Vitamin B complex blocks the dust fall PM2 .5 -induced acute lung injury through DNA methylation in rats.

This study aimed to explore whether vitamin B complex (folic acid, B6 , and B12 ) could avert DNA methylation changes associated with inflammation induced by acute PM2.5 exposure. Sprague-Dawley rats were administered by gavage with different concentrations of vitamin B complex once a day for 28 days, and then by intratracheal instillation with saline or PM2.5 once every 2 days for three times. Vitamin B continued to be taken during the PM2.5 exposure. Rats were sacrificed 24 h after the last exposure. The results showed that vitamin B complex could block the pathological changes and injury in lungs induced by PM2.5 . Meanwhile, vitamin B complex could prevent the abnormal DNA methylation of IL-4 and IFN-γ to antagonize the imbalance of IL-4/IFN-γ associated with inflammation. It was further found that vitamin B complex could regulate DNA methyltransferases (DNMTs) and increase the S-adenosylmethionine (SAM)/S-Adenosyl-L-homocysteine (SAH) ratio to reverse the hypomethylation of genomic DNA and the abnormal DNA methylation of IL-4 and IFN-γ. In conclusion, vitamin B complex has a protective effect on acute lung injury by attenuating abnormal DNA methylation induced by PM2.5 in rats. This study may provide a new insight into the physiological function of vitamin B to prevent the health effects induced by PM2.5 .

α-Lipoic acid protects against microcystin-LR induced hepatotoxicity through regeneration of glutathione via activation of Nrf2.

Microcystins (MCs), as the most dominant bloom-forming strains in eutrophic surface water, can induce hepatotoxicity by oxidative stress. Alpha-lipoic acid (α-LA) is a super antioxidant that can induce the synthesis of antioxidants, such as glutathione (GSH), by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the potential molecular mechanism of α-LA regeneration of GSH remains unclear. The present study aimed to investigate whether α-LA could reduce the toxicity of MCs induced in human hepatoma (HepG2), Bel7420 cells, and BALB/c mice by activating Nrf2 to regenerate GSH. Results showed that exposure to 10 µM microcystin-leucine arginine (MC-LR) reduced viability of HepG2 and Bel7402 cells and promoted the formation of reactive oxygen species (ROS) compared with untreated cells. Moreover, the protection of α-LA included reducing the level of ROS, increasing superoxide dismutase activity, and decreasing malondialdehyde. Levels of reduced glutathione (rGSH) and rGSH/oxidized glutathione were significantly increased in cells cotreated with α-LA and MC-LR compared to those treated with MC-LR alone, indicating an ability of α-LA to attenuate oxidative stress and MC-LR-induced cytotoxicity by increasing the amount of rGSH. α-LA can mediate GSH regeneration through the Nrf2 pathway under the action of glutathione reductase in MC-LR cell lines. Furthermore, the data also showed that α-LA-induced cytoprotection against MC-LR is associated with Nrf2 mediate pathway in vivo. These findings demonstrated the potential of α-LA to resist MC-LR-induced oxidative damage of liver.

The mechanism of interaction between tri-para-cresyl phosphate and human serum protein: a multispectroscopic and in-silico study.

Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown. In this study, through fluorescence and ultraviolet-visible (UV-vis) absorption spectroscopy, molecular docking and molecular dynamics (MD), tri-para-cresyl phosphate (TpCP) was selected to explore potential interactions between HSA and TCPs. The results of the fluorescence spectroscopy demonstrated that a decrease the fluorescence intensity of HSA and a blue shift were observed with the increasing concentrations of TpCP. The binding constant (Ka) was 2.575 × 104 L/mol, 4.701 × 104 L/mol, 5.684 × 104 L/mol and 9.482 × 104 L/mol at 293 K, 298 K, 303 K, and 310 K, respectively. The fluorescence process between HSA and TpCP involved a mix of static and dynamic quenching mechanism. The gibbs free energy (ΔG0) of HSA-TpCP system was -24.452, -25.907, 27.363, and 29.401 kJ/mol at 293 K, 298 K, 303 K, and 310 K, respectively, suggesting that the HSA-TpCP reaction was spontaneous. The enthalpy change (ΔH0) and thermodynamic entropy change (ΔS0) of the HSA-TpCP system were 291.08 J/K mol and 60.83 kJ/mol, respectively, indicating that hydrophobic force was the major driving forces in the HSA-TpCP complex. Furthermore, multispectral analysis also revealed that TpCP could alter the microenvironment of tryptophan residue and the secondary structure of HSA and bind with the active site I of HSA. Molecular docking and MD simulations confirmed that TpCP could spontaneously form a stable complex with HSA, which was consistent with the fluorescence experimental results. This study provides novel insights into the mechanisms of underlying the transportation and distribution of OFPRs in humans.

