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BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.
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Diabetes Mellitus Tipo 2 , Ferroptose , Osteoporose , Animais , Ratos , Autofagia , Ceramidas , Glucose , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Espécies Reativas de Oxigênio , Esfingomielina Fosfodiesterase/genética , Microtomografia por Raio-XRESUMO
This study aimed to summarize the evidence regarding the effects of dietary intake before conception on pregnancy outcomes by performing a systematic review and meta-analysis of prospective studies. Electronic databases were searched from inception up to August 2021. Overall, 65 studies involving 831 798 participants were included and 38 studies were quantitatively pooled. With regard to maternal outcomes, pre-pregnancy intake of fried food, fast food, red and processed meat, heme iron and a low-carbohydrate dietary pattern was positively associated with the risk of gestational diabetes mellitus (GDM) (all P < 0.05). However, a high dietary fiber intake and folic acid supplementation were negatively associated with GDM risk (both P < 0.05). With regard to neonatal outcomes, maternal caffeine intake before pregnancy significantly increased the risk of spontaneous abortion, while folic acid supplementation had protective effects on total adverse neonatal outcomes, preterm birth, and small-for-gestational age (SGA, all P < 0.05). However, no significant associations were found between adverse pregnancy outcomes (i.e., GDM and SGA) and the pre-pregnancy dietary intake of sugar-sweetened beverages, potato, fish, and carbohydrates and the Healthy Eating Index. Our study suggests that maintaining a healthy diet before conception has significant beneficial effects on pregnancy outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1989658.
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Diabetes Gestacional , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Estudos Prospectivos , Resultado da Gravidez , Ingestão de Alimentos , Ácido FólicoRESUMO
Sulfite (SO32-) activation is one of the most potential sulfate-radical-based advanced oxidation processes, and the catalysts with high efficiency and low-cost are greatly desired. In this study, the cobalt nanoparticles embedded in nitrogen-doped graphite layers (Co@NC), were used to activate SO32- for removal of Methyl Orange in aqueous solution. The Co@NC catalysts were synthesized via pyrolysis of Co2+-based metal-organic framework (Co-MOF), where CoO was firstly formed at 400â and then partially reduced to Co nanoparticles embedded in carbon layers at 800â. The Co@NC catalysts were more active than other cobalt-based catalysts such as Co2+, Co3O4 and CoFe2O4, due to the synergistic effect of metallic Co and CoxOy. A series of chain reaction between Co species and dissolved oxygen was established, with the production and transformation of SO3â¢-, SO52-, and subsequent active radicals SO4â¢- and HOâ¢. In addition, HCO3- was found to play a key role in the reaction by complexing with Co species on the surface of the catalysts. The results provide a new promising strategy by using the Co@NC catalyst for SO32- oxidation to promote organic pollutants degradation.
