Anti-Neuroinflammatory Activity of New Naturally Occurring Benzylated Hydroxyacetophenone Analogs from the Endophytic Fungus Alternaria sp. J030.

Chemical studies on the culture broth of the endophytic fungus Alternaria sp. J030 led to the identification of three benzylated hydroxyacetophenone derivatives, bauvaroalterins A-C (1-3), and 34 structurally diverse metabolites (4-37). The new structures were elucidated by extensive spectroscopic analyses including UV, IR, 1D and 2D NMR, HR-ESI-MS, and further confirmed using single crystal X-ray diffraction. The in vitro anti-neuroinflammatory effects of the co-isolated metabolites were evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Compounds 1-3 were shown to significantly reduce LPS-induced NO production by inhibiting the expression of iNOS, as well as inhibiting LPS-induced production of the inflammatory factors TNF-α, IL-1ß and IL-6. Further studies revealed that 1-3 were capable of down-regulating the expression of NF-κB subunits p50 and p65, thereby suppressing the activation of NF-κB by inhibiting the LPS-induced phosphorylation of IκB-α. Together these findings demonstrate that bauvaroalterins A-C (1-3) exert anti-neuroinflammatory effects via inhibition of the NF-κB/iNOS signalling pathway in LPS induced BV-2 cells.

Acorenone C: A New Spiro-Sesquiterpene from a Mangrove-Associated Fungus, Pseudofusicoccum sp. J003.

Mangrove-derived endophytes are rich in bioactive secondary metabolites with a variety of biological activities. Recently, a fungus Pseudofusicoccum sp. J003 was first isolated by our research group from mangrove species Sonneratia apetala Buch.-Ham. The subsequent chemical investigation of the methanol extract of the culture broth of this strain has led to the isolation of a new sesquiterpenoid named acorenone C (1), two alkaloids (2-3), four phenolic compounds (4-7), and four steroid derivatives (8-11). The new structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR spectroscopy, and HRESIMS. Its absolute configuration was elucidated by experimental ECD and ECD calculation. The in vitro AChE inhibitory, anti-inflammatory, and cytotoxic activities of the selected compounds were evaluated. The results showed that compound 1 showed mild AChE inhibitory activity, with an inhibition rate of 23.34% at the concentration of 50 µM. Compound 9 exerted a significant inhibitory effect against nitric oxide (NO) production in LPS-stimulated RAW 264.7 mouse macrophages, with an inhibition rate of 72.89% at the concentration of 25 µM, better than that of positive control L-NMMA. Compound 9 also displayed obvious inhibition effects on the growth of two human tumor cell lines, HL-60 and SW480 (inhibition rates 98.68 ± 0.97% and 60.40 ± 4.51%, respectively). The antimicrobial activities of the compounds (1-11) against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa were also tested; however, none of them showed antimicrobial activities.

Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim.

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9'-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.

A study on the risk factors of coronary artery disease in patients with Takayasu arteritis.

BACKGROUND: The aim of this study was to investigate the risk factors of Takayasu arteritis (TA) involving the coronary artery. METHODS: Patients with TA involving coronary artery were included in this study. According to the patients' condition of coronary artery involvement, they were divided into two groups: group A: TA involved coronary artery disease [at least one coronary artery stenosis (≥50%)] and group B: TA did not involve coronary artery. A logistic regression model was used to analyze the risk factors of arteritis involving the patients' coronary artery lesions. RESULTS: A total of 442 TA patients were included in this study. The patients were significantly older in group A than those patients in group B (52.54±11.17 vs. 37.73±12.72, P<0.001). The age of onset in group A was significantly older than those patients in group B (42.21±11.46 vs. 32.74±13.13, P<0.001). The patients in group A had a longer course of disease (P<0.001), larger BMI (P=0.002) and higher rates of smoking, drinking, diabetes, dyslipidemia (P<0.05) when compared with group B. The level of eGFR was significantly decreased and the UA and TG levels were significantly increased in group A when compared with group B(P<0.05). Besides, the risk factors for TA involving coronary artery included the age of TA onset (OR =1.143, 95% CI: 1.007-1.298, P=0.039), course of TA (OR =1.165, 95% CI: 1.025-1.324, P=0.020), and BMI (OR =1.100, 95% CI: 1.021-1.185, P=0.013). CONCLUSIONS: The later the age of TA onset, the longer the course of TA onset and the more traditional risk factors associated with atherosclerosis, the more vulnerable patients are to coronary artery involvement and this may not be related to clinical disease activity.

