Advanced biology最新文献

While aging is a natural biological process, it is associated with a greater risk for multiple diseases, including cancer, neurodegeneration, and cardiovascular disease. Thus, it is important to study the biochemical mechanisms involved in aging to understand how to treat and prevent these health conditions. The discovery that calorie restriction (CR) promoted longevity in various organisms is a major breakthrough for aging research. Molecular studies of CR have revealed that it mediates its anti-aging effects by activating key signaling pathways, including the AMPK pathway. This pathway is important for regulating various processes, including energy homeostasis, metabolism, and proteostasis. Despite the advantages associated with CR, this practice can have detrimental effects, including decreased liver, body, and muscle mass. Additionally, CR is difficult to track and maintain, limiting its long-term potential. Interestingly, direct activation of the AMPK pathway offers a potential approach to increase longevity and quality of life without dietary restrictions. Remarkably, a recent discovery revealed that lithocholic acid (LCA), a metabolite from bile acid, could directly activate the AMPK pathway. Activation of the AMPK pathway by LCA leads to the beneficial effects of CR without the negative effects. These recent findings point to the possibility that supplementation of specific doses of LCA could offer a novel approach to induce anti-aging pathways that lead to increased longevity and improved quality of life.

This study examined the effectiveness of a combined model using non-contrast computed tomography (NCCT) imaging, clinical data, and radiomics for predicting early hematoma enlargement in patients with spontaneous intracerebral hemorrhage. The study involved 232 patients with primary cerebral hemorrhage who met the inclusion criteria at the General Hospital of the Western Theater Command, PLA, between January 2018 and December 2023. Imaging and clinical features were compared, radiomic features were extracted from head CT scans, and a multivariate logistic regression model identified key imaging markers and clinical features. Univariate and multivariate logistic regression models were used for dimensionality reduction of radiomic features and to develop a radiomic signature/model. Patients were split into training and validation sets in a 7:3 ratio. Then, NCCT, clinical, radiomics, and combined NCCT-clinical-radiomics models were built, along with a nomogram. The AUC values for hematoma expansion prediction were as follows in the training set: NCCT model (0.758), clinical model (0.742), radiomics model (0.779), and combined model (0.872). In the validation set, the AUCs were: NCCT model (0.853), clinical model (0.754), radiomics model (0.778), and combined model (0.905). Calibration and decision curve analysis further confirmed the superior clinical utility of the combined model over the individual models. In conclusion, the combined NCCT-clinical-radiomics model significantly outperformed the individual models, leading to improved predictive accuracy, stability, and generalizability.

Cardiac Aging

A combination of endurance and resistance exercises can mitigate age-related pathological changes in the heart in late life, such as cardiac remodeling and dysfunction. These beneficial effects on the heart are likely attributed to the activation of the anti-aging factor, Usf 2. More details can be found in article number 2400137 by Wanling Xuan and co-workers.

In eukaryotic cell nuclei, chromatin exhibits a high degree of structural and functional dynamics. Recent findings suggest that chromatin has the ability to reorganize in response to changes within the cellular microenvironment. Such changes include oxidative stress found in hyperoxia. While hyperoxia is recognized for causing DNA damage and disrupting cellular functions, the effects it has on chromatin structure and the implications thereof remain poorly understood. In this work, an imaging-based technique is developed to visualize and characterize nanoscale chromatin remodeling under hyperoxia in mesenchymal stromal cells, created via hydrogen peroxide treatment. High spatiotemporal variability of remodeling in different chromatin domains is found. Chromatin remodeling is hindered by the GSK126-mediated inhibition of methyltransferase EZH2, which regulates the chromatin compaction. Independent assays such as ATAC seq further revealed that chromatin is compacted by hyperoxia, which is mitigated by GSK126 pretreatment. Epigenetic modifications and DNA damage under hyperoxia is investigated, which is also found to be affected by the pretreatment of GSK126. The techniques and discoveries provide mechanistic insights into chromatin remodeling, potentially paving the way for novel therapeutic strategies to combat genotoxic oxidative stress—commonly associated with degenerative diseases and aging—and to enhance cell-based therapies in regenerative medicine.

