Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.719
Filtrar
1.
Neural Regen Res ; 18(6): 1286-1292, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36453413

RESUMO

Although bone marrow mesenchymal stem cells (BMSCs) might have therapeutic potency in ischemic stroke, the benefits are limited. The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor (VEGF) on behavioral defects in a rat model of transient cerebral ischemia, which was induced by middle cerebral artery occlusion. VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke. We found that compared with the stroke-only group and the vehicle- and BMSCs-control groups, the VEGF-BMSCs treated animals displayed the largest benefits, as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke. Additionally, VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier, increased the regeneration of blood vessels in the region of ischemic penumbra, and reducedneuronal degeneration surrounding the infarct core. Further mechanistic studies showed that among all transplant groups, VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor. These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

2.
Drug Deliv ; 30(1): 1-8, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36453025

RESUMO

Skin infection is a major health issue that usually is caused by the continuous proliferation of bacteria in wounds. With the abuse of antibiotics worldwide, the battle against skin infection is becoming more and more difficult. Therefore, the development of new ways with different antibacterial mechanisms to current antibiotics is urgently needed. Inspired by the powerful inhibition of ferroptosis used in cancer therapy, here in our study, ferric-loaded lipid nanoparticles (Fe-LNPs) with unform size (∼130 nm) and surface charge (∼12 mV) were constructed and found to effectively inhibit the growth of both Gram positive (Staphylococcus aureus, S. aureus) and negative (Escherichia coli, E. coli) strains, possibly due to induction of ferroptosis-like cell death mechanisms. Most importantly, Fe-LNPs can also effectively inhibit the proliferation of S. aureus in a skin infection model and promote the healing of wounds. The Fe-LNPs can be applied as a powerful antibacterial formulation for future application in clinic.


Assuntos
Ferroptose , Staphylococcus aureus , Escherichia coli , Cicatrização , Eletrólitos , Antibacterianos/farmacologia , Morte Celular
3.
Enzyme Microb Technol ; 162: 110141, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36265247

RESUMO

A metagenomic library of mangrove soil samples consisting of approximately 11,000 clones was constructed, and a rare bifunctional cellobiohydrolase/ß-xylosidase Cbh2124 was identified by functional screening. Cbh2124 displayed the highest homology (56.43%) with a protein of the glycoside hydrolase 10 (GH10) family from Proteobacteria. Phylogenetic analysis confirmed that Cbh2124 belongs to the GH10 family. The recombinant enzyme showed a strong cellobiohydrolase activity and a relatively high ß-xylosidase activity, and its catalytic efficiency to the cellobiose substrate was as high as 1.27 × 105 s-1·mM-1, the highest efficiency among reported cellobiohydrolases. Of particular interest, some enzymatic properties of the ß-xylosidase activity of Cbh2124 were significantly different from those of the cellobiohydrolase activity. The optimal pH and temperature of the cellobiohydrolase activity of Cbh2124 was 6.4 and 36 °C, and the activity was essentially lost after treatment at 45 °C for 1 h. The optimal pH and temperature of the ß-xylosidase activity of Cbh2124 was 8.0 and 60 °C, and the residual activity was still over 90% after treatment at 80 °C for 6 h. The molecular docking results of the ß-xylosidase activity of Cbh2124 revealed the additional presence of catalytic amino acids Ser175 and Lys420, thus increasing the number of hydrogen bonds involved in the catalytic process, which possibly let to the improved thermostability compared with that of the cellobiohydrolase activity.


