Rhodiola rosea L extract shows protective activity against Alzheimer’s disease in 3xTg-AD mice

Purpose: To investigate the protective effect of Rhodiola rosea L. extract (RRLE) against Alzheimer's disease in 3xTg-AD mice.Methods: The cognitive function of 3xTg-AD mice was assessed using Morris water maze test. The levels of amyloid beta deposits and NeuN in the hippocampus were evaluated by immunohistochemistry. Brain neurotrophic-derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis.Results: RRLE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. The escape latency in animals treated with 400 mg/kg RRLE (20.5 ± 1.3 s) was significantly increased compared to the untreated mice (12.4 ± 1.3 s, p < 0.01). In addition, RRLE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expression of BDNF (1.4 ± 0.2, p < 0.05) and TrkB (1.1 ± 0.2, p < 0.05) in the mice.Conclusion: The findings suggest that RRLE treatment may be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.Keywords: Rhodiola rosea L., Alzheimer's disease, Neurodegenerative diseases, Memory impairment, NeuN-positive cells, Amyloid beta deposit

A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate

Glutamate is a ubiquitous neurotransmitter, mediating information flow between neurons. Defects in the regulation of glutamatergic transmission can result in glutamate toxicity, which is associated with neurodegeneration. Interestingly, glutamate receptors are expressed in glia, but little is known about their function, and the effects of their misregulation, in these non-neuronal cells. Here, we report a glio-protective role for Drosophila mir-263a mediated by its regulation of glutamate receptor levels in glia. mir-263a mutants exhibit a pronounced movement defect due to aberrant overexpression of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment

Explainable machine learning-based prediction model for diabetic nephropathy

The aim of this study is to analyze the effect of serum metabolites on diabetic nephropathy (DN) and predict the prevalence of DN through a machine learning approach. The dataset consists of 548 patients from April 2018 to April 2019 in Second Affiliated Hospital of Dalian Medical University (SAHDMU). We select the optimal 38 features through a Least absolute shrinkage and selection operator (LASSO) regression model and a 10-fold cross-validation. We compare four machine learning algorithms, including eXtreme Gradient Boosting (XGB), random forest, decision tree and logistic regression, by AUC-ROC curves, decision curves, calibration curves. We quantify feature importance and interaction effects in the optimal predictive model by Shapley Additive exPlanations (SHAP) method. The XGB model has the best performance to screen for DN with the highest AUC value of 0.966. The XGB model also gains more clinical net benefits than others and the fitting degree is better. In addition, there are significant interactions between serum metabolites and duration of diabetes. We develop a predictive model by XGB algorithm to screen for DN. C2, C5DC, Tyr, Ser, Met, C24, C4DC, and Cys have great contribution in the model, and can possibly be biomarkers for DN

A New ZrCuSiAs-Type Superconductor: ThFeAsN

We report the first nitrogen-containing iron-pnictide superconductor ThFeAsN, which is synthesized by a solid-state reaction in an evacuated container. The compound crystallizes in a ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters a=4.0367(1) {\AA} and c=8.5262(2) {\AA} at 300 K. The electrical resistivity and dc magnetic susceptibility measurements indicate superconductivity at 30 K for the nominally undoped ThFeAsN.Comment: 6 pages, 4 figures, 1 tabl

Effects of Tai Chi on telomerase activity and gerotranscendence in middle aged and elderly adults in Chinese society

