Synthesis and evaluation of in vitro and in vivo anti-Toxoplasma gondii activity of tetraoxane-substituted ursolic acid derivatives.

A series of derivatives of ursolic acid (UA) were synthesised, the anti-Toxoplasma gondii activity was tested, and the selectivity index (SI) of these compounds was calculated to determine the derivative with the best anti-Toxoplasma gondii activity. Compound A7 showed the best activity against the Toxoplasma gondii (IC50 in T. gondii infected GES-1 cells: 9.1 ± 7.2 µM), better than the lead compound UA and the positive control drug Spiramycin. Compound A7 was selected for further in vivo research: A7 was tested for its effect on the inhibition rate of tachyzoites in mice and its biochemical parameters, such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde were determined. Compound A7 was evaluated for its anti-Toxoplasma activity and partial damage to the liver. Therefore, the results show that compound A7 could be a potential lead compound for developing a novel anti-Toxoplasma gondii molecule.

Study on the vasodilatory activity of lotus leaf extract and its representative substance nuciferine on thoracic aorta in rats.

Lotus (Nelumbo nucifera) leaves are widely used for both edible and medicinal applications. For its further utilization, we studied the vasodilatory activity of lotus leaf extract for the first time. In this study, we obtained the extracts using different ratios of water and ethanol, which was followed by polarity-dependent extraction. We found that the CH2Cl2 layer exhibited better vasodilatory activity (EC50 = 1.21 ± 0.10 µg/ml). HPLC and ESI-HRMS analysis of the CH2Cl2 layer using the standard product as a control revealed that nuciferine (Emax = 97.95 ± 0.76%, EC50 = 0.36 ± 0.02 µM) was the main component in this layer. Further research revealed that nuciferine exerts a multi-target synergistic effect to promote vasodilation, via the NO signaling pathway, K+ channel, Ca2+ channel, intracellular Ca2+ release, α and ß receptors, etc. Nuciferine exhibits good vasodilatory activity, and it exhibits the potential to be utilized as a lead compound.

Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways.

A series of quillaic acid derivatives with different substituents on the 28-carboxyl group were designed and synthesized. Five human cancer cell lines (HCT116, BEL7402, HepG2, SW620, and MCF-7) were evaluated for their antitumor activity in vitro. Some of the tested derivatives showed improved antiproliferative activity compared to the lead compound, quillaic acid. Among them, compound E (IC50 = 2.46 ± 0.44 µM) showed the strongest antiproliferative activity against HCT116 cells; compared with quillaic acid (IC50 > 10 µM), its efficacy against HCT116 cancer cells was approximately 4-fold higher than that of quillaic acid. Compound E also induces cell cycle arrest and apoptosis by modulating NF-κB and MAPK pathways. Therefore, the development of compound E is certainly valuable for anti-tumor applications.

Anti-hypertensive and endothelia protective effects of Fufang Qima capsule on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway.

OBJECTIVE: To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule. METHODS: Spontaneous hypertensive rats (SHRs) were used to study the underlying mechanism of the anti-hypertension activity of QM. In this study, SHRs were randomly divided into 5 groups: model group, Telmisartan group (7.2 mg/kg, p.o.), and three QM groups (0.9298, 1.8596, and 3.7192 g/kg, p.o.). Wistar Kyoto rats (WKY) were used as normal control group. Blood pressure (BP), aorta, perivascular adipose tissue (PVAT) histology were investigated to evaluate the effect of QM. Nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) phosphorylation were measured. Adiponectin (APN) secretion, as well as APN signal pathway proteins including APN, adiponectin receptors (R1 and R2) and adenosine 5'-monophosphate-activated protein kinase (AMPK) were all analyzed. RESULTS: QM significantly reduced BP and ameliorated the vascular pathological change, i.e. intima media thicken and collagen fiber hyperplasia. Meanwhile, QM increased concentration of NO and the phosphorylation of eNOS in the aorta. The anti-hypertensive and endothelia-protective effect of QM could be attributed to activating APN/ AMPK pathway by up-regulating the expression of APN in PVAT and APN Receptor 2, AMPKα and phosphorylated AMPKα in the aorta. CONCLUSION: The QM alleviation effect mechanism for primary hypertension was via modulating the APN/AMPK signal pathway.

Potential α-glucosidase inhibitor from Hylotelephium erythrostictum.