Assuntos
Celulose 1,4-beta-Celobiosidase , Xilosidases , Celulose 1,4-beta-Celobiosidase/genética , Celulose 1,4-beta-Celobiosidase/metabolismo , Solo , Filogenia , Simulação de Acoplamento Molecular , Estabilidade Enzimática , Especificidade por Substrato , Concentração de Íons de Hidrogênio , Xilosidases/metabolismo , Clonagem Molecular , Glicosídeo Hidrolases/metabolismo
4.
Chemosphere ; 310: 136770, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228724

RESUMO

Huge volumes of wastewater containing organic flotation reagents such as xanthates have been released into the environment via mining activities, greatly threatening the eco-environment safety. A simple and fast method is urgently needed for accurate analysis of various xanthates in mining and environmental water. Here, a robust method is realized for simultaneous determination of three trace xanthates (i.e., potassium ethyl xanthate, potassium butyl xanthate, and potassium isopropyl xanthate) in environmental water samples, including eutrophic water and flotation wastewater using solid phase extraction (SPE) and HPLC-MS/MS. HPLC-MS/MS parameters, SPE cartridges and eluting solvents, pH values, and SPE procedures were optimized. The new method had an excellent linearity in the range of 1-1000 µg/L (R2 ≥ 0.998), low limits of detection (0.02-0.68 µg/L), and satisfactory accuracy and precision (72.9%-107.6% of average recoveries and <5% of relative standard deviations at 1, 10, 50, and 500 µg/L of xanthates). This is a first method developed for determination of trace xanthates in water samples. It was successfully applied to determine the target analytes in outdated flotation wastewater and river water samples, warranting the occurrence of trace xanthates (0.13-16.9 µg/L) in water and necessity of systematic investigation on environmental fate and risk of xanthates.


Assuntos
Inseticidas , Poluentes Químicos da Água , Espectrometria de Massas em Tandem/métodos , Águas Residuárias/química , Água/química , Poluentes Químicos da Água/análise , Extração em Fase Sólida/métodos , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Inseticidas/análise , Potássio
5.
Food Chem ; 404(Pt B): 134658, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36323019

RESUMO

This research aimed to investigate the effect of N-acetylglucosamine (GlcNAc) on the biocontrol activity of Kluyveromyces marxianus and involved possible mechanisms. The results indicated that 0.5% GlcNAc significantly improved the antagonistic efficacy of K. marxianus against Penicillium expansum. GlcNAc supplementation led to increases of biocontrol-related enzymes and stress-resistant substances in K. marxianus including chitinase, ß-1,3-glucanase, trehalose and proline, being beneficial for yeasts vigor maintenance under adverse circumstances. The antioxidative-related enzyme activities in K. marxianus, such as superoxide dismutase (SOD), catalase (CAT) and others, were increased by GlcNAc along with more quickly excess reactive oxygen species (ROS) scavenging. GlcNAc resulted in an enhancement of proliferative capacity in K. marxianus according to the transcriptomic analysis. Consequently, GlcNAc contributed to improvements of K. marxianus in the environmental adaptability and stress resistance. Our study demonstrated that both GlcNAc and K. marxianus could be regarded as potential candidates for postharvest technology application.


Assuntos
Kluyveromyces , Penicillium , Acetilglucosamina , Kluyveromyces/genética
6.
Adv Wound Care (New Rochelle) ; 12(1): 1-14, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35081741

RESUMO

Objective: Although the use of dexamethasone as an adjunct agent is associated with alleviating pain and prolonging analgesic duration in local wound infiltration (LWI), efficacy and safety of dexamethasone infiltration have not been fully explored. The study sought to quantify the pooled effects of dexamethasone infiltration on postoperative pain, analgesic consumption, and side effects through a review of randomized controlled trials (RCTs). Approach: RCTs comparing dexamethasone + LWI with LWI alone were retrieved from seven electronic databases. Co-primary outcomes were rest pain scores and cumulative morphine equivalent consumption within 24 h postoperatively. The study followed PRISMA, AMSTAR, and the Cochrane Collaboration. Results: Eight trials comprising 609 patients were included in the final analysis. Results indicated that dexamethasone infiltration effects were only statistical but not clinically significant at individual time points of rest pain and patient satisfaction scores. Notably, the effect of dexamethasone infiltration therapy on other pain-related parameters, including cumulative morphine consumption (mean difference, -9.05 mg; 95% CI: -22.47 to 4.37), was not significantly different compared with the control group. Analysis showed no significant differences in safety indicators between the two groups. The overall quality of evidence was high to very low. Innovation: Although statistically significant effects of dexamethasone infiltration were observed for some outcomes of postoperative wound pain, the overall benefits were below the expected minimal clinically important difference. Conclusions: In summary, the current evidence does not support routine clinical use of dexamethasone in LWI. However, further studies should explore the clinical value of preemptive analgesia and safety of a combination of dexamethasone with ropivacaine for LWI.