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Poluentes Ambientais , Grafite , Estruturas Metalorgânicas , Nanopartículas , Carbono , Cobalto , Nitrogênio , Óxidos , Oxigênio , Sulfatos , SulfitosRESUMO
BACKGROUND: Dysfunction in survival and differentiation of osteoblasts commonly occurs in patients with osteoporosis. Cannabinoid receptor type 2 (CNR2) is a major receptor of endocannabinoid system that is crucial for bone mass homeostasis. Our group prior demonstrated that activation of CNR2 signaling promoted osteogenic differentiation of bone marrow derived mesenchymal stem cells in vitro. Autophagy is reported to participate in osteoblastic differentiation. Whether autophagy is regulated by CNR2-mediated cannabinoid signaling is unknown, and how the autophagy-CNR2 interaction affects osteoblastic differentiation requires further elucidation. METHODS: hFOB 1.19 osteoblasts were treated with CNR2 agonists HU308 (5, 10, 25, 50 or 100 nM) and JWH133 (1, 2, 5, 10 or 20 µM) in presence or absence of autophagy inhibitor 3-Methyladenine (3-MA). The differentiation of hFOB 1.19 cells was determined via evaluating their alkaline phosphatase (ALP) activity and mineralization ability (Alizarin red staining). Alterations in autophagy-related molecules and osteogenic markers were analyzed via real-time PCR and/or immunoblotting assays. RESULTS: hFOB 1.19 cells spontaneously differentiated towards mature osteoblasts under 39 °C, during which CNR2 expression increased, and autophagy was activated. The strongest autophagy flux was observed at 192 h post differentiationâLC3I to LC3II conversion was enhanced and Beclin 1 expression was upregulated considerably, while p62 expression was downregulated. Treatment of HU308 and JWH133 promoted autophagy in a dose-dependent manner, and suppressed mTOR signaling pathway in hFOB 1.19 cells. In CNR2-silenced cells, HU308's and JWH133's effects on autophagy were weakened. HU308 and JWH133 enhanced the ALP activity and mineralization, and upregulated the expression of osteogenic markers, osteopontin and osteocalcin, in hFOB 1.19 cells. Intriguingly, such pro-osteogenic effects induced by CNR2 activation were markedly mitigated by 3-MA. In addition to provoking autophagy, CNR2 agonists also reduced nuclear Nrf2 accumulation and increased Keap1 expression. Further, re-expression of p62 inhibited CNR2 agonists-induced Nrf2 degradation. CONCLUSIONS: Osteogenic differentiation induced by CNR2 signaling activation involves autophagy induction and p62-mediated Nrf2 deactivation.
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Autofagia , Diferenciação Celular , Fator 2 Relacionado a NF-E2/metabolismo , Osteogênese , Receptor CB2 de Canabinoide/metabolismo , Proteína Sequestossoma-1/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Autofagia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Osteogênese/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Receptor CB2 de Canabinoide/agonistas , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Induction of osteoblast differentiation is an effective approach in promoting osteoblastogenesis and bone formation. MicroRNA (miR) is a kind of small regulatory RNA molecules that control both physiological and pathological processes. The purpose of this research was to explore the function of miR-187-3p in proliferation and osteogenic differentiation in human osteoblastic precursor cells (hFOB 1.19). Our results showed a significant promotion of cell proliferation by miR-187-3p in hFOB 1.19â¯cell accompanied by increased proliferating cell nuclear antigen (PCNA) and Ki67 expression, whereas miR-187-3p knockdown led to an inhibition of cell proliferation. Moreover, our data revealed that miR-187-3p was decreased in hFOB 1.19â¯cells undergoing osteoblastic differentiation. Silencing of miR-187-3p dramatically accelerated hFOB 1.19 osteoblastic differentiation, as evidenced by the increase of alkaline phosphatase (ALP) activity and calcium deposition, as well as elevated osteopontin (OPN), collagen type I alpha 1 (COL1A1), and bone sialoprotein (BSP) gene expression, whereas overexpression of miR-187-3p suppressed osteoblastic differentiation. Furthermore, we demonstrated that miR-187-3p could inhibit cannabinoid receptor type 2 (CNR2) expression by targeting its 3' untranslated region (UTR). Upregulation of CNR2 inversed the inhibiting influence of miR-187-3p on hFOB 1.19 osteogenic differentiation. Collectively, our results showed a pivotal role of miR-187-3p/CNR2 axis in osteoblastic differentiation, indicating that miR-187-3p may serve as a promising target in the therapy of osteoporosis.
