The (re)emergence of aerosol delivery: Treatment of pulmonary diseases and its clinical challenges.

Aerosol delivery represents a rapid and non-invasive way to directly reach the lungs while escaping the hepatic first-pass effect. The development of pulmonary drugs for respiratory diseases such as cystic fibrosis, lung infections, pulmonary fibrosis or lung cancer requires an enhanced understanding of the relationships between the natural physiology of the respiratory system and the pathophysiology of these conditions. This knowledge is crucial to better predict and thereby control drug deposition.

A facile assay for zDHHC palmitoyl transferase activation elucidates effects of mutation and modification.

At least 10% of proteins constituting the human proteome are subject to S-acylation by a long-chain fatty acid, thioesterified to a Cys thiol side chain. Fatty S-acylation (prototypically, S-palmitoylation) operates across eukaryotic phylogeny and cell type. S-palmitoylation is carried out in mammalian cells by a family of 23-24 dedicated zDHHC palmitoyl transferase enzymes, and mutation of zDHHCs is associated with a number of human pathophysiologies.

INFLUENCE OF RADIOIODINE THERAPY ON ORAL HEALTH AND SALIVARY PRODUCTION IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA.

Objectives: To evaluate the characteristics related to oral health and salivary production in patients with Differentiated Thyroid Carcinoma (DTC) after radioiodine therapy (RIT).

Methods: Cross-sectional study, which included patients with DTC after ablative and/or adjuvant RIT. Patients underwent assessment of oral health conditions, subjective assessment of xerostomia and measurement of salivary flow.

Macrophage membrane-camouflaged pure-drug nanomedicine for synergistic chemo- and interstitial photodynamic therapy against glioblastoma.

Glioblastoma (GBM) persists as a highly fatal malignancy, with current clinical treatments showing minimal progress over years. Interstitial photodynamic therapy (iPDT) holds promise due to its minimally invasive nature and low toxicity but is impeded by poor photosensitizer penetration and inadequate GBM targeting. Here, we developed a biomimetic pure-drug nanomedicine (MM@CT), which co-assembles the photosensitizer chlorin e6 (Ce6) and the first-line chemotherapeutic drug (temozolomide, TMZ) for GBM, then camouflaged with macrophage membranes.

Reversible light-responsive protein hydrogel for on-demand cell encapsulation and release.

The design of biomaterials that can reconfigure on-demand in response to external stimuli is an emerging area in materials research. However, achieving reversible assembly of protein-based biomaterials by light input remains a major challenge. Here, we present the engineering of a new protein material that is capable of switching between liquid and solid state reversibly, controlled by lights of different wavelengths.

Sodium hyaluronate microcapsules to promote antitumor selectivity of anacardic acid.

Anacardic acid (AA) is a phenolic lipid extracted from cashew nutshell liquid that has antitumor activity. Given the high hydrophobicity of this compound and aiming to create efficient vehicle for its administration in aqueous systems, the objective of the present work was to develop a microcapsule (MCAA) by spray dryer technique, based on the polysaccharide sodium hyaluronate (SH), containing AA as its core, encapsulated from nanoemulsion. The Encapsulation Efficiency of MCAA presented a value equal to 95.

Harnessing HDAC-targeted oleanolic acid derivatives for combined anti-cancer and hepatoprotective effects.

The development of anti-tumor drugs with hepatoprotective properties has always been highly valued due to their dual capabilities of safeguarding the liver and combating tumors. Moreover, when used in conjunction with specific chemotherapy drugs, they can enhance the efficacy of cancer treatment while simultaneously reducing liver damage caused by chemotherapeutic agents. Our research focused on oleanolic acid (OA), a natural compound known for its liver-protective effects.

Platinum micromotors for mucosal penetration and colorectal cancer therapy.

The therapeutic outcomes of medications were restricted by the colonic mucosal barrier during the treatment of colorectal cancer (CRC). Micro/nanomotors can overcome the mucus barriers to reach deep colorectal tumors. In this study, we constructed a novel microsized PLGA-Pt micromotor (MM) driven by hydrogen peroxide (HO) to enhance drug delivery to the CRC tissues and achieve effective antitumor therapy.

Genipin-crosslinked double PLL membranes overcome the strength-diffusion trade-off in cell encapsulation without compromising biocompatibility.

Cell microencapsulation technologies allow non-autologous implantation of therapeutic cells for sustained drug delivery purposes. The perm-selective membrane of these systems provides resistance to rupture, stablishes the upper molecular weight limit in bidirectional diffusion of molecules, and affects biocompatibility. Thus, despite being a decisive factor to succeed in terms of biosafety and therapeutic efficacy, little progress has been made in its optimization so far.

The design of the spheroids-based in vitro tumor model determines its biomimetic properties.

Cancer, one of the world's deadliest diseases, is expected to claim an estimated 16 million lives by 2040. Three-dimensional (3D) models of cancer have become invaluable tools for the study of tumor biology and the development of new therapies. The tumor microenvironment (TME) is a determinant of tumor progression and has implications for clinical therapies.

Phase I trial of phIL12 plasmid intratumoral gene electrotransfer in patients with basal cell carcinoma in head and neck region.

Introduction: In the treatment of cancer, immunomodulatory approaches are developed to support the organism in fighting cancer or to enhance the immunomodulatory effects of local ablative techniques. To this end, we conducted an interventional, open-label, single-arm Phase I trial to evaluate the safety and tolerability of intratumoral phIL12 plasmid DNA gene electrotransfer as primary objectives.

