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1.
Microsyst Nanoeng ; 10: 62, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38770032

RESUMEN

This study elaborates on the design, fabrication, and data analysis details of SPEED, a recently proposed smartphone-based digital polymerase chain reaction (dPCR) device. The dPCR chips incorporate partition diameters ranging from 50 µm to 5 µm, and these partitions are organized into six distinct blocks to facilitate image processing. Due to the superior thermal conductivity of Si and its potential for mass production, the dPCR chips were fabricated on a Si substrate. A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time. The optical design employs four 470 nm light-emitting diodes as light sources, with filters and mirrors effectively managing the light emitted during PCR. An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format, partition identification, skew correction, and the generation of an image correction mask. We validated the device using a range of deoxyribonucleic acid targets, demonstrating its potential applicability across multiple fields. Therefore, we provide guidance and verification of the design and testing of the recently proposed SPEED device.

2.
Microsyst Nanoeng ; 10: 66, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784376

RESUMEN

This study presents a rapid and versatile low-cost sample-to-answer system for SARS-CoV-2 diagnostics. The system integrates the extraction and purification of nucleic acids, followed by amplification via either reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or reverse transcription loop-mediated isothermal amplification (RT-LAMP). By meeting diverse diagnostic and reagent needs, the platform yields testing results that closely align with those of commercial RT-LAMP and RT‒qPCR systems. Notable advantages of our system include its speed and cost-effectiveness. The assay is completed within 28 min, including sample loading (5 min), ribonucleic acid (RNA) extraction (3 min), and RT-LAMP (20 min). The cost of each assay is ≈ $9.5, and this pricing is competitive against that of Food and Drug Administration (FDA)-approved commercial alternatives. Although some RNA loss during on-chip extraction is observed, the platform maintains a potential limit of detection lower than 297 copies. Portability makes the system particularly useful in environments where centralized laboratories are either unavailable or inconveniently located. Another key feature is the platform's versatility, allowing users to choose between RT‒qPCR or RT‒LAMP tests based on specific requirements.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38771252

RESUMEN

Developing a simple and rapidly preparative method for patterned flexible supercapacitors is essential and indispensable for the swift advancement of portable devices integrated with micro devices. In this study, we employed a cost-effective and rapid fabrication method based on transfer-printing technology to produce patterned micro flexible supercapacitors with various substrates. The resulting flexible micro supercapacitors not only allow for customized patterns with strong flexibility and resistance to bending, while maintaining a certain level of performance, but also facilitate the creation of diverse circuits to tailor voltage and current to specific requirements. Patterned micro flexible supercapacitors with a thickness of 0.02 mm, based on accordion-like Ti3C2Tx MXene materials coated on a substrate, demonstrate a specific capacitance of 142.7 mF cm-2 at 0.5 mA cm-2. The devices exhibit satisfactory capacitance retention (91% after 5000 cycles) and superb mechanical flexibility (71% capacitance retention at 180° bending after 2000 cycles). At a power density of 2.9 mW cm-2, the energy density of the sandwich structure device reaches 126.8 µWh cm-2. This study is expected to contribute new ideas for the design and preparation of patterned flexible supercapacitors.

4.
Environ Sci Technol ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691809

RESUMEN

Although electro-Fenton (EF) processes can avoid the safety risks raised by concentrated hydrogen peroxide (H2O2), the Fe(III) reduction has always been either unstable or inefficient at high pH, resulting in catalyst deactivation and low selectivity of H2O2 activation for producing hydroxyl radicals (•OH). Herein, we provided a strategy to regulate the surface dipole moment of TiO2 by Fe anchoring (TiO2-Fe), which, in turn, substantially increased the H2O2 activation for •OH production. The TiO2-Fe catalyst could work at pH 4-10 and maintained considerable degradation efficiency for 10 cycles. Spectroscopic analysis and a theoretical study showed that the less polar Fe-O bond on TiO2-Fe could finely tune the polarity of H2O2 to alter its empty orbital distribution, contributing to better ciprofloxacin degradation activity within a broad pH range. We further verified the critical role of the weakened polarity of H2O2 on its homolysis into •OH by theoretically and experimentally investigating Cu-, Co-, Ni-, Mn-, and Mo-anchored TiO2. This concept offers an avenue for elaborate design of green, robust, and pH-universal cathodic Fenton-like catalysts and beyond.

