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Stressed hepatocyte sustains alcohol-associated hepatitis progression by producing leukocyte cell-derived chemotaxin 2
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.
Alcohol exhibits contrasting effects on CD8+ T cells in the gut and liver in alcohol-associated liver disease
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,…
Associations between optimism and mental health in postradiotherapy cancer survivors: a cross-sectional survey study
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
Triangular perspectives of healthcare providers, patients and their families on ICU palliative care: a protocol for a systematic review of qualitative studies
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.
Evaluation of a virtual reality-directed brain-gut behavioural treatment inpatient program for patients with inflammatory bowel disease: protocol for a pilot feasibility trial
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.
La nuova mappa della depressione giovanile passa dagli smartphone
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…
Loss of PTSD Diagnosis in Response to Evidence-Based Treatments
This systematic review and meta-analysis estimates the percentage of patients in both military and veteran and non–military and veteran populations that lose their posttraumatic stress disorder (PTSD) diagnosis after psychotherapeutic treatment.
Distratti dopo appena 8 secondi, ansia e stress la prima causa
Ricerca Usa, anche sonno e dispositivi rubano la concentrazione
Mitochondrial Tumor Suppressor 1A Attenuates Myocardial Infarction Injury by Maintaining the Coupling Between Mitochondria and Endoplasmic Reticulum
Circulation, Ahead of Print. BACKGROUND:Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)–mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions.METHODS:Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of Mtus1 in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation–mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9).RESULTS:Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific knockout of Mtus1 in mice exacerbated cardiac dysfunction after MI. Both in vitro and in vivo studies demonstrated the vital role of Mtus1A in modulating mitochondria-associated ER membranes coupling and preserving mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining ER-mitochondria connectivity.CONCLUSIONS:Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.
Come la caffeina può rallentare l’invecchiamento cellulare
Uno studio della Queen Mary University di Londra ha scoperto che la […]
Daily mobility, activity and environmental determinants of stress in ecological momentary assessment (EMA) and GPS studies: a scoping review protocol
Introduction
Stress is omnipresent in our everyday lives and a key risk factor for our physical and mental health. Yet little is known about the impact of geographic life environments, linked to our daily activities and mobility patterns, on our momentary and daily stress levels.
We propose this review to gather evidence on the spatio-temporal determinants of momentary or daily stress in studies using ecological momentary assessment (EMA) or experience sampling methods (ESM) in addition to global positioning systems (GPS) tracking. We will focus on the spatio-temporal definition and modelling of environmental exposures accounting for participant daily activities and mobility patterns and their association with stress.
Methods and analysis
This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework for scoping reviews (2018). We will search the PubMed/Medline, Web of Science, PsycInfo and Scopus databases. We will include papers using EMA or ESM and GPS measuring chronic, daily or momentary stress as an outcome; these methods are also referred to as geographically-explicit ecological momentary assessment.
Articles published from January 2000–June 2025 will be screened. Two independent reviewers will screen titles and abstracts to agree on the inclusion of articles. No geographical or population limitation will be imposed.
Ethics and dissemination
This study is a scoping review based on previously published and publicly available literature. It does not involve the collection of primary data, human participants, or the processing of personal or sensitive information. Therefore, ethical approval is not required in accordance with institutional and international research ethics guidelines. The results will be submitted in peer-reviewed journals and presented at international conferences.
Cross-sectional study of the rates of military sexual trauma (MST) and associations with adverse mental health outcomes among UK female ex-service personnel: a study protocol
Introduction
This study investigates the rates of military sexual trauma (MST) and its associations with adverse mental health among a sample of UK female ex-service personnel who served during the Iraq/Afghanistan eras.
Methods and analysis
Female ex-service personnel, who participated in the fourth phase (Phase 4) of the King’s Centre for Military Health Research (KCMHR) Health and Well-being Cohort Study (2022–2023) and consented to be recontacted for follow-up studies (n=295), are being invited to participate in an online questionnaire between July 2024 and February 2025. The questionnaire contains surveys and questions related to experiences of sexual harassment and sexual assault during and outside of military service, disordered eating and broader female health issues. While the questionnaire relates to several female health topics, this study focuses on the surveys related to experiences of sexual trauma and eating disorders. Sociodemographic variables and some health variables, including post-traumatic stress disorder (PTSD), complex PTSD, common mental disorders, alcohol misuse, physical somatisation and social support, will be extracted from participants’ pre-existing data collected in Phase 4 of the KCMHR Cohort Study. Analyses will assess rates of MST, and hierarchical multiple logistic regressions will investigate associated health impacts. Rates and ORs, employing 95% CIs, will be reported.
Ethics and dissemination
This study has been granted full ethical approval by the King’s College London Research Ethics Committee (Ref: HR/DP-23/24–39040). Participants provide informed consent before participating and have access to a signposting booklet containing contact details for a range of support services. A risk protocol is in place, which outlines the procedure to be undertaken if a participant contacts the research team in distress. Findings will form part of a PhD thesis and will be further disseminated through peer-reviewed publication and dissemination with veteran mental health services and charities, and relevant government departments.
Beyond the puff: qualitative insights into smoking behaviours and societal perceptions among university students in India
Objectives
The objective of the study was to understand the smoking behaviour of adults and how societal perceptions influence the smoking behaviour of university students.
Design
Qualitative study.
Setting
National Institute of Medical Sciences university, India.
Participants
20 face-to-face interviews were carried out among university students who were in the age group of 19–30 years using a combination of purposive sampling, followed by snowball sampling methods.
Results
Qualitative responses revealed that stress, cravings for cigarettes and mealtimes were key triggers for smoking behaviour. Many participants felt guilty about their smoking and often became irritated by advice from non-smoking friends. All participants had experienced negative health effects, including physical and sensory issues, as well as other adverse experiences. Students expressed a dislike for judgemental attitudes from society. They respected elders and found it difficult to smoke in front of them. Rather than being blamed for their smoking, they preferred supportive assistance to help them quit.
Conclusions
The study highlights the importance of understanding college students’ smoking behaviour, as it greatly influences their smoking habits. Cessation efforts should target this group and emphasise the negative experiences associated with smoking. Additionally, students recommend creating a non-judgemental and supportive environment to aid in quitting, rather than a judgemental and blaming society.
Prolonged Caffeine Therapy for Preterm Infants
Approximately 13 million newborns were preterm (born before 37 weeks of gestation) across all member states of the World Health Organization in 2020. In 2023, the US preterm birth rate was 10.4%. Nearly all preterm infants require specialized in-hospital care to support their immature respiratory, cardiovascular, central nervous, digestive, and immune function. The length of the initial hospital stay depends on the duration of gestation, the medical condition at birth, and the development of complications such as infections or chronic lung disease. The main determinant of discharge readiness is the infant’s physiological maturity, defined as adequate control of breathing, respiratory stability, full oral feeding with appropriate weight gain, and good temperature control in a crib. In addition, the preparedness of the family and the suitability of the home environment should be confirmed. Most very preterm infants (those born between 28 and
Remote ischaemic preconditioning in cemented hip arthroplasty (the PRINCIPAL study)–randomised controlled trial: study protocol
Introduction
Total hip arthroplasty (THA) is an effective treatment for severe osteoarthritis. However, THA has a high surgical risk for patients with concomitant diseases and is associated with several serious complications, such as myocardial infarction, acute kidney injury and cognitive dysfunction. This study will explore the potential protective effects of remote ischaemic preconditioning (RIPC) in cemented THA patients.
Methods and analysis
The PRINCIPAL study is designed as a randomised, controlled, parallel-group, blinded trial to assess the impact of RIPC in cemented THA patients. The study will compare two patient groups—one group will have the RIPC procedure, and the second will have the sham procedure. The primary outcome is the peak troponin T concentration during the three postoperative days. Secondary outcomes include markers of arterial stiffness (augmentation index (AIx), carotid-femoral pulse wave velocity, central blood pressures), neural (neuron-specific enolase, S100B) and renal injury biomarkers (estimated glomerular filtration rate, creatinine, cystatin C), markers of systemic inflammation (hypoxia-inducible factor 1-alpha, interleukin (IL)-6, IL-1β, tumour necrosis factor-alpha, IL-10) and oxidative stress (total peroxide concentration, total antioxidant capacity), as well as clinical outcome measures such as major adverse cardiovascular events and all-cause mortality.
Ethics and dissemination
The ethical board of the University of Tartu has granted approval for the study (no. 384T-26). The results of this study will be disseminated in international peer-reviewed journals.
Trial registration number
NCT06323018.