Biocell最新文献

Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellular matrix. These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture. In humans, the integrin family is composed of 18 alpha (α) and 8 beta (β) subunits, constituting 24 distinct αβ combinations. Based on their structure and ligand-binding properties, only a subset of integrins, 8 out of 24, recognizes the arginine-glycine-aspartate (RGD) tripeptide motif in the native ligand. One of the major RGD binding integrins is integrin alpha 8 beta 1 (α8β1), a central Ras homolog gene family member A (RHOA)-dependent modulator highly expressed in cells with contractile function. This review focuses on the recent advances regarding α8β1 function during organ development, with a particular interest in kidney and inner ear development. We also discuss α8β1's role in injury and disease and its importance for mesenchymal to epithelial transition during cancer development. Finally, we highlight α8β1's importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.

Neutrophil extracellular traps (NET) have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases (CVD). These web-like structures, composed of DNA, histones, and granule proteins released by neutrophils, contribute significantly to both inflammation and thrombosis. This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis, highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD. Notably, the impact of radiation on NET formation is explored, emphasising how oxidative stress and inflammatory responses drive NET release, contributing to plaque instability. The role of histones, particularly citrullinated histones, in endothelial dysfunction and plaque progression is discussed, highlighting their significance in the pathophysiology of atherosclerosis. Furthermore, the complex relationship between lipoproteins and NET formation is examined, with a focus on how elevated low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) levels facilitate NET release, thus promoting vascular inflammation and plaque instability. The influence of cholesterol on NET formation is also explored, underscoring its contribution to plaque development and stability. The role of Peptidylarginine deiminase 4 (PAD4) in the regulation of NETosis is reviewed, with attention given to how PAD4-driven citrullination of histones affects atherosclerosis progression. Moreover, the manuscript examines the potential of NET components-such as double-stranded DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3-as biomarkers for assessing disease severity and predicting adverse cardiovascular events, including ST-elevation myocardial infarction (STEMI) and stroke. Elevated levels of these biomarkers correlate with worse clinical outcomes, suggesting their utility in guiding therapeutic interventions. In contrast to the existing body of work, this review highlights the novelty of integrating recent findings on NET interactions with lipid metabolism, histone modifications, and PAD4 activity in the context of atherosclerosis. Overall, NET plays an integral role in the inflammatory and thrombotic processes underpinning atherosclerosis, and their components hold promise as both diagnostic markers and therapeutic targets in cardiovascular disease management.

Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation. Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses. The most prevalent chronic inflammatory illness, rheumatoid arthritis (RA), is typified by persistent synovitis that makes it hard for the disease to go away on its own. Interestingly, a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients' synovium, especially while the disease is in remission. Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts. The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review. Based on the role of regulatory eosinophils, a new pathological model of inflammation resolution in RA is proposed, and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.

Background: Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface.

Methods: To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites.

Results: BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α, Scf, and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua in vitro. While hypoxic conditions in vitro did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR.

Conclusion: In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.

Backgorund: Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells. This study evaluates the effect of A. montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation.

Methods: MTT assay was performed to determine the proliferation of cancer cells. Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis. Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A. montana leaves hexane extract.

Results: A. montana leaves hexane (sub-fraction V) blocked the constitutive stimulation of the PI3K/mTOR signaling pathways. This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNNEL) staining, activation of caspase-3, and cleavage of PPAR. It also limited the expression of various downstream genes that regulate proliferation, survival, metastasis, and angiogenesis (i.e., cyclin D1, survivin, COX-2, and VEGF). It increased the expression of p53 and p21. Interestingly, we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.

Conclusion: Our study indicates that A. montana leaves (sub-fraction V) extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.

Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen, leading to the accumulation of advanced glycation end-products (AGEs) cross-links in collagenous tissues. More recently, AGEs content has been related to loss of bone quality, independent of bone mass, and increased fracture risk with aging and diabetes. Loss of bone quality is mostly attributed to changes in material properties, structural organization, or cellular remodeling. Though all these factors play a role in bone fragility disease, some common recurring patterns can be found between diabetic and age-related bone fragility. The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation. This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales, collagen deformation mechanisms at the nanoscale, and resistance to bone fracture at the macroscale.