The pretreatment of chronic restraint stress exerts little impact on the progression of heart failure in mice.

Stress is a potent risk factor for depression. Chronic stress can exacerbate and induce symptoms of depression. Clinical studies suggested that depressive patients are more likely to develop coronary artery diseases. However, the causal relationship between depression and heart failure progression remains unclear. In this study, we aimed to explore the relevance between stress and heart failure (HF) in a mouse model subjected to chronic restraint stress and left anterior descending coronary artery (LAD) ligation. Mice were restrained for 3 h daily for 21 days and the processes were repeated once 3 months later. After the repeated chronic restraint stress, mice showed dramatically increased immobility time in the forced swim test, indicating a state of despair. Restrained and control mice were further subjected to LAD ligation surgery. Echocardiography was conducted 1 week, 2 weeks, and 1 month afterward. LAD-operated mice showed a significant decrease in the values of left ventricular ejection fraction (LVEF), and there was no difference in the LVEF values between the restrained and control mice. Relevant gene expression, neurotransmitter system, glial activation, and morphology of the heart-brain axis were comprehensively evaluated. We found no overall differences between the restrained and control mice with HF. Our results revealed that the repeated chronic restraint stress may have little effects on the progression of heart failure.

Differential cardiac hypertrophy and signaling pathways in pressure versus volume overload.

Mechanical overload can be classified into pressure overload and volume overload, causing concentric and eccentric cardiac hypertrophy, respectively. Here, we aimed to differentiate the load-mediated signaling pathways involved in pressure versus volume overload cardiac hypertrophy. Pressure or volume overload was imposed on C57BL/6J mice by transverse aortic constriction (TAC) or aortic regurgitation (AR), respectively. After surgery (2 wk), left ventricular structure and function were evaluated by echocardiographic, hemodynamic, and histological analyses. Signaling pathways related to hypertrophy, fibrosis, angiogenesis, and apoptosis were studied by histological analysis, RT-PCR, and Western blot analysis. Although mean wall stress was similar in both TAC and AR mice, systolic wall stress was significantly increased in TAC and diastolic wall stress was mainly elevated in AR. TAC or AR induced concentric or eccentric compensated hypertrophy, respectively. TAC was associated with more significant fibrosis and apoptosis, whereas AR was associated with more significant angiogenesis. MAPK kinase family, ß-arrestin-2, Akt, and Ca2+-related signaling pathways were markedly activated in TAC but mildly upregulated or unchanged in AR. Pressure overload and volume overload induce different phenotypic and molecular adaptations in cardiac hypertrophy. Most load-related signaling pathways assessed in this study predominate in pressure but not volume overload. The stimulus-specific heterogeneity in the signaling pathways requires distinct manipulations for further mechanistic and pharmacological studies. NEW & NOTEWORTHY Using the transverse aortic constriction mouse model and the newly developed aortic regurgitation mouse model, we delineated the prominent differences between concentric and eccentric cardiac hypertrophy on morphological, functional, and molecular levels. Our findings are important for the precise diagnosis and treatment of these two types of cardiac hypertrophy. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/chinese-english-language-podcast-on-differential-cardiac-remodeling-in-tac-vs-ar/ .

Ultrasound biomicroscopy validation of a murine model of cardiac hypertrophic preconditioning: comparison with a hemodynamic assessment.

In mice, myocardial hypertrophic preconditioning (HP), which is produced by the removal of short-term transverse aortic constriction (TAC), was recently reported to render the heart resistant to hypertrophic responses induced by subsequent reconstriction (Re-TAC). However, there is no efficient noninvasive method for ensuring that the repeated aortic manipulations were successfully performed. We previously demonstrated that ultrasound biomicroscopy (UBM) is a noninvasive and effective approach for predicting TAC success. Here, we investigated the value of UBM for serial predictions of load conditions in establishing a murine HP model. C57BL/6J mice were subjected to a sham operation, TAC, or Re-TAC, and the peak flow velocity at the aortic banding site (PVb) was measured by UBM. Left ventricular end-systolic pressure (LVESP) was examined by micromanometric catheterization. The PVb was positively associated with LVESP (R2 = 0.8204, P < 0.001, for TAC at 3 days and R2 = 0.7746, P < 0.001, for Re-TAC at 4 wk). PVb and LVESP values were markedly elevated after aortic banding, became attenuated to the sham-operated level after debanding, and increased after aortic rebanding. The cardiac hypertrophic responses were examined by UBM, histology, RT-PCR, and Western blot analysis. Four weeks after the last operation, with PVb ≥ 3.5 m/s as an indicator of successful aortic constriction, Re-TAC mice showed less cardiac hypertrophy, fetal gene expression, and ERK1/2 activation than TAC mice. Therefore, we successfully established a UBM protocol for the serial assessment of aortic flow and the prediction of LVESP during repeated aortic manipulations in mice, which might be useful for noninvasive evaluations of the murine HP model.NEW & NOTEWORTHY We successfully developed an ultrasound biomicroscopy protocol for the serial assessment of aortic bandings and the relevant left ventricular pressure in a murine model of cardiac hypertrophic preconditioning. The protocol may be of great importance in the successful establishment of the hypertrophic preconditioning model for further mechanistic and pharmacological studies.

Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

AIM: To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. METHODS: Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. RESULTS: Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. CONCLUSION: Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

A survey on advancements in image-text multimodal models: From general techniques to biomedical implementations.

With the significant advancements of Large Language Models (LLMs) in the field of Natural Language Processing (NLP), the development of image-text multimodal models has garnered widespread attention. Current surveys on image-text multimodal models mainly focus on representative models or application domains, but lack a review on how general technical models influence the development of domain-specific models, which is crucial for domain researchers. Based on this, this paper first reviews the technological evolution of image-text multimodal models, from early explorations of feature space to visual language encoding structures, and then to the latest large model architectures. Next, from the perspective of technological evolution, we explain how the development of general image-text multimodal technologies promotes the progress of multimodal technologies in the biomedical field, as well as the importance and complexity of specific datasets in the biomedical domain. Then, centered on the tasks of image-text multimodal models, we analyze their common components and challenges. After that, we summarize the architecture, components, and data of general image-text multimodal models, and introduce the applications and improvements of image-text multimodal models in the biomedical field. Finally, we categorize the challenges faced in the development and application of general models into external factors and intrinsic factors, further refining them into 2 external factors and 5 intrinsic factors, and propose targeted solutions, providing guidance for future research directions. For more details and data, please visit our GitHub page: https://github.com/i2vec/A-survey-on-image-text-multimodal-models.

Effects of heart rate and anesthetic timing on high-resolution echocardiographic assessment under isoflurane anesthesia in mice.

OBJECTIVE: Anesthesia provides sedation and immobility, facilitating echocardiography in mice, but it influences cardiovascular function and therefore outcomes of measurement. This study aimed to determine the effect of the optimal heart rate (HR) and anesthetic timing on echocardiographic reproducibility under isoflurane anesthesia. METHODS: Male C57BL/6J mice underwent high-resolution echocardiography with relative fixed HRs and anesthetic timing. The same experiment was repeated once again after 1 week. RESULTS: Echocardiography was highly reproducible in repeated measurements under low-HR (350-400 beats per minute [bpm]) and high-HR (475-525 bpm) conditions except some M-mode parameters under low-HR conditions. With similar anesthetic timing, mice with a high HR had decreased preload indices and increased ejection phase and Doppler indices. Inversely, when the HR was similar, the echocardiographic results of mice under short anesthetic timing showed little difference from the ones under long anesthetic timing. CONCLUSIONS: This study shows that echocardiographic assessment is greatly reproducible under a high HR. The HR is more important than anesthetic timing for echocardiographic evaluation in mice.

Inflammation associated with chronic heart failure leads to enhanced susceptibility to depression.

Epidemiological and clinicopathological studies indicate that there is a high risk for chronic heart failure (CHF) in patients suffering from neuropsychiatric disorders, such as depression. However, it is unclear whether CHF causes depression, and the underlying mechanisms of this association remain largely unknown. In this study, mice with myocardial infarction and CHF were used to investigate behavioral alterations as well as changes in the brain-heart axis. During the first 6 months, abnormalities in neuropsychiatric behaviors were detected in mice with CHF. Using the sucrose preference test, a 9 months course of CHF resulted in two subgroups: mice with a significant decrease in sucrose preference, defined herein as "susceptible" (Sus), and mice with a normal sucrose preference, defined herein as "resilient." Compared to the resilient and sham-operated animals, the Sus mice displayed imbalances in glutamate transmission and hypothalamic-pituitary-adrenal axis activation, abnormal synaptic plasticity, and increased inflammatory responses. Furthermore, abnormal kynurenine metabolism was detected in Sus mice. Our results suggest that long-term CHF increases inflammatory responses in the central nervous system and leads to depression in Sus mice.

The Aß Containing Brain Extracts Having Different Effects in Alzheimer's Disease Transgenic Caenorhabditis elegans and Mice.

