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1.
J Med Virol ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35567325

RESUMO

It remains unclear how effective COVID-19 vaccinations will be in patients with weakened immunity due to diseases, transplantation, and dialysis. We conducted a systematic review comparing the efficacy of COVID-19 vaccination in patients with solid tumor, hematologic malignancy, autoimmune disease, inflammatory bowel disease, and patients who received transplantation or dialysis. A literature search was conducted twice using the Medline/PubMed database. As a result, 21 papers were included in the review, and seropositivity rate was summarized by specific type of disease, transplantation, and dialysis. When different papers studied the same type of patient group, a study with a higher number of participants was selected. Most of the solid tumor patients showed a seropositivity rate of more than 80% after the second inoculation, but a low seropositivity was found in certain tumors such as breast cancer. Research in patients with certain types of hematological malignancy and autoimmune diseases has also reported low seropositivity, and this may have been affected by the immunosuppressive treatment these patients receive. Research in patients receiving dialysis or transplantation has reported lower seropositivity rates than the general population, while all patients with inflammatory bowel disease have converted to be seropositive. Meta-analysis validating these results will be needed, and studies will also be needed on methods to protect patients with reduced immunity from COVID-19. This article is protected by copyright. All rights reserved.

2.
J Affect Disord ; 309: 71-76, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35452758

RESUMO

BACKGROUND: The aims of the present study were to examine prospective associations of multimorbidity (i.e., ≥2 chronic conditions) at baseline with incident and persistent anxiety over a two-year follow-up period among Irish older adults, and to quantify the extent to which sleep, pain, and disability mediate the multimorbidity-anxiety relationship. METHODS: Data from The Irish Longitudinal Study on Aging (TILDA) conducted between 2009 and 2011 with a follow-up after two years were analyzed. Anxiety referred to score ≥ 8 on the anxiety section of the Hospital Anxiety and Depression Scale. Lifetime diagnosis of 14 chronic conditions was obtained. Outcomes were incident and persistent anxiety at two-year follow-up. RESULTS: Data on 5871 adults aged ≥50 years at baseline were analyzed [Mean (SD) age 63.3 (9.0) years; 51.2% women]. After adjustment for potential confounders, compared to no chronic physical conditions at baseline, ≥3 chronic conditions were associated with a significant 1.89 (95% CI = 1.16-3.08) times higher risk for new onset anxiety at follow-up. Furthermore, having 1, 2, and ≥3 conditions at baseline were associated with significant 1.48 (95% CI 1.02, 2.14), 1.74 (95% CI 1.19, 2.53), and 1.84 (95% CI 1.27, 2.68) times higher risk for persistent anxiety at follow-up. Sleep problems, pain, and disability were identified as significant mediators, explaining 22.9%-37.8% of the associations. CONCLUSION: Multimorbidity was associated with both new onset and persistent anxiety among Irish older adults. Future interventional studies should examine whether addressing the identified mediators may lead to lower risk for incident or persistent anxiety among those with physical multimorbidity.

3.
QJM ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35385121

RESUMO

BACKGROUND: Sudden infant death syndrome (SIDS) still remains one of the leading causes of infant death worldwide, especially in high-income countries. To date, however, there is no detailed information on the global health burden of SIDS. AIMS: To characterize the global disease burden of SIDS and its trends from 1990 to 2019 and to compare the burden of SIDS according to the socio-demographic index (SDI). DESIGN: Systematic analysis based on the Global Burden of Disease (GBD) 2019 data. METHODS: Epidemiological data of 204 countries from 1990 to 2019 were collected via various methods including civil registration and vital statistics in the original GBD study. Estimates for mortality and disease burden of SIDS were modelled. Crude mortality and mortality rates per 100,000 population were analyzed. Disability-adjusted life years (DALYs) and DALY rates were also assessed. RESULTS: In 2019, mortality rate of SIDS accounted for 20.98 [95% Uncertainty Interval (UI), 9.15 to 46.16] globally, which was a 51% decrease from 1990. SIDS was most prevalent in Western sub-Saharan Africa, High-income North America and Oceania in 2019. The burden of SIDS was higher in males than females consistently from 1990 to 2019. Higher SDI and income level was associated with lower burden of SIDS; further, countries with higher SDI and income had greater decreases in SIDS burden from 1990 to 2019. CONCLUSIONS: The burden of SIDS has decreased drastically from 1990 to 2019. However, the improvements have occurred disproportionately between regions and SDI levels. Focused preventive efforts in under-resourced populations are needed.

