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1.
Bioact Mater ; 20: 598-609, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846837

RESUMO

There is a continuing need for artificial bone substitutes for bone repair and reconstruction, Magnesium phosphate bone cement (MPC) has exceptional degradable properties and exhibits promising biocompatibility. However, its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration. We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate (CMCS/SA) gel network. This had the advantages of: improved compressive strength, ease of handling, and an optimized interface for bioactive bone in-growth. The new composites with 2% CMCS/SA showed the most favorable physicochemical properties, including mechanical strength, wash-out resistance, setting time, injectable time and heat release. Biologically, the composite promoted the attachment and proliferation of osteoblast cells. It was also found to induce osteogenic differentiation in vitro, as verified by expression of osteogenic markers. In terms of molecular mechanisms, data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation of ß-catenin, which is dependent on focal adhesion kinase. Through micro-computed tomography and histological analysis, we found that the MPC-CMCS/SA scaffolds, compared with MPC alone, showed increased bone regeneration in a rat calvarial defect model. Overall, our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.

2.
Bioorg Chem ; 130: 106268, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399863

RESUMO

The phytoconstituents of the fraction with hemostatic activity of the 70% aqueous ethanol extract of Ypsilandra thibetica Franch. were investigated. As a result, fourteen previously unreported spirostanol saponins, ypsilandrosides Z1-Z14, and nine known analogues were isolated and characterized by MS, NMR, and chemical methods. Among them, ypsilandrosides Z1-Z4 (1-4) have a rare 12-O-ß-d-glucopyranosyl group, while ypsilandrosides Z5-Z8 (5-8) possess a rare double bond between C-4 and C-5, and a hydroxyl or carbonyl located at the C-6. All isolates were further tested for their hemostatic activity. The results suggested that five spirostanol tetraglycosides show favorable inducing platelet aggregation activities. Among them, ypsilandroside G (16) displayed significant inducing platelet aggregation activity with an EC50 value of 57.17 µM. Furthermore, the preliminary structure-activity relationship of these spirostanol glycosides' hemostatic activity was discussed.


Assuntos
Hemostáticos , Melanthiaceae , Espirostanos , Hemostáticos/farmacologia , Melanthiaceae/química , Glicosídeos/farmacologia , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Espirostanos/química
3.
Environ Pollut ; 316(Pt 1): 120598, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343854

RESUMO

Previous studies indicated that long-term exposure to high level of fine particulate matter (PM2.5) was associated with elevated blood pressure (BP) and hypertension, but most of them were conducted in high-income countries with low PM2.5 level. Therefore, we aimed to evaluate the adverse impacts of long-term exposure to PM2.5 on BP and hypertension in China with high concentration. A total of 99,084 adults aged ≥18 years old were included from three cohorts among the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. PM2.5 concentrations during 2000-2015 at 1 × 1 km spatial resolution were evaluated using satellite-based spatiotemporal models. Generalized estimating equation was applied to assess the impact of three-year average PM2.5 concentrations on BP level and hypertension. We also examined whether health status and lifestyles modified the effects of PM2.5 on BP and hypertension. Generally, high concentration of PM2.5 was associated with increased BP level and higher risk of hypertension. With each 10 µg/m3 increment in PM2.5 concentration, systolic BP (SBP) and diastolic BP (DBP) increased by 1.67 [95% confidence interval (CI): 1.48, 1.86] mmHg and 0.45 (95% CI: 0.35, 0.56) mmHg, and the prevalence of hypertension increased by 29% [odds ratio (OR): 1.29, 95% CI: 1.26, 1.32]. In comparison with the first quartile of PM2.5 concentration, SBP, DBP and prevalence of hypertension in the fourth quartile were increased by 8.26 (95% CI: 7.73, 8.80) mmHg, 2.85 (95% CI: 2.55, 3.15) mmHg, and 133% (OR: 2.33, 95% CI: 2.21, 2.47), respectively, in the fully adjusted model. However, the relationships of PM2.5 with BP might be non-linear, as BP level started to decline when PM2.5 exceeded 75 µg/m3. In conclusion, long-term PM2.5 exposure could elevate BP level and prevalence of hypertension. People living in high-polluted areas should strengthen their awareness of prevention.

