Biomedical Journal最新文献

Background: Cardiac remodeling is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure, and cardiac arrhythmias. Nuclear factor-activated T-cell cytoplasmic (NFATc) is a crucial transcription factor that regulates cardiac remodeling. MicroRNA (miR)-424/322 has pathophysiological roles in the cardiovascular and respiratory systems by modulating hypoxia and inflammatory pathways. The role of miR-424/322 in regulating cardiac remodeling is under investigation. We identified several cardiac hypertrophy and fibrosis-related molecules as putative targets of miR-424/322. We propose that miR-424/322 could have crucial roles in cardiac remodeling by modulating several key molecules for cardiac fibrosis and hypertrophy.

Methods: Human cardiac fibroblasts (HCFs) and a myogenic cell line H9c2 cells were used for in vitro experiments. A murine model of angiotensin II (AngII)-induced cardiac remodeling was used to assess the roles of miR-322 on cardiac hypertrophy and fibrosis in vivo. Immunoblotting, immunofluorescence, real-time polymerase chain reaction and cell proliferation, Sirius Red, and dual-luciferase reporter assays were used to decipher the molecular mechanism.

Results: We found that miR-322 knockout mice were susceptible to AngII-induced cardiac fibrosis and hypertrophy in vivo. Administration of miR-424/322 inhibitors aggravated AngII-induced overexpression of NFATc3, furin, natriuretic peptides and collagen 1A1 in H9c2 cells and HCFs. miR-424/322 mimics reversed the AngII-induced fibrosis, hypertrophy, and proliferation by targeting NFATc3 and furin in vitro. miR-424/322 could be transactivated by NFATc3. Exogenous miR-322 ameliorated AngII-induced hypertrophy and cardiac fibrosis in vivo.

Conclusions: The NFATc3/miR-424/322/furin axis is crucial for developing cardiac remodeling, and exogenous miR-322 mimics could have therapeutic potential in cardiac remodeling.

Background: Hidradenitis suppurativa (HS) and migraine share common inflammatory pathways and neuropsychological implications. Both conditions involve proinflammatory cytokines like tumor necrosis factor and are associated with psychological comorbidities. Despite these similarities, the association between HS and migraine remained unclear. This study aimed to evaluate the relation between HS and incident migraine.

Materials and methods: We conducted a multicenter cohort study using the TriNetX Research Network. Patients diagnosed with HS between January 1, 2005 and December 31, 2022 were identified with a control group of non-HS subjects established by propensity score matching at a 1:1 ratio. Our outcome was the hazard ratio (HR) of incident migraine in relation to HS. We also examined the HR for various subtypes of migraine. We conducted stratified analyses based on age, gender, insomnia, depression, and anxiety subgroups. Sensitivity analyses were performed to strengthen the robustness of our analysis.

Results: The HS group exhibited an increased risk of incident migraine compared to controls (HR 1.35, 95% confidence interval (CI) 1.28-1.42). Also, HS patients had increased risk of migraine with aura and migraine without aura than controls, with HR being 1.36 (95% CI 1.21-1.52), 1.36 (95% CI 1.20-1.45), respectively. Female HS patients demonstrated an increased risk of incident migraine compared to their controls (HR 1.38, 95% CI 1.30-1.45). Elevated risk of incident migraine was observed in both younger and older HS patients when compared to their respective controls. The increased risk of incident migraine among HS patients remained consistent across various sensitivity analyses.

Conclusions: HS patients present with an increased risk of incident migraine. Physicians should be aware of this association and provide timely referral and interventions when appropriate.

Despite advancements in medical care, surgical technologies, and the development of novel treatments over the past decade, the prognosis for patients with gastric cancer (GC) has only modestly improved. This is primarily due to the fact that the majority of patients are diagnosed at advanced stages or present with metastatic disease. Radical resection remains the cornerstone of potentially curative treatment, yet the overall 5-year survival rate remains below 35%. The management of GC varies globally, influenced by factors such as geographical disparities, patient comorbidities and performance status, surgical approaches, and available medical resources. Multidisciplinary collaboration and a multimodal treatment approach are essential for optimizing patient outcomes. Surgeons must stay updated on emerging surgical concepts and make informed decisions regarding patient selection, timing of intervention, and the adoption of appropriate surgical techniques to improve both quality of life and prognosis. This review aims to provide a surgical perspective on the management of GC across all stages, highlighting the importance of a comprehensive treatment approach. Endoscopic resection may be a viable option for early GC in patients with minimal risk of lymph node metastasis, particularly in elderly patients with high surgical risk or severe comorbidities. For advanced GC, neoadjuvant therapy followed by surgery could be a promising strategy to improve patient outcomes. Conversion surgery offers a potential survival benefit for patients who respond to treatment with tumor downstaging. The treatment of peritoneal carcinomatosis remains challenging; however, hyperthermic intraperitoneal chemotherapy combined with complete cytoreductive surgery or pressurized intraperitoneal aerosolized chemotherapy may prolong survival or improve quality of life in highly selected patients.

