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BACKGROUND: Prediabetes strongly increases the risk of type 2 diabetes and cardiovascular events. However, lifestyle intervention, the first-line treatment for prediabetes currently, was inconsistently beneficial for glucose metabolism, and the conventional medicines, such as metformin, is controversial for prediabetes due to the possible side effects. PURPOSE: This study was designed to evaluate the effects of Zhenyuan Capsule, a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng, on the glucose metabolism of prediabetic patients as a complementary therapy. STUDY DESIGN AND METHODS: In this randomized, double-Blinded, placebo-controlled, crossover trial, 195 participants with prediabetes were randomized 1:1 to receive either placebo followed by Zhenyuan Capsule, or vice versa, alongside lifestyle interventions. Each treatment period lasted 4 weeks with a 4-week washout period in between. The primary outcomes were the changes in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2-h PG) from baseline. Secondary outcomes includes the changes in fasting and 2-h postprandial insulin and C-peptide, the homeostatic model assessment-insulin resistance (HOMA-IR) index and quantitative insulin sensitivity check index (QUICKI) from baseline. Blood lipids and adverse events were also assessed. RESULTS: Compared with placebo, Zhenyuan Capsule caused remarkable reduction in 2-h PG (-0.98 mmol/l) after adjusting treatment order. Zhenyuan Capsule also reduced the fasting and 2-h postprandial levels of insulin and C-peptide, lowered HOMA-IR index (-1.26), and raised QUICKI index (+0.012) when compared to placebo. Additionally, a significant increase in high density lipoprotein cholesterol (HDL-C; +0.25 mmol/l) was found in patients with Zhenyuan Capsule. No serious adverse event occurred during the study. CONCLUSIONS: Among prediabetic patients, Zhenyuan Capsule further reduced 2-h PG level, alleviated insulin resistance and raised HDL-C level on the background of lifestyle interventions. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR2000034000).
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BACKGROUND: To test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event. METHODS: In this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event. RESULTS: We observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (ß=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (ß=-0.01, [95% CI: -0.01, -0.00], P = 0.0440). CONCLUSIONS: Dietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event.
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INTRODUCTION: Total ginsenosides (TG), the major active constituents of ginseng, have been proven to be beneficial in treatment of Alzheimer's disease (AD). However, the underlying mechanism of TG remains unclear. METHODS: APP/PS1 mice and N2a/APP695 cells were used as in vivo and in vitro model, respectively. Morris water maze (MWM) was used to investigate behavioral changes of mice; neuronal pathological changes were assessed by hematoxylin and eosin (H&E) and nissl staining; immunofluorescence staining was used to examine amyloid beta (Aß) deposition; Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of relative amyloidogenic genes and proteins. Moreover, the antagonist of PPARγ, GW9662, was used to determine whether the effects of TG on Aß production were associated with PPARγ activity. RESULTS: TG treatment increased the spatial learning and memory abilities of APP/PS1 mice while decreasing the Aß accumulation in the cortex and hippocampus. In N2a/APP695 cells, TG treatment attenuated the secretion of Aß1-40 and Aß1-42 acting as an PPARγ agonist by inhibiting the translocation of NF-κB p65. Additionally, TG treatment also decreased the expression of amyloidogenic pathway related gene BACE1, PS1 and PS2. CONCLUSIONS: TG treatment reduced the production of Aß both in vivo and in vitro. Activating PPARγ might be a potential therapeutic target of TG in facilitating Aß clearance and ameliorating cognitive deficiency in APP/PS1 mice.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Ginsenósidos , PPAR gamma , Animales , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ginsenósidos/farmacología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Transgénicos , Fragmentos de Péptidos/metabolismo , PPAR gamma/efectos de los fármacos , PPAR gamma/metabolismo , Presenilina-1/genéticaRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, cognitive disorder, language dysfunction, and mental disability. The main neuropathological changes in AD mainly include amyloid plaque deposition, neurofibrillary tangles, synapse loss, and neuron reduction. However, the current anti-AD drugs do not demonstrate a favorable effect in altering the pathological course of AD. Moreover, long-term use of these drugs is usually accompanied with various side effects. Ginsenosides are the major active constituents of ginseng and have protective effects on AD through various mechanisms in both in vivo and in vitro studies. In this review, we focused on discussing the therapeutic potential effects and the mechanisms of pharmacological activities of ginsenosides in AD, to provide new insight for further research and clinical application of ginsenosides in the future. Recent studies on the pharmacological effects and mechanisms of ginsenosides were retrieved from Chinese National Knowledge Infrastructure, National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and the Web of Science database up to April 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were used to predict the therapeutic effects and mechanisms of ginsenosides against AD. Ginsenosides presented a wide range of therapeutic and biological activities, including alleviating Aß deposition, decreasing tau hyperphosphorylation, regulating the cholinergic system, resisting oxidative stress, modulating Ca2+ homeostasis, as well as anti-inflammation and anti-apoptosis in neurons, respectively. For further developing the therapeutic potential as well as clinical applications, the network pharmacology approach was combined with a summary of published studies.
