Fine-tuning the cytotoxicity profile of N,N,N-trimethyl chitosan through trimethylation, molecular weight, and polyelectrolyte complex nanoparticles.

N,N,N-trimethyl chitosan (TMC) is a promising biopolymer for pharmaceutical applications due to its enhanced solubility and bioadhesive properties, though its cytotoxic limitations necessitate careful modification to ensure safety and efficacy. This study sought to investigate whether nanoparticle (NP) formation could reduce the anticipated cytotoxic effects of TMC, thus improving its applicability across a wider spectrum of pharmaceutical uses. TMC's capability to form NPs with anionic polyelectrolytes led to the application of chondroitin sulfate (ChS) in this study.

Master Regulators of Causal Networks in Intestinal- and Diffuse-Type Gastric Cancer and the Relation to the RNA Virus Infection Pathway.

Causal networks are important for understanding disease signaling alterations. To reveal the network pathways affected in the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to the poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) were analyzed. The network pathways in GC were analyzed using Ingenuity Pathway Analysis (IPA).

Facile Generation of Heterotelechelic Poly(2-Oxazoline)s Towards Accelerated Exploration of Poly(2-Oxazoline)-Based Nanomedicine.

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation.

Amphiphilic Poly(2-oxazoline)s with Glycine-Containing Hydrophobic Blocks Tailored for Panobinostat- and Imatinib-Loaded Micelles.

Aiming toward the development of tailored carrier materials for the cytostatics panobinostat and imatinib, an amphiphilic block copolymer composed of poly(2-ethyl-2-oxazoline) and a degradable poly(2-(3-phenylpropyl)-2-oxazoline) analogue () was synthesized a postpolymerization synthesis route based on reacylation of oxidized linear poly(ethylene imine). The obtained was found to readily self-assemble into well-defined micelles with a critical micelle concentration of 1 μg mL. The incubation of HUVEC cells with the blank micelles revealed their excellent cytocompatibility (up to 2 mg mL), thus confirming the polymers' suitability for potential drug delivery application.

Poly-γ-glutamic acid nanoparticles as adjuvant and antigen carrier system for cancer vaccination.

Vaccination is an innovative strategy for cancer treatment by leveraging various components of the patients' immunity to boost an anti-tumor immune response. Rationally designed nanoparticles are well suited to maximize cancer vaccination by the inclusion of immune stimulatory adjuvants. Also, nanoparticles might control the pharmacokinetics and destination of the immune potentiating compounds.

Nanomedicine targeting brain lipid metabolism as a feasible approach for controlling the energy balance.

Targeting brain lipid metabolism is a promising strategy to regulate the energy balance and fight metabolic diseases such as obesity. The development of stable platforms for selective delivery of drugs, particularly to the hypothalamus, is a challenge but a possible solution for these metabolic diseases. Attenuating fatty acid oxidation in the hypothalamus CPT1A inhibition leads to satiety, but this target is difficult to reach with the current drugs.

Abnormal Glycosylation in Cancer Cells and Cancer Stem Cells as a Therapeutic Target.

Tumor resistance and recurrence have been associated with the presence of cancer stem cells (CSCs) in tumors. The functions and survival of the CSCs have been associated with several intracellular and extracellular features. Particularly, the abnormal glycosylation of these signaling pathways and markers of CSCs have been correlated with maintaining survival, self-renewal and extravasation properties.

Bioresponsive Polymers for Nanomedicine-Expectations and Reality!

Bioresponsive polymers in nanomedicine have been widely perceived to selectively activate the therapeutic function of nanomedicine at diseased or pathological sites, while sparing their healthy counterparts. This idea can be described as an advanced version of Paul Ehrlich's magic bullet concept. From that perspective, the inherent anomalies or malfunction of the pathological sites are generally targeted to allow the selective activation or sensory function of nanomedicine.

Nanomedicine for brain cancer.

CNS tumors remain among the deadliest forms of cancer, resisting conventional and new treatment approaches, with mortality rates staying practically unchanged over the past 30 years. One of the primary hurdles for treating these cancers is delivering drugs to the brain tumor site in therapeutic concentration, evading the blood-brain (tumor) barrier (BBB/BBTB). Supramolecular nanomedicines (NMs) are increasingly demonstrating noteworthy prospects for addressing these challenges utilizing their unique characteristics, such as improving the bioavailability of the payloadsviacontrolled pharmacokinetics and pharmacodynamics, BBB/BBTB crossing functions, superior distribution in the brain tumor site, and tumor-specific drug activation profiles.

Psychological Distress among Bangladeshi Dental Students during the COVID-19 Pandemic.

Psychological sufferings are observed among dental students during their academic years, which had been intensified during the COVID-19 pandemic. This study assessed the levels and identified factors associated with psychological distress, fear and coping experienced by dental undergraduate students in Bangladesh. A cross sectional online survey was conducted during October-November, 2021.

Cell Cycle Regulation and DNA Damage Response Networks in Diffuse- and Intestinal-Type Gastric Cancer.

Dynamic regulation in molecular networks including cell cycle regulation and DNA damage response play an important role in cancer. To reveal the feature of cancer malignancy, gene expression and network regulation were profiled in diffuse- and intestinal-type gastric cancer (GC). The results of the network analysis with Ingenuity Pathway Analysis (IPA) showed that the activation states of several canonical pathways related to cell cycle regulation were altered.

Poly-ion complex micelles effectively deliver CoA-conjugated CPT1A inhibitors to modulate lipid metabolism in brain cells.

Carnitine palmitoyltransferase 1A (CPT1A) is a central player in lipid metabolism, catalyzing the first step to fatty acid oxidation (FAO). Inhibiting CPT1A, especially in the brain, can have several pharmacological benefits, such as in treating obesity and brain cancer. C75-CoA is a strong competitive inhibitor of CPT1A.

