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1.
Mol Cancer ; 21(1): 37, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130920

RESUMO

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
2.
Psych J ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922140

RESUMO

It is unclear how the ability to initially acquire information in a first learning trial relates to learning rate in subsequent repeated trials. The separation of memory span and learning rate is an important psychological dilemma that remains unaddressed. Given the potential effects of aging on memory and learning, this study investigated the separation of memory span and learning rate from behavior and spontaneous brain activity in older adults. We enrolled a total of 758 participants, including 707 healthy older adults and 51 mild cognitive impairment (MCI) patients. Sixty-five participants out of 707 completed resting-state functional magnetic resonance imaging (fMRI) scanning. Behaviorally, memory span and learning rate were not correlated with each other in the paired-associative learning test (PALT) but were negatively correlated in the auditory verbal learning test (AVLT). This indicated that the relationship between memory span and learning rate for item memory might be differentially affected by aging. Interaction analysis confirmed that these two capacities were differentially affected by test type (associative memory vs. item memory). Additionally, at three progressive brain activity indexes (ALFF, ReHo, and DC), the right brain regions (right inferior temporal gyrus and right middle frontal gyrus) were more negatively correlated with memory span, whereas, the left precuneus was more positively correlated with learning rate. Regarding pathological aging, none of the correlations between memory span and learning rate were significant in either PALT or AVLT in MCI. This study provides novel evidence for the dissociation of memory span and learning rate at behavioral and brain activity levels, which may have useful applications in detecting cognitive deficits or conducting cognitive interventions.

3.
Environ Toxicol ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913088

RESUMO

Procymidone (PCM) is a low toxicity fungicide, and an endocrine-disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low-, medium-, and high-dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three-dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10-5  M), medium dose (1 × 10-5  M), and high dose (3 × 10-5  M) PCM groups were established. We have found that, under both in vivo and in vitro conditions, all doses of PCM caused damage to mouse testes. Moreover, the levels of circZc3h4 RNA and Zc3h4 decreased while miR-212 increased in all treatment groups, with a corresponding rise in circRNA Scar and fall in Atp5b, compared to those in the control group, and all the changes showed a dose-response relationship. Besides, we have identified that low doses of PCM could activate the Ire1-Xbp1 pathway, whereas the medium and high doses activated the Perk-Elf2α-Atf4, Ire1-Xbp1, and Atf6 pathways. And it is, therefore, speculated that the unfolded protein response (UPR), circZc3h4 and circRNA Scar may have taken joint action in testicular injury in adolescent mice induced by PCM at the no observed adverse effect level (NOAEL, 100 mg/kg/day) and below NOAEL doses.

4.
Nutrients ; 14(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35956314

RESUMO

To examine the association of body mass index (BMI) and a plant-based diet (PBD) with cognitive impairment in older adults, this cohort study used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national, community-based, longitudinal, prospective study in China. Cognitive function was evaluated via the Mini-Mental State Examination (MMSE). Diet was assessed using a simplified food frequency questionnaire (FFQ), and PBD patterns were estimated using the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). BMI was measured objectively during the physical examination. Cox proportional hazard models and restricted cubic spline analyses were used. A total of 4792 participants with normal cognition at baseline were included, and 1077 participants were identified as having developed cognitive impairment during the 24,156 person-years of follow-up. A reverse J-shaped association was observed between BMI and cognitive impairment (p = 0.005 for nonlinearity). Participants who were overweight (HR = 0.79; 95% CI 0.66-0.95) and obese (HR = 0.72; 95% CI 0.54-0.96) had a decreased risk of cognitive impairment, while those who were underweight (HR = 1.42; 95% CI 1.21-1.66) had an increased risk. Lower PDI, lower hPDI, and higher uPDI were associated with an increased risk of cognitive impairment (HR = 1.32; 95% CI 1.16-1.50 for PDI; HR = 1.46; 95% CI 1.29-1.66 for hPDI; HR = 1.21; 95% CI 1.06-1.38 for uPDI). The protective effect of being overweight on cognitive impairment was more pronounced among participants with a higher PDI (HR = 0.74; 95% CI 0.57-0.95) than those with a lower PDI (HR = 0.87; 95% CI 0.67-1.12), among participants with a higher hPDI (HR = 0.73; 95% CI 0.57-0.94) than those with a lower hPDI (HR = 0.93; 95% CI 0.72-1.10), and among participants with a lower uPDI (HR = 0.61; 95% CI 0.46-0.80) than those with a higher uPDI (HR = 1.01; 95% CI 0.80-1.27). Our results support the positive associations of overweight status, obesity, an overall PBD, and a healthful PBD with cognitive function in older adults. A lower adherence to an overall PBD, a healthful PBD, and a higher adherence to an unhealthful PBD may attenuate the protective effect of being overweight on cognitive function.


