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Biomedical subjects

Hong Huang

Publications and source records attributed to Hong Huang.

At least 19 recordsLinked to original sources

Directed evolution of Lactiplantibacillus plantarum for utilizing ethanol to produce postbiotics.

Alcohol is a recognized carcinogen worldwide. In this study, we aimed to utilize probiotics to metabolize ethanol and produce postbiotics. Initially, we identified a lactic acid bacteria community in kimchi with excellent probiotic activity. By employing our previously developed directed evolution techniques, a Lactiplantibacillus plantarum mutant with safe characteristics and an ethanol utilization capacity of 40 g/L and 0.15 g/L/OD was obtained. Genome sequencing and RT-qPCR analysis revealed the up-regulated expression of alcohol dehydrogenase and aldehyde dehydrogenase genes greatly contributed to ethanol utilization. Furthermore, the mutant strain demonstrated marked superiority in producing postbiotics, including antimicrobial peptides and beneficial organic acids such as lactic acid, phenyllactic acid, succinic acid, and indole-3-lactic acid. In the ethanol-fed fermentation process, the mutant strain achieved a lactic acid yield of 8.47 g/L and a carbon conversion rate of 21.8%. In vivo testing further validated its safety and ability to assist alcohol metabolism.

Adaptive laboratory evolution↗

Does transforming growth factor-beta1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-beta1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed grade > or =1 RP, and 27 (22.3%) developed grade > or =2 RP. For the endpoint of grade > or =1 RP, those with V30>30% and an end-RT/baseline TGF-beta1 ratio> or =1 had a significantly higher incidence of RP than did those with V30>30% and an end-RT/baseline TGF-beta1 ratio<1. For most other patient groups, there were no clear associations between TGF-beta1 values and rates of RP. These findings suggest that TGF-beta1 is generally not predictive for RP except for the group of patients with a high V30.

Adult↗

[The relationship of the expression of principal pattern recognition receptor with the pulmonary injury in abdominal infection-induced sepsis].

OBJECTIVE: In order to investigate the evidence of the synergistic effects of bacterial components, to observe the relationship of the expression of lipopolysaccharide (LPS) receptors [CD14, Toll-like receptor 4 (TLR4), scavenger receptor (SR)], lipoprotein receptor (TLR2) and bacterial DNA receptor (TLR9) with pulmonary injury in abdominal infection-induced sepsis. METHODS: 30 mice were used and randomly divided into cecal ligation puncture (CLP) (n = 15) and sham (n = 15) groups. The animals were respectively sacrificed 8, 12 and 24 (each point n = 5) hours following CLP and sham CLP. The lungs were removed and immediately stored in liquid nitrogen for TLRs mRNA, tumor necrosis factor (TNF) alpha and myeloperoxidase (MPO) assay. To detect the expression of CD14, TLR4, SR, TLR2 and TLR9 mRNA by reverse-transcription polymerase chain reaction, to detect the TNF-alpha content of the lung tissue by enzyme-labeled immunosorbent assay, and to assay the MPO activity of the lung tissue spectrophotometer. RESULTS: It was found that the expression of receptors for LPS, BLP and bacterial DNA in pulmonary tissues was markedly changed in CLP-induced sepsis, showing upregulation of CD14 mRNA (1.143 +/- 0.139, t = 0.022, P < 0.05), TLR2 mRNA (0.418 +/- 0.102, t = 0.021, P < 0.05), TLR4 mRNA (0.595 +/- 0.052, t = 0.0001, P < 0.01) and TLR9 mRNA (0.743 +/- 0.178, t = 0.0023, P < 0.01) at different degrees (P < 0.05 or P < 0.01) after postinjury 8 h, among which the expression of TLR9 mRNA kept increasing. The expression of SR mRNA (8 h: 0.659 +/- 0.159; 12 h: 0.429 +/- 0.061; 24 h: 0.300 +/- 0.045; t = 0.029, P < 0.05; t = 0.001, P < 0.01; t = 0.003, P < 0.01) showed continuous down-regulation. CONCLUSION: There was a marked correlation between the changes of pattern-recognition receptor expression and the increases of MPO and TNF-alpha levels in pulmonary tissues.