In light of the adequate sources for Hylotelephium erythrostictum, its active components have aroused research interest. 2-(3',4'-dihydroxyphenyl)-2,3-dihydro-4,6-dihydroxy-2-(methoxy)- 3-benzofuranone(1), apigenin(2), diosmetin(3), kaempferol(4), kaempferide(5), rhamnocitrin(6), quercetin(7), and gallic acid(8) were isolated from H. erythrostictum. Rarely occurring naturally, 1 is 2-methoxybenzofuranone type compound against α-glucosidase and exhibits a potential inhibitory effect on α-glucosidase(IC50 = 1.8 µM), with a Ki value of 709 nM. In silico molecular docking was performed for the investigation of the inhibition mechanism. H. erythrostictum is a potential source of antidiabetic agent. This information is useful in finding more potent antidiabetic candidates from medicinal plants for the clinical development of therapeutics.

Evaluation of ursolic acid derivatives with potential anti-Toxoplasma gondii activity.

Toxoplasma gondii is an important pathogen that causes serious public health problems. Currently, therapeutic drugs for toxoplasmosis cause serious side effects, and more effective and novel substances with relatively low toxicity are urgently needed. Ursolic acid (UA) has many properties that can be beneficial to healthcare. In this study, we synthesized eight series of UA derivatives bearing a tetrazole moiety and evaluated their anti-T. gondii activity in vitro using spiramycin as a positive control. Most of the synthesized derivatives exhibited better anti-T. gondii activity in vitro than UA, among which compound 12a exhibited the most potent anti-T. gondii activity. Furthermore, the results of biochemical parameter determination indicated that 12a effectively restored the normal body weight of mice infected with T. gondii, reduced hepatotoxicity, and exerted significant anti-oxidative effects compared with the findings for spiramycin. Additionally, our molecular docking study indicated that the synthesized compounds could act as potential inhibitors of T. gondii calcium-dependent protein kinase 1 (TgCDPK1), with 12a possessing strong affinity for TgCDPK1 via binding to the key amino acids GLU129 and TYR131.

Prevalence and Risk Factors of Restless Legs Syndrome in Hemodialysis Patients.

OBJECTIVE: The current study aimed to investigate the prevalence and risk factors of restless legs syndrome (RLS) in patients undergoing hemodialysis, as well as the mortality and risks of cardiovascular and cerebrovascular events. METHODS: A total of 354 hemodialysis patients from four hospitals were enrolled. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria. The patients were evaluated face-to-face using the IRLSSG rating scale, Epworth Sleepiness Scale (ESS), Hamilton Anxiety Scale, Hamilton Depression Scale, and Pittsburgh Sleep Quality Index (PSQI). The patients were followed up for 9 months. Death was considered an endpoint event. The cardiovascular and cerebrovascular events were investigated. RESULTS: The prevalence of RLS in hemodialysis patients was 40.7% and was associated with factors such as duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. The scores of the PSQI, ESS, and Hamilton Depression Scale in the RLS group were significantly higher than those in the non-RLS group (p < 0.05). During follow-ups, the incidence rate of cardiovascular diseases was 18.8% in the RLS group and 8.6% in the non-RLS group (p < 0.005). The IRLSSG rating scores were significantly higher in RLS patients with kidney transplantation failure compared with those without transplantation (p < 0.05). CONCLUSION: The prevalence of RLS was high in hemodialysis patients. The risk factors of RLS included duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. RLS affected sleep quality and emotion and increased the risk of cardiovascular diseases in hemodialysis patients. RLS was more severe in patients with kidney transplantation failure compared with those without transplantation.

[Spatial and temporal variability of climatic potential productivity in Yunnan Province, China.] / 云南省气候生产潜力的时空变化.