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High glucose inhibits oral keratinocyte proliferation. Diabetes can lead to delayed oral wound healing and periodontal disease. L-Arginine, one of the most versatile amino acids, plays an important role in wound healing, organ maturation, and development. In this study, L-Arginine was found to enhance oral keratinocyte proliferation under high-glucose conditions. RNA sequencing analysis discovered a significant number of genes differentially upregulated following L-Arginine treatment under high-glucose conditions. Cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was the most significantly upregulated gene at 24 and 48 h after L-Arginine treatment. Gene Ontology enrichment analysis found that cell proliferation- and mitosis-related biological processes, such as mitotic nuclear division, mRNA processing, and positive regulation of cell cycle processes, were significantly upregulated. Pathway enrichment analysis found that S-phase kinase-associated protein 2 (SKP2) and serine- and arginine-rich splicing factor 5 (SRSF5) were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of CYP1A1, SKP2, and SRSF5 after L-Arginine treatment. Knockdown of CYP1A1, SKP2, and SRSF5 abolished the enhanced proliferative effect of L-Arginine on oral keratinocytes under high-glucose conditions. In conclusion, L-Arginine enhances oral keratinocyte proliferation under high-glucose conditions via upregulation of CYP1A1, SKP2, and SRSF5, suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration.
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Citocromo P-450 CYP1A1 , Proteínas Quinasas Asociadas a Fase-S , Regulación hacia Arriba , Proteínas Quinasas Asociadas a Fase-S/genética , Citocromo P-450 CYP1A1/metabolismo , Proliferación Celular , Queratinocitos/metabolismo , Arginina/metabolismo , Glucosa/farmacologíaRESUMEN
The conjunction of atrial fibrillation (AF) and venous thromboembolism (VTE) is common in clinical practice. Over the last 2 decades, a significant number of articles (2500) have been published about AF and VTE. To effectively analyze and present these vast amounts of information, this study uses bibliometric research methods to categorize and consolidate these publications. The number of publications has increased yearly, especially since 2012. The United States was the most prolific country, with 1054 studies published. The most productive institution was McMaster University. Gregory Y.H. Lip was the most prolific author. The keyword analysis identified that the research focuses from 2003 to 2014 were factor Xa inhibitor, dabigatran etexilate, direct thrombin inhibitor, double-blind, deep vein thrombosis, molecular weight heparin, stroke prevention, etc. From 2015 to 2016, research mainly focused on venous thromboembolism, antithrombotic therapy, anticoagulant, warfarin, atrial fibrillation, stroke, and pulmonary embolism. Studies during 2017 to 2022 focused on apixaban, direct oral anticoagulant, rivaroxaban, dabigatran, hemorrhage, edoxaban, medicine efficacy and safety, risk factors, clinical management, and vitamin K antagonists. Since 2018, novel oral anticoagulants have been the most commonly used keywords. On the whole, most studies of AF and VTE focus on pathogenesis and therapeutic drugs. The causal relationship between AF and VTE, the effectiveness and safety of novel oral anticoagulants in the treatments, the anticoagulant regimen of AF and VTE co-disease, and the treatment regimen for vulnerable populations such as the elderly or obese people were the focus of current research and will continue to be the central point of future research.