Assuntos
Analgesia , Dor Pós-Operatória , Humanos , Ropivacaina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Morfina/farmacologia , Morfina/uso terapêutico , Analgesia/métodos , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
J Environ Sci (China) ; 125: 750-760, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375957

RESUMO

Copper (Cu) is a kind of micronutrient element that is essential for human metabolism. However, it is also considered as an environmental pollutant which is toxic to organisms at a high concentration level. Probiotics, regarded as beneficial microorganisms for promoting human health, have functions of antioxidant capacity, immune-enhancing properties, intestinal barrier protection and regulation. Several studies have reported that probiotics show positive effects on alleviating and intervening heavy metals toxicity. However, evidence for relieving copper-induced toxicity by probiotics is still limited. In this study, we firstly conducted a zebrafish larvae model to screen out microorganisms which are helpful for CuSO4 toxicity resistance and one novel strain named as Bacillus coagulans XY2 was discovered with the best protective activity. B. coagulans XY2 significantly reduced the mortality of zebrafish larvae exposed to 10 µmol/L CuSO4 for 96 hr, as well as alleviated the neutrophils infiltration in the larvae lateral line under a 2 hr exposure. B. coagulans XY2 exhibited a high in vitro antioxidant activity and against CuSO4-induced oxidative stress in zebrafish larvae by up-regulating sod1, gstp1 and cat gene transcriptional levels and relevant enzymatic activities. CuSO4 stimulated the inflammation process resulting in obvious increases of gene il-1ß and il-10 transcription, which were suppressed by B. coagulans XY2 intervention. Overall, our results underline the bio-function of B. coagulans XY2 on protecting zebrafish larvae from copper toxicity, suggesting the potential application values of probiotics in copper toxicity alleviation on human and the environment.


Assuntos
Bacillus coagulans , Probióticos , Humanos , Animais , Bacillus coagulans/fisiologia , Peixe-Zebra , Cobre/toxicidade , Cobre/metabolismo , Larva , Antioxidantes/metabolismo
8.
Biomacromolecules ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454623

RESUMO

To alleviate the dilemma of drug administration in Alzheimer's disease (AD) patients, it is of great significance to develop a new drug delivery system. In this study, a subcutaneously implanted microneedle (MN) device with a swellable gelatin methacryloyl (GelMA) needle body and a dissolvable polyvinyl alcohol (PVA) backing layer was designed. The backing layer quickly dissolved once the MN was introduced into the subcutaneous, and the hydrogel needles were implanted in the subcutaneous to enable prolonged drug release. Compared with oral administration, the MN system offers the benefits of a high administration rate, a fast onset of effect, and a longer duration of action. By detecting the concentration of acetylcholine (ACH) and Aß 1-42, it was found that MN administration exhibited a stronger therapeutic effect. The biological safety of the MN system was also assessed, and no obvious signs of hemolysis, cytotoxicity, and inflammatory reaction were observed. Together, these findings suggested that the MN system is a convenient, efficient, and safe method of delivering donepezil hydrochloride (DPH) and may provide AD patients with a novel medicine administration option.

