Taraxasterol exhibits dual biological effects on anti-aging and anti-cancer in lung cells.

As numerous countries around the world have entered an aging society currently, understanding the impact of aging on human health becomes critically important. Notably, aging is associated with increased prevalence of age-related diseases, with the lungs being particularly susceptible. Aging contributes to a decline in lung function, including respiratory disorders, inflammation, and oxidative stress. Therefore, it is a very important to identify and develop active substances that can mitigate lung cell aging. In current study, we evaluated the impact of Taraxasterol on lung cell senescence, showing that Taraxasterol can alleviate lung cell senescence, as evidenced by reductions in senescence-related marker molecules, including p16 and p21. Additionally, Taraxasterol was found to ameliorate inflammation and oxidative stress in lung cells. Further mechanistic studies indicated that Taraxasterol exerts anti-aging effects through the PGC1α/NRF1 signaling pathway in lung cell models. Since aging is also closely related to lung cancer, we also explored the potential anti-tumor effect of taraxasterol. Utilizing non-small cell lung cancer cells (NSCLC) as a model, we systematically study the anti-tumor effect of Taraxasterol both in vivo and in vitro. Our findings suggest that Taraxasterol exhibited anti-cancer effect through EGFR-mediated signaling. Taken together, Taraxasterol shows dual biological activities, offering promising anti-aging and anti-lung cancer benefits.

Microvesicles from quiescent and TGF-ß1 stimulated hepatic stellate cells: Divergent impact on hepatic vascular injury.

BACKGROUND: This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-ß1 stimulated hepatic stellate cells (HSC-MVs, TGF-ß1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury. METHODS: HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-ß1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-ß1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. RESULTS: In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-ß1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-ß1HSC-MVs demonstrated opposite effects. CONCLUSION: HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-ß1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.

TBBPS caused necroptosis and inflammation in hepatocytes by blocking PINK1-PARKIN-mediated mitochondrial autophagy.

The widespread use of Tetrabromobisphenol S (TBBPS), as an alternative to tetrabromobisphenol A (TBBPA), has been detected at high frequency in environmental media in recent years, TBBPS can enter the body via the digestive tract and other routes, thus long-term TBBPS exposure may cause adverse health effects. Therefore, it is necessary to evaluate the toxicological effects of TBBPS. In the current work, two cell models of the liver were used (a human-derived cell line THLE-2 and a murine-derived AML12). The liver cells were then exposed to different concentrations of TBBPS. The results of cell proliferation assays showed that TBBPS resulted in a significant attenuation of the proliferative capacity of liver cells. Further results from ELISA and Western-blot assays showed that TBBPS induced an inflammatory response in liver cells by detecting the levels of inflammatory factors, such as TNFα, IL-1ß and IL-6. We also found that TBBPS promoted the necroptosis in liver cells by evaluating the levels of RIP3 and pMLKL, and the use of inhibitors of necroptosis confirmed that the type of cell death induced by TBBPS belongs to necroptosis. Molecular mechanistic studies showed that TBBPS suppressed mitochondrial autophagy mediated by the PINK1-PARKIN signaling pathway, which led to accumulation of damaged mitochondria in THLE-2 and AML12 cells. Subsequently, accumulated ROS activated necroptosis of liver cells. Current toxicological studies suggest that we need to better control and regulate the production and use of TBBPS, the current work provide a reference for studying the toxicology of TBBPS.

Dietary Ochratoxin A Contamination Modulates Oxidative Stress, Inflammation Processes and Causes Fibrosis in in vitro and in vivo Lung Models.

BACKGROUND: The prevalence of aging-related diseases has increased significantly and this imposes a burden on both families and society. The lung is one of the few internal organs that is continuously exposed to the external environment, and lung aging is associated with a number of lung diseases. Ochratoxin A (OTA) is a toxin that is widely present in food and the environment but an effect for OTA on lung aging has not been reported. METHODS: Using both cultured lung cell and in vivo model systems, we studied the effect of OTA on lung cell senescence using flow cytometry, indirect immunofluorescence, western blotting, and immunohistochemistry. RESULTS: Results obtained showed that OTA caused significant lung cell senescence in cultured cells. Furthermore, using in vivo models, results showed that OTA caused lung aging and aging fibrosis. Mechanistic analysis showed that OTA upregulated the levels of inflammation and oxidative stress, and that this may be the molecular basis of OTA-induced lung aging. CONCLUSIONS: Taken together, these findings indicate that OTA causes significant aging damage to the lung, which lays an important foundation for the prevention and treatment of lung aging.

Dual-Site Doping Strategy for Enhancing the Structural Stability of Lithium-Rich Layered Oxides.

Lithium-rich layered oxide (LLO) cathode materials are considered to be one of the most promising next-generation candidates of cathode materials for lithium-ion batteries due to their high specific capacity. However, some inherent defects of LLOs hinder their practical application due to the oxygen loss and structure collapse resulting from intrinsic anion and cation redox reactions, such as poor cycle stability, sluggish Li+ kinetics, and voltage decay. Herein, we put forward a facile synergistic strategy to respond to these shortcomings of LLOs via dual-site doping with cerium (Ce) and boron (B) ions. The doped Ce ions occupy the octahedral sites, which not only enlarge the cell volume but also stabilize the layered framework and introduce abundant oxygen vacancies for LLOs, while B ions occupy the tetrahedral sites in the lattice, which block the migration path of transition metal (TM) ions and reduce the oxygen loss using the strong B-O bond. Based on this dual-site doping effect, after 100 cycles at 1 C, the dual-site doped materials exhibit excellent structural stability with a capacity retention of 91.15% (vs 75.12%) and also greatly suppress the voltage decay in LLOs with a voltage retention of 93.60% (vs 87.83%).

Video-assisted thoracoscopic pneumonectomy: the anterior approach.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy is now a well-accepted way to perform a minimally invasive lobectomy. VATS lobectomy is different from the conventional surgery. Different incisions, instruments and camera positions have also been described in the past two decades. There are no fixed patterns in VATS lobectomy. We here describe our method for fissure-based VATS lobectomy using an anterior approach. The aim of this paper is to show our technique for VATS lobectomy and our experience and outcomes obtained. METHODS: A 57-year-old man, who was admitted to the Affiliated Hospital of the Guangdong Medical College, had coughing up blood tinged sputum, right chest pain for one month. Thoracic CT imaging revealed a 22 mm × 22 mm × 20 mm, T1bN1M0 lesion in the right lower lobe. The patient for clinical stage II non-small cell lung cancer underwent VATS lobectomy by using an anterior approach on January 2013. RESULTS: Total volume of chest tube drainage after operation was 450 mL, intraoperative blood loss was 80 mL, operation time was 105.8 min, chest tube duration was three days, length of postoperative hospital stay was eight days. Follow-up no recurrence and metastasis for six months. CONCLUSIONS: The main advantages of the anterior approach in our experience are easy to deal with the absence or incomplete fissure by the "tunneling" approach. In addition, the mediastinal node packets are clearly seen, allowing thorough lymphadenectomy. Therefore, VATS lobectomy by the anterior approach is a safe, feasible procedure.