PEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis.

PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here, we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity in vivo.

Exploring the connection between climatic conditions and genetic properties of Abies alba Mill., including warm and summer-dry Mediterranean environments.

Abies alba Mill. is a prominent European tree species predominantly inhabiting cool and humid montane environments. However, paleoecological evidence reveals that during the Eemian and mid-Holocene, A.

Whole Blood DNA Methylation Analysis Reveals Epigenetic Changes Associated with ARSACS.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited condition described worldwide and characterized by a wide spectrum of heterogeneity in terms of genotype and phenotype. How sacsin loss leads to neurodegeneration is still unclear, and current knowledge indicates that sacsin is involved in multiple functional mechanisms. We hence hypothesized the existence of epigenetic factors, in particular alterations in methylation patterns, that could contribute to ARSACS pathogenesis and explain the pleiotropic effects of SACS further than pathogenic mutations.

Targeting Kv7 Potassium Channels for Epilepsy.

Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.

Proteomic Analysis of the Murine Liver Response to Oral Exposure to Aflatoxin B1 and Ochratoxin A: The Protective Role to Bioactive Compounds.

Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) are considered the most important mycotoxins in terms of food safety. The aim of this study was to evaluate the hepatotoxicity of AFB1 and OTA exposure in Wistar rats and to assess the beneficial effect of fermented whey (FW) and pumpkin (P) as functional ingredients through a proteomic approach. For the experimental procedures, rats were fed AFB1 and OTA individually or in combination, with the addition of FW or a FW-P mixture during 28 days.

Targeting the 8-oxodG Base Excision Repair Pathway for Cancer Therapy.

Genomic integrity is critical for cellular homeostasis, preventing the accumulation of mutations that can drive diseases such as cancer. Among the mechanisms safeguarding genomic stability, the Base Excision Repair (BER) pathway plays a pivotal role in counteracting oxidative DNA damage caused by reactive oxygen species. Central to this pathway are enzymes like 8-oxoguanine glycosylase 1 (OGG1), which recognize and excise 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) lesions, thereby initiating a series of repair processes that restore DNA integrity.

Edge-AI Enabled Wearable Device for Non-Invasive Type 1 Diabetes Detection Using ECG Signals.

Diabetes is a chronic condition, and traditional monitoring methods are invasive, significantly reducing the quality of life of the patients. This study proposes the design of an innovative system based on a microcontroller that performs real-time ECG acquisition and evaluates the presence of diabetes using an Edge-AI solution. A spectrogram-based preprocessing method is combined with a 1-Dimensional Convolutional Neural Network (1D-CNN) to analyze the ECG signals directly on the device.

Impact of β-casein variants on the formation of β-casomorphins in blue cheeses: Investigating key drivers through peptidomic analysis.

β-Casomorphins (BCMs), food-associated peptides resulting from the proteolytic cleavage of β-casein (β-CN), have been widely investigated for their opioid-like activity. This research aimed to identify the presence of BCM7, BCM6, and BCM5 in different bovine milk-deriving blue cheese types and to describe the intricate mechanisms behind their formation, focusing on their origin from cheese with β-CN A1 and A2 variants. Using nanoLC-ESI-Q-Orbitrap-MS/MS and advanced computational tools, we explored the peptidomes of Bleu d'Auvergne, Gorgonzola, Stilton, and Bergader blue cheeses from milk containing both β-CN A1 and A2 variants.

Supplementation with essential amino acids in the early stage of carbohydrate reintroduction after a very-low energy ketogenic therapy (VLEKT) improves body cell mass, muscle strength and inflammation.

Background: Although little is yet known about the long-term maintenance of very low-energy ketogenic therapy (VLEKT) effects on body composition, muscle strength and inflammation, it is plausible to assume that changes may occur, particularly during the steps following the ketogenic step, due to the loss of the protective effects of ketones and the concomitant reintroduction of carbohydrates. For this reason, the present study aimed to evaluate the effects of supplementation with 8 g per day of essential amino acids (EAAs) on these parameters.

Methods: A total of 68 women of reproductive age and with grade I obesity who had completed 45 days of the ketogenic phase with VLEKT (KeNuT protocol) and 40 days of non-ketogenic phase of KeNuT protocol with VLEKT (phase 3, fruit reintroduction) were included in the study.

The cardiac response of the goldfish Carassius auratus to environmental hypoxia: from hemodynamics to mitochondria.

