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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120433, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34601370

RESUMO

Advances in food monitoring benefit tremendously from the naked-eye observation and device-miniaturization of colorimetric and fluorometric methods. Intelligent food packaging, containing a built-in sensor inside food bags, is capable of real-time monitoring of food quality by visibly discernible out-put signals, which effectively ensures food safety. We synthesized a donor-π-acceptor (D-π-A) compound DPABA, and disclosed its fluorescence response to amines. According to quantum chemical calculations, DPABA is apt to D-A coupling in aggregated state, causing the formation of exciplex/excimer together with intermolecular charge/energy transfer to the disadvantage of light emission; while the evasion of amine vapors would decouple the intermolecular D-A interactions to induce stronger emission with shorter wavelength. Utilizing the amine vapor generated by fish, DPABA can serve as an indicator for freshness monitoring. To create an intelligent food package, the compound was made into cellulose film, which was further cut into smart labels to be encapsulated into food bags. The as-prepared smart label exhibits red color under ambient light and glows weak red emission under UV light, while it turns into faint yellow color in response to putrid fish, and its emission changes to bright cyan. The output signals can be accurately recorded by instrument, and detected by naked eye, suggesting high signal contrast. In addition, the smart label exhibits different changing scope in response to different degree of freshness, showing high potential for in-field detection.


Assuntos
Embalagem de Alimentos , Qualidade dos Alimentos , Animais , Celulose , Cor , Concentração de Íons de Hidrogênio
2.
Sci Rep ; 11(1): 23282, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34857809

RESUMO

Medulloblastoma is the most common embryonic brain tumor in children. We investigated a cohort of 52 Asian medulloblastoma patients aged between 0 and 19 years old, who received surgical resections and post-resection treatments in the Taipei Medical University Hospital and the Taipei Veterans General Hospital. Genome-wide RNA sequencing was performed on fresh-frozen surgical tissues. These data were analyzed using the CIBERSORTx immune deconvolution software. Two external clinical and molecular datasets from United States (n = 62) and Canada (n = 763) were used to evaluate the transferability of the gene-signature scores across ethnic populations. The abundance of 13 genes, including DLL1, are significantly associated with overall survival (All Cox regression P < 0.001). A gene-signature score was derived from the deep transcriptome, capable of indicating patients' subsequent tumor recurrence (Hazard Ratio [HR] 1.645, confidence interval [CI] 1.337-2.025, P < 0.001) and mortality (HR 2.720, CI 1.798-4.112, P < 0.001). After the adjustment of baseline clinical factors, the score remains indicative of recurrence-free survival (HR 1.604, CI 1.292-1.992, P < 0.001) and overall survival (HR 2.781, CI 1.762-4.390, P < 0.001). Patients stratified by this score manifest not only distinct prognosis but also different molecular characteristics: Notch signaling ligands and receptors are comparatively overexpressed in patients with poorer prognosis, while tumor infiltrating natural killer cells are more abundant in patients with better prognosis. Additionally, immunohistochemical staining showed the DLL1 protein, a major ligand in the Notch signaling pathway, and the NCAM1 protein, a representative biomarker of natural killer cells, are present in the surgical tissues of patients of four molecular subgroups, WNT, SHH, Group 3 and Group 4. NCAM1 RNA level is also positively associated with the mutation burden in tumor (P = 0.023). The gene-signature score is validated successfully in the Canadian cohort (P = 0.009) as well as its three molecular subgroups (SHH, Group 3 and Group 4; P = 0.047, 0.018 and 0.040 respectively). In conclusion, pediatric medullablastoma patients can be stratified by gene-signature scores with distinct prognosis and molecular characteristics. Ligands and receptors of the Notch signaling pathway are overexpressed in the patient stratum with poorer prognosis. Tumor infiltrating natural killer cells are more abundant in the patient stratum with better prognosis.

