Mesenchymal Stem Cells: A Promising Treatment for Thymic Involution.

The thymus is the main immune organ in the body. However, the thymus gradually degenerates in early life, leading to a reduction in T-cell production and a decrease in immune function. Mesenchymal stem cells (MSCs) are a promising alternative for the treatment of thymus senescence due to their homing ability to the site of inflammation and their paracrine, anti-inflammatory, and antioxidant properties. However, the heterogeneity, difficulty of survival in vivo, short residence time, and low homing efficiency of the injected MSCs affect the clinical therapeutic effect. This article reviews strategies to improve the efficacy of mesenchymal stem cell therapy, including the selection of appropriate cell doses, transplantation frequency, and interval cycles. The survival rate of MSCs can be improved to some extent by improving the infusion mode of MSCs, such as simulating the in vivo environment, applying the biological technology of hydrogels and microgels, and iron oxide labeling technology, which can improve the curative effect and homing of MSCs, promote the regeneration of thymic epithelial cells, and restore the function of the thymus.

Synthetic flavagline derivative 1-chloroacetylrocaglaol promotes apoptosis in K562 erythroleukemia cells through miR-17-92 cluster genes.

Chronic myeloid leukemia accounts for human deaths worldwide and could enhance sevenfold by 2050. Thus, the treatment regimen for this disorder is highly crucial at this time. Flavaglines are a natural class of cyclopentane benzofurans exhibiting various bioactivities like anticancer action. Despite the antiproliferative activity of flavaglines against diverse cancer cells, their roles and mechanism of action in chronic myeloid leukemia (CML) remain poorly understood. Thus, this study examines the antiproliferative effect of a newly synthesized flavagline derivative, 1-chloracetylrocaglaol (A2074), on erythroleukemia K562 cells and the zebrafish xenograft model. The study revealed that A2074 could inhibit proliferation, promote apoptosis, and boost megakaryocyte differentiation of K562 cells. This flavagline downregulated c-MYC and miR-17-92 cluster genes, targeting upregulation of the apoptotic protein Bcl-2-like protein 11 (BIM). The work uncovered a critical role of the c-MYC-miR-17-92-BIM axis in the growth and survival of CML cells.

The Flavagline Compound 1-(2-(dimethylamino)acetyl)-Rocaglaol Induces Apoptosis in K562 Cells by Regulating the PI3K/Akt/mTOR, JAK2/STAT3, and MAPK Pathways.

Purpose: Chronic myelogenous leukemia (CML) is a hematological malignancy with increased proliferation of cells of the myeloid series. This can disrupt normal hematopoiesis. The 1-(2-(dimethylamino)acetyl)-rocaglaol (MQ-16) is a new synthetic flavagline compound that showed promising activity in chronic myeloid leukemia K562 cells. This study aims to analyze the underlying mechanisms of MQ-16 against CML. Methods: Growth, cell cycle progression, and apoptosis were assessed in K562 cells following MQ-16 exposure by MTT assay and flow cytometry. The effect of MQ-16 on DNA strands between nucleosomes was examined by 1% agarose gel electrophoresis. PI3K/Akt/mTOR, JAK2/STAT3, and mitogen-activated protein kinase (MAPK) pathway-related proteins were detected in MQ-16-treated K562 cells by Western blot. Results: MQ-16 significantly inhibited the proliferation of K562 cells and arrested the cell cycle at the G2/M phase in a time- and concentration-dependent manner. MQ-16 induced mitochondria-dependent apoptosis by downregulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and induced time- and concentration-dependent DNA fragmentation. In addition, MQ-16 affected the expression of PI3K/Akt/mTOR, JAK2/STAT3, and MAPK pathway-related proteins. Conclusion: In summary, MQ-16 appears to be a promising chemotherapeutic drug for treating CML.

Quantitative analysis of blended corn-olive oil based on Raman spectroscopy and one-dimensional convolutional neural network.

Blended vegetable oil is a vital product in the vegetable oil market, and quantifying high-value vegetable oil is of great significance to protect the rights and interests of consumers. In this study, we established a one-dimensional convolutional neural network (1D CNN) quantitative identification model based on Raman spectra to identify the amount of olive oil in a corn-olive oil blend. The results show that the 1D CNN model based on 315 extended average Raman spectra can quantitatively identify the content of olive oil, with R2p and RMSEP values of 0.9908 and 0.7183 respectively. Compared with partial least squares regression (PLSR) and support vector regression (SVR), although the index is not optimal, it provides a new analytical method for the quantitative identification of vegetable oil.

