Journal of Biomedical Research最新文献

Ionizing radiation is a popular and effective treatment option for glioblastoma (GBM). However, resistance to radiation therapy inevitably occurs during treatment. It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity. Here, we found that heat shock protein 90 beta family member 1 (HSP90B1) was significantly upregulated in radioresistant GBM cell lines. More importantly, HSP90B1 promoted the localization of glucose transporter type 1, a key rate-limiting factor of glycolysis, on the plasma membrane, which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells. These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients, a potential new approach to the treatment of glioblastoma.

Inconsistent findings have been reported regarding the associations between hypertensive disorders in pregnancy (HDP) and infant neurodevelopment. Leveraging data from the Jiangsu Birth Cohort, in the present study, we re-visited such associations in one-year-old infants from 2576 singleton pregnancies and 261 twin pregnancies. We first assessed infant neurodevelopment by the Bayley Scales of Infant and Toddler Development Screening Test (the Third Edition), and then estimated its association with maternal HDP using general linear regression models and Poisson regression models. In singleton pregnancies, compared with mothers unexposed to HDP, infants born to mothers with chronic hypertension exhibited a lower score ( β, -0.67; 95% confidence interval [CI], -1.19--0.15) and a higher risk of "non-optimal" gross motor development (risk ratio [RR], 2.21; 95% CI, 1.02-4.79); in twin pregnancies, infants born to mothers with HDP exhibited lower scores in cognition ( β, -0.49; 95% CI, -0.96--0.01), receptive communication ( β, -0.55; 95% CI, -1.03--0.06), and gross motor ( β, -0.44; 95% CI, -0.86--0.03), and at a higher risk of "non-optimal" gross motor development (RR, 2.12; 95% CI, 1.16-3.88). These findings indicate that infants born to mothers with HDP may have inferior neurodevelopment outcomes at the age of one year.

Scapular surgery has mainly been studied in the setting of fractures; regional anesthesia can be utilized as part of a multimodal analgesia regimen for postoperative pain relief. Previous studies are limited to scapular fracture pain. The available literature supports the use of various types of nerve blocks and even combinations of different blocks, of which the paravertebral nerve block is one such block that has been effective. We present a case of a patient undergoing excision of a scapular osteochondroma who received a single-shot paravertebral nerve block after surgery with an effective analgesia.

Hepatoblastoma is the most frequent liver malignancy in children. HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture. Intriguingly, we observed that the addition of calcium ions reduced cell clumping and disassociated HepG2 cells. The calcium signal is in connection with a series of processes critical in the tumorigenesis. Here, we demonstrated that extracellular calcium ions induced morphological changes and enhanced the epithelial-mesenchymal transition in HepG2 cells. Mechanistically, calcium ions promoted HepG2 proliferation and migration by up-regulating the phosphorylation levels of focal adhesion kinase (FAK), protein kinase B, and p38 mitogen-activated protein kinase. The inhibitor of FAK or Ca ²⁺/calmodulin-dependent kinase Ⅱ (CaMKⅡ) reversed the Ca ²⁺-induced effects on HepG2 cells, including cell proliferation and migration, epithelial-mesenchymal transition protein expression levels, and phosphorylation levels of FAK and protein kinase B. Moreover, calcium ions decreased HepG2 cells' sensitivity to cisplatin. Furthermore, we found that the expression levels of FAK and CaMKⅡ were increased in hepatoblastoma. The group with high expression levels of FAK and CaMKⅡ exhibited significantly lower ImmunoScore as well as CD8 ⁺ T and NK cells. The expression of CaMKⅡ was positively correlated with that of PDCD1 and LAG3. Correspondingly, the expression of FAK was negatively correlated with that of TNFSF9, TNFRSF4, and TNFRSF18. Collectively, extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMKⅡ and enhances cisplatin resistance. FAK and CaMKⅡ shape immune cell infiltration and responses in tumor microenvironments, thereby serving as potential targets for hepatoblastoma.

The role of reactive oxygen species (ROS) in ischemic and reperfusion (I/R) injury of the heart has been discussed for more than 40 years. It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart. Antioxidants were found to have the ability to mitigate I/R injury of the heart. However, it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues. Since high doses and high concentrations of antioxidants were experimentally used, it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules. It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning. Consequently, there is evidence that ROS protect the heart against the I/R injury.

The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon, also known as microvascular obstruction (MVO). However, studies performed in the isolated perfused hearts subjected to ischemia/reperfusion (I/R) do not suggest the involvement of microembolization and microthrombi in this phenomenon. The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction. Consequently, the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi, platelets, and neutrophils. Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries. However, reperfusion triggers more pronounced damage, possibly mediated by pyroptosis. MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling. Therefore, pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles. Ischemic conditioning protocols have been shown to prevent MVO, with L-type Ca ²⁺ channel blockers appearing the most effective in treating MVO.

Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis, which is associated with high morbidity and mortality. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), encoded by Hsd11b1, is a reductase that can convert inactive cortisone into metabolically active cortisol, but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood. The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide (LPS)-induced mouse model, in which LPS (10 mg/kg) was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice. We asscessed cardiac function by echocardiography, performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes, and determined the levels of reactive oxygen species and biomarkers of oxidative stress. We also employed polymerase chain reaction analysis, Western blotting, and immunofluorescent staining to determine the expression of related genes and proteins. To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction, we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes. We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury, oxidative stress, and inflammation, along with an improved myocardial function; furthermore, the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and silent information regulator 1 (SIRT1) protein levels both in vivo and in vitro. Therefore, the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.

Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database. We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis. Peroxisome and tumor necrosis factor-α (TNF-α) signaling and nuclear factor kappa B (NF-κB) were among the top 10 pathways, and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). We then constructed a competing endogenous RNA network, which is related to differentially expressed circRNAs. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was a common downstream event. The results of the current study may provide insights into the pathological processes of atrophic AMD.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial for improving prognosis and developing new targeted therapies. Accumulating evidence indicates that the integrated bone formation and dysfunction arise from complex interactions among a network of multiple cell types, including osteoblast-associated cells, immune cells, blood vessels, and lymphatic vessels. However, the role of these different cells in the inflammatory process and the 'rules' with which they interact are still not fully understood. Although many investigations have focused on specific pathological processes and molecular events in inflammatory jaw diseases, few articles offer a perspective of integration. Here, we review the changes and mechanisms of various cell types in inflammatory jaw diseases, with the hope of providing insights to drive future research in this field.