4.
J Affect Disord ; 320: 161-168, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36162662

RESUMO

BACKGROUND: Few studies have been conducted focusing on the non-suicidal self-injury (NSSI) incidence rate and influencing factors among left-behind children in northeastern Sichuan, China. In this study, we investigated the incidence rate of the NSSI behaviors, levels of anxiety and depression in left-behind children in northeastern Sichuan, and relevant sociodemographic factors. METHODS: The NSSI behaviors were identified using the Ottawa Self-injury Inventory (Chinese version). Its incidence rate and related influencing factors were evaluated by Cluster sampling; the Depression Anxiety Stress Scale-21 Items (DASS-21) was adopted to assess the levels of anxiety, depression, and stress. RESULTS: A total of 9450 adolescents met the inclusion criteria, including 543 with NSSI behaviors, and the prevalence of NSSI was 5.7 %. There were 3596 left-behind children, and 243 of them had NSSI behaviors, the NSSI incidence in left-behind children was 6.8 %. There were 5854 non-left-behind children, and the NSSI incidence in non-left-behind children was 5.1 %. Left-behind children's NSSI behaviors were remarkably correlated with five risk factors: being female (OR = 2.411, 95%CI = 1.773-3.279), parents' divorce (OR = 1.742, 95%CI = 1.262-2.404), elder age (OR = 1.120, 95%CI = 1.028-1.219), severe depression (OR = 1.212, 95%CI = 1.148-1.281), and high anxiety (OR = 1.170, 95%CI = 1.093-1.251). LIMITATIONS: This is a cross-sectional study, we cannot probe into the causality between NSSI behaviors and corresponding risk factors. Reporting and recalling biases may be unavoidable as questionnaires are performed by self-rating scales and retrospective reports. CONCLUSION: The NSSI behaviors are common in left-behind children in northeastern Sichuan. This study proposes that prevention and intervention measures are necessary for the healthy growth of such children.


Assuntos
Comportamento Autodestrutivo , Humanos , Adolescente , Criança , Feminino , Idoso , Masculino , Estudos Transversais , Estudos Retrospectivos , Comportamento Autodestrutivo/epidemiologia , Ansiedade/epidemiologia , Prevalência
5.
Sci Total Environ ; 857(Pt 1): 159205, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36202352

RESUMO

Prenatal triclosan (TCS) exposure has been reported to be associated with various birth outcomes and thyroid function, while the study of TCS exposure for congenital heart disease (CHD) patients is limited. In the present study, paired mother-fetus blood samples from CHD and healthy participants were collected to measure TCS exposure levels, and then check their relationship. Coupled with the concentrations of thyroid function biomarkers [free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid antibodies (TgAb)] in maternal blood, we aimed to investigate whether the hormone-disrupting properties of TCS will affect its association with CHD. Our results indicated that the maternal TCS concentrations in the CHD group (median 0.31 ng/mL) were significantly lower than those in the control group (0.48 ng/mL, Mann Whitney U test, p = 0.01). Higher interquartile of TCS levels in maternal blood was associated with decrease odds of CHD (adjusted OR = 0.61, 95%CI: 0.41-0.91, p = 0.02). Maternal blood TCS higher than the cut-off value (25th quantile, 0.17 ng/mL) was significantly negatively associated with CHD risk (adjusted OR = 0.24, 95%CI: 0.09-0.62, p < 0.01). Besides, none of the thyroid biomarkers were significantly associated with maternal TCS exposure. However, maternal FT4 concentrations were positively correlated with TCS transplacental transfer rate and cord blood TCS levels (general linear regression, both p < 0.01). The results of molecular docking and dynamics simulation suggested that these correlations might be related to the transthyretin, a thyroid hormone-binding protein involved in the placental thyroid hormone transport system. Overall, our findings indicated that at normal exposure levels, the increase of maternal blood TCS concentration may have an inverse association with CHD, which merits further investigation.