3.
Hu Li Za Zhi ; 68(6): 53-61, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34839491

RESUMO

BACKGROUND: The subacute respiratory care unit is an important relay station where respirator-dependent patients may access subsequent chronic respiratory care. Although there is relatively little information in the literature regarding respirator disconnections in subacute respiratory care units, assisting patients to disconnect successfully from respirators is a primary challenge for care teams. PURPOSE: The purpose of this study was to understand respirator disconnections and the factors affecting these events in subacute respiratory care units to improve the effectiveness of ventilator weaning and reduce the burden on families and medical care providers. METHODS: This was a retrospective chart review study. Patients admitted to the subacute respiratory care unit for respiratory training during the study period from January 2016 to December 2019 were recruited as subjects and the data were collected from the Chang Gung Medical Research Database`s health insurance secondary data using a self-made transcription form. RESULTS: The ventilator weaning success rate of the subjects in this study was 78.5%. A bivariate analysis revealed that consciousness status; disease severity; rapid shallow breathing index; days of hospitalization in a respiratory care center; days of ventilator use; blood urea nitrogen, white blood cell, hemoglobin, and blood albumin levels; and mean caloric intake were each significantly associated with successful ventilator withdrawal. The predictors of ventilator weaning in respiratory care center patients were identified as disease severity, rapid shallow breathing index, days of ventilator use, white blood cell level, and hemoglobin level. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Respirator-dependent patients should be evaluated and monitored as early as possible. Moreover, a ventilator weaning plan should be included as a regular testing and monitoring item. Also, a respirator removal program should be provided on a case-by-case basis. Individualized ventilator weaning programs may reduce the burden on families and medical care providers.


Assuntos
Desmame do Respirador , Ventiladores Mecânicos , Humanos , Unidades de Terapia Intensiva , Respiração Artificial , Estudos Retrospectivos
4.
Cell Rep ; 37(8): 110016, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34818535

RESUMO

Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.

5.
Clin Lab ; 67(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758224

RESUMO

BACKGROUND: The aim is to explore the value and significance of changes in neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the diagnosis and treatment of patients with influenza virus infection. METHODS: A total of 1,330 cases of influenza A diagnosed with the nucleic acid testing were collected according to the 2019 version of the influenza diagnosis and treatment regimen in our hospital from September 2020 to December 2020. During the same period, 1,330 cases of healthy subjects were used as controls. The colloidal gold method and fluorescent PCR were used to detect influenza A virus. The sysmex800i was used for routine blood test, and statistical analysis was then performed. RESULTS: Comparing the relevant indicators between the research group and the healthy control group showed that the differences in NLR, PLR, PLT, absolute lymphocyte values, etc. were all statistically significant (p < 0.001). Among them, the average results of NLR and PLR of the research group were all larger than those of the control group; the mean values of the absolute value of lymphocytes (x 109) and PLT (x 109) in the research group were all smaller than those of the control group. The NLR, PLR, LMR, age, and other parameters of the research group and the healthy control group were analyzed to determine whether there was influenza infection according to a binary logistic regression model. The results showed that the differences were not statistically significant except for age and LMR (p > 0.05) and did not enter the regression model. The differences in other parameters such as NLR and PLR were all statistically significant (all p < 0.001), which were all entered into the regression model. They were very significant for predictive diagnosis of influenza A. The areas under the ROC curve of NLR and PLR were 0.961 (95% CI: 0.953-0.968) and 0.749 (95% CI: 0.730-0.769), respectively; the sensitivity and specificity of NLR were 88.4% and 93.1%, respectively, and Youden's index was 0.815, the optimal diagnostic cutoff value was 1.478; the sensitivity and specificity of PLR were 56.70% and 89.60%, respectively; the Youden's index was 0.463, and the optimal diagnostic cutoff value was 124. CONCLUSIONS: NLR and PLR had a certain degree of accuracy in the diagnosis of viral infections in children with influenza A. The diagnostic effect of NLR was particularly good. In the early stage of the disease, cheap and easily available blood biomarkers can be used to diagnose influenza A. However, LMR had no diagnostic value for influenza A because the area under the curve was too small.