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Diferenciação Celular , Regulação da Expressão Gênica , MicroRNAs/genética , Osteoblastos/citologia , Osteogênese , Receptor CB2 de Canabinoide/antagonistas & inibidores , Células-Tronco/citologia , Proliferação de Células , Células Cultivadas , Cadeia alfa 1 do Colágeno Tipo I , Humanos , Osteoblastos/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Transdução de Sinais , Células-Tronco/metabolismoRESUMO
To date, no efficacious therapy exists that will prevent or treat the severe osteoporosis in individuals with neurologically motor-complete spinal cord injury (SCI). Recent preclinical studies have demonstrated that sclerostin antibody (Scl-Ab) can prevent sublesional bone loss after acute SCI in rats. However, it remains unknown whether sclerostin inhibition reverses substantial bone loss in the vast majority of the SCI population who have been injured for several years. This preclinical study tested the efficacy of Scl-Ab to reverse the bone loss that has occurred in a rodent model after chronic motor-complete SCI. Male Wistar rats underwent either complete spinal cord transection or only laminectomy. Twelve weeks after SCI, the rats were treated with Scl-Ab at 25 mg/kg/week or vehicle for 8 weeks. In the SCI group that did not receive Scl-Ab, 20 weeks of SCI resulted in a significant reduction of bone mineral density (BMD) and estimated bone strength, and deterioration of bone structure at the distal femoral metaphysis. Treatment with Scl-Ab largely restored BMD, bone structure, and bone mechanical strength. Histomorphometric analysis showed that Scl-Ab increased bone formation in animals with chronic SCI. In ex vivo cultures of bone marrow cells, Scl-Ab inhibited osteoclastogenesis, and promoted osteoblastogenesis accompanied by increased Tcf7, ENC1, and the OPG/RANKL ratio expression, and decreased SOST expression. Our findings demonstrate for the first time that Scl-Ab reverses the sublesional bone loss when therapy is begun after relatively prolonged spinal cord transection. The study suggests that, in addition to being a treatment option to prevent bone loss after acute SCI, sclerostin antagonism may be a valid clinical approach to reverse the severe bone loss that invariably occurs in patients with chronic SCI.
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Densidade Óssea/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Reabsorção Óssea/etiologia , Traumatismos da Medula Espinal/complicações , Animais , Anticorpos/farmacologia , Doença Crônica , Marcadores Genéticos , Masculino , Osteogênese/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts. Nrf2 has been considered a master regulator of cytoprotective genes against oxidative and chemical insults. The lack of Nrf2 can induce pathologies in multiple organs. Nrf2 deficiency promotes osteoclast differentiation and osteoclast activity, which leads to an increase in bone resorption. The role of Nrf2 in osteoblast differentiation and osteoblast activity is more complex. Nrf2 mediates anabolic effects within an ideal range. Nrf2 deletion suppresses load induced bone formation and delays fracture healing. Overall, Nrf2 plays an important role in the regulation of bone homeostasis in bone cells.
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Reabsorção Óssea/metabolismo , Diferenciação Celular , Fator 2 Relacionado a NF-E2/metabolismo , Osteoclastos/metabolismo , Osteócitos/metabolismo , Animais , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Humanos , Fator 2 Relacionado a NF-E2/genética , Osteoclastos/patologia , Osteócitos/patologiaRESUMO
Alternative splicing (AS) in eukaryotic organisms is closely related to the gene regulation in plant abiotic stress responses, in which serine/arginine-rich proteins (SR proteins) act as key regulators. The genome sequence of maize inbred line B73 was analyzed, showing that the promoter regions of SR genes possess about three to eight kinds of cis-acting regulatory elements. Twenty-seven SR genes encode alkaline proteins, and 23 of which are divided into five subgroups in terms of the first RNA recognition motif (RRM) at the amino terminal. The expression of SR genes showed tissue-specific and genotype-dependent features under drought stress in the hybrid Zhengdan-958 and its parents, Zheng-58 and Chang-7-2 via bidirectional hierarchical clustering. SR genes were down-regulated in roots while they were up-regulated in shoots under drought stress. However, SR genes were down-regulated in both roots and shoots in three different rehydration stages after severe drought stress. Additionally, a widespread alternative splicing exists in all SR genes although SR genes showed differential expression tendency under drought stress and/or during rehydration stages. Results above will deepen our understanding of the molecular mechanisms of plant response to abiotic stress from the perspective of AS-network.
