Adverse effects of hyperbaric oxygen therapy: a systematic review and meta-analysis.

Introduction: Hyperbaric oxygen therapy (HBOT) is one of the common clinical treatments, but adverse effects have hampered and limited the clinical application and promotion of hyperbaric oxygen therapy. A systematic review and meta-analysis of the adverse effects of hyperbaric oxygen therapy have conducted by our group to provide a theoretical basis for clinical treatment. Methods: Three electronic databases (PubMed, Web of Science, and The Cochrane Library) were comprehensively searched for randomized clinical trials (RCTs) from March 2012 to October 2022. Two reviewers independently screened titles and abstracts for eligibility and assessed the quality of the included studies. The meta-analysis was performed using RevMan 5.3. Results: A total of 24 RCTs involving 1,497 participants were identified. ① The HBOT group reported more adverse effects (30.11% vs. 10.43%, p < 0.05). ② The most frequent side effect of HBOT is ear discomfort (113 cases). ③ When the course of hyperbaric oxygen was >10 sessions, the incidence of adverse effects was higher than that of the control group; when the course of HBOT was ≤10 sessions, the adverse effects caused by hyperbaric oxygen were comparatively lower. ④ When the chamber pressure is above 2.0 ATA, the incidence of adverse effects is higher than that of the control group. While the chamber pressure is lower than 2.0 ATA, HBOT is relatively safe compared with the previous one. Conclusion: Hyperbaric oxygen therapy (HBOT) is more likely to cause adverse reactions when the chamber pressure is above 2.0 ATA. More attention should be paid to the possible occurrence of related adverse effects if the treatment course is >10 sessions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316605.

Tumor Microenvironment-Responsive Nanoherb Delivery System for Synergistically Inhibition of Cancer Stem Cells.

Multidrug resistance in cancer stem cells (CSCs) is a major barrier to chemotherapy; hence, developing CSC-specific targeted nanocarriers for efficient drug delivery is critical. In this study, monodisperse hollow-structured MnO2 (H-MnO2) with a mesoporous shell was created for efficient targeted drug delivery. An effective therapeutic compound isoliquiritigenin (ISL) was confirmed to inhibit the lung cancer stem-cell phenotype by natural compound screening based on integrated microfluidic devices. The resultant H-MnO2 showed a high drug-loading content of the potent CSC-targeting compound ISL and near-infrared fluorescent dye indocyanine green (ICG). In addition, H-MnO2 was successively modified with hyaluronic acid (HA) to enhance targeting CSCs with high CD44 expression levels. The H-MnO2@(ICG + ISL)@HA nanocomposites displayed promising chemotherapeutic and photothermal treatment capabilities, as well as NIR-triggered drug release, which showed excellent CSC-killing effects and tumor inhibition efficacy. Meanwhile, the development of the tumor was effectively restrained by NIR-triggered phototherapy and prominent chemotherapy without obvious side effects after tail vein injection of the nanocomposites in vivo. In summary, the prepared nanocomposites accomplished synergistic cancer therapy that targets CSCs, offering a versatile platform for lung cancer diagnosis and treatment.

Application of whey protein emulsion gel microparticles as fat replacers in low-fat yogurt: Applicability of vegetable oil as the oil phase.

Low-fat, healthy yogurt is becoming increasingly favored by consumers. In the present study, whey protein emulsion gel microparticles were used to improve the quality of low-fat yogurt, and the effects of vegetable oil emulsion gel as a fat substitute on the qualities of low-fat yogurt were investigated, expecting to obtain healthier and even more excellent quality low-fat yogurt by applying a new method. First, emulsion gel microparticles were prepared, and then particle size distribution of emulsion gel and water holding capacity (WHC), textural properties, rheological properties, microstructure, storage stability, and sensory evaluation of yogurt were carried out. The results showed that yogurt with emulsion gel had significantly superior qualities than yogurt made with skim milk powder, with better WHC, textural properties, rheological properties, and storage stability. The average particle size of whey protein-vegetable oil emulsion gel microparticles was significantly larger than that of whey protein-milk fat emulsion gel microparticles, and the larger particle size affected the structural stability of yogurt. The WHC of yogurt made with whey protein-vegetable oil emulsion gel microparticles (V-EY) was lower (40.41%) than that of yogurt made with whey protein-milk fat emulsion gel microparticles (M-EY; 42.81%), and the texture results also showed that the hardness, consistency, and viscosity index of V-EY were inferior to these of M-EY, whereas no significant differences were found in the cohesiveness. Interestingly, the microstructure of V-EY was relatively flatter, with more and finer network branching. The whey separation between V-EY and M-EY also did not show significant differences during the 14 d of storage. Compared with yogurt made with whey protein, vegetable oil, and skim milk powder, the structure of V-EY remained relatively stable and had no cracks after 14 d of storage. The sensory evaluation results found that the total score of V-EY (62) was only lower than M-EY (65) and significantly higher than that of yogurt made with skim milk powder. The emulsion gel addition improved the sensory qualities of yogurt. Whey protein emulsion gel microparticles prepared from vegetable oil can be applied to low-fat yogurt to replace fat and improve texture and sensory defects associated with fat reduction.

Synergistic photothermal cancer immunotherapy by Cas9 ribonucleoprotein-based copper sulfide nanotherapeutic platform targeting PTPN2.

Photothermal therapy (PTT) is a promising strategy for the treatment of advanced malignant neoplasm. However, the anti-tumor efficacy by PTT alone is insufficient to control tumor growth and metastasis. Here, we report a multifunctional nanotherapeutic system exerting a combined PTT and immunotherapy to synergistically enhance the therapeutic effect on melanoma. In particular, we selected the semiconductor nanomaterial copper sulfide (CuS), which served not only as a near-infrared (NIR) light-triggered photothermal converter for tumor hyperthermia but as a basic carrier to modify Cas9 ribonucleoprotein targeting PTPN2 on its surface. Efficient PTPN2 depletion was observed after the treatment of CuS-RNP@PEI nanoparticles, which caused the accumulation of intratumoral infiltrating CD8 T lymphocytes in tumor-bearing mice and upregulated the expression levels of IFN-ᵧ and TNF-α in tumor tissue, thus sensitizing tumors to immunotherapy. In addition, the effect worked synergistically with tumor ablation and immunogenic cell death (ICD) induced by PTT to amplify anti-tumor efficacy. Taken together, this exogenously controlled method provides a simple and effective treatment option for advanced malignant neoplasm.

Efficient expression of novel glutamate decarboxylases and high level production of γ-aminobutyric acid catalyzed by engineered Escherichia coli.

Glutamate decarboxylase (GAD) has the potential of converting L-glutamate to gamma-aminobutyric acid (GABA), which is an important non-proteinogenic amino acid that has a potential use as food additive or dietary supplement for its physiological functions. A novel pyridoxal 5'-phosphate (PLP)-dependent glutamate decarboxylase (LsGAD) was cloned from GRAS (generally recognized as safe) Lactobacillus senmaizukei by genome mining and efficiently expressed in Escherichia coli BL21. The LsGAD displayed excellent temperature property, pH property and kinetic parameters compared with the probe LbGAD and the other GADs. By increasing the copy number of the LsGAD encoding gene, the expression level of LsGAD and the biosynthesis yield of GABA were increased, which was near to 2 times of that was expressed in single copy. These results established a solid foundation for increasing the added value of L-glutamate and the biosynthesis of GABA.

Vasodilatory effects and underlying mechanisms of the ethyl acetate extracts from Gastrodia elata.

The objective of this study was to assess the ethyl acetate extracts of Gastrodia elata Blume (GEB) on vascular tone and the mechanisms involved. GEB was extracted with 95% EtOH followed by a further extraction with ethyl acetate. The effects of GEB and its ingredients on the isometric tensions of the aortic rings from rats were measured. The ethyl acetate extract of GEB induced a vasodilatory effect on rat aorta, which was partially dependent on endothelium. Four chemical compounds isolated from GEB were identified as 3,4-dihydroxybenzaldehyde (DB), 4-hydroxybenzaldehyde (HB), 4-methoxybenzyl alcohol (MA), and 4,4'-dihydroxydiphenyl methane (DM), respectively. All of these compounds induced vasodilatations, which were dependent on the endothelium to different degrees. After pretreatment with Nω-nitro-l-arginine methyl ester, indomethacin, or methylene blue, the vasodilatations induced by DB, HB, and MA were significantly decreased. In addition, the contractions of the rat aortic rings due to Ca2+ influx and intracellular Ca2+ release were also inhibited by DM. Furthermore, the administration of DB significantly enhanced the productions of nitric oxide (NO) and the activities of the endothelial NO synthase in aorta and in endothelial cells. Thus, GEB may play an important role in the amelioration of hypertension by modulating vascular tones.

Expression of the MYB transcription factor gene BplMYB46 affects abiotic stress tolerance and secondary cell wall deposition in Betula platyphylla.

Plant MYB transcription factors control diverse biological processes, such as differentiation, development and abiotic stress responses. In this study, we characterized BplMYB46, an MYB gene from Betula platyphylla (birch) that is involved in both abiotic stress tolerance and secondary wall biosynthesis. BplMYB46 can act as a transcriptional activator in yeast and tobacco. We generated transgenic birch plants with overexpressing or silencing of BplMYB46 and subjected them to gain- or loss-of-function analysis. The results suggest that BplMYB46 improves salt and osmotic tolerance by affecting the expression of genes including SOD, POD and P5CS to increase both reactive oxygen species scavenging and proline levels. In addition, BplMYB46 appears to be involved in controlling stomatal aperture to reduce water loss. Overexpression of BplMYB46 increases lignin deposition, secondary cell wall thickness and the expression of genes in secondary cell wall formation. Further analysis indicated that BplMYB46 binds to MYBCORE and AC-box motifs and may directly activate the expression of genes involved in abiotic stress responses and secondary cell wall biosynthesis whose promoters contain these motifs. The transgenic BplMYB46-overexpressing birch plants, which have improved salt and osmotic stress tolerance, higher lignin and cellulose content and lower hemicellulose content than the control, have potential applications in the forestry industry.

Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells.

In order to validate the antiviral effect against hepatitis B virus (HBV) of Taraxacum mongolicum (T. mongolicum), the protective effect on hepatocytes, and antiviral properties against duck hepatitis B virus (DHBV) and HBV of T. mongolicum extract (TME) were evaluated in chemically-injured neonatal rat hepatocytes, DHBV-infected duck fetal hepatocytes and HBV-transfected HepG2.2.15 cells, respectively. The results demonstrated that TME at 50-100 µg/ml improved D-galactosamine (D-GalN), thioacetamide (TAA) and tert-butyl hydroperoxide (t-BHP)-injured rat hepatocytes, and produced protection rates of 42.2, 34.6 and 43.8% at 100 µg/ml, respectively. Furthermore, TME at 1-100 µg/ml markedly inhibited DHBV DNA replication. Additionally, TME at 25-100 µg/ml reduced HBsAg and HBeAg levels and produced inhibition rates of 91.39 and 91.72% at 100 µg/ml, respectively. TME markedly inhibited HBV DNA replication at 25-100 µg/ml. The results demonstrate the potent antiviral effect of T. mongolicum against HBV effect. The protective of TME effect on hepatocytes may be achieved by its ability to ameliorate oxidative stress. The antiviral properties of TME may contribute to blocking protein synthesis steps and DNA replication. Furthermore, major components of TME were quantificationally analyzed. These data provide scientific evidence supporting the traditional use of TME in the treatment of hepatitis.