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1.
Food Chem ; 369: 130955, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488129

RESUMO

In countries like South Korea and the USA, origin labeling of shiitake grown using imported Chinese-inoculated medium is an issue. Therefore, we evaluated the use of compound-specific isotope analysis (CSIA) for the accurate identification of the geographical origin of shiitake (Korean, Chinese-inoculated medium, and Chinese); Chinese-inoculated medium shiitake were cultivated in Korea using inoculated sawdust medium from China. The CSIA-discriminant model showed an overall accuracy of 100% in the geographical classification of the original set and 96.4% for the cross-validated set. Glutamate and aspartate δ15N values were the most important variables for differentiating shiitake based on their origins. Compared to that observed upon using the bulk stable isotope analysis, the CSIA model was associated with significantly improved predictability of origin identification. Our findings elucidate the importance of isotope signatures in developing a reliable origin labeling method for shiitake cultured on the sawdust medium for the global market.


Assuntos
Isótopos de Carbono , Isótopos de Carbono/análise , China , Geografia , Projetos Piloto , República da Coreia
2.
Heart Vessels ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783873

RESUMO

Limited data regarding the prognostic impact of ventricular tachyarrhythmias related to out-of-hospital (OHCA) compared to in-hospital cardiac arrest (IHCA) is available. A large retrospective single-center observational registry with all patients admitted due to ventricular tachyarrhythmias was used including all consecutive patients with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Survivors discharged after OHCA were compared to those after IHCA using multivariable Cox regression models and propensity-score matching for evaluation of the primary endpoint of long-term all-cause mortality at 2.5 years. Secondary endpoints were all-cause mortality at 6 months and cardiac rehospitalization at 2.5 years. From 2.422 consecutive patients with ventricular tachyarrhythmias, a total of 524 patients survived cardiac arrest and were discharged from hospital (OHCA 62%; IHCA 38%). In about 50% of all cases, acute myocardial infarction was the underlying disease leading to ventricular tachyarrhythmias with consecutive aborted cardiac arrest. Survivors of IHCA were associated with increased long-term all-cause mortality compared to OHCA even after multivariable adjustment (28% vs. 16%; log rank p = 0.001; HR 1.623; 95% CI 1.002-2.629; p = 0.049) and after propensity-score matching (28% vs. 19%; log rank p = 0.045). Rates of cardiac rehospitalization rates at 2.5 years were equally distributed between OHCA and IHCA survivors. In patients presenting with ventricular tachyarrhythmias, survivors of IHCA were associated with increased risk for all-cause mortality at 2.5 years compared to OHCA survivors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34817392

RESUMO

BACKGROUND: Despite worldwide efforts, control of COVID-19 transmission and of its aftereffect is lagging. As seen from the case of SARS-CoV-2 and influenza, such worldwide crisis and its side effects are likely to recur in the future because of extensive international interactions. Consequently, there is an urgent need to find the determinants that can mitigate the disease spread. Meanwhile, we observed that the transmission speed and severity of consequences varied substantially across countries, signaling the need for country-level investigation. OBJECTIVE: We aimed to investigate how distancing-enabling information and communication technology (ICT) infrastructure and medical ICT infrastructures and related policies have affected the cumulative confirmed cases, fatality rates, and initial speed of transmission across different countries. METHODS: We analyzed the determinants of COVID-19 transmission during the relatively early days of the pandemic by conducting regression analysis based on our data for country-level characteristics including their demographics, culture, ICT infrastructure, policies, economic status, and transmission of COVID-19. To gain further insights, we conducted a subsample analysis for countries with low population density. RESULTS: Our full sample analysis showed that implied telehealth policy, which refers to the lack of specific telehealth related policy but is referred to in general eHealth policy, was associated with lower fatality rates when controlled for cultural characteristics (p-value =.004). Particularly, the fatality rate for countries with an implied telehealth policy was lower than that for others by 2.7 percent. Interestingly, stated telehealth policy, which refers to existence of specified telehealth policy, was found not to be associated with lower fatality rates (p-value =.299). Furthermore, countries with government-run health website had 36% fewer confirmed cases than those without it, when controlled for cultural characteristics (p-value=.03). Our analysis further revealed that the interaction between implied telehealth policy and training ICT health was significant (p-value<0.01), suggesting that implied telehealth policy may be more effective when in-service training on ICT is provided to health professionals. In addition, a rate of credit card ownership, as an enabler of convenient e-commerce transactions and distancing, showed a negative association with fatality rates in full sample analysis (p-value =.04), but not in subsample analysis (p-value =.76), highlighting that distancing-enabling ICT is more useful in densely populated countries. CONCLUSIONS: Our findings demonstrate important relationships between national traits and COVID-19 infections, suggesting guidelines for policymakers to minimize the negative consequences of pandemics. The findings suggest physicians' autonomous use of medical ICT and strategic allocation of distancing-enabling ICT infrastructure in countries with high population density to maximize efficiency. This study also encourages further research to investigate the role of health policies in combatting COVID-19 and other pandemics.