Assuntos
Vírus da Influenza A , Influenza Humana , Biomarcadores , Plaquetas , Criança , Humanos , Influenza Humana/diagnóstico , Linfócitos , Neutrófilos , Prognóstico , Estudos Retrospectivos
6.
Antioxidants (Basel) ; 10(11)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34829694

RESUMO

Oxidative stress plays a key role in the degeneration of dopaminergic neurons in Parkinson's disease (PD), which may be aggravated by concomitant PD-associated gut dysbiosis. Probiotics and prebiotics are therapeutically relevant to these conditions due to their antioxidant, anti-inflammatory, and gut microbiome modulation properties. However, the mechanisms by which probiotic/prebiotic supplementation affects antioxidant capacity and the gut microbiome in PD remains poorly characterized. In this study, we assessed the effects of a Lactobacillus salivarius AP-32 probiotic, a prebiotic (dried AP-32 culture medium supernatant), and a probiotic/prebiotic cocktail in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced PD. The neuroprotective effects and levels of oxidative stress were evaluated after eight weeks of daily supplementation. Fecal microbiota composition was analyzed by fecal 16S rRNA gene sequencing. The supplements were associated with direct increases in host antioxidant enzyme activities and short-chain fatty acid production, protected dopaminergic neurons, and improved motor functions. The supplements also altered the fecal microbiota composition, and some specifically enriched commensal taxa correlated positively with superoxide dismutase, glutathione peroxidase, and catalase activity, indicating supplementation also promotes antioxidant activity via an indirect pathway. Therefore, L. salivarius AP-32 supplementation enhanced the activity of host antioxidant enzymes via direct and indirect modes of action in rats with 6-OHDA-induced PD.

8.
Front Nutr ; 8: 708096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722603

RESUMO

In humans, aging is characterized by the progressive decline in biological, physiological, and psychological functions, and is a major risk factor in the development of chronic diseases. Therefore, the development of strategies aimed at attenuating aging-related disorders and promoting healthy aging is critical. In a previous study, we have demonstrated that Lactobacillus plantarum TWK10 (TWK10), a probiotic strain isolated from Taiwanese pickled cabbage, improved muscle strength, exercise endurance, and overall body composition in healthy humans. In this study, the effect of TWK10 on the progression of age-related impairments was investigated in mice. We found that TWK10 not only enhanced muscle strength in young mice, but also prevented the aging-related loss of muscle strength in aged mice, which was accompanied by elevated muscle glycogen levels. Furthermore, TWK10 attenuated the aging-associated decline in learning and memory abilities, as well as bone mass. Further analyses of gut microbiota using next-generation sequencing (NGS) of the 16S rRNA gene showed that the pattern of gut microbial composition was clearly altered following 8 weeks of TWK10 administration. TWK10-treated mice also experienced an increase in short-chain fatty acid (SCFA)-producing bacteria and higher overall levels of gut SCFA. Furthermore, TWK10 administration to some extent reversed the aging-associated accumulation of pathogenic bacterial taxa. In conclusion, TWK10 could be viewed as a potential therapeutic agent that attenuates aging-related disorders and provides health benefits by modulating the imbalance of gut microbiota.

9.
IUBMB Life ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724333

RESUMO

Alzheimer's disease (AD) is the most prevalent and devastating neurodegenerative disease occurred in the elderly. One of the pathogenic hallmarks is senile plaques composed of amyloid-ß (Aß) fibrils. Single mutations resided in Aß were found in familial AD (FAD) patients that have early onset of the disease. The molecular details and properties of each FAD Aß variants are still elusive. Here, we employed collective spectroscopic techniques to examine the properties of various Aß40 fibrils. We generated fibrils of wild type (WT) and three FAD mutants on residue E22 including E22G, E22K, and E22Q. We monitored fibril formation by thioflavin T (ThT) assay, examined secondary structure by Fourier transform infrared and far-UV circular dichroism spectroscopy, imaged fibril morphology by transmission electron microscopy, and evaluated ThT-binding kinetics. In the thermal experiments, we found E22K fibrils resisted to high temperature and retained significant ß-sheet content than the others. E22K fibril seeds after high-temperature treatment still possess the seeding property, whereas WT fibril seeds are disturbed after the treatment. Therefore, in this study we demonstrated the mutation at E22K increases the thermal stability and seeding function of amyloid fibrils.

