Christiekristiansen6657
The metabolic pathways of cryptotanshinone by these two fungi were presumed to be the opening and rearrangement of furan ring, and/or oxygenation of cyclohexane ring. Cryptotanshinone (1) and its metabolites displayed anti-inflammatory activities against NO production in LPS-stimulated BV-2 cells and antibacterial activities towards methicillin-resistant Staphylococcus aureus. These findings revealed the potential of marine fungi to transform the structures of natural products by biotransformation.Intracellular biothiols are correlated with many diseases such as nerve disorder and Parkinson's disease likely due to a redox imbalance. In this work, we designed an ultrafast fluorescent probe (Cou-DNBS) for biothiols with a large Stokes shift (131 nm). The probe was constructed through linking the 2,4-dinitrobenzenesulfonyl moiety as the specially recognizing biothiols site to an iminocoumarin fluorophore Cou-NH obtained by fusing an additional benzene ring. The presence of biothiols could ultrafast perform a significant fluorescence emission at 617 nm upon the excitation of 480 with the low limits of detection (2.5 nM for Cys, 1.7 nM for Hcy and 0.84 nM for GSH). HRMS spectra as well as theoretical calculations further evidenced the rationale of recognition mechanism. read more Furthermore, the probe can successfully visualize endogenous biothiol recovery in living cells damaged by H2O2.Capsaicinoids are plant secondary metabolites, and capsaicin is the main principal that responsible to the pungency of chili peppers, with widely application as food additive. In our study, capsaicin was characterized as lysine specific demethylase 1A (KDM1A/LSD1) inhibitor with IC50 of 0.6 ± 0.0421 μM in biochemical level, and can bind KDM1A recombinant directly and reversibly. Further cellular study confirmed that capsaicin can bind and inhibit KDM1A in gastric cancer cell line BGC-823 and further inhibit cell invasion and migration by reversing epithelial-mesenchymal transition (EMT). In sum, our findings identified KDM1A as a target of capsaicin and reveals capsaicin as a modifier of histone methylation for the first time, which may provide a new skeleton for further optimization of KDM1A inhibitor.
The effects of the COVID-19 pandemic on the mental health and emotional support among the general population are unclear. We therefore assessed if the prevalence of high Anxiety and Depression Symptoms (ADS) levels and lack of Emotional Support (ES) increased, and if risk factors of ADS and ES changed.
Data was extracted from surveys conducted with the Dutch longitudinal population-based LISS panel (N=3,983). ADS and ES were assessed in March 2019 and 2020. Risk factors for ADS and ES were extracted from surveys in November 2018 and 2019. These were ADS, gender, education, domestic situation, employment, age, ethnicity, lung and heart problems, and diabetes.
The prevalence of high ADS levels and lack of ES did not increase compared to the pre-outbreak prevalence. ADS, non-native ethnic background, (partial) work disabilities and lung problems were predictive of both ADS and lack of ES in March 2019 and 2020. Job seekers, students and those who take care of housekeeping were more at risk for ADS in March 2020, but not in 2019. While 35-49 years old respondents were less at risk for ADS in March 2019, they were more at risk in 2020. Parents with child(ren) at home and those who take care of housekeeping more often lacked ES in March 2020, but not in 2019.
No other mental health problems were assessed.
No increase in the prevalence of ADS and lack of ES was found. Some risk factors remained significant after the outbreak, while others changed notably.
No increase in the prevalence of ADS and lack of ES was found. Some risk factors remained significant after the outbreak, while others changed notably.
5-HTTLPR/rs25531 is suspected to be involved in the pathogenesis of both coronary heart disease (CHD)
and depression. We aimed to investigate the role of 5-HTTLPR/rs25531 in the development of depressive symptoms among CHD patients in a longitudinal design.
N=265 participants with CHD diagnosis were included while hospitalized in a department of cardiology and genotyped for the 5-HTTLPR/rs25531. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9)
at baseline and after 6 and 12 months. Binary logistic regression models were used to analyze the association of 5-HTTLPR/rs25531 with the prevalence of depressive symptoms at each time point as well as with the incidence and persistence of depressive symptoms at follow-up.
"L
L
" genotype was associated with a higher prevalence of depressive symptoms 12 months after study inclusion. "L
L
" genotype was associated with a higher incidence of depressive symptoms 6 and 12 months after study inclusion. There was no association of 5-HTTLPR/rs25531 with the persistence of depressive symptoms.
Inclusion criteria did not demand a particular cardiac event at baseline, which aggravated the interpretation of the time-specific results. The majority of the participants was of male gender which could cause bias. The present study only vaguely differentiated between ethnical groups which might cause bias regarding nationality-dependent allele distributions.
The present study suggests a time-dependent association of the "L
L
" genotype with depressive symptoms in CHD patients. 5-HTTLPR/rs25531 might be an important marker to detect risk groups for later onset depressive symptoms among CHD patients.
The present study suggests a time-dependent association of the "LALA" genotype with depressive symptoms in CHD patients. 5-HTTLPR/rs25531 might be an important marker to detect risk groups for later onset depressive symptoms among CHD patients.Radiopharmaceuticals with therapeutic applications are designed to deliver high doses of radiation to target organs with minimizing unwanted radiation to healthy tissues. Owing to the potential of targeted radiotherapy to treat a wide range of malignancies, 170Tm -EDTMP was developed for possible therapeutic applications. This study describes absorbed dose prediction of 170Tm-EDTMP in human organs after animal injection which is determined via medical internal radiation dose (MIRD) and MCNP-4C code methods. It was estimated that a 1-MBq administration of 170Tm-EDTMP into the human body would result in an absorbed dose of 37.9 mGy (MIRD method) and 38.02 mGy (MCNP-4C code) in the bone surface after 60 days post injection. Highest and lowest difference between MIRD and MCNP results are for lung and bone surface respectively. Finally, the results show that there is a good agreement between MIRD method and MCNP-4C simulation code for absorbed dose estimation.
Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab (NTZ) treatment in multiple sclerosis (MS) patients. Based on the analysis of cryopreserved cells, several reports have showed that CD62L+ CD4+ T-cells percentage drops before PML onset.
To analyze CD62L and CD45RA expression on fresh-blood CD4+ and CD8+ T-cells from NTZ-treated patients, according to their estimated PML risk.
We prospectively enrolled 74 MS patients, including 62 NTZ-treated, and stratified them into low, intermediate and high PML risk groups. Circulating naïve and memory T-cell subsets were analyzed by flow cytometry.
We found no correlation between the percentage of CD62L+ CD4+ T-cells and PML risk. In contrast, the repartition of CD8+ T-cells subpopulations was altered in the high risk group both the percentage and absolute count of CD8+ CD62L- CD45RA- effector memory T- cells (T
) was significantly higher compared to patients at lower risk despite similar CD3+ and CD8+ T-cell counts. One high-risk patient with elevated CD8+ T
and CD62L+ CD4+ T-cell levels developed PML six months after sampling.
Our results suggest that CD8+ T
cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients.
Our results suggest that CD8+ TEM cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients.
Inflammatory activity in children with paediatric onset multiple sclerosis (POMS) is higher than that in adults with MS. Chemokine/cytokine profiling in children may provide new insights into the disease pathogenesis and clinical course. The levels of chemokines/cytokines and their roles in POMS remain largely unknown.
To identify the possible utility of chemokines/cytokines in children with POMS, we analysed their levels at the time of disease diagnosis and in the context of subsequent clinical relapse.
CC and CXC motif ligand chemokines (CCL2, CXCL8, CXCL10, and CXCL13), interleukin (IL)-4, IL-17A, interferon gamma and B cell-activating factor in the blood and cerebrospinal fluid (CSF) of 34 POMS patients and 20 age-related controls were measured using Luminex multiplex bead and enzyme-linked immunosorbent assay techniques. Nonparametric tests were used for statistical analyses.
The CSF levels of CXCL8 (p=0.002), CXCL10 (p=0.001), and CXCL13 (p<0.0001) were higher in POMS than in controls; CXCL10 the involvement of adaptive immunity; elevated CXCL8 levels further indicate the involvement of innate immunity. An initial low CSF level of CCL2 may be associated with an unfavourable early MS course.
Fingolimod lowers the number of relapses in multiple sclerosis (MS) patients and slows down disease progression, but causes a broad spectrum of side effects. Our aim was to estimate the benefit-harm balance of fingolimod using individual patient data from FREEDOMS, a randomized controlled trial that compared two different dosages of fingolimod to placebo.
We modelled the health status of patients over two years on a scale ranging from 0 (worst health or death) to 100 (maximum health). The model considered Expanded Disability Status Scale measurements, relapses and adverse events. We compared the mean health status between arms, and the proportion of trial participants for whom health declined or improved compared to baseline by a predefined minimal important difference of 4.6 or more.
The main analysis showed a net benefit for fingolimod 0.5mg compared to placebo, with an average health status difference over two years of 2.7 (95% CI 2.2 to 3.2). Patients on fingolimod 0.5mg were 0.53 (95% CI 0.40-0.72, p<0.001) times less likely to have a relevant decline in health status compared to patients on placebo, corresponding to a number needed to treat of 8 to prevent one relevant decline in health status. All sensitivity analyses favoured fingolimod 0.5mg.
Although fingolimod's net benefit did not reach the clinical relevance on average, the decreased risk for a decline in health over two years may be relevant. This approach could be applied to other MS drugs and provide an objective evidence base for guideline recommendations.
Although fingolimod's net benefit did not reach the clinical relevance on average, the decreased risk for a decline in health over two years may be relevant. This approach could be applied to other MS drugs and provide an objective evidence base for guideline recommendations.
This study aimed to evaluate if laryngopharyngeal reflux (LPR) plays a role as a risk factor for vocal fold polyps (VFPs), and if pepsin is associated with higher oxidative DNA damage of VFPs in the presence of LPR.
Thirty patients with VFPs were recruited between 2017 and 2018. Prior to surgery, a laryngoscopy was performed on all subjects to evaluate VFPs. Polyp tissue and saliva samples were obtained scrupulously. Hematoxylin-eosin staining was performed for pathologic analysis. Immunohistochemistry and ELISA were used to detect pepsin in tissue and saliva of VFP patients. 8-OHdG and p-H2AX expression was detected to measure oxidative DNA damage in tissue. DNA damage was investigated in human immortalized laryngeal epithelial cells exposed to pepsin.
The pepsin concentration in saliva was significantly higher (t=2.38, P=.024) in the pepsin positive group. There was no significant difference in pepsin expression at different sites and pathological subtypes of VFPs. The levels of 8-OHdG and p-H2AX were significantly higher in the pepsin positive group and positively correlated with the tissue expression of pepsin.