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Família Multigênica , Proteínas de Plantas/genética , Água/metabolismo , Zea mays/fisiologia , Processamento Alternativo , Secas , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/metabolismo , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Zea mays/classificação , Zea mays/genética , Zea mays/crescimento & desenvolvimentoRESUMO
A high-performance liquid chromatography method of pre-column derivatization with 1-phenyl-3-methyl-5 -pyrazolone (PMP) has been established for determination of 6 kinds of monosaccharides simultaneously. A special Agilent HC-C18 column (4. 6 mm x 250 mm, 5 microm), optimized for the separation of PMP derivatives, was used at ambient temperature of 40 degrees C. The PMP derivatives elution was performed with a mixture of 0.1 mol x L(-1) phosphate buffer (pH 6. 8) and acetonitrile in a ratio of 84: 16 at a flow rate of 1 mL x min(-1), and UV absorbance of the effluent was monitored at 245 nm. The results showed that the polysaccharides from exopleura of Ginkgo biloba were acidic heteropolysaccharides mainly containing mannose, rhamnose, D-galacturonic acid, glucose, galactose, arabinose, with the molar ratio of 0.032: 0.14: 0.296: 0.403:0.106: 0.046.
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Ginkgo biloba/química , Monossacarídeos/análise , Componentes Aéreos da Planta/química , Polissacarídeos/química , HidróliseRESUMO
Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in postherpetic neuralgia (PHN). Methods: Through an extensive search in four databases until October 2023, we selected five randomized controlled trials adhering to our specific criteria, involving 257 patients in total. For continuous outcomes, the standardized mean difference (SMD) was calculated. Heterogeneity among the studies was assessed using Cochran's I 2 and Q statistics, adopting a random-effects model for I 2 values over 50%. For assessing potential publication bias, we utilized both funnel plot and Egger's test. Results: Our analysis found that rTMS reduced the overall visual analogue scale (VAS) (SMD: -1.52, 95% CI: -2.81 to -0.23, p = 0.02), VAS at 1 month post-treatment (SMD: -2.21, 95% CI: -4.31 to -0.10, p = 0.04), VAS at 3 months post-treatment (SMD: -1.51, 95% CI: -2.81 to -0.22, p = 0.02), as well as patients' global impression of change scale (PGIC) (SMD: -1.48, 95% CI: -2.87 to -0.09, p = 0.04) and short-form McGill pain questionnaire (SF-MPQ) (SMD: -1.25, 95% CI: -2.41 to -0.09, p = 0.03) compared to the sham-rTMS group. Conclusion: Our study suggests that rTMS might have a potential alleviating effect on PHN symptoms. However, due to the limited number of studies and variations in rTMS parameters, larger sample studies involving more diverse populations, as well as further clarification of the most appropriate stimulation protocol, are still needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier ID: CRD42023488420.
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The digestive instability of anthocyanins (ACNs) limits their application in food nutrition, especially precision nutrition. Blueberry ACNs-loaded nanoparticles (Lipo/GA-ACNs NPs) were prepared using gum arabic (GA) as the delivery carrier and liposomal vesicles (Lipo) prepared from soy lecithin as the targeting scaffold. The average particle size of the NPs was 99.4 nm, and the polydispersion index (PDI) was 0.46. The results showed that the presence of the Lipo-GA matrix enhanced the NPs' in vitro stability and antioxidant activity. In addition, the in vitro biocompatibility, uptake ability, lipid-lowering activity, and free-radical scavenging ability were improved to a certain extent. In a high-fat diet (HFD)-induced obese mouse model, oral administration of ACNs-LNP (LNP, liver-targeted nanoparticle) showed better effects on body weight, liver injury, and lipid droplet accumulation in the liver than ACNs. In addition, ACNs-LNP also played a role in regulating HFD-induced gut microbiota imbalance. These results provide a promising ACNs delivery strategy with the potential to be developed into a functional food that targets the liver to prevent fatty liver.