10.
Biomed Opt Express ; 12(10): 6129-6142, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34745726

RESUMO

The development of solar lentigines (SLs) is related to chronic ultraviolet exposure-induced cell senescence. We have previously demonstrated that basal keratinocyte enlargement is a morphological hallmark of skin senescence correlated to the process of skin aging, while clinical studies on the long-term monitoring of the cellular morphological changes in SLs after laser treatment are lacking. In this study, we have developed the harmonic generation microscopy (HGM) for in vivo monitoring the height of basal keratinocytes (HBK) and had administered Q-switched ruby laser or picosecond 532-nm Nd:YAG laser treatment on each side of the face of 25 Asian patients with facial SLs, respectively. In vivo HGM imaging was conducted to longitudinally analyze HBK and the horizontal cell size (HCS). Before treatment, the HBK was significantly higher in the SLs lesional area than that in the adjacent normal region, whereas there was no significant difference in the HCS. After treatment, the lesional HBK remained significantly higher than normal skin regardless of the laser treatment used. Our study indicates that the basal keratinocytes remain abnormal after laser treatment and demonstrates the capability of in vivo HGM for longitudinal, quantitative monitoring of cell senescence and therapeutic effect in SLs.

11.
Neurol Genet ; 7(6): e627, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34746377

RESUMO

Background and Objectives: To investigate the frequency, spectrum, and molecular functional effect of glycosyltransferase 8 domain-containing protein 1 (GLT8D1) variations in Taiwanese patients with amyotrophic lateral sclerosis (ALS). Methods: We performed genetic analyses of GLT8D1 in 410 unrelated patients with ALS by Sanger sequencing. The 410 patients were selected from a cohort of 477 unrelated patients with ALS after excluding variations in common ALS disease genes. Functional effects of the GLT8D1 variation were investigated by in vitro functional analysis. Results: We identified a novel heterozygous missense variation in GLT8D1, p.I290M (c.870C>G), in 1 single patient with familial ALS. The patient with the p.I290M variation had a spinal-onset ALS with disease onset at age 60 years and a survival of 6 years. Functional studies demonstrated that the variant I290M GLT8D1 protein was mislocalized to the endoplasmic reticulum (ER), provoked ER stress and unfolded protein response, compromised the glycosyltransferase activity, and led to an increased cytotoxicity. Discussion: GLT8D1 variations account for 0.2% (1/477) of the patients with ALS in Taiwan. These findings expand the spectrum of GLT8D1 variation and support the pathogenic role of GLT8D1 variations in ALS.

12.
J Formos Med Assoc ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34802834

RESUMO

BACKGROUND/PURPOSE: The long-term disease course and efficacy of maintenance therapies have rarely been investigated in Asian patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: Medical records of patients fulfilling the 2015 International Consensus Diagnostic Criteria for NMOSD at three medical centers in Taiwan were systematically analyzed. Linear regression analysis was performed to investigate factors related to annualized relapse rate (ARR); survival analysis was used to estimate the relapse-free intervals among therapies. RESULTS: A total of 557 relapses affecting 648 regions (202 optic neuritis, 352 acute myelitis, and 94 brain syndromes) in 204 patients were analyzed during a follow-up period of 69.5 months (range, 1-420). Up to 36.1% of myelitis-onset patients and 24.0% of optic neuritis-onset patients exhibited a limited form disease, defined as having one or more relapses confined to the same region. The median ARR was significantly lower in patients with limited form disease than those with relapses involving multiple regions (0.30 vs. 0.47, respectively). An older age at disease onset was associated with a lower ARR (p = 0.023). Kaplan-Meier analysis showed that the estimated time (months) to next relapse was longest in rituximab-treatment group (58.0 ± 13.2), followed by immunosuppressant (48.5 ± 4.8) or prednisone (29.6 ± 4.6) groups, and shortest in those without maintenance therapy (27.6 ± 4.2) (p = 8.1 × 10-7). CONCLUSION: Limited form disease and older age at disease onset are associated with a lower relapse rate in NMOSD. Compared to no maintenance therapy, rituximab and immunosuppressant significantly reduce the relapse risks.