Animals↗

Pharmacological profile of PMS777, a new AChE inhibitor with PAF antagonistic activity.

The key pathophysiological mechanisms in Alzheimer's disease involve the selective loss of cholinergic neurons and pro-inflammatory mediator-related chronic inflammatory responses in the brain, therefore interventions of these processes are crucial to the treatment of this disease. In the present study, the pharmacological profile of PMS777, a new acetylcholinesterase (AChE) inhibitor with platelet-activating factor (PAF) antagonistic activity, has been evaluated in vitro and in vivo. PMS777 (1-100 microM) dose-dependently inhibited PAF-induced rabbit platelet aggregation by competing with [3H]PAF for its receptor on platelets, and protected a human neuroblastoma cell line SH-SY5Y against PAF-induced neurotoxicity. Moreover, it markedly inhibited brain AChE activity in mice and showed a modest selectivity for AChE (AChE: IC50=2.48+/-0.12 microM; butyrylcholinesterase: IC50=4.47+/-0.15 microM). Ex vivo, PMS777 (5, 10, 20 or 40 mg/kg i.p.) reduced brain AChE activity in a dose-dependent manner. In-vivo studies revealed that PMS777 (0.25, 0.5, 1, 2.5 or 5 mg/kg i.p.) could reverse scopolamine-induced memory retrieval deficits in mice, and displayed a typical bell-shaped dose-response relationship. Taken together, these results demonstrate that PMS777 possesses dual activities for PAF receptor antagonism and AChE inhibition, suggesting that this compound may be a promising lead compound for further investigation related to the treatment for Alzheimer's disease.

Acetylcholinesterase↗

Characterizing the effects of caspofungin on Candida albicans, Candida parapsilosis, and Candida glabrata isolates by simultaneous time-kill and postantifungal-effect experiments.

We measured time-kills and postantifungal effects (PAFEs) of caspofungin against Candida albicans, C. parapsilosis, and C. glabrata isolates. One-hour exposure to caspofungin during PAFE experiments accounted for the majority of killing during time-kill experiments. Regrowth of all isolates was inhibited for at least 24 h following drug washout.

Antifungal Agents↗

[Processing GC-FTIR by the blind source separation].

An analysis method for separating chromatographic overlapped peaks and purifying infrared spectra is put forward, based on the blind source separation technique and the multi-dimensional data of GC-FTIR, Using various information from hyphenated instruments, this method was used to separate completely a organic mixture, the xylene isomerism system, a problem unable to solve usually. The method can confirm the rationality of theory and algorithm and give integral explanations of the independent component analysis data. The reason for the error in quantitative analysis is discussed.

Algorithms↗

Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity.

BACKGROUND: Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory/fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates acute radiation induced injury by inhibiting activation of TGFbeta1 and downregulating the Smad 3 arm of its signal transduction pathway. METHODS: Whole thorax radiation (single dose, 15 Gy) was delivered to EC-SOD overexpressing transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights, total/differential leukocyte count, activated TGFbeta1 and components of its signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to determine lung injury. RESULTS: Irradiated wild-type (XRT-WT) animals exhibited time dependent increase in breathing rates and right lung weights, whereas these parameters were significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks in irradiated transgenic (XRT-TG) mice. An inflammatory response characterized predominantly by macrophage infiltration was pronounced in XRT-WT mice. This acute inflammation was significantly attenuated (p < 0.05) in XRT-TG animals at 1, 3, 6 and 14 weeks. Expression of activated TGFbeta1 and components of its signal transduction pathway were significantly reduced (p < 0.05) at later time-points in XRT-TG vs. XRT-WT. CONCLUSION: This study shows that overexpression of EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to work, in part, via an attenuation of the macrophage response and also decreases TGFbeta1 activation with a subsequent downregulation of the profibrotic TGFbeta pathway.

