Hyperbaric oxygen enhanced the chemotherapy of mitochondrial targeting molecule IR-780 in bladder cancer.

BACKGROUND: Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. MATERIAL AND METHODS: The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. RESULTS: IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. CONCLUSION: We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

Modified Qing'e Formula protects against UV-induced skin oxidative damage via the activation of Nrf2/ARE defensive pathway.

Exposure to ultraviolet (UV) light triggers the rapid generation and accumulation of reactive oxygen species (ROS) in skin cells, which increases oxidative stress damage and leads to photoaging. Nuclear factor E2-related factor 2 (Nrf2) modulates the antioxidant defense of skin cells against environmental factors, especially ultraviolet radiation. Natural products that target Nrf2-regulated antioxidant reactions are promising candidates for anti-photoaging. The aim of this study was to investigate the protective effect of Modified Qing'e Formula (MQEF) on UV-induced skin oxidative damage and its molecular mechanisms. In this study, the photoaging models of human keratinocytes (HaCaT) and ICR mice were established by UV irradiation. In vitro models showed that MQEF displayed potent antioxidant activity, significantly increased cell viability and reduced apoptosis and excess ROS levels. Meanwhile, the knockdown of Nrf2 reversed the antioxidant and anti-apoptotic effects of MQEF. In vivo experiments indicated that MQEF could protect the skin against UV-exposed injury which manifested by water loss, sensitivity, tanning, wrinkling, and breakage of collagen and elastic fibers. The application of MQEF effectively increased the activity of antioxidant enzymes and reduced the content of malondialdehyde (MDA) in mice. In addition, MQEF was able to activate Nrf2 nuclear translocation in mouse skin tissue. In summary, MQEF may attenuate UV-induced photoaging by upregulating Nrf2 expression and enhancing antioxidant damage capacity. MQEF may be a potential candidate to prevent UV-induced photoaging by restoring redox homeostasis.

Adulteration detection of essence in sesame oil based on headspace gas chromatography-ion mobility spectrometry.

Sesame oil is a traditional and delicious edible oil in China and Southeast Asia with a high price. However, sesame oil essence was often illegally added to cheaper edible oils to counterfeit sesame oil. In this study, a rapid and accurate headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) method was proposed to detect the counterfeit sesame oil where the other cheap oils were adulterated with essence. Combined with chemometric methods including principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF), authentic and counterfeit sesame oils adulterated with sesame essence (0.5%, w/w) were easily separated into two groups. More importantly, 2-methylbutanoic acid, 2-furfurylthiol, methylpyrazine, methional, and 2,5-dimethylpyrazine were found to be markers of sesame essence, which were used to directly identify the sesame essence. The determination of volatile compounds based on HS-GC-IMS was proven to be an effective method for adulteration detection of essence in sesame oil.

Study for relevance of the acute myocardial ischemia to arrhythmia by the optical mapping method.

Ventricular arrhythmias are commonly observed in patients with acute coronary occlusion and ischemia. The purpose of the present study is to determine ischemic electrophysiological effects and their role in ischemia-induced arrhythmia. Optical mapping of the membrane potential with voltage-sensitive dyes was used in the study. The mapping was performed with di-4-ANEPPS in Langendorff-perfused rabbit hearts. The excitation-contraction decoupler 2,3-butanedione monoxime was used to suppress motion artifacts caused by contraction of the heart. The acute global ischemia was developed by a rapid reduction of the flow rate. The experiments revealed that ischemic tissues were characterized by an obvious reduction in action potential duration and action potential upstroke, slower conduction velocity (CV) and the property of post-repolarization refractoriness. Moreover, the magnitude of CV reduced both in control and ischemia when the pacing cycle length was short. CV reduction was even early in ischemia, resulting in a broader curve during ischemia. Moreover, the dominant frequency of ventricular tachycardia/ventricular fibrillation (VT/VF) in ischemia was less than that in control, implying a decreasing tendency of VT/VF frequency for low excitability. Therefore, combined with our previous simulation study, the dynamic changes of CV and longer refractory period were suggested to play an important role in the ischemia-related arrhythmia. Low excitability in ischemic tissue was the fundamental mechanism in it.