Nanosecond pulsed cold atmospheric plasma jet suppresses proliferation and migration of human glioblastoma cells via apoptosis promotion and EMT inhibition.

Glioblastoma (GBM) is one of the most aggressive and challenging cancers to treat. Despite extensive research on dozens of cancer cells, including GBM, the effect of cold atmospheric plasma (CAP) on the invasive migration of GBM cells has received limited attention, and the underlying mechanisms remain poorly understood. This study aims to investigate the potential molecular mechanism of ns-CAPJ in inhibiting the invasive migration of human GBM cells. The findings indicate that ns-CAPJ significantly reduces GBM cell invasion and migration, and induces apoptosis in GBM cells. Further mechanistic studies demonstrate a direct correlation between the suppression of the epithelial-mesenchymal transition (EMT) signaling pathway and ns-CAPJ's inhibitory effect on GBM cell invasion and migration. Additionally, combined with the N-acetyl cysteine (NAC, a ROS inhibitor) assay, we found that the ROS stimulated by the ns-CAPJ plays an important role in suppressing the EMT process. This work is expected to provide new insight into understanding the molecular mechanisms of how ns-CAPJ inhibits the proliferation and migration of human GBM cells.

Effect of small vessel disease burden and lacunes on gait/posture impairment in Parkinson's disease.

INTRODUCTION: The comorbidity of cerebral small vessel disease (CSVD) may worsen gait impairment of Parkinson's disease (PD). However, the evidence remains scarce and controversial, and the mechanism of their potential interaction remains largely unknown. The present study aimed to investigate the overall impact of quantity and location of CSVD on gait/posture function in PD. METHODS: This cross-sectional study included 315 consecutive eligible patients with PD from Beijing Tiantan Hospital from May 2016 to August 2018. Associations of gait/posture subscores with the burden score of CSVD and four CSVD imaging markers were assessed using multivariate linear regression models. RESULTS: Burden of CSVD was significantly associated with more severe gait/posture impairment in PD in the unadjusted model (ß = 0.521, P = 0.011, 95% CI 0.118-0.923) and in the model adjusted for age, hypertension, ischemic stroke, low-density lipoprotein level, cholesterol level, and cognitive statues (ß = 0.448, P = 0.047, 95% CI 0.006-0.891). The presence of lacunes, but not other CSVD markers, was significantly associated with higher gait/posture subscores after the adjustment (ß = 0.492, P = 0.041, 95% CI 0.021-0.964), and the number of lacunes in the basal ganglia significantly correlated with the gait/posture subscores in patients with PD (P = 0.012, Spearman r = 0.161). CONCLUSIONS: CSVD and lacunes in the basal ganglia may independently contribute to gait/posture dysfunction in PD. Promoting neurovascular health may preserve some gait/posture function of PD.

Nanosecond pulse electric field treatment initiates mitochondrial apoptosis pathway by inducing mitochondrial morphological changes in myocardial cells.

BACKGROUND: As an emerging myocardial ablation technique, the mechanism of nanosecond pulse electric field (nsPEF) ablation is currently less studied. Mitochondria are one of the important membrane structure organelles in cells, participating in numerous life activities within the cell. This study aimed to explore the morphological changes of mitochondria in living cells following nsPEF treatment. METHODS: Myocardial cells were treated with a self-made solid-state LTD high-voltage nanosecond pulse generator with a pulse width of 100 ns for 80 times. The changes in mitochondrial membrane potential and cell apoptosis in rat myocardial cells after nsPEFs were investigated using JC-1 assay kit, apoptosis double staining assay kit, and mitochondrial fluorescence probe. RESULTS: The results showed that after nsPEF treatment, the mitochondrial membrane potential decreased, apoptosis increased, and the average mitochondrial area decreased from 0.48 µm2 in live myocardial cells to 0.16 µm2. The average circumference ranges from 3.17 µm dropped to 1.60 µm. The shape factor decreased from 1.92 to 1.41. The aspect ratio has decreased from 2.16 to 1.59. nsPEF treatment induces changes in the morphology of myocardial cell mitochondria. CONCLUSIONS: Based on the results of mitochondrial membrane potential and apoptosis, it can be inferred that under this equipment and parameter conditions, nsPEF treatment first causes changes in mitochondrial morphology, and then initiates the mitochondrial apoptosis pathway, which may provide experimental basis for investigating the potential mechanism of nsPEF ablation of myocardial cells.

In vitro and in vivo study of novel antimicrobial gellan-polylysine polyion complex fibers as suture materials.

GELLAN GUM: and gellan-derived materials have never been used for suture materials due to their lack of strength and toughness. In this study, gellan and ε-polylysine formed a polyion complex in water solution, and the complex was transformed into fibers via wet-spinning. The fibers were bundled, twisted, and elongated, and the resultant twisted and elongated yarn (GPF) had a diameter of 97.53-103.76 µm and tensile strength of 4 N. The swelling ratio of GPF was 165.55%-183.23% in weight in normal saline, and the linear density was 2.84-3.31 g/km. GPF was tested using agar diffusion tests and it was found that the fibers had good antibacterial activity against Escherichia coli and Staphylococcus epidermidis. In weight loss experiments, GPF was found to be undegradable in normal saline and slightly degradable (residual weight ratio was 83.2 ± 1.2%) in simulated body fluid with trypsin within 7 days. Moreover, GPF showed no cytotoxicity toward BV-2 cells in cytotoxity tests with CCK8 and no hemolysis in hemolytic tests with fresh C57 mice blood. Finally, GPF was assessed using mouse dorsal cross-cutting model, and none of the mice that were tested with GPF showed infection or rejection reaction. Therefore, GPF is a promising suture material, and this study provides a new development direction for the application of gellan materials with improved mechanical properties.

Identification and application of novel low pH-inducible promoters for lactic acid production in the tolerant yeast Candida glycerinogenes.

Bioproduction of organic acids under low pH condition without adding inducer and neutralizer is an economical craft to decrease downstream cost. Candida glycerinogenes had higher tolerances to low pH and lactic acid than Saccharomyces cerevisiae. QRT-PCR analysis showed that four of fifteen candidates functioned as potentially acid-inducible promoters in C. glycerinogenes. In particular, PCggmt1 showed the strongest induction ability at pH 2.5. Fluorescence analysis indicated that the induction ability of PCggmt1 gradually increased as the pH decreased. In addition, PCggmt1 had the binding sites of Msn2p/4p, Azf1p, and Nrg1p. PCggmt1 was further used to control the expression of lactate dehydrogenase gene from Rhizopus oryzae in C. glycerinogenes. Compared with pH 5.5, the specific activity of lactate dehydrogenase and lactic acid titer at pH 2.5 were increased by 229% and 218%, reaching 13.8 mU/mg and 12.3 g/L, respectively. These results presented here showed a potential to produce organic acid economically at low pH by the stress tolerant C. glycerinogenes and the novel low-pH inducible promoter PCggmt1.