ABSTRACT
Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) and mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopyï¼flow cytometry, fluorescence staining, and Western blotting and other methods. AS-IV was administered to db/db mice for in vivo experimentation. Our findings indicated that AS-IV treatment significantly reduced diabetes-associated markers, proteinuria, and kidney damage. It also diminished ROS levels in the kidney, enhanced the expression of endogenous antioxidant enzymes, and improved mitochondrial health. Phenyl sulfate (PS), a protein-bound uremic solute of enteric origin, has been closely linked with DN and represents a promising avenue for further research. In vitro, PS exposure induced OS and mitochondrial dysfunction in podocytes, increasing ROS levels while decreasing antioxidant enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, and Glutathione Peroxidase). ROS inhibitors (N-acetyl-L-cysteine, NAC) as the positive control group can significantly reduce the levels of ROS and restore antioxidant enzymes protein levels. Additionally, PS reduced markers associated with mitochondrial biosynthesis and function (SIRT1, PGC1α, Nrf1, and TFAM). These adverse effects were partially reversed by AS-IV treatment. However, co-treatment with AS-IV and the SIRT1 inhibitor EX527 failed to restore these indicators. Overall, our study demonstrates that AS-IV effectively attenuates DN and mitigates PS-induced OS and mitochondrial dysfunction in podocytes via the SIRT1/PGC1α/Nrf1 pathway.
Subject(s)
Mitochondria , Oxidative Stress , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Podocytes , Saponins , Signal Transduction , Sirtuin 1 , Triterpenes , Animals , Podocytes/drug effects , Podocytes/metabolism , Podocytes/pathology , Sirtuin 1/metabolism , Oxidative Stress/drug effects , Saponins/pharmacology , Signal Transduction/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Mice , Triterpenes/pharmacology , Male , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Nuclear Respiratory Factor 1/metabolism , Mice, Inbred C57BL , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , NF-E2-Related Factor 1/metabolismABSTRACT
Developing a novel catalyst with lower noble-metal loading and higher catalytic efficiency is significant for promoting the widespread application of direct alcohol fuel cells (DAFCs). In this work, poly(3,4-ethylenedioxythiophene) (PEDOT) supported the PdSn alloy (PdSn/PEDOT) were simply synthesized and their electrocatalytic performance toward the oxidation of ethylene glycol and ethanol (EGOR and EOR) were investigated in alkaline media, respectively. In comparison with other control catalysts, the optimized Pd4Sn6/PEDOT catalyst exhibits the highest mass activity (7125/4166 mA mgPd-1) and specific activity (26/15 mA cm-2) towards EGOR/EOR. The mass activity of Pd4Sn6/PEDOT for EGOR and EOR are 11.9 and 10.9 times higher than commercial Pd/C, respectively. Moreover, chronoamperometry (CA) and successive cyclic voltammetry (CV) tests show that the CO resistance ability and durability of the Pd4Sn6/PEDOT catalyst were superior to Pd4Sn6, Pd/PEDOT and commercial Pd/C catalysts, which can be attributed to the d-band center of Pd can be effectively downshifted and the interface strain effect between electrons caused by the conjugated structure between PEDOT groups. This work provides an effective strategy for the development of highly efficient anode catalysts of DAFCs.
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Introduction: P. gingivalis (W83), as the keystone pathogen in chronic periodontitis, has been found to be tightly bound to systemic diseases. Outer membrane vesicles (OMVs) produced by P. gingivalis (W83) are thought to serve key functions in bacterial virulence and pathogenicity. This study aims to comprehend the biological functions of P. gingivalis OMVs isolated from different growth stages by comparing their physicochemical properties and pathogenicity. Methods: Protein composition was analyzed via isotope-labeled relative and absolute quantification (iTRAQ). Macrophage polarization and the expression of IL-6 and IL-1ß were detected. The proliferation, migration, osteogenic differentiation, and IL-1b/NLRP3 expression of periodontal ligament stem cells (PDLSCs) were evaluated. P. gingivalis/P. gingivalis OMVs-induced periodontal models were also constructed in Sprague Dawley rats. Results: The protein composition of P. gingivalis OMVs isolated from different growth stages demonstrated obvious differences ranging from 25 KDa to 75 KDa. In the results of flow cytometry, we found that in vitro experiments the M1 subtype of macrophages was more abundant in the late-log OMVs and stationary OMVs groups which boosted the production of inflammatory cytokines more than pre-log OMVs. Compared to pre-log OMVs, late-log OMVs and stationary OMVs had more pronounced inhibitory effects on proliferation, migration, and early osteogenesis of PDLSCs. The NLRP3 inflammasome was activated to a larger extent in the stationary OMVs group. Micro-computed tomography (Micro CT), hematoxylin-eosin staining (HE), and tartrate acid phosphatase (TRAP) results showed that the periodontal damage in the stationary OMVs group was worse than that in the pre-log OMVs and late-log OMVs group, but almost equal to that in the positive control group (P. gingivalis). Discussion: In general, both in vivo and in vitro experiments showed that late-log OMVs and stationary OMVs have more significant pathogenicity in periodontal disease.