4.
Scand Cardiovasc J ; : 1-9, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738853

RESUMO

Objectives. Galectin-3 (gal-3) is a mediator of extracellular matrix metabolism and reflects an ongoing cardiac fibrotic process. The aim of this study was to determine the potential use of gal-3 in evaluating the structural and functional parameters of the right ventricle as determined by echocardiography. Design. Ninety-one patients undergoing routine echocardiography were prospectively enrolled in this monocentric study. Serum samples for gal-3 and aminoterminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 h of echocardiographic examination. Patients were arbitrarily divided into subgroups based on right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and these included TAPSE >24 mm (n = 23); TAPSE 18-24 mm (n = 55); TAPSE ≤17 mm (n = 13); permitting the detailed statistical analysis of derived data. Results. Serum levels of gal-3 in all patients correlated with age (r = 0.36. p < .001), creatinine (r = 0.60, p < .001), NT-proBNP (r = 0.53, p < .001), RA area (r = 0.38, p < .001) and TAPSE (r = -0.3. p < .01). The distribution of echocardiographic indices according to TAPSE subgroups revealed an association between gal-3 and its ability to identify patients with right ventricular failure (RVF) as diagnosed by a TAPSE ≤17 mm (r = 0.04, p < .001). The multivariable logistic regression model with adjusted odds ratio showed the ability of gal-3 to identify RVF when adjusted to age and gender (adjusted odds ratio 3.60, 95% CI 1.055-12.282, p < .05). Conclusion. Gal-3 correlated with echocardiographic indices of RVF and could effectively diagnose these patients. The supplementary use of NT-proBNP strengthened the diagnostic capability of each biomarker. Trial Registration: The 'Cardiovascular Imaging and Biomarker Analyses' (CIBER Study), clinicaltrials.gov identifier: NCT03074253. Registered 3/8/2017. https://www.clinicaltrials.gov/ct2/show/NCT03074253.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34798939

RESUMO

Although radiological accidents often result in partial-body radiation exposure, most biodosimetry studies focus on estimating whole-body exposure doses. We have evaluated time-dependent changes in chromosomal aberrations before, during, and after localized fractionated radiotherapy. Twelve patients with carcinoma in situ of the breast who underwent identical adjuvant radiation therapy (50 Gy in 25 fractions) were included in the study. Lymphocytes were collected from patients before, during, and after radiotherapy, to measure chromosome aberrations, such as dicentric chromosomes and translocations. Chromosome aberrations were then used to calculate whole- and partial-body biological absorbed doses of radiation. Dicentric chromosome frequencies in all study participants increased during radiotherapy (p < 0.05 in Kruskal-Wallis test). Increases of translocation frequencies during radiotherapy were observed in seven of the twelve patients. The increased levels of dicentric chromosomes and translocations persisted throughout our 1-year follow-up, and evidence of partial-body exposure (such as Papworth's U-value > 1.96) was observed more than 1 year after radiotherapy. We found that cytogenetic biomarkers reflected partial-body fractionated radiation exposure more than 1 year post-exposure. Our findings suggest that chromosome aberrations can be used to estimate biological absorbed radiation doses and can inform medical intervention for individuals suspected of fractionated or partial-body radiation exposure.