We used the mean annual temperature and mean annual precipitation data during 1961 and 2017 of 101 national meteorological stations in Yunnan Province to calculate three climate-induced potential productivity in Yunnan Province by Miami model and the Thornthwaite Memorial model. The abrupt test was carried out by Mann-Kendell method. The spatial and temporal distribution characteristics and future trends of the three climate-induced potential productivities were analyzed. Results showed that the average values of the temperature potential productivity (Yt), precipitation potential productivity (Yr) and evapotranspiration potential productivity (Ye) during the study period was 1968, 1477 and 1434 g·m-2·a-1, respectively. The value of Yt was rising in Yunnan Province. For the value of Yr /Yt, there was a large difference in water-heat ratio among regions, as well as the binding conditions. There was an abrupt change in climate-induced potential productivity, with Yt began to abrupt change significantly in 2001. There was no abrupt change in Yr, but Ye had abrupt change in 2002-2004. The spatial distribution of climate production potential and climate tendency were uneven. The annual average value of Yt, Yr and Ye was 1030-2465, 927-2341 and 832-1995 g·m-2·a-1, respectively. The climate-induced potential productivity was the lowest in the northwestern and northeastern Yunnan and the highest in the southwestern and southern Yunnan. Most of the climatic propensity rates of Yt, Yr and Ye showed increase, decrease and increase trends respectively. Eight schemes simulating future climate change (i.e., temperature increased by 1 ℃, precipitation increased by 10%, temperature decreased by 1 ℃, precipitation decreased by 10%, temperature increased by 1 ℃ and precipitation decreased by 10%, temperature increased by 1 ℃ and precipitation increased by 10%, the temperature decrease by 1 ℃ and the precipitation increased by 10%, the temperature decrease by 1 ℃ and precipitation decreased by 10%) would lead to Ye changes of 6-45, 13-77.2, 15-67, -87 to -17, -74-46, 58-96, -54-57, -101 to -59 g·m-2·a-1, respectively. On the whole, if the climate tends to be "warm and wet" in the future, it will be beneficial for crop production. However, if it tends to be "cold and dry", it will be unfavorable to crop production in the study area.

Value of cystatin C in predicting atrial fibrillation recurrence after radiofrequency catheter ablation.

BACKGROUD: Recent studies have demonstrated that cystatin C is a valuable risk marker for cardiovascular disease morbidity and mortality. Therefore, we hypothesized that the pre-ablation cystatin C level was associated with post-ablation atrial fibrillation (AF) recurrence. METHODS: 207 patients were enrolled and completed in this prospective observational study. Patients with AF scheduled for receive radiofrequency catheter ablation (RFCA) therapy were screened for the study. Before ablation therapy, electrocardiogram, 24 h holter monitor, transesophageal echocardiography, serum cystatin C, high-sensitivity C-reactive protein, creatinine levels, and routine blood examinations were examined. After ablation, patients were followed up every week for the first month, and then at 2, 3, 6, 9, and 12 months. Thereafter, patients came back to out-patient clinic every six months regularly. Electrocardiogram or 24 h holter monitor were repeated if the patient experienced palpitations or every six months. AF recurrence was defined as atrial fibrillation/atrial flutter or atrial tachycardia lasting ≥ 30 seconds within three months after therapy. RESULTS: Compared to patients with no AF recurrence, patients with recurrence had longer AF history (P = 0.007), more early recurrence (P = 0.000), a larger left atrium (P = 0.004), and higher pre-ablation cystatin C levels (P = 0.000). Multivariate regression analysis revealed that cystatin C and left atria (LA) diameter were risk factors for AF recurrence. After adjusting for LA diameter, the risk of AF recurrence increased 30% with every milligram cystatin C elevation (95% CI: 1.117-1.523). CONCLUSIONS: Pre-ablation cystatin C levels were associated with AF recurrence after RFCA therapy, an optimal cut-off value of 1.190 mg/L (sensitivity = 0.576; specificity = 0.851).

Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO2 fluid extract (SFE-CO2) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO2 extract may be a useful agent in BPH treatment.

Synthesis and antiproliferative activity of 1,4-bis(dimethylamino)-9,10-anthraquinone derivatives against P388 mouse leukemic tumor cells.

A series of 2-substituted-1,4-bis(dimethylamino)-9,10-anthraquinone derivatives were synthesized and their in vitro antiproliferative activities against p388 mouse leukemic tumor cells were evaluated. In addition, the effect of substituents on the phenyl ring was investigated. Among the derivatives tested, seven showed a high antiproliferative effect and three showed a moderate effect. In addition, introduction of a series of substituted phenyl groups into 1,4-bis(dimethylamino)-9,10-anthraquinone at 2-position were shown to enhance its antiproliferative activity. The antiproliferative activity also increased upon substitution of the benzene ring by an electron donating group such as an amine or methoxyl group.

Characterization of antimicrobial peptides isolated from the skin of the Chinese frog, Rana dybowskii.