Background: The deposition of ß-sheet rich amyloid in senile plaques is a pathological hallmark of Alzheimer's disease (AD), which is thought to cause neuronal dysfunction. Previous studies have strongly implicated that intracerebral infusion of brain extract containing aggregated ß-amyloid (Aß) is able to induce cerebral amyloidosis thus causing neuronal damage and clinical abnormalities in rodents and nonhuman primates, which are reminiscent of a prion-like mechanism. Prion disease has been documented in cases of prion-contaminated food consumption. Methods: We investigated whether cerebral transmission of Aß was possible via oral administration of Aß-rich brain extract in non-susceptible and susceptible host mice by immunohistochemistry, western blotting and behavior tests. Also brain extracts were supplied to AD transgenic Caenorhabditis elegans, and paralysis curve were conducted, following detection of Aß amyloid. RNA sequencing of nematodes was applied then inhibitors for relevant dysregulated genes were used in the paralysis induction. Results: The oral treatment of AD brain extract or normal brain extract neither aggravated nor mitigated the Aß load, glial activation or the abnormal behaviors in recipient Amyloid precursor protein/presenilin 1 (APP/PS1) mice. Whereas, a significant improvement of AD pathology was detected in worms treated with Aß-rich or normal brain extracts, which was attributable to the heat-sensitive components of brain extracts. Transcriptome sequencing of CL4176 nematodes suggested that brain extracts could delay worm paralysis through multiple pathways, including ubiquitin mediated proteolysis and Transforming growth factor ß (TGF-ß) signaling pathway. Inhibitors of the ubiquitin proteasome system and the TGF-ß signaling pathway significantly blocked the suppressive effects of brain extracts on worm paralysis. Conclusions: Our results suggest that systemic transmissible mechanisms of prion proteopathy may not apply to ß amyloid, at least in terms of oral administration. However, brain extracts strongly ameliorated AD pathology in AD transgenic nematodes partially through TGF-ß signaling pathway and ubiquitin mediated proteolysis, which indicated that some natural endogenous components in the mammalian tissues could resist Aß toxicity.

Rapid full volume data acquisition by real-time 3-dimensional echocardiography for assessment of left ventricular indexes in children: a validation study compared with magnetic resonance imaging.

OBJECTIVE: We sought to assess the feasibility, accuracy, and reproducibility of a rapid full volume acquisition strategy using real-time (RT) 3-dimensional (3D) echocardiography (3DE) for measurement of left ventricular (LV) volumes, mass, stroke volume (SV), and ejection fraction (EF) in children. METHODS: A total of 19 healthy children (mean 10.6 +/- 2.8 years, 11 male and 9 female) were prospectively enrolled in this study. RT 3DE was performed using an ultrasound system to acquire full volume 3D dataset from the apical window with electrocardiographic triggering in 8 s/dataset. The images were processed offline using software. The LV endocardial and epicardial borders were traced manually to derive LV end-systolic volume, end-diastolic volume, mass, SV, and EF. Magnetic resonance imaging (MRI) studies were performed on a 1.5-T scanner using a breath hold 2-dimensional cine-FIESTA (fast imaging employing steady-state acquisition) sequence. RESULTS: All RT 3DE and MRI data were acquired successfully for analysis. Measurements of LV end-systolic volume, end-diastolic volume, mass, SV, and EF by RT 3DE correlated well by Pearson regression ( r = 0.86-0.97, P < .001) and agreed well by Bland-Altman analysis with MRI. The interobserver and intraobserver variability of RT 3DE measurements were less than 5%. CONCLUSIONS: This prospective study demonstrated that RT 3DE measurements of LV end-systolic volume, end-diastolic volume, mass, SV, and EF in children using rapid full volume acquisition strategy are feasible, accurate, and reproducible and are comparable with MRI measurements.

A real-time 3-dimensional digital Doppler method for measurement of flow rate and volume through mitral valve in children: a validation study compared with magnetic resonance imaging.

We developed and assessed a real-time 3-dimensional (3D) digital Doppler method for measurement of flow volumes through the mitral valve in children. A total of 13 children (aged 10.46 +/- 2.5 years; 8 boys/5 girls) were enrolled. An ultrasound system (Sonos 7500, Philips, Andover, Mass) was used to acquire raw 3D velocity data for flow measurement based on Gaussian control surface theorem [flow (mL/s) = mean velocity x flow area]. Stroke volume (SV) measured by real-time 3D digital Doppler with the control surface at the mitral valve annulus or orifice was compared with the SV by phase velocity cine magnetic resonance imaging (MRI) at the ascending aorta and by left ventricular volumetric MRI measurement. The best correlation and agreement were seen at the mitral valve orifice by real-time 3D digital Doppler compared with SV by phase velocity cine MRI at the ascending aorta (r = 0.92, mean difference = -5.2 +/- 12.0 mL) and SV by left ventricular volumetric MRI measurement (r = 0.94, mean difference = -0.2 +/- 10.3 mL).