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1.
ACS Appl Mater Interfaces ; 16(15): 19838-19848, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38569046

RESUMO

Environment-friendly antisolvents are critical for obtaining highly efficient, reproducible, and sustainable perovskite solar cells (PSCs). Here, we introduced a green mixture antisolvent of ethyl acetate-isopropanol (EA/IPA) to finely regulate the crystal grain growth and related film properties, including the morphology, crystal structure, and chemical composition of the perovskite thin film. The IPA with suitable content in EA plays a key role in achieving a smooth and compact high-quality perovskite thin film, leading to the suppression of film defect-induced nonradiative recombination. As a result, the PSCs based on the EA/IPA (5:1) antisolvent showed a power conversion efficiency of 22.9% with an open-circuit voltage of 1.17 V.

2.
PLoS One ; 19(3): e0299509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451930

RESUMO

INTRODUCTION: Obesity has been found to be correlated with numerous health issues, including an elevated risk of albuminuria in adults. However, this correlation is still controversial among children and adolescents, as several recent large-scale cross-sectional studies have observed a negative correlation between obesity and albuminuria. Our study aimed to investigate the link between the body roundness index (BRI) and albuminuria among children and adolescents, in order to further understand the correlation between obesity and albuminuria in this demographic. METHODS: We employed information from the National Health and Nutrition Examination Survey (NHANES) 1999-2010 for cross-sectional analysis. Weighted logistic regression was employed to explore the linear relationship between BRI and albuminuria, with subgroup analyses performed for more detailed insights. Weighted linear regression analysis was employed to explore the relationship between BRI and the urine albumin-creatinine ratio (UACR). Additionally, we applied smooth curve fitting to investigate their non-linear relationship and conducted threshold effect analysis to identify any turning point. RESULTS: In this study of 15,487 participants aged 8-19 years, multivariate logistic regression analysis revealed a significant negative correlation between BRI and albuminuria (OR = 0.616, 95%CI: 0.526-0.722). The relationship between BRI and UACR, as shown by multivariate linear regression analysis, was significantly inversely correlated (ß: -5.424, 95%CI: -7.416 to -3.433). Furthermore, smooth curve fitting and threshold effect analysis showed a non-linear relationship between BRI and albuminuria, with a BRI inflection point identified at 2.906. CONCLUSIONS: These findings of our study suggest a significant nonlinear negative association between BRI and the presence of albuminuria among children and teenagers, and maintaining an appropriate BRI may decrease the occurrence of albuminuria in this population.


Assuntos
Albuminúria , Obesidade , Adulto , Criança , Humanos , Adolescente , Estudos Transversais , Inquéritos Nutricionais , Albuminúria/epidemiologia , Obesidade/epidemiologia , Urinálise , Índice de Massa Corporal , Fatores de Risco
3.
Int J Biol Macromol ; 265(Pt 1): 130911, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492693

RESUMO

In this study, the solubilization and structural changes of lignin in naked oat stems were investigated under subcritical water autohydrolysis systems (170-210 °C, 0.68-1.85 MPa). In this system, Hemicellulose was preferentially hydrolyzed in the liquid water at elevated temperatures, leading to the production of acetic acid and glucuronic acid, which acidified the reaction system. Under acidic and high-temperature conditions, lignin primarily underwent degradation and condensation reactions. At autohydrolysis temperatures below 190 °C and autohydrolysis pressures below 1.22 MPa, lignin degradation was predominant, realizing a maximum lignin removal of 47.8 % and breakage of numerous ß-O-4 bonds from lignin. At autohydrolysis temperatures above 190 °C and autohydrolysis pressures above 1.22 MPa, lignin condensation dominated, with an increase in the amount of organic acids generated upon hemicellulose degradation, leading to condensation reactions with the degraded low-molecular-weight lignin. The degree of lignin condensation was positively correlated with the temperature of the reaction system. This study provides essential insights into the dynamic changes in the structure of lignin in both the hydrolysis residue and hydrolysis solution during subcritical water autohydrolysis.