5.
Adv Mater ; : e2405832, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38759109

RESUMEN

A broad range of chemical transformations driven by catalytic processes necessitates the electron transfer between catalyst and substrate. The redox cycle limitation arising from the inequivalent electron donation and acceptance of the involved catalysts, however, generally leads to their deactivation, causing substantial economic losses and environmental risks. Here, a "non-redox catalysis" strategy is provided, wherein the catalytic units are constructed by atomic Fe and B as dual active sites to create tensile force and electric field, which allows directional self-decomposition of peroxymonosulfate (PMS) molecules through internal electron transfer to form singlet oxygen, bypassing the need of electron transfer between catalyst and PMS. The proposed catalytic approach with non-redox cycling of catalyst contributes to excellent stability of the active centers while the generated reactive oxygen species find high efficiency in long-term catalytic pollutant degradation and selective organic oxidation synthesis in aqueous phase. This work offers a new avenue for directional substrate conversion, which holds promise to advance the design of alternative catalytic pathways for sustainable energy conversion and valuable chemical production.

6.
J Am Chem Soc ; 146(12): 8464-8471, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38483268

RESUMEN

One-dimensional (1D) high-entropy compounds (HECs) with subnano diameters are highly attractive because long-range electron delocalization may occur along the high-entropy atomic chain, which results in extraordinary properties. Nevertheless, synthesizing such 1D HECs presents a substantial challenge, and the physicochemical attributes of these novel structures remain ambiguous. Herein, we developed a comelting-filling-freezing-modification (co-MFFM) method for synthesizing 1D high-entropy metal phosphide (HEP) by simultaneously encapsulating various metal cations within single-walled carbon nanotubes (SWCNTs) followed with a phosphorization process. The resulting 1D HEP nanowires confined within SWCNTs exhibit crucial features, including an ultrafine, high-entropy, and amorphous structure, along with a core-shell arrangement. The SWCNT as a shell could donate π electrons to 1D HEP for enhanced electron delocalization and protect 1D HEP as an atomically single-layered protective covering, thus boosting high electrocatalytic activity and stability. Moreover, the co-MFFM method demonstrates scalability for mass production and displays universal applicability to the synthesis of various 1D HECs.

7.
Hum Exp Toxicol ; 43: 9603271241232609, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38320548

RESUMEN

Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25 µg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.


Asunto(s)
Fructosa , Lipidómica , Fenoles , Humanos , Ratas , Animales , Fructosa/metabolismo , Tejido Adiposo , Compuestos de Bencidrilo/farmacología , Lípidos , Metabolismo de los Lípidos
8.
Food Chem ; 439: 138168, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38103491

RESUMEN

Papaya is a climacteric fruit that undergoes rapid ripening and quality deterioration during postharvest storage, resulting in significant economic losses. This study employed biochemical techniques and targeted metabolomics to investigate the impact of exogenous AsA + CTS application on the energy metabolism regulation of papaya fruit during postharvest storage. We found that AsA + CTS treatment significantly increased the levels of key metabolic compounds and enzymes, such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and the energy charge, as well as the succinic acid content and the activities of succinic dehydrogenase (SDH), cytochrome c oxidase (CCO), H+-ATPase, and Ca2+-ATPase. Moreover, AsA + CTS coating augmented the nicotinamide adenine dinucleotide kinase (NADK) activity and increased the NADH and NADPH concentrations. Regarding sugar metabolism, it increased the activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase and raised d-glucose-6-phosphate levels. These findings suggest that AsA + CTS coating application can mitigate the metabolic deterioration and sustain a primary metabolism homeostasis in papaya fruit by enhancing the tricarboxylic acid (TCA) cycle and pentose phosphate pathway (PPP), thereby preserving their quality attributes during postharvest storage.