Circular RNA circ_0040823 inhibits the proliferation of acute myeloid leukemia cells and induces apoptosis by regulating miR-516b/PTEN.

OBJECTIVE: Endogenous circular RNAs (circRNAs) and microRNAs (miRNAs) have been shown to regulate the pathogenesis of acute myeloid leukemia (AML). The current study aimed to identify the role of circRNA 0040823 (circ_0040823) in AML. METHODS: Microarray datasets were analyzed to identify differentially expressed circRNAs in AML patients. Peripheral blood samples were obtained from healthy volunteers and AML patients for the measurement of circ_0040823 and miR-516b levels. The overexpression or knockdown of a target gene in AML cells was achieved by the transfection with lentiviral vectors or small interfering RNAs. BALB/c nude mice were inoculated with AML cells and monitored for tumor growth. Dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay were used to determine the binding relationship between circRNA and miRNA. RESULTS: circ_0040823 was significantly downregulated in AML patients and leukemia cells. Overexpression of circ_0040823 inhibited AML cell proliferation, and induced apoptosis and cell cycle arrest. Upregulation of circ_0040823 also repressed the growth of xenograft tumors in vivo. circ_0040823 acted as a miR-516b sponge and regulated key cellular events in leukemia cells via downregulating miR-516b. Moreover, tumor suppressor phosphatase and tensin homolog (PTEN) was a downstream target of miR-516b. The inhibition of miR-516b impaired the proliferation capacity of leukemia cells and induced apoptosis, while PTEN deficiency attenuated these effects. CONCLUSION: This study showed that circ_0040823 inhibited proliferation and induced apoptosis of AML cells by sponging miR-516b, thereby diminishing the regulatory effect of miR-516b on PTEN. These findings identified circ_0040823/miR-516b/PTEN as a new therapeutic target for AML.

Analysis of the mechanism for enhanced pyrene biodegradation based on the interactions between iron-ions and Rhodococcus ruber strain L9.

A slow degradation rate and low transformation efficiency are the main problems in the biodegradation of polycyclic aromatic hydrocarbons (PAHs). This study selected pyrene as the target PAH to investigate the effect of ferrous ion and ferric ion on pyrene degradation. The driving effect and mechanism, including the interaction between pyrene and iron ions and the bacterial physiological response during the biodegradation process by Rhodococcus ruber strain L9, were investigated. The results showed that iron ions did not enhance bacterial growth but improved bacteria's pyrene removal capacity, contributing to the total efficiency of pyrene biodegradation. The process started with an initial formation of "cation-π" between Fe (III) and pyrene, which subsequently drove the pyrene removal process and accelerated the bacterial metabolic process. Moreover, a significant increase in the protein concentration, catechol dioxygenase (C12O and C23O) activities, and intracellular protein regulation in crude enzyme solution indicate a positive response of the bacteria during the iron ion-enhanced pyrene degradation process.

Mesenchymal stem cell carriers enhance antitumor efficacy induced by oncolytic reovirus in acute myeloid leukemia.

Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the therapeutic efficacy is modest, and most commonly manifests as relapse from remission. Thus, improving long-term AML survival is a crucial clinical challenge. In recent years, oncolytic virotherapy has provided an alternative approach for AML treatment. The use of oncolytic reoviruses has been explored in more than 30 clinical trials for safety and feasibility issues. However, like other oncolytic viruses, neutralizing antibodies (NAbs) reduce therapeutic efficacy. To tackle this problem, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used to deliver reovirus using in vitro and in vivo models. Human UC-MSCs were successfully loaded with reovirus, without impairing biological function.We also observed in vitro protective effects of hUC-MSCs on reovirus in the presence of NAbs. In the immunocompromised AML mouse model, hUC-MSCs effectively carried reoviruses to tumor lesions and significantly prolonged the survival of AML xenografts in mice in the presence of a high titer anti-reovirus antibody (p = 0.001). However, reovirus-induced activation of AKT, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and NF-κB signaling led to the maintenance of intrinsic migratory properties and secretion of pro-inflammatory cytokines from hUC-MSCs, particularly CXCL10. In immuno-competent AML mice, MSCs carrying reovirus triggered immune responses, and eventually inhibited tumor growth. Therefore, these results suggest that MSCs as carriers of oncolytic reoviruses can enhance the antitumor efficacy of virotherapy.