Assuntos
Disfunção Cognitiva , Dieta Vegetariana , Idoso , Índice de Massa Corporal , China/epidemiologia , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Dieta , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso , Estudos Prospectivos
5.
Front Microbiol ; 13: 975610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958155

RESUMO

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV), is a highly contagious disease that brings tremendous economic losses to the global swine industry. As an intracellular obligate pathogen, PRRSV infects specific host cells to complete its replication cycle. PRRSV attachment to and entry into host cells are the first steps to initiate the replication cycle and involve multiple host cellular factors. In this review, we recapitulated recent advances on host cellular factors involved in PRRSV attachment and entry, and reappraised their functions in these two stages, which will deepen the understanding of PRRSV infection and provide insights to develop promising antiviral strategies against the virus.

6.
Transl Androl Urol ; 11(7): 959-973, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35958893

RESUMO

Background: Several studies report that sexuality is often affected by inflammatory bowel diseases (IBD). The aim of this meta-analysis was to investigate the association between IBD and sexual function. Methods: A literature search was conducted in PubMed, Web of Science, and EMBASE databases (up to September 1, 2020). Scores of sexual functions with a standard deviation and odds ratio (OR) or relative risk (RR) with a 95% CI were used to analysis the association between IBD and sexual function. Results: Eleven studies with 7,018 male IBD cases and 1,803 female IBD cases were included in the meta-analysis. In male individuals, the pooled results revealed that IBD was significantly associated with impaired erectile function and poor sexual satisfaction (RR for erectile function =1.50, 95% CI: 1.22 to 1.84, P<0.0001; standard mean difference for sexual satisfaction =-0.24, 95% CI: -0.33 to -0.15, P<0.0001). And among female individuals, IBD had impact on most sub-domains of sexual function, except pains. Conclusions: IBD is associated with worse sexual function. It has significant impact on erectile function and satisfaction for male individuals and has impact on most sub-domains of sexual function for female individuals.

7.
Front Aging Neurosci ; 14: 927625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959296

RESUMO

Background: Parkinson's disease (PD) is a common neurodegenerative disease affecting the movement of elderly patients. Environmental exposures are the risk factors for PD; however, gut environmental risk factors for PD are critically understudied. The proof-of-concept study is to identify gut metabolites in feces, as environmental exposure risk factors, that are associated with PD and potentially increase the risk for PD by using leverage of known toxicology results. Materials and methods: We collected the data regarding the gut metabolites whose levels were significantly changed in the feces of patients with PD from the original clinical studies after searching the following databases: EBM Reviews, PubMed, Embase, MEDLINE, and Elsevier ClinicalKey. We further searched each candidate metabolite-interacting PD gene set by using the public Comparative Toxicogenomics Database (CTD), identified and validated gut metabolites associated with PD, and determined gut metabolites affecting specific biological functions and cellular pathways involved in PD by using PANTHER tools. Results: Sixteen metabolites were identified and divided into the following main categories according to their structures and biological functions: alcohols (ethanol), amino acids (leucine, phenylalanine, pyroglutamic acid, glutamate, and tyrosine), short-chain fatty acids (propionate and butyrate), unsaturated fatty acids (linoleic acid and oleic acid), energy metabolism (lactate, pyruvate, and fumarate), vitamins (nicotinic acid and pantothenic acid), and choline metabolism (choline). Finally, a total of three identified metabolites, including butyrate, tyrosine, and phenylalanine, were validated that were associated with PD. Conclusion: Our findings identified the gut metabolites that were highly enriched for PD genes and potentially increase the risk of developing PD. The identification of gut metabolite exposures can provide biomarkers for disease identification, facilitate an understanding of the relationship between gut metabolite exposures and response, and present an opportunity for PD prevention and therapies.

