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1.
Inorg Chem ; 63(37): 17215-17224, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39231309

RESUMEN

We report an investigation on the structures and chemical bonding in a series of di-lanthanum boron clusters, La2Bn- (n = 4-6), using photoelectron spectroscopy and theoretical calculations. Well-resolved photoelectron spectra are obtained and used to verify the global minima of the lanthanide boron clusters. The structures of La2B4- and La2B5- are found to consist of open B4 and B5 rings, respectively, around the La2 dimer equatorially. Theoretical evidence of La-La σ bonding is obtained in La2B4-, whereas the bonding in La2B5- is similar to that of an incomplete inverse sandwich without real La-La bonding. The global minimum of La2B6- is completely different, where one of the La atoms can be viewed as substituting a B atom of the B7 cluster due to the high electronic stability of the B73- borozene. The resulting lanthaborozene [LaB6]3- forms a half-sandwich structure with the second La atom, with evidence of La-La σ bonding. Lanthanide-lanthanide bonds are relatively rare in chemistry. The current work suggests that binary lanthanide boron clusters provide interesting systems to study lanthanide-lanthanide bonding.

2.
Front Pharmacol ; 15: 1457780, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239657

RESUMEN

Introduction: The prevalence of male infertility has been increasing globally, necessitating the search for safe and nontoxic active compounds to alleviate reproductive dysfunction. Although the precise mechanism remains unknown, Cynomorium songaricum Rupr. (CS) extract has protective effects on the reproductive system. The effect of C. songaricum Rupr. flavonoids (CSF) on reproductive injury and testicular mesenchymal stem cell viability in male mice and TM3 cells was investigated. Methods: We explored the possible association between these effects and the testosterone (T) synthesis pathway. Mice were administered cyclophosphamide to induce reproductive damage, followed by CSF administration. Body mass and organ index were recorded. Pathological changes in T and the epididymis were observed using hematoxylin-eosin staining. ELISA measured the serum levels of T, luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and estradiol (E2) in mice. Fructose and zinc ion levels in the seminal plasma were measured. TM3 cells were treated with Bisphenol A (BPA) and different concentrations of CSF, followed by proliferative evaluations using the CCK-8 assay and T and LH level assessments using ELISA. Furthermore, the expression of steroidogenic enzyme genes and proteins was investigated using western blotting and RT-PCR. Results: CSF exhibited a notable reduction in reproductive damage and improved pathological changes in testicular and epididymal tissues. CSF group demonstrated substantially higher levels of seminal plasma fructose and zinc ions; markedly elevated serum levels of T, LH, GnRH, and FSH; and lower levels of E2 than those of the model group. Intracellular T content and secretion of T and LH increase with CSF while effectively mitigating BPA-induced damage to TM3 cells. CSF group exhibited substantially higher gene and protein expression of steroidogenic enzymes than those of the model group, both in vivo and in vitro. CSF ameliorates reproductive impairment by enhancing the expression of pivotal enzymes involved in synthesizing T. Discussion: CSF ameliorates cyclophosphamide-induced reproductive impairment and bisphenol A-induced TM3 cell damage in mice by regulating sex hormone levels in the Hypothalamic-Pituitary-Gonadal Axis (HPG axis) and upregulating the expression of steroidogenic enzymes. Therefore, CS is a potential treatment for male reproductive impairment.

3.
J Photochem Photobiol B ; 260: 113020, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39244873

RESUMEN

While solar ultraviolet radiation (UVR) is known to impact zooplankton, little has been documented on its impacts under elevated pCO2. Here, we show that exposure to UVR decreased the feeding and survival rates of the copepod Acartia spinicauda, that artificial UV-B of 2.25 W·m-2 for 4 h resulted in a 52 % inhibition of its grazing rates and a 45 % reduction in survival rates compared to visible light alone. On the other hand, an increase in pCO2 to 1000 µatm (pH drop of 0.4) immediately and significantly increased the UVR-induced inhibition of feeding. Subsequently, the combination of the high pCO2 (1000 µatm) and UVR resulted in about 65 % lethal impact, with UV-A contributing 21 % and UV-B 44 % compared to the visible light alone and ambient pCO2 conditions. While the copepod was shown to be able to sense and escape from UV-exposed areas, these findings suggest that UVR impacts on the copepod can be exacerbated with progressive ocean acidification or in high CO2 waters, including upwelled regions.