The skins of amphibians secrete small antimicrobial peptides that fight infection and are being explored as potential alternatives to conventional antibiotics. In this study we combined mass spectrometry with cDNA sequencing to examine antimicrobial peptides in skin secretions from the Chinese frog Rana dybowskii. Thirteen peptides having precursor sequences that resemble known antimicrobial peptides from this genus were identified, ten of which were members of previously described peptide families based on their primary structures; i.e., brevinin-1, Japonicin-1, brevinin-2 and temporin. The other three peptides from R. dybowskii, which were named dybowskin-1CDYa, dybowskin-2 CDYa and dybowskin-2CDYb, had different amino acid compositions and little sequence similarity to known antimicrobial peptides. The carboxyl terminus of dybowskin-1CDY lacked amidation and is therefore clearly distinct from temporin peptides, whereas dybowskin-2CDYa and dybowskin-2CDYb consisted of 18 amino acids and were rich in Arg residues. Chemically synthesized peptides corresponding to mature dybowskin-1CDYa and dybowskin-2CDYa had strong antimicrobial activity and caused little hemolysis of human erythrocytes, suggesting they may serve as interesting templates for the development of novel antibiotics.

5 alpha-reductase and aromatase inhibitory constituents from Brassica rapa L. pollen.

In the screening of biologically active constituents from Brassica rapa pollen, the supercritical CO(2) fluid extract (SFE-CO(2)) showed potent 5 alpha-reductase and aromatase inhibiting activity. The SFE-CO(2) extract was separated by various chromatographic methods to give two new phytosterol derivatives, 24-methylenecholesterol linolenate (1) and cycloeucalenol linolenate (2), as well as eight known compounds, 24-methylenecholesterol palmitate (3), cycloeucalenol (4), pollinastanol (5), 24-methylenecholesterol (6), linolenic acid (7), palmitic acid (8), monolinolein (9) and monopalmitin (10), compounds 7 and 9 showed potent 5 alpha-reductase inhibitory activity; compounds 1-6 and 10 showed potent aromatase inhibitory activity.

[Molecular diversities and functions of antibacterial peptides from the skins of Ranidae of amphibians.].

Granular glands in the frog skins of Ranidae of amphibians, a widely distributed group with over 650 species, synthesize and secrete a remarkably diverse array of peptides with the broad-spectrum antibacterial, antifungal and other biologic activities to protect the organism against a wide range of pathogens, which are believed to have arisen as a result of multiple gene duplication events. Almost without exception, these components are hydrophobic, cationic and form an amphipathic a-helix in a membrane-mimetic solvent. The peptides can be grouped into families on the basis of structural similarity. To date, brevinin-1, esculentin-1, esculentin-2, and temporin peptides, ranalexin, ranatuerin-1, ranatuerin-2 and palustrin, brevinin-2, tigerinin, japonicin, nigrocin and melittin-related peptides have been found in amphibians of Ranidae. In this paper, the molecular diversity, structural feature and the biological ac-tivity of Ranidae antibacterial peptides were reviewed.

Thermal dosimetric study on hyperthermia combined with radiotherapy for deep seated pelvic malignancies / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To ascertain a clinically meaningful thermal dose unit-temperature equivalent minute (TEM) 42.5 degrees C and the relationship between TEM 42.5 degrees C and tumor response rate.</p><p><b>METHODS</b>From August 1998 to December 2002, 49 patients with recurrent or metastatic malignancies in the pelvis were treated with hyperthermia combined with conventional radiotherapy. Direct thermometry with high resistance lead needle was used whenever possible to measure the temperature by inserting Teflon catheter into the tumor. TEM 42.5 degrees C was used as the thermal dose unit and the relationship between TEM 42.5 degrees C and tumor response rate was monitored.</p><p><b>RESULTS</b>There was a positive correlation between response rate TEM 42.5 degrees C and the radiation dose. The tumor volume and number of heat treatment showed no influence on response.</p><p><b>CONCLUSION</b>Both univariate analysis and multivariate logistic regression analysis indicate that there is a positive correlation between the response rate, TEM 42.5 degrees C and the radiation dose. TEM 42.5 degrees C may act as a useful thermal dose unit in the combination of hyperthermia and radiotherapy. To lower the incidence of complications in thermometry, direct thermometry with high resistance lead needle can be used to measure the temperature by inserting Teflon catheter into the deep-seated malignancies.</p>

[ERIC-PCR on identification of Listeria species and strain].

Enterobacteria repetitive intergenic consensus sequences-based PCR(ERIC-PCR) was used to generate DNA fingerprints for Listeria spp. We got the specific profiles with ERIC-PCR technique that enables to identify Listeria species and the L.monocytogenes strains of different stereotype, and the same stereotype of L. monocytogenes from different sources also could be identified. Moreover,the species-specific 1600 bp DNA fragment was obtained from the fingerprint of L. monocytogenes. The study indicates that ERIC-PCR technique can be used in the identification of Listeria species and strains and its further typing, which is simple and quickly.