Research progress on the relationship between axonal transport dysfunction in neuronal cells and Alzheimer’s disease

Alzheimer’s disease is known as one of the “top ten killers in the world”. Due to lack of effective therapy at present， early pathological changes have captivated widespread attention. Axonal transport dysfunction has been reported as an early pathological feature of many neurodegenerative diseases. However， multiple factors can cause axonal transport dysfunction. In this article， the relationship between axonal transport dysfunction caused by kinesins， microtubules and mitochondria and Alzheimer’s disease was discussed， aiming to provide new ideas for the prevention and treatment of Alzheimer’s disease by in-depth study on axonal transport mechanism of neure

Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice

Aim: To investigate the effects of ATPM-ET [(−)-3-N-Ethylaminothiazolo [5,4-b]-N-cyclopropylmethylmorphinan hydrochloride] on physical dependence and behavioral sensitization to morphine in mice. Methods: The pharmacological profile of ATPM-ET was characterized using competitive binding and GTPγS binding assays. We then examined the antinociceptive effects of ATPM-ET in the hot plate test. Morphine dependence assay and behavioral sensitization assay were used to determine the effect of ATPM-ET on physical dependence and behavior sensitization to morphine in mice. Results: The binding assay indicated that ATPM-ET ATPM-ET exhibited a high affinity to both κ- and μ-opioid receptors with Ki values of 0.15 nmol/L and 4.7 nmol/L, respectively, indicating it was a full κ-opioid receptor agonist and a partial μ-opioid receptor agonist. In the hot plate test, ATPM-ET produced a dose-dependent antinociceptive effect, with an ED50 value of 2.68 (2.34–3.07) mg/kg. Administration of ATPM-ET (1 and 2 mg/kg, sc) prior to naloxone (3.0 mg/kg, sc) injection significantly inhibited withdrawal jumping of mice. In addition, ATPM-ET (1 and 2 mg/kg, sc) also showed a trend toward decreasing morphine withdrawal-induced weight loss. ATPM-ET (1.5 and 3 mg/kg, sc) 15 min before the morphine challenge significantly inhibited the morphine-induced behavior sensitization (P<0.05). Conclusion: ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse

Effects of artemisinin on ventricular arrhythmias in response to left ventricular afterload increase and microRNA expression profiles in Wistar rats

Background Patients with dilated cardiomyopathy, increased ventricular volume, pressure overload or dysynergistic ventricular contraction and relaxation are susceptible to develop serious ventricular arrhythmias (VA). These phenomena are primarily based on a theory of mechanoelectric feedback, which reflects mechanical changes that produce alterations in electrical activity. However, very few systematic studies have provided evidence of the preventive effects of artemisinin (ART) on VA in response to left ventricle (LV) afterload increases. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate expression of multiple genes by suppressing mRNAs post-transcriptionally. Aims The aims of this study were to investigate preventive effects of ART on mechanical VA and the underling molecular mechanisms of differentially expressed miRNAs (DEMs). Methods For the study, 70 male Wistar rats were randomly divided into seven groups: group 1 was a control group (sham surgery); group 2 was a model group that underwent transverse aortic constriction (TAC) surgery; groups 3, 4, 5 and 6 were administered ART 75, 150, 300 and 600 mg/kg before TAC surgery, respectively; and group 7 was administered verapamil (VER) 1 mg/kg before TAC surgery. A ventricular arrhythmia score (VAS) was calculated to evaluate preventive effects of ART and VER on mechanical VA. The high throughput sequencing-based approach provided DEMs that were altered by ART pretreatment between group 2 and group 4. All predicted mRNAs of DEMs were enriched by gene ontology (GO) and Kyoto Encyclopedia annotation of Genes and Genomes (KEGG) databases. These DEMs were validated by a real time quantitative polymerase chain reaction (RT-qPCR). Results The average VASs of groups 3, 4, 5, 6 and 7 were significantly reduced compared with those of group 2 (2.70 ± 0.48, 1.70 ± 0.95, 2.80 ± 0.79, 2.60 ± 0.97, 1.40 ± 0.52, vs 3.70 ± 0.67, p < 0.01, respectively). The three top GO terms were neuron projection, organ morphogenesis and protein domain specific binding. KEGG enrichment of the 16 DEMs revealed that MAPK, Wnt and Hippo signaling pathways were likely to play a substantial role in the preventive effects of ART on mechanical VA in response to LV afterload increases. All candidate DEMs with the exception of rno-miR-370-3p, rno-miR-6319, rno-miR-21-3p and rno-miR-204-5p showed high expression levels validated by RT-qPCR. Conclusions Artemisinin could prevent mechanical VA in response to LV afterload increases. Validated DEMs could be biomarkers and therapeutic targets of ART regarding its prevention of VA induced by pressure overload. The KEGG pathway and GO annotation analyses of the target mRNAs could indicate the potential functions of candidate DEMs. These results will help to elucidate the functional and regulatory roles of candidate DEMs associated with antiarrhythmic effects of ART