4.
Biomolecules ; 14(8)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39199295

RESUMEN

Due to the limited supply of autologous bone grafts, there is a need to develop more bone matrix materials to repair bone defects. Xenograft bone is expected to be used for clinical treatment due to its exact structural similarity to natural bone and its high biocompatibility. In this study, decellularized antler cancellous bone matrix (DACB) was first prepared, and then the extent of decellularization of DACB was verified by histological staining, which demonstrated that it retained the extracellular matrix (ECM). The bioactivity of DACB was assessed using C3H10T1/2 cells, revealing that DACB enhanced cell proliferation and facilitated cell adhesion and osteogenic differentiation. When evaluated by implanting DACB into nude mice, there were no signs of necrosis or inflammation in the epidermal tissues. The bone repair effect of DACB was verified in vivo using sika deer during the antler growth period as an animal model, and the molecular mechanisms of bone repair were further evaluated by transcriptomic analysis of the regenerated tissues. Our findings suggest that the low immunogenicity of DACB enhances the production of bone extracellular matrix components, leading to effective osseointegration between bone and DACB. This study provides a new reference for solving bone defects.


Asunto(s)
Cuernos de Venado , Hueso Esponjoso , Ciervos , Ratones Desnudos , Osteogénesis , Andamios del Tejido , Animales , Cuernos de Venado/química , Andamios del Tejido/química , Ratones , Proliferación Celular , Diferenciación Celular , Matriz Extracelular Descelularizada/química , Ingeniería de Tejidos/métodos , Matriz Extracelular/metabolismo , Regeneración Ósea , Línea Celular , Adhesión Celular
5.
J Sci Food Agric ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189446

RESUMEN

BACKGROUND: Deer oil (DO), a byproduct of deer meat processing, possesses high nutritional value. This study aims to evaluate the protective effects of DO on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and to explore its potential mechanisms of action. RESULTS: DO was found to inhibit weight loss and colon shortening in colitis mice, significantly reduce disease activity index scores, and notably enhance the levels of tight junction proteins in colon tissues, thus improving intestinal barrier function. ELISA results indicated that DO markedly alleviated the mice's oxidative stress and inflammatory responses. Western blot analysis further demonstrated that DO significantly inhibited the phosphorylation of NF-κB while up-regulating the expression levels of Nrf2 and HO-1 proteins. Additionally, DO increased the abundance of beneficial bacteria such as Odoribacter, Blautia, and Muribaculum, reduced the abundance of harmful bacteria such as Bacteroides, Helicobacter, and Escherichia-Shigella, and promoted the production of short-chain fatty acids. CONCLUSION: Our study provides the first evidence that DO can effectively improve DSS-induced UC in mice. The underlying mechanisms may involve maintaining intestinal barrier function, inhibiting inflammation, alleviating oxidative stress, and modulation of gut microbiota. These findings offer valuable insights for developing DO as an adjunct treatment for UC and as a functional food. © 2024 Society of Chemical Industry.

6.
Nutrients ; 16(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39203724

RESUMEN

The by-product of deer skin, which has mostly been used as a decorative material, is rich in collagen and amino acids that could bind to Ca2+. Therefore, the preparation process, stability, antioxidant activity and calcium transport capacity of deer skin collagen peptide calcium chelate (Ca-DSCP) were investigated. In addition, the structure of the new chelate was characterized. The preparation process of Ca-DSCP was optimized using one-way experiments and response surface methodology. The ideal conditions were pH 9, 48 °C, and a peptide-to-calcium mass ratio of 5:1. The chelation rate was (60.73 ± 1.54)%. Zeta potential, XRD, UV-vis and FTIR analyses yielded that deer skin collagen peptides (DSCP) underwent a chelating reaction with calcium ions to form new structures. The stability of Ca-DSCP and the fraction of bioavailability of calcium ions were determined using in vitro gastrointestinal digestion and a Caco-2 cell monolayer model. The results showed that fraction of bioavailability and stability of DSCP were improved by influencing the structural characterization. The antioxidant activities of DSCP and Ca-DSCP were evaluated by measuring relevant oxidative stress indicators, DPPH radical scavenging capacity and hydroxyl radical scavenging capacity. Finally, bioinformatics and molecular docking techniques were utilized to screen and study the antioxidant mechanism of DSCP.


