Unraveling the protein kinase C/NDRG1 signaling network in breast cancer.

N-myc downstream-regulated gene 1 (NDRG1) is a member of the NDRG family of intracellular proteins and plays a central role in a wide range of biological processes including stress response, differentiation, and metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in various types of cancer. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC).

Return to sport activity following ultrasonographic diagnosis and conservative management of spontaneous injuries of the serratus cervicis ventralis and serratus thoracis ventralis muscles in 11 endurance horses.

Objective: To describe the clinical diagnosis, ultrasound findings, and outcome of 11 endurance horses with injuries to the serratus ventralis thoracis (SVT) or serratus ventralis cervicis (SVC) muscle.

Animals: 11 endurance horses competing in medium- to high-level competitions and presenting with lameness caused by injuries to the SVT or SVC muscle, as confirmed by ultrasonography.

Clinical Presentation: Physical examinations revealed swelling caudal to the shoulder region associated with dorsocranial displacement of the scapula and edema of the ventral thorax for horses with SVT injuries.

Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis.

is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication.

DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis.

Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate to maintain hematopoiesis, increasing their susceptibility to DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, and prevent aging-driven dysregulation are unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar DNA replication fork reversal biochemical functions, Zranb3 and Smarcal1, have surprisingly specialized roles in distinct HSPC populations.

Harnessing inter-kingdom metabolic disparities at the human-fungal interface for novel therapeutic approaches.

Humans interact with a multitude of microorganisms in various ecological relationships, ranging from commensalism to pathogenicity. The same applies to fungi, long recognized for their pathogenic roles in infection-such as in invasive fungal diseases caused, among others, by and spp.-and, more recently, for their beneficial activities as an integral part of the microbiota.

The immune and microbial homeostasis determines the -mast cells cross-talk in celiac disease.

Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation.

Engineering carrier nanoparticles with biomimetic moieties for improved intracellular targeted delivery of mRNA therapeutics and vaccines.

Biological membrane-engineered lipid nanoparticles (LNP) have shown enormous potential as vehicles for drug delivery due to their outstanding biomimetic properties. To make these nanoparticles more adaptable to complex biological systems, several methods and cellular sources have been adopted to introduce biomembrane-derived moieties onto LNP and provide the latter with more functions while preserving their intrinsic nature. In this review, we focus on LNP decoration with specific regard to mRNA therapeutics and vaccines.

Ketorolac Loaded Poly(lactic-co-glycolic acid) Coating of AZ31 in the Treatment of Bone Fracture Pain.

Biodegradable metal alloys may be successfully used to support bone repair, avoiding second surgery commonly needed when inert metal alloys are used. Combining a biodegradable metal alloy with a suitable pain relief agent could improve patient quality of life. AZ31 alloy was coated using a poly(lactic-co-glycolic) acid (PLGA) polymer loaded with ketorolac tromethamine using the solvent casting method.

Artificial Intelligence-Based Quantitative Structure-Property Relationship Model for Predicting Human Intestinal Absorption of Compounds with Serotonergic Activity.

Oral medicines represent the largest pharmaceutical market area. To achieve a therapeutic effect, a drug must penetrate the intestinal walls, the main absorption site for orally delivered active pharmaceutical ingredients (APIs). Indeed, predicting drug absorption can facilitate candidate screening and reduce time to market.

Turning Microbial AhR Agonists into Therapeutic Agents via Drug Delivery Systems.

Developing therapeutics for inflammatory diseases is challenging due to physiological mucosal barriers, systemic side effects, and the local microbiota. In the search for novel methods to overcome some of these problems, drug delivery systems that improve tissue-targeted drug delivery and modulate the microbiota are highly desirable. Microbial metabolites are known to regulate immune responses, an observation that has resulted in important conceptual advances in areas such as metabolite pharmacology and metabolite therapeutics.

Alginate Ag/AgCl Nanoparticles Composite Films for Wound Dressings with Antibiofilm and Antimicrobial Activities.

Recently, silver-based nanoparticles have been proposed as components of wound dressings due to their antimicrobial activity. Unfortunately, they are cytotoxic for keratinocytes and fibroblasts, and this limits their use. Less consideration has been given to the use of AgCl nanoparticles in wound dressings.

Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?

As an appealing alternative to treat and prevent diseases ranging from cancer to COVID-19, mRNA has demonstrated significant clinical effects. Nanotechnology facilitates the successful implementation of the systemic delivery of mRNA for safe human consumption. In this manuscript, we provide an overview of current mRNA therapeutic applications and discuss key biological barriers to delivery and recent advances in the development of nonviral systems.

Pulmonary drug delivery technology enables anakinra repurposing in cystic fibrosis.

Inflammation is a key pathological driver in cystic fibrosis (CF). Current therapies are ineffective in treating and preventing the escalation of inflammatory events often exacerbated by superimposed infection. In this work, we propose a novel treatment based on the pulmonary administration of anakinra, a non-glycosylated recombinant form of IL-1Ra.

MgAl and ZnAl-Hydrotalcites as Materials for Cosmetic and Pharmaceutical Formulations: Study of Their Cytotoxicity on Different Cell Lines.

The knowledge about the effect of hydrotalcites (HTlcs), largely used in pharmaceutics, on non-malignant cell lines is limited. The effect of MgAl-HTlc-and ZnAl-HTlc- (NO3−/Cl−/CO32−) on the cell viability of HaCat, fibroblasts and HepG2 was studied by MTT assay. Cells were incubated either with HTlc suspensions in the culture media and with the supernatant obtained from the suspension being centrifuged.

Prognosis of ALK-rearranged non-small-cell lung cancer patients carrying TP53 mutations.

Non-small-cell lung cancer (NSCLC) is the primary cause of cancer-related death. Gene rearrangements involving the anaplastic lymphoma kinase (ALK) tyrosine kinase identify a clinical and molecular subset of NSCLC patients, who benefit from the monotherapy with ALK tyrosine kinase inhibitors. Nonetheless, responsiveness to TKIs and prognosis of these patients are influenced by several factors, including resistance mechanisms and mutations affecting genes involved in key molecular pathways of cancer cells.

Case Report: Analysis of Plasma Extracellular Vesicles in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient.

Metaplastic breast cancer (MpBC) is a rare tumor representing 1% of all breast malignancies. The prognosis of this histologic subtype is actually poor and there are no current clear-cut therapeutic guidelines. Hence, despite its uniqueness, its aggressive prognostic profile strongly encourages further studies to identify new markers and therapeutic targets.