Asunto(s)
Carica , Quitosano , Frutas/química , Ácido Ascórbico/análisis , Quitosano/análisis , Homeostasis
9.
Sci Rep ; 13(1): 22704, 2023 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-38123624

RESUMEN

The consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.


Asunto(s)
Fructosa , Glutamina , Humanos , Ratas , Animales , Glutamina/metabolismo , Fructosa/efectos adversos , Multiómica , Aminoácidos , China
10.
Hum Exp Toxicol ; 42: 9603271231217992, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37990541

RESUMEN

Background: Adipose tissue is a dynamic endocrine organ that plays a key role in regulating metabolic homeostasis. Previous studies confirmed that bisphenol A (BPA) or fructose can interfere with the function of adipose tissue. Nonetheless, knowledge on how exposure to BPA and fructose impacts energy metabolism in adipose tissue remains limited.Purpose: To determine impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue.Method: 57 energy metabolic intermediates in adipose tissue and 7 adipocytokines in serum from Sprague Dawley rats were examined after combined exposure to two levels of BPA (lower dose: 0.25, and higher dose: 25 µg/kg every other day) and 5% fructose for 6 months.Results: combined exposure to lower-dose BPA and fructose significantly increased omentin-1, pyruvic acid, adenosine triphosphate (ATP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and l-lactate; however, these parameters were not significantly affected by higher-dose BPA combined with fructose. Interestingly, the level of succinate (an intermediate of the citric acid cycle) increased dose-dependently in adipose tissue, and the level of apelin 13 (a versatile adipocytokine) decreased dose-dependently in serum after combined exposure to BPA and fructose. Phosphoenolpyruvic acid, phenyl-lactate, and ornithine were significantly correlated with asprosin, omentin-1, apelin, apelin 13, and adiponectin, while l-tyrosine was significantly correlated with irisin and a-FABP under combined exposure to BPA and fructose.Conclusions: these findings indicated that lower-dose BPA combined with fructose could amplify the impact on glycolysis, energy storage, and purine nucleotide biosynthesis in adipose tissue, and adipocytokines, such as omentin-1 and apelin 13, may be related to metabolic interference induced by BPA and fructose exposure.


Asunto(s)
Adipoquinas , Fructosa , Ratas , Animales , Fructosa/metabolismo , Ratas Sprague-Dawley , Apelina/metabolismo , Tejido Adiposo/metabolismo , Compuestos de Bencidrilo/toxicidad , Tejido Adiposo Blanco/metabolismo , Metaboloma , Lactatos/metabolismo
12.
Biosens Bioelectron ; 232: 115319, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37087984

RESUMEN

We demonstrate a smartphone integrated handheld (SPEED) digital polymerase chain reaction (dPCR) device for point-of-care application. The device has dimensions of ≈100 × 200 × 35 mm3 and a weight of ≈400 g. It can perform 45 PCR cycles in ≈49 min. The device also features integrated, miniaturized modules for thermal cycling, image taking, and wireless data communication. These functions are controlled by self-developed Android-based applications. The only consumable is the developed silicon-based dPCR chip, which has the potential to be recycled. The device's precision and accuracy are comparable with commercial dPCR machines. We have verified the SPEED dPCR prototype's utility in the testing of severe acute respiratory syndrome coronavirus 2, the detection of cancer-associated gene sequences, and the confirmations of Down syndrome diagnoses. Due to its low upfront capital investment, as well as its nominal running cost, we envision that the SPEED dPCR device will help to perform cancer screenings and non-invasive prenatal tests for the general population. It will also aid in the timely identification and monitoring of infectious disease testing, thereby expediting alerts with respect to potential emerging pandemics.