Animals↗

Stereoselective synthesis of new conformationally restricted analogues of a potent CGRP receptor antagonist.

[structures: see text] A stereocontrolled racemic synthesis of conformationally restricted analogues 2a and 2b of a potent CGRP receptor antagonist 1 by novel functionalization of 2-substituted octahydropyrido[1,2-a]pyrazin-6-ones is described. The new diastereoselective LDA-promoted alpha-nitration of intermediate lactams established the required trans-configuration in the desired products.

Benzimidazoles↗

[The synergistic effects of lipopolysaccharide, bacterial lipoprotein and bacterial DNA on mouse alveolar macrophage activation].

OBJECTIVE: To investigate the synergistic effects of lipopolysaccharide (LPS), bacterial lipoprotein (BLP), and bacterial DNA on the expression of pattern recognition receptors (PRRs) on the cell surface of mouse alveolar macrophages and cellular activation at the level of receptor and its possible mechanism. METHODS: Mouse alveolar macrophages were isolated, cultivated and randomly divided into 7 groups: control group, LPS group, CpG oligonucleoetide (CpG-ODN) group, BLP group, LPS + BLP group, LPS + CpG-ODN group, and LPS + BLP + CpG-ODN group. Six hours later the supernatants were collected to detect the level of tumor growth factor alpha (TNFalpha) by ELISA. RT-PCR was used to detect the expression of the main PRRs: CD14, SR, TLR2, TLR4, and TLR9. RESULTS: The TNFalpha levels in the supernatant were 234 pg/ml +/- 30 pg/ml in the LPS group, 274 pg/ml +/- 30 pg/ml in the BLP group, and 308 pg/ml +/- 28 pg/ml in the CpG-ODN group, all significantly higher than that in the control group (92 pg/ml +/- 27 pg/ml, P < 0.01 or P < 0.01). The TNFalpha levels in the supernatant were 483 pg/ml +/- 31 pg/ml in the LPS + BLP group, and 511 pg/ml +/- 46 pg/ml in the LPS + CpG-ODN group, both significantly higher than those of the groups of the 3 factor alone (all P < 0.05). And the TNFalpha levels in the supernatant was 665 pg/ml +/- 24 pg/ml in the LPS + BLP + CpG-ODN group, significantly higher than those of the LPS + ODN group and LPS + BLP group (both P < 0.05). LPS, BL, and CpG-ODN alone, combinations of any 2 of them, and the combination of the three all up-regulated the expression of CD14 mRNA more and more strongly in sequence. LPS, BLP, and CpG-ODN alone all up-regulated the expression of SR mRNA (all P < 0.01), however, the combinations of any 2 factors or of the 3 factors failed to further up-regulate the expression of SR. LPS and BLP up-regulated the expression of TLR2 mRNA (both P < 0.05), LPS combined with BLP showed a stronger up-regulation of TLR2 mRNA (P < 0.05) than those by LPS and BLP alone. CPG-ODN alone failed to up-regulate the expression of TLR2 mRNA (P > 0.05) but significantly increased the up-regulation by LPS (P < 0.05). In comparison with the combinations of any 2 factors, LPS and BLP with CPG-ODN together up-regulated the expression of TLR2 mRNA more strongly (all P < 0.05). LPS, BLP, and CpG-ODN alone did not significantly up-regulate the expression of TLR4 mRNA (P > 0.05), LPS + BLP significantly regulated the expression of TLR4 mRNA than the groups of any factor alone (all P < 0.05). LPS + BLP + CpG-ODN further up-regulated the expression of TLR4 mRNA. LPS and CpG-ODN, especially LPS + CpG-ODN significantly up-regulated the expression of TLR9 mRNA (all P < 0.05). BLP failed to up-regulate the expression of TLR9 mRNA (P > 0.05) and did not coordinate the upregulation by LPS, however, in comparison with any combinations of the 3 factors, the combination of LPS, BLP, and ODN up-regulated the expression of TLR9 mRNA the most strongly (all P < 0.05). CONCLUSION: Bacterial LPS, BLP and bacterial DNA not only up-regulate the expression of PRRs of each other, but also synergistically increase the each other's effects on the cell surface of mouse alveolar macrophages.