6.
Sci Rep ; 11(1): 22749, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815435

RESUMO

Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls. We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated. The nodes with the highest predictability and expected influence in both patients and controls were cognitive and emotional components of the BS and emotional abuse of the ETI. The emotional abuse was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative others and negative self of the BCSS mediated emotional abuse to other BCSS or BS for patients and controls, respectively. Our findings suggest that rumination and emotional abuse were central symptoms in both groups and that negative others and negative self played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002.

7.
J Asthma Allergy ; 14: 1219-1230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675552

RESUMO

Background: Cysteinyl leukotrienes (CysLTs) are key mediators for bronchoconstriction, eosinophil recruitment and mucus production in the airways of asthmatic patients. To better understand the role of CysLTs in different asthma phenotypes, we compared the levels of arachidonic acid metabolites in relation to asthma control status and phenotypes in adult asthmatics on regular anti-asthma medications. Methods: A total of 137 adult asthmatics (47 with aspirin-exacerbated respiratory disease [AERD] and 90 asthmatics with aspirin-tolerant asthma [ATA]) and 20 healthy controls were enrolled. Arachidonic acid metabolites in serum and urine were analyzed using LC-MS/MS methods, and clinical data, including asthma control status, exhaled NO (FeNO) and lung function tests, were collected. Results: Urine LTE4 levels were significantly higher in AERD patients on inhaled corticosteroid-long-acting ß2- agonist plus leukotriene receptor antagonist (LTRA) treatment than in ATA patients (P=0.001). No differences were found in the serum or urine levels of 15-HETE, TXB2, or PGF2α. High serum LTE4 levels were associated with lower FEV1% and uncontrolled status in AERD patients (P=0.006 and P=0.002, respectively), but not in ATA patients. Multivariate analysis demonstrated that blood eosinophil counts, FeNO levels and aspirin hypersensitivity were significant factors affecting urine LTE4 levels. Conclusion: Despite LTRA treatment in AERD, the LTE4 levels remained high and showed close associations with blood eosinophilia, high FeNO levels and impaired disease control. Our real-world evidence indicates that control of asthma is not fully achieved by blocking the CysLT pathway with LTRA. Thus, introduction of treatment modalities targeting eosinophilia could be a better option for patients with high CysLTs.

8.
PLoS One ; 16(10): e0256848, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710121

RESUMO

In recent years, there has been a rapid increase in microbiome studies to explore microbial alterations causing disease status and unveil disease pathogenesis derived from microbiome environmental modifications. Convincing evidence of lung microbial changes involving asthma has been collected; however, whether lung microbial changes under obesity leads to severe asthma in a state of allergen exposure has not been studied sufficiently. Here, we measured bacterial alterations in the lung of an allergen mouse model induced by a high fat diet (HFD) by using 16S rRNA gene sequencing. A total of 33 pathogen­free 3­week­old male C57BL/6 mice were used, and they divided randomly into two groups. The Chow diet (n = 16) and high fat diet (n = 17) was administrated for 70 days. Mice were sensitized with PBS or Dermatophagoides pteronyssinus extract (Der.p), and concentration levels of total IgE and Der.p-IgE in the blood were measured to quantify immune responses. Although there were no meaningful differences in bacterial species richness in the HFD mouse group, momentous changes of bacterial diversity in the HFD mouse group were identified after the mouse group was exposed to allergens. At a genus level, the fluctuations of taxonomic relative abundances in several bacteria such as Ralstonia, Lactobacillus, Bradyrhizobium, Gaiella, PAC001932_g, Pseudolabrys, and Staphylococcus were conspicuously observed in the HFD mouse group exposed to allergens. Also, we predicted metabolic signatures occurring under microbial alterations in the Chow group versus the Chow group exposed to allergens, as well as in the HFD mouse group versus the HFD group exposed to allergens. We then compared their similarities and differences. Metabolic functions associated with macrophages such as propanoate metabolism, butanoate metabolism, and glycine-serine-threonine metabolism were identified in the HFD group versus the Chow group. These results provide new insights into the understanding of a microbiome community of obese allergic asthma, and shed light on the functional roles of lung microbiota inducing the pathogenesis of severe asthma.