8.
BMC Ophthalmol ; 22(1): 334, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933331

RESUMO

BACKGROUND: To describe the distribution of corneal endothelial cell density (ECD), and to explore its correlation with birth weight (BW), anthropometric parameters, and ocular biometric parameters in Chinese school children. METHODS: In the population-based cross-sectional Nanjing Eye Study, children were measured for anthropometric information, for ECD by the noncontact specular microscope and for ocular biometric parameters by the optic low-coherent reflectometer. Data from right eyes were analyzed to illustrate the distribution of ECD and for determining correlated factors with ECD using univariate and multiple linear regression analysis. Comparisons among three different BW groups were performed using a one-way ANOVA analysis followed by the Bonferroni correction for pairwise comparisons. RESULTS: Of 1171 children, the mean (± standard deviation) ECD was 2875.34 ± 195.00 cells/mm2. In the Multiple Linear Regression analysis, BW, gender and central corneal thickness were significantly associated with ECD. The ECD increased by 36.16 cells/mm2 with BW increasing by 1 kg (P = 0.001) and increased by 0.44 cells/mm2 for every additional 1 mm in central corneal thickness (P = 0.01). The ECD of girls was 54.41 cells/mm2 higher than boys (P < 0.001). Children born with low BW presented significantly lower ECD than those born with normal BW (P < 0.05) and high BW (P < 0.05). Age and axial length were not significantly associated with ECD (P = 0.06 and P = 0.21, respectively). CONCLUSIONS: In Chinese school children aged 82 to 94 months, the ECD is positively correlated with BW and central corneal thickness, in which BW is a newly identified associated factor. It is like that gender plays an important role in ECD distribution while girls have relatively greater ECD than boys.


Assuntos
Biometria , Endotélio Corneano , Peso ao Nascer , Contagem de Células , Criança , China/epidemiologia , Estudos Transversais , Células Endoteliais , Feminino , Humanos , Masculino
9.
Front Immunol ; 13: 887471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935930

RESUMO

Chimeric antigen receptor-T (CAR-T) cell therapy is a revolutionary adoptive cell therapy, which could modify and redirect T cells to specific tumor cells. Since CAR-T cell therapy was first approved for B cell-derived malignancies in 2017, it has yielded unprecedented progress in hematological tumors and has dramatically reshaped the landscape of cancer therapy in recent years. Currently, cumulative evidence has demonstrated that CAR-T cell therapy could be a viable therapeutic strategy for solid cancers. However, owing to the immunosuppressive tumor microenvironment (TME) and heterogenous tumor antigens, the application of CAR-T cell therapy against solid cancers requires circumventing more challenging obstacles. Breast cancer is characterized by a high degree of invasiveness, malignancy, and poor prognosis. The review highlights the underlying targets of CAR-T cell therapy in breast cancer, summarizes the challenges associated with CAR-T cell therapy, and proposes the strategies to overcome these challenges, which provides a novel approach to breast cancer treatment.


Assuntos
Neoplasias da Mama , Receptores de Antígenos Quiméricos , Neoplasias da Mama/terapia , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Humanos , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos/genética , Microambiente Tumoral
10.
Front Nutr ; 9: 899137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923199