Animals↗

[The effects of TNF alpha and IFN gamma on the expression of pattern recognition receptors on the surface of mouse alveolar macrophages].

OBJECTIVE: To investigate the effects of tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) on the expression of pattern recognition receptors (PRRs) on the surface of mouse alveolar macrophages. METHODS: Alveolar macrophages from mouse were cultured in DMEM supplemented with 10% (V/V) endotoxin-free calf serum. After the alveolar macrophages were stimulated with TNF alpha and IFN gamma (concentration, 20 ng/ml) for 3 h, 6 h and 12 h, the expression of PRRs, including cluster of differentiation 14 (CD14), scavenger receptor (SR), toll-like receptor 4 (TLR4), TLR2 and TLR9 mRNA and proteins were examined by RT-PCR and immunohistochemistry. RESULTS: The expressions of CD14, TLR2 and TLR9 receptors, which were related with cellular activation, were up-regulated by the stimulation of TNF alpha and IFN gamma (P < 0.05), while SR, which was related with cellular defense action, was down-regulated (P < 0.05). Although the expression of TLR4 was up-regulated, there was no statistical significance (P > 0.05). CONCLUSIONS: The cytokines such as TNF alpha and IFN gamma could also produce feedback regulation on the expression of PRRs at the levels of genes and proteins. Such regulation on the PRRs expression would be significant for further amplification of inflammation cascade and eventually leading to uncontrolled inflammation.

Animals↗

Integrin engagement increases histone H3 acetylation and reduces histone H1 association with DNA in murine lung endothelial cells.

Engagement of integrin cell adhesion receptors in mouse lung endothelial cells induces global sensitivity of DNA to nuclease digestion, reflecting alterations in chromatin structure. These structural changes may contribute to the antigenotoxic effects of integrin engagement in lung endothelium. Because histone acetylation and poly(ADP-ribosyl)ation modulate chromatin structure, we investigated the effects of beta1 integrin engagement with antibody on these post-translational modifications and the presence of histones at discrete DNA sequences in the mouse lung endothelial cell genome using chromatin immunoprecipitation. Integrin engagement increased acetylation of core histone H3. The presence of acetylated histone H3 at intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) promoters, and a nonpromoter sequence was also increased. As with integrin engagement, the histone deacetylase inhibitor trichostatin A caused global hypersensitivity of DNA to nuclease digestion and induced acetylation of histone H3 and its coimmunoprecipitation with VCAM-1 and ICAM-1 promoters and nonpromoter DNA. In contrast to acetyl-histone H3, the association of linker histone H1 with specific DNA sequences was either reduced or unaffected by integrin engagement and trichostatin A. Although integrin engagement and trichostatin A treatment did not affect histone H1 poly(ADP-ribosyl)ation, deletion of poly(ADP-ribose) polymerase-1 increased core histone H3 acetylation and increased its level at the iNOS promoter while decreasing the amount of histone H1. The results suggest that integrin engagement, as well as trichostatin A and PARP-1 deletion, regulate chromatin structure via core histone H3 acetylation and reduced linker histone H1-DNA association.

Acetylation↗

Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy.

The ability to optimize treatments for cancer on the basis of relative risks for normal tissue injury has important implications in oncology, because higher doses of radiation might, in some diseases, improve both local control and survival. To achieve this goal, a thorough understanding of the molecular mechanisms responsible for radiation-induced toxicity will be essential. Recent research has demonstrated that ionizing radiation triggers a series of genetic and molecular events, which might lead to chronic persistent alterations in the microenvironment and an aberrant wound-healing response. Disrupted epithelial-stromal cell communication might also be important. With the application of a better understanding of fundamental biology to clinical practice, new approaches to treating and preventing normal tissue injury can focus on correcting these disturbed molecular processes.

Cell Hypoxia↗

[Expression of retinoic acid receptor-beta mRNA and p16, p53, Ki67 proteins in esophageal carcinoma and its precursor lesions].