Assuntos
Asma/complicações , Pulmão/microbiologia , Obesidade/complicações , Animais , Asma/microbiologia , Bactérias/isolamento & purificação , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Microbiota , Obesidade/microbiologia
9.
Materials (Basel) ; 14(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576544

RESUMO

Due to high demand but limited supply, there has been an increase in the need to replace autologous bone grafts with alternatives that fulfill osteogenic requirements. In this study, two different types of bone grafts were tested for their drug carrying abilities along with their osteogenic properties. Two different types of alendronate-loaded bone grafts, Bio-Oss (bovine bone graft) and InRoad (biphasic synthetic bone graft) were observed to see how different concentrations of alendronate would affect the sustained release to enhance osteogenesis. In this study, defected ovariectomize-induced osteoporotic rat calvarias were observed for 28 days with three different concentrations of alendronate (0 mg, 1 mg, 5 mg) for both Bio-Oss and InRoad. A higher concentration (5 mg) allowed for a more controlled and sustained release throughout the 28-day comparison to those of lower concentrations (0 mg, 1 mg). When comparing Bio-Oss and InRoad through histology and Micro-CT, InRoad showed higher enhancement in osteogenesis. Through this study, it was observed that alendronate not only brings out robust osteogenesis with InRoad bone grafts, but also enhances bone regeneration in an alendronate-concentration-dependent manner. The combination of higher concentration of alendronate and multiple porous bone graft containing internal micro-channel structure of InRoad resulted in higher osteogenesis with a sustained release of alendronate.

10.
ACS Appl Mater Interfaces ; 13(36): 42429-42441, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472351

RESUMO

A critical challenge in many pharmaceutical fields is developing versatile adjuvant devices that can reduce the off-target delivery of therapeutic materials to target lesions. Herein, a biphasic hybrid fibrous system that can manipulate the spatial and temporal delivery of various therapeutic agents to target lesions by integrating multiple distinct systems and technologies such as fluffy coaxial electrospun polycaprolactone (PCL)/polystyrene (PS) fibers, cyclohexane-mediated leaching to remove PS layers selectively, amine display on PCL fibers, conjugation of naturally occurring adhesive gallol molecules onto hyaluronic acid (HA-g), and electrostatically complexing the aminated PCL fibers with the gallol-conjugated HA. In the context of "paintable" systems on target lesions, the resulting system is called a PAINT matrix (abbreviated according to the initial letter of its features: pastable, adhesive, injectable, nanofibrous, and tunable). Its viscoelastic property, which was attributed by coalescing aminated PCL fibers with viscous HA-g, enabled it to be noninvasively injected and fit into any cavity in the body with various morphologies, manually pasted on tissue surfaces, and adhered onto moisture-rich surfaces to ensure the secure delivery of therapeutics toward the target lesions. The PAINT matrix efficiently supplied immunomodulatory human neural stem cells (hNSCs) at rat hemisectioned spinal cord injury (SCI) sites and promoted both locomotive and sensory recovery in SCI models, presumably by protecting hNSCs against host immunosurveillance. The PAINT matrix will be broadly utilized for efficiently delivering therapeutics to difficult-to-reach target lesions by direct infusion or conventional biomaterial-mediated approaches due to their locations, wet surfaces, or complicated ambient environments.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34518333

RESUMO

OBJECTIVE: The only identified cause of amyotrophic lateral sclerosis (ALS) are mutations in a number of genes found in familial cases but also in sporadic cases. De novo mutations occurring in a parental gonadal cell, in the zygote or postzygotic during embryonal development can result in an apparently sporadic/isolated case of ALS later in life. We searched for de novo mutations in SOD1 as a cause of ALS. METHODS: We analysed peripheral-blood exome, genome and Sanger sequencing to identify deleterious mutations in SOD1 in 4000 ALS patients from Germany, South Korea and Sweden. Parental kinship was confirmed using highly polymorphic microsatellite markers across the genome. Medical genealogical and clinical data were reviewed and compared with the literature. RESULTS: We identified four sporadic ALS cases with de novo mutations in SOD1. They aggregate in hot-spot codons earlier found mutated in familial cases. Their phenotypes match closely what has earlier been reported in familial cases with pathogenic mutations in SOD1. We also encountered familial cases where de novo mutational events in recent generations may have been involved. CONCLUSIONS: De novo mutations are a cause of sporadic ALS and may also be underpinning smaller families with few affected ALS cases. It was not possible to ascertain if the origin of the de novo mutations was parental germline, zygotic or postzygotic during embryonal development. All ALS patients should be offered genetic counselling and genetic screening, the challenges of variant interpretation do not outweigh the potential benefits including earlier confirmed diagnosis and possible bespoken therapy.