Total synchronous fluorescence spectroscopy coupled with deep learning to rapidly identify the authenticity of sesame oil.

The quality of sesame oil (SO) has been paid more and more attention. In this study, total synchronous fluorescence (TSyF) spectroscopy and deep neural networks were utilized to identify counterfeit and adulterated sesame oils. Firstly, typical samples including pure SO, counterfeit sesame oil (CSO) and adulterated sesame oil (ASO) were characterized by TSyF spectra. Secondly, three data augmentation methods were selected to increase the number of spectral data and enhance the robustness of the identification model. Then, five deep network architectures, including Simple Recurrent Neural Network (Simple RNN), Long Short-Term Memory (LSTM) network, Gated Recurrent Unit (GRU) network, Bidirectional LSTM (BLSTM) network and LSTM fortified with Convolutional Neural Network (LSTMC), were designed to identify the CSO and trace the source with 100% accuracy. Finally, ASO samples were also 100% correctly identified by training these network architectures. These results supported the feasibility of the novel method.

Exploration of total synchronous fluorescence spectroscopy combined with pre-trained convolutional neural network in the identification and quantification of vegetable oil.

In order to distinguish different vegetable oils, adulterated vegetable oils, and to identify and quantify counterfeit vegetable oils, a method based on a small sample size of total synchronous fluorescence (TSyF) spectra combined with convolutional neural network (CNN) was proposed. Four typical vegetable oils were classified by three ways of fine-tuning the pre-trained CNN, the pre-trained CNN as a feature extractor, and traditional chemometrics. The pre-trained CNN was combined with support vector machines to distinguish adulterated sesame oil and counterfeit sesame oil separately with 100% correct classification rates. The pre-trained CNN combined with partial least square regression was used to predict the level of counterfeit sesame oil. The coefficient of determination for calibration (Rc2) values were all greater than 0.99, and the root mean square errors of validation were 0.81% and 1.72%, respectively. These results show that it is feasible to combine TSyF spectra with CNN for vegetable oil identification.

Identification and quantification of counterfeit sesame oil by 3D fluorescence spectroscopy and convolutional neural network.

The method of 3D fluorescence spectroscopy combined with convolutional neural network (CNN) was developed to identify the counterfeit sesame oil. AlexNet, a pre-trained CNN architecture, was transferred to extract spectral characteristics. Then these features extracted by AlexNet were used as the input of the support vector machine (SVM) to determine whether the sample was counterfeit and its ingredients simultaneously, and both the accuracy were 100%. According to different counterfeit ingredients, these features extracted by AlexNet were used as the input of partial least squares (PLS) to predict the volume percentage concentration of sesame oil essence. There was a good linear relationship between the predicted and actual values of the three sets of counterfeit samples (R2 > 0.99), and the root mean square error of prediction (RMSEP) values were 0.99%, 2.20% and 1.64%, respectively. The results confirmed the validity of this novel method in sesame oil identification.

[Molecular Mechanisms of Apoptosis of Leukemia Cell Induced by Reovirus].

OBJECTIVE: To investigate the molecular mechanism of apoptosis of HL60 cells induced by oncolytic virus Reovirus type 3 (Reo3). METHODS: HL60 cells were infected with Reo3 at different multiplicity of infection (MOI) with the uninfected HL60 cells as control group. After 48 h of infection, the activity of HL60 cells infected with virus at different MOI was detected by CCK8 method to investigate the influence of MOI to cell activity. Simultaneously, the apoptotic rate of HL60 cells was detected by flow cytometry, and the activation level of double-stranded RNA-dependent protein kinase (PKR) and the expression of apoptotic-related protein in HL60 cells were detected by Western blot. Before infection with Reo3 for 48 h, HL60 cells were treated with 2-aminopurine (2-AP), a specific inhibitor of PKR, for 24 h. Afterward, the apoptotic level and expression of apoptotic related proteins were detected. RESULTS: Activity of HL60 cells was obviously inhibited after infected with Reo3 with a MOI of 1 for 48 h. The cell survival rate was (24.333±3.396)% and the apoptotic rate was (29.96±2.06)%. Both rates were all higher than those in the control group (P < 0.05). Western blot results showed that the expression levels of PKR, p-PKR, Bax, Caspase3 and cleaved Caspase3 in HL60 cells infected with Reo3 were higher than those in the control group (P < 0.05), while the expression level of Bcl-2 was lower (P < 0.05). Compared with the group without inhibitor, the apoptotic rate of HL60 cells pretreated with 2-AP decreased (P < 0.05), the phosphorylation level of PKR and the expression level of apoptotic-related protein also decreased (P < 0.05). CONCLUSION: Oncolytic virus Reo3 could activate PKR in HL60 cells and thus induce apoptosis of HL60 cells.