Under low O, the heart of Carassius auratus (goldfish) shows an enhanced hemodynamics. This is observed in ex vivo cardiac preparations from animals acclimated to both normoxia and short-term (4 days) moderate hypoxia and perfused for 90 min with a hypoxic medium. Under short-term hypoxia, this is associated with a higher ventricular muscularity and an expanded mitochondrial compartment.

Challenges in treating patients with comorbid asthma and bronchiectasis.

The management of patients with overlapping asthma and bronchiectasis requires a tailored approach, starting with a comprehensive assessment of the patient's clinical profile, including the severity of asthma and the extent of bronchiectasis. Inhaled corticosteroids (ICS) are often recommended, but their use should be carefully monitored because of the risk of increased infection. If the asthma is well controlled and the bronchiectasis remains stable, a gradual reduction in the dose of ICS may be considered.

Gut Microbiota-Bone Axis.

Background: Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest.

Summary: Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis.

Conventional MRI-Based Structural Disconnection and Morphometric Similarity Networks and Their Clinical Correlates in Multiple Sclerosis.

Background And Objectives: Although multiple sclerosis (MS) can be conceptualized as a network disorder, brain network analyses typically require advanced MRI sequences not commonly acquired in clinical practice. Using conventional MRI, we assessed cross-sectional and longitudinal structural disconnection and morphometric similarity networks in people with MS (pwMS), along with their relationship with clinical disability.

Methods: In this longitudinal monocentric study, 3T structural MRI of pwMS and healthy controls (HC) was retrospectively analyzed.

Real-Life Experience with Tildrakizumab in Plaque Psoriasis with Palmoplantar Involvement: A Multi-Center Retrospective Italian Study.

Introduction: Palmoplantar psoriasis (PPp) has a profound negative impact on patients' quality of life, and it represents a therapeutic challenge, as palms and soles are difficult to treat area. Although the efficacy profile of tildrakizumab has been well evaluated in the literature, data on its use for PPp are still limited. The objective of the study was to evaluate the efficacy and safety of tildrakizumab on moderate-to-severe plaque psoriasis with involvement of the palmoplantar area.

Cocaine and aortic dissection: the need for collaboration to overcome the underreporting bias.

The dissection of the aorta is a serious and potentially fatal consequence of cocaine use. Nonetheless, the underlying mechanisms and characteristics of this phenomenon remain to be deeply studied. The autopsy case of a 46-year-old white male found irresponsive and unconscious in his house and had a history of abusing cocaine is presented.

Allergic Rhinitis and its Impact on Asthma (ARIA) Classes in MASK-air Users.

Background And Objectives: The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify rhinitis as "intermittent" or "persistent" and "mild" or "moderate-severe". To assess ARIA classes in a real-world study in terms of phenotypic differences and their association with asthma.

Methods: We performed a cross-sectional real-world study based on users of the MASK-air® app who reported data for at least 3 different months.

Enhancing Biomedicine: Proteomics and Metabolomics in Action.

The rapid and substantial advancements in proteomic and metabolomic technologies have revolutionized our ability to investigate biological systems [...

Association of sodium-glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis.

Background: The impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit.

A map of the rubisco biochemical landscape.

Rubisco is the primary CO-fixing enzyme of the biosphere, yet it has slow kinetics. The roles of evolution and chemical mechanism in constraining its biochemical function remain debated. Engineering efforts aimed at adjusting the biochemical parameters of rubisco have largely failed, although recent results indicate that the functional potential of rubisco has a wider scope than previously known.

Regulatory non-coding somatic mutations as drivers of neuroblastoma.

Background: Emerging evidence suggests that non-coding somatic single nucleotide variants (SNVs) in cis-regulatory elements (CREs) contribute to cancer by disrupting gene expression networks. However, the role of non-coding SNVs in cancer, particularly neuroblastoma, remains largely unclear.

Methods: SNVs effect on CREs activity was evaluated by luciferase assays.

Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation.

Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET's effects on healthspan in aged animals, revealing lifespan extension and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD levels in muscle.

Importance of integrin transmembrane helical interactions for antagonistic versus agonistic ligand behavior: Consequences for medical applications.

Integrins are well-characterized receptors involved in cell adhesion and signaling. With six approved drugs, they are recognized as valuable therapeutic targets. Here, we explore potential activation mechanisms that may clarify the agonist versus antagonist behavior of integrin ligands.