Assuntos
Mirtilos Azuis (Planta) , Microbioma Gastrointestinal , Nanopartículas , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Antocianinas/farmacologia , Camundongos Obesos , Lecitinas , Goma Arábica/farmacologia , Gotículas Lipídicas , Camundongos Endogâmicos C57BLRESUMO
The bicarbonate-activated hydrogen peroxide (BAP) system is widely studied for organic pollutant degradation in wastewater treatment. Ca2Co2O5, a heterogeneous catalyst containing multivalent cobalt including Co(II) and Co(III), was herein investigated as a BAP activator, and Acid Orange 7 (AO7) was used as a model pollutant. Ca2Co2O5 exhibited good activation performance. The degradation rate and the initial rate constant of the Ca2Co2O5-activated BAP system were 5.4 and 11.2 times as high as the BAP system, respectively. The removal rate of AO7 reached 90.9% in 30 min under optimal conditions (AO7 20 mg/L, Ca2Co2O5 0.2 g/L, H2O2 1 mM, NaHCO3 5 mM, pH 8.5, 25â). The Ca2Co2O5 catalyst exhibited good stability and recyclability, retaining 85% of AO7 removal rate in the fifth run. Compared to the BAP system, a lower dosage of H2O2 was required and a higher initial concentration of pollutants allowed for effective degradation in the Ca2Co2O5-BAP system. X-ray photoelectron spectroscopy was used to analyze the catalytic mechanism. The analysis showed that the good catalytic performance of Ca2Co2O5 attributes to its high proportion of oxygen vacancies and Co(III) species, and the presence of Ca. The active species O2â¢-, â¢OH, and 1O2 are responsible for the degradation, as indicated by the quenching experiments. The degradation mechanism of AO7 was speculated based on UV-Vis spectral analysis and the identification of degradation intermediates. The azo form, naphthalene and benzoic rings in the AO7 structure are destroyed in the decomposition. This research provides a feasible approach to designing effective and reusable BAP activators for pollutant degradation in wastewater treatment.
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Peróxido de Hidrogênio , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Poluentes Químicos da Água/química , Cobalto/química , Bicarbonatos/química , Catálise , Águas Residuárias/química , Compostos Azo , BenzenossulfonatosRESUMO
BACKGROUND: Hypertension is a highly prevalent chronic metabolic illness affecting individuals of all age groups. Furthermore, it is a significant risk factor for the development of atherosclerosis (AS), as a correlation between hypertension and AS has been observed. However, the effective treatments for either of these disorders appear to be uncommon. METHODS: A systematic search of articles published in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar databases over the last decade was performed using the following keywords: hypertension, AS, anthocyanins, antioxidants, gut microbes, health benefits, and bioactivity. RESULTS: The available research indicates that anthocyanin consumption can achieve antioxidant effects by inducing the activation of intracellular nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, previous reports showed that anthocyanins can enhance the human body's ability to fight against inflammation and cancer through the inhibition of inflammatory factors and the regulation of related signaling pathways. They can also protect the blood vessels and nervous system by regulating the production and function of endothelial nitric oxide synthase (eNOS). Gut microorganisms play an important role in various chronic diseases. Our research has also investigated the role of anthocyanins in the metabolism of the gut microbiota, leading to significant breakthroughs. This study not only presents a unique strategy for reducing the risk of cardiovascular diseases (CVDs) without the need for medicine but also provides insights into the development and utilization of intestinal probiotic dietary supplements. CONCLUSION: In this review, different in vitro and in vivo studies have shown that anthocyanins slow down the onset and progression of hypertension and AS through different mechanisms. In addition, gut microbial metabolites also play a crucial role in diseases through the gut-liver axis.
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Antocianinas , Anti-Hipertensivos , Antioxidantes , Aterosclerose , Microbioma Gastrointestinal , Hipertensão , Humanos , Antocianinas/farmacologia , Antocianinas/química , Aterosclerose/tratamento farmacológico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6â³-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group-conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.