RESUMO

Background: Observational studies have revealed that dried fruit intake may be associated with cancer incidence; however, confounding factors make the results prone to be disturbed. Therefore, we conducted a two-sample Mendelian randomization (MR) study to explore the causal relationship between dried fruit intake and 11 site-specific cancers. Materials and methods: Forty-three single nucleoside polymers (SNPs) with robust genome-wide association study (GWAS) evidence, strongly correlated with dried fruit intake, were used as instrumental variables (IVs) in this study. The summary-level genetic datasets of site-specific cancers were obtained from the Oncoarray oral cavity and oropharyngeal cancer consortium, International Lung Cancer Consortium, Breast Cancer Association Consortium (BCAC), Ovarian Cancer Association Consortium, PanScan1, and GWAS of other scholars. We analyzed the causality between dried fruit intake and 11 site-specific cancers using the inverse-variance-weighted (IVW) and weighted median (WM) methods. For the results of the MR analysis, Cochran's Q test was used to check for heterogeneity, and multiplicative random effects were used to evaluate the heterogeneity further. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. In addition, the main results of this study were validated by using the summary statistical data from the FinnGen and UK Biobank databases, and adjusted body mass index (BMI), years of education, fresh fruit intake, and vitamin C using multivariable MR analysis to ensure the stability of the research results. Results: The evidence from IVW analyses showed that each increase of dried fruit intake by one standard deviation was statistically significantly associated with 82.68% decrease of oral cavity/pharyngeal cancer incidence risk (P = 0.0131), 67.01% decrease of lung cancer incidence risk (P = 0.0011), 77% decrease of squamous cell lung cancer incidence risk (P = 0.0026), 53.07% decrease of breast cancer incidence risk (P = 4.62 × 10-5), 39.72% decrease of ovarian cancer incidence risk (P = 0.0183), 97.26% decrease of pancreatic cancer incidence risk (P = 0.0280), 0.53% decrease of cervical cancer incidence risk (P = 0.0482); however, there was no significant effect on lung adenocarcinoma (P = 0.4343), endometrial cancer (P = 0.8742), thyroid cancer (P = 0.6352), prostate cancer (P = 0.5354), bladder cancer (P = 0.8996), and brain cancer (P = 0.8164). In the validation part of the study results, the causal relationship between dried fruit intake and lung cancer (P = 0.0043), squamous cell lung cancer (P = 0.0136), and breast cancer (P = 0.0192) was determined. After adjusting for the potential impact of confounders, the causal relationship between dried fruit intake and lung cancer (P = 0.0034), squamous cell lung cancer (P = 0.046), and breast cancer (P = 0.0001) remained. The sensitivity analysis showed that our results were stable and reliable. Conclusion: The intake of dried fruits may have a protective effect against some site-specific cancers. Therefore, health education and a reasonable adjustment of dietary proportions may help in the primary prevention of cancer.

11.
Front Psychiatry ; 13: 927817, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923457

RESUMO

Lipidomics has been established as a potential tool for the investigation of mental diseases. However, the composition analysis and the comparison of the peripheral lipids regarding adult women with major depressive depression (MDD) or bipolar depression (BPD) has been poorly addressed. In the present study, age-matched female individuals with MDD (n = 28), BPD (n = 22) and healthy controls (HC, n = 25) were enrolled. Clinical symptoms were assessed and the plasma samples were analyzed by comprehensive lipid profiling based on liquid chromatography-mass spectrometry (LC/MS). We found that the composition of lipids was remarkably changed in the patients with MDD and BPD when compared to HC or compared to each other. Moreover, we identified diagnostic potential biomarkers comprising 20 lipids that can distinguish MDD from HC (area under the curve, AUC = 0.897) and 8 lipids that can distinguish BPD from HC (AUC = 0.784), as well as 13 lipids were identified to distinguish MDD from BPD with moderate reliability (AUC = 0.860). This study provides further understanding of abnormal lipid metabolism in adult women with MDD and BPD and may develop lipid classifiers able to effectively discriminate MDD from BPD and HC.

12.
Patient Prefer Adherence ; 16: 1819-1829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923659

RESUMO

Aim: To explore the correlation of exercise anticipation, self-efficacy and lower limb function in the elderly, and identify active predictors of exercise. The time up and go (TUG) has been used to access basic mobility skills, as well as strength, balance and agility, which is used in a range of population. Methods: A cross-sectional survey approach was employed in this study, assessing the functional relationship of the level of exercise anticipation, modified gait efficacy scale (mGES), self-efficacy for exercise scale (SEE), perceived efficacy of patient-physician interactions (PEPPI-10), behavioral regulation in exercise questionnaire (BREQ), and the time up and go (TUG) and International Physical Activity Questionnaire (IPAQ). Consequently, we constructed the Bayesian network model utilizing Genie 2.3, in order to effectively determine clear negative and positive correlations. Results: This investigation incorporated a total of 285 patients. The results of Spearman's correlation analysis indicated that the TUG effectively correlated with age (r = 0.158, P < 0.01), drinking (r=-0.362, P < 0.01), mGES (r=-0.254, P < 0.01), PEPPI (r=-0.329, P < 0.01), SEE (r =-0.408, P < 0.01), BREQ (r = 0.676, P < 0.01), EA (r =-0.688, P < 0.01) and IPAQ (r =-0.742, P < 0.01). TUG can be used as the direct influencing factor of IPA, and five nodes in the model can be considered the primary indirect influencing factors of TUG, such as drinking, EA, age, sex and mGES in Bayesian network. The sensitivity analysis of the model confirmed that TUG (0.059), drinking (0.087), EA (0.335), age (0.080), sex (0.164), mGES (0.028) and hypertension (0.030) can become the sensitivity evaluation indicators of IPAQ in the elderly community population, in which the area under the ROC curve (AUC) was 59.6% (2207/3705), indicating a suitable prediction performance. Conclusion: Exercise anticipation and life behavior habit can effectively predict physical activity capability in the elderly. These findings can help clinicians establish effective intervention to improve the physical activity regularly of the elderly.