13.
Clin Psychopharmacol Neurosci ; 19(4): 789-792, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34690134

RESUMO

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

14.
Parkinsonism Relat Disord ; 92: 7-12, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649108

RESUMO

BACKGROUND: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder caused by mutations in the ABCD1 gene. The clinical manifestations of ALD vary widely with some patients presenting with adrenomyeloneuropathy (AMN) that resembles the phenotype of hereditary spastic paraplegia (HSP). The aim of this study is to investigate the frequency, spectrum, and clinical features of ABCD1 mutations in Taiwanese patients with HSP phenotype. METHODS: Mutational analysis of the ABCD1 gene was performed in 230 unrelated Taiwanese patients with clinically suspected HSP by targeted resequencing. Clinical, electrophysiological, and neuroimaging features of the patients carrying an ABCD1 pathogenic mutation were characterized. RESULTS: Ten different ABCD1 mutations were identified in eleven patients, including two novel mutations (p.Q177Pfs*17 and p.Y357*) and eight ever reported in ALD cases of other ethnicities. All patients were male and exhibited slowly progressive spastic paraparesis with onset ages ranging from 21 to 50 years. Most of them had additional non-motor symptoms, including autonomic dysfunction in nine patients, sensory deficits in seven, premature baldness in seven, skin hyperpigmentation in five, psychiatric symptoms in one and cerebellar ataxia in one. Seven of the ten patients who ever received nerve conduction studies showed axonal polyneuropathy. Magnetic resonance imaging (MRI) revealed diffuse spinal cord atrophy in seven patients, cerebral white matter hyperintensity in one patient, and cerebellar involvement in one patient. CONCLUSIONS: ABCD1 mutations account for 4.8% (11/230) of the cases with HSP phenotype in Taiwan. This study highlights the importance to consider ABCD1 mutations in patients with clinically suspected HSP of unknown genetic causes.

15.
Ann Clin Transl Neurol ; 8(11): 2121-2131, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34652888

RESUMO

OBJECTIVE: Mutations in the colony-stimulating factor 1 receptor gene (CSF1R) were identified as a cause of adult-onset inherited leukoencephalopathy. The present study aims at investigating the frequency, clinical characteristics, and functional effects of CSF1R mutations in Taiwanese patients with adult-onset leukoencephalopathy. METHODS: Mutational analysis of CSF1R was performed in 149 unrelated individuals with leukoencephalopathy by a targeted resequencing panel covering the entire coding regions of CSF1R. In vitro analysis of the CSF1-induced autophosphorylation activities of mutant CSF1R proteins was conducted to assess the pathogenicity of the CSF1R mutations. RESULTS: Among the eight CSF1R variants identified in this study, five mutations led to a loss of CSF1-induced autophosphorylation of CSF1R proteins. Four mutations (p.K586*, p.G589R, p.R777Q, and p.R782C) located within the tyrosine kinase domain of CSF1R, whereas the p.T79M mutation resided in the immunoglobulin-like domain. The five patients carrying the CSF1R mutations developed cognitive decline at age 41, 43, 50, 79, and 86 years, respectively. Psychiatric symptoms and behavior changes were observed in four of the five patients. The executive function and processing speed were severely impaired at an early stage, and their cognitive function deteriorated rapidly within 3-4 years. Diffusion-restricted lesions at the subcortical regions and bilateral corticospinal tracts were found in three patients. INTERPRETATION: CSF1R mutations account for 3.5% (5/149) of the adult-onset leukoencephalopathy in Taiwan. CSF1R mutations outside the tyrosine kinase domain may also disturb the CSF1R function and lead to the clinical phenotype. Molecular functional validation is important to determine the pathogenicity of novel CSF1R variants.