Asunto(s)
Antioxidantes , Calcio , Colágeno , Ciervos , Digestión , Péptidos , Piel , Animales , Humanos , Antioxidantes/farmacología , Células CACO-2 , Colágeno/metabolismo , Calcio/metabolismo , Péptidos/farmacología , Péptidos/química , Piel/metabolismo , Simulación del Acoplamiento Molecular , Disponibilidad Biológica , Tracto Gastrointestinal/metabolismo , Quelantes/farmacología
7.
Int Immunopharmacol ; 140: 112812, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39094360

RESUMEN

Diabetic nephropathy (DN) is one of the leading clinical causes of end-stage renal failure. The classical aldose reductase (AR) inhibitor epalrestat shows beneficial effect on renal dysfunction induced by DN, with metabolic profile and molecular mechanisms remains to be investigated further. In the current study, integrated untargeted metabolomics, network pharmacology and molecular dynamics approaches were applied to explore the therapeutic mechanisms of epalrestat against DN. Firstly, untargeted serum and urine metabolomics analysis based on UPLC-Q-TOF-MS was performed, revealed that epalrestat could regulate the metabolic disorders of amino acids metabolism, arachidonic acid metabolism, pyrimidine metabolism and citrate cycle metabolism pathways after DN. Subsequently, metabolomics-based network analysis was carried out to predict potential active targets of epalrestat, mainly involving AGE-RAGE signaling pathway, TNF signaling pathway and HIF-1 signaling pathway. Moreover, a 100 ns molecular dynamics approach was employed to validate the interactions between epalrestat and the core targets, showing that epalrestat could form remarkable tight binding with GLUT1 and NFκB than it with AR. Surface-plasmon resonance assay further verified epalrestat could bind GLUT1 and NFκB proteins specifically. Overall, integrated system network analysis not only demonstrated that epalrestat could attenuate DN induced metabolic disorders and renal injuries, but also revealed that it could interact with multi-targets to play a synergistic regulatory role in the treatment of DN.


Asunto(s)
Nefropatías Diabéticas , Metabolómica , Simulación de Dinámica Molecular , Rodanina , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Animales , Masculino , Rodanina/análogos & derivados , Rodanina/uso terapéutico , Rodanina/farmacología , Tiazolidinas/farmacología , Tiazolidinas/uso terapéutico , Humanos , Aldehído Reductasa/metabolismo , Aldehído Reductasa/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Transportador de Glucosa de Tipo 1/metabolismo , FN-kappa B/metabolismo , Farmacología en Red , Ratas
8.
Neuropharmacology ; 260: 110129, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39179173

RESUMEN

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants.


Asunto(s)
Depresión , Sistema Hipotálamo-Hipofisario , Ratones Endogámicos C57BL , MicroARNs , Núcleo Hipotalámico Paraventricular , Sistema Hipófiso-Suprarrenal , Estrés Psicológico , Animales , MicroARNs/metabolismo , MicroARNs/genética , Núcleo Hipotalámico Paraventricular/metabolismo , Masculino , Ratones , Sistema Hipotálamo-Hipofisario/metabolismo , Depresión/metabolismo , Depresión/genética , Sistema Hipófiso-Suprarrenal/metabolismo , Estrés Psicológico/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Derrota Social
9.
Anal Chem ; 96(36): 14490-14498, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39185815

RESUMEN

Bacterial infections have emerged as a significant contributor to global mortality and morbidity rates. Herein, we introduce a dual fluorescence "turn-on" supramolecular sensor array composed of three assembled complexes (C1-C3), formed from three positively charged fluorophores (A1-A3) and one cucurbit[7]uril (CB[7]). The ability of this three-element array to simultaneously recognize 10 bacterial species within just 30 s was remarkable, boasting an impressive 100% accuracy. Additionally, the array excelled at distinguishing among various bacterial mixtures and enabled the quantitative detection of common bacterial strains. Notably, it has been skillfully applied to differentiate 10 bacterial samples in urine, achieving excellent differentiation and showcasing promising potential for medical diagnostic applications.