Effects of allopurinol pretreatment on the risk of contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials
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BACKGROUND: Treatment with allopurinol has been suggested to reduce the incidence of contrast-induced acute kidney injury (CI-AKI). However, results of previous randomized controlled trials (RCTs) are not consistent. We performed a meta-analysis to evaluate the influence of allopurinol on the risk of CI-AKI. MATERIALS AND METHODS: Related RCTs were identified via systematic search of electronic databases including PubMed, Embase, and Cochrane's Library. The influence of allopurinol on the incidence of CI-AKI was defined as the primary outcome. Results were pooled using a random-effects model or a fixed-effects model according to the heterogeneity. RESULTS: Five RCTs with 754 patients who underwent percutaneous coronary intervention (PCI) were included. All patients received preprocedural hydration therapy with intravenous normal saline. Pooled results showed that allopurinol significantly reduced the incidence of CI-AKI (risk ratio (RR): 0.37, p = 0.01). Subgroup analyses demonstrated that allopurinol significantly reduced the incidence of CI-AKI in high-risk patients (incidence of CI-AKI ≥ 30%, RR: 0.10, p = 0.04) but not in low-risk patients (incidence of CI-AKI < 30%, RR: 0.67, p = 0.14). Moreover, allopurinol significantly prevented the increment of serum creatinine (weighted mean difference (WMD): -0.13 mg/dL, p < 0.001) and attenuated the loss of estimated glomerular filtration rate (WMD: 4.78 mL/min, p = 0.04). However, serum uric acids were not significantly affected (WMD: -0.26 mg/dL, p = 0.72). CONCLUSION: Pretreatment with allopurinol reduces the incidence of CI-AKI in patients undergoing contrast exposure in PCI. The benefits of allopurinol on CI-AKI may be more remarkable in high-risk patients.

Hydrophobicity and iron coagulation of extracellular polymeric substance from colonial Microcystis.

The bloom-forming cyanobacterium Microcystis occurs mainly as colonial aggregates under the natural conditions. This paper investigated the hydrophobicity and iron coagulation of extracellular polymeric substances (EPSs) from colonial Microcystis in order to understand the impact of EPS on the water treatment process. The higher contents of dissolved EPS (dEPS) and bound EPS (bEPS, mucilaginous matrix around the cells), lower dEPS/bEPS ratio and greater negative zeta potential of bEPS and dEPS were found in colonial Microcystis compared with unicellular Microcystis. XAD resin fractionation analysis indicated that the hydrophobicity could be ranked in an order as follows: bEPS > dEPS > dissolved extracellular organic matter (dEOM) for all the Microcystis strains. Correlation analysis showed that there was a statistically significant correlation between the amounts of carbohydrate and dissolved organic carbon in the hydrophobic fraction of EOM (dEOM, dEPS and bEPS), indicating that the hydrophobicity of Microcystis EOM might be related to carbohydrate. The coagulation experiment showed that for each colonial Microcystis strain, the removal efficiency of bEPS was higher than that of dEPS within the pH range from 3 to 10. The implications of the EPS characteristics were further discussed with respect to water treatment.

Probucol for the prevention of contrast-induced acute kidney injury in patients undergoing coronary angiography or percutaneous coronary intervention: A meta-analysis of randomized controlled trials
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BACKGROUND: The results of pilot randomized controlled trials (RCTs) evaluating probucol treatment on the risk of contrast-induced acute kidney injury (CI-AKI) are inconsistent. We aimed to perform a meta-analysis of RCTs to systematically evaluate the influence of probucol on the incidence of CI-AKI. MATERIALS AND METHODS: Related RCTs were identified via searching of PubMed, Embase, and Cochrane's Library databases. Results were pooled using a random-effect model or a fixed-effect model according to the heterogeneity. RESULTS: Five RCTs with 1,367 patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) were included. Meta-analysis indicated that probucol in addition to periprocedural hydration significantly reduced the incidence of CI-AKI (risk ratio (RR): 0.37, 95% confidence interval (CI): 0.24 - 0.56, p < 0.001) with insignificant heterogeneity (I2 = 0%). Moreover, treatment with probucol significantly lowered the increment of serum creatinine (weighted mean difference (WMD): -0.04 mg/dL, 95% CI: -0.07 to -0.02 mg/dL, p < 0.001) and preserved the loss of estimated glomerular filtrating rate (WMD: 2.46 mL/min, 95% CI: 0.84 - 4.07 mL/min, p = 0.003) as compared with control treatment. No significant publication bias was noticed. CONCLUSION: Treatment with probucol reduces the incidence of CI-AKI in patients undergoing contrast exposure during CAG or PCI. The influence of probucol on the clinical outcome in these patients deserves further investigation.
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Occupational exposure to 50 Hz magnetic fields does not alter responses of inflammatory genes and activation of splenic lymphocytes in mice.