Apolipoprotein A-I binding protein (AIBP) interacts with both apolipoprotein A-I and high-density lipoprotein. It modulates lipid raft-related signaling pathways and affects mitochondrial function, oxidative stress, and inflammatory responses, thereby playing an important role in atherosclerosis, neuroinflammation, and neurological disorders. The role of AIBP in cardiovascular diseases has been intensively studied. Nevertheless, recent studies have uncovered correlations between NAD(P)HX differential isomerase variants and various neurological disorders, further highlighting their substantial role in neurological diseases. This review outlines the current investigations on AIBP in neurometabolic diseases, neurodegenerative diseases, and neuropathic pain. The present advances are also updated in the function and regulation of AIBP in cholesterol metabolic and inflammatory signaling and explored the potential of AIBP as a promising strategy and target for neurological disorders.

Hirschsprung-associated enterocolitis (HAEC) is the most common and severe complication in patients with Hirschsprung's disease (HSCR) and is characterized by high morbidity, frequent recurrence and substantial mortality. The formation of macrophage extracellular traps (METs), a novel inflammatory mode of cell death, plays a significant role in the progression of various inflammatory diseases. However, the mechanisms underlying METs formation and their role in the progression of HAEC remain unclear. Here, the findings indicate that METs formation induced by the pyroptotic microenvironment enhances inflammatory responses and induces colonic epithelial cells (CECs) injury in HAEC. Mechanistically, high mobility group box 1 protein (HMGB1), derived from this pyroptotic environment, mediates METs formation through toll-like receptor 4 (TLR4)-p38 MAPK/p65 NF-kB signaling pathways. Furthermore, incubation of CECs with METs induces suppression of cell viability, more production of reactive oxygen species (ROS) and pyroptosis. In conclusion, HMGB1 mediates the communication between pyroptotic microenvironment and METs formation, triggering enhanced inflammatory responses and damage to CECs. Targeting HMGB1 presents a potential therapeutic strategy for HAEC.

Protoplast regeneration into plant cells and further into plants is an ongoing challenge in agricultural biotechnology. Inspired by mammalian tissue engineering, a strategic shift is proposed in plant tissue engineering to steer protoplast culture using fully synthetic materials-based culture platforms. Here a supramolecular materials method to engineer modular culture methods for protoplasts is chosen to use. Supramolecular monomers as modular building blocks allow to make various hydrogel formulations and to study different protoplast cultures; including 2D cultures on top of supramolecular hydrogels, 2.5D cultures using supramolecular fibers in solution, and 3D cultures when encapsulated in bulk hydrogels or microgels. Importantly, the need is shown for bioactive functionalization of the supramolecular hydrogels with a peptide additive in 2D protoplast cultures. After 11 days, the bioactive hydrogel induced protoplast enlargement, which is absent on pristine hydrogels. The opposite effect is present for protoplasts cultured in 3D, showing plasmolysis as a result of the bioactive additive. Interestingly, in 2.5D lower bioactive additive concentrations in supramolecular fibers stimulated protoplast enlargement, demonstrated by similar morphological changes as in 2D. Finally, protoplast encapsulation in supramolecular microgels is showcased. This work demonstrates the potential to modularly engineer various synthetic platforms to facilitate cellular agriculture.

Head and neck squamous cell carcinoma (HNSCC) is characterized by a high recurrence rate and poor prognosis. Ferroptosis, a regulated cell death, plays a significant role in inhibiting tumor progression. However, its role and regulatory mechanisms in HNSCC remain unclear. In this study, the expression of ferroptosis-related molecules in HNSCC is analysed and NCOA4 and FTH1 are identified as prognostic markers. TU177 and TU686 cells are transfected with plasmids for the overexpression or knockdown of NCOA4 and FTH1. MTT assays demonstrated reduced cell viability following either NCOA4 overexpression or FTH1 knockdown alone. Concurrently, ferroptosis hallmarks such as iron overload and ROS overproduction are upregulated in these conditions. Conversely, NCOA4 knockdown or FTH1 overexpression has the opposite effects. Furthermore, miR-182-5p is found to be significantly upregulated in HNSCC tissues. Mechanistic studies revealed that miR-182-5p directly binding to the NCOA4 3′ UTR, leading to the downregulation of NCOA4 expression and suppression of NCOA4/FTH1-mediated ferroptosis. In conclusion, the finding elucidate the role of miR-182-5p/NCOA4/FTH1 signaling axis in regulating ferroptosis in HNSCC and provide insights into the molecular mechanism underlying ferroptosis in HNSCC cells.