Assuntos
Lignina , Água , Lignina/química , Avena , Compostos Orgânicos , Temperatura , Hidrólise
5.
Int Immunopharmacol ; 130: 111641, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38368770

RESUMO

Acute lung injury (ALI) is a common life-threatening illness characterized by a lung inflammatory response and oxidative stress, and effective agent therapies are currently lacking. mtDNA can be recognized by cGAS/STING, the dysregulation of which leads to inflammatory diseases, such as ALI. Perillaldehyde(PAH), one of the major active components of traditional Chinese medicine made from Perilla frutescens, has antioxidant and antiinflammatory effects. The aim of this study was to explore whether PAH can protect against lipopolysaccharide (LPS)-induced ALI and whether its protective effect is exerted through the regulation of cGAS/STING signaling. We found that PAH significantly inhibited lung histological changes, inflammatory cell infiltration, and the overproduction of inflammatory cytokines induced by LPS. Moreover, PAH inhibited LPS-induced oxidative stress, as shown by the deceases in superoxide dismutase (SOD) and glutathione(GSH) levels and increased in malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. In addition, PAH markedly downregulated the expression of cGAS, STING, p-TBK, p-IRF3, p-P65, and p-IκB, and pharmacological inhibition of cGAS/STING inhibited ALI- induced by LPS. Furthermore, the levels of mitochondrial ROS (mROS) and mtDNA were increased, and cGAS/STING-mediated IRF3/NF-κB signaling was activated during the inflammatory response- induced by LPS in RAW264.7 cells. In addition, pretreatment with the STING activator partially abolished the inhibitory effect of PAH on the inflammation and activation of STING-mediated IRF3/NF-κB signaling induced by LPS. Overall, the results revealed that PAH can effectively alleviate ALI by inhibiting cGAS/STING-mediated IRF3/NF-κB signaling, and that PAH may be a potential candidate agent for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Monoterpenos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Transdução de Sinais , Nucleotidiltransferases/metabolismo , DNA Mitocondrial
6.
J Hazard Mater ; 467: 133705, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335618

RESUMO

Generation of sulfate radicals (SO4•-) from sulfite activation has emerged as a promising method for abatement of organic pollutants in the water and wastewater treatment. Co(II) has garnered attention due to its high catalytic activity in the sulfite activation, which is compromised by the slow Co(II)/Co(III) redox cycling. Regarding the regulation of Co(II) electronic structure via the complexation effect, monoethanolamine (MEA), a common chelator, is introduced into the Co(II)/sulfite system. MEA addition results in a significant improvement in iohexol abatement efficiency, increasing from 40% to 92%. The superior iohexol abatement relies on the involvement of SO4•-, hydroxyl radicals (HO•) and Co(IV). Hydrogen radical (•H) is unexpectedly detected, acting as a strong reducing agent, contributing to the reduction of Co(III). This enhancement of sulfite activation by MEA is due to the formation of the Co(II)-MEA complex, in which the complexation ratio of Co(II) and MEA is critical. Electrochemical characterization and theoretical calculations demonstrate that the complexation can facilitate the Co(II)/Co(III) redox cycling with the concomitant enhancement of sulfite activation. This work provides a new insight into the Co(II)/sulfite system in the presence of organic ligands.

8.
In Vitro Cell Dev Biol Anim ; 59(10): 778-789, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38048028

RESUMO

Breast cancer (BC) is a significant tissue for women's health worldwide. The spindle assembly checkpoint protein family includes BUBR1 (Bub1-related kinase or MAD3/Bub1b). High expression of BUBR1 promotes cell cycle disorders, leading to cell carcinogenesis and cancer progression. However, the underlying molecular mechanism and the role of BUBR1 in BC progression are unclear. The published dataset was analyzed to evaluate the clinical relevance of BUBR1. BUBR1 was knocked down in BC cells using shRNA. The CCK-8 assay was used to measure the cell viability, and mRNA and protein expression levels were detected by RT-qPCR and Western blot (WB). Cell apoptosis and cell cycle were detected by flow cytometry. Subcutaneous xenograft model was used to assess in vivo tumor growth. BUBR1 was found to be highly expressed in BC. The high expression of BUBR1 was associated with poor prognosis of BC patients. Upon BUBR1 knockdown using shRNA, the proliferation and metastatic ability of cells were decreased. Moreover, the cells with BUBR1 knockdown underwent cell cycle arrest. And the results showed that BUBR1 loss inhibited the phosphorylation of TAK1/JNK. In vitro and in vivo studies indicated the knockdown of BUBR1 rendered the BC cells more sensitive to cisplatin. In summary, BUBR1 may be a potential therapeutic target for BC and targeting BUBR1 may help overcome cisplatin resistance in BC patients.