Efficacy of pH-Sensitive Nanomedicines in Tumors with Different c-MYC Expression Depends on the Intratumoral Activation Profile.

Effective inhibition of the protein derived from cellular myelocytomatosis oncogene (c-Myc) is one of the most sought-after goals in cancer therapy. While several c-Myc inhibitors have demonstrated therapeutic potential, inhibiting c-Myc has proven challenging, since c-Myc is essential for normal tissues and tumors may present heterogeneous c-Myc levels demanding contrasting therapeutic strategies. Herein, we developed tumor-targeted nanomedicines capable of treating both tumors with high and low c-Myc levels by adjusting their ability to spatiotemporally control drug action.

Core-Cross-linked Fluorescent Worm-Like Micelles for Glucose-Mediated Drug Delivery.

We herein report the fabrication of core-crosslinked, fluorescent, and surface-functionalized worm-like block copolymer micelles as drug delivery vehicles. The polyether-based diblock terpolymer [allyl-poly(ethylene oxide)--poly(2-ethylhexyl glycidyl ether--furfuryl glycidyl ether)] was synthesized anionic ring opening polymerization, and self-assembly in water as a selective solvent led to the formation of long filomicelles. Subsequent cross-linking was realized using hydrophobic bismaleimides as well as a designed fluorescent cross-linker for thermally induced Diels-Alder reactions with the furfuryl units incorporated in the hydrophobic block of the diblock terpolymer.

Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer.

VisExPreS: A Visual Interactive Toolkit for User-Driven Evaluations of Embeddings.

Although popularly used in big-data analytics, dimensionality reduction is a complex, black-box technique whose outcome is difficult to interpret and evaluate. In recent years, a number of quantitative and visual methods have been proposed for analyzing low-dimensional embeddings. On the one hand, quantitative methods associate numeric identifiers to qualitative characteristics of these embeddings; and, on the other hand, visual techniques allow users to interactively explore these embeddings and make decisions.

Supramolecularly enabled pH- triggered drug action at tumor microenvironment potentiates nanomedicine efficacy against glioblastoma.

The crucial balance of stability in blood-circulation and tumor-specific delivery has been suggested as one of the challenges for effective bench-to-bedside translation of nanomedicines (NMs). Herein, we developed a supramolecularly enabled tumor-extracellular (T) pH-triggered NM that can maintain the micellar structure with the entrapped-drug during systemic circulation and progressively release drug in the tumor by rightly sensing heterogeneous tumor-pH. Desacetylvinblastine hydrazide (DAVBNH), a derivative of potent anticancer drug vinblastine, was conjugated to an aliphatic ketone-functionalized poly(ethylene glycol)-b-poly(amino acid) copolymer and the hydrolytic stability of the derived hydrazone bond was efficiently tailored by exploiting the compartmentalized structure of polymer micelle.

Antipredatory Responses of Mosquito Pupae to Non-Lethal Predation Threat-Behavioral Plasticity Across Life-History Stages.

Antipredatory behavioral responses tend to be energetically expensive, and prey species thus need to resolve trade-offs between these behaviors and other activities such as foraging and mating. While these trade-offs have been well-studied across taxa, less is known about how costs and benefits vary in different life-history contexts, and associated consequences. To address this question, we compared responses of the yellow fever mosquito (Aedes aegypti [Diptera: Culicidae]) to predation threat from guppy (Poecilia reticulata [Cyprinodontiformes: Poeciliidae]) across two life-history stages-larvae (data from previous study) and pupae (from this study).

Translational Nanomedicine Boosts Anti-PD1 Therapy to Eradicate Orthotopic PTEN-Negative Glioblastoma.

Glioblastoma (GBM) is resistant to immune checkpoint inhibition due to its low mutation rate, phosphatase and tensin homologue (PTEN)-deficient immunosuppressive microenvironment, and high fraction of cancer stem-like cells (CSCs). Nanomedicines fostering immunoactivating intratumoral signals could reverse GBM resistance to immune checkpoint inhibitors (ICIs) for promoting curative responses. Here, we applied pH-sensitive epirubicin-loaded micellar nanomedicines, which are under clinical evaluation, to synergize the efficacy of anti-PD1antibodies (aPD1) against PTEN-positive and PTEN-negative orthotopic GBM, the latter with a large subpopulation of CSCs.

Interplay of EMT and CSC in Cancer and the Potential Therapeutic Strategies.

The mechanism of epithelial-mesenchymal transition (EMT) consists of the cellular phenotypic transition from epithelial to mesenchymal status. The cells exhibiting EMT exist in cancer stem cell (CSC) population, which is involved in drug resistance. CSCs demonstrating EMT feature remain after cancer treatment, which leads to drug resistance, recurrence, metastasis and malignancy of cancer.

An overview of nanomedicines for neuron targeting.

Medical treatments of neuron-related disorders are limited due to the difficulty of targeting brain cells. Major drawbacks are the presence of the blood-brain barrier and the lack of specificity of the drugs for the diseased cells. Nanomedicine-based approaches provide promising opportunities for overcoming these limitations.

Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain.

Delivering therapeutic antibodies into the brain across the blood-brain barrier at a therapeutic level is a promising while challenging approach in the treatment of neurological disorders. Here, we present a polymeric nanomicelle (PM) system capable of delivering therapeutically effective levels of 3D6 antibody fragments (3D6-Fab) into the brain parenchyma for inhibiting Aβ aggregation. PM assembly was achieved by charge-converting 3D6-Fab through pH-sensitive citraconylation to allow complexation with reductive-sensitive cationic polymers.