Co-delivery of salinomycin and curcumin for cancer stem cell treatment by inhibition of cell proliferation, cell cycle arrest, and epithelial-mesenchymal transition

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence

A simple method for deriving functional MSCs and applied for osteogenesis in 3D scaffolds

We describe a simple method for bone engineering using biodegradable scaffolds with mesenchymal stem cells derived from human induced-pluripotent stem cells (hiPS-MSCs). The hiPS-MSCs expressed mesenchymal markers (CD90, CD73, and CD105), possessed multipotency characterized by tri-lineages differentiation: osteogenic, adipogenic, and chondrogenic, and lost pluripotency – as seen with the loss of markers OCT3/4 and TRA-1-81 – and tumorigenicity. However, these iPS-MSCs are still positive for marker NANOG. We further explored the osteogenic potential of the hiPS-MSCs in synthetic polymer polycaprolactone (PCL) scaffolds or PCL scaffolds functionalized with natural polymer hyaluronan and ceramic TCP (PHT) both in vitro and in vivo. Our results showed that these iPS-MSCs are functionally compatible with the two 3D scaffolds tested and formed typically calcified structure in the scaffolds. Overall, our results suggest the iPS-MSCs derived by this simple method retain fully osteogenic function and provide a new solution towards personalized orthopedic therapy in the future

The Impact of the COVID-19 Pandemic on Chinese Postgraduate Students’ Mental Health

To understand the mental health status of Chinese postgraduate students during the COVID-19 pandemic, we used three online questionnaires: self-rating anxiety (SAS) scale, self-rating depression (SDS) scale, and social avoidance and distress (SAD) scale. A total of 3137 postgraduate students from different regions of China participated in our study. We explored the relationship between participant characteristics and mental health using an analysis of variance (ANOVA). We found that the proportions of respondents with severe, mild, and moderate depression were 1.4%, 10.48%, and 21.99%, respectively, and the corresponding proportions of respondents with anxiety were 1.56%, 4.65%, and 14.69%, respectively. A one-way ANOVA revealed that the mental health statuses of the participants were different between the subgroups based on majors, classes, degree types, and the method of communication with advisors and students. A two-way ANOVA revealed significant effects on interaction and the method of communication with advisors and peers. These findings suggest that the mental health of postgraduate students should be monitored during the pandemic, especially when they are unable to communicate directly with their advisors or peers, and targeted psychological counselling must be focused on anxiety and depression

Effects of the establishment of trauma centres on the mortality rate among seriously injured patients: a propensity score matching retrospective study

Abstract Background Little evidence suggests that trauma centres are associated with a lower risk of mortality in severely injured patients (Injury Severity Score (ISS) ≥16) with multiple injuries in China. The objective of this study was to determine the association between the establishment of trauma centres and mortality among severely injured patients with multiple injuries and to identify some risk factors associated with mortality. Methods A retrospective single-centre study was performed including trauma patients admitted to the First Affiliated Hospital of Nanchang University (FAHNU) between January 2016 and December 2021. To determine whether the establishment of a trauma centre was an independent predictor of mortality, logistic regression analysis and propensity score matching (PSM) were performed. Results Among 431 trauma patients, 172 were enrolled before the trauma centre was built, while 259 were included after the trauma centre was built. A higher frequency of older age and traffic accident injury was found in patients diagnosed after the trauma centre was built. The times for the completion of CT examinations, emergency operations and blood transfusions in the “after trauma centre” group were shorter than those in the “before trauma centre” group. However, the total expenditure of patients was increased. In the overall group, univariate and multivariate logistic regression analyses showed that a higher ISS was an independent predictor for worse mortality (OR = 17.859, 95% CI, 8.207–38.86, P < 0.001), while the establishment of a trauma centre was favourable for patient survival (OR = 0.492), which was also demonstrated by PSM. After determining the cut-off value of time for the completion of CT examination, emergency operation and blood transfusion, we found that the values were within the “golden one hour”, and it was better for patients when the time was less than the cut-off value. Conclusion Our study showed that for severely injured patients, the establishment of a trauma centre was favourable for a lower mortality rate. Furthermore, the completion of a CT examination, emergency surgery and blood transfusion in a timely manner and a lower ISS were associated with a decreased mortality rate

Simple-based Dynamic Decentralized Community Detection Algorithm in socially aware networks

This paper introduces a novel, Simple-based Dynamic Decentralized Community Detection Algorithm (S-DCDA) for Socially Aware Networks. This algorithm aims to address the resource-intensive nature, instabilities and inaccuracies of traditional distributed community detection algorithms. The dynamics of decentralization is evident in the threefold nature of the algorithm: (i) each node of the community is the core of the entire network or community for a certain period of time dependent on their need, (ii) nodes are not centralized around themselves, requiring the consent of the other node to join a community, and (iii) Communities start from a single node to form an initial scale community, the number of nodes and the relationship among them are constantly changing. The algorithm requires low processor performance and memory capacity size of each node, to a certain extent, effectively improve the accuracy and stability of community detection and maintenance. Experimental results demonstrate that in comparison to classical and classical-based improved community detection algorithms, S-DCDA yields superior detection results