Hepatocellular carcinoma (HCC) ranks the sixth most common malignancy but the third leading cause of cancer-related mortality in the world. Significant breakthroughs have been made in systemic treatment for HCC over the past two decades, which have improved treatment outcomes. In addition to multiple tyrosine kinase inhibitors (mTKIs), immune checkpoint inhibitors (ICIs) and antiangiogenic drugs are increasingly being applied. The combination of ICI and antiangiogenic or dual ICIs has become the new standard of care due to remarkable response rates. However, currently available systemic regimens are primarily reserved for certain patients in the intermediate and advanced stages who will not benefit from locoregional treatments. Evidence supporting the use of systemic treatment as neoadjuvant or adjuvant therapies in patients with early-stage HCC, especially the high risk of recurrence after curative treatments, remains limited. This review identified recent developments in systemic therapy, including mTKIs and ICIs, considering results on first- and second-line treatment, role of neoadjuvant and adjuvant settings, and combination with loco-regional therapy. Various ongoing clinical trials regarding the role of systemic therapies and potential novel targets in patients with early-, intermediate-, and advanced-stage HCC were also summarized and revealed that systemic therapy is no longer limited to advanced-stage HCC. Moreover, the introduction of T-cell redirecting strategies, including bispecific antibodies and chimeric antigen receptor T cells, has revolutionized the treatment landscape for HCC. Future research should focus on an in-depth exploration of the mechanisms governing the establishment of tumor barriers.

Background: CISD-1 is a mitochondrial iron-sulfate [2Fe-2S] protein known to be associated with various human diseases, including cancer and diabetes. Previously, we demonstrated that CISD-1 deficiency in worms lowers glucose and ATP levels. In this study, we further explored how worms compensate for lower ATP levels by analyzing changes in cytoplasmic and mitochondrial iron content, AMPK activities, and total lipid profiles.

Materials and methods: Expression levels of CISD-1 and CISD-1::GFP fusion proteins in wild-type worms (N2), cisd-1-deletion mutants (tm4993 and syb923) and GFP insertion transgenic worms (PHX953 and SJL40) were examined by western blot. Fluorescence microscopy analyzed CISD-1::GFP pattern in PHX953 embryos and adults, and lipid droplet sizes in N2, cisd-1, aak-2 and aak-2;cisd-1 worms. Total and mitochondrial iron content, electron transport complex profiles, and AMPK activity were investigated in tm4993 and syb923 mutants. mRNA levels of mitochondrial β-oxidation genes, acs-2, cpt-5, and ech-1, were quantified by RT-qPCR in various genetic worm strains. Lipidomic analyses were performed in N2 and cisd-1(tm4993) worms.

Results: Defects in cisd-1 lead to an imbalance in iron transport and cause proton leak, resulting in lower ATP production by interrupting the mitochondrial electron transport chain. We identified a signaling pathway that links ATP deficiency-induced AMPK (AMP activated protein kinase) activation to the expression of genes that facilitate lipolysis via β-oxidation.

Conclusion: Our data provide a functional coordination between CISD-1 and AMPK constitutes a mitochondrial bioenergetics quality control mechanism that provides compensatory energy resources.

Cell-to-cell communication is a major process for accommodating cell functioning to changes in the environments and to preserve tissue and organism homeostasis. It is achieved by different mechanisms characterized by the origin of the message, the molecular nature of the messenger, its speed of action and its reach. Purinergic signalling is a powerful mechanism initiated by extracellular nucleotides, such as ATP, acting on plasma membrane purinoreceptors. Purinergic signalling is tightly controlled in time and space by the action of ectonucleotidases. Recent studies have highlighted the critical role of purinergic signalling in controlling the generation, release and fate of extracellular vesicles and, in this way, mediating long-distance responses. Most of these discoveries have been made in immune and cancer cells. This review is aimed at establishing the current knowledge on the way which purinoreceptors control extracellular vesicle-mediated communications and consequences for recipient cells.

The electromagnetic characteristics of many environments have changed significantly in recent decades. This is in large part due to the increased presence of equipment that emits electromagnetic radiation and materials that may often readily gain excess charge. The presence of excess charge can often increase risk of infection from pathogens, and likelihood of individuals experiencing compromised performance, respiratory problems and other adverse health issues from increased uptake of particulate matter. It is proposed that adopting improved electromagnetic hygiene measures, including optimized humidity levels, to reduce the presence of inappropriate levels of electric charge can help reduce the likelihood of ill health, infection and poor performance arising from contaminant inhalation and deposition, plus reduce the likelihood of medical devices and other electronic devices getting damaged and/or having their data compromised. It is suggested that such measures should be more widely adopted within clinical practice guidelines and water, sanitation and hygiene programs.

Background: Recently, as a relatively novel technology, artificial intelligence (especially in the deep learning fields) has received more and more attention from researchers and has successfully been applied to many biomedical domains. Nonetheless, just a few research works use deep learning skills to predict the cardiac resynchronization therapy (CRT)-response of heart failure patients.

Objective: We try to use the deep learning-based technique to construct a model which is used to predict the CRT response of patients with high prediction accuracy, precision, and sensitivity.

Methods: Using two-dimensional echocardiographic strain traces from 131 patients, we pre-processed the data and synthesized 2,000 model inputs through the synthetic minority oversampling technique (SMOTE). These inputs trained and optimized deep neural networks (DNN) and one-dimensional convolution neural networks (1D-CNN). Visualization of prediction results was performed using t-distributed stochastic neighbor embedding (t-SNE), and model performance was evaluated using accuracy, precision, sensitivity, F1 score, and specificity. Variable importance was assessed using Shapley additive explanations (SHAP) analysis.

Results: Both the optimal DNN and 1D-CNN models demonstrated exceptional predictive performance, with prediction accuracy, precision, and sensitivity all around 90%. Furthermore, the area under the receiver operating characteristic curve (AUROC) of the optimal 1D-CNN and DNN models achieved 0.8734 and 0.9217, respectively. Crucially, the most significant input variables for both models align well with clinical experience, further corroborating their robustness and applicability in real-world settings.

Conclusions: We believe that both the DL models could be an auxiliary to help in treatment response prediction for doctors because of the excellent prediction performance and the convenience of obtaining input data to predict the CRT response of patients clinically.

Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2-13C]pyruvate and [1-13C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.