Search Results for: La caffeina è efficace nella lotta contro la depressione e lo stress

Nei pazienti con obesità ipotalamica acquisita, setmelanotide ha ridotto in misura clinicamente significativa l’indice di massa corporea dopo 52 settimane rispetto al placebo, come rilevato dallo studio TRANSCEND presentato al congresso 2025 della Endocrine Society (ENDO).

Può essere paragonata al laser, utilizzabile per varie patologie. In questo caso, si può applicare nel campo della neurologia, per curare cefalee ed emicranie. In quello della psichiatria, per trattare…

Circulation, Ahead of Print. BACKGROUND:Hereditary hemorrhagic telangiectasia is an inherited vascular disorder characterized by arteriovenous malformations (AVMs). Loss-of-function variations in activin receptor-like kinase 1 (ALK1) cause type 2 hereditary hemorrhagic telangiectasia, andAlk1knockout mice develop AVMs, along with overactivation of vascular endothelial growth factor receptor 2/phosphoinositide 3-kinase/AKT signaling. The full spectrum of signaling alterations resulting fromALK1variations remains unknown, and more effective and specific inhibitors to combat AVM formation in patients are needed.METHODS:Single-cell RNA sequencing of endothelial-specificAlk1knockout mouse retinas and controls was performed. Overexpression of fluid shear stress signaling signatures including the mechanosensitive ion channel PIEZO1 was confirmed in mouse and human type 2 hereditary hemorrhagic telangiectasia lesions. Genetic and pharmacological PIEZO1 inhibition was tested inAlk1knockout mice, along with downstream PIEZO1 signaling.RESULTS:A cluster ofAlk1mutant endothelial cells with altered arterio-venous identity overexpressed pathways related to fluid shear stress, hypoxia, inflammation, cell cycle, and vascular endothelial growth factor receptor 2/phosphoinositide 3-kinase/AKT signaling.Piezo1deletion and pharmacological inhibition inAlk1-deficient mice mitigated AVM formation, whereasPiezo1overexpression enhanced AVM formation induced by ALK1 ligand blockade. Mechanistically, PIEZO1 inhibition reduced elevated vascular endothelial growth factor receptor 2/AKT, ERK5-p62-KLF4, endothelial nitric oxide synthase, hypoxia, proliferation, and inflammation in ALK1-deficient endothelium.CONCLUSIONS:PIEZO1 expression and signaling are elevated in type 2 hereditary hemorrhagic telangiectasia. PIEZO1 blockade reduces AVM formation and alleviates cellular and molecular hallmarks of ALK1-deficient cells. This finding provides new insights into the mechanistic underpinnings of ALK1-related vascular diseases and identifies potential therapeutic targets to prevent AVMs.

Stroke, Ahead of Print. BACKGROUND:Epigenetic modifications 5-methylcytosine and 5-hydroxymethylcytosine in DNA regulate neuronal survival under ischemic stress. We previously showed that TET3 (ten-eleven translocation 3)–mediated 5-methylcytosine to 5-hydroxymethylcytosine conversion induces neuroprotective gene transcription after stroke. As TET3 neuronal isoform lacks the DNA-binding domain, how TET3 drives 5-hydroxymethylcytosine–mediated transcriptional induction in the ischemic brain remains unclear. Long noncoding RNAs (lncRNAs) act as structural scaffolds to recruit chromatin-modifying proteins and other RNAs to specific genomic loci. However, whether TET3 requires an lncRNA to drive DNA hydroxymethylation in the ischemic brain is unknown.METHODS:Adult male and female mice were subjected to transient middle cerebral artery occlusion. TET3-bound lncRNAs were immunoprecipitated from peri-infarct cortex, and TILR (TET3-interacting lncRNA; AK020504) identified was inhibited with small interfering RNA injected at 5 minutes of reperfusion. Ascorbate was administered at 30 minutes of reperfusion to induce TET3 activity. Poststroke DNA hydroxymethylation was assessed with hydroxymethylation DNA immunoprecipitation sequencing, and sensorimotor deficits, and infarct volume were evaluated between days 1 and 7 of reperfusion.RESULTS:TILR binds to TET3 with high affinity and was significantly upregulated in the peri-infarct cortex at 12 hours of reperfusion. Knockdown of TILR increased the infarct volume and reduced the motor function recovery after transient middle cerebral artery occlusion, in a TET3-dependent manner. On contrary, TET3 activation by ascorbate decreased brain damage and improved motor function recovery after ischemia. However, ascorbate-induced postischemic protection was abrogated by TILR knockdown. Genome-wide profiling showed that ascorbate increases the number of differentially hydroxymethylated regions in the poststroke genome, a neuroprotective effect that is reversed by TILR knockdown. Moreover, TILR inhibition significantly reduced the DNA hydroxymethylation in the intergenic regions associated with enhancers, super enhancers, and the promoters of other lncRNAs, microRNAs, and PIWI-interacting RNAs.CONCLUSIONS:These findings highlight the essential role of TILR in TET3-mediated 5-hydroxymethylcytosine-dependent epigenetic reprogramming in the ischemic brain.