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Antocianinas , Glucosídeos , Antocianinas/química , Acilação , Glucosídeos/química , Antioxidantes/química , Ésteres/química , Espectrometria de Massas , Estrutura Molecular , Cromatografia Líquida de Alta PressãoRESUMO
Lung adenocarcinoma (ADC) is one of the major histological types of lung cancer. Genetic polymorphism in DNA repair genes and lung ADC susceptibility is well documented. In this case-control study, the association between the polymorphic sites of DNA repair genes XPD-751, XRCC1-399, and OGG1-326, and lung ADC susceptibility in ethnic Han Chinese population has been investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 82 lung ADC patients from the people of Hunan Province, China. Polymorphisms of the investigated genes were analyzed by using polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference between the samples from lung ADC patients and healthy controls about the genotype frequencies of XPD-751, XRCC1-399, and OGG1-326 sites. However, multifactor dimensionality reduction analysis showed that the genetic polymorphisms of the three-loci models of DNA repair genes (XPD-751/XRCC1-399/OGG1-326) are associated with lung ADC. Thus, this study reveals that a three-order interaction among the polymorphic sites of XPD-751, XRCC1-399, and OGG1-326 is associated with lung ADC risk in the studied population, although polymorphism in individual gene was not associated.
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Adenocarcinoma/genética , DNA Glicosilases/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adenocarcinoma de Pulmão , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Análise de Sequência de DNA , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Neuronal apoptosis and inflammation exacerbate the secondary injury after spinal cord injury (SCI). Four and a half domains 2 (FHL2) is a multifunctional scaffold protein with tissue- and cell-type specific effects on the regulation of inflammation, but its role in SCI remains unclear. The T10 mouse spinal cord contusion model was established, and the mice were immediately injected with lentiviruses carrying FHL2 shRNA after SCI. The results showed that FHL2 expression was increased following SCI, and then gradually decreased. Moreover, FHL2 depletion aggravated functional impairment, neuronal necrosis, and enlarged lesion cavity areas in the injured spinal cord. FHL2 deficiency facilitated neuronal apoptosis by elevating cleaved caspase 3/9 expression, neuroinflammation by regulating microglia polarization, and bone loss. Indeed, FHL2 deficiency increased the secretion of TNF-α and IL-6, M1 microglia polarization, and the activation of STAT1 pathway but decreased the secretion of IL-10 and IL-4, M2 microglia polarization, and the activation of the STAT6 pathway in the spinal cord. In vitro, FHL2 silencing promoted LPS + IFN-γ-induced microglia M1 polarization through activating the STAT1 pathway and alleviated IL-4-induced microglia M2 polarization via inhibiting the STAT6 pathway. FHL2 positively regulated the expression of poly (ADP-ribose) polymerase family member 14 (PARP14) by promoting its transcription. PARP14 overexpression inhibited FHL2 silencing-induced microglia M1 polarization and relieved the inhibitory effect of FHL2 silencing on microglia M2 polarization. Collectively, the study suggests that FHL2 reduces the microglia M1/M2 polarization-mediated inflammation via PARP14-dependent STAT1/6 pathway and thereby improves functional recovery after SCI.
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Islet autoimmune syndrome (IAS) is an autoimmune disease caused by high concentrations of insulin autoantibodies (IAA) in the blood. It is characterized by hyperinsulinemia and spontaneous hypoglycemia. The incidence of IAS is low, and the hypoglycemia symptom is usually mild. Hence, the severe manifestations (up to seizures and coma) are rarely reported. Here, we reported two cases of Graves' disease who developed insulin autoimmune syndrome after methimazole treatment. The patients exhibited sudden hypoglycemic coma after receiving methimazole treatment for approximately 2 or 6 months. The patients' serum glucose levels were below 2.8 mmol/L, and laboratory tests showed high levels of serum insulin and high titers of insulin autoantibodies. Patient 1 discontinued methimazole treatment and the hypoglycemic symptoms disappeared after 7 days. However, patient 2 experienced severe hypoglycemia after discontinuation of methimazole, and the patient condition improved after glucocorticoid therapy. He developed thyroid storm during the treatment, and his condition improved after receiving standard treatment procedures for thyroid storm. To the best of our knowledge, this is the first case report of IAS in Graves' disease with thyroid storm.