Subject(s)
Chronic Periodontitis , Porphyromonas gingivalis , Rats , Animals , Virulence , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Osteogenesis , X-Ray Microtomography , Rats, Sprague-DawleyABSTRACT
Periodontal bone regeneration using bone marrow mesenchymal stem cell (BMMSC) transplantation is a promising method; however, the method for osteogenic differentiation of BMMSCs needs to be improved. In this research, we sought to identify the roles of let-7a in the osteogenesis of BMMSCs and to provide a potential method for periodontal bone regeneration. Our previous study revealed that Fas/FasL is a target of let-7a. In this study, we demonstrated that let-7a overexpression significantly enhanced BMMSC-CAs osteogenesis both in vitro and in vivo. Mechanistically, upregulation of Fas/FasL using the rfas/rfaslg plasmid obstructed the osteogenesis of BMMSCs by inhibiting autophagy. Furthermore, we confirmed that overexpression of let-7a activated autophagy and alleviated the inhibited osteogenesis by the autophagy inhibitor 3-MA and the rfas/rfaslg plasmid of BMMSCs. In general, our findings showed that let-7a promoted the osteogenesis of BMMSCs through the Fas/FasL-autophagy pathway, suggesting that the application of let-7a in BMMSC-CAs based periodontal bone regeneration could be a promising strategy.
Subject(s)
Bone Regeneration , Mesenchymal Stem Cells , MicroRNAs , Osteogenesis , Animals , Rats , Bone Marrow Cells/metabolism , Bone Regeneration/genetics , Cell Differentiation/genetics , Cells, Cultured , Mesenchymal Stem Cells/metabolism , Osteogenesis/genetics , Up-Regulation , MicroRNAs/genetics , MicroRNAs/metabolism , Autophagy/genetics , fas Receptor/metabolism , Fas Ligand Protein/metabolismABSTRACT
Purpose: Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism. Methods: DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1ß, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining. Results: DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis. Conclusion: DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.
Subject(s)
Alveolar Bone Loss , Exosomes , Periodontitis , Animals , Rats , Periodontal Ligament , Alveolar Bone Loss/therapy , Dental Pulp , Interleukin-6 , Osteogenesis , Periodontitis/therapy , Anti-Inflammatory Agents , InflammationABSTRACT
Background: Streptococcus mutans (S. mutans) is a pivotal cariogenic pathogen contributing to its multiple virulence factors, one of which is synthesizing exopolysaccharides (EPS). VicK, a sensor histidine kinase, plays a major role in regulating genes associated with EPS synthesis and adhesion. Here we first identified an antisense vicK RNA (ASvicK) bound with vicK into double-stranded RNA (dsRNA). Objective: This study aims to investigate the effect and mechanism of ASvicK in the EPS metabolism and cariogenesis of S. mutans. Methods: The phenotypes of biofilm were detected by scanning electron microscopy (SEM), gas chromatography-mass spectrometery (GC-MS) , gel permeation chromatography (GPC) , transcriptome analysis and Western blot. Co-immunoprecipitation (Co-ip) assay and enzyme activity experiment were adopted to investigate the mechanism of ASvicK regulation. Caries animal models were developed to study the relationship between ASvicK and cariogenicity of S. mutans. Results: Overexpression of ASvicK can inhibit the growth of biofilm, reduce the production of EPS and alter genes and protein related to EPS metabolism. ASvicK can adsorb RNase III to regulate vicK and affect the cariogenicity of S. mutans. Conclusions: ASvicK regulates vicK at the transcriptional and post-transcriptional levels, effectively inhibits EPS synthesis and biofilm formation and reduces its cariogenicity in vivo.
