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Objective: To compare the macular area parameters and aqueous humor factors between myopia and emmetropia. Methods: Convenience sampling was used to select patients who visited the Changzhi Aier Eye Hospital's department of ophthalmology from December 2018 to December 2022 as the study participants. They were divided into three groups according to whether they were diagnosed as mild myopia myopic, highly myopic or not as follows: the mild myopia group (60 cases, 108 eyes), the high myopia group (46 cases, 78 eyes) and the healthy emmetropia group (40 cases, 65 eyes). The differences in the macular integrity (MI) assessment, optical coherence tomography and optical coherence tomography angiography parameters and aqueous humor factors were compared between the three groups. Results: AL in high myopia group was the highest, and that in emmetropia group was the lowest. The BCVA of mild myopia group was the highest. The RS in the high myopia group were significantly lowest in the three groups (26.42 ± 1.04 vs. 28.34 ± 0.76 vs. 31.92 ± 0.77) (F = 5.374, p = 0.013). The 63% BCEA, 95% BCEA and MI in the high myopia group were significantly highest (p < 0.05). The mean RPE thickness, mean CT and mean RT in the high myopia group were lowest (p < 0.05). The blood flow density were lowest in the superficial fovea, paracentral fovea and different subdivisions of the paracentral fovea in the high myopia group (p < 0.05). The VEGF concentration in the aqueous humor of the high myopia group was lowest (25.62 ± 17.43 vs. 32.45 ± 24.67 vs. 64.37 ± 21.14) (F = 9.237, p < 0.001). The MMP-2 concentration was highest (483 ± 201.48 vs. 410 ± 142.37 vs. 386 ± 154.34) (F = 5.542, p = 0.018). The VEGF concentration in the aqueous humor factor was negatively correlated with the AL in the myopia group (r = -0.438, p = 0.002), the MMP-2 concentration was positively correlated with the AL (r = 0.484, p = 0.010). Conclusion: Patients with high myopia showed decreased retinal light sensitivity, fixation stability, superficial blood flow density and retinal thickness compared with people with emmetropia. A decreased VEGF concentration and increased MMP-2 concentration in the aqueous humor factor have potential associations with the development of high myopia.
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Objective: The current study aimed to investigate the potential therapeutic impact of allantoin on diabetes produced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Subjects and methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The effect of oral treatment of allantoin (200, 400 and 800 mg/kg/day) for 8 weeks was evaluated by calculating the alteration in metabolic parameters, biochemical indicators, the oral glucose tolerance tests (OGTT) and hyperinsulinemic-euglycemic clamp tests were performed. Histopathological studies were performed in the liver, kidney and pancreas. Next, the expressions of the MAPK and insulin signaling pathway were measured by Western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. Results: The administration of allantoin resulted in a significant decrease in fasting blood glucose (FBG) levels, glycogen levels, and glycosylated hemoglobin levels in diabetic rats. Additionally, allantoin therapy led to a dose-dependent increase in body weight growth and serum insulin levels. In addition, the administration of allantoin resulted in a considerable reduction in lipid profile levels and amelioration of histological alterations in rats with diabetes. The administration of allantoin to diabetic rats resulted in a notable decrease in Malondialdehyde (MDA) levels, accompanied by an increase in the activity of antioxidant enzymes in the serum, liver, and kidney. The findings of oral glucose tolerance and hyperinsulinemic-euglycemic clamp tests demonstrated a significant rise in insulin resistance following the administration of allantoin. The upregulation of IRS-2/PI3K/p-Akt/GLUT expression by allantoin suggests a mechanistic relationship between the PI3K/Akt signaling pathway and the antihyperglycemic activity of allantoin. Furthermore, it resulted in a reduction in the levels of TGF-ß1/p38MAPK/Caspase-3 expression in the aforementioned rat tissues affected by diabetes. Conclusions: This study implies that allantoin treats type 2 diabetes by activating PI3K. Additionally, it reduces liver, kidney, and pancreatic apoptosis and inflammation-induced insulin resistance.re.