10.
J Sci Food Agric ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460628

RESUMO

BACKGROUND: The production of Russian sturgeon expands rapidly in China. It is necessary to adopt some restrictive measures which can extend the shelf life of sturgeon meat. Previous studies found that sous-vide cooking (SVC) at 60°C increased the protein and lipid oxidation. The addition of antioxidant substances reduced the acceptance of the product. Therefore, the effect of combination of sous-vide cooking (SVC) and ultrasound pretreatment was investigated. RESULTS: Results showed that SVC 50°C combined with ultrasound effectively restrained the growth of total viable counts (TVC) in samples. Meanwhile, the main dominant genera transformed from Pseudomonas to Carnobacterium and the number of microbial species decreased. The odor profile of Russian sturgeon meat was more stable and the Lipoxygenase (LOX) activity decreased more rapidly after treating with SVC and ultrasound. Importantly, more stable protein aggregates were formed in samples treated by SVC 50°C with ultrasound pretreatment, so the protein and lipid oxidation were slowed down during storage. Additionally, higher springiness values were obtained and the color of sturgeon meat was lighter under these conditions. CONCLUSION: The combination of SVC 50°C and ultrasound pretreatment effectively inhibited the microbial growth of Russian sturgeon meat at lower oxidation levels. These findings can theoretically support the preservation and development of sturgeon meat, as well as the application of SVC technology. This article is protected by copyright. All rights reserved.

11.
J Anesth ; 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36462032

RESUMO

PURPOSE: Anxiety and pain commonly occur during nerve block, we aimed to investigate the sedation efficacy of different doses of remimazolam with sufentanil in young and elderly patients. METHODS: In this randomized trial, patients aged 18-85 years who underwent nerve block was enrolled. All patients received sufentanil 0.08 µg/kg for analgesia. Young patients (age < 65 years) were randomized into the control group (Group C, 0.9% saline), medium-dose remimazolam (Group M, 0.06 mg/kg) and high-dose remimazolam group (Group H, 0.08 mg/kg). Elderly patients (age ≥ 65 years) were randomized into the Group C, low-dose remimazolam group (Group L, 0.04 mg/kg) and Group M. Primary outcome was the success rate of procedure sedation. Respiratory depression and hypoxia were the interested safety outcomes. RESULTS: Ninety young and 114 elderly patients were enrolled, respectively. In comparison with Groups C and M, young patients in Group H had the highest success rate of procedure sedation (80.0 vs. 73.3 vs. 43.3%, P = 0.006). Elderly patients in Groups M and L had similar success rates of procedure sedation, which were significantly higher than that in Group C (78.9 vs. 78.9 vs. 50.0%, P = 0.007). In elderly patients, the incidence of respiratory depression and hypoxia tended to be higher in Group M than those in Groups L and C (both P < 0.001). CONCLUSION: Remimazolam 0.08 mg/kg provided the best sedation efficacy in young patients while remimazolam 0.04 mg/kg with the trend of less respiratory adverse events was more optimal for elderly patients. TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=122016 .

12.
Int Immunopharmacol ; 113(Pt A): 109426, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461588

RESUMO

Ulcerative colitis (UC) is an inflammatory disease with a complex pathogenic mechanism. Mounting evidence suggests that UC pathogenesis is linked to excessive production of reactive oxygen species (ROS) and cellular DNA damage. Recent studies have shown that bone mesenchymal stem cells (BMSCs) mainly exert their therapeutic effects through paracrine exosomes, and oxygen concentration is extremely important to BMSCs and exosomes. The main objective of this study was to determine whether exosomes from BMSCs under hypoxic conditions (HP-Exos) exhibit a greater therapeutic effect on UC compared to exosomes under normoxic conditions (Exos) and to resolve the mechanism of HP-Exos. We observed that hypoxia enhances the activity and migration of BMSCs and inhibits BMSC apoptosis without changing their morphological characteristics. Furthermore, HP-Exos significantly relieved UC symptoms and pathological damage. In order to further understand the mechanism of HP-Exos in UC, findings from in vivo experiments demonstrated that HP-Exos reduces ROS production, DNA damage and apoptosis in intestinal epithelial cells. As hypoxia-inducible factor 1α (HIF-1α) plays an important role in hypoxia, we knocked down HIF-1α in BMSCs. HIF-1α knockout reversed the effects of hypoxia on the activity, migration and apoptosis of BMSCs. Moreover, inhibition of HIF-1α expression also reversed the regulation of UC by HP-Exos. Therefore, we conclude that HP-Exos regulates ROS accumulation, DNA damage and immune homeostasis in intestinal epithelial cells via HIF-1α.


