ADSL deficiency is a secondary mitochondrial disease affecting organelle homeostasis and ERK2/AKT signaling in a linear genotype-phenotype relation.

Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production.

Genotype-specific interferon signatures in amyotrophic lateral sclerosis relate to disease severity.

Innate immune signaling pathways are hyperactivated in the central nervous system (CNS) of patients with Amyotrophic Lateral Sclerosis (ALS), as well as in preclinical models with diverse causative backgrounds including TDP-43, SOD1, and C9orf72 mutations. This raises an important question of whether these pathways are key pathogenic features of the disease, and whether therapeutic amelioration could be beneficial. Here, we systematically profile Type-I interferon (IFN)-stimulated gene (ISG) expression signatures using a non-biased approach in CNS tissue from a cohort of 36 individuals with ALS, including sporadic ALS (sALS; n=18), genetic ALS caused by (i) a C9orf72 hexanucleotide repeat expansion (C9-ALS; n=11), and (ii) a SOD1 mutation (SOD1-ALS; n=5), alongside age- and sex-matched individuals who died of a non-neurological cause (n=12).

European Respiratory Society statement on advanced telemedicine for obstructive sleep apnoea (e-Sleep).

Telemedicine (TM) as a means of remote patient-physician interaction is gaining popularity in nearly every field, and (respiratory) sleep medicine is no exception. Because obstructive sleep apnoea (OSA) is a chronic condition, and requires a continuous treatment and monitoring of therapy success, telematic communications could be useful to establish diagnostic and therapeutic strategies. This Statement summarises the evidence and efficacy of TM options in OSA.

Cargoes move from cis to trans-Golgi compartments and concentrate in the TGN before exiting.

The classical models of intra-Golgi transport envision a movement of cargoes from cis- to trans-Golgi, followed by their sorting at the trans-Golgi network (TGN). During this vectorial transport, the cargoes are processed by sequentially acting glycosylation enzymes. A number of studies challenged the vectorial transport model and proposed alternative transport routes bypassing either directional transport or the TGN.

Control of Allergic Rhinitis and Asthma Test for Children (CARATkids): A systematic review and meta-analysis of its measurement properties.

Control of Allergic Rhinitis and Asthma Test for Children (CARATkids) is the first patient-reported outcome measure (PROM) designed to assess both allergic rhinitis and asthma simultaneously in children aged 6 to 12 years. CARATkids has been validated in several languages and countries, highlighting the need for a review of its psychometric properties. This study aims to evaluate the measurement properties of CARATkids.

The Interplay Between Oxidant/Antioxidant System, Transcription Factors, and Non-Coding RNA in Lung Cancer.

The exposure to risk factors, such as cigarette smoke and air pollution (containing metabolic oxidants and toxic substances), leading to cellular and molecular alterations, promotes the development of lung cancer at multiple stages. The antioxidant defence system plays a critical role in counteracting the mechanisms of oxidative stress. In physiological conditions, the balance between pro-oxidant and antioxidant species is critically important for the correct performance of cellular functions.

Beyond One-Size-Fits-All: Addressing Methodological Constraints in Novel Antimicrobials Discovery.

: Antimicrobial resistance is a growing global health concern that requires multiple strategies to be tackled effectively. While the discovery of new antimicrobial molecules is essential, the repurposing of existing compounds also plays a significant role. Standard methods to evaluate antimicrobial efficacy, regulated by the Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory Standards Institute (CLSI), such as the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), are available.

Expression of Reelin, Aβ1-42, Tau and FTH1 in Idiopathic Epiretinal Membranes: Exploring the Link Between Reelin and Neurodegenerative Biomarkers.

Growing evidence suggests that Reelin signals and cleavages are affected in neurodegenerative diseases, prospecting a potential role for Reelin in the pathogenesis of neurodegenerative processes occurring in insulted retinas. We sought to determine whether Reelin, Aβ1-42, FTH1 and TAU proteins accumulate in ocular fluids of idiopathic epiretinal membrane (iERM) specimens and whether such accumulations depend on disease severity. Comparisons and correlation studies were used to verify the hypothesis of a Reelin, Aβ1-42, TAU and FTH1 marker expressions in this vitreoretinal disease, extending the knowledge on the pathological spectrum of neurodegenerative eye diseases.