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Cistanche deserticola Y. C. Ma (CD), is mainly distributed in the regions of China (Xinjiang, Inner Mongolia, Gansu), Mongolia, Iran and India. Cistanche deserticola polysaccharide (CDPs), as one of the main components and a crucial bioactive substance of CD, has a variety of pharmacological activities, including immunomodulatory, anti-aging, anti-oxidant, hepatoprotective, anti-osteoporotic, anti-inflammatory, intestinal flora regulatory effects. Many polysaccharides have been successfully obtained in the last three decades from CD. However, there is currently no comprehensive review available concerning CDPs. Considering the importance of CDPs for biological study and drug discovery, the present review aims to systematically summarize the recent major studies on extraction and purification methods of polysaccharides from CD, as well as the characterization of their chemical structure, biological activity, structure-activity relationship, and the application of CDPs in pharmaceutical field. Meanwhile, the shortcomings of CDPs research are further discussed in detail, and new valuable insights for future CDPs research as therapeutic agents and functional foods are proposed.
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Background: The purpose of this study was to explore the relationship between infertility-related stress and dyadic coping with quality of life (QoL) in couples with infertility issues, and verify gender differences and dyadic interactions in the associations between them. Methods: This cross-sectional study included 340 couples who were recruited from the First Affiliated Hospital of Lanzhou University between March 2022 and November 2022. The Fertility Problem Inventory, Dyadic Coping Inventory and FertiQoL were used to measure infertility-related stress, dyadic coping and QoL. The Actor-Partner Interdependence Model was used to analyze the effects of infertility-related stress and dyadic coping on the couple's own QoL (actor effect) as well as on their partner's QoL (partner effect). Results: Female patients perceived significantly lower levels of QoL and dyadic coping than those of husbands. There was no statistically significant difference in the infertility-related stress between wives and husbands. Husbands' infertility-related stress had actor and partner effects on their own and their wives' QoL, while wives' infertility-related stress only had an actor effect on their own QoL. Husbands' dyadic coping had both actor effect and partner effects on their own and their wives' QoL, meanwhile wives' dyadic coping had both actor effect and partner effects on their own and their husbands' QoL. Conclusion: Husbands' QoL was impacted by their own infertility-related stress, dyadic coping and their wives' dyadic coping. Whereas wives' QoL was influenced by infertility-related stress and dyadic coping from both their own and their spouses. Therefore, elevating the level of dyadic coping may contribute to improving QoL for both husbands and wives. Moreover, enhancing the ability to cope with infertility-related stress might be useful for husbands and indirectly contribute to wives' QoL.
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BACKGROUND: Harmine has many pharmacological activities and has been found to significantly inhibit the fibrosis of keloid fibroblasts. DNA damage repair (DDR) is essential to prevent fibrosis. This study aimed to investigate the effects of harmine on pulmonary fibrosis and its underlying mechanisms. METHODS: Bleomycin and TGF-ß1 were used to construct pulmonary fibrosis models in vivo and in vitro, then treated with harmine to explore harmine's effects in treating experimental pulmonary fibrosis and its related mechanisms. Then, RNA sequencing was applied to investigate further the crucial DDR-related genes and drug targets of harmine against pulmonary fibrosis. Finally, the expression levels of DDR-related genes were verified by real-time quantitative PCR (RT-qPCR) and western blot. RESULTS: Our in vivo experiments showed that harmine treatment could improve weight loss and lung function and reduce tissue fibrosis in mice with pulmonary fibrosis. The results confirmed that harmine could inhibit the viability and migration of TGF-ß1-induced MRC-5 cells, induce their apoptosis, and suppress the F-actin expression, suggesting that harmine could suppress the phenotypic transition from lung fibroblasts to lung myoblasts. In addition, RNA sequencing identified 1692 differential expressed genes (DEGs), and 10 DDR-related genes were screened as critical DDR-related genes. RT-qPCR and western blotting showed that harmine could down-regulate the expression of CHEK1, ERCC1, ERCC4, POLD1, RAD51, RPA1, TOP1, and TP53, while up-regulate FEN1, H2AX and GADD45α expression. CONCLUSIONS: Harmine may inhibit pulmonary fibrosis by regulating DDR-related genes and activating the TP53-Gadd45α pathway.
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Bleomicina , Proteínas de Ciclo Celular , Dano ao DNA , Reparo do DNA , Fibroblastos , Harmina , Fibrose Pulmonar , Transdução de Sinais , Proteína Supressora de Tumor p53 , Animais , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Humanos , Harmina/farmacologia , Harmina/uso terapêutico , Camundongos , Reparo do DNA/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Linhagem Celular , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Masculino , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologia , Proteínas GADD45RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.