Assuntos
Colite Ulcerativa , Exossomos , Células-Tronco Mesenquimais , Humanos , Espécies Reativas de Oxigênio , Colite Ulcerativa/terapia , Hipóxia , Células Epiteliais , Dano ao DNA
13.
J Hazard Mater ; 445: 130334, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36462243

RESUMO

Thermoacidophilic Cyanidiales maintain a competitive edge in inhabiting extreme environments enriched with metals. Here, species of Cyanidioschyzon merolae (Cm), Cyanidium caldarium (Cc), and Galdieria partita (Gp) were exploited to remove hexavalent chromium [Cr(VI)]. Cm and Gp could remove 168.1 and 93.7 mg g-1 of Cr(VI) at pH 2.0 and 7.0, respectively, wherein 89% and 62% of sorbed Cr on Cm and Gp occurred as trivalent chromium [Cr(III)]. Apart from surface-sorbed Cr(VI), the in vitro Cr(III) bound with polysaccharide and in vivo chromium(III) hydroxide [Cr(OH)3] attested to the reduction capability of Cyanidiales. The distribution of Cr species varied as a function of sorbed Cr amount, yet a relatively consistent proportion of Cr(OH)3, irrespective of Cr sorption capacity, was found only on Cm and Cc at pH 2.0. In conjunction with TXM (transmission X-ray microscopy) images that showed less impaired cell integrity and possible intracellular Cr distribution on Cm and Cc at pH 2.0, the in vivo Cr(OH)3 might be the key to promoting the Cr sorption capacity (≥ 152 mg g-1). Cyanidiales are promising candidates for the green and sustainable remediation of Cr(VI) due to their great removal capacity, the spontaneous reduction under oxic conditions, and in vivo accumulation.

14.
Food Chem ; 406: 135095, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36463600

RESUMO

Binding to phenolics can improve the functional properties of proteins. Changes in structure, functional properties, and antigenicity of ß-lactoglobulin (ß-LG) after covalent conjugation with ferulic acid (FA) at different mass ratios were reported here. The results of SDS-PAGE and gel exclusion chromatography confirmed that covalent complexes were formed. When the mass ratio of ß-LG and FA was 10:6, the binding content of FA was the highest. Fluorescence spectroscopy, UV-visible absorption spectrometry, and FTIR analysis showed that the structure of the complexes was more stretched compared to native ß-LG. The addition of FA significantly improved the emulsifying property of ß-LG. When the mass ratio was 10:6, the radical scavenging activities of DPPH and ABTS reached 65.06% and 88.22%, respectively, and the antigenicity of ß-LG reduced by about 35%. This study provides novel ß-LG-FA complexes in food systems to reduce the antigenicity of ß-LG and improve functional properties.

15.
Plant Sci ; : 111546, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464025

RESUMO

N6-methyladenosine (m6A) is the most widely distributed and most abundant type of mRNA modification in eukaryotic. It provides a posttranscriptional level regulation of gene expression by regulating pre-mRNA splicing, mRNA degradation, or mRNA translational efficiency etc. The function of m6A modification is decoded by binding proteins that can specially bind to m6A. YT521-B homology (YTH) family proteins are the most important m6A-binding proteins in mammals and Arabidopsis. However, their roles in growth and development remain unknown. Here, we demonstrated that the YTH family proteins YTH03, YTH05 and YTH10 specifically bind to m6A-containing RNAs. Knockout of YTH03, YTH05 or YTH10 causes reduced plant height. Further research showed that simultaneously knockout of YTH03, YTH05 and YTH10 shows severe dwarf phenotype, suggesting these three genes regulate rice plant height in a functionally redundant manner. Additional transcriptome study showed that the reduced plant height of the yth03/05/10 triple mutant may be due to the blocked of diterpenoid and brassinolide synthesis pathway. Overall, we demonstrate that YTH03, YTH05 and YTH10 are all the m6A readers in rice and redundantly regulate rice plant height through the hormonal related pathway.