16.
J Oncol ; 2021: 8820691, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603450

RESUMO

Objective: To investigate the clinical significance of the mRNA expression of RRM1, TUBB3, and ERCC1 in non-small-cell lung cancer (NSCLC) tissues for the selection of adjuvant/postoperative chemotherapy regimens. Methods: Patients diagnosed with stage Ib-IIIa NSCLC were enrolled and randomly divided into a control group (undetected group) and an experimental group (detected group) after radical operation. The control group randomly received chemotherapy with gemcitabine plus cisplatin or paclitaxel plus cisplatin. The mRNA expression of RRM1, TUBB3, and ERCC1 was detected in the experimental group before chemotherapy, and based on the detected expression, the chemotherapy regimen of cisplatin plus gemcitabine or cisplatin plus paclitaxel was chosen. The disease-free survival (DFS) of the control group and experimental group was compared. Results: Pathological type, stage, gene expression detection, and treatment method were not significantly correlated with DFS (P > 0.05). In the subgroups treated with gemcitabine, the median DFS was 17 months in the detected group and 10.5 months in the undetected group (hazard ratio = 0.2147, 95% confidence interval: 0.07909-0.5827, P=0.0025). Multivariate regression analysis was performed to analyse whether gene expression detection was independently correlated with DFS in the subgroups treated with gemcitabine (P=0.025). In the detected group, the prognosis of patients with low expression of RRM1 was better than that of patients with high expression of RRM1 after paclitaxel treatment (P=0.0039). Conclusions: The selection of chemotherapy regimen based on mRNA expression of the RRM1, TUBB3, and ERCC1 genes may improve selection of candidate patients to receive clinical chemotherapy. However, large-scale prospective clinical studies are needed for in-depth investigation.

17.
Macromol Biosci ; : e2100267, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713970

RESUMO

A clinically approved, tissue engineered graft is needed as an alternative for small-diameter artery replacement. Collagen type I is commonly investigated for naturally derived grafts. However, collagen promotes thrombosis, currently requiring a graft pre-seeding step. This study investigates unique impacts of blending low collagen amounts with synthetic polymers on scaffold platelet response, which would allow for viable acellular grafts that can endothelialize in vivo. While platelet adhesion and activation are confirmed to be high with 50% collagen samples, low collagen ratios surprisingly exhibit the opposite, anti-thrombogenic effect. Different platelet interactions in these blended materials can be related to collagen structure. Low collagen ratios show homogenous distribution of the components within individual fibers. Importantly, blended collagen scaffolds exhibit significant differences from gelatin scaffolds, including retaining percentage of collagen after incubation. These findings correlate with functional benefits including better endothelial cell spreading on collagen versus gelatin blended materials. This appears to differ from the current paradigm that processing with harsh solvents will irreversibly denature collagen into less desirable gelatin, but an important distinction is the interaction between collagen and synthetic materials during processing. Overall, excellent anti-thrombogenic properties of low collagen blends and benefits after grafting show promise for this vascular graft strategy.