13.
Pain Med ; 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35972368

RESUMO

OBJECTIVE: Female chronic pelvic pain (CPP) has multiple pain generators and significant psychosocial sequalae. Biopsychosocial-based phenotyping could help identify clinical heterogeneity that may inform tailored patient treatment. This study sought to identify distinct CPP profiles based on routinely collected clinical information and evaluate the validity of the profiles through associations with social histories and subsequent health care utilization. METHODS: Women (18-77 years, n = 200) seeking care for CPP in a tertiary gynecological pelvic pain clinic between 2017-2020 were included. Baseline data of pain intensity, interference, catastrophizing, acceptance, overlapping pelvic pain syndromes, and co-occurring psychiatric disorders were subject to a partition around medoids clustering to identify patient profiles. Profiles were compared across social history and subsequent treatment modality, prescribed medications, and surgeries performed. RESULTS: Two profiles with equal proportion were identified. Profile 1 was vulvodynia and myofascial pelvic pain-dominant characterized by lower pain burden and better psychological functioning. Profile 2 was visceral pain-dominant featuring higher pain interference and catastrophizing, lower pain acceptance, and higher psychiatric comorbidity. Patients in Profile 2 had 2-4 times higher prevalence of childhood and adulthood abuse history (Ps < 0.001), were more likely to subsequently receive behavioral therapy (46% vs 27%, P = 0.005) and hormonal treatments (34% vs 21%, P = 0.04), and were prescribed more classes of medications for pain management (P = 0.045) compared to patients in Profile 1. CONCLUSIONS: Treatment-seeking women with CPP could be separated into two groups distinguished by pain clusters, pain burden, pain distress and coping, and co-occurring mental health disorders.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35972374

RESUMO

OBJECTIVES: This study aimed to analyse the immune cell profiles of adult-onset Still's disease (AOSD) and to stratify disease-associated endotypes. METHODS: We included 95 cases of treatment-naïve patients with AOSD and 66 cases of healthy controls (HCs). Patients with AOSD were classified via an unbiased hierarchical cluster analysis based on circulating immune cells. Their clinical and laboratory characteristics, treatment management, systemic scores, and outcomes were then analysed. RESULTS: The proportions of neutrophils and CD8+ T cells were significantly higher while monocytes and natural killer and CD4+ T cells were decreased in patients with AOSD (all p < 0.005). Unbiased hierarchical cluster analysis classified 95 AOSD into three endotype-based groups: group 1 had the highest percentage of neutrophils (Neu-dominant group), group 2 had the highest percentage of monocytes (Mono-dominant group), and group 3 had the highest percentage of CD8+ T cells (CD8-dominant group). Patients in group 3 had the highest systemic score at diagnosis and were more likely to have pulmonary infiltrates, pericarditis, splenomegaly, and poorer treatment responses. A correlation study revealed that the CD4 to CD8 ratio was negatively correlated with the systemic score and positively correlated with treatment response in patients with AOSD (p = 0.001 and p = 0.0091). During the 24.6 ± 15.2 months of follow-up, the highest total number of disease flares occurred in group 3 (p < 0.0001). CONCLUSION: Hierarchical cluster analysis of peripheral immune cells classified AOSD into three disease-related endotypes. Group 3 showed higher systemic score and poorer treatment responses.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35969357

