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1.
Parkinsonism Relat Disord ; 93: 19-26, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34763304

RESUMO

BACKGROUND: The association between nonalcoholic fatty liver disease (NAFLD) and Parkinson's disease (PD) remains uncertain. This study sought to assess the sex-specific association between NAFLD and PD risk considering that sex is an important factor in both conditions. METHODS: We included 2,651,169 men and 2,998,904 women (≥40 years of age) who underwent health examinations in 2009 using database of the Korean National Health Insurance Service. To define NAFLD, the Fatty Liver Index (FLI) was used and a score of at least 60 points was regarded as suggesting the presence of NAFLD. Cox proportional hazards analyses were performed to evaluate the association between the presence of NAFLD/each component of FLI and the risk of PD. All analyses were stratified by sex. RESULTS: The median follow-up duration was 7.3 years in both men and women. Of the total study population, 23,233 patients with PD (10,578 men and 12,655 women) were identified. Among men, a decreased risk of PD was observed in those with NAFLD [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI): 0.82-0.91]. In contrast, among women, an increased risk of PD was observed in those with NAFLD (aHR: 1.09, 95% CI: 1.02-1.16). This different association according to sex was more prominent among younger participants but was not significant in the old age group. CONCLUSIONS: NAFLD defined by FLI is differently associated with the risk of PD by sex (i.e., low risk of PD in men with NAFLD vs. high risk of PD in women with NAFLD).

2.
PLoS One ; 16(11): e0256651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34807933

RESUMO

BACKGROUND: Preconditioning with lipopolysaccharide (LPS) is used to improve the secretion of anti-inflammatory agents in B cells. However, there are only a few studies on canine B cells. OBJECTIVE: This study aimed to evaluate the immune regulatory capacity of canine peripheral blood mononuclear cell-derived B cells pretreated with LPS. METHODS: Canine B cells were isolated from canine peripheral blood mononuclear cells, which were obtained from three healthy canine donors. The B cells were preconditioned with LPS, and then cell viability and the expression of the regulatory B cell marker were assessed. Finally, RNA extraction and immunofluorescence analysis were performed. RESULTS: LPS primed B cells expressed the interleukin (IL)-10 surface marker and immunoregulatory gene expression, such as IL-10, programmed death-ligand 1, and transforming growth factor beta. Macrophages in the inflammatory condition cocultured with primed B cells were found to have significantly down-regulated pro-inflammatory cytokine, such as tumor necrosis factor-α, and up-regulated anti-inflammatory cytokines such as IL-10. Additionally, it was revealed that co-culture with primed B cells re-polarized M1 macrophages to M2 macrophages. CONCLUSIONS: This study revealed that LPS-primed B cells have an anti-inflammatory effect and can re-polarize macrophages, suggesting the possibility of using LPS-primed B cells as a therapeutic agent for its anti-inflammatory effects and immune modulation.

3.
J Clin Med ; 10(21)2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34768709

RESUMO

Although both obesity and menopause are associated with increased risk of diabetes mellitus (DM), the association between obesity and DM according to menopausal status remains uncertain. Therefore, we conducted a study to examine the relationship between obesity and incidence of diabetes mellitus (DM) in premenopausal and postmenopausal women. Total of 926,196 premenopausal and 1,193,881 postmenopausal women who underwent health examinations from 2009 to 2014 were identified using the database of the Korean National Health Insurance Service. We compared the incidence and risk of DM according to body mass index (BMI) and waist circumference (WC) in the two groups of women. Cox proportional hazards analyses were performed to evaluate the association between the presence of obesity and risk of DM according to menopausal state. During the 7.8-year follow-up period, 37,736 (4.1%) premenopausal women and 121,102 (10.1%) postmenopausal women were diagnosed with DM. Compared to the reference group (BMI 18.5-23), a stronger association between obesity and risk of DM was observed in both pre- and postmenopausal women: multivariable-adjusted hazard ratios and 95% confidence intervals for BMI subgroups <18.5, 23-25, 25-30, and >30 were 0.62 (0.54, 0.70), 1.91 (1.85, 1.97), 3.38 (3.28, 3.47), and 6.25 (6.02, 6.48), respectively (p trend < 0.001) in premenopausal women and 0.87 (0.82, 0.92), 1.44 (1.41, 1.46), 2.00 (1.97, 2.03), and 2.96 (2.89, 3.02) in postmenopausal women (p trend < 0.001, p-interaction < 0.001). A similar trend was observed for WC. Subgroup analyses of women aged 45 to 55 also showed a stronger association with DM in premenopausal than in postmenopausal women. In conclusion, the association between obesity and DM was stronger in premenopausal women than in postmenopausal women. As estrogens are synthesized in adipose tissue by aromatization of androgens after menopause, increased estrogen levels in obese postmenopausal might have a protective effect against DM.