Assuntos
Cardiopatias Congênitas , Triclosan , Humanos , Feminino , Gravidez , Triclosan/toxicidade , Sangue Fetal/química , Simulação de Acoplamento Molecular , Placenta/química , Tireotropina , Exposição Materna , Cardiopatias Congênitas/induzido quimicamente , Tiroxina
6.
Food Chem ; 404(Pt A): 134188, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36244074

RESUMO

Rheological properties and chemical interactions of doughs prepared at different temperatures were evaluated. The results showed that the rigidity of pretreated doughs was enhanced, and the processing performance of doughs was weakened. Preheating resulted in the polymerization of gluten through the conversion of sulfhydryl groups to disulfide bonds. The noncovalent interaction of dough played a dominant role and further led to the production of glutenin macropolymers (55.77 mg/g). CLSM images verified that preheating promoted the formation of the coarse and scattered gluten network, while preheating at 80 °C led to a higher gluten area percentage (40.27 %) and lower lacunarity (6.74 × 10-2) structure. The migration of water promoted changes in hydrogen bond and hydrophobic interaction in doughs, which directly affect the processability of doughs. The study provides information for predicting the rheological behavior of dough in actual production and makes it possible to modify gluten by preheating treatment without complicating existing operations.


Assuntos
Farinha , Triticum , Farinha/análise , Temperatura , Triticum/química , Glutens/química , Reologia , Pão/análise
7.
J Environ Manage ; 325(Pt A): 116597, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308785

RESUMO

Currently, the influence of elevated atmospheric CO2 concentration (eCO2) on ammonia oxidation to nitrite, the rate-limiting step of nitrification in paddy soil, is poorly known. Previous studies that simulate the effect of eCO2 on nitrification are primarily based on an abrupt increase of atmospheric CO2 concentration. However, paddy ecosystems are experiencing a gradual increase of CO2 concentration. To better understand how the nitrification potential, abundance and communities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) respond to eCO2 in paddy ecosystems, a field experiment was conducted using the following two treatments: a gradual increase of CO2 (EC, increase of 40 ppm per year until 200 ppm above ambient) and ambient CO2 (CK). The results demonstrated that the EC treatment significantly (P < 0.05) stimulated the soil potential nitrification rate (PNR) at the jointing and milky stages, which increased by 127.83% and 27.35%, respectively, compared with CK. Furthermore, the EC treatment significantly (P < 0.05) stimulated the AOA and AOB abundance by 56.60% and 133.84%, respectively, at the jointing stage. Correlation analysis showed that the PNR correlated well with the abundance of AOB (R2 = 0.7389, P < 0.001). In addition, the EC treatment significantly (P < 0.05) altered the community structure of AOB, while it had little effect on that of AOA. A significant difference in the proportion of Nitrosospira was observed between CO2 treatments. In conclusion, the gradual increase of CO2 positively influenced the PNR and abundance of ammonia oxidizers, and AOB could be more important than AOA in nitrification under eCO2.


Assuntos
Betaproteobacteria , Nitrificação , Amônia , Dióxido de Carbono , Microbiologia do Solo , Ecossistema , Archaea , Solo/química , Oxirredução , Filogenia
8.
Front Pharmacol ; 13: 1027112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457705