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Fibrilación Atrial , Accidente Cerebrovascular , Tromboembolia Venosa , Humanos , Anciano , Fibrilación Atrial/complicaciones , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/complicaciones , Warfarina , Anticoagulantes/efectos adversos , Rivaroxabán/efectos adversos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Dabigatrán/efectos adversos , Administración Oral , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Many factors regulate scar formation, which yields a modified extracellular matrix (ECM). Among ECM components, microfibril-associated proteins have been minimally explored in the context of skin wound repair. Microfibril-associated protein 5 (MFAP5), a small 25 kD serine and threonine rich microfibril-associated protein, influences microfibril function and modulates major extracellular signaling pathways. Though known to be associated with fibrosis and angiogenesis in certain pathologies, MFAP5's role in wound healing is unknown. Using a murine model of skin wound repair, we found that MFAP5 is significantly expressed during the proliferative and remodeling phases of healing. Analysis of existing single-cell RNA-sequencing data from mouse skin wounds identified two fibroblast subpopulations as the main expressors of MFAP5 during wound healing. Furthermore, neutralization of MFAP5 in healing mouse wounds decreased collagen deposition and refined angiogenesis without altering wound closure. In vitro, recombinant MFAP5 significantly enhanced dermal fibroblast migration, collagen contractility, and expression of pro-fibrotic genes. Additionally, TGF-ß1 increased MFAP5 expression and production in dermal fibroblasts. Our findings suggest that MFAP5 regulates fibroblast function and influences scar formation in healing wounds. Our work demonstrates a previously undescribed role for MFAP5 and suggests that microfibril-associated proteins may be significant modulators of wound healing outcomes and scarring.
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Cicatriz , Proteínas Contráctiles , Péptidos y Proteínas de Señalización Intercelular , Cicatrización de Heridas , Animales , Ratones , Cicatriz/patología , Fibroblastos/metabolismo , Fibrosis , Microfibrillas , Piel/metabolismo , Cicatrización de Heridas/fisiología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas Contráctiles/metabolismoRESUMEN
INTRODUCTION: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. Resultsï¼The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.
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BACKGROUND: The effects of dietary saturated, monounsaturated, or polyunsaturated fatty acids on the risk of cardiovascular events remain controversial. METHODS: This cross-sectional study was performed in 4211 patients, aged 40 to 79 years, from the National Health and Nutrition Examination Survey between 1999 and 2018. The independent variables were saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. The dependent variable was the 10-year risk of a first hard atherosclerotic cardiovascular event. The other variables were considered as the potential confounding factors. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between saturated fatty acids, polyunsaturated fatty acids, or monounsaturated fatty acids and the 10-year risk. RESULTS: There was no association between dietary saturated fatty acids and 10-year risk after adjusting for all the potential confounding factors; 10-year risk decreased by 0.022% each 1-g increase in monounsaturated fatty acids intake from 0 to 153.772 g, and 0.025% each 1-g increase in polyunsaturated fatty acids intake from 0 to 98.323 g, respectively. Moreover, subgroup analysis showed that monounsaturated fatty acids and polyunsaturated fatty acids were both negatively correlated to 10-year risk in nondiabetes and non-high-low-density lipoprotein patients; monounsaturated fatty acids were also negatively associated with 10-year risk in hypertensive patients. CONCLUSIONS: There was no association between dietary saturated fatty acids and 10-year risk. Increased dietary intake of monounsaturated fatty acids or polyunsaturated fatty acids decreased 10-year risk, particularly in nondiabetes, non-high-low density lipoprotein patients.
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Grasas de la Dieta , Hipertensión , Humanos , Grasas de la Dieta/efectos adversos , Encuestas Nutricionales , Estudios Transversales , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos/efectos adversos , Ácidos Grasos Monoinsaturados/farmacologíaRESUMEN
Most human tissue injuries lead to the formation of a fibrous scar and result in the loss of functional tissue. One adult tissue that exhibits a more regenerative response to injury with minimal scarring is the oral mucosa. We generated a microarray gene expression dataset to examine the response to injury in human palate and skin excisional biopsies spanning the first 7 days after wounding. Differential expression analyses were performed in each tissue to identify genes overexpressed or underexpressed over time when compared to baseline unwounded tissue gene expression levels. To attribute biological processes of interest to these gene expression changes, gene set enrichment analysis was used to identify core gene sets that are enriched over the time-course of the wound healing process with respect to unwounded tissue. This analysis identified gene sets uniquely enriched in either palate or skin wounds and gene sets that are enriched in both tissues in at least one time point after injury. Finally, a cell type enrichment analysis was performed to better understand the cell type distribution in these tissues and how it changes over the time course of wound healing. This work provides a source of human wound gene expression data that includes two tissue types with distinct regenerative and scarring phenotypes.