5.
Food Sci Anim Resour ; 41(6): 950-966, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34796323

RESUMO

This study investigated the effects of lemon extract powder and vinegar powder on the physicochemical and microbiological characteristics of pork sausages naturally cured using white kimchi powder during storage for 30 days. Six batches were included: control (0.01% sodium nitrite and 0.05% sodium ascorbate); treatment 1 (0.3% white kimchi powder and 0.5% lemon extract powder); treatment 2 (0.3% white kimchi powder and 1.0% lemon extract powder); treatment 3 (0.3% white kimchi powder and 0.5% vinegar powder); treatment 4 (0.3% white kimchi powder and 1.0% vinegar powder); and treatment 5 (0.3% white kimchi powder, 0.5% lemon extract powder, and 0.5% vinegar powder). Treatment 2 had significantly lower pH values and higher cooking loss than the other batches (p<0.05). Treatments 1, 2, and 5 had similar (p>0.05) CIE a* as the control, while treatments 3 and 4 showed significantly lower values (p<0.05). The residual nitrite content in naturally cured products was lower than the control (p<0.05), while treatments 1 and 2 showed significantly higher nitrosyl hemochrome content and curing efficiency (p<0.05). TBARS values were similar for all treatments and the control (p>0.05). Treatments 1 and 2 showed significantly reduced aerobic plate counts (APC; p<0.05) than the control and other treatments. However, across all batches, TBARS values and APC significantly increased during storage (p<0.05). Our results suggest that lemon extract powder, rather than vinegar powder, may offer a promising alternative for supplementing the functions of nitrite in naturally cured sausages.

6.
Diabetes Obes Metab ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726318

RESUMO

AIM: Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular diseases (CVDs). Because studies of young adults are limited, we investigated the relationship between NAFLD and cardiovascular events among a nationally representative sample of young adults in Korea. METHODS AND RESULTS: This population-based cohort study from the Korean National Health Insurance Service included adults who were 20-39 years old when they underwent a health examination from 2009-2012. NAFLD was defined as fatty liver index (FLI) ≥60, and participants were divided into three groups according to FLI (<30, 30-59, and ≥60) to investigate the dose-dependent effect of FLI scores. Among 5,324,410 participants, 9.8% had an FLI ≥60. There were 13,051 myocardial infarctions (MI, 0.39%) and 8,573 strokes (0.26%) during a median follow-up of 8.4 years. In multivariable analysis, NAFLD was associated with a higher risk of MI and stroke (hazard ratio [HR]=1.69; 95% confidence interval [CI]: 1.61-1.77 and HR=1.73; 95% CI: 1.63-1.84, respectively). MI and stroke had dose-depended relationships with FLI (HR=1.28 in FLI 30-59 and 1.73 in FLI ≥60 for MI and HR=1.18 in FLI 30-59 and 1.41 in FLI ≥60 for stroke, respectively). CONCLUSIONS: NAFLD was an independent predictor of MI and stroke in young adults. These results suggest that primary prevention of CVD should be emphasized in young adults with NAFLD. This article is protected by copyright. All rights reserved.

7.
J Neuroinflammation ; 18(1): 268, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774090

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a devastating age-related neurodegenerative disorder and characterized by progressive loss of memory and cognitive functions, which are associated with amyloid-beta (Aß) plaques. Immune cells play an important role in the clearance of Aß deposits. Immune responses are regulated by immune regulators in which the B7 family members play a crucial role. We have recently identified erythroid membrane-associated protein (ERMAP) as a novel B7 family-related immune regulator and shown that ERMAP protein affects T cell and macrophage functions. METHODS: We produced a monoclonal antibody (mAb) against ERMAP protein and then determined the ability of the mAb to affect cognitive performance and AD pathology in mice. RESULTS:  We have shown that the anti-ERMAP mAb neutralizes the T cell inhibitory activity of ERMAP and enhances macrophages to phagocytose Aß in vitro. Administration of the mAb into AD mice improves cognitive performance and reduces Aß plaque load in the brain. This is related to increased proportion of T cells, especially IFNγ-producing T cells, in the spleen and the choroid plexus (CP), enhanced expression of immune cell trafficking molecules in the CP, and increased migration of monocyte-derived macrophages into the brain. Furthermore, the production of anti-Aß antibodies in the serum and the macrophage phagocytosis of Aß are enhanced in the anti-ERMAP mAb-treated AD mice. CONCLUSIONS: Our results suggest that manipulating the ERMAP pathway has the potential to provide a novel approach to treat AD patients.

