Conformations and molecular interactions of poly-γ-glutamic acid as a soluble microbial product in aqueous solutions.

Soluble microbial products (SMPs) are of significant concern in the natural environment and in engineered systems. In this work, poly-γ-glutamic acid (γ-PGA), which is predominantly produced by Bacillus sp., was investigated in terms of pH-induced conformational changes and molecular interactions in aqueous solutions; accordingly, its sedimentation coefficient distribution and viscosity were also elucidated. Experimental results indicate that pH has a significant impact on the structure and molecular interactions of γ-PGA. The conformation of the γ-PGA acid form (γ-PGA-H) is rod-like while that of the γ-PGA sodium form (γ-PGA-Na) is sphere-like. The transformation from α-helix to random coil in the γ-PGA secondary structure is primarily responsible for this shape variation. The intramolecular hydrogen bonds in the γ-PGA-H structure decrease and intramolecular electrostatic repulsion increases as pH increases; however, the sedimentation coefficient distributions of γ-PGA are dependent on intermolecular interactions rather than intramolecular interactions. Concentration has a more substantial effect on intermolecular electrostatic repulsion and chain entanglement at higher pH values. Consequently, the sedimentation coefficient distributions of γ-PGA shift significantly at pH 8.9 from 0.1 to 1.0 g/L, and the viscosity of γ-PGA (5% w/v) significantly increases as pH increases from 2.3 to 6.0.

[Immune regulation effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque].

To evaluate the effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. Eight SIV rhesus macaques of the same age were randomly divided into Chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as Chinese medicine group) and anti-virus drug(HAART) group. The traditional Chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detection in every 4 weeks. The results showed that Chinese medicine of invigorating spleen and kidney detoxification could not obviously decrease plasma viral load as HAART, but it can increase CD4 number in peripheral blood, especially the CD4 naive cells, and increase the number of CD4 and CD8 cells, enhance the immune response to pathogens. Therefore, it delayed the occurrence and development of spleen deficiency to a certain extent, indicating that the medicine had immune regulation effect, with considerable clinical value and application prospects.

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models.

AIM: Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models. METHODS: Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg(-1)·d(-1)) or PEG-CDs (size: 8.3 nm, 5 mg·kg(-1)·d(-1)) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf. RESULTS: Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 µg/mL) caused heart development delay, whereas addition of CDs (80 µg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments. CONCLUSION: CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.

[Experimental observation of SIVmac239 Chinese rhesus monkey model at sub-acute phase of AIDS].

OBJECTIVE: To observe T lymphocyte subsets and indicators of changes in viral load in sub-acute period in Chinese rhesus monkey model of AIDS SIVmac239. To explore Virology related index variation in sub-acute period of the Chinese rhesus monkey model of AIDS. METHOD: To replicate Chinese rhesus monkey model of AIDS, healthy Chinese rhesus monkey was inoculated with SIVmac239 viral strain. To observe changes in T lymphocyte subsets indexes and viral load after infection with the simian immunodeficiency virus (SIV) in sub-acute period on an animal model. The clinical symptoms of the animal model was recorded simultaneously. RESULT: During the 10 weeks after SIV acute infection, body weight and BMI index were relatively stable, the difference was not significant at all time points. Twelve monkeys were tested SIV positive by real-time PCR after three days of infection. On the 7th day after infection, 15 monkeys were tested SIV positive. Viral load increased rapidly, but reached a peak on the 10th-14th day after infection, then showed a level of volatility decline. T lymphocyte subsets showed significant changes, among them, CD3% and CD3 counts fluctuated upward trend and reached to the highest level in two weeks after infection; of CD4% and CD4 count changes were not synchronized, CD4% declined trend while the CD4 count was an increasing trend after the infection; of CD8% and CD8 counts fluctuate upward trend, and reached to a highest level in two weeks after infection ;the ratio of CD4/CD8 and the counts of CD4CD28 T cells decreased significantly in two weeks after infection; the former followed by a slow decline, the latter followed by a rapid rise. Three mouths after the infection 3 monkeys showed significant clinical symptoms. One of the rhesus monkeys had symptoms of diarrhea and two of them had reduced food intake. CONCLUSION: This experiments established standardization of Chinese Rhesus monkeys used in the research of AIDS and provide a detailed contents in the changes of sub-acute phase.

New cytotoxic oxygenated sterols from marine bryozoan Bugula neritina.

Two new oxygenated sterols, 3ß,24(S)-dihydroxycholesta-5,25-dien-7-one and 3ß,25-dihydroxycholesta-5,23-dien-7-one, were isolated from the marine bryozoan Bugula neritina. Their chemical structures were established on the basis of spectroscopic analysis. Both compounds exhibited cytotoxicity to three human cancer cell lines (HepG2, HT-29 and NCI-H460), with IC50 values between 22.58 and 53.41 µg mL⁻¹.