4.
Rev Med Virol ; : e2349, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416354

RESUMO

Among coronavirus disease 2019 (COVID-19) patients, physically active individuals may be at lower risk of fatal outcomes. However, to date, no meta-analysis has been carried out to investigate the relationship between physical activity (PA) and fatal outcomes in patients with COVID-19. Therefore, this meta-analysis aims to explore the hospitalisation, intensive care unit (ICU) admissions, and mortality rates of COVID-19 patients with a history of PA participation before the onset of the pandemic, and to evaluate the reliability of the evidence. A systematic search of MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and medRxiv was conducted for articles published up to January 2022. A random-effects meta-analysis was performed to compare disease severity and mortality rates of COVID-19 patients in physically active and inactive cases. Twelve studies involving 1,256,609 patients (991,268 physically active and 265,341 inactive cases) with COVID-19, were included in the pooled analysis. The overall meta-analysis compared with inactive controls showed significant associations between PA with reduction in COVID-19 hospitalisation (risk ratio (RR) = 0.58, 95% confidence intervals (CI) 0.46-0.73, P = 0.001), ICU admissions (RR = 0.65, 95% CI 0.52-0.81, P = 0.001) and mortality (RR = 0.47, 95% CI 0.38-0.59, P = 0.001). The protective effect of PA on COVID-19 hospitalisation and mortality could be attributable to the types of exercise such as resistance exercise (RR = 0.27, 95% CI 0.15-0.49, P = 0.001) and endurance exercise (RR = 0.41, 95% CI 0.23-0.74, P = 0.003), respectively. Physical activity is associated with decreased hospitalisation, ICU admissions, and mortality rates of patients with COVID-19. Moreover, COVID-19 patients with a history of resistance and endurance exercises experience a lower rate of hospitalisation and mortality, respectively. Further studies are warranted to determine the biological mechanisms underlying these findings.

5.
Int J Infect Dis ; 119: 130-139, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35339716

RESUMO

OBJECTIVES: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. METHODS: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. RESULTS: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). CONCLUSIONS: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.

6.
Adv Sci (Weinh) ; : e2103526, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35322595

RESUMO

Kidney organoids derived from human pluripotent stem cells (hPSCs) have extensive potential for disease modelling and regenerative medicine. However, the limited vascularization and immaturity of kidney organoids have been still remained to overcome. Extracellular matrix (ECM) can provide mechanical support and a biochemical microenvironment for cell growth and differentiation. Here in vitro methods using a kidney decellularized extracellular matrix (dECM) hydrogel to culture hPSC-derived kidney organoids, which have extensive vascular network and their own endothelial cells, are reported. Single-cell transcriptomics reveal that the vascularized kidney organoids cultured using the kidney dECM have more mature patterns of glomerular development and higher similarity to human kidney than those cultured without the kidney dECM. Differentiation of α-galactosidase A (GLA)-knock-out hPSCs generated using CRISPR/Cas9 into kidney organoids by the culture method using kidney dECM efficiently recapitulate Fabry nephropathy with vasculopathy. Transplantation of kidney organoids with kidney dECM into kidney of mouse accelerates the recruitment of endothelial cells from the host mouse kidney and maintains vascular integrity with the more organized slit diaphragm-like structures than those without kidney dECM. The kidney dECM methodology for inducing extensive vascularization and maturation of kidney organoids can be applied to studies for kidney development, disease modeling, and regenerative medicine.

