Design, synthesis, and evaluation of cell-penetrating anticancer peptides to enhance the antitumor activity of liposomal daunorubicin: A molecular dynamics and experimental study

Targeted delivery and effective penetration into cancer cells are key factors in the success of drug delivery systems. This study aimed to design, synthesize, and evaluate cell-penetrating anticancer peptides (ACPs), and to develop functionalized nanoliposomes with ACPs and an antibody to enhance the specificity and cellular uptake of liposomal daunorubicin (daunosome) in multidrug-resistance cancer cells. Here, a library of 1290 peptides was screened for anticancer potential and physicochemical properties, and the top candidates were evaluated for permeability to cell membrane models using molecular dynamics simulations. The selected peptides (Pep5 and Pep6) were synthesized, used to modify daunosomes, and evaluated for cytotoxicity, apoptosis, drug accumulation, and efflux kinetics in HDF, EPG85.257, and EPG85.257RDB cell lines. The liposomal formulations were characterized using FTIR, TEM, X-ray diffraction, and DLS analysis. The potential of mean force (PMF) profiles predicted that Pep6 required less energy than Pep5 to cross the membrane of cancer cells. The cytotoxicity assay showed that the peptides selectively reduced the viability of the cancer cell lines (EPG85.257RDB and EPG85.257) more than that of normal HDF cells. The daunorubicin encapsulation rate and average diameter of the daunosome formulations were approximately 93 % and 264–314 nm, respectively. The highest apoptosis rates were observed in the EPG85.257 cell line following treatment with Ab+TAT+daunosome (44.4 %) and in EPG85.257RDB cells treated with Ab+Pep6+daunosome (29.3 %). Drug accumulation was significantly increased following the decoration of daunosomes with trastuzumab, TAT, Pep5, and Pep6. The results indicate that the designed ACPs, in combination with the trastuzumab, can enhance the antitumor activity of liposomal daunorubicin

Retraction notice to “In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin/alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing” [Int. J. Biol. Macromol. 277(2024) 134362]

This article has been retracted: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). The article has been retracted at the request of the Editor-in-Chief. The journal was notified of possible image duplication. An investigation by the editorial office confirmed that the publication contained duplicated images in Figs. 3 and 6, as well as duplications with figures from other publications (https://doi.org/10.1002/mabi.202200574 and https://doi.org/10.1021/acsabm.3c00814). While the corresponding author initially collaborated with the investigation, they were unable to provide satisfactory explanations regarding the image duplications, leading the editors to lose trust in the integrity of the presented data. Additionally, concerns about authorship have been raised, as two co-authors (Morteza Koruji and Ali Mohammad Sharifi) have stated that they never consented to being listed as authors on the submission and were not consulted by the corresponding author. The corresponding author has not responded to the allegations concerning authorship

The effect of an educative-supportive program based on the continuous care model on daily living activities and sleep quality in peoples with epilepsy

The impairment of sleep quality and the occurrence of frequent nocturnal awakenings significantly contribute to the reduction of effective sleep duration in individuals diagnosed with epilepsy. This deterioration not only compromises overall life satisfaction but also adversely affects cognitive functioning and concentration on daily living activities. Therefore, the imperative for enhanced management strategies for this disorder among individuals with epilepsy is critically important. This study is designed to systematically assess the impact of an educational-support program grounded in the Continuous Care Model on the daily living activities and sleep quality of individuals with epilepsy. Methods: This clinical trial was conducted in 2023, involving 70 patients diagnosed with epilepsy, who were selected through purposive sampling and subsequently randomized into intervention and control groups. The intervention group participated in a 12-week program formulated according to the principles of the Continuous Care Model. Data collection was executed utilizing a demographic questionnaire, the Barthel Activities of Daily Living Scale, and the Pittsburgh Sleep Quality Index (PSQI). Statistical analyses were performed using SPSS software version 22 to evaluate the data. Findings: The study population consisted of 42.9 % females and 57.1 % males, with a mean age of 37.8 ± 16.6 years. The mean age for the intervention group was 34.9 ± 12.9 years, while the control group had a mean age of 40.7 ± 19.4 years. Prior to the intervention, no statistically significant differences were identified between the intervention and control groups concerning the mean scores for daily living activities (P = 0.24) and sleep quality (P = 0.377). However, immediately following the intervention and at the two-month follow-up, statistically significant differences were observed between the two groups in the mean scores for daily living activities (P < 0.001) and sleep quality (P < 0.001). Conclusion: The implementation of a structured care program based on the Continuous Care Model has demonstrated beneficial effects on both daily living activities and sleep quality in individuals with epilepsy. Given its safety profile, cost-effectiveness, and proven efficacy, the integration of this model into standard care practices is strongly advocated to enhance the functional capabilities and sleep quality of individuals living with epilepsy

Correction: Decellularized skin pretreatment by monophosphoryl lipid A and lactobacillus casei supernatant accelerate skin recellularization

The original article has been published with incorrect Fig. 4a; for completeness and transparency, the old incorrect version and the corrected version of Fig. 4 are displayed below. The original article has been corrected. Incorrect version of Fig. 4. Recellularization of FAMs by hucMSCs on days 4, 8, and 12. (a) H&E staining in different days showed that MPLA-treated FAMs resulted in the most effective recellularization on the 12th day (200x magnification). (b) Fluorescent staining with Hoechst. The nuclei of the cells are bright spots, which are more fluorescent in the MPLA-treated FAM, on day 12 (100x magnification). (c) SEM images of recellularized MPLA treated-FAMs showed a significant increase in the number of migrated cells on day 12 compared to other groups Correct version of Fig. 4. Recellularization of FAMs by hucMSCs on days 4, 8, and 12. (a) H&E staining in different days showed that MPLA-treated FAMs resulted in the most effective recellularization on the 12th day (200x magnification). (b) Fluorescent staining with Hoechst. The nuclei of the cells are bright spots, which are more fluorescent in the MPLA-treated FAM, on day 12 (100x magnification). (c) SEM images of recellularized MPLA treated-FAMs showed a significant increase in the number of migrated cells on day 12 compared to other group

Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?

Cellular senescence is understood to be a biological process that is defined as irreversible growth arrest and was originally recognized as a tumor-suppressive mechanism that prevents further propagation of damaged cells. More recently, cellular senescence has been shown to have a dual role in prevention and tumor promotion. Senescent cells carry a senescence-associated secretory phenotype (SASP), which is altered by secretory factors including pro-inflammatory cytokines, chemokines, and other proteases, leading to the alteration of the tissue microenvironment. Though senescence would eventually halt the growth of cancerous potential cells, SASP contributes to the tumor environment by promoting inflammation, matrix remodeling, and tumor cell invasion. The paradox of tumor prevention/promotion is particularly relevant to the bone niche tumor microenvironment, where longer-lasting, chronic inflammation promotes tumor formation. Insights into a mechanistic understanding of cellular senescence and SASP provide the basis for targeted therapies, such as senolytics, which aim to eliminate senescent cells, or SASP inhibitors, which would eliminate the tumor-promoting effects of senescence. These therapeutic interventions offer significant clinical implications for treating cancer and healthy agin

Nanocarriers for cutting-edge cancer immunotherapies

Cancer immunotherapy aims to harness the body's own immune system for effective and long-lasting elimination of malignant neoplastic tissues. Owing to the advance in understanding of cancer pathology and immunology, many novel strategies for enhancing immunological responses against various cancers have been successfully developed, and some have translated into excellent clinical outcomes. As one promising strategy for the next generation of immunotherapies, activating the multi-cellular network (MCN) within the tumor microenvironment (TME) to deploy multiple mechanisms of action (MOAs) has attracted significant attention. To achieve this effectively and safely, delivering multiple or pleiotropic therapeutic cargoes to the targeted sites of cancerous tissues, cells, and intracellular organelles is critical, for which numerous nanocarriers have been developed and leveraged. In this review, we first introduce therapeutic payloads categorized according to their predicted functions in cancer immunotherapy and their physicochemical structures and forms. Then, various nanocarriers, along with their unique characteristics, properties, advantages, and limitations, are introduced with notable recent applications in cancer immunotherapy. Following discussions on targeting strategies, a summary of each nanocarrier matching with suitable therapeutic cargoes is provided with comprehensive background information for designing cancer immunotherapy regimen

GLP-1-based therapies for type 2 diabetes: from single, dual and triple agonists to endogenous GLP-1 production and L-cell differentiation

Glucagon-like peptide-1 (GLP-1) is an incretin peptide hormone mainly secreted by enteroendocrine intestinal L-cells. GLP-1 is also secreted by α-cells of the pancreas and the central nervous system (CNS). GLP-1 secretion is stimulated by nutrient intake and exerts its effects on glucose homeostasis by stimulating insulin secretion, gastric emptying confiding the food intake, and β-cell proliferation. The insulinotropic effects of GLP-1, and the reduction of its effects in type 2 diabetes mellitus (T2DM), have made GLP-1 an attractive option for the treatment of T2DM. Furthermore, GLP-1-based medications such as GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have been shown to improve diabetes control in preclinical and clinical trials with human subjects. Importantly, increasing the endogenous production of GLP-1 by different mechanisms or by increasing the number of intestinal L-cells that tend to produce this hormone may be another effective therapeutic approach to managing T2DM. Herein, we briefly describe therapeutic agents/compounds that enhance GLP-1 function. Then, we will discuss the approaches that can increase the endogenous production of GLP-1 through various stimuli. Finally, we introduce the potential of L-cell differentiation as an attractive future therapeutic approach to increase GLP-1 production as an attractive therapeutic alternative for T2DM

N-acetyl cysteine through modulation of HDAC2 and GCN5 in the hippocampus mitigates behavioral disorders in the first and second generations of socially isolated mice

Objective(s): Social isolation stress (SIS) in early life can lead to behavioral disorders. N-acetylcysteine (NAC), an antioxidant, may aid treatment. This study explored NAC's impact on behavior in first and second-generation mice after SIS, focusing on HDAC2 and GCN5 expression in the hippocampus. Materials and methods: In this study, 24 male and 24 female mice were bred for one generation. The pups were divided into six (3male, 3female) groups (n = 20): 1- Control receiving normal saline, 2- SIS with normal saline, 3- SIS with NAC (150 mg/kg) IP for four weeks. Eight mice from each group underwent behavioral, histopathological, and molecular tests, while others were mated (4 males + 4 females) to produce second generations. These pups were divided into 9 groups (n = 8) for behavioral tests, including elevated plus maze, open field, forced swimming, and histopathological and molecular assessments (HDAC2 and GCN5 expression) in the hippocampus. Results: The SIS group showed increased HDAC2 and GCN5 expression. Following SIS, there was a decrease in open arm entries and passes in the open field test, alongside increased immobility in the forced swimming test and reduced CA1 and CA3 hippocampal diameters. NAC mitigated the adverse molecular, behavioral, and histopathological impacts of SIS across both generations. Conclusion: NAC reduces behavioral disorders after SIS (first and second generation) by reducing the expression of GCN5 and HDAC2 and increasing neuronal diameter in the hippocampus. Future research should investigate the long-term therapeutic effects of NAC for behavioral disorders after SIS

Identification of novel diagnostic and prognostic microRNAs in sarcoma on TCGA dataset: bioinformatics and machine learning approach

The discovery of unique microRNA (miR) patterns and their corresponding genes in sarcoma patients indicates their involvement in cancer development and suggests their potential use in medical management. MiRs were identified from The Cancer Genome Atlas (TCGA) dataset, with a Deep Neural Network (DNN) employed for novel miR identification. MiRDB facilitated target predictions. Functional enrichment analysis, identify critical pathways, protein-protein interaction network, and diseases/clinical data correlations were explored. COX regression, Kaplan-Meier analyses, and CombioROC was also utilized. The population consisted of 119 females and 142 males, and 1046 miRs were uncovered. Ten miRs was selected for further analysis using DNN. Upon analyzing for gene ontology, it was found that these genes showed enrichment in various activities. We identified a significant association between the overall survival rate of sarcoma patients and miRs levels. The combination of miR.3688 and miR.3936 achieved the greatest diagnostic standing. MiRs have the capability to screen sarcoma patients to identify undetected tumors, predict prognosis, and pinpoint prospective targets for treatment. Further large clinical trials are required to validate our findings

Providing Ethical Care for Children with Cancer: Nurses’ Perspectives

Background: Diagnosing a child with cancer is one of the most intense and challenging experiences that a family can face. Caring for children with cancer is one of the most challenging areas of the nursing profession, technically and emotionally, and nurses face various ethical issues in this regard. This study aims to explore nurses' perceptions of providing ethical care for children with cancer. Materials and Methods: This study applied a qualitative design and a purposive sampling method. Participants included 21 nurses with experience in caring for children with cancer. Data were collected using semi-structured interviews and analyzed using inductive content analysis. Results: Data analysis revealed three categories and seven subcategories. First, barriers to providing ethical care (subcategories: parents making decisions instead of the child, cultural misinterpretations, and reference to fortune-tellers). Second, facilitators of providing ethical care (subcategories: family hopefulness and parents' religious background). Third, approaches for providing ethical care (subcategories: the necessity of conducting research in the field of cultural backgrounds and the establishment of ethical-religious committees). Conclusions: This study presents some significant barriers, facilitators, and approaches to providing ethical care for children with cancer. These results are based on nurses' experiences and perceptions. All healthcare professionals can use our results to provide high-quality and ethical care for children with cancer