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Cicatriz , Cicatrización de Heridas , Adulto , Humanos , Cicatrización de Heridas/fisiología , Cicatriz/patología , Piel/patología , Hueso Paladar/patologíaRESUMEN
Keratinocytes are essential cells for wound repair. Impaired oral wound healing is common in diabetic patients with periodontal disease. High glucose, or hyperglycemia, impairs the cellular function of different cell types. However, it is unknown whether high glucose has a detrimental effect on the functions of oral keratinocytes. In the current study, a human gingival keratinocyte cell line, telomerase immortalized gingival keratinocytes (TIGK), was treated with high glucose (24 and 48 mM) for up to 120 h. Proliferation, migration, cell viability, and production of markers of differentiation, growth factors and enzymatic antioxidants were assessed after high glucose treatment. The results showed that high glucose significantly inhibited TIGK proliferation and migration. High glucose also induced significant cell death through apoptosis and necrosis as determined by flow cytometry, especially at 120 h after high glucose treatment. Necrosis was the dominant form of cell death induced. Real-time PCR showed that high glucose treatment upregulated mRNA expression of late keratinocyte differentiation makers, such as keratin 1, 10, 13 and loricrin, and downregulated enzymatic antioxidants, including superoxide dismutase 1, catalase, nuclear factor erythroid 2 -related factor 2, heme oxygenase 1. In conclusion, high glucose impairs the proliferation and migration of oral keratinocytes and likely induces cell death through the promotion of late cell differentiation and down-regulation of enzymatic antioxidants.
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Background: Remnant cholesterol (Remnant-C), rather than TG, is believed to increase the risk of atherosclerotic cardiovascular disease. We evaluated whether Remnant-C is associated with an estimated 10-year risk of a first hard atherosclerotic cardiovascular disease event. Methods: This cross-sectional study was performed on 2,048 participants (1,130 men and 918 women), aged 40 to 79 years, from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The independent variable was Remnant-C; the dependent variable was the 10-year risk of a first hard atherosclerotic cardiovascular disease event (defined as non-fatal myocardial infarction, coronary heart disease death, or stroke, over a 10-year period among people free from atherosclerotic cardiovascular disease at the beginning of the period). The other variables, such as smoking behavior, hypertension, diabetes etc., were considered as the potential effect modifiers. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between Remnant-C and the 10-year risk of a first hard atherosclerotic cardiovascular disease event. Subgroup analyses stratified by gender and race were also performed. Results: A positive association between Remnant-C and the 10-year risk of a first hard atherosclerotic cardiovascular disease event was demonstrated in the fully adjusted model (ß = 0.078, [95%CI: 0.061-0.094], P < 0.001). The 10-year risk was increased by 0.078% for each 1 mg/dl increase in Remnant-C. In the subgroup analysis for gender, this association remained in both men (ß = 0.128, [95%CI: 0.108-0.148], P < 0.001) and women (ß = 0.043, [95%CI: 0.016-0.070], P = 0.00179). However, in the subgroup analysis for race, the association between Remnant-C and the 10-year risk reached an inflection point at remnant-C 38 mg/dL, where a positive association was not as obvious for the non-Hispanic Black population as for other racial groups. Conclusions: Remnant-C positively correlates with a 10-year risk of a first hard atherosclerotic cardiovascular disease event.
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Protein kinase C (PKC) is a protein kinase with important cellular functions. PKC-δ, a member of the novel PKC subfamily, has been well-documented over the years. Activation of PKC-δ plays an important regulatory role in myocardial ischemia/reperfusion (IRI) injury and myocardial fibrosis, and its activity and expression levels can regulate pathological cardiovascular diseases such as atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. This article aims to review the structure and function of PKC-δ, summarize the current research regarding its activation mechanism and its role in cardiovascular disease, and provide novel insight into further research on the role of PKC-δ in cardiovascular diseases.