RESUMO

Background: Pregnancy-induced Hypertension (PIH) is a disease that causes serious maternal and fetal morbidity and mortality. Alisma Orientale (AO) has a long history of use as traditional Chinese medicine therapy for PIH. This study explores its potential mechanism and biosafety based on network pharmacology, network toxicology, molecular docking and molecular dynamics simulation. Methods: Compounds of AO were screened in TCMSP, TCM-ID, TCM@Taiwan, BATMAN, TOXNET and CTD database; PharmMapper and SwissTargetPrediction, GeneCards, DisGeNET and OMIM databases were used to predict the targets of AO anti-PIH. The protein-protein interaction analysis and the KEGG/GO enrichment analysis were applied by STRING and Metascape databases, respectively. Then, we constructed the "herb-compound-target-pathway-disease" map in Cytoscape software to show the core regulatory network. Finally, molecular docking and molecular dynamics simulation were applied to analyze binding affinity and reliability. The same procedure was conducted for network toxicology to illustrate the mechanisms of AO hepatotoxicity and nephrotoxicity. Results: 29 compounds with 78 potential targets associated with the therapeutic effect of AO on PIH, 10 compounds with 117 and 111 targets associated with AO induced hepatotoxicity and nephrotoxicity were obtained, respectively. The PPI network analysis showed that core therapeutic targets were IGF, MAPK1, AKT1 and EGFR, while PPARG and TNF were toxicity-related targets. Besides, GO/KEGG enrichment analysis showed that AO might modulate the PI3K-AKT and MAPK pathways in treating PIH and mainly interfere with the lipid and atherosclerosis pathways to induce liver and kidney injury. The "herb-compound-target-pathway-disease" network showed that triterpenoids were the main therapeutic compounds, such as Alisol B 23-Acetate and Alisol C, while emodin was the main toxic compounds. The results of molecular docking and molecular dynamics simulation also showed good binding affinity between core compounds and targets. Conclusion: This research illustrated the mechanism underlying the therapeutic effects of AO against PIH and AO induced hepato-nephrotoxicity. However, further experimental verification is warranted for optimal use of AO during clinical practice.

9.
Inorg Chem ; 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464846

RESUMO

An inclusion complex of a trigonal-prismatic metallacage with two coronene guests was constructed by multicomponent coordination-driven self-assembly from a 90° platinum(II) acceptor [cis-Pt(PEt3)2(OTf)2], disodium terephthalate, and 2,4,6-tri(4-pyridyl)-1,3,5-triazine in the presence of excess coronene. This platinum(II)-based trigonal prism was found to be a highly matched host to simultaneously encapsulate two coronene molecules. The encapsulation of coronene can effectively promote the formation of a pure single-prismatic metallacage and can stabilize the self-assembled structure via strong π-π-stacking interactions between coronene and the metallacage.

10.
Front Med (Lausanne) ; 9: 1028694, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465933

RESUMO

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease with a wide range of heterogeneity. Accurate biomarkers or predictors are the keys to instructing personalized tailored precise treatment. The development of technology such as transcriptomics, genomics, and proteomics provides novel insights into the possibility to find potential biomarkers. Meanwhile, emerging minimally invasive methods such as tape stripping were used to reveal different profiles of patients' skin without biopsy. Several potential biomarkers or predictors have been found. In this review, we summarized the current development of potential biomarkers of AD. Nitric oxide synthase 2/inducible nitric oxide synthase (NOS2/iNOS), human beta-defensin-2 (hBD-2), and matrix metalloproteinases 8/9 (MMP8/9) may be the candidate biomarkers for AD diagnosis. Filaggrin (FLG) gene mutation increased the occurrence risk of AD. Fatty-acid-binding protein 5 (FABP5) may serve as an effective biomarker for the atopic march (AM). Squamous cell carcinoma antigen 2 (SCCA2), serum thymus and activation-regulated chemokine (TARC), cutaneous T-cell-attracting chemokine (CTACK), eosinophil-derived neurotoxin (EDN), macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH), and interleukin (IL)-18 can be the candidate biomarkers for disease severity monitoring. IL-17, IL-23, IL-33, and indoleamine 2,3-dioxygenase (IDO1) can be used as predictive biomarkers for AD comorbidities. LDH, TARC, pulmonary and activation-regulated chemokine (PARC), periostin, IL-22, eotaxin-1/3, and IL-8 may be the candidate biomarkers for monitoring treatment effects. There are still unmet needs and a long way to go for more convenient, non-invasive, and effective predictors and biomarkers to better guide personalized precise treatment.