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Medicamentos de Ervas Chinesas , Metabolômica , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Masculino , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR alfa/metabolismo , PPAR alfa/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Análise de Sequência de RNA , Linhagem Celular , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismoRESUMO
Transition metal chalcogenides (TMCs) emerge as promising anode materials for sodium-ion batteries (SIBs), heralding a new era of energy storage solutions. Despite their potential, the mechanisms underlying their performance enhancement and susceptibility to failure in ether-based electrolytes remain elusive. This study delves into these aspects, employing CoS2 electrodes as a case in point to elucidate the phenomena. The investigation reveals that CoS2 undergoes a unique irreversible and progressive solid-liquid-solid phase transition from its native state to sodium polysulfides (NaPSs), and ultimately to a Cu1.8S/Co composite, accompanied by a gradual morphological transformation from microspheres to a stable 3D porous architecture. This reconstructed 3D porous structure is pivotal for its exceptional Na+ diffusion kinetics and resilience to cycling-induced stress, being the main reason for ultrastable cycling and ultrahigh rate capability. Nonetheless, the CoS2 electrode suffers from an inevitable cycle life termination due to the microshort-circuit induced by Na metal corrosion and separator degradation. Through a comparative analysis of various TMCs, a predictive framework linking electrode longevity is established to electrode potential and Gibbs free energy. Finally, the cell failure issue is significantly mitigated at a material level (graphene encapsulation) and cell level (polypropylene membrane incorporation) by alleviating the NaPSs shuttling and microshort-circuit.
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Recent studies have uncovered that noncoding sequence variants may relate to Axenfeld-Rieger syndrome (ARS), a rare developmental anomaly with genetic heterogeneity. However, how these genomic regions are functionally and structurally associated with ARS is still unclear. In this study, we performed genome-wide linkage analysis and whole-genome sequencing in a Chinese family with ARS and identified a heterozygous deletion of about 570 kb (termed LOH-1) in the intergenic sequence between paired-like homeodomain transcription factor 2 (PITX2) and family with sequence similarity 241 member A. Knockout of LOH-1 homologous sequences caused ARS phenotypes in mice. RNA-Seq and real-time quantitative PCR revealed a significant reduction in Pitx2 gene expression in LOH-1-/- mice, while forkhead box C1 expression remained unchanged. ChIP-Seq and bioinformatics analysis identified a potential enhancer region (LOH-E1) within LOH-1. Deletion of LOH-E1 led to a substantial downregulation of the PITX2 gene. Mechanistically, we found a sequence (hg38 chr4:111,399,594-111,399,691) that is on LOH-E1 could regulate PITX2 by binding to RAD21, a critical component of the cohesin complex. Knockdown of RAD21 resulted in reduced PITX2 expression. Collectively, our findings indicate that a potential enhancer sequence that is within LOH-1 may regulate PITX2 expression remotely through cohesin-mediated loop domains, leading to ARS when absent.
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Segmento Anterior do Olho , Anormalidades do Olho , Oftalmopatias Hereditárias , Proteína Homeobox PITX2 , Proteínas de Homeodomínio , Fatores de Transcrição , Animais , Feminino , Humanos , Masculino , Camundongos , Segmento Anterior do Olho/anormalidades , Segmento Anterior do Olho/metabolismo , DNA Intergênico/genética , Elementos Facilitadores Genéticos/genética , Anormalidades do Olho/genética , Oftalmopatias Hereditárias/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos Knockout , Linhagem , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: This study aims to decipher the genetic basis governing yield components and quality attributes of peanuts, a critical aspect for advancing molecular breeding techniques. Integrating genotype re-sequencing and phenotypic evaluations of seven yield components and two grain quality traits across four distinct environments allowed for the execution of a genome-wide association study (GWAS). RESULTS: The nine phenotypic traits were all continuous and followed a normal distribution. The broad heritability ranged from 88.09 to 98.08%, and the genotype-environment interaction effects were all significant. There was a highly significant negative correlation between protein content (PC) and oil content (OC). The 10× genome re-sequencing of 199 peanut accessions yielded a total of 631,988 high-quality single nucleotide polymorphisms (SNPs), with 374 significant SNP loci identified in association with the nine traits of interest. Notably, 66 of these pertinent SNPs were detected in multiple environments, and 48 of them were linked to multiple traits of interest. Five loci situated on chromosome 16 (Chr16) exhibited pleiotropic effects on yield traits, accounting for 17.64-32.61% of the observed phenotypic variation. Two loci on Chr08 were found to be strongly associated with protein and oil contents, accounting for 12.86% and 14.06% of their respective phenotypic variations, respectively. Linkage disequilibrium (LD) block analysis of these seven loci unraveled five nonsynonymous variants, leading to the identification of one yield-related candidate gene and two quality-related candidate genes. The correlation between phenotypic variation and SNP loci in these candidate genes was validated by Kompetitive allele-specific PCR (KASP) marker analysis. CONCLUSIONS: Overall, molecular markers were developed for genetic loci associated with yield and quality traits through a GWAS investigation of 199 peanut accessions across four distinct environments. These molecular tools can aid in the development of desirable peanut germplasm with an equilibrium of yield and quality through marker-assisted breeding.