α-LA attenuates microcystin-LR-induced hepatocellular oxidative stress in mice through Nrf2-mediated antioxidant and detoxifying enzymes.

Microcystins constitute a class of toxins synthesized by cyanobacteria and are known to inflict significant damage on the antioxidant defense system of living organisms, primarily targeting the liver. α-Lipoic acid (α-LA) is universally recognized as a potent antioxidant in biological systems. It exerts its beneficial effects through multiple mechanisms-directly neutralizing reactive oxygen species (ROS) and free radicals, and indirectly enhancing antioxidant defenses by facilitating the regeneration of glutathione (GSH). However, the precise modus operandi of α-LA's protective effect against Microcystin-LR-induced hepatotoxicity remains incompletely elucidated. The present study, therefore, employed α-LA to explore its protective role against Microcystin-LR exposure in mice. A model of Microcystin-LR-induced hepatic injury was established by administering Microcystin-LR into the peritoneal cavity of BALB/c mice daily over a two-week period. Thereafter, BALB/c mice were pre-treated with varying concentrations of α-LA via oral gavage for a duration of 7 days, followed by a 7-day exposure to Microcystin-LR. Our findings reveal that α-LA pre-treatment significantly mitigated hepatic pathologies in Microcystin-LR-exposed mice. Furthermore, α-LA administration led to a notable elevation in the activities and expression levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione-indicative of its antioxidative capacity. Concurrently, a significant decrease was observed in the activities and expression levels of malondialdehyde and cytochrome P450 2E1. Consequently, α-LA emerges as a promising therapeutic candidate for the amelioration of liver oxidative damage subsequent to Microcystin-LR exposure.

Clinical Indications for Extubation in Coma Patients with Severe Neurological Craniocerebral Injury with Meta-Analysis.

Computer searches of the PubMed, Cochrane Library, and Embase databases for randomized controlled studies on the effects of intensive nutrition on clinical outcomes in patients with severe craniocerebral injury were conducted from the time of database creation to June 11, 2022, along with manual searches of the relevant literature. Two investigators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies before the effect sizes were combined using RevMan 5.3 statistical software provided by the Cochrane Collaboration Network, and publication bias was detected using Stata 12.0 software. Meta-analysis showed that total protein levels were higher in the intensive nutrition group than in the regular nutrition group (WMD = 4.96 g/L (1.57-8.34), P < 0.001); IgA levels were significantly higher in the intensive nutrition group than in the regular nutrition group (SMD = 0.79 (0.51-1.07), P < 0.001; SMD = 0.98 (0.58-1.38), P < 0.001); IgG levels were significantly higher in the fortified group than in the regular group (SMD = 0.98 (0.58-1.38), P < 0.001); CD4/CD8 was significantly higher in the fortified patients than in the regular patients with a combined effect size of WMD = 0.33 (0.18-0.48) (P < RR = 0.45 (0.27-0.75), P = 0.002). The results show that effective support of early enteral nutrition can reduce the occurrence of gastrointestinal complications in patients, give them a better adaptation process to the gastrointestinal tract, and ensure the degree of tolerance of their gastric mucosa, thus absorbing more nutrition. Fortification significantly reduced the incidence of gastric retention in patients with craniocerebral injury (RR = 0.19 (0.07-0.49), P < 0.001). In the subgroup analysis of the three groups, it was shown that, depending on the starting time, the total protein level and IgG level were better in the early nutrition at 24 h than in the late nutrition above 24h and that, depending on the starting dose, the total protein level, IgA, IgG, and CD4/CD8 were better in the intervention at doses above 30 mL/h, using the starting dose of 30 mL/h as the cut-off point. In the subgroup analysis based on different nutrition methods (enteral and parenteral nutrition), IgA levels and the incidence of bloating and diarrhea were better than those of parenteral nutrition in the indicators of enteral nutrition.