Asunto(s)
Hidrocarburos Aromáticos con Puentes , Colorantes Fluorescentes , Imidazoles , Imidazoles/química , Hidrocarburos Aromáticos con Puentes/química , Colorantes Fluorescentes/química , Bacterias/aislamiento & purificación , Humanos , Espectrometría de Fluorescencia , Compuestos Heterocíclicos con 2 Anillos , Compuestos Macrocíclicos , Imidazolidinas
10.
Int J Biol Macromol ; 276(Pt 2): 133925, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032904

RESUMEN

Phytopolysaccharides are a class of natural macromolecules with a range of biological activities. Ginseng, red ginseng, American ginseng, and Panax notoginseng are all members of the Araliaceae family. They are known to contain a variety of medicinal properties and are typically rich in a wide range of medicinal values. Polysaccharides represent is one of the principal active ingredients in the aforementioned plants. However, there is a paucity of detailed reports on the separation methods, structural characteristics and comparison of various pharmacological effects of these polysaccharides. This paper presents a review of the latest research reports on ginseng, red ginseng, American ginseng and ginseng polysaccharides. The differences in extraction, separation, purification, structural characterization, and pharmacological activities of the four polysaccharides are compared and clarified. Upon examination of the current research literature, it becomes evident that the extraction and separation processes of the four polysaccharides are highly similar. Modern pharmacological studies have corroborated the multiple biological activities of these polysaccharides. These activities encompass a range of beneficial effects, including antioxidant stress injury, fatigue reduction, tumor inhibition, depression alleviation, regulation of intestinal flora, immunomodulation, diabetes management, central nervous system protection, anti-aging, and improvement of skin health. This paper presents a review of studies on the extraction, purification, characterization, and bioactivities of four natural plant ginseng polysaccharides. Furthermore, the review presents the most recent research findings on their pharmacological activities. The information provides a theoretical basis for the future application of natural plant polysaccharides and offers a new perspective for the in-depth development of the medicinal value of ginseng in the clinical practice of traditional Chinese medicine.


Asunto(s)
Panax , Polisacáridos , Panax/química , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Humanos , Animales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación
11.
Med Sci Monit ; 30: e943955, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985697

RESUMEN

Deep vein thrombosis (DVT) of the lower extremities is divided into 2 categories according to the extent of thrombosis involvement. Thrombosis involving the popliteal vein, femoral vein, and iliac vein is classified as proximal DVT, while thrombosis involving the anterior tibial vein, posterior tibial vein, peroneal vein, and calf muscles vein is regarded as distal DVT. There are updated guidelines for the anticoagulant treatment for proximal DVT, but the best anticoagulant treatment for distal DVT is still controversial, especially for isolated calf muscular vein thrombosis (CMVT). The risk of isolated CMVT extending to the proximal deep veins and developing into pulmonary embolism is lower than with distal DVT. Some scholars believe that isolated CMVT has the risk of evolving into proximal deep vein thrombosis and pulmonary embolism, and active early anticoagulation therapy can reduce the risk and benefit patients. In addition, based on the characteristics of CMVT and the bleeding risk of anticoagulation therapy, some studies have recommended use of non-anticoagulation methods such as compression therapy. There is still a lack of multicenter, big-data, randomized, controlled trials on the benefits or risks of anticoagulation therapy. Among scholars who support anticoagulation therapy, there is still a lack of consensus on the optimal duration. This article reviews the current evidence on anticoagulant therapy for patients with isolated CMVT and how long the anticoagulation course should be if anticoagulation is required. Our research will provide a theoretical basis for subsequent research. More prospective studies with larger sample sizes are needed to provide more clinical evidence.


Asunto(s)
Anticoagulantes , Pierna , Trombosis de la Vena , Humanos , Anticoagulantes/uso terapéutico , Trombosis de la Vena/tratamiento farmacológico , Pierna/irrigación sanguínea , Músculo Esquelético/irrigación sanguínea , Embolia Pulmonar/tratamiento farmacológico
12.
Pharmacol Biochem Behav ; 242: 173820, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996926