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Reduced resolution of polarized images makes it difficult to distinguish detailed polarization information and limits the ability to identify small targets and weak signals. A possible way to handle this problem is the polarization super-resolution (SR), which aims to obtain a high-resolution polarized image from a low-resolution one. However, compared with the traditional intensity-mode image SR, the polarization SR is more challenging because more channels and their nonlinear cross-links need to be considered as well as the polarization and intensity information need to be reconstructed simultaneously. This paper analyzes the polarized image degradation and proposes a deep convolutional neural network for polarization SR reconstruction based on two degradation models. The network structure and the well-designed loss function have been verified to effectively balance the restoration of intensity and polarization information, and can realize the SR with a maximum scaling factor of four. Experimental results show that the proposed method outperforms other SR methods in terms of both quantitative evaluation and visual effect evaluation for two degradation models with different scaling factors.
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Background: Ischemic stroke (IS) was a multifactorial disease, which was the main cause of death and adult disability. Genetic factors cannot be ignored. Objective: The present study discussed the relationship between MMP17 variants and the susceptibility of IS. Methods: Based on the Agena MassARRAY platform, we genotyped single nucleotide polymorphisms (SNPs) on the MMP17 gene in 1345 participants (670 controls and 675 cases). We used logistic regression analysis to analyze the association of MMP17 SNPs with the risk of IS in the Chinese population, with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) detected false positives on the significant results. Besides, we detected the SNP-SNP interaction to predict IS risk by multi-factor dimensionality reduction (MDR) analysis. Results: In the total analysis, MMP17 rs7975920 conferred an increased susceptibility to IS. After a stratified analysis by age and gender, the significant association between rs7975920 and IS risk was displayed in the subjects aged >55 years old and females. After stratified analysis by smoking and drinking, MMP17 rs6598163 was related to the risk of IS in smokers and rs7975920 was associated with the risk of IS in smokers and was in correlation with IS risk in drinkers. Conclusion: In short, we first observed that MMP17 rs7975920 and rs6598163 were related to the risk of IS. The above results provided a theoretical basis for the elaboration of the role of MMP17 in IS in the Chinese population.
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Excessive free fatty acids (FFAs) accumulation is a leading risk factor for the pathogenesis of insulin resistance (IR) in metabolic tissues, including the liver. Ethanolamine-phosphate phospho-lyase (ETNPPL), a newly identified metabolic enzyme, catalyzes phosphoethanolamine (PEA) to ammonia, inorganic phosphate, and acetaldehyde and is highly expressed in hepatic tissue. Whether it plays a role in regulating FFA-induced IR in hepatocytes has yet to be understood. In this study, we established an in vitro palmitic acid (PA)-induced IR model in human HepG2 cells and mouse AML12 cells with chronic treatment of PA. Next, we overexpressed ETNPPL by using lentivirus-mediated ectopic to investigate the effects of ETNPPL per se on IR without PA stimulation. We show that ETNPPL expression is significantly elevated in PA-induced IR and that silencing ETNPPL ameliorates this IR in hepatocytes. Inversely, overexpressing ETNPPL under normal conditions without PA promotes IR, reactive oxygen species generation, and ARG2 activation in both HepG2 and AML12 cells. Moreover, ETNPPL depletion markedly down-regulates ARG2 expression in hepatocytes. Besides, silencing ARG2 prevents ETNPPL-induced ROS accumulation and inhibition of autophagic flux and IR in hepatocytes. Finally, we found that phytopharmaceutical disruption of ETNPPL by quercetin ameliorates PA-induced IR in hepatocytes. Our study discloses that ETNPPL inhibiting autophagic flux mediates insulin resistance triggered by PA in hepatocytes via ARG2/ROS signaling cascade. Our findings provide novel insights into elucidating the pathogenesis of obesity-associated hepatic IR, suggesting that targeting ETNPPL might represent a potential approach for T2DM therapy.
