Advanced biology最新文献

Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality. This study investigates the cytotoxic effects of Euphorbia rigida extract on A549 NSCLC cells and its potential as a therapeutic agent. Cellular morphology was observed microscopically, and cell viability was evaluated using dose-dependent proliferation assays. Apoptosis-related gene expression—including Bax, Bcl-2, and Caspase-9—was analyzed via quantitative PCR (qPCR). Chromatographic methods identified bioactive flavonoids, and molecular docking assessed their binding to cancer-related proteins. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles were evaluated. The extract induced apoptotic morphological changes such as cell shrinkage and loss of intercellular contact. A dose-dependent reduction in A549 viability was observed, with an IC₅₀ of 0.5 mg mL⁻¹. Gene expression indicated activation of the intrinsic mitochondrial apoptotic pathway, with increased Bax and Caspase-9 and decreased Bcl-2 expression. Flow cytometry using Annexin V-allophycocyanin (V-APC) staining revealed selective cytotoxicity: significant apoptosis in A549 cells while preserving viability in BEAS-2B normal lung epithelial cells. Identified flavonoids included quercetin, apigenin, and myricetin, which showed strong binding affinities in docking studies. ADMET profiling supported their drug-likeness. These findings highlight E. rigida potential in NSCLC treatment via apoptosis induction and selective cytotoxicity.

Guilongwan (GLW), a representative of traditional Chinese Medicine (TCM) has been utilized to treating diabetic foot ulcer (DFU)-related syndrome including an intolerance of cold with cold limbs, blood circulation disorder, and immune dysfunction for decades. However, the chemical and biological mechanisms of GLW remain unclear. This study aims to discover the biological mechanisms of GLW on DFU by using streptozotocin- and skin-puncher-induced DFU rat models, in vitro macrophage models, and in silico analysis. The alterations in pathology, Notch1 signaling, and macrophage polarization are detected. The results indicated that GLW promoted wound healing, cutaneous cell proliferation, and angiogenesis in DFU rats by inhibiting delta-like (DLL) 4/Notch1 signaling. In addition, GLW inhibited M1 polarization and promoted M2 polarization in diabetic wounds. Seventeen chemical compounds in GLW-medicated serum are identified. In silico analysis and in vitro experiments demonstrated that GLW-medicated serum and its main compounds inhibited the expression of DLL4 in matrix metalloproteinase-9-induced M1 macrophages. In conclusion, GLW ameliorated experimental DFU rats via the inhibition of DLL4/Notch1 signaling in M1 macrophages. This study provided a new biologic mechanism for GLW in the treatment of DFU.

Scaling Up Synthetic Cell Production

Where biology meets technology: synthetic cells generated under machine learning guidance using robotic arms. This image captures the leap toward efficient, scalable, and precise synthetic cell production for therapeutic applications. More details can be found in article number 2400671 by Noga Sharf-Pauker, Avi Schroeder, Shanny Ackerman, and co-workers.

Artificial Biology – Assemble, Imitate, Adapt

The cover highlights the interdisciplinary character of bottom-up synthetic biology (artificial biology), where artificial cells are (self-)assembled from natural and synthetic components. It showcases the design and construction of cell-like systems that mimic key features of life, including motility, encapsulated catalysis, and compartmentalization, reflecting advances at the interface of chemistry, molecular biology, and nanoscience. More details can be found in the editorial number 2500236 by Brigitte Städler and co-workers. Image credit: Dr. Miguel Alexandre Ramos Docampo, Interdisciplinary Nanoscience Center (iNANO), Aarhus University.