RESUMEN

BACKGROUND: Emerging data has demonstrated that in mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Thus, it is possible that SorCS2 plays a role in the pathophysiology of depression by regulating the BDNF-TrkB system. METHODS: In the present study, SorCS2 expression in different brain regions [hippocampus, medial prefrontal cortex (mPFC), hypothalamus, amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc)] was thoroughly investigated in the chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression. The changes in depressive-like behaviors, the hippocampal BDNF signaling cascade, and amounts of hippocampal immature neurons were further investigated after SorCS2 overexpression by microinjection of the adenovirus associated virus vector containing the coding sequence of mouse SorCS2 (AAV-SorCS2) into the hippocampus of mice exposed to CSDS or CUMS. RESULTS: It was found that both CSDS and CUMS significantly decreased the protein and mRNA expression of SorCS2 in the hippocampus but not in other brain regions. Chronic stress also notably downregulated the level of hippocampal SorCS2-TrkB binding in mice. In contrast, AAV-based genetic overexpression of hippocampal SorCS2 fully reversed the chronic stress-induced not only depressive-like behaviors but also decreased SorCS2-TrkB binding, BDNF signaling pathway, and amounts of immature neurons in the hippocampus of mice. CONCLUSION: All these results suggest that enhancing the hippocampal SorCS2 expression protects against chronic stress, producing antidepressant-like actions. Hippocampal SorCS2 may participate in depression neurobiology and be a potential antidepressant target. SIGNIFICANCE STATEMENT: Targeting of proteins to distinct subcellular compartments is essential for neuronal activity and modulated by VPS10P domain receptors which include SorCS2. In mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Our study is the first direct evidence preliminarily showing that SorCS2 plays a role in depression neurobiology. It was found that chronic stress induced not only depressive-like behaviors but also decreased SorCS2 expression in the hippocampus. Chronic stress did not affect SorCS2 expression in the mPFC, hypothalamus, amygdala, VTA, or NAc. In contrast, genetic overexpression of hippocampal SorCS2 prevented against chronic stress, producing antidepressant-like actions in mice. Thus, hippocampal SorCS2 is a potential participant underlying depression neurobiology and may be a novel antidepressant target. Our study may also extend the knowledge of the neurotrophic hypothesis of depression.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Depresión , Hipocampo , Ratones Endogámicos C57BL , Receptor trkB , Estrés Psicológico , Animales , Masculino , Ratones , Conducta Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Depresión/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Neuronas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/genética , Receptor trkB/metabolismo , Transducción de Señal , Estrés Psicológico/metabolismo
13.
Biology (Basel) ; 13(7)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39056731

RESUMEN

The changing global climate has significantly impacted the spread of plant pests. The cassava mealybug (Phenacoccus manihoti) is among the most dangerous quarantine pests affecting cassavas worldwide, causing substantial losses in agricultural production and food security across several regions. Although China is currently free of the cassava mealybug, its proximity to affected countries and extensive trade with these regions necessitate a detailed understanding of the pest's distribution pattern and dynamic ecological niche changes. Using the Biomod2 model, we selected two historical climate scenarios and two future climate scenarios (SSP1-2.6 and SSP5-8.5) to investigate the distribution patterns, potential habitats, distribution centers, and dynamic ecological niches of cassava mealybugs in China. Key environmental variables influencing the distribution were identified, including bio4, bio8, bio12, bio18, and bio19. The potential habitat of cassava mealybugs is mainly located in several provinces in southern China. In the future, the suitable habitat is projected to expand slightly under the influence of climate change, maintaining the overall trend, but the distribution center of suitable areas will shift northward. Dynamic ecological niche prediction results indicate the potential for further expansion; however, the ecological niches may be unequal and dissimilar in the invaded areas. The predictions could serve as a valuable reference for early warning systems and management strategies to control the introduction of cassava mealybugs.

14.
Langmuir ; 40(28): 14291-14302, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38950193

RESUMEN

The key to enhancing water electrolysis efficiency lies in selecting highly efficient catalysts. Currently, high-entropy alloys (HEAs) are utilized in electrocatalysis applications owing to their diverse elemental composition, disordered elemental distribution, and the high solubility of each element, endowing them with excellent catalytic performance. The experiments were conducted using isoatomic FeNiCrMo HEA as a precursor, with a high-activity three-dimensional nanoporous structure rapidly synthesized via electrochemical one-step dealloying in a choline chloride-thiourea (ChCl-TU) deep eutectic solvent (DES). The results indicate that the dealloyed Fe20Co20Ni20Cr20Mo20 HEA mainly consists of two phases: face-centered cubic and σ phases. The imbalance in the distribution of elements in these two phases leads to quite different corrosion speeds with the FCC phase being preferentially corroded. Furthermore, synergistic electron coupling between surface atoms in the three-dimensional nanoporous structure strengthens the behavior of the oxygen evolution reaction (OER). At a current density of 40 mA cm-2, the overpotential after dealloying decreased to 370 mV, demonstrating excellent stability. The technique demonstrated in this work provides a novel approach to improve the catalytic activity of OER.