RESUMO

Heart failure remains a leading cause of morbidity and mortality globally and has been recognized as a common complication of diabetes, especially type 2 diabetes mellitus. Heart failure occurs in diabetic patients even in the absence of hypertension, coronary heart disease, or valvular heart disease, and is, therefore, a major cardiovascular complication in this vulnerable population. Given the continued rise in the prevalence of type 2 diabetes mellitus worldwide, the burden of heart failure on the healthcare system will continue to increase. Recent evidence demonstrates that empagliflozin, a sodium-glucose co-transporter-2 inhibitor, brings clinical benefit to patients with established heart failure and type 2 diabetes mellitus. Herein, we critically reviewed the clinical evidence of empagliflozin for patients with heart failure and type 2 diabetes mellitus with the comparison with other sodium-glucose co-transporter-2 inhibitors and potential mechanism to provide the optimal and evidence-based management for patients with established heart failure and type 2 diabetes mellitus with the goal to be conducive to the mechanism exploration of empagliflozin to advance a more comprehensive understanding of empagliflozin.

16.
Sci Immunol ; 7(74): eabn6373, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930657

RESUMO

CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs. Rather, CD48 was also needed on T cells. One exception was during cytotoxicity, which required CD48 on T cells and APCs. Fluorescence resonance energy transfer (FRET) studies in nonimmune cells provided evidence that cis interactions between CD2 and CD48 existed within individual cells. CD2-CD48 interactions on T cells enabled more robust T cell receptor (TCR) signals, including protein tyrosine phosphorylation. Using T cells from a CD2 knock-in mouse in which a tag was inserted at the carboxyl terminus of CD2, mass spectrometry analyses revealed that the role of CD2 in T cell activation correlated with its ability to interact with components of the TCR complex and the protein tyrosine kinase Lck. CD2-CD58 provided a similar function in human T cells. Thus, our data imply that T cell-intrinsic cis interactions of CD2 with its ligands are required for TCR signaling and T cell activation. Interactions with ligands on APCs contribute during cytotoxicity.


Assuntos
Antígenos CD , Ativação Linfocitária , Linfócitos T , Animais , Antígenos CD2/química , Antígenos CD2/metabolismo , Antígeno CD48/metabolismo , Antígenos CD58/metabolismo , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T/metabolismo
17.
Dis Markers ; 2022: 9716424, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909890

RESUMO

Background: The misdiagnosis of aortic dissection (AD) can lead to a catastrophic prognosis. There is currently a lack of stable serological indicators with excellent efficacy for the differential diagnosis of AD and coronary artery disease (CAD). A recent study has shown an association between AD and iron metabolism. Thus, we investigated whether iron metabolism could discriminate AD from CAD. Methods: This retrospective and multicenter cross-sectional study investigated the efficacy of biomarkers of iron metabolism for the differential diagnosis of AD. We collected biomarkers of iron metabolism, liver function, kidney function, and other biochemistry test, and further, logistic regression analysis was applied. Results: Between Oct. 8, 2020, and Mar. 1, 2021, we recruited 521 patients diagnosed with AD, CAD, and other cardiovascular diseases (OCDs) with the main symptoms of chest and back pain and assigned them to discovery set (n = 330) or validation set (n = 191). We found that six serum biomarkers, including serum iron, low-density lipoprotein, uric acid, transferrin, high-density lipoprotein, and estimated glomerular filtration rate, can serve as a novel comprehensive indicator (named FLUTHE) for the differential diagnosis of AD and CAD with a sensitivity of 0.954 and specificity of 0.905 to differentially diagnose AD and CAD more than 72 h past symptom onset. Conclusion: Our findings provide insight into the role of iron metabolism in diagnosing and distinguishing AD, which might in the future be a key component in AD diagnosis. Furthermore, we establish a novel model named "FLUTHE" with higher efficiency, safety, and economy, especially for patients with chest pain for more than 72 h.