OBJECTIVE: To study the expression of retinoic acid receptor-beta (RAR-beta) mRNA and p16, p53, Ki67 proteins in squamous-cell carcinoma of the esophagus and its precursor lesions in a high risk population. METHODS: A total of 397 tissue specimens were collected from individuals with normal mucosa (NM, n = 25), mild dysplasia (MiD, n = 69), moderate dysplasia (MoD, n = 106), severe dysplasia (SD, n = 51), carcinoma in situ (CIS, n = 78), and squamous-cell carcinoma (SC, n = 68). Expression of RAR-beta mRNA was detected by in situ hybridization, and that of p16, p53 and Ki67 proteins by immunohistochemistry. RESULTS: The frequencies of RAR-beta mRNA expression in NM, MiD, MoD, SD, CIS and SC were 96.0%, 89.9%, 67.9%, 68.6%, 62.8%, and 63.2%, respectively. The frequencies of p16 expression were 88.0%, 71.0%, 64.2%, 51.0%, 53.8% and 52.9%; those of p53 expression were 4.0%, 39.1%, 57.5%, 52.9%, 67.9% and 69.1%; those of Ki67 expression were 0, 40.6%, 61.3%, 58.8%, 59.0% and 75.0%, respectively. CONCLUSION: There are no significant differences in four biomarkers expression between carcinoma of the esophagus and its precursor lesions.

Biomarkers, Tumor↗

[Characteristics and effect factors for sorption of trichlorobenzene on sediment in Huaihe River (Jiangsu reach)].

The characteristics for sorption of trichlorobenzene on sediment in Huaihe River (Jiangsu reach) was studied. It was also in vestigated at the same time that some factors of influence on the sorption, such as initial consistence of adsorbate, concentration of adsorbent and pH value, by ortho-experiment. The results indicate that the sorption isotherms of trichlorobenzene to sediment in Huaihe River (Jiangsu reach) are linear in the experiments condition,and distribution plays a leading role. The affected degrees of different environmental factors are different for sorption of trichlorobenzene on sediment in Huaihe River. The results of ortho-experiment are analysis with SPSS(Statistical Package for the Social Science) and the results are indicate that the affection of initial consistence of adsorbate is the biggest in all environmental factors,and initial consistences of adsorbate have expressly significant influence for sorption of trichlorobenzene on sediment in fresh water, and yet the pH has almost no influence for the sorption of trichlorobenzene on same sediment.

Adsorption↗

[Hologram quantitative structure-activity relationship for predicting acute toxicity of benzene derivatives to the tadpoles (Rana japonica)].

Acute lethal toxicity, the negative logarithm of 12 h acute median lethal molar concentration (expressed as 12h-log1/LC50, mol/L) of a series of benzene derivatives to Rana japonica tadpoles was determined. The relationship between the structure of benzene derivatives and their acute lethal toxicity was investigated by using hologram quantitative structure-activity relationship (HQSAR). The influence of hologram length, fragment size and distinction parameters on the quality of HQSAR model was studied. The robustness and predictive ability of the model were also validated by Leave-One-Out cross-validation procedure. The tested 51 compounds revealed a range of acute median lethal toxicity (12h-log1/LC50, mol/L) from 2.07 to 4.56. As a result, the best model was generated using a fragment size of 6-7 from a hologram length of 83 with 6 components. The HQSAR model showed a conventional correlation coefficient r2 of 0.942 and a Leave-One-Out cross-validation r2(cv) equal to 0.849, indicating the model possess high statistical quality in the prediction of acute toxicity of novel benzene analogs.

Animals↗

[Anxiety state and its related factors in Shanghai high school students].

