FM (OR = 1.39, 95%CI: 1.20-1.62, P = 1.35E-0.5) kept significantly related to the risk of HF. Reverse MR analysis showed no association of changes in body size or composition with the onset of HF. CONCLUSION: The two-sample bidirectional MR study found that general obesity, measured by BMI, was an independent indicator of the development of HF, while other related indicators were associated with HF incidence dependent on BMI, besides, no association was observed between HF diagnosis and the body size or composites.


Subject(s)
Body Composition , Body Mass Index , Body Size , Genome-Wide Association Study , Heart Failure , Mendelian Randomization Analysis , Humans , Heart Failure/genetics , Heart Failure/epidemiology , Body Size/physiology , Body Composition/physiology , Obesity/genetics , Obesity/epidemiology , Risk Factors , Male , Waist-Hip Ratio , Female , Waist Circumference/physiology
5.
Sci Adv ; 10(9): eadh8689, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38416840

ABSTRACT

Extracellular vesicles (EVs) play important roles in cell-cell communication but are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm with very limited amounts of cargos encapsulated. The technique of NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) reported in the present work permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, thus enables colocalization assessment for selected protein and microRNA (miRNA) markers in the EVs produced by various cell lines, or present in clinical sera samples. EV subpopulations marked by the colocalization of unique protein and miRNA combinations were discovered to be able to detect early-stage (stage I or II) breast cancer (BC). NOBEL-SPA can be adapted to analyze other types of cargo molecules or other small submicron biological particles. Study of the sorting of specific cargos to heterogeneous vesicles under different physiological conditions can help discover distinct vesicle subpopulations valuable in clinical examination and therapeutics development and gain better understanding of their biogenesis.


Subject(s)
Breast Neoplasms , Extracellular Vesicles , MicroRNAs , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Extracellular Vesicles/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Protein Transport , Cell Line
6.
Chem Biodivers ; 21(2): e202301684, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38224313

ABSTRACT

To develop new chemicals that are stable at high temperatures with biological activity, a pyrrole intermediate was firstly synthesized using glucosamine hydrochloride as raw materials through cyclization and oxidation. Further, two novel pyrrole ester derivatives were prepared via Steglich esterification from pyrrole intermediate with vanillin and ethyl maltol, respectively. Nuclear magnetic resonance (1 H-NMR, 13 C NMR), infrared spectroscopy (IR) and high resolution mass spectrometry (HRMS) were used to confirm the target compounds. Thermal behavior of the compounds was investigated by thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) methods. The plausible pyrolytic mechanism was proposed. Additionally, their biological activities against the pathogens Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Phytophthora nicotianae, and Rhizoctonia solani were assessed. These target compounds showed outstanding antifungal activities and the highest inhibitor rates of 62.50 % and 68.75 % against R. solani with EC50 values of 0.0296 and 0.0200 mg mL-1 , respectively. SDHI protein sequence was molecularly docked to identify the binding mechanisms in the active pocket and examine the interactions between both the molecules and the SDHI protein.


Subject(s)
Antifungal Agents , Fusarium , Antifungal Agents/chemistry , Esters/pharmacology , Pyrroles/pharmacology , Mass Spectrometry , Magnetic Resonance Spectroscopy , Structure-Activity Relationship
7.
Anal Chem ; 95(42): 15778-15785, 2023 10 24.
Article in English | MEDLINE | ID: mdl-37795969

ABSTRACT

Extracellular vesicles (EVs) play important roles in cell-cell communication and pathological development. Cargo profiling for the EVs present in clinical specimens can provide valuable insights into their functions and help discover effective EV-based markers for diagnostic and therapeutic purposes. However, the highly abundant and complex matrix components pose significant challenges for specific identification of low-abundance EV cargos. Herein, we combine asymmetrical flow field-flow fractionation (AF4) with large-volume sample stacking and capillary electrophoresis (LVSS/CE), to attain EVs with high purity for downstream protein profiling. This hyphenated system first separates the EVs from the contamination of smaller serum proteins by AF4, and second resolves the EVs from the coeluted, nonvesicular matrix components by CE following LVSS. The optimal LVSS condition permits the injection of 10-fold more EVs into CE compared to the nonstacking condition without compromising separation resolution. Collection and downstream analysis of the highly pure EVs after CE separation were demonstrated in the present work. The high EV purity yields a much-improved labeling efficiency when detected by fluorescent antibodies compared to those collected from the one-dimension separation of AF4, and permits the identification of more EV-specific cargos by LC-MS/MS compared to those isolated by ultracentrifugation (UC), the exoEasy Maxi Kit, and AF4. Our results strongly support that AF4-LVSS/CE can improve EV isolation and cargo analysis, opening up new opportunities for understanding EV functions and their applications in the biomedical fields.


Subject(s)
Extracellular Vesicles , Tandem Mass Spectrometry , Chromatography, Liquid/methods , Extracellular Vesicles/metabolism , Ultracentrifugation , Blood Proteins/metabolism
8.
Ecotoxicol Environ Saf ; 263: 115361, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37597289

ABSTRACT

Cadmium (Cd) removal from soil to reduce Cd accumulation in plants is essential for agroecology, food safety, and human health. Cd enters plants from soil and affects plant growth and development. Hydrogels can easily combine with Cd, thereby altering its bioavailability in soil. However, few studies have evaluated the effects of hydrogel on the complex phytotoxicity caused by Cd uptake in plants and the microbial community structure. Herein, a new poly (acrylic acid)-grafted starch and potassium humate composite (S/K/AA) hydrogel was added to soil to evaluate its impact on tobacco growth and the soil microenvironment. The results indicate that the addition of S/K/AA hydrogel can significantly improve the biomass, chlorophyll (Chl) content, and photosynthetic capacity of tobacco plants during Cd stress conditions, and decrease Cd concentration, probably by affecting Cd absorption through the expression of Cd absorption transporters (e.g., NRAMP5, NRAMP3, and IRT1). Moreover, the application of S/K/AA hydrogel not only reduced the accumulation of reactive oxygen species (ROS), but also reduced the antioxidant activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), suggesting that S/K/AA hydrogel alleviates Cd toxicity via a non-antioxidant pathway. Notably, we further analyzed the effectiveness of the hydrogel on microbial communities in Cd-contaminated soil and found that it increased the Cd-tolerant microbial community (Arthrobacter, Massilia, Streptomyces), enhancing the remediation ability of Cd-contaminated soil and helping tobacco plants to alleviate Cd toxicity. Overall, our study provides primary insights into how S/K/AA hydrogel affects Cd bioavailability and alleviates Cd toxicity in plants.


Subject(s)
Arthrobacter , Cadmium , Humans , Cadmium/toxicity , Biological Availability , Nicotiana , Hydrogels
9.
ACS Sens ; 8(8): 3195-3204, 2023 08 25.
Article in English | MEDLINE | ID: mdl-37477362

ABSTRACT

Flexible, water-soluble hosts are capable of selective molecular recognition in cellular environments and can detect neurotransmitters such as choline in cells. Both cationic and anionic water-soluble self-folded deep cavitands can recognize suitable styrylpyridinium dyes in cellular interiors. The dyes selectively accumulate in nucleotide-rich regions of the cell nucleus and cytoplasm. The hosts bind the dyes and promote their relocation to the outer cell membrane: the lipophilic cavitands predominantly reside in membrane environments but are still capable of binding suitable targets in other cellular organelles. Incubating the cells with structurally similar biomarkers such as choline, cholamine, betaine, or butyrylcholine illustrates the selective recognition. Choline and butyrylcholine can be bound by the hosts, but minimal binding is seen with betaine or cholamine. Varying the dye allows control of the optical detection method, and both "turn-on" sensing and "turn-off" sensing are possible.


Subject(s)
Betaine , Choline , Choline/metabolism , Coloring Agents , Water/chemistry , Neurotransmitter Agents
10.
bioRxiv ; 2023 Apr 18.
Article in English | MEDLINE | ID: mdl-37131582

ABSTRACT

Extracellular vesicles (EVs) play important roles in cell-cell communication but they are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm thus encapsulates very limited amounts of cargos. We report the technique of NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) that utilizes NOBs, which are superparamagnetic nanorods easily handled by a magnet or a rotating magnetic field, to act as isolated "islands" for EV immobilization and cargo confinement. NOBEL-SPA permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, and can assess the colocalization of selected protein/microRNA (miRNA) pairs in the EVs produced by various cell lines or present in clinical sera samples. Specific EV sub-populations marked by the colocalization of unique protein and miRNA combinations have been revealed by the present work, which can differentiate the EVs by their cells or origin, as well as to detect early-stage breast cancer (BC). We believe NOBEL-SPA can be expanded to analyze the co-localization of other types of cargo molecules, and will be a powerful tool to study EV cargo loading and functions under different physiological conditions, and help discover distinct EV subgroups valuable in clinical examination and therapeutics development.

11.
ACS Omega ; 8(5): 4716-4726, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36777589

ABSTRACT

To overcome the shortcomings of high relative humidity and harmful oxidation products from traditional humectants, excellent humectants and flavor precursors were reported herein. Glucosamine hydrochloride was used as the starting material for the cyclization, oxidation, and alkylation processes that produced pyrrole acid. Then, esterification occurred with polyol catalyzed by EDC and DMAP to give the target compounds 2-(2,3-dihydroxypropyl) 4-methyl 5-methyl-1-propyl-1H-pyrrole-2,4-dicarboxylate (Gpe) and (2-hydroxypropyl) 4-methyl 5-methyl-1-propyl-1H-pyrrole-2,4-dicarboxylate (Ppe). Nuclear magnetic resonance (1H NMR, 13C NMR), infrared spectroscopy (IR), and high-resolution mass recorded spectrometry (HRMS) were used to confirm the two novel polyol pyrrole ester compounds. When Gpe and Ppe were added to the tobacco shred, low-field nuclear magnetic resonance (LF-NMR) imaging was applied to assess the hygroscopicity and moisturizing capacity. Furthermore, thermogravimetry (TG) and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) techniques were applied to study their thermal behaviors. These results showed that the target compounds (Gpe and Ppe) are good humectants with thermal properties of high-temperature stability and flavor release.

12.
Antioxidants (Basel) ; 11(12)2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36552599

ABSTRACT

Diabetes mellitus is a burdensome public health problem. Diabetic cardiomyopathy (DCM) is a major cause of mortality and morbidity in diabetes patients. The pathogenesis of DCM is multifactorial and involves metabolic abnormalities, the accumulation of advanced glycation end products, myocardial cell death, oxidative stress, inflammation, microangiopathy, and cardiac fibrosis. Evidence suggests that various types of cardiomyocyte death act simultaneously as terminal pathways in DCM. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with lengths greater than 200 nucleotides and no apparent coding potential. Emerging studies have shown the critical role of lncRNAs in the pathogenesis of DCM, along with the development of molecular biology technologies. Therefore, we summarize specific lncRNAs that mainly regulate multiple modes of cardiomyopathy death, oxidative stress, and cardiac fibrosis and provide valuable insights into diagnostic and therapeutic biomarkers and strategies for DCM.

13.
Anal Chem ; 94(41): 14083-14091, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36191238

ABSTRACT

Extracellular vesicles (EVs) play important roles in cell-to-cell communications and carry high potential as markers targeted in disease diagnosis, prognosis, and therapeutic development. The main obstacles to EV study are their high heterogeneity; low amounts present in samples; and physical similarity to the abundant, interfering matrix components. Multiple rounds of separation and purification are often needed prior to EV characterization and function assessment. Herein, we report the offline coupling of asymmetrical flow field-flow fractionation (AF4) and capillary electrophoresis (CE) for EV analysis. While AF4 provides gentle and fast EV separation by size, CE resolves EVs from contaminants with similar sizes but different surface charges. Employing Western Blotting, ELISA, and SEM, we confirmed that intact EVs were eluted within a stable time window under the optimal AF4 and CE conditions. We also proved that EVs could be resolved from free proteins and high-density lipoproteins by AF4 and be further separated from the low-density lipoproteins co-eluted in AF4. The effectiveness of the coupled AF4-CE system in EV analysis was demonstrated by monitoring the changes in EV secretion from cells and by direct injection of human serum and detection of serum EVs. We believe that coupling AF4 and CE can provide rapid EV quantification in biological samples with much reduced matrix interference and be valuable for the study of total EVs and EV subpopulations produced by cells or present in clinical samples.