11.
Front Neurosci ; 16: 1046518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466167

RESUMO

Background: There were limited studies that directly compare the outcomes of various mind-body exercise (MBE) therapies on chronic non-specific low back pain (CNLBP). Objectives: To compare the efficacy of the four most popular MBE modes [Pilates, Yoga, Tai Chi (TC), and Qigong] in clinically CNLBP patients, we conducted a systematic review and network meta-analysis (NMA). Methods: We searched databases for eligible randomized controlled trials (RCTs) (from origin to July 2022). RCTs were eligible if they included adults with CNLBP, and implemented one or more MBE intervention arms using Pilates, yoga, TC, and qigong. In addition, pain intensity and physical function were evaluated using validated questionnaires. Results: NMA was carried out on 36 eligible RCTs involving 3,050 participants. The effect of exercise therapy on pain was in the following rankings: Pilates [Surface under cumulative ranking (SUCRA) = 86.6%], TC (SUCRA = 77.2%), yoga (SUCRA = 67.6%), and qigong (SUCRA = 64.6%). The effect of exercise therapy on function: Pilates (SUCRA = 98.4%), qigong (SUCRA = 61.6%,), TC (SUCRA = 59.5%) and yoga (SUCRA = 59.0%). Conclusion: Our NMA shows that Pilates might be the best MBE therapy for CNLBP in pain intensity and physical function. TC is second only to Pilates in improving pain in patients with CNLBP and has the value of promotion. In the future, we need more high-quality, long-term follow-up RCTs to confirm our findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306905, identifier: CRD42022306905.

12.
Arch Gerontol Geriatr ; 106: 104881, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36470181

RESUMO

BACKGROUND: Acute cholecystitis (AC) is a life-threatening infectious/inflammatory disease in older patients. This study aimed to investigate the safety and optimal timing of surgery in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: From January 2008 to February 2021, 152 patients were retrospectively enrolled. Clinical outcomes were compared among patients who received laparoscopic cholecystectomy (LC), open cholecystectomy (OC), and conversion surgery, and between those who received early (< 6 weeks after PTGBD) and delayed cholecystectomy (≥ 6 weeks after PTGBD). Logistic regression analysis was used to identify risk factors for recurrent AC, further biliary events, conversion, and perioperative complications. RESULTS: Sixty-seven patients underwent LC, 62 underwent OC, and 23 underwent conversion surgery. Operation-related complications and mortality rates did not differ among the types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two patients underwent early cholecystectomy, while 70 underwent delayed cholecystectomy. There were no differences in operative time, operation-related complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio [OR] = 19.42, p < 0.001) and further biliary events (OR = 15.95, p < 0.001). CONCLUSIONS: Early cholecystectomy is recommended for patients aged ≥ 80 years with moderate to severe AC following PTGBD.

13.
J Couns Psychol ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455023

RESUMO

Group climate is an important factor in group counseling and psychotherapy process and outcome research. The current investigation examined group climate changes (from early to late sessions) at the within-group (i.e., group members) and between-group (i.e., group-as-a-whole) levels in predicting changes in group members' emotional cultivation in group counseling. A total of 236 Taiwanese children and adolescents across 41 groups participated in this study. Members' ratings of group climate (i.e., engagement and conflict) were partitioned into within-group and between-group components, and polynomial regression with response surface analysis was used to examine the association between changes in group engagement and conflict (at the member- and group-level) from early to late group sessions on changes in emotional cultivation. Results supported the theoretical hypothesis that when a group-as-a-whole reported increasing engagement from early to late group sessions, relative to other groups (i.e., between-group effect), members of that group experienced greater growth in emotional cultivation. Results also indicated that group members reported greater growth in emotional cultivation when there was consistent and high engagement or consistent and low conflict from early to late group sessions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