Subject(s)
Insulin Resistance , Humans , Mice , Animals , Insulin Resistance/genetics , Reactive Oxygen Species/metabolism , Palmitic Acid/toxicity , Liver/metabolism , Hepatocytes/metabolism , Autophagy/geneticsABSTRACT
Background and purpose: Distinguishing between intracranial atherosclerosis-related occlusion (ICAS-O) and non-ICAS-O can benefit strategies of identifying the need for surgical plans prior to thrombectomy. We investigated the association between vertebrobasilar artery calcification (VBAC) and ICAS-O in acute ischemic stroke patients undergoing thrombectomy. Methods: Patients were recruited from a prospective single-center registration study who had undergone thrombectomy between October 2017 and October 2021. The enrolled patients were divided into ICAS-O and non-ICAS-O, as determined by the intraarterial therapy process. The occurrences of VBAC were recorded on intracranial non-contrast computed tomography (NCCT) scans before thrombectomy. The association between VBAC and ICAS-O was assessed using binary logistic regression. Results: A total of 2732 patients who had undergone digital subtraction angiography were reviewed, and 314 thrombectomy patients (mean age: 65.4 years, 36.6% female) with NCCT were enrolled in this study. VBAC was detected before thrombectomy in 113 (36%) out of 314 patients. Age, hypertension, and diabetes were associated with VBAC, and a higher frequency of VBAC was identified in patients presenting posterior circulation. ICAS-O accounts for 43% (135/314) in eligible patients. From multivariable analyses, VBAC was identified as an independent predictor of ICAS-O (adjusted odds ratio, 6.16 [95% CI, 2.673-14.217], P < 0.001). Meanwhile, the (VBAC[+] atrial fibrillation[-]) group displayed higher rates of ICAS-O than the (VBAC[-] atrial fibrillation [-]) group (P < 0.001). Conclusions: We demonstrated that VBAC is an independent risk factor for ICAS-O in patients who underwent thrombectomy. Patients free of atrial fibrillation with VBAC have more trend to be ICAS-O.
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Background: Ischemic stroke (IS) is a complex neurological disease affected by genetics and environment. Matrix metalloproteinase-2 (MMP2) is involved in extracellular matrix (ECM) degradation, inflammation and angiogenesis to regulate the development and recovery of IS. Purposes: The aim of this study was to explore the association of rs1053605, rs243849 and rs14070 in MMP2 with the risk of IS in Chinese Shaanxi population. Methods: In this study, 677 IS patients and 681 normal controls were recruited. Rs1053605, rs243849 and rs14070 in MMP2 were genotyped. Logistic regression analysis was applied to evaluate the association of rs1053605, rs243849 and rs14070 in MMP2 with IS susceptibility and the association of environmental factors with MMP2 genetic susceptibility to IS. Results: The results of the overall analysis demonstrated that rs14070 in MMP2 significantly reduced the risk of IS in Chinese Shaanxi population (OR = 0.767, 95% CI = 0.619-0.952, P = 0.016). Subgroup analysis illustrated that rs243849 in MMP2 evidently increased the risk of IS among drinkers, while rs14070 in MMP2 apparently reduced IS susceptibility among females, participants with aged >55, smokers and drinkers. Conclusions: Collectively, rs243849 and rs14070 in MMP2 were significantly associated with the risk of IS in Chinese Shaanxi population, and the effect of MMP2 to IS may be associated with its genetic susceptibility.