CircRNA_0026344 via exosomal miR-21 regulation of Smad7 is involved in aberrant cross-talk of epithelium-fibroblasts during cigarette smoke-induced pulmonary fibrosis.

For smoking-induced pulmonary fibrosis (PF), a serious disease endangering human health, there is no effective clinical treatment. Aberrant epithelium-fibroblast cross-talk is involved in formation of the excessive extracellular matrix (ECM) that contributes to PF. Circular RNAs have been associated with various pulmonary diseases. However, the mechanisms of circRNAs in PF are not clear. Herein, our goals were to investigate the involvement of circRNA_0026344 in the aberrant epithelium-fibroblast cross-talk induced by cigarette smoke (CS) and to define its mechanism. Chronic exposure (16 weeks) of BALB/c mice to 500 mg/m3 CS induced lung injury and fibrosis in lung tissues. From HBE cells, circRNA_0026344 was selected by microarray analysis and verified as that with the most severe down-regulation caused by cigarette smoke extract (CSE). The regulatory relationship between circRNA_0026344 and miR-21 was assessed by use of bioinformatics, RNA pull-down assays, and qRT-PCR. We found that miR-21 binding sites were present in circRNA_0026344 and, in HBE cells, it could act as a sponge for miR-21. When pcDNA3.0-circRNA_0026344, a high expression plasmid of circRNA_0026344, was transfected into HBE cells, the CSE-induced up-regulation of miR-21 levels was reversed. In MRC-5 cells, HBE-secreted exosomal miR-21 decreased levels of Smad7 and activated the TGF-ß1/Smad3 pathway. By using the Targetscan database, the presence of species-conserved miR-21 binding sites in the Smad7 3'UTR region were predicted. We verified, by use of a luciferase reporter gene, that miR-21 bound to the 3'UTR region of Smad7 mRNA to inhibit its transcription. In conclusion, the results reveal that, in CS-induced pulmonary fibrosis, circRNA_0026344, via exosomal miR-21 regulation of Smad7, is involved in aberrant cross-talk of epithelium-fibroblasts. These results will be useful for the discovery of early biomarkers and for providing therapeutic targets for smoking-induced pulmonary fibrosis.

Ultralow Threshold Lasing from Carbon Dot-Ormosil Gel Hybrid-Based Planar Microcavity.

The absence of an ideal solid matrix with resistance to harsh conditions for carbon dots (CDs) and high transmittance in the visible/near infrared region is the bottleneck in CD applications. In this study, we show that a stable rigid structure can be formed between CDs and organically modified silicates (ormosil) gel when CDs are incorporated into ormosil gel hybrids as a solid matrix. A high photoluminescence quantum yield (PLQY) of 63% is achieved at a 583 nm emission. Peak optical gain of the hybrids was found to be 67 cm-1 at peak wavelength. Ultralow threshold (~70 W/cm2) lasing can also be demonstrated from a planar microcavity by using CD-ormosil gel hybrids as a gain medium.

[The antagonistic action of epigallocatechin-3-gallate on microcystin LR-induced oxidative damage on hepatocytes of mice and the expression of cytochrome P450 2E1].