Assuntos
Cisplatino , Mitose , Feminino , Animais , Cisplatino/farmacologia , Regulação para Baixo/genética , RNA Interferente Pequeno , Proliferação de Células/genética , Linhagem Celular Tumoral
9.
Eur J Cardiothorac Surg ; 64(6)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070151

RESUMO

OBJECTIVES: Perivascular adipose tissue (PVAT) surrounding human internal mammary artery (IMA) possesses anticontractile property. Its function under pathological conditions is barely studied. We previously reported that homocysteine impairs the vasodilator function of IMA through endothelium and smooth muscle-dependent mechanisms. This study investigated the effect of homocysteine on the function of PVAT and the associated mechanisms. METHODS: Residual IMA tissues were collected from patients undergoing coronary artery bypass grafting. Vasoreactivity was studied using myograph. Adiponectin was measured by ELISA. Expressions of adiponectin receptors (AdipoRs), eNOS and p-eNOS were determined by RT-qPCR and Western blot. RESULTS: Exposure to homocysteine augmented the contractile responses of PVAT-intact IMA to U46619 and potassium chloride, regardless with or without endothelium. Such augmentation was also observed in skeletonized IMA with transferred, homocysteine-exposed PVAT. Homocysteine attenuated the relaxant response of PVAT-intact while endothelium-denuded vessels to acetylcholine. Homocysteine lowered adiponectin content in the PVAT, downregulated the expression of AdipoR1 and AdipoR2 as well as eNOS and p-eNOS in skeletonized IMA. The relaxant response of skeletonized IMA to AdipoR agonist AdipoRon was blunted by homocysteine or eNOS inhibitor, and homocysteine significantly attenuated the inhibitory effect of eNOS inhibitor on AdipoRon-induced relaxation. CONCLUSIONS: Homocysteine impairs the anticontractile/vasorelaxing activity of PVAT surrounding the IMA through inhibiting adiponectin/AdipoR/eNOS/nitric oxide signalling pathway.


Assuntos
Adiponectina , Artéria Torácica Interna , Humanos , Adiponectina/metabolismo , Adiponectina/farmacologia , Artéria Torácica Interna/cirurgia , Tecido Adiposo , Vasodilatadores/farmacologia , Ponte de Artéria Coronária
10.
J Chem Phys ; 159(23)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126624

RESUMO

Boron-based compounds have triggered substantial attention due to their multifunctional properties, incorporating excellent hardness and superconductivity. While tetragonal metal borides LiB4 and NaB4 with BaAl4-type structure and striking clathrate boron motif have been induced under compression, there is still a lack of deep understanding of their potential properties at ambient pressure. We herein conduct a comprehensive study on I4/mmm-structured LiB4 and NaB4 under ambient pressure via first-principles calculations. Remarkably, both LiB4 and NaB4 are found to possess high Vickers hardness of 39 GPa, which is ascribed to the robust boron framework with strong covalency. Furthermore, their high hardness values together with distinguished stability make them highly potential superhard materials. Meanwhile, electron-phonon coupling analysis reveals that both LiB4 and NaB4 are conventional phonon-mediated superconductors, with critical temperatures of 6 and 8 K at 1 atmosphere pressure (atm), respectively, mainly arising from the coupling of B 2p electronic states and the low-frequency phonon modes associated with Li-, Na-, and B-derived vibrations. This work provides valuable insights into the mechanical and superconducting behaviors of metal borides and will boost further studies of emergent borides with multiple functionalities.

11.
Medicine (Baltimore) ; 102(50): e36613, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115339

RESUMO

Chronic kidney disease (CKD), a pervasive public health concern, can lead to complications like sarcopenia and reduced bone mineral density (BMD). However, it is still unclear exactly how muscle mass correlates with BMD in youngsters and adolescents with CKD. We aimed to investigate the association between appendicular skeletal muscle index (ASMI) and BMD among children and adolescents with CKD. In our research, we utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2014 to investigate the association of ASMI with BMD among this population. The association linking ASMI with total BMD was examined through multivariate linear regression models. Furthermore, fitted smoothing curves were employed, as well as generalized additive models. Our analysis finally included 503 CKD participants aged between 8 and 19 years. We found a significant association linking ASMI with total BMD among children and adolescents with CKD. The connection persisted even after accounting for covariates. Upon subgroup analysis, there was a statistically significant association of ASMI with total BMD for both males and females, as well as for Mexican-American and non-Hispanic White populations. However, no significant association was observed in other Hispanic, non-Hispanic Black, or populations of other races. We discovered a positive correlation linking the ASMI and the total BMD in children and teenagers with CKD. In CKD patients, maintaining skeletal muscle mass may be crucial for managing and preventing renal osteodystrophy.