OBJECTIVES: The objective of the present study was to observe the effects of 50 Hz magnetic fields (MFs) on the immune function of splenic lymphocytes in mice. MATERIAL AND METHODS: Twenty male Kunming mice (6 weeks old), weighing 18- 25 g, were randomly divided into sham exposure (N = 10) and 500 µT MFs (N = 10) groups. The mice in the MFs group were exposed to 500 µT MFs for 8 h daily (5 days/week) for up to 60 days. In vitro study was carried out to examine the effects of 50 Hz MFs on the expression of inflammatory factor genes and a cluster of differentiation 69 (CD69) in mouse prime splenic lymphocytes activated by para-Methoxyamphetamine (PMA) and ionomycin. In the in vitro experiments, lymphocytes were isolated from the spleen of 10 healthy Kunming mice, the cells were cultured in the Roswell Park Memorial Institute 1640 medium (RPMI-1640) and exposed to 0 µT, 250 µT, 500 µT, or 1 mT MFs in an incubator under 5% carbon dioxide (CO2) at 37°C for 6 h. The levels of interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-γ), GATA binding protein 3 (GATA-3) and T cell-specific T-box transcription factor (T-bet) were assessed by the real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively. The expression of CD69 was checked using the flow cytometry. RESULTS: Under our experimental conditions, body weight of the mice exposed to occupational, extremely low frequency- electromagnetic fields (ELF-EMFs) significantly decreased on day 20 and day 30. There were no significant changes observed in vivo in spleen weight, splenic coefficient, splenic histology profile and cytokine production in spleen tissues. Our in vitro experiments showed that 50 Hz MFs had no effect on the expression of these genes and CD69 to primary splenic cells. CONCLUSIONS: In conclusion, under the applied experimental conditions, occupational exposure to 50 Hz magnetic field did not alter responses of inflammatory genes and activation of splenic lymphocytes in mice, except for body weight.

Suppressive effects of subchronic aluminum overload on the splenic immune function may be related to oxidative stress in mice.

Aluminum (Al) is widely used in daily life and was recently recognized as a possible source of human intoxication because of its ability to accumulate in organs. The objective of the present study was to investigate the effects of subchronic Al overload on splenic immune function in mice. Furthermore, we have preliminarily explored its mechanism. The Al overload model was established via intragastric administration of Al once a day for 60 days. The body weight, spleen weight, and splenic coefficient were determined. The concentration of Al in the spleen was detected by inductively coupled plasma-mass spectrometry. The cytokine mRNA expression of spleen tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Biochemical methods were used to detect superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) contents in spleen tissue. Body weight, spleen weight, and cytokine mRNA expression of spleen tissues were significantly reduced by Al overload. SOD and GSH-Px activities were also decreased, while the MDA content was increased in subchronic Al overload mice. The results indicate that subchronic exposure to aluminum trichloride (AlCl3) would result in Al accumulation, which suppressed spleen immune function through a mechanism related to oxidative stress.

Effects of aluminum and extremely low frequency electromagnetic radiation on oxidative stress and memory in brain of mice.

This study was aimed to investigate the effect of aluminum and extremely low-frequency magnetic fields (ELF-MF) on oxidative stress and memory of SPF Kunming mice. Sixty male SPF Kunming mice were divided randomly into four groups: control group, ELF-MF group (2 mT, 4 h/day), load aluminum group (200 mg aluminum/kg, 0.1 ml/10 g), and ELF-MF + aluminum group (2 mT, 4 h/day, 200 mg aluminum/kg). After 8 weeks of treatment, the mice of three experiment groups (ELF-MF group, load aluminum group, and ELF-MF + aluminum group) exhibited firstly the learning memory impairment, appearing that the escaping latency to the platform was prolonged and percentage in the platform quadrant was reduced in the Morris water maze (MWM) task. Secondly are the pathologic abnormalities including neuronal cell loss and overexpression of phosphorylated tau protein in the hippocampus and cerebral cortex. On the other hand, the markers of oxidative stress were determined in mice brain and serum. The results showed a statistically significant decrease in superoxide dismutase activity and increase in the levels of malondialdehyde in the ELF-MF group (P < 0.05 or P < 0.01), load aluminum group (P < 0.01), and ELF-MF + aluminum group (P < 0.01). However, the treatment with ELF-MF + aluminum induced no more damage than ELF-MF and aluminum did, respectively. In conclusion, both aluminum and ELF-MF could impact on learning memory and pro-oxidative function in Kunming mice. However, there was no evidence of any association between ELF-MF exposure with aluminum loading.