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All-trans retinoic acid (ATRA), a main derivative of vitamin A, has been shown to affect the osteogenic differentiation of mesenchymal stem cells (MSCs). Periodontal ligament stem cells (PDLSCs) possess characteristics of MSC and show strong potential for use in periodontal tissue restoration. However, the effect of ATRA on the osteogenic differentiation of PDLSCs remains unclear. In this study, we explored the effect of ATRA on the PDLSCs osteogenic differentiation. PDLSCs were harvested from the periodontalmembrane and treated with or without ATRA. CCK-8 and cell cycle analysis were used to evaluate PDLSC proliferation. PDLSC migration was assessed by scratch tests. qRT-PCR, western blotting, alkaline phosphatase staining, alizarin red staining and calcium quantification were performed to estimate the PDLSCs osteogenic differentiation capability and RNA sequencing to select differentially expressed genes (DEGs). Expression and activation of signaling elements were assessed by qRT-PCR, western blotting and immunofluorescence. Finally, we discovered that ATRA repressed the migration, proliferation, and osteogenesis ability of PDLSCs. RNA sequencing revealed 493 DEGs. Levels of interleukin-1ß (IL-1ß) were increased at varied time points after ATRA treatment. The inhibitive influence of ATRA on the osteogenesis of PDLSCs was partially reversed after neutralizing IL-1ß. In addition, IL-1ß levels were significantly attenuated by nuclear factor-κB (NF-κB) inhibitor BAY11-7082 and NLRP3 inhibitor MCC950. Taken together, our results demonstrate that ATRA disrupts the osteogenesis and mineralizationof PDLSCs by promoting IL-1ß expression via activating NF-κB signaling and NLRP3 inflammasome, which may offer a new method for improving the ATRA-induced disruption of osteoblast differentiation.
Subject(s)
Osteogenesis , Periodontal Ligament , Cell Differentiation , Cell Proliferation , Cells, Cultured , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Stem Cells , Tretinoin/metabolism , Tretinoin/pharmacologyABSTRACT
Vasostatin 1 (VS-1) plays an important role in the regulation of various tissue injury and repair processes, but its role in aortic aneurysm remains unclear. The plasmid-like nanoparticles containing the vasostatin-1 gene Pul-PGEA-pCas-sgVs-1 were constructed, and their guarantee, safety, hemolysis, and particle size were analyzed. Eighty-four eight-week-old male ApoE-mice were randomly divided into blank group (without any treatment), model group (Ang II aortic aneurysm model + tail injection of PBS), control group (modeling + tail injection of Pul-PGEA-pCas9), and experimental group (modeling + tail injection of Pul-PGEA-pCas-sgVs-1), with 21 rats in each group. The incidence, mortality, and maximum diameter of abdominal aortic aneurysm (AAA) and the contents of high sensitivity C-reactive protein (HS-CRP), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), and TNF-a in serum were compared in different groups of mice. The results showed that Pul-PGEA-pCas-sgVs-1 had good biosafety and transfection ability. The maximum diameter of abdominal aorta, incidence of abdominal aortic aneurysm, mortality, and the expression levels of HS-CRP, ICAM-1, VCAM-1, and TNF-a in the experimental group were lower than those in the model group (P< 0.05). These results indicated that the plasmid-like nanoparticles Pul-PGEA-pCas-sgVs-1 can inhibit the development of aorta by down-regulating the expression of inflammatory factors, which played a good protective role on the aorta.
Subject(s)
Aortic Aneurysm, Abdominal , Chromogranin A , Gene Expression Regulation , Nanoparticles , Peptide Fragments , Plasmids , Animals , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/prevention & control , Chromogranin A/biosynthesis , Chromogranin A/genetics , Disease Models, Animal , Male , Mice , Mice, Knockout, ApoE , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Peptide Fragments/biosynthesis , Peptide Fragments/genetics , Plasmids/chemistry , Plasmids/genetics , Plasmids/pharmacologyABSTRACT
The effects of transfection of N-terminal fragment of chromogranin A Vasostatin-1 (VS-1) nanocarriers on formation of abdominal aortic aneurysm (AAA) were discussed, and its mechanism was analyzed. Nanoparticles containing VS-1 genes were prepared by emulsion solvent evaporation method, and property of nanoparticles was examined. A total of 30 male SD rats were divided randomly into sham group (normal saline), AAA group (Type I porcine pancreatic elastase), and VS-1 group (Type I porcine pancreatic elastase+VS-1 suspension liquid). The diameter dilation of rats was measured, abdominal aortic morphology was observed by HE staining, and levels of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were examined by immunohistochemistry and Western blot. Correlation between AMPK as well as mTOR and diameter dilation was analyzed by Pearson correlation. VS-1 genes in VS-1 nanoparticles were 4.51% and coating efficiency of genes was 88%. Compared with rats in sham group, diameter dilation of rats in AAA group increased, damage of abdominal aorta in rats was obvious, p-AMPK decreased, and p-mTOR increased in AAA group. Compared with AAA group, diameter dilation of rats in VS-1 group decreased, abdominal aorta of rats was improved, p-AMPK increased, and p-mTOR decreased. The comparison of all above indicators had statistical meaning (P < 0.05). p-AMPK and p-mTOR were negatively (r = -0.9150 and P = 0.006) and positively correlated with the diameter dilation (r = -0.9206 and P = 0.001). VS-1 nanoparticles could inhibit the formation of AAA, which might be related to the activation of AMPK/mTOR signal path.