7.
Int J Mol Sci ; 23(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35163260

RESUMO

Autoimmune diseases are disorders that destruct or disrupt the body's own tissues by its own immune system. Several studies have revealed that polymorphisms of multiple genes are involved in autoimmune diseases. Meanwhile, gene therapy has become a promising approach in autoimmune diseases, and clustered regularly interspaced palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) has become one of the most prominent methods. It has been shown that CRISPR-Cas9 can be applied to knock out proprotein convertase subtilisin/kexin type 9 (PCSK9) or block PCSK9, resulting in lowering low-density lipoprotein cholesterol. In other studies, it can be used to treat rare diseases such as ornithine transcarbamylase (OTC) deficiency and hereditary tyrosinemia. However, few studies on the treatment of autoimmune disease using CRISPR-Cas9 have been reported so far. In this review, we highlight the current and potential use of CRISPR-Cas9 in the management of autoimmune diseases. We summarize the potential target genes for immunomodulation using CRISPR-Cas9 in autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes mellitus (DM), psoriasis, and type 1 coeliac disease. This article will give a new perspective on understanding the use of CRISPR-Cas9 in autoimmune diseases not only through animal models but also in human models. Emerging approaches to investigate the potential target genes for CRISPR-Cas9 treatment may be promising for the tailored immunomodulation of some autoimmune diseases in the near future.


Assuntos
Doenças Autoimunes/genética , Sistemas CRISPR-Cas/genética , Animais , Edição de Genes/métodos , Humanos , RNA Guia/genética
8.
Pharmacol Res ; 176: 106052, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34999224

RESUMO

Various melatonin supplementations have been developed to improve health outcomes in various clinical conditions. Thus, we sought to evaluate and summarize the effect of melatonin treatments in clinical settings for health outcomes. We searched PubMed/Medline, Embase, and Cochrane Library from inception to 4 February 2021. We included meta-analyses of randomized controlled trials investigating the melatonin intervention for any health outcome. Based on the different effect sizes of each meta-analysis, we calculated random models' standardized mean differences or risk ratios. We observed robust evidence supported by statistical significance with non-considerable heterogeneity between studies for sleep-related problems, cancer, surgical patients, and pregnant women. Patients with sleep disorder, sleep onset latency (SMD 0.33, 95% CI: 0.10 - 0.56, P < 0.01) were significantly improved whereas no clear evidence was shown with sleep efficiency (1.10, 95% CI: -0.26 to 2.45). The first analgesic requirement time (SMD 5.81, 95% CI: 2.57-9.05, P < 0.001) of surgical patients was distinctly improved. Female patients under artificial reproductive technologies had significant increase in the top-quality embryos (SMD 0.53, 95% CI: 0.27 - 0.79, P < 0.001), but no statistically clear evidence was found in the live birth rate (SMD 1.20, 95% CI: 0.83 - 1.72). Survival at one year (RR 1.90, 95% CI: 1.28 - 2.83, P < 0.005) significantly increased with cancer patients. Research on melatonin interventions to treat clinical symptoms and sleep problems among diverse health conditions was identified and provided considerable evidence. Future well-designed randomized clinical trials of high quality and subgroup quantitative analyses are essential.


Assuntos
Melatonina/uso terapêutico , Humanos , Transtornos Mentais/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos do Sono-Vigília/tratamento farmacológico
9.
J Clin Med ; 11(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35054037

RESUMO

BACKGROUND: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. RESULT: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. INTERPRETATION: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years.