16.
J Formos Med Assoc ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36463082

RESUMO

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

17.
BMC Geriatr ; 22(1): 925, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457076

RESUMO

BACKGROUND: Aging and empty-nesting in China are becoming more and more serious. Empty-nesters refer to older adults who were not living with their children, were living alone, or were living independently with their spouses. The mental health of empty-nesters needs timely attention. Satisfying the needs of older adults is primarily dependent on their children. Therefore, this study aimed to explore relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China. METHODS: This study employs the Children-related Factors Questionnaire (CFQ), the Chinese Version of the Basic Psychological Need Satisfaction (BPNS) Scale, and the Multiple Happiness Questionnaire (MHQ) to explore children-related factors, basic psychological need satisfaction and multiple happiness of urban empty-nesters in Fuzhou, China. A total of 507 samples were recruited by cluster sampling. RESULTS: Factors that affect BPNS include physical condition, the number of children, satisfaction with children's marriage, employment and income, retirement, gender, monthly personal income, and self-care have statistical differences (P < 0.05). Factors that affect MHQ include physical condition, the number of children, satisfaction with children's marriage, employment and income, gender, monthly personal income, living status, and self-care have statistical significances (P < 0.05). Structural equation model results showed that BPNS directly impacted MHQ, and factors about children indirectly affect MHQ through BPNS. The mediating role of BPNS in the relationship between children-related factors and MHQ. CONCLUSION: We should encourage our children to spend more time with the empty-nesters and communicate with them, which could help them relieve their negative emotions, satisfy their psychological needs, and improve their well-being. TRIAL REGISTRATION: Reg date: 20/08/2021; No. ChiCTR2100050175.


Assuntos
Felicidade , Satisfação Pessoal , Humanos , Idoso , Análise de Classes Latentes , China/epidemiologia , Família
18.
Gerontology ; : 1-22, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470214

RESUMO

INTRODUCTION: Senile osteoporosis is one of the most common age-related diseases worldwide. Glucagon like peptide-2 (GLP-2), a naturally occurring gastrointestinal peptide, possesses therapeutic effects on bone loss in postmenopausal women and ovariectomized rats. However, the role of GLP-2 in senile osteoporosis and underlying mechanisms has not been explored. METHODS: GLP-2 was subcutaneously injected into the 6-month-old male senile osteoporosis model of senescence-accelerated mouse prone 6 (SAMP6) mice for 6 weeks. SAMP6 subjected to normal saline and senescence-accelerated mouse resistant 1 served as control groups. Micro-computed tomography was performed to evaluate the bone mass and microarchitecture of the mice. Osteoblastic and osteoclastic activities were determined by biochemical, quantitative real-time PCR, histological, and histomorphometric analyses combined with hematoxylin-eosin, toluidine blue, and tartrate-resistant acid phosphatase staining. We also examined the proteins and structure of intestinal tight junction using immunohistochemical assay as well as a transmission electron microscope. Serum inflammation marker levels were measured using ELISA. Additionally, anti-oxidative enzymes GPX-4 and SOD-2 and receptors of GLP-2 and vitamin D expression in the ileum and colon were detected under immunofluorescence staining. RESULTS: Six-week GLP-2 treatment attenuated bone loss in SAMP6 mice, as evidenced by increased bone mineral density, improved microarchitecture in femora, and enhanced osteogenic activities. In contrast, the activity of osteoclastic activity was not obviously inhibited. Moreover, GLP-2 ameliorated tight junction structure and protein expression in the intestinal barrier, which was accompanied by the reduction of TNF-α level. The expression of receptors of intestinal GLP-2 and vitamin D in the ileum was elevated. Furthermore, the oxidative stress in the intestines was improved by increasing the GPX-4 and SOD-2 signaling. CONCLUSION: Our findings suggest that GLP-2 could ameliorate age-associated bone loss, tight junction structure, and improved antioxidant enzyme activity in the gut in SAMP6 mice. Amelioration of gut barrier dysfunction may potentially contribute to improving bone formation and provide evidence for targeting the entero-bone axis in the treatment of senile osteoporosis.

