Analysis of Long Noncoding RNAs in Aila-Induced Non-Small Cell Lung Cancer Inhibition

Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality among all carcinomas. However, it is difficult to diagnose in the early stage, and current therapeutic efficacy is not ideal. Although numerous studies have revealed that Ailanthone (Aila), a natural product, can inhibit multiple cancers by reducing cell proliferation and invasion and inducing apoptosis, the mechanism by which Aila represses NSCLC progression in a time-dependent manner remains unclear. In this study, we observed that most long noncoding RNAs (lncRNAs) were either notably up- or downregulated in NSCLC cells after treatment with Aila. Moreover, alterations in lncRNA expression induced by Aila were crucial for the initiation and metastasis of NSCLC. Furthermore, in our research, expression of DUXAP8 was significantly downregulated in NSCLC cells after treatment with Aila and regulated expression levels of EGR1. In conclusion, our findings demonstrate that Aila is a potent natural suppressor of NSCLC by modulating expression of DUXAP8 and EGR1

Dissociated mouse tooth germ epithelial cells retain the expression of tooth developmental genes during reaggregation process

Generation of bio-engineered teeth by using stem cells will be a major approach for bioengineered implantation. Previous studies have demonstrated that dissociated tooth germ cells are capable of generating a tooth after reaggregation in vitro. However, the cellular and molecular mechanisms underlying this tooth regeneration are not clear. In this study, we dispersed E13.5 molar germ into single cells, immediately reaggregated them into cell pellet, then grafted the reaggregates under mouse kidney capsule for various times of culture. We investigated the morphogenesis and the expression of several developmental genes in dental epithelial cells in reaggregates of tooth germ cells. We found that dissociated tooth germ cells, after reaggregation, recapitulated normal tooth developmental process. In additon, dissociated dental epithelial cells retained the expression of Fgf8, Noggin, and Shh during reaggregation and tooth regeneration processes. Our results demonstrated that, despite of under dissociated status, dental epithelial cells maintained their odontogenic fate after re-aggregation with dental mesenchymal cells. These results provided important information for future in vitro generation of bio-engineered teeth from stem cells

Uncovering the complexity of childhood undernutrition through strain-level analysis of the gut microbiome

Abstract Background Undernutrition (UN) is a critical public health issue that threatens the lives of children under five in developing countries. While evidence indicates the crucial role of the gut microbiome (GM) in UN pathogenesis, the strain-level inspection and bacterial co-occurrence network investigation in the GM of UN children are lacking. Results This study examines the strain compositions of the GM in 61 undernutrition patients (UN group) and 36 healthy children (HC group) and explores the topological features of GM co-occurrence networks using a complex network strategy. The strain-level annotation reveals that the differentially enriched species between the UN and HC groups are due to discriminated strain compositions. For example, Prevotella copri is mainly composed of P. copri ASM1680343v1 and P. copri ASM345920v1 in the HC group, but it is composed of P. copri ASM346549v1 and P. copri ASM347465v1 in the UN group. In addition, the UN-risk model constructed at the strain level demonstrates higher accuracy (AUC = 0.810) than that at the species level (AUC = 0.743). With complex network analysis, we further discovered that the UN group had a more complex GM co-occurrence network, with more hub bacteria and a higher clustering coefficient but lower information transfer efficiencies. Moreover, the results at the strain level suggested the inaccurate and even false conclusions obtained from species level analysis. Conclusions Overall, this study highlights the importance of examining the GM at the strain level and investigating bacterial co-occurrence networks to advance our knowledge of UN pathogenesis

The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer

Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications

Targeted delivery of CEBPA-saRNA for the treatment of pancreatic ductal adenocarcinoma by transferrin receptor aptamer decorated tetrahedral framework nucleic acid