Subject(s)
Aortic Aneurysm, Abdominal/therapy , Chromogranin A/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Peptide Fragments/pharmacology , AMP-Activated Protein Kinases/metabolism , Animals , Aorta, Abdominal/pathology , Base Sequence , Chromogranin A/pharmacology , DNA/genetics , DNA Restriction Enzymes/metabolism , Drug Liberation , Male , Nanoparticles/ultrastructure , Pancreatic Elastase , Particle Size , Plasmids/genetics , Rats , Swine , TOR Serine-Threonine Kinases/metabolism , TransfectionABSTRACT
Eucommia ulmoides Oliver (EUO), an economic tree grown specifically in China, is widely used in various fields. To satisfy the requirements of industrial development, superior varieties need to be selected for different uses. However, there is no unified standard for breeders to reference. In this study, leaf-related traits were classified by a probability grading method. The results indicated there were significant differences between different planting models for the studied traits, and the traits in the Arbor forest model showed more abundant variation. Compared with genotype, the planting model accounted for relatively bigger variance, indicating that the standard should be divided according to planting models. Furthermore, the optimum planting model for different traits would be obtained by analyzing the variation range. Association analyses were conducted among traits to select the crucial evaluation indexes. The indexes were divided into three grades in different planting models. The evaluation system on leaf-related traits of EUO germplasm was established preliminarily, which considered planting models and stability across years for the first time. It can be treated as a reference to identify and evaluate EUO germplasm resources. Additionally, the study served as an example for the classification of quantitative traits in other economically important perennial plants.
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OBJECTIVES: Colitis has a high prevalence rate, limited treatment options, and needs to be solved urgently. Application of Licochacone A (LA) or rBMMSCs alone in the treatment of colitis has a certain but limited effect. This study aims to develop an LA-based strategy to improve mesenchymal stem cells' (MSCs') therapeutic capacity in mice DSS-induced colitis by increasing the number of MSCs migrating to the inflammation site. MATERIALS AND METHODS: In vivo, we injected MSCs pretreated with LA, MSCs alone, or PBS into the tail vein of colitis mice, and assessed the colon length, disease activity index (DAI) score, body weight, HAI score, and tracked the location of MSCs at day 10. In vitro, we knocked down the CXCR4 gene by siRNA and then treated it with LA, then tested the mRNA level of CXCR4 and the migration ability of group CXCR4, CXCR4+LA, LA, and control to verify the relationship between this effect and the SDF-1-CXCR4 signaling pathway. RESULTS: The mice that received LA- pretreated MSCs had ameliorated body weight loss, preserved colon morphology, and decreased DAI and histological activity index (HAI) compared with the MSCs group. Besides, the number of MSCs migrating to the inflammation site signiï¬cantly increased in group LA+MSCs, and expression of CXCR4 signiï¬cantly increased too. Furthermore, we found that LA could partly revise the decrease of the migration of MSCs and the expression of CXCR4 mRNA caused by CXCR4-siRNA. CONCLUSION: LA may improve the migration ability of MSCs through increasing CXCR4 expression therapy enhancing their therapeutic activity.