18.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638975

RESUMO

Candida albicans is a commensal fungus of humans but can cause infections, particularly in immunocompromised individuals, ranging from superficial to life-threatening systemic infections. The cell wall is the outermost layer of C. albicans that interacts with the host environment. Moreover, antimicrobial peptides (AMPs) are important components in innate immunity and play crucial roles in host defense. Our previous studies showed that the human AMP LL-37 binds to the cell wall of C. albicans, alters the cell wall integrity (CWI) and affects cell adhesion of this pathogen. In this study, we aimed to further investigate the molecular mechanisms underlying the C. albicans response to LL-37. We found that LL-37 causes cell wall stress, activates unfolded protein response (UPR) signaling related to the endoplasmic reticulum (ER), induces ER-derived reactive oxygen species and affects protein secretion. Interestingly, the deletion of the SFP1 gene encoding a transcription factor reduced C. albicans susceptibility to LL-37, which is cell wall-associated. Moreover, in the presence of LL-37, deletion of SFP1 attenuated the UPR pathway, upregulated oxidative stress responsive (OSR) genes and affected bovine serum albumin (BSA) degradation by secreted proteases. Therefore, these findings suggested that Sfp1 positively regulates cell wall integrity and ER homeostasis upon treatment with LL-37 and shed light on pathogen-host interactions.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Candida albicans/metabolismo , Parede Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Parede Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/genética , Proteínas Fúngicas/genética , Deleção de Genes , Homeostase/efeitos dos fármacos , Homeostase/genética , Interações Hospedeiro-Patógeno , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
19.
Sci Rep ; 11(1): 21012, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697327

RESUMO

Risk factors of recurrence and distant metastasis of acral lentiginous melanoma (ALM) are of great interest for the high percentage of ALM in cutaneous melanoma in Asian populations. This single-center retrospective cohort including 177 patients with localized melanoma diagnosed from 2004 to 2020 aims to identify adverse predictors in cutaneous melanoma in Taiwan, with a focus on ALM. The relationship between clinicopathological features and outcomes, including incidences of recurrence and distant metastasis in 5 years from diagnosis, was analyzed. This study included 124 patients (70.1%) with ALM and 53 (29.9%) with non-ALM melanoma. Regarding clinicopathological characteristics, ALM patients were diagnosed at an older age and received sentinel lymph node biopsies (SLNBs) more often, while adjacent melanocytic nevi were more prevalent in non-ALM patients. With respect to prognostic implications of clinicopathological features, in ALM, implementation of SLNB was associated with a lower 5-year distant metastasis rate. Thickness of melanoma lesions over 4 mm, ulceration, and neurotropism, were related to both higher 5-year recurrence and distant metastasis rates. With regard to non-ALM patients, diagnoses made at or over 65 years old was linked to a higher 5-year recurrence rate, whereas ulceration was associated with both higher 5-year recurrence and distant metastasis rates. In conclusion, several clinicopathological characteristics have been identified to be associated with poor prognosis of cutaneous melanoma, especially ALM.

20.
J Formos Med Assoc ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34696937

RESUMO

BACKGROUND/PURPOSE: Betel nut chewing is the major risk factor of oral submucous fibrosis (OSF). Various studies have sought to discover alternative strategies to alleviate oral fibrogenesis. In the present study, we aimed to evaluate the anti-fibrosis effect of paeonol, a phenolic component derived from Paeonia Suffruticosa. METHODS: The cytotoxicity of paeonol was tested using normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues. Collagen gel contraction, Transwell migration, invasion, and wound healing capacities were examined. Besides, the activation of TGF-ß/Smad2 signaling and expression levels of type I collagen, α-SMA, and long non-coding RNA HOTAIR were measured as well. RESULTS: Paeonol exerted a higher cytotoxic effect on fBMFs compared to normal BMFs. The arecoline-induced myofibroblast activities, including collagen gel contractility, cell motility, and wound healing ability were all suppressed by paeonol treatment. In addition, the activation of the TGF-ß/Smad2 pathway was inhibited along with a lower expression of α-SMA and type I collagen in paeonol-treated cells. Also, the administration of paeonol decreased the mRNA expression of HOTAIR in fBMFs. CONCLUSION: Our results indicate that paeonol may be a promising compound to attenuate the progression of oral fibrogenesis in OSF patients.

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