OBJECTIVE: To evaluate the effects of antagonistic action of epigallocatechin-3-gallate (EGCG) on microcystin LR (MC-LR) induced oxidative damage on mice and the expression of cytochrome P450 2E1 (CYP2E1) which was one of phase Iota detoxification enzymes. METHODS: A total of 24 specific pathogen free (SPF) male BALB/c mice were randomly divided into four groups, including control group, MC-LR group, low concentration EGCG group, and high concentration EGCG group. Mice were sacrificed on the 15th day, body weight, and the relative organ weight, liver antioxidant enzyme level and lipid peroxidation product, liver histopathology and CYP2E1 gene and protein expression were detected and analyzed respectively. RESULTS: (1) EGCG could antagonise the liver injury which had been damaged by MC-LR. (2) The malonaldehyde (MDA) level ((2.87 +/- 0.03) nmol/mg prot) and superoxide dismutase (SOD) level ((168.18 +/- 2.86) U/mg prot) in MC-LR group were significantly different when compared with the two EGCG treatment groups (the MDA values of the low and high concentration EGCG group were (2.37 +/- 0.05) nmol/mg prot and (1.44 +/- 0.05) nmol/mg prot, F = 906.63, P < 0.01; the SOD values were (176.55 +/- 2.98) U/mg prot and (184.89 +/- 1.53) U/mg prot, F = 32.32, P < 0.01). (3) MC-LR up-regulated the mRNA and protein expression of CYP2E1 (the mRNA values of MC-LR group and control were 1.41 +/- 0.26, 0.86 +/- 0.13, t = -4.22, P = 0.003; the protein values of MC-LR group and control were 0.24 +/- 0.03, 0.12 +/- 0.02, t = -9.21, P < 0.05). EGCG down-regulated the mRNA (the values of the low and high concentration EGCG group were 1.09 +/- 0.08, 0.99 +/- 0.09, F = 9.03, P = 0.004) and protein expression (the values of the low and high concentration EGCG group were 0.21 +/- 0.03, 0.14 +/- 0.02, F = 24.76, P < 0.05) of CYP2E1 which activated by MC-LR. CONCLUSION: The up-regulation of CYP2E1 which induced by MC-LR was inhibited by EGCG intervention. EGCG might antagonize the oxidation damage of hepatocytes in a certain degree.

Highly efficient and ultra-narrow bandwidth orange emissive carbon dots for microcavity lasers.

Luminescent materials with high efficiency, narrow emission bandwidth and long emission wavelength have attracted extensive attention in recent years. However, for novel luminescent carbon dots, it is still a major challenge to obtain these properties simultaneously. Here, this type of carbon dot was proposed using 1,4-diaminonaphthalene as the initial source. The carbon dots demonstrate strong orange emission with the highest quantum yield of 82% and an extremely narrow emission bandwidth of 30 nm. It is found that the orange emission of carbon dots is attributed to the high defect amounts including nitrogen and oxygen doping. The high carboxyl group content leads to a high efficiency and the uniform size distribution results in a narrow bandwidth. The carbon dots are used as the gain medium of a whispering gallery mode microcavity laser. A low excitation threshold of 12 kW cm-2 and a high quality factor of ∼3600 can be obtained from the microcavity lasers. This work has provided a didactic example to develop high-quality long emission-wavelength carbon dots with strong emission and an ultra-narrow emission bandwidth, which makes it possible to expand the application of original and high-performance lasers or other optical devices.

Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells.

According to global estimates, at least 107,000 people die each year from asbestos-related lung cancer, mesothelioma, and asbestosis resulting from occupational exposure. Chrysotile accounts for approximately 90% of asbestos used worldwide. Artificial substitutes can also be cytotoxic to the same degree as chrysotile. But only a few researchers focused on their genetic effects and mutagenicity information which is useful in evaluating the carcinogenicity of chemicals. In this study, chrysotile from Mangnai, Qinghai, China, and an artificial substitute, rock wool fiber were prepared as suspensions and were tested at concentrations of 50, 100, and 200 µg/ml in V79 lung fibroblasts. Chromosome aberrations were detected by micronucleus assay after exposure for 24 h, and DNA damage were estimated by single cell gel electrophoresis after exposure for 12, 24, or 48 h. According to the results, chrysotile and rock wool fibers caused micronuclei to form in a dose-dependent manner in V79 cells; olive tail moment values increased in a dose- and time-dependent manner. When V79 cells were exposed to a concentration of 200 µg/ml, the degree of DNA damage induced by chrysotile fibers was greater than rock wool fibers. Our study suggests that both chrysotile and rock wool fibers could induce chromosome aberrations and DNA damage. These materials are worthy of further study.

Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P < .001). Sleep quality, prevalence of hypertension, and attention in transportation hub areas were significantly different from those in the other 3 areas (P < .05); only 24.46% of people knew the health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise.