Effect of the Timing of Hyperbaric Oxygen Therapy on the Prognosis of Patients with Idiopathic Sudden Sensorineural Hearing Loss.

This study aimed to evaluate the effects of hyperbaric oxygen therapy (HBOT) on the hearing recovery of patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The clinical data of 79 patients diagnosed with ISSNHL and treated with HBOT between January 2017 and December 2019 were retrospectively reviewed. The pure tone audiometry (PTA) scores before and after HBOT were recorded. The associations of HBOT efficacy with demographic and clinical characteristics and the duration from disease onset to HBOT administration were determined. The average PTA score was 80.06 ± 25.94 dB before and 60.75 ± 21.26 dB after HBOT; the difference was significant. HBOT improved the hearing of 55.7% of the patients with ISSNHL (defined as an average PTA ≥ 11dB or a final average PTA score below 29 dB). There was a significant inverse relationship between the duration from symptom onset to HBOT administration and PTA score reduction after HBOT, which was adjusted for factors including age, sex, laterality of hearing loss, initial PTA score, reception of intratympanic steroid injections, tinnitus, dizziness, vertigo, diabetes, hypertension, and coronary artery disease. Commencing HBOT at an earlier stage is closely linked to greater improvements in hearing for patients with ISSNHL.

Age-dependent alteration in metabolism of vitamin B6 , neurotransmitters, and amino acids after 4'-O-methylpyridoxine administration in rats.

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba L. In this work, the effects of MPN on the metabolism of vitamin B6 , neurotransmitters, and amino acids were compared in the plasma and brain of young and adult rats under various administration times. Results showed that the contents of MPN residues in the plasma and brain of young rats were 12.72 and 14.76 µM higher than adult rats, respectively. Moreover, the levels of 5-hydroxytryptamine and dopamine in the brain of young rats have decreased by 13.78% and 7.19%, respectively, compared with the control group, at 2 h after MPN administration. Furthermore, the principal component analysis revealed that MPN was an important contributor to the amino acid composition in the brain of young rats. These results suggest that age may lead to different toxic effects of MPN. PRACTICAL APPLICATION: 4'-O-methylpyridoxine is primarily responsible for poisoning due to overconsumption of Ginkgo biloba seeds. This study will provide an exploratory understanding of the age-dependent toxicity of 4'-O-methylpyridoxine.

In vivo toxicity assessment of 4'-O-methylpyridoxine from Ginkgo biloba seeds: Growth, hematology, metabolism, and oxidative parameters.

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba seeds and leaves. In this work, the body weights, histopathological changes, plasma vitamin B6 (VB6), biochemical parameters, oxidative stress responses, and amino acids of rats were investigated after intragastric administration of MPN for 15 days. Results showed that intragastric administration of 50 mg/kg BW MPN caused pathological changes in the brain and heart tissues of rats. Administration of 10 mg/kg and 30 mg/kg BW MPN can significantly increase VB6 analogs in the plasma of rats, such as pyridoxal-5'-phosphate, pyridoxal. Results of biochemical parameters indicated that MPN can damage brains and hearts by changing the enzyme activity of these organs. These results suggest that consumption of Ginkgo biloba seeds for the long term, even in a small quantity, may lead to poisoning.

4'-O-methylpyridoxine: Preparation from Ginkgo biloba Seeds and Cytotoxicity in GES-1 Cells.

Ginkgo biloba seeds are wildly used in the food and medicine industry. It has been found that 4'-O-methylpyridoxine (MPN) is responsible for the poisoning caused by G. biloba seeds. The objective of this study was to explore and optimize the extraction method of MPN from G. biloba seeds, and investigate its toxic effect on human gastric epithelial cells (GES-1) and the potential related mechanisms. The results showed that the extraction amount of MPN was 1.933 µg/mg, when extracted at 40 °C for 100 min, with the solid-liquid ratio at 1:10. MPN inhibited the proliferation of GES-1 cells, for which the inhibition rate was 38.27% when the concentration of MPN was 100 µM, and the IC50 value was 127.80 µM; meanwhile, the cell cycle was arrested in G2 phase. High concentration of MPN (100 µM) had significant effects on the nucleus of GES-1 cells, and the proportion of apoptotic cells reached 43.80%. Furthermore, the Western blotting analysis showed that MPN could reduce mitochondrial membrane potential by increasing the expression levels of apoptotic proteins Caspase 8 and Bax in GES-1 cells. In conclusion, MPN may induce apoptosis in GES-1 cells, which leads to toxicity in the human body.

Determination and Comparison of 4'- O-Methylpyridoxine Analogues in Ginkgo biloba Seeds at Different Growth Stages.

The antivitamin B6, 4'- O-methylpyridoxine (MPN); its glucoside, 4'- O-methylpyridoxine-5'-glucoside (MPNG); and vitamin B6 compounds, including pyridoxal (PL), pyridoxamine, pyridoxine, pyridoxal-5'-phosphate (PLP), and pyridoxamine-5'-phosphate, exist in Ginkgo biloba seeds, which are widely used as food and medicine. This work aimed to determine the MPN analogues in G. biloba seeds at different growth stages in terms of cultivars and ages of trees. The highest total MPN contents of 249.30, 295.62, and 267.85 µg/g were obtained in the mature stages of three selected G. biloba samples. The total contents of vitamin B6 compounds decreased significantly in the entire growth period of the three samples. Principal-component analysis revealed that MPN and MPNG were important contributors in the MPN-analogue metabolism of G. biloba seeds. The influence of the cultivar on the content and composition of MPN analogues was greater than that of the age of the G. biloba tree.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing.

Nanomaterials-mediated photothermal therapy (PTT) often suffers from the fundamental cellular defense mechanism of heat shock response which leads to therapeutic resistance of cancer cells and reduces the therapeutic efficacy. Herein, a gold nanorods (GNRs)-siRNA platform with gene silencing capability is produced to improve the PTT efficiency. After surface modification, the GNRs show the ability to deliver siRNA oligos targeting BAG3 which is an efficient gene to block the heat-shock response. The synthesized GNRs-siRNA nanoplex exhibits excellent ability in the delivery of siRNA into cancer cells with high silencing efficiency which is even better than that of commercial Lipofectamine 2000. The in vitro and in vivo studies demonstrate the ability of the GNRs-siRNA nanoplex to sensitize the cancer cells to PTT under moderate laser irradiation by down-regulating the increased BAG3 expression and enhancing apoptosis. The GNRs-siRNA mediated PTT has large potential in clinical cancer therapy due to the elimination of therapeutic resistance and enhanced photothermal therapeutic efficacy by means of gene silencing. It also suggests an efficient platform for gene delivery and controllable gene therapy.

Rose-bengal-conjugated gold nanorods for in vivo photodynamic and photothermal oral cancer therapies.

Gold nanorods (GNRs) conjugated with rose bengal (RB) molecules exhibit efficient singlet oxygen generation when illuminated by 532 nm green light and high photothermal efficiency under 810 nm near-infrared (NIR) irradiation. In vitro experiments show that reactive oxygen species generated by green light and hyperthermia produced by NIR light constitute two different mechanisms for cancer cell death. The RB-GNRs also exhibit improved photodynamic efficacy by enhancing the uptake of RB by cancer cells. In vivo experiments are conducted on hamster cheek pouches to resemble the human oral cancer conditions more accurately to assess the therapeutic effectiveness. Compared to the single photodynamic therapy (PDT) or photothermal therapy (PTT), the RB-GNRs with combined PDT-PTT capabilities provide better therapeutic effects against oral cancer and have large potential in cancer treatment.