8.
Mol Ther ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34793975

RESUMO

Alternative pre-mRNA splicing (AS) provides the potential to produce diversity at RNA and protein levels. Disruptions in the regulation of pre-mRNA splicing can lead to diseases. With the development of transcriptome and genome sequencing technology, increasing diseases have been identified to be associated with abnormal splicing of mRNAs. In tumors, abnormal alternative splicing frequently plays critical roles in cancer pathogenesis and may be considered as new biomarkers and therapeutic targets for cancer intervention. Metabolic abnormalities and immune disorders are important hallmarks of cancer. Alternative pre-mRNA splicing produces multiple different isoforms and diversify protein expression, which is utilized by the immune and metabolic reprogramming systems to expand gene functions. The abnormal splicing events contributed to tumor progression, partially due to effects on immune response and metabolic reprogramming. Herein, we reviewed the vital role of alternative splicing in regulating cancer metabolism and immune response. We discussed how alternative splicing regulates metabolic reprogramming of cancer cells and antitumor immune response and the possible strategies to targeting alternative splicing pathways or splicing-regulated metabolic pathway in the context of anticancer immunotherapy. Further, we highlighted the challenges that discuss the perspectives for RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms.

10.
Front Oncol ; 11: 728224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790569

RESUMO

Background: A wide variety of benign and malignant processes can manifest as non-mass enhancement (NME) in breast MRI. Compared to mass lesions, there are no distinct features that can be used for differential diagnosis. The purpose is to use the BI-RADS descriptors and models developed using radiomics and deep learning to distinguish benign from malignant NME lesions. Materials and Methods: A total of 150 patients with 104 malignant and 46 benign NME were analyzed. Three radiologists performed reading for morphological distribution and internal enhancement using the 5th BI-RADS lexicon. For each case, the 3D tumor mask was generated using Fuzzy-C-Means segmentation. Three DCE parametric maps related to wash-in, maximum, and wash-out were generated, and PyRadiomics was applied to extract features. The radiomics model was built using five machine learning algorithms. ResNet50 was implemented using three parametric maps as input. Approximately 70% of earlier cases were used for training, and 30% of later cases were held out for testing. Results: The diagnostic BI-RADS in the original MRI report showed that 104/104 malignant and 36/46 benign lesions had a BI-RADS score of 4A-5. For category reading, the kappa coefficient was 0.83 for morphological distribution (excellent) and 0.52 for internal enhancement (moderate). Segmental and Regional distribution were the most prominent for the malignant group, and focal distribution for the benign group. Eight radiomics features were selected by support vector machine (SVM). Among the five machine learning algorithms, SVM yielded the highest accuracy of 80.4% in training and 77.5% in testing datasets. ResNet50 had a better diagnostic performance, 91.5% in training and 83.3% in testing datasets. Conclusion: Diagnosis of NME was challenging, and the BI-RADS scores and descriptors showed a substantial overlap. Radiomics and deep learning may provide a useful CAD tool to aid in diagnosis.

11.
Front Genet ; 12: 742992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659363

RESUMO

An increasing number of experiments had verified that miRNA expression is related to human diseases. The miRNA expression profile may be an indicator of clinical diagnosis and provides a new direction for the prevention and treatment of complex diseases. In this work, we present a weighted voting-based model for predicting miRNA-disease association (WVMDA). To reasonably build a network of similarity, we established credibility similarity based on the reliability of known associations and used it to improve the original incomplete similarity. To eliminate noise interference as much as possible while maintaining more reliable similarity information, we developed a filter. More importantly, to ensure the fairness and efficiency of weighted voting, we focus on the design of weighting. Finally, cross-validation experiments and case studies are undertaken to verify the efficacy of the proposed model. The results showed that WVMDA could efficiently identify miRNAs associated with the disease.

12.
Exp Ther Med ; 22(6): 1368, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34659514

RESUMO

Ding's herbal enema (DHEP) is a traditional Chinese medicinal therapy that has been used to treat ulcerative colitis (UC) in China. The present study determined the molecular mechanism of the effect of DHEP in UC treatment. C57BL/6J mice were treated with 3.5% (w/v) dextran sulfate sodium (DSS) for 7 days to establish an animal model of colitis. The mice were divided into five groups (n=5): Control, vehicle, DHEP, mesalazine and ß-sitosterol. After oral administration for 7 days, the body weight, disease activity index, histopathology and inflammatory factors were analyzed. The fractions of CD4+Foxp3+ regulatory T (Treg) cells and CD4+IL-17A+ T helper (Th) cells were determined by flow cytometry. Gut microbiota composition was analyzed by next-generation sequencing. The results revealed that DHEP and ß-sitosterol could significantly alleviate the symptoms of DSS-induced UC. Furthermore, the levels of IL-6, cyclooxygenase-2, TNF-α and p65 were reduced after administration of DHEP. Additionally, the data indicated that DHEP could increase the abundance of seven operational taxonomic units (OTUs) and decrease the abundance of 12 OTUs in the gut microbiota. The content of short-chain fatty acids in the colon remodeled the balance of Treg/Th17 cells in DSS-induced UC in mice. The present study preliminarily defined the mechanism of action of DHEP in UC that may be associated with the regulation of the gut microbiota composition, and maintenance of the balance between Treg and Th17 cells. Furthermore, ß-sitosterol exhibited the same effects with DHEP and it could be a possible substitute for DHEP in UC treatment.

13.
Cureus ; 13(9): e17975, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34667662

RESUMO

Patients undergoing prolonged surgery in a lithotomy position may develop acute lower limb compartment syndrome in the absence of trauma or pre-existing vascular disease, otherwise known as well-leg compartment syndrome (WLCS). Early recognition and management would prevent the potential, lethal complications associated with this condition. We present a case of a 55-year-old gentleman who developed bilateral WLCS after prolonged abdominoperineal resection of his pelvic liposarcoma.

14.
J Cell Physiol ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34676546

RESUMO

Circular RNAs (circRNAs) are closed back-splicing products of precursor mRNA in eukaryotes. Compared with linear mRNAs, circRNAs have a special structure and stable expression. A large number of studies have provided different regulatory mechanisms of circRNAs in tumors. Challenges exist in understanding the control of circRNAs because of their sequence overlap with linear mRNA. Here, we survey the most recent progress regarding the regulation of circRNA biogenesis by RNA-binding proteins, one of the vital functional proteins. Furthermore, substantial circRNAs exert compelling biological roles by acting as protein sponges, by being translated themselves or regulating posttranslational modifications of proteins. This review will help further explore more types of functional proteins that interact with circRNA in cancer and reveal other unknown mechanisms of circRNA regulation.

15.
J Plant Physiol ; 266: 153534, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601338

RESUMO

Cold stress is one of the harsh environmental stresses that adversely affect plant growth and crop yields in the Qinghai-Tibet Plateau. However, plants have evolved mechanisms to overcome the impact of cold stress. Progress has been made in understanding how plants perceive and transduce low-temperature signals to tolerate cold stress. Small signaling molecules are crucial for cellular signal transduction by initiating the downstream signaling cascade that helps plants to respond to cold stress. These small signaling molecules include calcium, reactive oxygen species, nitric oxide, hydrogen sulfide, cyclic guanosine monophosphate, phosphatidic acid, and sphingolipids. The small signaling molecules are involved in many aspects of cellular and physiological functions, such as inducing gene expression and activating hormone signaling, resulting in upregulation of the antioxidant enzyme activities, osmoprotectant accumulation, malondialdehyde reduction, and photosynthesis improvement. We summarize our current understanding of the roles of the small signaling molecules in cold stress in plants, and highlight their crosstalk in cold signaling transduction. These discoveries help us understand how the plateau plants adapt to the severe alpine environment as well as to develop new crops tolerating cold stress in the Qinghai-Tibet Plateau.

16.
Cancers (Basel) ; 13(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638244

RESUMO

There have been conflicting results regarding the association between diabetes and the risk of hematologic malignancies, and its interaction with obesity is unknown. This study determined the risk of hematologic malignancies according to the glycemic status in a population-based study involving health screening 9,774,625 participants. The baseline glycemic status of the participants was categorized into no diabetes, impaired fasting glucose (IFG), newly detected diabetes, diabetes duration <5 years, and diabetes duration ≥5 year groups. The risks of overall and specific hematologic malignancies were estimated using a Cox regression analysis. During a median follow up of 7.3 years, 14,733 hematologic malignancies developed. The adjusted hazard ratio (aHR) for the risk of all the hematologic malignancies was 0.99 (95% confidence interval (CI) 0.95-1.02) for IFG, 0.99 (95% CI 0.91-1.08) for newly detected diabetes, 1.03 (95% CI 0.96-1.11) for diabetes duration <5 years, and 1.11 (95% CI 1.03, 1.20) for diabetes duration ≥5 year groups. The association was independent from obesity. The risk of non-Hodgkin's lymphoma (NHL) increased according to the progression of dysglycemia towards a longer diabetes duration, while Hodgkin's lymphoma did not. This study in Korea demonstrated diabetes to be associated with an increased risk of hematologic malignancies independent of obesity. The NHL risk increased with the diabetes duration.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34696553