Asunto(s)
Técnicas Biosensibles , COVID-19 , Neoplasias , Humanos , Teléfono Inteligente , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa , Prueba de COVID-19
13.
J Environ Manage ; 336: 117561, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36868154

RESUMEN

The objective of this study was to investigate the microbial mechanisms for the improvement of composting efficiency after Bacillus subtilis inoculation with soluble phosphorus function in the spent mushroom substrate (SMS) aerobic composting. The methods in this study, including redundant analysis (RDA), co-occurrence network analyze and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt 2) were carried out studying the dynamic changes of phosphorus (P) components, microbial interactions and metabolic characteristics in the SMS aerobic composting inoculated with phosphorus-solubilizing B. subtilis (PSB). An increase in germination index (GI) (up to 88.4%), total nitrogen (TN) (16.6 g kg-1), available P content (0.34 g kg-1) and total P (TP) content (3.20 g kg-1) and a decrease in total organic carbon (TOC), C/N and electrical conductivity (EC) in final composting stage indicated B. subtilis inoculation could further improve maturity quality of the composting product compared with CK. Other results also demonstrated that PSB inoculation increased the stability of compost, humification degree and bacterial diversity, contributing to P fractions transformation in the composting process. Co-occurrence analysis suggested that PSB strengthened microbial interactions. Metabolic function of bacterial community analysis showed pathways such as carbohydrate metabolism, and amino acid metabolism in the composting were increased by effects of PSB inoculation. In summary, this study reveals a useful basis for better regulating the P nutrient level of the SMS composting and reducing environmental risks by inoculating B. subtilis with P solubilizing function.


Asunto(s)
Agaricales , Compostaje , Fosfatos/química , Bacillus subtilis , Filogenia , Suelo/química , Fósforo , Nitrógeno , Estiércol
14.
Brain Sci ; 13(3)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36979335

RESUMEN

OBJECTIVES: Postoperative neurological deficits remain a challenge in cardiac surgery employing deep hypothermic circulatory arrest (DHCA). This study aimed to investigate the effect of WIN55, 212-2, a cannabinoid agonist, on brain injury in a rat model of DHCA. METHODS: Twenty-four male Sprague Dawley rats were randomly divided into three groups: a control group (which underwent cardiopulmonary bypass (CPB) only), a DHCA group (CPB with DHCA), and a WIN group (WIN55, 212-2 pretreatment before CPB with DHCA). Histopathological changes in the brain were evaluated by hematoxylin-eosin staining. Plasma levels of superoxide dismutase (SOD) and proinflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-a) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression of SOD in the hippocampus was detected by Western blot and immunofluorescence staining. Levels of apoptotic-related protein caspase-3 and type 1 cannabinoid receptor (CB1R) in the hippocampus were evaluated by Western blot. RESULTS: WIN55, 212-2 administration attenuated histopathological injury of the hippocampus in rats undergoing DHCA, associated with lowered levels of IL-1ß, IL-6, and TNF-α (p < 0.05, p < 0.001, and p < 0.01, vs. DHCA, respectively) and an increased level of SOD (p < 0.05 vs. DHCA). WIN55, 212-2 treatment also increased the content of SOD in the hippocampus. The protein expression of caspase-3 was downregulated and the expression of CB1R was upregulated in the hippocampus by WIN55, 212-2. CONCLUSIONS: the administration of WIN55, 212-2 alleviates hippocampal injury induced by DHCA in rats by regulating intrinsic inflammatory and oxidative stress responses through a CB1R-dependent mechanism.