Assuntos
Densidade Óssea , Insuficiência Renal Crônica , Masculino , Feminino , Criança , Humanos , Adolescente , Adulto Jovem , Adulto , Densidade Óssea/fisiologia , Estudos Transversais , Inquéritos Nutricionais , Músculo Esquelético/diagnóstico por imagem , Insuficiência Renal Crônica/complicações
12.
Opt Express ; 31(20): 32591-32600, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859059

RESUMO

Materials based on group IV chalcogenides, are considered to be one of the most promising materials for high-performance, broadband photodetectors due to their wide bandgap coverage, intriguing chemical bonding and excellent physical properties. However, the reported photodetectors based on SnS are still worked at relatively narrow near-infrared band (as far as 1550 nm) hampered by the nonnegligible bandgap of 1.1-1.5 eV. Here, a novel photodetector based on Te alloyed SnS thin film was demonstrated with an ultra-broadband response up to 10.6 µm. By controlling the Te alloyed concentration in SnS increasing to 37.64%, the bandgap narrows to 0.23 eV, exhibiting a photoresponse potential at long-wavelength infrared excitation. Our results show Te-alloying can remarkably enhance the detection properties of SnS/Te photodetectors. The photoresponsivity and detectivity of 1.59 mA/W and 2.3 × 108 Jones were realized at 10.6 µm at room temperature. Moreover, the nonzero photogain was observed generated by nonlinearly increased photocurrent density, resulting in a superlinear dependency between photoresponsivity and light intensity. Our studies successfully broaden photoresponse spectrum of SnS toward the mid-infrared range for the first time. It also suggests that alloying is an effective technique for tuning the band edges of group IV chalcogenides, contributing deep implications for developing future optoelectronic applications.

13.
J Craniofac Surg ; 34(7): 2077-2081, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37315290

RESUMO

OBJECTIVE: To investigate the effectiveness and feasibility of selective trigeminal nerve motor branching in the repair of facial palsy. MATERIALS AND METHODS: The clinical data of patients with advanced facial palsy from 2016 to 2021 were retrospectively analyzed, including pictures and videos before and 18 months after surgery. The House-Brackmann grading system was used to evaluate facial nerve function before and after repair, and the symmetry scale of oral commissure at rest and Terzis' smile functional evaluation scale were used to qualitatively assess the symmetry of the mouth angle and smile function. The distance of oral commissure movement was assessed to evaluate the dynamic repair effect, and the FaCE facial muscle function scale was used to assess patients' subjective perception before and after surgery. RESULTS: A total of four patients were included in the study, all of whom showed signs of recovery of facial nerve function within six months. In all four cases, significant improvements were observed in House-Brackmann ratings, the smile function score and the symmetry scale of oral commissure at rest. Compared to the pre-operative period, the four patients demonstrated various degrees of eye-closing function recovery, and a significant improvement in oral commissure movement was observed ( P <0.001). FaCE scores also improved significantly after surgery ( P =0.019). CONCLUSION: Concurrent selective facial nerve repair with trigeminal branch-facial nerve anastomosis resulted in eye-closing function recovery while improving static and dynamic symmetry, yielding acceptable postoperative results.


Assuntos
Paralisia Facial , Transferência de Nervo , Humanos , Paralisia Facial/cirurgia , Estudos Retrospectivos , Nervo Facial/cirurgia , Expressão Facial , Sorriso/fisiologia , Nervo Trigêmeo/cirurgia , Transferência de Nervo/métodos
14.
Opt Express ; 31(6): 9779-9789, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157541

RESUMO

Materials based on group IV chalcogenides exhibit extensive technologically important properties. Its unusual chemical bonding and off-centering of in-layer sublattices could cause chemical polarity and weakly broken symmetry, making optical field controlling feasible. Here, we fabricated large-area SnS multilayer films and observed unexpected strong SHG response at 1030 nm. The appreciable SHG intensities were obtained with an independence on layer, which is opposite to the generation principle of overall nonzero dipole moment only in odd-layer material. Taking GaAs for reference, the second-order susceptibility was estimated to be 7.25 pm/V enhanced by mixed-chemical bonding polarity. Further polarization-dependent SHG intensity confirmed the crystalline orientation of SnS films. The results imply surface inversion symmetry broken and nonzero polarization field modified by metavalent bonding should be the origin of SHG responses. Our observations establish multilayer SnS as a promising nonlinear material, and will guide in design of IV chalcogenides with improved optics and photonics properties for the potential applications.