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Arachis , Estudo de Associação Genômica Ampla , Arachis/genética , Locos de Características Quantitativas/genética , Melhoramento Vegetal , Mapeamento Cromossômico/métodos , Fenótipo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Detecting road cracks is essential for inspecting and assessing the integrity of concrete pavement structures. Traditional image-based methods often require complex preprocessing to extract crack features, making them challenging when dealing with noisy concrete surfaces in diverse real-world scenarios, such as autonomous vehicle road detection. This study introduces an image-based crack detection approach that combines a Random Forest machine learning classifier with a deep convolutional neural network (CNN) to address these challenges. Three state-of-the-art models, namely MobileNet, InceptionV3, and Xception, were employed and trained using a dataset of 30,000 images to build an effective CNN. A systematic comparison of validation accuracy across various base learning rates identified a base learning rate of 0.001 as optimal, achieving a maximum validation accuracy of 99.97%. This optimal learning rate was then applied in the subsequent testing phase. The robustness and flexibility of the trained models were evaluated using 6,000 test photos, each with a resolution of 224 × 224 pixels, which were not part of the training or validation sets. The outstanding results, boasting a remarkable 99.95% accuracy, 99.95% precision, 99.94% recall, and a matching 99.94% F1 Score, unequivocally affirm the efficacy of the proposed technique in precisely identifying road fractures in photographs taken on real concrete surfaces.
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Sodium-ion batteries (SIBs) are a promising electrochemical energy storage system; however, their practical application is hindered by the sluggish kinetics and interfacial instability of anode-active materials. Here, to circumvent these issues, we proposed the multiscale interface engineering of S-doped TiO2 electrodes with minor sulfur/carbon inlaying (S/C@sTiO2), where the electrode-electrolyte interface (SEI) and electrode-current collector interface (ECI) are tuned to improve the Na-storage performance. It is found that the S dopant greatly promotes the Na+ diffusion kinetics. Moreover, the ether electrolyte generates much less NaF in the cycled electrode, but relatively richer NaF in the SEI in comparison to fluoroethylene carbonate-contained ester electrolyte, leading to a thin (9 nm), stable, and kinetically favorable SEI film. More importantly, the minor sodium polysulfide intermediates chemically interact with the Cu current collector to form a Cu2S interface between the electrode and the Cu foil. The conductive tree root-like Cu2S ECI serves not only as active sites to boost the specific capacity but also as a 3D "second current collector" to reinforce the electrode and improve the Na+ reaction kinetics. The synergy of S-doping and optimized SEI and ECI realizes large specific capacity (464.4 mAh g-1 at 0.1 A g-1), ultrahigh rate capability (305.8 mAh g-1 at 50 A g-1), and ultrastable cycling performance (91.5% capacity retention after 3000 cycles at 5 A g-1). To the best of our knowledge, the overall SIB performances of S/C@sTiO2 are the best among all of the TiO2-based electrodes.
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Storage capacity, average open circuit voltage (OCV), diffusion barrier, lattice parameter changes, etc. are key indicators of whether a material would be suitable for use as a Li-ion or non-Li-ion battery (LIB or NLIB) anode. The rapid development of 2D materials over the past few decades has opened up new possibilities for these metrics. Using first-principles calculations, we prove that two 2D materials, TiB4 and SrB8, show excellent performance in terms of the above metrics when used as anodes for LIBs or NLIBs. As detailed, TiB4 has an Li\Na\K\Ca storage capacity of 588 mA h g-1, 588 mA h g-1, 588 mA h g-1, and 1176 mA h g-1, respectively, and SrB8 has an Li\Na\K\Ca storage capacity of 308 mA h g-1, 308 mA h g-1, 462 mA h g-1, and 616 mA h g-1, respectively, and they show good electrical conductivity whether existing Li, Na, K or Ca is adsorbed or not. The diffusion barriers on both surfaces are low, indicating good rate performance. The average OCV is also very low. In particular, the lattice parameters of the two materials change very little during the embedding of Li\Na\K\Ca. For Ti9B36 the corresponding values are about 0.37% (Li), 0.33% (Na), 0.64% (K) and 0.03% (Ca), and for Sr8B64 the corresponding values are about 0.70% (Li), 0.16% (Na), 0.13% (K) and 0.004% (Ca), which imply zero strain-like character and great cycling performance. All the above results show that TiB4 and SrB8 monolayers are very promising Li\Na\K\Ca ion battery anodes.
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Ischemic stroke (IS) can cause severe harm, inducing oxidative stress, inflammation, and pyroptotic death. IS treatment efficacy remains limited, and microglia are important regulators of IS-related blood-brain barrier (BBB) damage. It is thus vital that new therapeutic agents capable of targeting microglia be identified to treat IS-related damage to the BBB. Acteoside (ACT), which is a compound derived from Cistanche tubulosa (Schenk) Wight., offers promising bioactivity, but its ability to protect against central nervous system injury remains to be documented. To clarify the protective benefits and mechanisms through which ACT can protect against damage to the BBB, a rat middle cerebral artery occlusion (MCAO) model system was herein employed. These in vivo analyses demonstrated that ACT was able to significantly reduce cerebral infarct size while improving their neurological scores and altering neurotrophic and inflammatory factor release. RNA sequencing and molecular docking studies highlighted the ability of ACT to exert its protective benefits via the HMGB1/TLR4/NLRP3 axis. Western immunoblotting and immunofluorescent staining for tight junction proteins additionally confirmed the ability of ACT to preserve BBB integrity. The underlying mechanisms were then explored with an oxygen-glucose deprivation (OGD) model in vitro with BV2 cells. This strategy thus confirmed that the ability of ACT to suppress microglial inflammatory and pyroptotic activity was HMGB1/TLR4/NLRP3 pathway-dependent. These data thus offer novel evidence that ACT can protect against IS-related damage to the BBB through the abrogation of inflammatory and pyroptotic activity, underscoring its promise as a novel lead compound for the therapeutic treatment of IS.
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Isquemia Encefálica , Glucosídeos , Proteína HMGB1 , AVC Isquêmico , Polifenóis , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Ratos , Animais , Barreira Hematoencefálica/metabolismo , Microglia/metabolismo , Receptor 4 Toll-Like/metabolismo , AVC Isquêmico/tratamento farmacológico , Proteína HMGB1/metabolismo , Simulação de Acoplamento Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Nonalcoholic steatohepatitis (NASH) is emerging as the primary driver of liver diseaseinduced fibrosis. The imperative need for noninvasive biomarkers to ascertain disease progression stage is evident. The present study elucidated the biological roles of hub genes that could potentially serve as diagnostic markers for NASH. Using an in vivo approach, C57BL/6J mice were subjected to a highfat and fructose diet (HFFD) for 6, 10, 14, 18 or 22 weeks. Serological biochemical indices were assessed and liver specimens were obtained to identify potential markers linked to the NASH process, employing a comprehensive strategy that combined transcriptomic and histopathological analyses. The HFFD regimen induced hyperlipidemia, obesity and insulin resistance, progressively culminating in NASH with fibrosis over time. The transcriptomic analyses indicated temporal patterns of pivotal gene sets intricately connected to NASH progression, which encompassed processes such as glucose homeostasis, inflammatory responses, reactive oxygen speciesmediated damage, lipid metabolism disruptions and the formation of fibrotic tissue. Among these genes, Serpine1 and Mmp9 demonstrated promising diagnostic potential for NASH, with their intrahepatic mRNA expression levels serving as robust indicators. Moreover, the levels of PAI1 (encoded by the Serpine1 gene) and MMP9 in the serum of mice demonstrated a parallel increase with the duration of HFFD intervention. In vitro experiments utilizing HepG2 cells further validated these findings, demonstrating a significant elevation in the protein expression levels of both PAI1 and MMP9 upon exposure to free fatty acids, in agreement with the results of the animal study. Consequently, PAI1 and MMP9 are promising noninvasive biomarkers for assessing the progression of NASH.
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Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transcriptoma , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Fibrose , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de DoençasRESUMO
Background: This study aims to examine the relationship between anxiety and depression and dyadic coping in infertile couples, exploring gender differences and dyadic interactions in these associations. Methods: A cross-sectional study was conducted involving 288 couples recruited from the First Affiliated Hospital of Lanzhou University between November 2021 and November 2022. The Dyadic Coping Scale, Anxiety Scale, and Depression Scale were utilized to measure dyadic coping, anxiety, and depression, respectively. The Actor-Partner Interdependence Model was used to analyze the actor effect and partner effect. Results: Wives exhibited significantly higher anxiety and depression scores compared to husbands (p<0.001). No statistically significant difference was found in dyadic coping between wives and husbands. Positive dyadic coping in infertile couples had significant actor effects on anxiety and depression (p<0.05) and partner effects (p<0.05). Positive dyadic coping negatively predicted anxiety and depression of oneself and one's partner. Negative dyadic coping in infertile couples also had significant actor effects on anxiety and depression (p<0.05) and partner effects (p<0.05). Negative dyadic coping positively predicted anxiety and depression of oneself and one's partner. Conclusion: The dyadic coping style of infertile couples has both actor and partner effects on their own and their partner's anxiety and depression. Anxiety and depression in infertile couples are influenced by their own and their partner's dyadic coping style, respectively. Therefore, dyadic coping serves as an important indicator for predicting psychological outcomes in these couples.
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Novel two-dimensional (2D) electrode materials have become a new frontier for mining electrode materials for Li-ion batteries (LIBs) and Na-ion batteries (NIBs). Herein, based on first-principles calculations, we present a systematic study on the Li and Na storage behaviors in Calypso-predicted completely flat 2D boron oxide (l-B2O) with large mesh pores. We start our calculations from geometrical optimization, followed by a performance evaluation of Li/Na adsorption and migration processes. Finally, the specific capacity and average open-circuit voltage are evaluated. Our study reveals that l-B2O has good electrical conductivity before and after Li/Na adsorption and the Li/Na diffusion barrier height and average open-circuit voltage are both low, which is beneficial to the rate performance and full-cell operation voltage, respectively. Furthermore, it suffers a small lattice change (<1.7%), ensuring good cycling performance. In particular, we find that the Li and Na theoretical specific capacities of l-B2O can reach up to 1068.5 mA h g-1 and 712.3 mA h g-1, respectively, which are almost 2-3 times higher than graphite (372 mA h g-1). All the above outcomes indicate that 2D l-B2O is a promising anode material for LIBs and NIBs.
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This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 µg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.
Assuntos
Cistanche , Medicamentos de Ervas Chinesas , Neoplasias , Animais , Camundongos , Farmacologia em Rede , Proteína Beclina-1 , Espécies Reativas de Oxigênio , Extratos Vegetais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Medicina Tradicional Chinesa , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) has both high morbidity and mortality. Previous research conducted by our group demonstrated that the bioactive ingredients of the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) have various pharmacological effects in treating nervous system diseases. However, the effect of CT on the blood-brain barrier (BBB) after IS are still unknown. AIM OF THE STUDY: This study aimed to identify CT's curative effect on IS and explore its underlying mechanism. MATERIALS AND METHODS: IS injury was established in a rat model of middle cerebral artery occlusion (MCAO). Gavage administration of CT at dosages of 50, 100, and 200 mg/kg/day was carried out for seven consecutive days. Network pharmacology was used for predicting the pathways and potential targets of CT against IS, and subsequent studies confirmed the relevant targets. RESULTS: According to the results, both neurological dysfunction and BBB disruption were exacerbated in the MCAO group. Moreover, CT improved BBB integrity and neurological function and protected against cerebral ischemia injury. Network pharmacology revealed that IS might involve neuroinflammation mediated by microglia. Extensive follow-up studies verified that MCAO caused IS by stimulating the production of inflammatory factors and microglial infiltration. CT was found to influence neuroinflammation via microglial M1-M2 polarization. CONCLUSION: These findings suggested that CT may regulate microglia-mediated neuroinflammation by reducing MCAO-induced IS. The results provide theoretical and experimental evidence for the efficacy of CT therapy and novel concepts for the prevention and treatment of cerebral ischemic injuries.