15.
Crit Care ; 28(1): 239, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004760

RESUMEN

BACKGROUND: The optimal administration of polymyxins for treating multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia remains unclear. This study aimed to systematically assess the efficacy and safety of three polymyxin-containing regimens by conducting a comprehensive network meta-analysis. METHODS: We comprehensively searched nine databases. Overall mortality was the primary outcome, whereas the secondary outcomes encompassed microbial eradication rate, clinical success, acute kidney injury, and incidence of bronchospasm. Extracted study data were analyzed by pairwise and network meta-analyses. Version 2 of the Cochrane risk-of-bias tool and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool were used to assess the risk of bias in randomized trials and cohort studies, respectively. RESULTS: This study included 19 observational studies and 3 randomized controlled trials (RCTs), encompassing 3318 patients. Six studies with high risk of bias were excluded from the primary analysis. In the pairwise meta-analysis, compared to the intravenous (IV) polymyxin-containing regimen, the intravenous plus inhaled (IV + IH) polymyxin-containing regimen showed a significant decrease in overall mortality, while no statistically significant difference was found in the inhaled (IH) polymyxin-containing regimen. The network meta-analysis indicated that the IV + IH polymyxin-containing regimen had significantly lower overall mortality (OR 0.67; 95% confidence interval [CI] 0.50-0.88), higher clinical success rate (OR 1.90; 95% CI 1.20-3.00), better microbial eradication rate (OR 2.70; 95% CI 1.90-3.90) than the IV polymyxin-containing regimen, and significantly better microbial eradication rate when compared with the IH polymyxin-containing regimen (OR 2.30; 95% CI 1.30-4.20). Furthermore, compared with IV + IH and IV polymyxin-containing regimens, the IH polymyxin-containing regimen showed a significant reduction in acute kidney injury. CONCLUSIONS: Our study indicates that among the three administration regimens, the IV + IH polymyxin-containing regimen may be the most effective for treating MDR-GNB pneumonia, with a significantly lower overall mortality compared to the IV regimen and a considerably higher microbial eradication rate compared to the IH regimen. The IH regimen may be considered superior to the IV regimen due to its substantially lower incidence of acute kidney injury, even though the reduction in overall mortality was not significant.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas , Polimixinas , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Metaanálisis en Red , Polimixinas/uso terapéutico , Polimixinas/administración & dosificación
16.
Int J Mol Sci ; 25(14)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39062817

RESUMEN

Depression is one of the most common psychological disorders nowadays. Studies have shown that 20(S)-protopanaxatriol (PPT) can effectively improve depressive symptoms in mice. However, its mechanism needs to be further explored. In this study, we used an integrated approach combining network pharmacology and transcriptomics to explore the potential mechanisms of PPT for depression. First, the potential targets and pathways of PPT treatment of depression were screened through network pharmacology. Secondly, the BMKCloud platform was used to obtain brain tissue transcription data of chronic unpredictable mild stress (CUMS) model mice and screen PPT-altered differential expression genes (DEGs). Gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using network pharmacology and transcriptomics. Finally, the above results were verified by molecular docking, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). In this study, we demonstrated that PPT improved depression-like behavior and brain histopathological changes in CUMS mice, downregulated nitric oxide (NO) and interleukin-6 (IL-6) levels, and elevated serum levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) after PPT treatment compared to the CUMS group. Eighty-seven potential targets and 350 DEGs were identified by network pharmacology and transcriptomics. Comprehensive analysis showed that transthyretin (TTR), klotho (KL), FOS, and the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway were closely associated with the therapeutic effects of PPT. Molecular docking results showed that PPT had a high affinity for PI3K, AKT, TTR, KL, and FOS targets. Gene and protein level results showed that PPT could increase the expression of PI3K, phosphorylation of PI3K (p-PI3K), AKT, phosphorylation of AKT (p-AKT), TTR, and KL and inhibit the expression level of FOS in the brain tissue of depressed mice. Our data suggest that PPT may achieve the treatment of depression by inhibiting the expression of FOS, enhancing the expression of TTR and KL, and modulating the PI3K-AKT signaling pathway.