AbstractIntroductionTelomeres are DNA protein structures at the end of chromosomes and are linked to the physical aging process. The improvement of quality of life is closely associated with aerobic exercise, and the dynamic effects of exercise on physiology and psychology are evident with aging. Tai Chi is popularly practiced in China. However, findings on the effects of Tai Chi on telomerase activity (TA) in peripheral blood mononuclear cells, and gerotranscendence (GT), as well as the association of TA and GT with Tai Chi, have been inconsistent.PurposeThis study aims to assess TA in peripheral blood mononuclear cells, GT, and the associations between them. The associations among these variables are determined during six months of Tai Chi intervention among Chinese middle aged and elderly adults.MethodsTA assessment was obtained by TE-ELISA (human telomerase–enzyme linked immunosorbent assay), and GT was measured at the baseline level after six months of Tai Chi intervention.ResultsTA increased significantly in the Tai Chi group from 23.75 ± 3.78 u/mmol (pre-intervention) to 26.31 ± 2.93 u/mmol (after 6 months) (p < 0.05). Compared with the TA in the control group, the TA in the intervention group was statistically significant after six months (p < 0.05). Compared with the GT in the control group, the GT in the intervention group improved significantly after six months (p < 0.05). TA and GT had a positive correlation (r = 0.325, p < 0.01).ConclusionOur data illustrated that Tai Chi had a protective effect on TA and might improve the GT in Chinese middle aged and elderly adults. The TA increased with the increasing GT in Chinese middle aged and elderly adults

Eriodictyol protects skin cells from UVA irradiation-induced photodamage by inhibition of the MAPK signaling pathway

Solar UVA irradiation-generated reactive oxygen species (ROS) induces the expression of matrix metalloproteinase 1 (MMP-1), leading to photoaging, however the molecular mechanism remains unclear. In the present study, we found that eriodictyol remarkably reduces UVA-mediated ROS generation and protects the skin cells from oxidative damage and the ensuing cell death. Moreover eriodictyol pretreatment significantly down-regulates the UVA-induced MMP-1 expression, and lowers the inflammatory responses within the skin cells. Pretreatment with eriodictyol upregulates the expression of tissue inhibitory metalloproteinase 1 (TIMP-1) and collagen-I (COL-1) at the transcriptional level in a dose-dependent manner. UVA-induced phosphorylation levels of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 leading to increased MMP-1 expression are significantly reduced in eriodictyol-treated skin cells. In addition, eriodictyol pretreatment significantly suppresses inflammatory cytokines and inhibits the activation of MAPK signaling cascades in skin cells. Taken together, our results demonstrate that eriodictyol has both potent anti-inflammatory and anti-photoaging effects.</p

Association between body fat distribution and age at menarche: a two sample Mendelian randomization study

BackgroundNumerous studies have examined the association between obesity and age at menarche (AAM), with most focusing on traditional obesity indicators such as body mass index. However, there are limited studies that explored the connection between body fat distribution and AAM, as well as a scarcity of Mendelian randomization (MR) studies.MethodsIn this study, we conducted a two-sample MR study to evaluate the causal effects of eight body fat distribution indicators on AAM. Inverse variance weighted (IVW) method was used for primary analysis, while supplementary approaches such as MR-Egger and weighted median were also utilized. Considering that the eight exposures were highly correlated, we performed an MR Bayesian model averaging (MR-BMA) analysis to prioritize the effect of major exposure on AAM. A series of sensitivity analyses were also performed.ResultsFrom a range of 82–105 single nucleotide polymorphisms (SNPs) were utilized as genetic instrumental variables for each of the exposure factors. After Bonferroni correction, we found that whole body fat mass (β: −0.17; 95% CI: −0.24, −0.11), left leg fat percentage (β: −0.14; 95% CI: −0.21, −0.07), left leg fat mass (β: −0.20; 95% CI: −0.27, −0.12), left arm fat percentage (β: −0.18; 95% CI: −0.26, −0.11) and left arm fat mass (β: −0.18; 95%CI: −0.26, −0.10) were associated with decreased AAM using random effects IVW method. And the beta coefficients for all MR evaluation methods exhibited consistent trends. MR-BMA method validated that left arm fat percentage plays a dominant role in AAM.ConclusionsOur MR study suggested that body fat has broad impacts on AAM. Obtaining more information on body measurements would greatly enhance our comprehension of pubertal development

Identification of subtype-specific metastasis-related genetic signatures in sarcoma

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma. Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma. Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma