Targeted TGF-ßR2 Knockdown in the Retrotrapezoid Nucleus Mitigates Respiratory Dysfunction and Cognitive Decline in a Mouse Model of Cerebral Amyloid Angiopathy with and without Stroke.

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO2 sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-ß) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke. Methods: Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-ß2R2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-ßR2 and GFAP expressions in the RTN. Results: CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-ßR2 knockdown in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-ßR2 knockdown similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-ßR2 and GFAP expressions in the RTN following knockdown. Conclusions: Our findings demonstrate that increased TGF-ß signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-ßR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models.

The prevalence of self-reported anxiety, depression, and associated factors among Hanoi Medical University's students during the first wave of COVID-19 pandemic.

BACKGROUND: Medical students are known to have higher levels of these issues than the general population but in Vietnam the effects of the pandemic on medical student mental health was not documented. OBJECTIVES: To estimate the prevalence and identify factors associated with self-reported anxiety disorder, depression, and perception of worsening mental health among Vietnamese medical students during the COVID-19 pandemic. METHOD: A cross-sectional study was conducted from April 7th to 29th, 2020. All students in Doctor of General Medicine, Doctor of Preventive Medicine, and Bachelor of Nursing tracks at Hanoi Medical University (3672 students) were invited to participate. Data were collected using an online questionnaire including demographic characteristics, Generalized Anxiety Disorder 7 items, Patient Health Questionnaire 9 items, Fear of COVID-19 scale, and question about worsening mental health status. Robust Poisson regression was used to assess the association between mental health status and associated factors. RESULTS: Among 1583 students (43.1% response rate), the prevalence of students screened positive for anxiety disorder was 7.3%(95%C.I.:6.0-8.7), depression was 14.5%(95%C.I.:12.8-16.3), and perceiving worsening mental health was 6.9%(95%C.I.:5.7-8.3). In multivariable regression models, significant factors associated with self-reported anxiety disorder included being male (PR = 1.99,95%C.I.:1.35-2.92), difficulty in paying for healthcare services (PR = 2.05,95%C.I.:1.39-3.01), and high level of fear of COVID-19 (Q3:PR = 2.36,95%C.I.:1.38-4.02 and Q4:PR = 4.75,95%C.I.:2.65-8.49). Significant factors associated with self-reported depression were difficulty in paying for healthcare services (PR = 1.78,95%C.I.:1.37-2.30), and high level of fear of COVID-19 (Q3:PR = 1.41,95%C.I.:1.02-1.95 and Q4:PR = 2.23,95%C.I.:1.51-3.29). Significant factors associated with perceived worsening mental health status included having clinical experience (PR = 1.83,95%C.I.:1.17-2.88) and having atypical symptoms of COVID-19 (PR = 1.96,95%C.I.:1.31-2.94). CONCLUSION: The prevalence of self-reported depression, anxiety disorder, and worsening mental health among Vietnamese students during the first wave of COVID-19 was lower than in medical students in other countries. Further investigation is needed to confirm this finding.

Evaluating the mechanisms of action and subcellular localization of ruthenium(II)-based photosensitizers.

The identification of ruthenium(II) polypyridyl complexes as photosensitizers in photodynamic therapy (PDT) for the treatment of cancer is progressing rapidly. Due to their favorable photophysical and photochemical properties, Ru(II)-based photosensitizers have absorption in the visible spectrum, can be irradiated via one- and two-photon excitation within the PDT window, and yield potent oxygen-dependent and/or oxygen-independent photobiological activities. Herein, we present a current overview of the mechanisms of action and subcellular localization of Ru(II)-based photosensitizers in the treatment of cancer. These photosensitizers are highlighted from a medicinal chemistry and chemical biology perspective. However, although this field is burgeoning, challenges and limitations remain in the photosensitization strategies and clinical translation.