10.
J Med Virol ; 94(5): 1935-1949, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34958144

RESUMO

The COVID-19 pandemic and related restrictions can impact mental health. To quantify the mental health burden of COVID-19 pandemic, we conducted a systematic review and meta-analysis, searching World Health Organization COVID-19/PsycInfo/PubMed databases (09/29/2020), including observational studies reporting on mental health outcomes in any population affected by COVID-19. Primary outcomes were the prevalence of anxiety, depression, stress, sleep problems, posttraumatic symptoms. Sensitivity analyses were conducted on severe mental health problems, in high-quality studies, and in representative samples. Subgroup analyses were conducted stratified by age, sex, country income level, and COVID-19 infection status. One-hundred-seventy-three studies from February to July 2020 were included (n = 502,261, median sample = 948, age = 34.4 years, females = 63%). Ninety-one percent were cross-sectional studies, and 18.5%/57.2% were of high/moderate quality. The highest prevalence emerged for posttraumatic symptoms in COVID-19 infected people (94%), followed by behavioral problems in those with prior mental disorders (77%), fear in healthcare workers (71%), anxiety in caregivers/family members of people with COVID-19 (42%), general health/social contact/passive coping style in the general population (38%), depression in those with prior somatic disorders (37%), and fear in other-than-healthcare workers (29%). Females and people with COVID-19 infection had higher rates of almost all outcomes; college students/young adults of anxiety, depression, sleep problems, suicidal ideation; adults of fear and posttraumatic symptoms. Anxiety, depression, and posttraumatic symptoms were more prevalent in low-/middle-income countries, sleep problems in high-income countries. The COVID-19 pandemic adversely impacts mental health in a unique manner across population subgroups. Our results inform tailored preventive strategies and interventions to mitigate current, future, and transgenerational adverse mental health of the COVID-19 pandemic.


Assuntos
COVID-19 , Pandemias , Adulto , COVID-19/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Saúde Mental , Prevalência , SARS-CoV-2 , Adulto Jovem
11.
Comput Struct Biotechnol J ; 19: 5920-5930, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34849196

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus (T2D), and these two metabolic diseases demonstrate bidirectional influences. The identification of microbiome profiles that are specific to liver injury or impaired glucose metabolism may assist understanding of the role of the gut microbiota in the relationship between NAFLD and T2D. Here, we studied a biopsy-proven Asian NAFLD cohort (n = 329; 187 participants with NAFLD, 101 with NAFLD and T2D, and 41 with neither) and identified Enterobacter, Romboutsia, and Clostridium sensu stricto as the principal taxa associated with the severity of NAFLD and T2D, whereas Ruminococcus and Megamonas were specific to NAFLD. In particular, the taxa that were associated with both severe liver pathology and T2D were also significantly associated with markers of diabetes, such as fasting blood glucose and Hb1Ac. Enterotype analysis demonstrated that participants with NAFLD had a significantly higher proportion of Bacteroides and a lower proportion of Ruminococcus than a Korean healthy twin cohort (n = 756). However, T2D could not be clearly distinguished from NAFLD. Analysis of an independent T2D cohort (n = 185) permitted us to validate the T2D-specific bacterial signature identified in the NAFLD cohort. Functional inference analysis revealed that endotoxin biosynthesis pathways were significantly enriched in participants with NAFLD and T2D, compared with those with NAFLD alone. These findings may assist with the development of effective therapeutic approaches for metabolic diseases that are associated with specific bacterial signatures.

12.
ACS Appl Mater Interfaces ; 13(50): 60425-60432, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34902240

RESUMO

Polymer nanofiber-based porous structures ("breathable devices") have been developed for breathable epidermal electrodes, piezoelectric nanogenerators, temperature sensors, and strain sensors, but their applications are limited because increasing the porosity reduces device robustness. Herein, we report an approach to produce ultradurable, cost-effective breathable electronics using a hierarchical metal nanowire network and an optimized photonic sintering process. Photonic sintering significantly reduces the sheet resistance (16.25 to 6.32 Ω sq-1) and is 40% more effective than conventional thermal annealing (sheet resistance: 12.99 Ω sq-1). The mechanical durability of the sintered (648.9 Ω sq-1) sample is notably improved compared to that of the untreated (disconnected) and annealed (19.1 kΩ sq-1) samples after 10,000 deformation cycles at 40% tensile strain. The sintered sample exhibits ∼29 times less change in electrical performance compared to the thermally annealed sample. This approach will lead to the development of affordable and ultradurable commercial breathable electronics.