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Fogging on optical devices may severely impair vision, resulting in unacceptable adverse consequences. Hydrophilic coatings can prevent surface fogging by instantly facilitating pseudo-film water condensation but suffer from short antifogging duration due to water film thickening with further condensation. Here, an innovative strategy is reported to achieve longer antifogging duration via thickening the robust bonded hydrophilic/hydrophobic polymer heteronetwork coating to enhance its water absorption capacity. The combination of strong interfacial adhesion and hydrophilic/hydrophobic heteronetwork structure is key to this approach, which avoids interfacial failure and swelling-induced wrinkles under typical fogging conditions. The developed antifogging coating exhibits prolonged antifogging durations over a wide temperature range for repetitious usages. Eyeglasses coated with this coating successfully maintained fog-free vision in two typical scenarios. Besides, the coating recipes developed in this study also have potential as underwater glues as they demonstrate strong adhesions to both glass and polymer substrates in wet conditions.
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Materiales Biocompatibles Revestidos , Polímeros , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Propiedades de Superficie , AguaRESUMEN
Pyroptosis is a special way of programmed cell death which is dependent on the activation of cysteinyl aspartate specific proteinase 1 (Caspase-1) and Caspase-4/5/11. Ferroptosis is an iron-dependent cell death that characterized by the intra-cellular lipid peroxidation-mediated membrane damage. Pyroptosis or ferroptosis in macrophages, smooth muscle cells, and vascular endothelial cells are believed to be closely related to the progression of atherosclerotic plaques. Therefore, we discuss the role of pyroptosis and ferroptosis in the development of atherosclerotic plaques and may provide new strategies for the treatment of atherosclerosis.
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Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, exacerbate the deterioration of renal function and increase the risk of cardiovascular events in chronic kidney disease (CKD) patients. The effects of microbiota-driven therapy (probiotics, prebiotics, or synbiotics) on decreasing circulating IS and PCS concentrations are controversial; thus, we performed the present systematic review and meta-analysis to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to 22 July, 2021, and randomized controlled trials (RCTs) investigating the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients were included. In all, 14 RCTs with 513 participants were eligible for the meta-analysis. The effects of microbiota-driven therapy on the circulating IS and PCS concentrations were evaluated with weighted mean differences (WMDs) measured by a fixed-effects model or a random-effects model. Compared with placebo, microbiota-driven therapy had no statistically significant effect on the circulating IS concentration (WMD: -1.64 mg/L; 95% CI: -3.46, 0.18 mg/L; P = 0.077) but it decreased the circulating PCS concentration (WMD: -2.42 mg/L; 95% CI: -3.81, -1.04 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 6) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, whereas probiotic (n = 3) supplementation did not. Meta-regression showed that the effects of microbiota-driven therapy were not associated with the supplementation time or the year of publication. Moreover, there was no significant evidence of publication bias. This review found that microbiota-driven therapy decreased the circulating PCS concentration in CKD patients. Additional large, well-designed RCTs with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in the long term. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42021269146.
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Microbiota , Insuficiencia Renal Crónica , Humanos , Indicán/farmacología , Indicán/uso terapéutico , Prebióticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica/terapia , Sulfatos/farmacología , Sulfatos/uso terapéuticoRESUMEN
PURPOSE: To study effects of bioactive glass with high phosphorus content (10.8% P2O5, 54.2% SiO2, 35% CaO, mol%, named PSC) on mineralization of type I collagen fibrils. METHODS: (1) PSC, and PSC combining 0.1 mg/mL, 0.5 mg/mL, or 1.0 mg/mL polyacrylic acid (PAA), were used to induce the mineralization of self-assembled type I collagen fibrils. After 3 and 7 days of mineralization, collagen fibrils were observed by transmission electron microscopy (TEM) and selected area electron diffraction (SAED). (2) PSC suspension was dialyzed in simulated body fluid (SBF), or in SBF containing 0.1 mg/mL, 0.5 mg/mL, or 1.0 mg/mL PAA, to form amorphous calcium phosphate (ACP), then observed by TEM. RESULTS: (1) PSC and PSC combining 0.1 mg/mL or 0.5 mg/mL PAA induced mainly extrafibrillar mineralization. PSC combining 1.0 mg/mL PAA induced both extrafibrillar and intrafibrillar mineralization. (2) The ACP induced by PSC or PSC combining 0.1 mg/mL PAA partly formed lattice structure after 24 h. The particle size of the ACP induced by PSC combining 0.5 mg/mL PAA was 100-150 nm, and that induced by PSC combining 1.0 mg/mL PAA was 30-50 nm. CONCLUSION: PSC induced mainly extrafibrillar mineralization, and PSC combining an appropriate concentration (1.0 mg/mL) of PAA induced both extrafibrillar and intrafibrillar mineralization.