[Wnt/ß-catenin signaling pathway involved in the expression and drug resistance of abcb4 gene in transgenic zebrafish induced by chemotherapeutic drugs].

Objective To explore the relationship between the drug resistance gene ATP binding cassette sub-family B member 4 (abcb4) in zebrafish and Wnt/ß-catenin signaling pathway. Methods Wild-type zebrafish and transgenic zebrafish were set in the blank control group, doxorubicin treatment group, vinblastine treatment group, gefitinib treatment group, doxorubicin combined with gefitinib treatment group, and vinblastine combined with gefitinib treatment group. The 100 embryos of each group were treated with drugs until the 5th day, and 50 zebrafish juveniles were tested on the 5th day in each group. The drug resistance of wild-type zebrafish was tested by rhodamine 123 experiment. The fluorescence intensity of transgenic zebrafish was tested by microplate reader, and the fluorescence distribution was tested by living cell workstation. The protein levels of transgenic zebrafish ß-catenin, GSK-3ß, ABCB4 and enhanced green fluorescent protein (EGFP) were tested by Western blot analysis. Results Rhodamine 123 experiments proved that there was drug resistance in zebrafish when treated with doxorubicin and vinblastine. Compared with the blank group, the EGFP fluorescence intensity increased in the transgenic zebrafish when treated with doxorubicin and vinblastine. Western blot assay showed the accumulation of ß-catenin accompanied by the increase of EGFP and ABCB4 proteins in the transgenic zebrafish exposed to adriamycin and vincristine. Conclusion The Wnt/ß-catenin signaling pathway in zebrafish is involved in the activation and drug resistance of zebrafish abcb4 gene.

Withaferin A activates stress signalling proteins in high risk acute lymphoblastic leukemia.

Withaferin A, the principal bio-active component isolated from the Withaniasomnifera, has shown promising anti-leukemic activity in addition to anti-invasive and anti-metastatic activity. The present study demonstrates the effect of withaferin A on the cell cycle status and the phosphorylation/activation of proteins involved in signal transduction in t(4;11) and non-t(4;11) acute lymphoblastic leukemia (ALL) cell lines after treatment with withaferin A. The cells after treatment with the vehicle or 25 µM withaferin A for 1, 2, 4 and 8 h were examined using flow cytometric analysis. The results revealed that withaferin A treatment induced cell growth arrest at the S to G2/M phase transition of the cell cycle. Withaferin A treatment also induced the phosphorylation of stress signalling proteins, including the p38 mitogen-activated protein kinase, the c-Jun N-terminal kinase, c-Jun, the heat shock protein 27 and protein kinase B within 0 to 16 h. These results were observed using multiplex technology and Western blotting analysis. Thus withaferin A induces stress response leading to cell death. Therefore, withaferin A can be a potent therapeutic agent for the treatment of high risk ALL with chromosomal translocation t(4;11).

[Research on fiber methane sensing system based on prism gas cell].

A novel fiber methane detection system was constructed based on integration of prism gas cell and harmonic detection technique. The system can be applied to broad-range concentration detection. Grounded on the Beer-Lambert approximation, the detection of various concentration (0-20%) of methane was completed using subtraction of background and ratio processing method, as the atmosphere surroundings was treated as background. The direct absorption spectra for various concentration were measured using GRIN gas cell, combined with available DFB-LD, and the R5 line of the 2v3 band of methane was selected as absorption peak. The system was tested online during gas mixing process and the linear relation between system indication and concentration variation was validated, while the stability and dynamic response characteristics was confirmed by experiments. The system sensitivity can be adjusted according to the concentration level of various field environments by changing the prism distance using step motor. So that, the system can be applied to various application fields and can be adopted as a monitoring instrument for coalmine tunnel and natural gas pipeline.