14.
J Urol ; 206(6): 1361-1372, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34288714

RESUMO

PURPOSE: Ejaculatory dysfunction (EjD) and erectile dysfunction after cancer treatment are clinically important complications, but their exact prevalence by various kinds of cancer site and type of treatment is unknown. The aim of this systematic review and meta-analysis was to examine the available evidence and provide pooled estimates for prevalence of EjD and erectile dysfunction in relation to all cancer sites and identify characteristics associated with EjD in cancer patients. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of cross-sectional and case-control studies. We searched 4 electronic databases (Medline®, CINAHL, PsychInfo and Embase®) until July 22, 2020. All retrospective or prospective studies reporting the prevalence of EjD in male patients with cancer were included in this review. A random effects meta-analysis was conducted calculating prevalence proportions with 95% confidence intervals. Prevalence proportions were calculated for the incidences of EjD by cancer site and type of treatment. RESULTS: A total of 64 studies (a total of 10,057 participants) were included for analysis. The most common cancer sites were bladder, colon, testis and rectum. The prevalence rates of EjD after surgical intervention ranged from 14.5% (95% CI 2.2-56.3) in colon cancer to 53.0% (95% CI 23.3-80.7) in bladder cancer. The prevalence rates of erectile dysfunction ranged from 6.8% (95% CI 0.8-39.1) in bladder cancer to 68.7% (95% CI 55.2-79.6) in cancer of the rectum. CONCLUSIONS: In a large study-level meta-analysis, we looked at a high prevalence of EjD and erectile dysfunction at various cancer sites and across different treatment types. Prospective studies of EjD and erectile dysfunction after various kinds of cancer treatments are warranted.


Assuntos
Ejaculação , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Neoplasias/complicações , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Humanos , Masculino , Prevalência
15.
Mol Biol Rep ; 48(3): 2173-2181, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33630206

RESUMO

BACKGROUND: The pawpaw tree has several beneficial effects. However, no studies have been conducted to address the mechanisms underlying the cytotoxic effects of pawpaw extracts against cancer cells, and no study has investigated the anti-inflammatory effects. Hence, in this study, the growth-inhibitory effects of pawpaw (Asimina triloba [L.] Dunal) extracts against gastric (AGS) and cervical (HeLa) cancer cells and the inhibitory effects of pawpaw extracts against inflammatory factors (NO, TNF-α, IL-6, iNOS, and COX-2) were investigated. METHODS AND RESULTS: The viability of AGS and HeLa cells, the analysis of cell cycle, and the expression of apoptosis marker protein were determined using MTT assay, FACS, western blotting, and TUNEL assays. The inflammatory factors were determined using Griess method, ELISA assay kit, and RAW 264.7 cells. The IC50 values of twig and unripe fruit extracts for AGS cells were 82.01 and 100.61 µg/mL, respectively. For HeLa cells, pawpaw twig extracts exhibited the strongest ability to inhibit cervical cancer cell growth (IC50 = 97.73 µg/mL). Analysis of the cell cycle phase distribution and expression of the apoptosis regulatory proteins BCL-2, BAX, caspase-3, and PARP showed that pawpaw twig, root, and unripe fruit extracts induced Sub G1 cell cycle arrest and apoptosis of AGS and HeLa cells. In addition, the twig, root, and unripe fruit extracts of pawpaw effectively inhibited the inflammatory makers NO, TNF-α, IL-6, and iNOS. Particularly, the twig, root, and unripe fruit extracts at concentrations of 50 µg/mL exhibited > 50% inhibition of TNF-α. CONCLUSIONS: These findings indicate that pawpaw extracts are natural therapeutic agents that may be used for the prevention and treatment of gastric and cervical cancers, and encourage further studies on the anti-inflammatory potential of the pawpaw tree.


