Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target.

Background: Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs.

Methods: Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels.

Noninvasive assessment of liver fibrosis in mini pigs using an F-AlF-NOTA-RGD2 PET/CT molecular probe.

To evaluate the efficacy of the 18F-AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F-AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment.

Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation.

Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytic/signaling cell-surface receptor that regulates diverse cellular functions, including cell survival, differentiation, and proliferation. LRP1 has been previously implicated in the pathogenesis of neurodegenerative disorders, but there are inconsistencies in its functions. Therefore, whether and how LRP1 maintains brain homeostasis remains to be clarified.

Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets.

Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target.

[Effect of 2 Gene Silencing on Mouse Macrophage Resistance Against Infection via TLR Pathway].

Objective: To investigate the effect of silencing protein phosphatase 2cm ( 2) gene on the expression of inflammatory factors in macrophages infected with ( . ) and the mechanisms involved.

Methods: The effects of 2 knockdown on inflammatory factors, proliferation, apoptosis, and Toll-like receptor (TLR) signaling were analyzed in RAW 264.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence.

Obesity Enables NLRP3 Activation and Induces Myocardial Fibrosis via Hyperacetylation of HADHa.

Obesity increases the risk of myocardial fibrosis, a pathological change in most heart diseases, but the mechanism has not been fully elucidated. Here, we found that mice with high-fat diet-induced obesity had more severe myocardial fibrosis than control mice under normal and ischemia/reperfusion (I/R) conditions, which could be alleviated by neutralizing antibodies against interleukin (IL)-1β and IL-18, downstream products of the nucleotide-binding oligomerization-like receptor protein 3 (NLRP3) inflammasome, and the NLRP3 inhibitor MCC950. Mechanistically, mitochondrial hyperacetylation in obese mouse hearts recruited apoptosis-associated speck-like protein containing a CARD (ASC) to mitochondria and thus facilitated NLRP3 inflammasome assembly.

Upper-critical solution temperature (UCST) polymer functionalized nanomedicine for controlled drug release and hypoxia alleviation in hepatocellular carcinoma therapy.

Recently, bioinspired material such as nanoparticle has been successfully applied in the cancer therapy. However, how to precisely control the drug release from nanomedicine in tumor tissue and overcome the hypoxic microenvironment of tumor tissue is still an important challenge in the development of nanomedicine. In this work, a new type of drug-loaded nanoparticles P(AAm-co-AN)-AuNRs@CeO2-DOX (PA-DOX) was prepared by combining high-efficiency photothermal reagents, critical up-conversion temperature polymer layer and anti-cancer drug doxorubicin (DOX) for the treatment of hepatocellular carcinoma (HCC).

Circulating metabolic signatures of heart failure in precision cardiology.

Precision cardiology aims to implement personalized health care and precise medical decisions based on the specific characteristics of individuals. Metabolic remodeling plays a causal role in the pathogenesis of heart failure (HF). Changes in metabolic pathways such as substrate preference, high-energy phosphate metabolism and amino acid metabolism, are involved in pathological structural remodeling and functional impairment.

Nanomedicine-Based Therapeutics for Myocardial Ischemic/Reperfusion Injury.

Myocardial ischemic/reperfusion (IR) injury is a global cardiovascular disease with high mortality and morbidity. Therapeutic interventions for myocardial ischemia involve restoring the occluded coronary artery. However, reactive oxygen species (ROS) inevitably impair the cardiomyocytes during the ischemic and reperfusion phases.

Gold-based nanoparticles realize photothermal and photodynamic synergistic treatment of liver cancer and improve the anaerobic tumor microenvironment under near-infrared light.

In order to solve the different pains caused by traditional cancer treatment methods such as surgical treatment, the nano-drug delivery system provides new ideas for cancer treatment. In this paper, a novel anti-tumor therapy nanoparticle, P(AAm-co-AN)-AuNRs@CeO-Ce6(PA/Ce6), is prepared, which provides a novel idea for liver cancer treatment. The CeO-coated gold nanorods were grafted onto the surface of the temperature-sensitive polymer P(AAm-co-AN)-CTPD.

Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate-glutamine cycle and reduces sensitivity to sevoflurane in mice.

Background: Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood.

Methods: Mice were acclimated to hypoxia (oxygen 10% for 8 h day) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined.

Ketone Body -Hydroxybutyrate Prevents Myocardial Oxidative Stress in Septic Cardiomyopathy.

Septic cardiomyopathy is a life-threatening complication of severe sepsis and septic shock. Oxidative stress and mitochondrial dysfunction have been identified as significant abnormalities in septic cardiomyopathy. However, specific treatments are rare.

Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice.

Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction (HFrEF). The prevalence of HFpEF continues to increase, while the pathogenic mechanisms underlying HFpEF remain largely elusive and evidence-based therapies are still lacking. This study was designed to investigate the metabolic signature of HFpEF and test the potential therapeutic intervention in a mouse model.

Tumor-Targeting Multifunctional Nanoprobe for Enhanced Photothermal/Photodynamic Therapy of Liver Cancer.

Numerous researchers have committed to the development of combined therapy strategies for tumors, since their use in the treatment of tumors has more ideal therapeutic outcomes. In the study, we designed and prepared gold nanostars with CD147 modified on the surface and then efficiently loaded a photosensitive drug IR820 to construct a multifunctional nanoprobe. Due to the protection effect of gold, the nanoprobe has oxygen/heat energy generation capability and can also efficiently deliver the loaded drugs inside the tumor cells.

Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation.

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain to be elucidated.

Ultra-small gold nanoparticles self-assembled by gadolinium ions for enhanced photothermal/photodynamic liver cancer therapy.

Gold nanomaterials are widely used in biomedical research as drug delivery systems, imaging agents and therapeutic materials owing to their unique physicochemical properties and high biocompatibility. In this study, we prepared ultra-small gold nanoparticles (AuNPs) and induced them with gadolinium ions to form a spherical self-assembly. The nanoparticles were coupled with matrix metalloproteinase-2 (MMP-2) and loaded with the photosensitive drug IR820 for photothermal/photodynamic combination therapy of liver cancer.

Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF.

Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF.

Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model.

Chronic Alcohol Intake Exacerbates Cardiac Dysfunction After Myocardial Infarction.

Aims: Alcohol intake is a risk factor for cardiovascular diseases. This study was designed to investigate whether chronic alcohol intake affects myocardial infarction (MI)-induced cardiac remodeling and heart failure.

Methods: Eight-week-old male C57BL/6 mice were randomly divided into four groups: Sham group (Sham), MI plus drinking water group (MI + Vehicle), and MI plus daily alcohol intake for 6 weeks with or without gavage of additional alcohol every 3 days (MI + Alcohol and MI + Alcohol + G).