15.
Adv Mater ; 35(23): e2209552, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36932043

RESUMEN

High-valence metal species generated in peroxymonosulfate (PMS)-based Fenton-like processes are promising candidates for selective degradation of contaminants in water, the formation of which necessitates the cleavage of OH and OO bonds as well as efficient electron transfer. However, the high dissociation energy of OH bond makes its cleavage quite challenging, largely hampering the selective generation of reactive oxygen species. Herein, an asymmetrical configuration characterized by a single cobalt atom coordinated with boron and nitrogen (CoB1 N3 ) is established to offer a strong local electric field, upon which the cleavage of OH bond is thermodynamically favored via a promoted coupled electron-proton transfer process, which serves an essential step to further allow OO bond cleavage and efficient electron transfer. Accordingly, the selective formation of Co(IV)O in a single-atom Co/PMS system enables highly efficient removal performance toward various organic pollutants. The proposed strategy also holds true in other heteroatom doping systems to configure asymmetric coordination, thus paving alternative pathways for specific reactive species conversion by rationalized design of catalysts at atomic level toward environmental applications and more.

16.
Proc Natl Acad Sci U S A ; 120(13): e2213480120, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36952380

RESUMEN

Peroxidase-like catalysts are safe and low-cost candidates to tackle the dilemma in constructing sustainable cathodic heterogeneous electro-Fenton (CHEF) catalysts for water purification, but the elusive structure-property relationship of enzyme-like catalysts constitutes a pressing challenge for the advancement of CHEF processes in practically relevant water and wastewater treatment. Herein, we probe the origins of catalytic efficiency in the CHEF process by artificially tailoring the peroxidase-like activity of Fe3O4 through a series of acetylated chitosan-based hydrogels, which serve as ecofriendly alternatives to traditional carbon shells. The optimized acetylated chitosan wrapping Fe3O4 hydrogel on the cathode shows an impressive activity and stability in CHEF process, overcoming the complicated and environmentally unfavored procedures in the electro-Fenton-related processes. Structural characterizations and theoretical calculations reveal that the amide group in chitosan can modulate the intrinsic redox capacity of surficial Fe sites on Fe3O4 toward CHEF catalysis via the neutral hydrogen bond. This work provides a sustainable path and molecule-level insight for the rational design of high-efficiency CHEF catalysts and beyond.

17.
Med Chem Res ; 32(4): 705-712, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36816432

RESUMEN

Fifteen novel butyric ester tethered dihydroartemisinin-isatin hybrids 4a-d and 5a-k were designed, synthesized, and evaluated for cytotoxicity against four human breast cancer cell lines, including MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR using the MTT method. A significant part of them were active against the four tested cancer cell lines, and the representative hybrid 5b (IC50: 1.27 µM) was 14.88 -> 78.74 times more active than adriamycin (IC50: 18.90 µM), DHA (IC50: 28.28 µM) and ART (IC50: > 100 µM) against MCF-7 breast cancer cells, whereas hybrid 5c (IC50: 2.39 and 3.95 µM) was superior to adriamycin (IC50: 3.38 and >100 µM), DHA (IC50: 48.80 and 82.78 µM) and ART (IC50: >100 and >100 µM) against MDA-MB-231 and MDA-MB-231/ADR breast cancer cell lines. Moreover, the selected hybrids (IC50: >100 µM) displayed non-cytotoxicity towards normal MCF-10A breast cells, and the SI values of hybrids 5b,c were >78.74 and >41.84 respectively, demonstrating their excellent selectivity and safety profiles. Accordingly, hybrids 5b,c could serve as promising anti-breast cancer candidates and deserved further preclinical evaluations.

18.
J Clin Med ; 12(3)2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36769462

RESUMEN

Neurological dysfunction is a common complication of deep hypothermic circulatory arrest (DHCA). Endoplasmic reticulum (ER) stress plays a role in neuronal ischemia-reperfusion injury; however, it is unknown whether it contributes to DHCA-induced brain injury. Here, we aimed to investigate the role of ER stress in a rat DHCA model and cell hypothermic oxygen-glucose deprivation reoxygenation (OGD/R) model. ER stress and apoptosis-related protein expression were identified using Western blot analysis. Cell counting assay-8 and flow cytometry were used to determine cell viability and apoptosis, respectively. Brain injury was evaluated using modified neurological severity scores, whereas brain injury markers were detected through histological examinations and immunoassays. We observed significant ER stress molecule upregulation in the DHCA rat hippocampus and in hypothermic OGD/R PC-12 cells. In vivo and in vitro experiments showed that ER stress or activating transcription factor 6 (ATF6) inhibition alleviated rat DHCA-induced brain injury, increased cell viability, and decreased apoptosis accompanied by C/EBP homologous protein (CHOP). ER stress is involved in DHCA-induced brain injury, and the inhibition of the ATF6 branch of ER stress may ameliorate this injury by inhibiting CHOP-mediated apoptosis. This study establishes a scientific foundation for identifying new therapeutic targets for perioperative brain protection in clinical DHCA.