Abstract Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC

Additional file 1 of Role of surgery in T4N0-3M0 esophageal cancer

Additional file 1: Supplementary Table S1. Selection procedure of study cohort. Supplementary Table S2. Univariable and multivariable Cox regression analysis comparing no surgery with surgery for the OS of AJCC 8th T4aN0-3M0 EC patients. Supplementary Table S3. Univariable and multivariable Cox regression analysis comparing no surgery with surgery for the OS of AJCC 8th T4bN0-3M0 EC patients. Supplementary Table S4. Univariable and multivariable Cox regression analysis comparing no surgery with neoadjuvant therapy plus surgery for the OS of AJCC 8th T4N0-3M0 EC patients. Supplementary Table S5. Univariable and multivariable Cox regression analysis comparing no surgery with no neoadjuvant therapy plus surgery for the OS of AJCC 8th T4N0-3M0 EC patients. Supplementary Table S6. Univariable and multivariable Cox regression analysis comparing neoadjuvant therapy plus surgery with no neoadjuvant therapy plus surgery for the OS of AJCC 8th T4N0-3M0 EC patients. Supplementary Table S7. Univariable and multivariable Cox regression analysis comparing no surgery with surgery for the OS of AJCC 8th IIIB-IVA esophageal adenocarcinoma patients. Supplementary Table S8. Univariable and multivariable Cox regression analysis comparing no surgery with surgery for the OS of AJCC 8th IIIB-IVA esophageal squamous cell carcinoma patients. Supplementary Figure S1. Baseline standardized mean difference before and after PSM for surgery vs. no surgery in T4N0-3M0 EC (A), surgery vs. no surgery in T4aN0-3M0 EC (B), surgery vs. no surgery in T4bN0-3M0 EC (C), Neo + surgery vs. no surgery in T4N0-3M0 EC (D), surgery without Neo vs. no surgery in T4N0-3M0 EC (E), and Neo + surgery vs. surgery without Neo in T4N0-3M0 EC (F). PSM, propensity score matching; EC, esophageal cancer; Neo, neoadjuvant therapy. Supplementary Figure S2. Subgroup analysis of HR for surgery vs. no surgery in OS of stage T4aN0-3M0 EC. HR, hazard ratio; OS, overall survival; EC, esophageal cancer; CI, confidential interval. Supplementary Figure S3. Subgroup analysis of HR for surgery vs. no surgery in OS of stage T4bN0-3M0 EC. HR, hazard ratio; OS, overall survival; EC, esophageal cancer; CI, confidential interval. Supplementary Figure S4. Baseline standardized mean difference before and after PSM for surgery vs. no surgery in IIIB-IVA esophageal adenocarcinoma patients (A), and IIIB-IVA esophageal squamous cell carcinoma patients (B). PSM, propensity score matching. Supplementary Figure S5. Survival curves of OS for stage IIIB-IVA esophageal adenocarcinoma comparing surgery with no surgery before PSM (A) and after PSM (B), IIIB-IVA esophageal squamous cell carcinoma comparing surgery with no surgery before PSM (C) and after PSM (D). OS, overall survival; PSM, propensity score matching

Implementing Symptom Management Follow-up Using an Electronic Patient-Reported Outcome Platform in Outpatients With Advanced Cancer: Longitudinal Single-Center Prospective Study

BackgroundPatients with cancer experience multiple symptoms related to cancer, cancer treatment, and the procedures involved in cancer care; however, many patients with pain, depression, and fatigue, especially those outside the hospital, receive inadequate treatment for their symptoms. Using an electronic patient-reported outcome (ePRO) platform to conduct symptom management follow-up in outpatients with advanced cancer could be a novel and potentially effective approach. However, empirical evidence describing in detail the preparation and implementation courses in a real setting is needed. ObjectiveThe purpose of this paper was to describe the implementation process and evaluation of an ePRO platform that facilitates symptom management for patients with cancer, share our experiences and the problems we encountered during the process of implementation, and share the solutions we identified for those problems. Moreover, we tested the feasibility, safety, and efficacy of the ePRO platform. MethodsThis was a real-world, ongoing, longitudinal, single-center, prospective study with a total of 7 follow-ups conducted within 4 weeks after the first visit to the symptom management clinic (on days 1, 3, 7, 10, 14, 21, and 28). Participants were encouraged to complete scales for physical symptoms (pain, fatigue, and shortness of breath), cognitive symptoms (memory problems and impaired concentration), and affective symptoms (especially depression and anxiety) during follow-up. The design and function of the ePRO-doctor client and ePRO-patient client, the patient-reported outcome (PRO) scales used in the study, and the strategies to promote symptom tracking have been described. Moreover, the training and evaluation for research assistants have been presented. The efficacy of the ePRO platform was assessed with a comparison of the baseline and 4-week outcomes on the MD Anderson Symptom Inventory. ResultsUsing the ePRO platform for symptom management follow-ups in advanced cancer patients was associated with a high completion rate (72.7%-86.4%) and a low drop-off rate (23.6%). The ePRO platform sent 293 alert notifications to both patients and doctors, which promoted patient security. The short and sharp PRO tool selection, user-friendly interface, automatic reminder notifications and alerts, and multiple dimensional training were essential components for the preparation and implementation of the ePRO system. The results showed significant improvements in the mean scores of pain, fatigue, and numbness from baseline to day 28 (P=.02, P=.02, and P<.001, respectively). ConclusionsThe use of an ePRO platform for symptom management follow-ups in advanced cancer patients is time-saving, energy-saving, and effective. PRO tool selection, platform design, and training of research assistants are important aspects for implementation. Future research should validate the ePRO platform in a larger randomized controlled study

X-Ray-Induced Fragmentation of Imidazolium-Based Ionic Liquids Studied by Soft X-Ray Absorption Spectroscopy

We investigated the X-ray absorption spectroscopy (XAS) fingerprint of EMImTFSI ionic liquid (IL) and its fragmentation products created by X-ray irradiation. To accomplish this, we used an open geometry where an IL droplet is directly exposed in the vacuum chamber and an enclosed geometry where the IL is confined in a cell covered by an X-ray transparent membrane. In the open geometry, the XAS signature was stable and consistent with experimental and theoretical spectra reported in the literature. In contrast, when the IL is enclosed, its XAS evolves continuously under X-ray illumination due to the accumulation of volatile fragmentation products inside the closed cell, while they evaporate in the open geometry. The changes in the XAS from the core levels of relevant elements (C, N, S, F) together with density functional theory calculations allowed us to identify the chemical nature of the fragment products and the chemical bonds most vulnerable to rupture under soft X-ray irradiation