Uno studio prospettico pubblicato su Pain and Therapy condotto presso il centro regionale per le cure palliative dell’Ospedale La Maddalena di Palermo ha analizzato, a distanza di 12 anni da una precedente indagine, le strategie di prescrizione degli oppioidi e l’efficacia analgesica in pazienti ricoverati in un’Unità di Cure Palliative Acute (APCU). I risultati mostrano che un approccio intensivo e personalizzato consente un controllo efficace del dolore senza necessità di aumentare l’equivalente in morfina orale (OME), e sottolineano l’importanza di una gestione esperta nella terapia del dolore oncologico.

Un nuovo inibitore selettivo dell’aldosterone, baxdrostat, ha mostrato in uno studio di Fase III un’efficace riduzione della pressione arteriosa sistolica a 12 settimane, aprendo nuovi scenari terapeutici per pazienti con ipertensione non controllata o resistente.

MannKind Corporation pianifica di chiedere l’ok alla Fda

Nei pazienti con anemia emolitica autoimmune da anticorpi caldi (wAHIA), il trattamento con l’inibitore della tirosin chinasi di Bruton (BTK) rilzabrutinib è efficace, anche nel lungo termine, nel migliorare i valori di emoglobina (Hb), ridurre i biomarcatori di emolisi e migliorare la fatigue, con un buon profilo di sicurezza. Lo dimostrano i risultati di una nuova analisi dello studio di fase 2b LUMINA 2, con un periodo più lungo di osservazione, presentati di recente a Milano, in occasione del congresso annuale della European Hematology Association (EHA).

Nei bambini affetti da orticaria cronica spontanea, compresi quelli di età inferiore ai 12 anni, omalizumab ha prodotto un elevato tasso di risposta con un profilo di sicurezza accettabile, secondo quanto rilevato da una metanalisi pubblicata sulla rivista Pediatric Allergy and Immunology.

Alcohol-associated liver disease (ALD) is a leading cause of chronic liver disease and liver-related mortality worldwide. The progression of ALD can range from simple fatty liver (steatosis) to severe liver damage, including alcohol-associated hepatitis (AH), liver fibrosis or cirrhosis, and hepatocellular carcinoma.1 Research over the past few decades has shown that the mechanisms behind the development of ALD are complex, involving multiple cellular factors and interactions between different organs. At the cellular level, alcohol and its metabolites, such as acetaldehyde, can lead to the production of reactive oxygen species, increase in endoplasmic reticulum stress, mitochondrial damage and megamitochondria formation, impaired autophagy-lysosomal functions, and the accumulation of Mallory-Denk bodies resulting in hepatocyte death and degeneration, as well as increased infiltration of immune cells, particularly neutrophils with high IL-8 expression.1 2 Consequently, these changes also contribute to an increased ductular reaction (DR) and cholestasis, fibrosis,…

Background
Neutrophil infiltration and hepatocyte damage are indispensable hallmarks in alcohol-associated hepatitis (AH), yet the underlying crosstalk between neutrophils and hepatocytes and its role in AH pathogenesis remain unclear.

Objective
We investigate the regulatory role of leucocyte cell-derived chemotaxin 2 (LECT2) in hepatocyte–neutrophil interaction and its impact on AH progression.

Design
We used bulk and single-cell RNA sequencing to identify hepatocyte-secreted factors targeting neutrophils. We analysed serum and liver samples from AH patients and employed genetically modified mice alongside in vitro studies.

Results
RNA-sequencing analysis identified several neutrophil chemokines that are elevated in hepatocytes from AH patients, including LECT2 whose role in AH remains largely unknown. AH patients exhibited increased levels of LECT2 in hepatocytes, positively correlating with the severity of AH. Ethanol-fed mice also exhibited elevated liver LECT2, which was abolished by inhibiting endoplasmic reticulum stress. Functional studies revealed that ethanol-induced liver injury was ameliorated in Lect2-deficient mice but was exacerbated in mice with hepatic overexpression of Lect2. Furthermore, LECT2 exacerbated ethanol-induced liver injury by promoting reactive oxygen species (ROS) through its interaction with prohibitin 2 (PHB2), a neutrophil membrane protein. By directly binding to PHB2, LECT2 disrupts the stable structure of PHB1/PHB2 heterodimerisation, consequently leading to PHB2 degradation, ROS accumulation, neutrophil activation and neutrophil extracellular trap formation. Moreover, therapeutic intervention of LECT2 via Lect2 shRNA ameliorated ethanol-induced liver injury.