19.
EMBO Mol Med ; 15(4): e17450, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-36847712

RESUMEN

Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone. Though POI affects many aspects of women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch-chain amino acid (BCAA) insufficiency-related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency-induced POI is associated with abnormal activation of the ceramide-reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS-induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.


Asunto(s)
Menopausia Prematura , Insuficiencia Ovárica Primaria , Humanos , Femenino , Ratones , Animales , Especies Reactivas de Oxígeno , Aminoácidos , Ratones Endogámicos C57BL , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/patología , Insuficiencia Ovárica Primaria/terapia
20.
Am J Physiol Regul Integr Comp Physiol ; 324(2): R227-R241, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36572554

RESUMEN

The study was performed to evaluate the effects of the reduced lactate production by sodium oxamate (SO) on growth performance, lactate and glucose and lipid metabolism, and glucose tolerance of Micropterus salmoides fed high-carbohydrate (CHO) diets. In in vitro study, primary hepatocytes were incubated for 48 h in a control medium (5.5 mM glucose), a high-glucose medium (25 mM glucose, HG), or a SO-containing high-glucose medium (25 mM glucose + 50 mM SO, HG-SO). Results indicated lactate and triglyceride (TG) levels, and lactate dehydrogenase a (LDH-a) expression in the HG-SO group were remarkably lower than those of the HG group. In in vivo study, M. salmoides (5.23 ± 0.03 g) were fed four diets containing a control diet (10% CHO, C) and three SO contents [0 (HC), 100 (HC-SO1), and 200 (HC-SO2) mg·kg-1, respectively] of high-CHO diets (20% CHO) for 11 wk. High-CHO diets significantly reduced weight gain rate (WGR), specific growth rate (SGR), p-AMPK-to-t-AMPK ratio, and expression of insulin receptor substrate 1 (IRS1), insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), fructose-1,6-biphosphatase (FBPase), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase 1α (CPT1α) compared with the C group, whereas the opposite was true for plasma levels of glucose, TG, lactate, tissue glycogen, and lipid contents, and expression of LDH-a, monocarboxylate transporter 1 and 4 (MCT1 and MCT4), insulin, glucokinase (GK), pyruvate dehydrogenase E1 subunit (PDH), sterol-regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). The HC-SO2 diets remarkably increased WGR, SGR, p-AMPK-to-t-AMPK ratio, and expression of IRS1, IGF-I, IGF-IR, GK, PDHα, PDHß, FAS, acetyl-CoA carboxylase 1 (ACC1), PPARα, and CPT1α compared with the HC group. Besides, HC-SO2 diets also enhanced glucose tolerance of fish after a glucose loading. Overall, the reduced lactate production by SO benefits growth performance and glucose homeostasis of high-CHO-fed M. salmoides through the enhancement of glycolysis, lipogenesis, and fatty acid ß-oxidation coupled with the suppression of glycogenesis and gluconeogenesis.


Asunto(s)
Lubina , Factor I del Crecimiento Similar a la Insulina , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lubina/metabolismo , Ácido Láctico/metabolismo , PPAR alfa , Proteínas Quinasas Activadas por AMP/metabolismo , Lactato Deshidrogenasa 5/metabolismo , Lactato Deshidrogenasa 5/farmacología , Dieta , Glucosa/metabolismo , Homeostasis , Hígado/metabolismo
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