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Colágeno Tipo I , Fósforo , Vidrio , Tamaño de la Partícula , Dióxido de SilicioRESUMEN
Unloading-induced bone loss is a critical complication characterized by the imbalance of bone formation and resorption induced by long-term confinement in bed or spaceflight. CD31hiEmcnhi (type H) vessel is a specific subtype of capillary, which was coupled with osteogenesis. However, the change of type H vessel and its contributions to the unloading-induced bone loss remains undisclosed. Herein, we found that bone formation and the number of type H vessels were synchronously reduced in the hindlimb-unloading (HU) mice. Panax quinquefolium saponin (PQS) could increase bone mass, osteoblast function and the number of type H vessels in the HU mice. In vitro, PQS treatment accelerated HMECs migration, augmented the total tube loops and increased the secretion of VEGF and Noggin. Primary osteoblasts function was obviously increased when treated with supernatant from PQS-treated HMECs. These effects of PQS were substantially counteracted when VEGF and Noggin in HMECs were knocked down by siRNA. These results demonstrated that unloading-induced bone loss is coupled with reduction of type H vessels and PQS performs preventive function via promoting type H vessel angiogenesis, which is closely associated with endothelial cell-derived VEGF and Noggin.
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Enfermedades Óseas Metabólicas , Saponinas , Animales , Masculino , Ratones , Osteoblastos , Osteogénesis , Saponinas/farmacologíaRESUMEN
Scar forming wounds are often characterized by higher levels of vascularity than non-scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause-effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full-thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post-wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF-A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium-derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post-wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF-335). rPEDF and PEDF-335 were administered intradermally from day 4 post-wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF-335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF-335, as a potential new strategy for the prevention or treatment of HSs.
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Inhibidores de la Angiogénesis/farmacología , Cicatriz Hipertrófica/metabolismo , Colágeno/metabolismo , Proteínas del Ojo/farmacología , Neovascularización Patológica/prevención & control , Factores de Crecimiento Nervioso/farmacología , Serpinas/farmacología , Animales , Modelos Animales de Enfermedad , Oído Externo/lesiones , Oído Externo/metabolismo , ConejosRESUMEN
Bicellular tight junctions are multiprotein complexes that are required for maintenance of barrier function and fence function in epithelial tissues. Wound healing in the oral cavity leads to minimal scar formation compared to the skin, and the precise mechanisms for this regenerative response remain to be elucidated. We hypothesized that oral and skin tissues express a different tight junction repertoire both at baseline and during the wound healing response, and that these molecules may be critical to the differential repair between the two tissues. We re-analyzed a mouse skin and palate epithelium microarray dataset to identify the tight junction repertoire of these tissue types. We then re-analyzed a skin and tongue wound healing microarray dataset to see how expression levels of tight junction genes change over time in response to injury. We performed in vitro scratch assays on human oral and skin keratinocyte cell lines to assay for tight junction expression over time, tight junction expression in response to lipopolysaccharide and histamine treatment, and the effects of siRNA knockdown of claudin 1 or occludin on migration and proliferation. Our data showed that oral and skin epithelium expressed different tight junction genes at baseline and during the wound healing response. Knockdown of claudin 1 or occludin led to changes in proliferation and migration in human skin keratinocytes but not oral keratinocytes. Furthermore, we also showed that skin keratinocytes were more permeable than oral keratinocytes upon histamine treatment. In conclusion, this study highlights a specific subset of functional tight junction genes that are differentially expressed between the oral and skin tissues, which may contribute to the mechanisms leading to distinct healing phenotypes in response to injury in the two tissues.