15.
Anal Chem ; 94(47): 16319-16327, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36372951

RESUMO

Although surface-enhanced Raman spectroscopy (SERS) can rapidly identify molecular fingerprints and has great potential for analysis, the need for delicate plasmonic substrates and complex laboratory instruments seriously limits its applicability for on-site detection. This paper describes the development of an inexpensive aluminum nanoparticle (AlNP)-decorated paper that functions as a facile SERS-based detection platform (Al-PSERS). Polydopamine-protected AlNPs were chemically synthesized and then simply drop-cast onto a hydrophobic cellulose paper, forming a monolayer AlNP cluster array. Because of the abundance of hot spots arising from the plasmonic clusters, the inherent quasi-three-dimensional structure of the cellulose fibers, and the concentration effect of the hydrophobic surface, the Al-PSERS provided significant enhancements to the signal of various analytes, measured using a portable 785 nm Raman spectrometer. Near-field optical simulations and experimental spectroscopic results revealed that the local electric fields and corresponding SERS signal intensities of the AlNP array exhibited clear particle-length and cluster-size dependencies. Therefore, the Al-PSERS could be optimized to provide high sensitivity (enhancement factor: 2 × 103) and excellent reproducibility (variation: 8.72%). Moreover, the optimal Al-PSERS was capable of detecting colorants and environmental pollutants; for example, the detection limits of allura red and benzo[a]pyrene reached as low as 3.5 and 0.15 ppm, respectively. Furthermore, the Al-PSERS could rapidly identify illegal (rhodamine B) and edible (allura red, erythrosine) colorants from a mixture of multiple colorants or from adulterated candies. Because it facilitates rapid detection, is of low cost, and has minimal technical requirements, Al-PSERS should be applicable to on-site detection in, for example, food inspection and environmental monitoring.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Análise Espectral Raman/métodos , Alumínio , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Celulose
16.
J Soc Psychol ; : 1-18, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36331089

RESUMO

Using original texts of Confucian and Taoist primary classics as materials, we conducted an eight-week educational intervention experiment combining classroom teaching and post-class reflection as cultural manipulation. Ninety-four sixth-grade students from three parallel mainstream classes were randomly assigned to three intervention groups, comprising two experimental groups (Confucian and Taoist values interventions) and a control group (natural science intervention). The results suggest that the Confucian intervention had a positive effect on interdependent self and holistic thinking, the Taoist intervention had a positive effect on independent self and holistic thinking, and the natural science intervention promoted analytical thinking.

17.
Eur J Pharmacol ; 938: 175411, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36436590

RESUMO

Glioblastoma multiforme (GBM) is a deadly brain malignancy, and current therapies offer limited survival benefit. The phytosterol guggulsterone (GS) has been shown to exhibit antitumor efficacy. This study aimed to investigate the effects of GS on migration and invasion and its underlying mechanisms in human GBM cell lines. After GS treatment, the survival rate of GBM cells was reduced, and the migration and invasion abilities of GBM cells were significantly decreased. There was also concomitant decreased expression of focal adhesion complex, matrix metalloproteinase-2 (MMP2), MMP9 and cathepsin B. Furthermore, GS induced ERK phosphorylation and autophagy, with increased p62 and LC3B-II expression. Notably, treatment of in GBM cells with the proteasome inhibitor MG132 or the lysosome inhibitor NH4Cl reversed the GS-mediated inhibition of migration and invasion. In an orthotopic xenograft mouse model, immunohistochemical staining of brain tumor tissues demonstrated that MMP2 and cathepsin B expression was reduced in GS-treated mice. GS treatment inhibited GBM cell migration and invasion via proteasomal and lysosomal degradation, suggesting its therapeutic potential in clinical use in the future.