Asunto(s)
Depresión , Farmacología en Red , Sapogeninas , Transcriptoma , Animales , Ratones , Depresión/tratamiento farmacológico , Depresión/metabolismo , Sapogeninas/farmacología , Transcriptoma/efectos de los fármacos , Masculino , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Simulación del Acoplamiento Molecular , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Perfilación de la Expresión Génica , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos
17.
Korean J Physiol Pharmacol ; 28(4): 361-377, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38926843

RESUMEN

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aß1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aß and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

18.
Chin J Nat Med ; 22(6): 515-529, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38906599

RESUMEN

Depression ranks among the most common neuropsychiatric disorders globally. Current studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin (PF) are sparse. This study aimed to elucidate PF's antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation (CUMS)-induced C57BL/6 mouse models in vivo and corticosterone (CORT)-induced HT22 cell models in vitro. Results demonstrated that PF enhanced the viability of HT22 cells following CORT exposure, restored mitochondrial membrane potential (MMP), reduced reactive oxygen species accumulation, increased LC3 fluorescence intensity, and suppressed inflammatory cytokine secretion and inflammation activation. Additionally, PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal neurons. It also reduced the expression of NLRP3, ASC, Caspase-1, IL-1ß, and the assembly of the NLRP3 inflammasome. Moreover, PF upregulated the expression of autophagy-related proteins in the hippocampus, facilitating the clearance of damaged mitochondria and enhancing autophagy. The role of autophagy in PF's antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine (3-MA), which reduced the efficacy of PF. In conclusion, PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro, likely via the induction of autophagy.


Asunto(s)
Autofagia , Depresión , Glucósidos , Inflamasomas , Ratones Endogámicos C57BL , Mitocondrias , Monoterpenos , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Glucósidos/farmacología , Autofagia/efectos de los fármacos , Monoterpenos/farmacología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Masculino , Depresión/tratamiento farmacológico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Especies Reactivas de Oxígeno/metabolismo
19.
BMC Complement Med Ther ; 24(1): 208, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816744

RESUMEN

BACKGROUND: Galangin, a flavonoid compound, is derived from Alpinia officinarum Hance. Previous studies have shown that galangin can inhibit the proliferation of hepatocellular carcinoma (HCC), but its mechanism is still unclear. This study aims to investigate the potential targets and molecular mechanisms of galangin on HCC through network pharmacology, bioinformatics, molecular docking, and experimental in vitro validation. METHODS: In this study, network pharmacology was used to investigate the targets and mechanisms of galangin in the treatment of HCC. AutoDockTools software was used to simulate and calculate the binding of galangin to its core targets. GO and KEGG enrichment analyses were conducted in the DAVID database to explore the main biological functions and signaling pathways impacted by galangin intervention. In addition, bioinformatics was applied to examine the correlation between the differential expressions of the anti-HCC core targets of galangin and the survival of patients with HCC. Finally, the findings obtained from network pharmacology and bioinformatics were verified in cell experiments. RESULTS: A total of 67 overlapping target genes of galangin and HCC were identified. Through the analysis of the protein-protein interaction (PPI) network, 10 hub genes with the highest degree of freedom were identified, including SRC, ESR1, MMP9, CDK4, CCNB1, MMP2, CDK2, CDK1, CHK1, and PLK1. These genes were found to be closely related to the degradation of the extracellular matrix, signal transduction, and the cell cycle. GO and KEGG enrichment analyses revealed that galangin exerts an anti-HCC role by affecting various signaling pathways, including the cell cycle, pathways in cancer, and the PI3K-Akt signaling pathway. The results of molecular docking indicated a significant interaction between galangin and CCNB1, CDK4, CDK1, and PLK1. Bioinformatics analysis revealed that CCNB1, CDK4, CDK1, and PLK1 were upregulated in the liver of patients with HCC at both the mRNA and protein levels. Flow cytometry analysis showed that galangin induced G0/G1 phase arrest and cell apoptosis in HepG2 and Huh7 cells. Additionally, galangin suppressed the expression of key proteins and mRNAs involved in the cell cycle pathway. CONCLUSIONS: These results suggest that galangin inhibits the growth of HCC cells by arresting the cell cycle at the G0/G1 phase.


Asunto(s)
Carcinoma Hepatocelular , Biología Computacional , Flavonoides , Neoplasias Hepáticas , Simulación del Acoplamiento Molecular , Farmacología en Red , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Flavonoides/farmacología , Flavonoides/química , Mapas de Interacción de Proteínas , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos
20.
BMC Geriatr ; 24(1): 331, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605326

RESUMEN

BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Pueblos del Este de Asia , Humanos , Anciano , Trastornos del Conocimiento/diagnóstico , Estudios Transversales , 8-Hidroxi-2'-Desoxicoguanosina , Longevidad , Envejecimiento/psicología , Factores de Riesgo , Cognición , Disfunción Cognitiva/epidemiología
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