15.
Genes (Basel) ; 14(4)2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-37107539

RESUMO

Layer and broiler hens show a dramatic difference in the volume and frequency of egg production. However, it is unclear whether the intrinsic competency of oocyte generation is also different between the two types of chicken. All oocytes were derived from the primordial germ cells (PGC) in the developing embryo, and female PGC proliferation (mitosis) and the subsequent differentiation (meiosis) determine the ultimate ovarian pool of germ cells available for future ovulation. In this study, we systematically compared the cellular phenotype and gene expression patterns during PGC mitosis (embryonic day 10, E10) and meiosis (E14) between female layers and broilers to determine whether the early germ cell development is also subjected to the selective breeding of egg production traits. We found that PGCs from E10 showed much higher activity in cell propagation and were enriched in cell proliferation signaling pathways than PGCs from E14 in both types of chicken. A common set of genes, namely insulin-like growth factor 2 (IGF2) and E2F transcription factor 4 (E2F4), were identified as the major regulators of cell proliferation in E10 PGCs of both strains. In addition, we found that E14 PGCs from both strains showed an equal ability to initiate meiosis, which was associated with the upregulation of key genes for meiotic initiation. The intrinsic cellular dynamics during the transition from proliferation to differentiation of female germ cells were conserved between layers and broilers. Hence, we surmise that other non-cell autonomous mechanisms involved in germ-somatic cell interactions would contribute to the divergence of egg production performance between layers and broilers.


Assuntos
Galinhas , Células Germinativas , Animais , Feminino , Galinhas/genética , Células Germinativas/metabolismo , Meiose/genética , Oócitos , Mitose/genética
16.
Neuroscience ; 521: 110-122, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37087022

RESUMO

N6-methyl adenosine (m6A) modification is known to play a crucial role in various aging-related diseases. However, its involvement in presbycusis, a type of age-related hearing loss, is not yet clear. We examined the changes in oxidative stress levels in both plasma of presbycusis patients and mice. To determine the expression of m6A and its functional enzymes, we used liquid chromatography tandem-mass spectrometry (LC-MS/MS), enzyme-linked immunosorbent assay (ELISA), and RT-PCR to analyze the total RNA of presbycusis patients blood cells (n = 8). Additionally, we detected the expression of m6A functional enzymes in the cochlea of presbycusis mice using immunohistochemistry. We assessed the effects of m6A methyltransferase METTL3 on SIRT1 protein expression, reactive oxygen species (ROS) levels, and apoptosis in an oxidative stress model of organ of Corti 1 (OC1) cells. To observe the effect on SIRT1 protein expression, we interfered with the m6A recognition protein IGF2BP3 using siRNA. In both presbycusis patients and mice, there was an increased level of oxidative stress in plasma.There was a decrease in the expression of m6A, METTL3, and IGF2BP3 in presbycusis patients blood cells. The expression of METTL3 and IGF2BP3 was also reduced in the cochlea of presbycusis mice. In OC1 cells, METTL3 positively regulated SIRT1 protein levels, while reversely regulated the level of ROS and apoptosis. IGF2BP3 was found to be involved in the regulation of SIRT1 protein expression. In addition, METTL3 may play a protective role in oxidative stress-induced injury of OC1 cells, while both METTL3 and IGF2BP3 cooperatively regulate the level of m6A and the fate of SIRT1 mRNA in OC1 cells.


Assuntos
Presbiacusia , Sirtuína 1 , Animais , Camundongos , Adenosina/metabolismo , Apoptose , Cromatografia Líquida , Metiltransferases/genética , Metiltransferases/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio , RNA Mensageiro/metabolismo , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , Humanos
17.
Future Sci OA ; 9(3): FSO847, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37056578

RESUMO

Aim: It is to be elucidated the risk-predictive role of differentially expressed fatty acid metabolism related genes (DE-FRGs) in dilated cardiomyopathy (DCM) and myocardial infarction. Materials & methods: Four gene enrichment analyses defined DE-FRGs' biological functions and pathways. Three strategies were applied to identify risk biomarkers and construct a nomogram. The 4-DE-FRG correlation with immune cell infiltration, drugs, and ceRNA was explored. Results: DE-FRGs were enriched in lipid metabolism. A risk nomogram was established by ACSL1, ALDH2, CYP27A1 and PPARA, demonstrating a good ability for DCM and myocardial infarction prediction. PPARA was positively correlated with adaptive immunocytes. Thirty-five drugs are candidate therapeutic targets. Conclusion: A nomogram and new biological targets for early diagnosis and treatment of DCM and myocardial infarction were provided.