Subject(s)
Extracellular Vesicles , Fractionation, Field Flow , Electrophoresis, Capillary/methods , Fractionation, Field Flow/methods , Humans , Lipoproteins, HDL , Lipoproteins, LDL
14.
ACS Appl Mater Interfaces ; 14(37): 41800-41808, 2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36083615

ABSTRACT

Metal-organic frameworks (MOFs) have many attractive features, including tunable composition, rigid structure, controllable pore size, and large specific surface area, and thus are highly applicable in molecular analysis. Depending on the MOF structure, a high number of unsaturated metal sites can be exposed to catalyze chemical reactions. In the present work, we report that using both Co(II) and Fe(III) to prepare the MIL-88(NH2) MOF, we can produce the bimetallic MOF that can catalyze the conversion of 3,3',5,5″-tetramethylbenzidine (TMB) to a color product through a reaction with H2O2 at a higher reaction rate than the monometallic Fe-MIL-88(NH2). The Michaelis constants (Km) of the catalytic reaction for TMB and H2O2 are 3-5 times smaller, and the catalytic constants (kcat) are 5-10 times higher than those of the horseradish peroxidase (HRP), supporting ultrahigh peroxidase-like activity. These values are also much more superior to those of the HRP-mimicking MOFs reported previously. Interestingly, the bimetallic MOF can be coupled with glucose oxidase (GOx) to trigger the cascade enzymatic reaction for highly sensitive detection of extracellular vesicles (EVs), a family of important biomarkers. Through conjugation to the aptamer that recognizes the marker protein on EV surface, the MOF can help isolate the EVs from biological matrices, which are subsequently labeled by GOx via antibody recognition. The cascade enzymatic reaction between MOF and GOx enables the detection of EVs at a concentration as low as 7.8 × 104 particles/mL. The assay can be applied to monitor EV secretion by cultured cells and also can successfully detect the different EV quantities in the sera samples collected from cancer patients and healthy controls. Overall, we prove that the bimetallic Fe/Co-MIL-88(NH2) MOF, with its high peroxidase activity and high biocompatibility, is a valuable tool deployable in clinical assays to facilitate disease diagnosis and prognosis.


Subject(s)
Extracellular Vesicles , Metal-Organic Frameworks , Benzidines , Colorimetry , Coloring Agents/chemistry , Extracellular Vesicles/chemistry , Ferric Compounds , Glucose Oxidase/metabolism , Horseradish Peroxidase , Hydrogen Peroxide/chemistry , Metal-Organic Frameworks/chemistry , Peroxidase/chemistry , Peroxidases/chemistry
15.
ACS Sens ; 7(8): 2164-2169, 2022 08 26.
Article in English | MEDLINE | ID: mdl-35917160

ABSTRACT

An arrayed host:guest fluorescence sensor system can discriminate DNA G-quadruplex structures that differ only in the presence of single oxidation or methylation modification in the guanine base. These small modifications make subtle changes to G4 folding that are often not detectable by CD but induce differential fluorescence responses in the array. The sensing is functional in diluted serum and is capable of distinguishing individual modifications in DNA mixtures, providing a powerful method of detecting folding changes caused by DNA damage.


Subject(s)
G-Quadruplexes , DNA/chemistry , Fluorescence , Guanine/chemistry , Oxidation-Reduction
16.
Chem Res Toxicol ; 35(7): 1244-1256, 2022 07 18.
Article in English | MEDLINE | ID: mdl-35706338

ABSTRACT

Applications of reduced graphene oxide (rGO) in many different areas have been gradually increasing owing to its unique physicochemical characteristics, demanding more understanding of their biological impacts. Herein, we assessed the toxicological effects of rGO in mammary epithelial cells. Because the as-synthesized rGO was dissolved in sodium cholate to maintain a stable aqueous dispersion, we hypothesize that changing the cholate concentration in the dispersion may alter the surface property of rGO and subsequently affect its cellular toxicity. Thus, four types of rGO were prepared and compared: rGO dispersed in 4 and 2 mg/mL sodium cholate, labeled as rGO and concentrated-rGO (c-rGO), respectively, and rGO and c-rGO coated with a protein corona through 1 h incubation in culture media, correspondingly named pro-rGO and pro-c-rGO. Notably, c-rGO and pro-c-rGO exhibited higher toxicity than rGO and pro-rGO and also caused higher reactive oxygen species production, more lipid membrane peroxidation, and more significant disruption of mitochondrial-based ATP synthesis. In all toxicological assessments, pro-c-rGO induced more severe adverse impacts than c-rGO. Further examination of the material surface, protein adsorption, and cellular uptake showed that the surface of c-rGO was coated with a lower content of surfactant and adsorbed more proteins, which may result in the higher cellular uptake observed with pro-c-rGO than pro-rGO. Several proteins involved in cellular redox mediation were also more enriched in pro-c-rGO. These results support the strong correlation between dispersant coating and corona formation and their subsequent cellular impacts. Future studies in this direction could reveal a deeper understanding of the correlation and the specific cellular pathways involved and help gain knowledge on how the toxicity of rGO could be modulated through surface modification, guiding the sustainable applications of rGO.