Assuntos
Anti-Inflamatórios/farmacologia , Asimina/química , Frutas/química , Folhas de Planta/química , Raízes de Plantas/química , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7
16.
Plants (Basel) ; 11(1)2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35009012

RESUMO

Trans-lycopene is a functional phytochemical abundant in red-fleshed watermelons, and its contents vary among cultivars. In this study, the genetic basis of high trans-lycopene contents in scarlet red flesh was evaluated. Three near-isogenic lines (NILs) with high trans-lycopene contents were derived from the scarlet red-fleshed donor parent DRD and three coral red-fleshed (low trans-lycopene contents) recurrent parents. The lycopene contents of DRD (589.4 ± 71.8 µg/g) were two times higher than that of the recurrent parents, and values for NILs were intermediate between those of the parents. Coral red-fleshed lines and F1 cultivars showed low trans-lycopene contents (135.7 ± 18.0 µg/g to 213.7 ± 39.5 µg/g). Whole-genome resequencing of two NILs and their parents and an analysis of genome-wide single-nucleotide polymorphisms revealed three common introgressed regions (CIRs) on chromosomes 6, 9, and 10. Twenty-eight gene-based cleaved amplified polymorphic sequence (CAPS) markers were developed from the CIRs. The CAPS markers derived from CIR6 on chromosome 6, spanning approximately 1 Mb, were associated (R2 = 0.45-0.72) with the trans-lycopene contents, particularly CIR6-M1 and CIR6-M4. Our results imply that CIR6 is a major genomic region associated with variation in the trans-lycopene contents in red-fleshed watermelon, and CIR6-M1 and CIR6-M4 may be useful for marker-assisted selection.

17.
Nat Commun ; 11(1): 4982, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020474

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal/fisiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/metabolismo , Biomarcadores , Fezes/química , Fezes/microbiologia , Fibrose , Microbioma Gastrointestinal/genética , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Cirrose Hepática/microbiologia , Cirrose Hepática/patologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/patologia , Propionatos/análise , Propionatos/metabolismo , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes
18.
Int J Mol Sci ; 21(17)2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32846909

RESUMO

Air pollution reportedly contributes to the development and exacerbation of atopic dermatitis (AD). However, the exact mechanism underlying this remains unclear. To examine the relationship between air pollution and AD, a clinical, histological, and genetic analysis was performed on particulate matter (PM)-exposed mice. Five-week-old BALB/c mice were randomly divided into four groups (control group, ovalbumin (OVA) group, PM group, OVA + PM group; n = 6) and treated with OVA or PM10, alone or together. Cutaneous exposure to OVA and PM10 alone resulted in a significant increase in skin severity scores, trans-epidermal water loss (TEWL) and epidermal thickness compared to the control group at Week 6. The findings were further accentuated in the OVA + PM group showing statistical significance over the OVA group. A total of 635, 501, and 2149 genes were found to be differentially expressed following OVA, PM10, and OVA + PM10 exposure, respectively. Strongly upregulated genes included RNASE2A, S100A9, SPRR2D, THRSP, SPRR2A1 (OVA vs. control), SPRR2D, S100A9, STFA3, CHIL1, DBP, IL1B (PM vs. control) and S100A9, SPRR2D, SPRR2B, S100A8, SPRR2A3 (OVA + PM vs. control). In comparing the groups OVA + PM with OVA, 818 genes were differentially expressed with S100A9, SPRR2B, SAA3, S100A8, SPRR2D being the most highly upregulated in the OVA + PM group. Taken together, our study demonstrates that PM10 exposure induces/aggravates skin inflammation via the differential expression of genes controlling skin barrier integrity and immune response. We provide evidence on the importance of public awareness in PM-associated skin inflammation. Vigilant attention should be paid to all individuals, especially to those with AD.