Subject(s)
Adrenal Cortex Hormones/adverse effects , Forearm/physiopathology , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/physiopathology , Skin Diseases, Bacterial , Aged , Aged, 80 and over , Female , Humans , Male , Singapore , Skin Diseases, Bacterial/diagnosis , Skin Diseases, Bacterial/drug therapy , Skin Diseases, Bacterial/physiopathologyABSTRACT
Thanks to the advantages of easy harvesting and escape from immune rejection, autologous bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for immunosuppressive therapy against inflammation and autoimmune diseases. However, the therapy is still challenging because the immunomodulatory properties of BMSCs are always impaired by immunopathogenesis in patients. Because of its reliable and extensive biological activities, osthole has received increased clinical attention. In this study, we found that BMSCs derived from osteoporosis donors were ineffective in cell therapy for experimental inflammatory colitis and osteoporosis. In vivo and in vitro tests showed that because of the down-regulation of Fas and FasL expression, the ability of osteoporotic BMSCs to induce T-cell apoptosis decreased. Through the application of osthole, we successfully restored the immunosuppressive ability of osteoporotic BMSCs and improved their treatment efficacy in experimental inflammatory colitis and osteoporosis. In addition, we found the immunomodulatory properties of BMSCs were enhanced after osthole pre-treatment. In this study, our data highlight a new approach of pharmacological modification (ie osthole) to improve the immune regulatory performance of BMSCs from a healthy or inflammatory microenvironment. The development of targeted strategies to enhance immunosuppressive therapy using BMSCs may be significantly improved by these findings.
Subject(s)
Coumarins/pharmacology , Fas Ligand Protein/metabolism , Immunomodulation , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Osteoporosis/therapy , fas Receptor/metabolism , Animals , Apoptosis , Calcium Channel Blockers/pharmacology , Cells, Cultured , Colitis/complications , Colitis/immunology , Estrogens/deficiency , Fas Ligand Protein/genetics , Female , Immune Tolerance , Mice , Mice, Inbred C57BL , Osteoporosis/etiology , Osteoporosis/metabolism , Osteoporosis/pathology , fas Receptor/geneticsABSTRACT
Three series of copper hydride clusters [Cu8H6L6]2+ (1), [Cu4HX2L4]+ where X- = Cl- (2a), Br- (2b), I- (2c), N3- (2d) and SCN- (2e), and [Cu4HX3L3] where X- = Br- (3b) and I- (3c) (L = 2-(diphenylphosphino)pyridine, dppy) were synthesized and characterized by single-crystal X-Ray crystallography and standard spectroscopic techniques. The metal core of 1, Cu8, can be described as a bicapped octahedron, while those of 2 and 3 series adopt tetrahedral structures. The hydride positions were deduced from difference electron density maps and corroborated by NMR and DFT calculations. For 1, there are two µ4-H-, one each in the two tetrahedral cavities of the two capping atoms and four µ3-H- on the six triangular faces around the waist of the octahedron. For [Cu4HX2L4]+ and [Cu4HX3L3] series, the single µ4-H- resides in the center of the Cu4 tetrahedron. It was found that these three series of copper clusters are intimately connected and can convert from one to another under specific reaction conditions. Their transformation pathways were investigated in detail. Spontaneous resolution to form optically pure enantiomeric single crystals was observed for [Cu4H(SCN)2L4]+ (2e) and [Cu4HBr3L3] (3b). Photoluminescence was observed for [Cu4HX2L4]+, as well as [Cu4HX3L3] with strong emissions from green to yellow regions.
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Three face-centered-cubic (fcc) silver clusters-namely, [Ag14(LA)2(HLA)4(PPh3)8]2- (1), [Ag14(HLA)6(PPh3)8] (2), and [Ag14(NLA)6(PPh3)8] (3)-that are coprotected by lipoic acid (or its amide derivative) and phosphine ligands have been synthesized and structurally characterized (HLA = (±)-α-lipoic acid, LA = (±)-α-lipoate, and NLA = d,l-6,8-thioctamide). These clusters possess two superatomic electrons (the Jellium model), in harmony with a bonding octahedral Ag6 core capped with 8 Ag atoms. Alternatively, the metal framework of 1-3 can be described as adopting a face-centered cubic (fcc) structure elongated along one of the 3-fold axes. The 12 S atoms from the six bioligands bridge the 12 edges of the (fcc) cube, forming a distorted icosahedron. The counterions, solvent or guest molecules play an important role in dictating the crystal lattices of the products. This is the first report of atom-precise structures of Ag-lipoic acid (or its derivatives) clusters, paving the way for further study of structure-property relationships of these bioligand protected metal nanoclusters. Photoluminescence was observed for cluster 3 with complex temperature-dependent emission patterns and efficiencies.