OBJECTIVE: To investigate the anxiety state in high school students and related factors in order to get reasonable suggestions for prevention. METHODS: The mental health test (MHT) for high school students, and the living environmental and parental style were used in this study. RESULTS: MHT served as an assessment scale of anxiety. The efficiency sample was 3,050, aged 11 to 18 years old. The level of total anxiety and its each contents was low to moderate (0.24 to 0.54). The percentage of moderate to high of total anxiety was 16.7%, the percentage of moderate to high of each anxiety aspects were 8.8%-21.8%. The mostly high aspects were self-blame, schooling anxiety, social anxiety and over sensitiveness. In general, the girls' anxiety level was higher than boys', but the boys' lonely feeling was higher than the girls'. The total score of anxiety was decreased with age. Except of the over sensitiveness, the decrease tendency of each anxiety contents was significant in boys. For girls, the lonely feeling was deceased and the over sensitiveness increased with age. The age of fifteen seems as a significant changing age. The related disadvantage factors of students' anxiety were: the low education level, the parents' anxiety and depression characters, the authoritarian or neglecting parental style, the often contradiction parental styles between mother and father, parents often quarrel, the experience of often being scalded and physical punishment, lacking in care of others when in difficulties. CONCLUSIONS: The schooling pressure should be decreased to an appropriate level. The students' self-confidence and social ability should be emphasized. Good family environments and the support outside the family should be quite important for adolescents' mental health, these factors might decrease the adolescents' anxiety.

Adolescent↗

p38 Mitogen-activated protein kinase mediates synergistic induction of inducible nitric-oxide synthase by lipopolysaccharide and interferon-gamma through signal transducer and activator of transcription 1 Ser727 phosphorylation in murine aortic endothelial cells.

Nitric oxide (NO) can be produced in large amounts by up-regulation of inducible NO synthase (iNOS). iNOS is induced in many cell types by pro-inflammatory agents, such as bacterial lipopolysaccharide (LPS) and cytokines. Overproduction by endothelial cells (EC) may contribute to vascular diseases. In contrast to macrophages, murine aortic endothelial cells (MAEC) produced no NO in response to either LPS or interferon gamma (IFNgamma), whereas combined treatment was highly synergistic. In this study, we investigated the mechanisms of synergy in MAEC. LPS activated p38 mitogen-activated protein kinase (MAPK), whereas IFNgamma activated Janus kinase and signal transducer and activator of transcription-1 (STAT1). Both pathways were required for iNOS induction because herbimycin A, a tyrosine kinase inhibitor, and 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole. HCl (SB202190), a p38 MAPKalpha/beta inhibitor, each blocked induction. LPS increased the phosphorylation of STAT1alpha at serine 727 in IFNgamma-treated MAEC. SB202190, but not 2'-amino-3'-methoxyflavone (PD98059), an inhibitor of p44/p42 MAPK activation, abolished the phosphorylation and induction of iNOS. SB202190 did not affect tyrosine 701 phosphorylation or nuclear translocation of STAT1. However, STAT1-DNA binding activity was reduced by SB202190. Although LPS stimulated the DNA binding activity of nuclear factor kappaB and activating protein-1, combined treatment with IFNgamma did not enhance activation, and SB202190 did not inhibit it. The results indicate that p38 MAPKalpha and/or beta are required for the synergistic induction of iNOS by LPS and IFNgamma in MAEC. Furthermore, the synergistic induction is associated with phosphorylation of STAT1alpha serine 727 in MAEC. This observation may explain potentially beneficial effects of p38 MAPK inhibitors in vascular inflammatory diseases.

Animals↗

Holographic quantitative structure-activity relationship for prediction acute toxicity of benzene derivatives to the guppy (Poecilia reticulata).

Holographic quantitative structure-activity relationship (HQSAR) is an emerging QSAR technique with the combined application of molecular hologram, which encoded the frequency of occurrence of various molecular fragment types, and the subsequent partial least squares (PLS) regression analysis. In this paper, the acute toxicity data to the guppy (Poecilia reticulata) for a series of 56 substituted benzenes, phenols, aromatic amines and nitro-aromatics were subjected and this resulted in a model with a high predictive ability. The influence of fragment size and fragment distinction parameters on the quality of HQSAR model was investigated. The robustness and predictive ability of the model were also validated by leave-one-out (LOO) cross-validation procedure and external testing data set.

Animals↗