Assuntos
Lesões Encefálicas , Isquemia Encefálica , Cistanche , AVC Isquêmico , Ratos , Animais , Microglia , Barreira Hematoencefálica , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , Doenças Neuroinflamatórias , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Lesões Encefálicas/metabolismoRESUMO
Cognitive impairment is the main central nervous system complication of diabetes, affecting the quality of life of patients. Herba Cistanche is a homologous plant widely used as a health food and therapeutic drug. Verbascoside, a signature component of Herba Cistanche, has anti-diabetic and neuroprotective effects. However, it is quickly metabolized by the gut microbiota, and the mechanism of its neuroprotection and improvement of learning and memory remains unclear. We investigated the effectiveness and potential mechanisms of verbascoside on cognitive dysfunction in db/db mice using a 16S rRNA microbiome and serum metabolomics approach. We found that 12-week treatment with verbascoside significantly inhibited insulin resistance, reduced blood glucose and lipids, and improved cognitive deficits. In addition, verbascoside increased the gut microbiota diversity, improved intestinal dysbiosis, attenuated intestinal barrier disruption, reduced the levels of inflammatory factors, regulated the expression of the metabolites associated with cognitive function, and enhanced the central insulin sensitivity and hippocampal synaptogenesis signaling. We revealed that verbascoside induced the enrichment of Alistipes, Roseburia, and Intestinimonas in the gut, suppressed the abundance of Escherichia-Shigella, increased the serum levels of gamma-aminobutyric acid, L-glutamic acid, and L-lysine, and decreased taurine expression. Finally, a strong association between gut microbes, serum metabolites, and cognitive performance affected by verbascoside was observed. Our research suggests that alterations in gut microbes/metabolites are involved in the development of diabetic cognitive dysfunction, which is alleviated by verbascoside in the db/db mice through restructuring the gut microbiota composition, ameliorating diabetic metabolic disorders, and attenuating pathological brain damage.
Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Resistência à Insulina , Camundongos , Animais , RNA Ribossômico 16S , Qualidade de Vida , Disfunção Cognitiva/tratamento farmacológicoRESUMO
BACKGROUND: Neuroglia are important modulators of neuronal functionality, and thus play an integral role in the pathogenesis and treatment of neuropathic pain (NP). According to traditional Chinese medicine, Frankincense-Myrrh is capable of "activating blood and dissipating blood stasis", and as such these two biological compounds are commonly used to treat NP, however, the mechanisms underlying the efficacy of such treatment are unclear. PURPOSE: This study aimed to further elucidate the protective effects associated with the Frankincense-Myrrh treatment of NP. METHODS: A chronic sciatic nerve compression injury (CCI) model of NP was established, after which animals were gavaged with Frankincense, Myrrh, Frankincense-Myrrh, or the positive control drug pregabalin for 14 days. Network pharmacology approaches were used to identify putative pathways and targets associated with the Frankincense-Myrrh-mediated treatment of NP, after which these targets were subjected to in-depth analyses. The impact of TLR4 blockade on NP pathogenesis was assessed by intrathecally administering a TLR4 antagonist (LRU) or the MyD88 homodimerization inhibitory peptide (MIP). RESULTS: Significant alleviation of thermal and mechanical hypersensitivity in response to Frankincense and Myrrh treatment was observed in NP model mice, while network pharmacology analyses suggested that the pathogenesis of NP may be related to TLR4/MyD88-mediated neuroinflammation. Consistently, Frankincense-Myrrh treatment was found to reduce TLR4, MyD88, and p-p65 expression in spinal dorsal horn neuroglia from treated animals, in addition to inhibiting neuronal TRPV1 and inflammatory factor expression. Intrathecal LRU and MIP delivery were sufficient to alleviate thermal and mechanical hyperalgesia in these CCI model mice, with concomitant reductions in neuronal TRPV1 expression and neuroglial activation in the spinal dorsal horn. CONCLUSION: These data suggest that Frankincense-Myrrh treatment was sufficient to alleviate NP in part via inhibiting TLR4/MyD88 pathway and TRPV1 signaling activity. Blocking TLR4 and MyD88 activation may thus hold value as a means of treating NP.