RESUMO

The hypoglossal canal (HC) is an unusual location of the posterior fossa dural arteriovenous fistula (AVF), which usually occurs in the transverse or sigmoid sinus. Herein, we report a case of HC dural AVF successfully treated with transvenous coil embolization using detachable coils in a 68-year-old woman who presented with headache and left pulsatile tinnitus for 2 months. Brain magnetic resonance imaging (MRI) and cerebral angiography revealed left HC dural AVF. The pulsatile bruit disappeared immediately after the procedure. Follow-up MRI showed complete disappearance of the fistula. Precise localization of the fistula through careful consideration of the anatomy and transvenous coil embolization using a detachable coil can facilitate the treatment for HC dural AVF.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34656489

RESUMO

OBJECTIVES: The aim of this study was to compare the incremental prognostic value of coronary computed tomography (CT) angiography (CCTA)-derived machine learning fractional flow reserve CT (ML-FFRct) versus that of ischemia detected on single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) on incident cardiovascular outcomes. BACKGROUND: SPECT MPI and ML-FFRct are noninvasive tools that can assess the hemodynamic significance of coronary atherosclerotic disease. METHODS: We studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and SPECT MPI. ML-FFRct was computed using a ML prototype. The primary outcome was all-cause mortality and nonfatal myocardial infarction (D/MI), and the secondary outcome was D/MI and unplanned revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) occurring more than 90 days postimaging. Multiple nested multivariate cox regression was used to model a scenario wherein an initial anatomical assessment was followed by a functional assessment. RESULTS: A total of 471 patients (mean age: 64 ± 13 year; 53% males) were included. Comorbidities were prevalent (78% hypertension, 66% diabetes, 81% dyslipidemia). ML-FFRct was <0.8 in at least 1 proximal/midsegment was present in 41.6% of patients, and ischemia on MPI was present in 13.8%. After a median follow-up of 18 months, 7% of patients (n = 33) experienced D/MI. On multivariate Cox proportional analysis, the presence of ischemia on MPI but not ML-FFRct significantly predicted D/MI (HR: 2.3; 95% CI: 1.0-5.0; P = 0.047; or HR: 0.7; 95% CI: 0.3-1.4; P = 0.306 respectively) when added to CCTA obstructive stenosis. Furthermore, the model with SPECT ischemia had higher global chi-square result and significantly improved reclassification. Results were similar using the secondary outcome and on several sensitivity analyses. CONCLUSIONS: In a high-risk patient cohort, SPECT MPI but not ML-FFRct adds independent and incremental prognostic information to CCTA-based anatomical assessment and clinical risk factors in predicting incident outcomes.

20.
BJU Int ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617385

RESUMO

OBJECTIVES: To determine the preoperative assessment and perioperative outcomes of men undergoing bladder outlet obstruction (BOO) surgery in the UK. PATIENTS AND METHODS: A retrospective cohort study was conducted of all men undergoing BOO surgery in 105 UK hospitals over a 1-month period. The study included 1456 men, of whom 42% were catheter dependent prior to undergoing surgery. RESULTS: There was no evidence that a frequency-volume chart or urinary symptom questionnaire had been completed in 73% or 50% of men, respectively in the non-catheter-dependent group. Bipolar transurethral resection of the prostate (TURP) was the most common BOO surgical procedure performed (38%). Monopolar TURP was the next most prevalent modality (23%); however, minimally invasive BOO surgical procedures combined accounted for 17% of all procedures performed. Of the cohort 5% of men had complications within 30 days of surgery, only 1% had Clavien-Dindo Grade ≥III complications. Less than 1% of the cohort received a blood transfusion after BOO surgery and 2% were re-admitted to hospital after their BOO surgery. In total only 4% of the whole cohort were catheter dependent after BOO surgery. Pre- and postoperative paired International Prostate Symptom Score scores reviewed suggest that minimally invasive surgical procedures achieved comparable levels of improvement in both symptoms and bother at 3 months postoperatively in men who were not catheter dependent preoperatively. CONCLUSIONS: There has been a substantial shift in the available choice of procedure for BOO surgery around the UK in recent years. However, men can be reassured that overall BOO surgery treatments are safe and effective. Evidence of adherence to guidelines in the preoperative assessment of men with lower urinary tract symptoms undergoing surgery was poorly documented and must be improved.

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