Breakthroughs in nanoparticle-based strategies for pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide, mainly due to its high heterogeneity, resistance to therapy and late diagnosis, with a 5-year survival rate of less than 10%. This dismal prognosis has promoted strategies to develop more effective treatments. Nanoparticle-based strategies have emerged, in the last decades, as a great opportunity because they can enhance drug delivery and promote controlled release, presenting lower side effects than conventional therapeutic regimens.

Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response.

Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients.

Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment.

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %.

Mitochondrial respiratory chain dysfunction alters ER sterol sensing and mevalonate pathway activity.

Mitochondrial dysfunction induces a strong adaptive retrograde signaling response; however, many of the downstream effectors of this response remain to be discovered. Here, we studied the shared transcriptional responses to three different mitochondrial respiratory chain inhibitors in human primary skin fibroblasts using QuantSeq 3'-RNA-sequencing. We found that genes involved in the mevalonate pathway were concurrently downregulated, irrespective of the respiratory chain complex affected.

Systematic Analysis of FASTK Gene Family Alterations in Cancer.

The FASTK family of proteins have been recently reported to play a key role in the post-transcriptional regulation of mitochondrial gene expression, including mRNA stability and translation. Accumulated studies have provided evidence that the expression of some FASTK genes is altered in certain types of cancer, in agreement with the central role of mitochondria in cancer development. Here, we obtained a pan-cancer overview of the genomic and transcriptomic alterations of FASTK genes.

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.

BackgroundThere is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.MethodsWe combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank.

Mitochondrial Ca Dynamics in MCU Knockout Worms.

Mitochondrial [Ca] plays an important role in the regulation of mitochondrial function, controlling ATP production and apoptosis triggered by mitochondrial Ca overload. This regulation depends on Ca entry into the mitochondria during cell activation processes, which is thought to occur through the mitochondrial Ca uniporter (MCU). Here, we have studied the mitochondrial Ca dynamics in control and MCU-defective worms in vivo, by using worms expressing mitochondrially-targeted YC3.

The Role of Ca Signaling in Aging and Neurodegeneration: Insights from Models.

Ca is a ubiquitous second messenger that plays an essential role in physiological processes such as muscle contraction, neuronal secretion, and cell proliferation or differentiation. There is ample evidence that the dysregulation of Ca signaling is one of the key events in the development of neurodegenerative processes, an idea called the "calcium hypothesis" of neurodegeneration. () is a very good model for the study of aging and neurodegeneration.

The Neuroprotector Benzothiazepine CGP37157 Extends Lifespan in Worms.

The benzothiazepine CGP37157 has shown neuroprotective effects in several models of excitotoxicity involving dysregulation of intracellular Ca homeostasis. Although its mechanism of neuroprotection is unclear, it is probably related with some of its effects on Ca homeostasis. CGP37157 is a well-known inhibitor of the mitochondrial Na/Ca exchanger (mNCX).

Regulation of inositol 1,4,5-trisphosphate-induced Ca release from the endoplasmic reticulum by AMP-activated kinase modulators.

The 5' AMP-activated protein kinase (AMPK) is a nutrient-sensitive kinase that plays a key role in the control of cellular energy metabolism. We have explored here the relationship between AMPK and Ca signaling by looking at the effect of an AMPK activator (A769662) and an AMPK inhibitor (dorsomorphin) on histamine-induced Ca-release from the endoplasmic reticulum (ER) in HeLa cells. Our data show that incubation with A769662 (EC = 29 μM) inhibited histamine-induced Ca-release from the ER in intact cells, as well as inositol-1,4,5-trisphosphate (IP)-induced Ca release in permeabilized cells.

Pharynx mitochondrial [Ca] dynamics in live worms during aging.

Progressive decline in mitochondrial function is generally considered one of the hallmarks of aging. We have expressed a Ca sensor in the mitochondrial matrix of pharynx cells and we have measured for the first time mitochondrial [Ca] ([Ca]) dynamics in the pharynx of live worms during aging. Our results show that worms stimulated with serotonin display a pharynx [Ca] oscillatory kinetics that includes both high frequency oscillations (up to about 1Hz) and very prolonged "square-wave" [Ca] increases, indicative of energy depletion of the pharynx cells.

Type 3 inositol 1,4,5-trisphosphate receptor is dispensable for sensory activation of the mammalian vomeronasal organ.

Signal transduction in sensory neurons of the mammalian vomeronasal organ (VNO) involves the opening of the canonical transient receptor potential channel Trpc2, a Ca-permeable cation channel that is activated by diacylglycerol and inhibited by Ca-calmodulin. There has been a long-standing debate about the extent to which the second messenger inositol 1,4,5-trisphosphate (InsP) and type 3 InsP receptor (InsPR3) are involved in the opening of Trpc2 channels and in sensory activation of the VNO. To address this question, we investigated VNO function of mice carrying a knockout mutation in the Itpr3 locus causing a loss of InsPR3.

Calcium signaling and cell cycle: Progression or death.

Cytosolic Ca concentration levels fluctuate in an ordered manner along the cell cycle, in line with the fact that Ca is involved in the regulation of cell proliferation. Cell proliferation should be an error-free process, yet is endangered by mistakes. In fact, a complex network of proteins ensures that cell cycle does not progress until the previous phase has been successfully completed.

Long-term monitoring of Ca2+ dynamics in C. elegans pharynx: an in vivo energy balance sensor.

Ca2+ is a key signal transducer for muscle contraction. Continuous in vivo monitoring of intracellular Ca2+-dynamics in C. elegans pharynx muscle revealed surprisingly complex Ca2+ patterns.

Functional Overexpression of Vomeronasal Receptors Using a Herpes Simplex Virus Type 1 (HSV-1)-Derived Amplicon.

In mice, social behaviors such as mating and aggression are mediated by pheromones and related chemosignals. The vomeronasal organ (VNO) detects olfactory information from other individuals by sensory neurons tuned to respond to specific chemical cues. Receptors expressed by vomeronasal neurons are implicated in selective detection of these cues.

Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial.

Background: Osteoarthritis is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. Conventional treatments demonstrate only modest clinical benefits without lesion reversal. Autologous mesenchymal stromal cell (MSC) treatments have shown feasibility, safety, and strong indications for clinical efficacy.