Assuntos
Aneurisma Dissecante , Doença da Artéria Coronariana , Aneurisma Dissecante/diagnóstico , Biomarcadores , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Humanos , Ferro/metabolismo , Estudos Retrospectivos
18.
Biosens Bioelectron ; 216: 114622, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35973273

RESUMO

To develop various biosensors, several 2D nanomaterials adsorb DNA probes (aptamers) via π-π stacking interactions. However, interference from DNA displacement by external non-targeted ligands has precluded their practical applications for specific detection and imaging at high protein concentrations. Metal coordination is an attractive strategy for biomolecular crosslinking and functional molecular self-assembly. Herein, a robust 2D biosensor nanoplatform was developed to enhance DNA adsorption and affinity using Mn2+-modified black phosphorus nanosheets (BPNS@Mn2+) via metal coordination. The Mn2+ can simultaneously coordinate with the lone pair electrons (π bonds) of the BPNS and nucleotide bases to provide binding sites for DNA nucleobases on the BPNS surface, which greatly enhances the stability of the inner BPNS and improves DNA adsorption and affinity. The DNA adsorption mechanism of BPNS@Mn2+ was also characterized, and is extensively discussed. Without any further modification, this BPNS@Mn2+/DNA biosensor specifically detected single-stranded DNA (linear range: 10-200 nM, detection limit: 5.76 nM) and thrombin (linear range: 20-180 nM, detection limit: 2.39 nM) in 100 nM bovine serum albumin solution. The nonspecific ligands in the environment did not affect the detection performance of the robust biosensor. In addition, the expression levels of microRNA-21 can be imaged and analyzed in living cells using this biosensor, which is consistent with the results of the polymerase chain reaction. This study highlights the potential of metal coordination in surface modification and provides new opportunities for biomedical applications of 2D nanomaterials with superior DNA-adsorption capacity, facilitating the development of biosensor design and nucleic acid/drug delivery.

19.
Dalton Trans ; 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35975572

RESUMO

The scaling relations between nitrogen adsorption and NHx destabilization are key challenges to the widespread adoption of the photocatalytic synthesis of ammonia. In this work, a FeII-rich MIL-101(Fe) (MIL-101(FeII/FeIII)) was synthesized using a one-step solvent thermal method with ethylene glycol (EG) as a reducing agent, which can break the scaling relationship by photoinduced FeII (high nitrogen adsorption ability) and FeIII (high NHz destabilization ability) cycling. XPS was used to detect the change in iron valence state in the MIL-101(FeII/FeIII) material. The photocatalytic nitrogen fixation efficiency of MIL-101(FeII/FeIII) under visible light without any sacrificial agent was 466.8 µmol h-1 g-1, five times that of MIL-101(Fe). After photocatalytic experiments, MIL-101(FeII/FeIII) retained an unchanged FeII/FeIII rate, indicating that this FeII/FeIII cycling can be maintained. DFT modeling of the FeII-rich MOF material showed that a FeII1 FeIII2 system has a higher N2 activation capacity than a FeIII3 system. The catalytic mechanism was further proved by in situ infrared spectra and N15 isotopic tracers. Therefore, the improvement of photocatalytic activity was mainly attributed to the change in the nitrogen adsorption capacity during the photoinduced FeII/FeIII cycling.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35976485

RESUMO

A Gram stain-positive, rod-shaped, motile, aerobic and terminal endospore formation bacterium, designated YIM B00362T, was isolated from saline soil samples collected from a salt lake in Xinjiang Province, north-west China. Phylogenetic analysis based on the 16S rRNA gene sequences and whole genomes indicated that the isolate belongs to the genus Paenibacillus. However, the highest sequence similarity between strain YIM B00362T and the relatives was only 94.4%. Moreover, the DNA-DNA relatedness and ANI values between the novel isolate and the relative type strain, Paenibacillus antri SYSU K30003T was 13.6% and 70.3%, respectively. The major cellular fatty acids were anteiso-C15:0, C16:0 and the major quinone was MK-7. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylglyceride, and two unidentified polar lipids. The genomic DNA G + C content was 50.9 mol%. The major whole-cell sugars contained glucose and galactose. On the basis of physiological, phenotypic, and chemotaxonomic data, strain YIM B00362T represents a novel species of genus Paenibacillus, for which the name Paenibacillus alkalitolerans sp. nov. is proposed. The type strain is YIM B00362T (= KCTC 43272 T = CGMCC 1.18801 T = NBRC 114667 T).

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