Methods: The study was dose-escalating with 3 consecutive cohorts of 3 patients per phIL12 dose level (0.

Proton therapy of lung cancer patients - Treatment strategies and clinical experience from a medical physicist's perspective.

Purpose: Proton therapy of moving targets is considered a challenge. At Maastro, we started treating lung cancer patients with proton therapy in October 2019. In this work, we summarise the developed treatment strategies and gained clinical experience from a physics point of view.

Novel screening approach for stem cell selective inhibitors and their possible translational therapeutic potential for endometriosis.

Endometriosis is an estrogen-dependent benign disease characterized by growth of the endometrial tissue outside the uterine wall. Several reports suggest the possibility of the pathogenesis and recurrence of endometriosis being related to functions of stem/progenitor cells of the endometrium. The drawback of the widely used method of using Hoechst 33342, a fluorescent dye, to collect stem cell-like populations, is the requirement of an ultraviolet (UV) excitation source not commonly provided on standard flow cytometers.

The role of artificial intelligence in gynecologic and obstetric emergencies.

Objective: To investigate the potential of artificial intelligence (AI) in emergency medicine, focusing on its utility in triaging and managing acute gynecologic and obstetric emergencies.

Methods And Materials: This feasibility study assessed Chat-GPT's performance in triaging and recommending management interventions for gynecologic and obstetric emergencies, using ten fictive cases. Five common conditions were modeled for each specialty.

A mitochondria-interfering nanocomplex cooperates with photodynamic therapy to boost antitumor immunity.

Immunotherapeutics against triple-negative breast cancer (TNBC) hold great promise. In this work, we provide a combination therapy for simultaneous increasing tumor immunogenicity and down-regulating programmed cell death ligand 1 (PD-L1) to boost antitumor immunity in TNBC. We prepare bis (diethyldithiocarbamate)-copper/indocyanine green nanoparticles (CuET/ICG NPs) simply in aqueous with one-pot method.

Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials.

Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.

Nano-polymeric platinum activates PAR2 gene editing to suppress tumor metastasis.

Metastasis as the hallmark of cancer preferentially contributes to tumor recurrence and therapy resistance, aggrandizing the lethality of patients with cancer. Despite their robust suppressions of tumor progression, chemotherapeutics failed to attenuate cancer cell migration and even triggered pro-metastatic effects. In parallel, protease-activated receptor 2 (PAR2), a member of the G protein-coupled receptor subfamily, actively participates in cancer metastasis via multiple signal transduction pathways.

Compound K promotes thermogenic signature and mitochondrial biogenesis via the UCP1-SIRT3-PGC1α signaling pathway.

Compound K (CK), an active ingredient in ginseng, has anti-cancer, anti-inflammatory, and antioxidant properties. However, its effects on thermogenesis and mitochondrial dynamics in white adipose tissue (WAT) adipocytes are not well understood. This study explores CK's impact on thermogenesis and mitochondrial metabolism in cold-exposed mice and mouse stromal vascular fraction (SVF) cells.

Endothelial Cpt1a Inhibits Neonatal Hyperoxia-Induced Pulmonary Vascular Remodeling by Repressing Endothelial-Mesenchymal Transition.

Pulmonary hypertension (PH) increases the mortality of preterm infants with bronchopulmonary dysplasia (BPD). There are no curative therapies for this disease. Lung endothelial carnitine palmitoyltransferase 1a (Cpt1a), the rate-limiting enzyme of the carnitine shuttle system, is reduced in a rodent model of BPD.

Protocol to generate a 3D atherogenesis-on-chip model for studying endothelial-macrophage crosstalk in atherogenesis.

The endothelium is the gatekeeper of vessel health, and its dysfunction is pivotal in driving atherogenesis. Here, we present a protocol to replicate endothelial-macrophage crosstalk during atherogenesis, called the "atherogenesis-on-chip" model, based on the Emulate dual-channel perfusion system. We describe a model for studying endothelial-macrophage interactions during atherogenesis in human aortic endothelial cells and human macrophages using qPCR and secretome analysis, fluorescence microscopy, and flow cytometry.

A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.

Polycomb repressive complex 2 (PRC2), composed of the core subunits EED, SUZ12, and either EZH1 or EZH2, is critical for maintaining cellular identity in multicellular organisms. PRC2 deposits H3K27me3, which is thought to recruit the canonical form of PRC1 (cPRC1) to promote gene repression. Here, we show that EZH1-PRC2 and cPRC1 are the primary Polycomb complexes on target genes in non-dividing, quiescent cells.

IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4 T cell proliferation.

Interleukin (IL)-7 promotes T cell expansion during lymphopenia. We studied the metabolic basis in CD4 T cells, observing increased glucose usage for nucleotide synthesis and oxidation in the tricarboxylic acid (TCA) cycle. Unlike other TCA metabolites, glucose-derived citrate does not accumulate upon IL-7 exposure, indicating diversion into other processes.

miR-449a/miR-340 reprogram cell identity and metabolism in fusion-negative rhabdomyosarcoma.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, arises in skeletal muscle and remains in an undifferentiated state due to transcriptional and post-transcriptional regulators. Among its subtypes, fusion-negative RMS (FN-RMS) accounts for the majority of diagnoses in the pediatric population. MicroRNAs (miRNAs) are non-coding RNAs that modulate cell identity via post-transcriptional regulation of messenger RNAs (mRNAs).