Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells.

The global population over 60 years old is projected to reach 1.5 billion by 2050. Understanding age-related disorders and gender-specificities is crucial for a healthy aging.

Drug-induced accelerated nodulosis: review of the literature.

Accelerated nodulosis, the rapid progression/extension of preexisting nodules, is a recognized complication of immunomodulatory therapy, occurring mostly in patients with rheumatoid arthritis treated with methotrexate. As of today, its physiopathology remains incompletely understood, and there are no standardized guidelines regarding its management. Here, we conduct a literature review of the reported cases of drug-induced accelerated nodulosis and add our case of a 79-year-old female with an atypical clinical presentation.

Fin ray branching is defined by TRAP osteolytic tubules in zebrafish.

The shaping of bone structures relies on various cell types and signaling pathways. Here, we use the zebrafish bifurcating fin rays during regeneration to investigate bone patterning. We found that the regenerating fin rays form via two mineralization fronts that undergo an osteoblast-dependent fusion/stitching until the branchpoint, and that bifurcation is not simply the splitting of one unit into two.

Impact of Beer and Nonalcoholic Beer Consumption on the Gut Microbiota: A Randomized, Double-Blind, Controlled Trial.

Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. In this randomized, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.

Graphene Biosensors-A Molecular Approach.

Graphene is the material elected to study molecules and monolayers at the molecular scale due to its chemical stability and electrical properties. The invention of scanning tunneling microscopy has deepened our knowledge on molecular systems through imaging at an atomic resolution, and new possibilities have been investigated at this scale. Interest on studies on biomolecules has been demonstrated due to the possibility of mimicking biological systems, providing several applications in nanomedicine: drug delivery systems, biosensors, nanostructured scaffolds, and biodevices.

Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors.

Structure modeling hints at a granular organization of the Golgi ribbon.

Background: In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this "ribbon" architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks.

Intestinal Alkaline Phosphatase: A Review of This Enzyme Role in the Intestinal Barrier Function.

Intestinal alkaline phosphatase (IALP) has recently assumed a special relevance, being the subject of study in the prevention and treatment of certain diseases related to leaky gut. This brush border enzyme (ecto-enzyme) plays an important role in the maintenance of intestinal microbial homeostasis and intestinal barrier function through its ability to dephosphorylate lipopolysaccharide (LPS). This review addresses how IALP and intestinal barrier dysfunction may be implicated in the pathophysiology of specific diseases such as inflammatory bowel disease, necrotizing enterocolitis, and metabolic syndrome.

Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease-activated receptor-2 internalization.

In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred-either in a membrane-bound melanosome or as a melanosome core, that is, melanocore. Here, we investigated the endocytic route followed by melanocores and melanosomes during internalization by keratinocytes, by comparing the uptake of melanocores isolated from the supernatant of melanocyte cultures, with melanosomes isolated from melanocytes.

Characteristic Immune Dynamics in COVID-19 Patients with Cardiac Dysfunction.

Background: We aimed to explore immune parameters in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: A total of 30 COVID-19 patients >18 years admitted to the ICU were studied on days D1, D3 and D7 after admission. Cardiac function was assessed using speckle-tracking echocardiography (STE).

Brolucizumab 12- and 16-Week Fixed Dosing Potential in Neovascular AMD: A post hoc Evaluation of Data from the HAWK and HARRIER Trials.

Introduction: This post hoc analysis applies a fixed dosing stratification approach to patient-level brolucizumab data from the phase III HAWK and HARRIER trials to determine the proportion of patients who would have been assigned to fixed dosing regimens with treatment intervals of 8, 12, or 16 weeks (q8w, q12w, or q16w) based on the presence/absence of disease activity (DA) following the loading phase. The analysis also simulates central subfield thickness (CSFT) data to estimate the anatomical outcomes if the patients had been thus assigned. Of note, the limitations of this analysis include the post hoc nature of the work and the inability to directly compare HAWK and HARRIER with TENAYA and LUCERNE due to the differences in design.

Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma.