18.
Front Cell Infect Microbiol ; 12: 938286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439226

RESUMO

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes severe infections in humans and the swine industry. Acquisition and utilization of available carbon sources from challenging host environments is necessary for bacterial pathogens to ensure growth and proliferation. Glycogen is abundant in mammalian body and may support the growth of SS2 during infection in hosts. However, limited information is known about the mechanism between the glycogen utilization and host adaptation of SS2. Here, the pleiotropic effects of exogenous glycogen on SS2 were investigated through transcriptome sequencing. Analysis of transcriptome data showed that the main basic metabolic pathways, especially the core carbon metabolism pathways and virulence-associated factors, of SS2 responded actively to glycogen induction. Glycogen induction led to the perturbation of the glycolysis pathway and citrate cycle, but promoted the pentose phosphate pathway and carbohydrate transport systems. Extracellular glycogen utilization also promoted the mixed-acid fermentation in SS2 rather than homolactic fermentation. Subsequently, apuA, a gene encoding the unique bifunctional amylopullulanase for glycogen degradation, was deleted from the wild type and generated the mutant strain ΔapuA. The pathogenicity details of the wild type and ΔapuA cultured in glucose and glycogen were investigated and compared. Results revealed that the capsule synthesis or bacterial morphology were not affected by glycogen incubation or apuA deletion. However, extracellular glycogen utilization significantly enhanced the hemolytic activity, adhesion and invasion ability, and lethality of SS2. The deletion of apuA also impaired the pathogenicity of bacteria cultured in glucose, indicating that ApuA is indeed an important virulence factor. Our results revealed that exogenous glycogen utilization extensively influenced the expression profile of the S. suis genome. Based on the transcriptome response, exogenous glycogen utilization promoted the carbon adaption and pathogenicity of SS2.


Assuntos
Infecções Estreptocócicas , Streptococcus suis , Humanos , Suínos , Animais , Streptococcus suis/metabolismo , Virulência/genética , Transcriptoma , Glicogênio/metabolismo , Sorogrupo , Infecções Estreptocócicas/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Glucose/metabolismo , Carbono/metabolismo , Mamíferos/genética
19.
Kaohsiung J Med Sci ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394149

RESUMO

This study investigated the relationship between body composition parameters and changes in future liver remnant volume (FLRV) in hepatocellular carcinoma (HCC) patients undergoing portal vein embolization (PVE) in preparation for right hepatectomy. This retrospective study enrolled 21 patients between May 2013 and October 2020. Body composition parameters, including skeletal muscle attenuation (SMA), skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR), were measured by computed tomography (CT) prior to PVE. Liver volumetry was measured before and at least 5 weeks after PVE. The mean interval between two CT volumetries was 9.1 ± 4.9 weeks, the mean value of increase in FLRV (ΔFLRV) was 236.0 ± 118.3 cm3 , the ratio of increased FLRV (ΔFLRV%) was 55.7 ± 29.4%, and the rate of increased FLRV was 31.0 ± 18.8 (cm3 /week). Subjects with high IMAC showed significantly lower (p = 0.044) ΔFLRV% than those with normal IMAC. Furthermore, ΔFLRV% was linearly reduced (p for trend = 0.043) among those with low Ishak fibrosis stage (<3) + normal IMAC (76.1 ± 36.8%), those with low Ishak fibrosis stage (<3) + high IMAC or high Ishak fibrosis stage (>3) + normal IMAC (54.0 ± 24.1%), and those with high Ishak fibrosis stage (>3) + low IMAC (28.7 ± 1.6%) (p for trend = 0.043). Our data indicated that high IMAC with a high Ishak fibrosis stage (>3) had a significant negative effect on ΔFLRV%.

20.
Cancers (Basel) ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36358838

RESUMO

Medulloblastoma (MB) was classified into four molecular subgroups: WNT, SHH, group 3, and group 4. In 2017, 12 subtypes within 4 subgroups and 8 subtypes within non-WNT/non-SHH subgroups according to the differences of clinical features and biology were announced. In this study, we aimed to identify the heterogeneity of molecular features for discovering subtype specific factors linked to diagnosis and prognosis. We retrieved 70 MBs in children to perform RNA sequencing and a DNA methylation array in Taiwan. Integrated with clinical annotations, we achieved classification of 12 subtypes of pediatric MBs in our cohort series with reference to the other reported series. We analyzed the correlation of cell type enrichment in SHH MBs and found that M2 macrophages were enriched in SHH ß, which related to good outcomes of SHH MBs. The high infiltration of M2 macrophages may be an indicator of a favorable prognosis and therapeutic target for SHH MBs. Furthermore, C11orf95-RELA fusion was observed to be associated with recurrence and a poor prognosis. These results will contribute to the establishment of a molecular diagnosis linked to prognostic indicators of relevance and help to promote molecular-based risk stratified treatment for MBs in children.

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