19.
J Immunol Res ; 2022: 1403788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36471700

RESUMO

Tissue-resident memory T (TRM) cells are immune sentinels that bear a key role in the local immune system and rapidly respond to infection. Our previous studies showed that mucosal immunization via intranasal pathways was more effective than intramuscular route. However, the mechanism of enhanced protective immunity remains unclear. Here, we formulated a Pseudomonas aeruginosa vaccine composed of type III secretion protein PcrV from P. aeruginosa and curdlan adjuvant and then administered by the intranasal route. Flow cytometry and immunofluorescence staining showed that the ratio of CD44+CD62L-CD69+CD4+ TRM cells induced by this vaccine was significantly increased, and IL-17A production was notably enhanced. Further analysis revealed that vaccinated mice can protect against the P. aeruginosa challenge even after administration with FTY720 treatment. What is more, our results showed that CD4+ TRM might be involved in the recruitment of neutrophils and provided partial protection against Pseudomonas aeruginosa. Taken together, these data demonstrated that CD4+ TRM cells were elicited in lung tissues after immunization with rePcrV and contributed to protective immunity. Furthermore, it provided novel strategies for the development of vaccines for P. aeruginosa and other respiratory-targeted vaccines.

20.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6217-6226, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471948

RESUMO

To investigated the mechanisms underlying the effects of modified Kaixin San(MKXS) on improving memory and synaptic damage of Alzheimer's disease(AD) mouse model with conditional presenilin 1/2 conditional double knockout(PS cDKO). Specifically, 60 PS cDKO mice(3-3.5 months old) and their age-matched wild-type(WT) littermates were randomized into three groups: WT group(n=20), PS cDKO group(n=20), and PS cDKO+MKXS group(n=20). Mice in WT and PS cDKO groups were fed with standard chow and those in PS cDKO+MKXS group were given chow containing MKXS(at 2.55 g·kg~(-1)) for 60 days. Novel object reco-gnition task was employed to detect the recognition memory of mice, and Western blot to detect the protein levels of synapse-associated proteins in the hippocampus(HPC) of mice, such as NR1, NR2 A, NR2 B, p-αCaMKⅡ, tau, and p-tau. Microglial morphology in the HPC CA1 of mice was observed based on immunohistochemistry. Quantitative real time-PCR(qRT-PCR) was employed to detect the mRNA levels of the pro-inflammatory factors and synapse-associated proteins in the HPC of mice, including COX-2, iNOS, IL-1ß, IL-6, TNF-α, PSD95, NR1, NR2 A, NR2 B, and MAP2. The protein levels of IL-1ß, TNF-α, and IL-6 were tested by enzyme-linked immunosorbent assay(ELISA). The interaction between PSD95 and αCaMKⅡ and between PSD95 and p-αCaMKⅡ was tested by co-immunoprecipitation(Co-IP). The results showed that PS cDKO+MKXS demonstrated significantly higher preference index and recognition index of the new objects, lower protein level of p-tau(ser 396/404) and mRNA levels of COX-2, iNOS, TNF-α, IL-1ß, and IL-6 in HPC, higher protein levels of NR1, NR2 A, NR2 B, and p-αCaMKⅡ and mRNA levels of NR1, NR2 A, NR2 B, PSD95, and MAP2, and stronger interaction of αCaMKⅡ with PSD95 and interaction of p-αCaMKⅡ with PSD95 than the PS cDKO group. Immunohistoche-mical staining showed that MKXS inhibited the activation of microglia. In conclusion, MKXS improves memory and synaptic damage in mice with AD by modulating αCaMKⅡ-PSD95 protein binding through inhibition of neuroinflammation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...