Protein ubiquitylation coordinates crucial cellular events in physiological and pathological conditions. A comparative analysis of the ubiquitin proteome from bortezomib (BTZ)-sensitive and BTZ-resistant mantle cell lymphoma (MCL) revealed an enrichment of the autophagy-lysosome system (ALS) in BTZ-resistant cells. Pharmacological inhibition of autophagy at the level of lysosome-fusion revealed a constitutive activation of proteaphagy and accumulation of proteasome subunits within autophagosomes in different MCL cell lines with acquired or natural resistance to BTZ.

Urinary immune cell phenotype of severe AKI in critically ill patients.

Purpose: Cellular mechanisms involved in human renal recovery after an episode of acute kidney injury (AKI) are understudied. We aim to characterize the urinary immune cell phenotype of patients with AKI and evaluate its ability to predict renal recovery.

Methods: A prospective study of critically ill patients with stage ≥ 2 AKI by KDIGO and sterile leukocyturia at admission was performed.

Interleukin-7 receptor α mutational activation can initiate precursor B-cell acute lymphoblastic leukemia.

Interleukin-7 receptor α (encoded by IL7R) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related IL7R gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant IL7R, expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage in which B-cell precursors display self-renewal ability, initiating leukemia resembling PAX5 P80R or Ph-like human B-ALL.

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing.

Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity.

COVID-19 mRNA vaccine and antibody response in lactating women: a prospective cohort study.

Background: Immunological protection via breastfeeding is well known. The immunological profile of human milk changes during lactation. No clinical trials have been conducted in lactating women with the newest mRNA vaccines against SARS- CoV-2.

Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction.

Purpose: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers.

Methods: We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo.

Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008-2017.

Influence of Human Milk on Very Preterms' Gut Microbiota and Alkaline Phosphatase Activity.

The FEEDMI Study (NCT03663556) evaluated the influence of infant feeding (mother's own milk (MOM), donor human milk (DHM) and formula) on the fecal microbiota composition and alkaline phosphatase (ALP) activity in extremely and very preterm infants (≤32 gestational weeks). In this observational study, preterm infants were recruited within the first 24 h after birth. Meconium and fecal samples were collected at four time points (between the 2nd and the 26th postnatal days.

A Pilot Study on the Metabolic Impact of Mediterranean Diet in Type 2 Diabetes: Is Gut Microbiota the Key?

The Mediterranean diet (MD) has been recommended for type 2 diabetes (T2D) treatment. The impact of diet in shaping the gut microbiota is well known, particularly for MD. However, the link between MD and diabetes outcome improvement is not completely clear.

A simple method to measure sulfonation in man using paracetamol as probe drug.

Sulfotransferase enzymes (SULT) catalyse sulfoconjugation of drugs, as well as endogenous mediators, gut microbiota metabolites and environmental xenobiotics. To address the limited evidence on sulfonation activity from clinical research, we developed a clinical metabolic phenotyping method using paracetamol as a probe substrate. Our aim was to estimate sulfonation capability of phenolic compounds and study its intraindividual variability in man.

MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile.

Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel.

Impact of sterile leukocyturia on outcome of critically ill patients with severe acute kidney injury.

Introduction: The role of immunological mechanisms on renal regeneration and functional recovery after an episode of Acute Kidney Injury (AKI) is still understudied. We aim to evaluate the impact of sterile leukocyturia on outcomes of critically-ill AKI patients.

Methods: A retrospective analysis of critically-ill patients with stage ≥2 AKI by KDIGO was performed.

Haploidentical α/β T-cell and B-cell depleted stem cell transplantation in severe mevalonate kinase deficiency.

Objective: Mevalonic aciduria represents the most severe form of mevalonate kinase deficiency (MKD). Patients with mevalonic aciduria have an incomplete response even to high doses of anti-cytokine drugs such as anakinra or canakinumab and stem cell transplantation (SCT) represents a possible therapy for this severe disease.

Methods: We report the first two children affected by severe MKD who received haploidentical α/β T-cell and B-cell depleted SCT.