Assuntos
Poluição do Ar/efeitos adversos , Dermatite Atópica/patologia , Material Particulado/toxicidade , Pele/efeitos dos fármacos , Animais , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Fatores de Risco , Pele/metabolismo , Pele/patologia
19.
J Clin Med ; 9(1)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936262

RESUMO

Systemic antibiotics are extensively used to control moderate to severe acne. Hence, it is crucial to understand their impact on the skin microbiota, which is supposedly perturbed. The purpose of this study was to compare the makeup and diversity of the skin microbiota in acne patients before and after taking oral antibiotics. A longitudinal cohort study was performed on 20 participants with moderate to severe facial acne with no recent use of oral and topical antibiotics/retinoids. Patients were prescribed oral doxycycline, 100 mg, twice daily for six weeks. Skin areas on the cheek were sampled for 16S ribosomal RNA gene sequencing at baseline, and after six weeks of doxycycline treatment. Ten males and 10 females aged 11 to 44 years with a median Investigator's Global Assessment score of 3 (moderate) were enrolled. At baseline, Cutibacterium acnes (formerly Propionibacterium acnes) was the most dominant species followed by Staphylococcus epidermidis. Acne severity showed a positive correlation with the abundance of Cutibacterium acnes. Across all subjects, antibiotic treatment reduced clinical acne grades and was associated with a 1.96-fold reduction in the relative abundance of Cutibacterium acnes (p = 0.01, 95% CI -22% to -3%). Marked changes were also identified in other bacterial species, such as Cutibacterium granulosum (formerly Propionibacterium granulosum), which increased by 4.46-fold (p = 0.02, 95% CI 0.004% to 0.9%) in the treated samples. In general, antibiotics administration was associated with an increase in bacterial diversity (alpha diversity). Principal coordinates analysis showed mild clustering of samples by patient (analysis of similarity, R = 0.135, p = 0.04) whereas there was scant clustering with treatment (ANOSIM, R = 0.005; p = 0.29). In conclusion, we found individuals with acne to have a unique microbial signature. Acne treatment with systemic antibiotics was associated with changes in the composition and diversity of skin microbiota, especially Cutibacterium acnes, which correlates with acne severity. Our study provides insight into the skin microbiota in acne and how it is modulated by systemic antibiotics.

20.
Int Ophthalmol ; 40(2): 325-333, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31564048

RESUMO

PURPOSE: To investigate the features of the choriocapillaris using four different optical coherence tomography angiography (OCTA) devices. METHODS: OCTA images of the choriocapillaris from consecutive healthy subjects were obtained with four different OCTA devices (Zeiss PLEX Elite, Topcon DRI OCT-1 Atlantis, Zeiss AngioPlex, and Heidelberg Spectralis OCTA). The 3 × 3 mm OCTA images were processed with ImageJ. The mean vascular density and mean flow void area of the choriocapillaris were compared among devices. Flow voids were analyzed with two different imaging adjustment methods, auto-local threshold with the Phansalkar method and a method using a device-specific threshold value. RESULTS: The mean vascular density of the choriocapillaris differed among the four devices (all P < 0.001). The mean flow void area as measured with the auto-local threshold method also differed among devices (P < 0.001) and was not correlated among devices (all P > 0.05). Results for mean flow void area measured with a device-specific threshold value using the Plex-Elite and DRI OCT-1 Atlantis were correlated (ß = 2.271, P < 0.001), but there were no correlations among other devices (P > 0.05). For the Plex-Elite and DRI OCT-1 Atlantis, the mean flow void area was positively correlated between the two image adjustment methods (all P < 0.05). CONCLUSIONS: Vascular densities and flow void areas of the choriocapillaris varied according to the device used and the image adjustment method. The characteristics of different devices and the image adjustment method should be considered for analysis of the choriocapillaris.


Assuntos
Corioide/irrigação sanguínea , Angiofluoresceinografia/instrumentação , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/instrumentação , Adulto , Desenho de Equipamento , Feminino , Seguimentos , Fundo de Olho , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes
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