Upregulation of miRNA-10a-5p promotes tumor progression in cervical cancer by suppressing UBE2I signaling

Cervical cancer (CC) is a common malignant neoplasm in gynecology. There is increasing evidence to suggest that microRNAs (miRNAs) act as crucial regulators of CC. However, whether miR-10a-5p plays a role in CC is under investigation. The aim of this stuy was to assess the miR-10a-5p expression pattern in the development of CC and investigate its downstream target. MiR-10a-5p inhibition decreased CC cell proliferation and impaired CC cell invasion and migration but enhanced apoptosis. UBE2I was a direct target of miR-10a-5p. QRT-PCR results showed a down-regulation of UBE2I in CC cells, opposing miR-10a-5p. Besides, overexpression of miR-10a-5p down-regulated UBE2I. Functional rescue experiments further indicated the miR-10a-5p-UBE2I axis was linked to CC cell growth, apoptosis and metastasis. MiR-10a-5p upregulation promotes cervical cancer development by inhibiting UBE2I. These results also predict that miR-10a-5p may be a potential target for the clinical treatment of CC.IMPACT STATEMENT What is already known on this subject? As a widely researched cancer-related miRNA, the overexpression of miR-10a-5p has been verified in various cancers. It has been described in a meta-analysis report that there were 42 miRNAs up-regulated and 21 miRNAs down-regulated in different stages of cervical cancer tissue versus healthy tissue. What do the results of this study add? We verified that miR-10a-5p initiates and promotes tumor cell development by decreasing UBE2I abundance. This miR-10a-5p-mediated post-transcriptional regulation of UBE2I is involved in the tumorigenesis, invasion and migration of human cervical cancer. What are the implications of these findings for clinical practice and/or further research? These findings provide mechanistic insights into how miR-10a-5p regulates cervical cancer hyper-proliferation and metastasis, as well as a new target for clinical treatment. Nevertheless, whether miR-10a-5p/UBE2I axis can be regulated by non-invasive methods need further exploration, which will be the focus of our future research

Perturbation of arachidonic acid and glycerolipid metabolism promoted particulate matter-induced inflammatory responses in human bronchial epithelial cells

Particulate matter (PM) has become the main risk factor for public health, being linked with an increased risk of respiratory diseases. However, the potential mechanisms underlying PM-induced lung injury have not been well elucidated. In this study, we systematically integrated the metabolomics, lipidomics, and transcriptomics data obtained from the human bronchial epithelial cells (HBECs) exposed to PM to reveal metabolic disorders in PM-induced lung injury. We identified 170 differentially expressed metabolites (82 upregulated and 88 downregulated metabolites), 218 differentially expressed lipid metabolites (125 upregulated and 93 downregulated lipid metabolites), and 1417 differentially expressed genes (643 upregulated and 774 downregulated genes). Seven key metabolites (prostaglandin E2, inosinic acid, L-arginine, L-citrulline, L-leucine, adenosine, and adenosine monophosphate), and two main lipid subclasses (triglyceride and phosphatidylcholine) were identified in PM-exposed HBECs. The amino acid metabolism, lipid metabolism, and carbohydrate metabolism were the significantly enriched pathways of identified differentially expressed genes. Then, conjoint analysis of these three omics data and further qRT-PCR validation showed that arachidonic acid metabolism, glycerolipid metabolism, and glutathione metabolism were the key metabolic pathways in PM-exposed HBECs. The knockout of AKR1C3 in arachidonic acid metabolism or GPAT3 in glycerolipid metabolism could significantly inhibit PM-induced inflammatory responses in HBECs. These results revealed the potential metabolic pathways in PM-exposed HBECs and provided a new target to protect from PM-induced airway damage

Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway

Abstract Background Drug resistance is common in cancer chemotherapy. This study investigates the role of Glycerol kinase 5 (GK5) in mediating gefitinib resistance in NSCLC. Methods The exosomal mRNA of GK5 was detected using a tethered cationic lipoplex nanoparticle (TCLN) biochip. Real-time PCR and Western blot were used to examine the expression of GK5 mRNA and protein in gefitinib-sensitive and -resistant human lung adenocarcinoma cells. The cell counting kit-8, EdU assay, flow cytometry, and JC-1 dye were used to measure cell proliferation, cell cycle, and the mitochondrial membrane potential. Results We found that the exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma was significantly higher compared with that of gefitinib-sensitive patients. The mRNA and protein levels of GK5 were significantly upregulated in gefitinib-resistant human lung adenocarcinoma PC9R and H1975 cells compared with gefitinib-sensitive PC9 cells. Silencing GK5 in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway. Conclusions We demonstrated that GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest. GK5 could be a novel therapeutic target for treatment of NSCLC with resistance to EGFR tyrosine kinase inhibitors