Three-Dimensional-Printed Biomimetic Scaffolds for Investigating Osteoblast-Like Cell Interactions in Simulated Microgravity: An In Vitro Platform for Bone Tissue Engineering Research.

Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to assess the effects of scaffold architecture and dynamic culture conditions on cell adhesion, proliferation, and metabolic activity, with implications for osteoporosis research.

Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections.

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations.

New Approach for Enhancing Survival in Glioblastoma Patients: A Longitudinal Pilot Study on Integrative Oncology.

: Glioblastoma (GBM IDH-wildtype WHO 2021) is an aggressive central nervous system malignancy with a poor prognosis despite standard therapy. Integrative oncology approaches involving natural compounds have shown potential in preclinical studies to enhance the efficacy of chemoradiotherapy. : This prospective, longitudinal observational pilot study, lacking a randomized control group, followed 72 newly diagnosed glioblastoma patients (diagnosed by histological examination and MGMT promoter molecular study alone, grade 4 glioma patients) treated with the STUPP protocol.

A phosphoserine phosphatase variant present in the brain of Alzheimer's disease patients favors nuclear mistargeting.

Phosphoserine phosphatase (PSP) catalyzes the dephosphorylation of 3-phosphoserine, which is the final step in the de novo biosynthesis of l-serine (l-Ser) via the phosphorylated pathway in human astrocytes. Individuals who are homozygous or compound heterozygous for functionally defective PSP variants exhibit reduced cerebrospinal fluid l-Ser levels and severe neurological symptoms. In the present study, single nucleotide polymorphisms in PSP were identified in hippocampal samples from Alzheimer's disease (AD) patients.

Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.

Essential transcription and cell cycle progression controllers are CDKs, whose dysregulation is a defining trait of many human cancers. CDKs have grown to be very crucial therapeutic targets in cancer. Although traditional CDK inhibitors have demonstrated therapeutic efficacy, they frequently encounter limitations due to resistance mechanisms and off-target effects.

European Respiratory Society and European Sleep Research Society statement on the treatment of central sleep apnoea with adaptive servo-ventilation.

Adaptive servo-ventilation (ASV) has been considered effective in controlling various forms of central sleep apnoea (CSA) and also any additional obstructive sleep apnoea (OSA) component. However, after the publication of the SERVE-HF study, its use was restricted in patients with systolic heart failure (HF) and prevalent CSA, and was withheld from many patients with symptomatic CSA. In the meantime, the devices have been further developed and the algorithms adapted, and there is new evidence from randomised controlled trials and observational studies that makes it necessary to re-evaluate some societies' statements on the use of ASV, especially in patients with HF and CSA and with the current ASV devices.

Gene expression analyses in mouse sensory ganglia determine a crucial role of NGF/TrkA in knee osteoarthritis chronification.

Objective: Osteoarthritis (OA) can be experimentally induced by injecting monoiodoacetate (MIA) in the knee capsule of mice. Our aim was to assess the role of nerve growth factor (NGF)/TrkA axis in OA, identifying differentially expressed genes (DEGs) and functional pathways in knee-innervating dorsal root ganglia (DRG) from wild type (WT) and hypersensitive TrkAP782S (KI) mice after MIA injection.

Method: We performed saline or MIA-injection in knee joints of WT and KI mice and harvested L3-L5 DRGs at 5 and 21 days after injection, pooling males and females (n = 4/group).

α-Synuclein-Related Mitochondria-Nrf2 Dysfunction in Parkinson's Disease Olfactory Mucosa.

Objective: The objective of this study was to outline the dynamics of the mitochondrial network and cytoprotective response in patients with Parkinson's disease (PD)-derived olfactory mucosa neurons (ONs) at different disease stages.

Methods: ONs obtained by nasal brush from 41 well-phenotyped patients with PD (n = 24 PD de novo [PD] and n = 17 under treatment [PD]) and 29 healthy controls were examined through real-time polymerase chain reaction (RT-PCR), immunofluorescence, and Western blot. An integrative set of experiments using SH-SY5Y neuronal cells was also performed.

Functional Characterization of LTR12C as Regulators of Germ-Cell-Associated TA-p63 in U87-MG and T98-G In Vitro Models.