Conclusion
Our studies identified a novel vicious cycle between neutrophils and hepatocytes through the LECT2–PHB2 interaction, presenting a promising therapeutic intervention by targeting LECT2 to mitigate AH in patients.

Objectives
Cancer patients often experience psychological distress, while optimism has been identified as a protective factor. However, the mental health of postradiotherapy cancer survivors and its association with optimism remain largely unexplored. This study assesses the mental health status and optimism levels of postradiotherapy cancer survivors and evaluates their associations.

Design
Cross-sectional survey study.

Participants
114 Hong Kong cancer survivors who (1) were aged 18 years or above and (2) had received radiotherapy for their cancer treatment and finished the radiotherapy within the previous 3 years (2021–2024).

Outcome measures
Mental health was assessed using the Chinese Depression, Anxiety and Stress Scale, and optimism was measured using the Revised Life Orientation Test. Correlation and regression analyses were used to examine the associations between these measures.

Results
Participants reported overall low optimism with mild to moderate depression, anxiety and stress. Strong negative correlations were identified between optimism and depression (r=–0.833, p

Introduction
In the intensive care unit (ICU), palliative care encounters obstacles such as decision conflicts, psychological stress and cultural differences among patients, families and healthcare providers. The well-being and the care quality of patients are influenced by these factors. The highly technical and curative-focused environment of the ICU presents a challenge for palliative care without appropriate integration. Certainly, it is imperative to comprehend these issues and devise strategies to reconcile curative and palliative needs. This paper employs qualitative metaintegration to appraise the experiences and perspectives of palliative care in the ICU, emphasising its outcomes, barriers and the necessity of balanced care and treatment.

Methods and analysis
This study conducted a comprehensive search of both the published and unpublished literature (such as grey literature) from a variety of databases, concerning PubMed, Google Scholar, Cochrane Library, CINAHL, Web of Science, Embase, Scopus, PsycINFO, CNKI, Wanfang, CBM and VIP, up to 10 July 2024. The articles will be retrieved and incorporated into EndNote X9 to facilitate organisation. Two independent researchers will evaluate the studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research, and a third researcher will resolve all discrepancies. Data extraction and results synthesis will be performed independently based on the JBI qualitative data extraction tool. Finally, the ConQual method will be employed to estimate the calibre of the compiled results.

Ethics and dissemination
The systematic review was conducted without the necessity of obtaining ethical clearance from a research committee, as it analysed previously published studies that did not contain any personal identifying information of participants. The review’s findings were presented to key stakeholders and submitted for consideration in peer-reviewed journals.

PROSPERO registration number
CRD42024571594.

Introduction
Pain is one of the most bothersome symptoms that affects patients with inflammatory bowel disease (IBD) but is often inadequately treated. Inadequate pain control in the inpatient setting not only impacts patients’ experience but increases opioid use and hospital length of stay. Opioids are often considered first-line treatment for severe pain but are associated with significant morbidity and mortality in IBD. Non-steroidal anti-inflammatory drugs are a non-opioid analgesic option, but concerns regarding their contribution to IBD flares have limited their use. Brain-gut behavioural therapies (BGBT), such as cognitive behavioural therapy, meditation and gut-directed hypnotherapy, are effective for pain management and have a role in the treatment of IBD symptoms. However, the use of BGBT in IBD is challenging, given limited access to behavioural health specialists, especially in the inpatient setting. Virtual reality (VR)-directed BGBT programmes can bridge this gap and enhance pain treatment for inpatients with IBD. Therefore, in this study, we aim to establish feasibility and acceptability for a VR-directed BGBT inpatient programme for patients with IBD.

Methods and analysis
We will recruit 40 patients with IBD who are hospitalised at Michigan Medicine and who endorse IBD-related pain. We will assess patient-reported outcomes (pain rating, IBD-specific symptoms, perceived stress, mood) before and after treatment, cumulative inpatient analgesic requirements and hospital length of stay. Our primary objective will be to establish intervention feasibility defined by the frequency and percentage of enrolled participants that use the VR-directed BGBT inpatient intervention in any capacity. Our secondary objective will be to evaluate intervention acceptability by conducting semistructured interviews with study participants. We will also explore the preliminary effectiveness of VR-directed BGBT on patient-reported outcomes and healthcare utilisation as compared with historic controls.

Ethics and dissemination
The study was approved by the institutional review board of the University of Michigan Medical School on 10 October 2023 (HUM00240999). All human subjects will be required to sign an informed consent document prior to study participation. Study findings will be reported through peer-reviewed publication.

Trial registration number
NCT06188793.

In un mondo sempre più dominato dagli smartphone e dai tablet, il benessere mentale degli adolescenti potrebbe pagare un prezzo molto alto. Una nuova ricerca dell’Università di Pittsburgh, pubblicata su…