Renal tubular epithelial cell injury is a significant factor in the formation of kidney stones. However, the regulatory mechanisms behind this injury, especially the association with autophagy-mediated ferroptosis, remain unclear. This study first identified the upregulated ferroptosis related gene ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 (CHAC1) in kidney stone samples through bioinformatics analysis. Subsequently, a damage model is established by treating renal tubular epithelial cells (HK-2) cells with calcium oxalate (CaOx) and investigated its function by downregulating CHAC1 expression through shRNA transfection. Autophagy status and oxidative stress are evaluated by detecting autophagy (LC3I, LC3II, Beclin 1) and ferroptosis (GPX4) related protein expression using GFP-LC3 adenovirus and Western Blot. In addition, the interaction between small molecule drug Paliperidone (Pali) and CHAC1 is also investigated through molecular docking and cell thermal migration assays to explore therapeutic potential. CHAC1 is upregulated in kidney stones and associated with ferroptosis. Knockdown of CHAC1 weakened CaOx-induced autophagy and ferroptosis. Moreover, Pali can target CHAC1 protein, reduce CHAC1 activity, and inhibit autophagy-mediated ferroptosis during cellular injury. Pali can inhibit autophagy-mediated ferroptosis in renal tubular epithelial cells by targeting CHAC1, offering a new direction for the treatment of kidney stones.

Magnesium phosphate cement (MPC) continues to gain attention in the field of biomedicine. However, its suboptimal mechanical strength and weak biological activity hinder its wider clinical application. Given the excellent biological characteristics of bioglass fiber (BGF), In this study, magnesium phosphate bone cement (BMPC) containing MPC and BGF with different concentrations (0%, 10%, 20%) are fabricated. Called (MPC, 10BMPC, 20BMPC) respectively. BGF-induced mechanical strengthening is verified through physical and chemical performance tests. In vitro experiments showed that BMPC have better osteogenic properties than MPC and can enhance the proliferation and adhesion capacity of human umbilical vein endothelial cells. In vivo experiment, 20BMPC can significantly promote bone regeneration and vascular network formation, and histological analysis further confirmed the osteogenic capacity of 20BMPC. Transcriptomic analyses confirmed that the activities of the Notch pathway and Hif1 pathway are upregulated in the 20BMPC group, reflecting the strong interconnection between osteogenesis and angiogenesis. 20BMPC, which have the highest BGF content, showed the best performance among all the tested materials. This study showed that BGF improved the mechanical strength of bone cement and enhanced its osteogenic and angiogenic abilities. Therefore, 20BMPC can be used as a new bone repair material.

Influenza A

Mucus serves as a physical and adhesive barrier to infectious agents in the lung. The article number 2400329 by Gregg A. Duncan and co-workers demonstrates how the penetration of flu virus through the mucus barrier is significantly limited by the gel's internal microstructure and, to a lesser extent, by adhesive binding to mucin glycans.

3D Confinement Regulates Muscle Stem Cell Fate

In this study a 3D hydrogel bilayer platform is developed that mimics the regenerating muscle stem cell (MuSC) niche by modulating confinement and stiffness. Increased 3D confinement preserves MuSC stemness, limiting activation, proliferation, and differentiation. Findings suggest mechanical cues act as a “brake” on myogenic commitment through nuclear and epigenetic regulation. More details can be found in article number 2400717 by Woojin M. Han and co-workers.

Aortic valve stenosis (AVS) is characterized by altered mechanics of the valve leaflets, which disrupts blood flow through the aorta and can cause left ventricle hypotrophy. These changes in the valve tissue result in the activation of resident valvular interstitial cells (VICs) into myofibroblasts, which have increased levels of αSMA in their stress fibers. The persistence of VIC myofibroblast activation is a hallmark of AVS. In recent years, the tumor suppressor gene phosphatase and tensin homolog (PTEN) has emerged as an important player in the regulation of fibrosis in various tissues (e.g., lung, skin), which motivated to investigate PTEN as a potential protective factor against matrix-induced myofibroblast activation in VICs. In aortic valve samples from humans, high levels of PTEN are found in healthy tissue and low levels of PTEN in diseased tissue. Then, using pharmacological inducers to treat VIC cultures, it is observed that PTEN overexpression prevented stiffness-induced myofibroblast activation, whereas genetic and pharmacological inhibition of PTEN further activated myofibroblasts. The increased nuclear PTEN localization is also observed in VICs cultured on stiff matrices, and nuclear PTEN also correlated with smaller nuclei, altered expression of histones, and a quiescent fibroblast phenotype. Together, these results suggest that PTEN not only suppresses VIC activation, but functions to promote quiescence, and can serve as a potential pharmacological target for the treatment of AVS.