Dilated cardiomyopathy (DCM) and myocardial infarction (MI) are two common types of heart disease. This study investigated the fatty acid metabolism related genes to predict the risk of DCM or MI. Four of them (ACSL1, ALDH2, CYP27A1 and PPARA) were effective in predicting disease risk. Additionally, PPARA was found to be associated with immune cell infiltration, and 35 drugs emerged as potential therapeutic targets for these diseases. This study may provide insights into the early diagnosis and treatment of DCM and MI.

18.
Biochim Biophys Acta Mol Basis Dis ; 1869(4): 166643, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36669577

RESUMO

OBJECTIVES: Studies in certain cardiac hypertrophy models suggested the individual role of soluble epoxide hydrolase (sEH) and canonical transient receptor potential 3 (TRPC3) channels, however, whether they jointly mediate hypertrophic process remains unexplored. Hyperhomocysteinemia promotes cardiac hypertrophy while the involvement of sEH and TRPC3 channels remains unknown. This study aimed to explore the role of, and interrelation between sEH and TRPC3 channels in homocysteine-induced cardiac hypertrophy. METHODS: Rats were fed methionine-enriched diet to induce hyperhomocysteinemia. H9c2 cells and neonatal rat cardiomyocytes were incubated with homocysteine. Cardiac hypertrophy was evaluated by echocardiography, histological examination, immunofluorescence imaging, and expressions of hypertrophic markers. Epoxyeicosatrienoic acids (EETs) were determined by ELISA. TRPC3 current was recorded by patch-clamp. Gene promotor activity was measured using dual-luciferase reporter assay. RESULTS: Inhibition of sEH by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) reduced ventricular mass, lowered the expression of hypertrophic markers, decreased interstitial collagen deposition, and improved cardiac function in hyperhomocysteinemic rats, associated with restoration of EETs levels in myocardium. TPPU or knockdown of sEH suppressed TRPC3 transcription and translation as well as TRPC3 current that were enhanced by homocysteine. Exogenous 11,12-EET inhibited homocysteine-induced TRPC3 expression and cellular hypertrophy. Silencing C/EBPß attenuated, while overexpressing C/EBPß promoted homocysteine-induced hypertrophy and expressions of sEH and TRPC3, resulting respectively from inhibition or activation of sEH and TRPC3 gene promoters. CONCLUSIONS: sEH and TRPC3 channels jointly contribute to homocysteine-induced cardiac hypertrophy. Homocysteine transcriptionally activates sEH and TRPC3 genes through a common regulatory element C/EBPß. sEH activation leads to an upregulation of TRPC3 channels via a 11,12-EET-dependent manner.


Assuntos
Cardiomegalia , Epóxido Hidrolases , Hiper-Homocisteinemia , Animais , Ratos , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Cardiomegalia/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Eicosanoides , Epóxido Hidrolases/genética , Epóxido Hidrolases/metabolismo , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/complicações , Miocárdio/metabolismo , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo
20.
Reprod Sci ; 30(6): 1841-1853, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474131

RESUMO

Endometriosis (EMs) is a life-long endocrine disorder and a common cause for female infertility and pelvic pain. The key characteristics of eutopic endometrium of EMs patients are high proliferative and migratory potentials. Cuproptosis is a recently identified copper- and-mitochondrial-dependent regulated cell death. Regretfully, its role in EMs remains unclear. In this study, Kyoto Encyclopedia of Genes and Genomes analyses of differentially expressed genes (DEGs) indicated strong activation of the PI3K-Akt-mTOR pathway and biological process analysis reported positive regulation of kinase activity. Next, we screened 11 cuproptosis-related DEGs and found all of them were downregulated in the EMs group, which indicated the suppression of cuproptosis in EMs. One key cuproptosis-related gene, PDHA1, was selected via support vector machine, random forest algorithm and lasso regularization to build a risk-scoring model, which was tested in both internal and external validations. In conclusion, the downregulation and kinase activity of PDHA1 may function with the PI3K-Akt-mTOR pathway in some way, which could suppress the cuproptosis level and account for the cancer-like pathology in EMs.


Assuntos
Apoptose , Endometriose , Feminino , Humanos , Endometriose/metabolismo , Endométrio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Cobre
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