Effect of amino acid addition on the micelle formation of the surface‐active ionic liquid 1‐tetradecyl‐3‐methylimidazolium bromide in aqueous solution

The effect of 3 amino acids on the self‐assembly properties of the surface‐active ionic liquid: 1‐tetradecyl‐3‐methyl imidazolium bromide, [C14mim][Br], was studied in neutral and basic aqueous solution. The critical micelle concentrations were determined by different techniques, and the thermodynamic parameters of micellization (ΔG0 mic, ΔH0mic, and ΔS0mic) were measured by isothermal titration calorimetry. The critical micelle concentration values decrease in the presence of all the amino acids used in this study. The most substantial effect was observed in the presence of L‐tryptophan at pH 12, due to the electrostatic and π‐π interactions with the imidazolium headgroup of the surfactant. Always entropy‐driven micellization occurred. Both the enthalpy and entropy changes upon association to micelles increased when the pH was enhanced from 7 to 12. 1H NMR measurements demonstrated that among the used amino acids, L‐tryptophan interacts most strongly with the headgroup of the surfactant cation. The knowledge on the surfactant‐amino acid interactions significantly contributes to the deeper understanding of the effect of surfactants on the properties of peptides

The MALATANG Survey : Dense Gas and Star Formation from High Transition HCN and HCO+ maps of NGC253

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2020 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.To study the high-transition dense-gas tracers and their relationships to the star formation of the inner $\sim$ 2 kpc circumnuclear region of NGC253, we present HCN $J=4-3$ and HCO$^+ J=4-3$ maps obtained with the James Clerk Maxwell Telescope (JCMT). With the spatially resolved data, we compute the concentration indices $r_{90}/r_{50}$ for the different tracers. HCN and HCO$^+$ 4-3 emission features tend to be centrally concentrated, which is in contrast to the shallower distribution of CO 1-0 and the stellar component. The dense-gas fraction ($f_\text{dense}$, traced by the velocity-integrated-intensity ratios of HCN/CO and HCO$^+$/CO) and the ratio $R_\text{31}$ (CO 3-2/1-0) decline towards larger galactocentric distances, but increase with higher SFR surface density. The radial variation and the large scatter of $f_\text{dense}$ and $R_\text{31}$ imply distinct physical conditions in different regions of the galactic disc. The relationships of $f_\text{dense}$ versus $\Sigma_\text{stellar}$, and SFE$_\text{dense}$ versus $\Sigma_\text{stellar}$ are explored. SFE$_\text{dense}$ increases with higher $\Sigma_\text{stellar}$ in this galaxy, which is inconsistent with previous work that used HCN 1-0 data. This implies that existing stellar components might have different effects on the high-$J$ HCN and HCO$^+$ than their low-$J$ emission. We also find that SFE$_\text{dense}$ seems to be decreasing with higher $f_\text{dense}$, which is consistent with previous works, and it suggests that the ability of the dense gas to form stars diminishes when the average density of the gas increases. This is expected in a scenario where only the regions with high-density contrast collapse and form stars.Peer reviewe

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility

Plasma cell subtypes analyzed using artificial intelligence algorithm for predicting biochemical recurrence, immune escape potential, and immunotherapy response of prostate cancer

BackgroundPlasma cells as an important component of immune microenvironment plays a crucial role in immune escape and are closely related to immune therapy response. However, its role for prostate cancer is rarely understood. In this study, we intend to investigate the value of a new plasma cell molecular subtype for predicting the biochemical recurrence, immune escape and immunotherapy response in prostate cancer.MethodsGene expression and clinicopathological data were collected from 481 prostate cancer patients in the Cancer Genome Atlas. Then, the immune characteristics of the patients were analyzed based on plasma cell infiltration fractions. The unsupervised clustering based machine learning algorithm was used to identify the molecular subtypes of the plasma cell. And the characteristic genes of plasma cell subtypes were screened out by three types of machine learning models to establish an artificial neural network for predicting plasma cell subtypes. Finally, the prediction artificial neural network of plasma cell infiltration subtypes was validated in an independent cohort of 449 prostate cancer patients from the Gene Expression Omnibus.ResultsThe plasma cell fraction in prostate cancer was significantly decreased in tumors with high T stage, high Gleason score and lymph node metastasis. In addition, low plasma cell fraction patients had a higher risk of biochemical recurrence. Based on the differential genes of plasma cells, plasma cell infiltration status of PCa patients were divided into two independent molecular subtypes(subtype 1 and subtype 2). Subtype 1 tends to be immunosuppressive plasma cells infiltrating to the PCa region, with a higher likelihood of biochemical recurrence, more active immune microenvironment, and stronger immune escape potential, leading to a poor response to immunotherapy. Subsequently, 10 characteristic genes of plasma cell subtype were screened out by three machine learning algorithms. Finally, an artificial neural network was constructed by those 10 genes to predict the plasma cell subtype of new patients. This artificial neural network was validated in an independent validation set, and the similar results were gained.ConclusionsPlasma cell infiltration subtypes could provide a potent prognostic predictor for prostate cancer and be an option for potential responders to prostate cancer immunotherapy