12.
Mol Psychiatry ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34456336

RESUMO

Breakthroughs in molecular medicine have positioned the amyloid-ß (Aß) pathway at the center of Alzheimer's disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aß cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aß science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aß pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aß species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aß-targeting therapeutic strategies in development for the early treatment of AD.

13.
Pharmaceuticals (Basel) ; 14(8)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34451869

RESUMO

Juglans mandshurica Maxim., a traditional folk medicinal plant, is widely distributed in Korea and China. In our previous study, we isolated a new phenylpropanoid compound, 4-((1R,2R)-3-hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol (HHMP), from J. mandshurica. In the present study, we evaluated the anti-inflammatory activity of HHMP on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and zebrafish larvae. HHMP significantly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 production in a dose-dependent manner. Moreover, HHMP treatment considerably suppressed LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. We also demonstrated the mechanisms of HHMP inhibition of inflammatory responses in LPS-stimulated RAW 264.7 cells via Western blot analysis and immunofluorescence staining. Furthermore, HHMP significantly inhibited NO production in LPS-stimulated zebrafish larvae. Consequently, we established that HHMP significantly inhibited the LPS-induced activation of NF-κB and MAPK and the nuclear translocation of p65 in RAW 264.7 cells. Taken together, our findings demonstrate the effect of HHMP on LPS-induced inflammatory responses in vitro and in vivo, suggesting its potential to be used as a natural anti-inflammatory agent.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34448549

RESUMO

AIM: In the present study, the prevalence and predictors of symptomatic and full remission were investigated in patients with first-episode psychosis (FEP) at the 12-month follow-up. METHODS: A total of 308 participants aged 18-45 years fulfilled the study inclusion criteria and 214 completed the 12-month follow-up. RESULTS: At the 12-month follow-up, 67.3% (142) and 25.9% (55) of the FEP patients met the criteria for symptomatic and full remission, respectively. Stepwise logistic regression analysis showed a shorter duration of untreated psychosis (DUP), no family history, lower Positive and Negative Syndrome Scale (PANSS) negative symptom scores at baseline and higher familial support predicted symptomatic remission at the 12-month follow-up. A higher educational level, shorter DUP, lower PANSS general symptoms scores at baseline and higher subjective well-being under neuroleptics emotional regulation scores predicted full remission. CONCLUSIONS: Our findings regarding the rates of symptomatic and full remission are consistent with previous studies. The results indicate a large discrepancy between symptomatic versus full remission rates at a 12-month follow-up in patients with FEP. Effective psychosocial interventions are necessary to improve the outcomes of FEP patients.

15.
J Affect Disord ; 295: 93-100, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34418779

RESUMO

BACKGROUND: This study aimed to investigate the 1-year changes in neuropsychological test results in older adults with concomitant late-life depression (LLD) and mild cognitive impairment (MCI) according to the presence or absence of brain amyloidopathy. METHODS: All subjects underwent 18F-florbetaben-positron emission tomography and a standardized neuropsychological battery. The subjects were divided based on brain amyloidopathy and severity of depressive symptoms into the following groups: LLD-MCI-A(+), subthreshold depression (STD)-MCI-A(+), major depressive disorder (MDD)-MCI-A(+), LLD-MCI-A(-), STD-MCI-A(-), and MDD-MCI-A(-). After one year, follow-up neurocognitive tests were conducted. Fifty-nine participants completed both the baseline and 1-year follow-up neurocognitive tests. RESULTS: In the LLD-MCI-A(+) group, the word list recall and word list recognition scores decreased during the follow-up period. The STD-MCI-A(+) group also showed a significant decrease in word list recall score and the score/Z-score of word list recognition. On the other hand, the word list recall Z-score improved at the 1-year follow-up in the LLD-MCI-A(-) group. In particular, the MDD-MCI-A(-) group showed significant increases in word list memory score/Z-score and word list recall Z-score during the follow-up period. LIMITATIONS: Considering that AD progresses slowly, a longer follow-up period may be required. CONCLUSIONS: Our findings showed differences in the extent of change of neuropsychological test results depending on the severity of depressive symptoms and presence or absence of brain amyloidopathy. Our results suggest that clinicians might explore the underlying neuropathology when assessing older adults with concomitant depression and cognitive impairment, even if the symptoms of depression are not severe.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Transtorno Depressivo Maior , Idoso , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/complicações , Depressão , Transtorno Depressivo Maior/complicações , Seguimentos , Humanos , Testes Neuropsicológicos
16.
J Cell Biol ; 220(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34347016

RESUMO

Cholesterol metabolism operates autonomously within the central nervous system (CNS), where the majority of cholesterol resides in myelin. We demonstrate that TDP-43, the pathological signature protein for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), influences cholesterol metabolism in oligodendrocytes. TDP-43 binds directly to mRNA of SREBF2, the master transcription regulator for cholesterol metabolism, and multiple mRNAs encoding proteins responsible for cholesterol biosynthesis and uptake, including HMGCR, HMGCS1, and LDLR. TDP-43 depletion leads to reduced SREBF2 and LDLR expression, and cholesterol levels in vitro and in vivo. TDP-43-mediated changes in cholesterol levels can be restored by reintroducing SREBF2 or LDLR. Additionally, cholesterol supplementation rescues demyelination caused by TDP-43 deletion. Furthermore, oligodendrocytes harboring TDP-43 pathology from FTD patients show reduced HMGCR and HMGCS1, and coaggregation of LDLR and TDP-43. Collectively, our results indicate that TDP-43 plays a role in cholesterol homeostasis in oligodendrocytes, and cholesterol dysmetabolism may be implicated in TDP-43 proteinopathies-related diseases.


Assuntos
Colesterol/metabolismo , Proteínas de Ligação a DNA/genética , Demência Frontotemporal/genética , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Animais , Proteínas de Ligação a DNA/deficiência , Modelos Animais de Doenças , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Demência Frontotemporal/metabolismo , Demência Frontotemporal/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Hidroximetilglutaril-CoA Sintase/genética , Hidroximetilglutaril-CoA Sintase/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Bainha de Mielina/patologia , Oligodendroglia/patologia , Organoides/metabolismo , Organoides/patologia , Cultura Primária de Células , Receptores de LDL/genética , Receptores de LDL/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo , Medula Espinal/patologia , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Lobo Temporal/metabolismo , Lobo Temporal/patologia
17.
J Ginseng Res ; 45(4): 482-489, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34295208

RESUMO

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE2 pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

18.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209531

RESUMO

Sorghum is a major cereal food worldwide, and is considered a potential source of minerals and bioactive compounds. Its wide adaptive range may cause variations in its agronomic traits, antioxidant properties, and phytochemical content. This extensive study investigated variations in seed characteristics, antioxidant properties, and total phenolic (TPC) and flavonoid contents (TFC) of sorghum collected from different ecological regions of 15 countries. The antioxidant potential of the seed extracts of various sorghum accessions was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis 3-ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging assays. Significant variations in TPC were observed among the sorghum accessions. All 78 sorghum accessions used in this study exhibited significant variations in TFC, with the lowest and highest amount observed in accessions C465 and J542, respectively. DPPH scavenging potential of the seed extracts for all the accessions ranged from 11.91 ± 4.83 to 1343.90 ± 81.02 µg mL-1. The ABTS assay results were similar to those of DPPH but showed some differences in the accessions. Pearson's correlation analysis revealed a wide variation range in the correlation between antioxidant activity and TPC, as well as TFC, among the sorghum accessions. A wide diversity range was also recorded for the seed characteristics (1000-seed weight and seed germination rate). A dendrogram generated from UPGMA clustering, based on seed traits, antioxidant activity, TPC, and TFC was highly dispersed for these accessions. Variations among the accessions may provide useful information regarding the phytoconstituents, antioxidant properties, and phytochemical contents of sorghum and aid in designing breeding programs to obtain sorghum with improved agronomic traits and bioactive properties.


Assuntos
Antioxidantes , Flavonoides , Fenóis , Sementes/química , Sorghum/química , Antioxidantes/análise , Antioxidantes/química , Flavonoides/análise , Flavonoides/química , Fenóis/análise , Fenóis/química
19.
Am J Cardiol ; 154: 54-62, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34247729

RESUMO

This study evaluates the prognostic impact of anemia in patients presenting with ventricular tachyarrhythmias. The present longitudinal, observational, registry-based, monocentric cohort study included retrospectively all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016. Anemic patients (hemoglobin levels <12.0 g/dl) were compared with non-anemic patients (hemoglobin levels ≥12.0 g/dl). The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were cardiac death at 24 hours, all-cause mortality at index hospitalization, and the composite endpoint of cardiac death at 24 hours, recurrent ventricular tachyarrhythmias, and appropriate ICD therapies at 2.5 years. A total of 2,184 consecutive patients were included, of whom 30% were anemic and 70% non-anemic. Anemia was associated with the primary endpoint of all-cause mortality at 2.5 years (65% vs 29%, p = 0.001; HR = 2.441; 95% CI 2.086 to 2.856), cardiac death at 24 hours (26% vs 11%, p = 0.001), all-cause mortality at index hospitalization (45% vs 20%, p = 0.001), and the composite endpoint (35% vs 27%, p = 0.001; HR = 2.923; 95% CI 2.564 to 4.366). After multivariable adjustment, anemia was no longer associated with the composite endpoint. Predictors of adverse prognosis for anemics were CKD (HR = 2.191), LVEF <35% (HR = 1.651), cardiogenic shock (HR = 1.591), CPR (HR = 1.460), male gender (HR = 1.379), and age (HR = 1.017). In conclusion, anemic patients presenting with ventricular tachyarrhythmias were associated with increased long-term mortality at 2.5 years but not with the composite arrhythmic endpoint at 2.5 years. Predictors of adverse prognosis at 2.5 years were CKD, LVEF <35%, cardiogenic shock, CPR, male gender, and age.


Assuntos
Anemia/epidemiologia , Mortalidade , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/estatística & dados numéricos , Causas de Morte , Desfibriladores Implantáveis , Cardioversão Elétrica , Feminino , Mortalidade Hospitalar , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Sistema de Registros , Insuficiência Renal Crônica/epidemiologia , Fatores Sexuais , Choque Cardiogênico/epidemiologia , Volume Sistólico , Taquicardia Ventricular/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Fibrilação Ventricular/epidemiologia , Adulto Jovem
20.
Australas J Dermatol ; 62(3): e386-e392, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34110005

RESUMO

BACKGROUND: Recent data suggested that dysbiosis of the gut microbiome is associated with childhood allergic diseases. Oral administration of probiotic formulations may improve the severity of atopic dermatitis (AD) by restoring imbalanced gut microbiota and reducing intestinal inflammation in children. OBJECTIVES: The aim of this study was to investigate the effects of a probiotic mixture on the clinical severity of AD, gut inflammatory markers and alterations in microbiome dysbiosis in children with AD. METHODS: A total of 25 subjects were enrolled in this study and administered with a mixture of probiotic strains consisting of Lactobacilli and Bifidobacteria for 4 weeks. The clinical efficacy of the probiotic mixture was assessed using SCORAD index and TEWL. Faecal calprotectin levels were measured as a marker for intestinal inflammation. The composition and diversity of the gut microbiome were analysed using 16S rRNA pyrosequencing. RESULTS: The SCORAD (38.9 ± 17.2 vs 29.0 ± 15.4, P < 0.001) and TEWL (58.3 ± 12.5 vs 27.3 ± 8.7 g/m2 /h, P = 0.028) were significantly decreased after 4 weeks administration of the probiotic mixture. The faecal calprotectin level (121.5 [27.7-292.9] vs 37.0 µg/g [12.6-108.9 µg/g], P = 0.038) was significantly decreased. The α-diversity and composition of the gut microbiome were not significantly changed, but ß-diversity was increased after 4 weeks. CONCLUSIONS: The oral administration of the probiotic mixture was effective in reducing clinical severity and intestinal inflammation in children with AD. Gut microbial diversity was slightly increased after administration of the probiotic mixture. The results of this study suggest that a probiotic mixture can alleviate AD by decreasing inflammation and modulating the gut microbiota in children with AD.

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