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Poly(ADP-ribose)polymerase family member 14 (PARP14), which is an intracellular mono(ADP-ribosyl) transferase, has been reported to promote post-stroke functional recovery, but its role in spinal cord injury (SCI) remains unclear. To investigate this, a T10 spinal cord contusion model was established in C57BL/6 mice, and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression. We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury, accompanied by obvious neuronal apoptosis, severe neuroinflammation, and slight bone loss. Furthermore, PARP14 levels were elevated in microglia after SCI, PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia (anti-inflammatory phenotype) to M1-polarized microglia (pro-inflammatory phenotype) that may have been mediated by the signal transducers and activators of transcription (STAT) 1/6 pathway. Next, microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γ and interleukin-4, respectively. The results showed that PARP14 knockdown promoted microglia M1 polarization, accompanied by activation of the STAT1 pathway. In addition, PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway. In conclusion, these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.
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The development of new strategies to improve the removal of organic pollutants with permanganate (KMnO4) is a hot topic in water treatment. While Mn oxides have been extensively used in Advanced Oxidation Processes through an electron transfer mechanism, the field of KMnO4 activation remains relatively unexplored. Interestingly, this study has discovered that Mn oxides with high oxidation states including γ-MnOOH, α-Mn2O3 and α-MnO2, exhibited excellent performance to degrade phenols and antibiotics in the presence of KMnO4. The MnO4- species initially formed stable complexes with the surface Mn(III/IV) species and showed an increased oxidation potential and electron transfer reactivity, caused by the electron-withdrawing capacity of the Mn species acting as Lewis acids. Conversely, for MnO and γ-Mn3O4 with Mn(II) species, they reacted with KMnO4 to produce cMnO2 with very low activity for phenol degradation. The direct electron transfer mechanism in α-MnO2/KMnO4 system was further confirmed through the inhibiting effect of acetonitrile and the galvanic oxidation process. Moreover, the adaptability and reusability of α-MnO2 in complicated waters indicated its potential for application in water treatment. Overall, the findings shed light on the development of Mn-based catalysts for organic pollutants degradation via KMnO4 activation and understanding of the surface-promoted mechanism.
RESUMO
The development of efficient and eco-friendly Mn-based hybrids for the degradation of biorefractory organic pollutants via peroxymonosulfate (PMS) activation is highly desired. In this study, a novel graphite nanosheet (GNs)-based Fe-Mn bimetallic oxide (Fe doped birnessite MnO2, FeMn/GNs) was synthesized under mild conditions. Compared with monometallic Fe or Mn oxide on GNs, FeMn/GNs exhibited a higher surface area, decreased Mn oxidation states, stronger interaction with GNs, and more active sites for PMS adsorption. Among different Fe/Mn ratios, Fe2Mn1/GNs showed the optimum performance for bisphenol A (BPA) degradation with the first-order rate constant of 0.22 min-1, which was about 8.5 and 12.9 times higher than that of Mn/GNs and Fe/GNs, respectively. Different from the pollutant-catalyst-PMS electron transfer mechanism for Mn/GNs, the direct two-electron transfer in FeMn/GNs+PMS system, was mainly processed between the simultaneously activated BPA and PMS. This was probably based on the double adsorption sites of Fe and Mn species on the same catalyst: PMS was adsorbed by Fe species through hydroxyl groups, while BPA was mainly coordinated with Mn species due to the layered structure and hydrophobicity of the Mn oxide. This study is expected to provide the rational design of efficient Mn-based hybrids for PMS activation.