Subject(s)
Graphite , Protein Corona , Graphite/chemistry , Reactive Oxygen Species/metabolism , Sodium Cholate
17.
Nat Cell Biol ; 24(6): 954-967, 2022 06.
Article in English | MEDLINE | ID: mdl-35637408

ABSTRACT

Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM in ß-cells to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC tumours exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance and fasting hyperglycaemia. These effects contribute to tumour growth and are abolished by inhibiting EV secretion or miR-122, restoring PKM in ß-cells or supplementing insulin. Compared with non-cancer controls, patients with BC have higher levels of circulating EV-encapsulated miR-122 and fasting glucose concentrations but lower fasting insulin; miR-122 levels are positively associated with glucose and negatively associated with insulin. Therefore, EV-mediated impairment of whole-body glycaemic control may contribute to tumour progression and incidence of type 2 diabetes in some patients with BC.


Subject(s)
Breast Neoplasms , Diabetes Mellitus, Type 2 , Extracellular Vesicles , MicroRNAs , Animals , Breast Neoplasms/pathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Extracellular Vesicles/metabolism , Female , Glucose/metabolism , Homeostasis , Humans , Insulin/metabolism , Insulin Secretion , Mice , MicroRNAs/genetics , MicroRNAs/metabolism
18.
Anal Bioanal Chem ; 414(1): 115-130, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33754195

ABSTRACT

Development of new capillary electrophoresis (CE) methodology and instrumentation, as well as application of CE to solve new problems, remains an active research area because of the attractive features of CE compared to other separation techniques. In this review, we focus on the representative works about sample preconcentration, separation media or capillary coating development, detector construction, and multidimensional separation in CE, which are judiciously selected from the papers published in 2018-2020.

19.
J Am Chem Soc ; 143(32): 12791-12799, 2021 08 18.
Article in English | MEDLINE | ID: mdl-34346209

ABSTRACT

An arrayed host:guest fluorescence sensor system can discriminate among and classify multiple different noncanonical DNA structures by exploiting selective molecular recognition. The sensor is highly selective and can discriminate between folds as similar as native G-quadruplexes and those with bulges or vacancies. The host and guest can form heteroternary complexes with DNA strands, with the host acting as mediator between the DNA and dye, modulating the emission. By applying machine learning algorithms to the sensing data, prediction of the folding state of unknown DNA strands is possible with high fidelity.


Subject(s)
DNA/chemistry , Machine Learning , Nucleotide Motifs
20.
J Eat Disord ; 7: 17, 2019.
Article in English | MEDLINE | ID: mdl-31171970

ABSTRACT

BACKGROUND: Although "clean eating" is widely propagated through social media and anecdotal reports in the popular press, there is almost no scientific research on this potentially risky dietary strategy. The current investigation explored definitions and perceptions of "clean eating" and its associations with indicators of disordered eating among diverse U.S.-based undergraduates. METHOD: Undergraduates (N = 148, M age = 19.41 years, 70.3% women) were asked to define "clean eating" via an open-ended question and then read vignettes featuring five "clean" diets, all of which caused mild functional impairment across multiple domains. Participants rated the extent to which they believed the diet was 1) "healthy," 2) reflective of "clean eating," and 3) likely to be adopted by them. Finally, participants completed questionnaires to assess body appearance evaluation, obsessive-compulsive symptoms, eating disorder symptoms, and symptoms of orthorexia nervosa. RESULTS: Open-ended responses indicated that participants defined "clean eating" in varied but overwhelmingly positive terms. Repeated measures ANOVAs indicated that the "meal substitution" vignette was perceived as the least healthy, least "clean," and least likely to be adopted, whereas the "new" (balanced) diet vignette was rated the highest on these domains. Correlations among diet perceptions and indicators of disordered eating were positive and significant. CONCLUSIONS: "Clean eating" is likely a heterogeneous phenomenon that is viewed favorably by U.S.-based college students even when it is linked with functional impairment and emotional distress. Ongoing examination of "clean eating" could clarify the potential benefits and risks posed by this dietary strategy and thus inform eating disorder prevention efforts.

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