Glioblastoma multiforme (GBM) is a deadly disease known for its genetic heterogeneity. LTR12C is an endogenous retrovirus-derived regulator of pro-apoptotic genes and is normally silenced by epigenetic regulation. In this study, we found that the treatment of two glioblastoma cell lines, T98-G and U87-MG, with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors activated LTR12C expression.

Endonasal filters for the prevention and control of respiratory allergy and infections. A multi-stakeholder assessment.

Healthcare innovations aim to develop and provide technologies, services, and health policies to improve population health and well-being at a global level. Among innovative medical devices (MD), endonasal filters (EF) are designed to improve breathing and capture fine dust and allergens in the surrounding environment acting as a mechanical barrier to the passage of allergens, pathogenic microorganisms and dust. This paper aimed to: i) review the features of EF commercially available, regulatory classification, and their potential role in public health as useful innovative devices; ii) review their role in prevention and control of respiratory infections; iii) review their role in prevention and control of allergic respiratory diseases.

Genetic deletion of microRNA-34 unmasks cardiac vulnerability to psychosocial stress in male mice.

Exposure to chronic psychosocial stress is a major risk for cardiovascular disease. While the cardiovascular response to acute psychological stress is well known, the mechanisms underlying the risk to develop cardiovascular consequences in response to chronic stress exposure are poorly understood. The family of microRNA-34 (miR-34 s) is widely investigated for its role in cardiovascular dysfunctions, and recently miR-34 s were found involved in the brain adaptation to chronic stress.

MACanalyzeR scRNAseq analysis tool reveals PPARγ/GDF15 lipid-associated macrophages facilitate thermogenic expansion in BAT.

Macrophages are key regulators of adipose tissue plasticity. Obesity impairs brown adipose tissue (BAT) function in humans, yet macrophage-mediated mechanisms remain elusive. Here, we introduce MACanalyzeR, a single-cell RNA sequencing (scRNAseq) tool designed for comprehensive monocyte/macrophage metabolic profiling.

Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.

Even though the number of patients suffering from Alzheimer's Disease (AD) is rapidly growing worldwide, only a few symptomatic treatments have been approved for clinical use, pointing out the urgent need for more effective disease-modifying therapies that actually alter the progression of this neurodegenerative disorder which is characterized by co-occurence of both Amyloid beta (Aβ) and tau neuropathologies. Preclinical and clinical evidence suggests that a link between Aβ and tau drives the entire continuum of AD pathobiology. 12A12 is a monoclonal antibody (mAb) which offers neuroprotection into two transgenic lines of AD, including Tg2576 that overexpresses Swedish mutation (KM670/671NL) of Amyloid Precursor Protein (APP, isoform 695) and 3xTg (APP Swedish, MAPT P301L, and PSEN1 M146V), by targeting the 20-22kDa N-terminal tau fragments (NHhtau).

DNA damage response defects induced by the formation of TDP-43 and mutant FUS cytoplasmic inclusions and their pharmacological rescue.

Formation of cytoplasmic inclusions (CIs) of TDP-43 and FUS, along with DNA damage accumulation, is a hallmark of affected motor neurons in Amyotrophic Lateral Sclerosis (ALS). However, the impact of CIs on DNA damage response (DDR) and repair in this pathology remains unprobed. Here, we show that CIs of TDP-43 and FUS, co-localizing with stress granules, lead to a dysfunctional DDR activation associated with physical DNA breakage.

Defining the transcriptional routes controlling lncRNA NEAT1 expression: implications in cellular stress response, inflammation, and differentiation.

NEAT1 (Nuclear Enriched Abundant Transcript 1) is a long non-coding RNA playing a critical role in both physiological and pathological settings by directly modulating a variety of biological events, including transcriptional regulation, RNA processing, and chromatin remodeling. Multiple evidence demonstrated that different transcription factors and signaling pathways modulate biological processes by tightly regulating NEAT1 expression. These regulatory mechanisms act at different levels, allowing cells to rapidly modulate NEAT1 expression and dynamically respond to sudden changes in cellular conditions.

Could an external Medical Center with telemonitoring help in home positive airway pressure treatment? A pilot study.

Purpose: Telemedicine is useful for home management of sleep disordered breathing (SDB). However, the number of patients with SDB is high and public resources are low. The aim of this pilot study, conducted by the Universities of Pisa and Palermo, was to assess whether an external Medical Center, based on telemonitoring, could help in the management of patients on home positive airway pressure (PAP) treatment.