Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H2O2-induced cell apoptosis through modulating PI3K/Akt pathway.

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

Fermented Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer alleviates diabetic erectile dysfunction by attenuating oxidative stress and regulating PI3K/Akt/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer (G. officinalis) has been historically as tonics to treat impotence. Fermentation is an ancient processing method for traditional Chinese medicine. Whether fermentation affects the therapeutic effects of G. officinalis on diabetic erectile dysfunction has so far remained unknown. AIMS OF THE STUDY: In this research, we aim to determine the effect of fermented or unfermented G. officinalis root extract on diabetes mellitus-induced erectile dysfunction (DMED) and the potential mechanisms. MATERIALS AND METHODS: Candida sp. B5, Lactobacillus sp. Y5 and Lactobacillus sp. R2 are applied for the fermentation of G. officinalis. The optimum fermentation conditions of G. officinalis are investigated. Sprague-Dawley rats were used to establish a diabetic erectile dysfunction model, treated with different concentrations of fermented or unfermented G. officinalis, to compare the effect of fermented or unfermented G. officinalis on DMED and explore underlying mechanisms by assessment of intracavernous pressure, ELISA, Western blot, Masson's trichrome staining, and immunofluorescence. The corpus cavernosum smooth muscle cells (CCSMCs) and Schwann cells were isolated and used to investigate the effect of fermented or unfermented G. officinalis on hydrogen peroxide (H2O2)-induced apoptosis. RESULTS: The results reveal the optimum fermentation conditions of G. officinalis using Lactobacillus sp. Y5 were determined to be 35 °C, the ratio of solid to liquid 1:10, and six days of fermentation. The fermentation increases the abundance of major active ingredients within G. officinalis. After fermented or unfermented G. officinalis treatment for eight weeks by oral gavage at a dose of 100 mg kg-1 or 300 mg kg-1, the results show that the fermentation enhances the effect of G. officinalis on diabetic erectile dysfunction detected by intracavernous pressure. The protein expressions of the PI3K/Akt/eNOS pathway were upregulated in diabetic rats after fermented or unfermented G. officinalis treatment, while the level of oxidative stress was significantly reduced. Meanwhile, Masson's trichrome staining also displayed an improvement in the ratio of smooth muscle to collagen. In vitro experiments confirmed that fermented or unfermented G. officinalis protected CCSMCs and Schwann cells from apoptosis. In contrast, fermented G. officinalis showed a fortified protective effect over unfermented G. officinalis. CONCLUSION: Our findings suggest that fermentation can increase the composition of main active ingredients in G. officinalis and enhance its role in diabetic erectile dysfunction. It augurs the potential therapeutic application of fermented G. officinalis well for treating diabetic erectile dysfunction.

New Thio-Compounds and Monoterpenes With Anti-inflammatory Activities From the Fungus Aspergillus sp. CYH26.

Two new thio-compounds named aspergerthinol A and B (1 and 2) and two new monoterpenes named aspergerthinacids A and B (3 and 4) were isolated from the fungus Aspergillus sp. CYH26 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds were elucidated by spectroscopic data and quantum NMR and ECD calculations. Compounds 1 and 2 represented a new family of sulfur containing natural products with a 3-methyl-4H-cyclopenta[b]thiophen-4-one skeleton. Compounds 1-4 showed inhibitory activities against nitric oxide (NO) with IC50 values of 38.0, 19.8, 46.3, and 56.6 µM, respectively.

Indole-Terpenoids With Anti-inflammatory Activities From Penicillium sp. HFF16 Associated With the Rhizosphere Soil of Cynanchum bungei Decne.

Four new indole-terpenoids (1-4) named encindolene A, 18-O-methyl-encindolene A, encindolene B, and encindolene C, as well as three known analogs (5-7), were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds including absolute configurations were elucidated by spectroscopic data and electronic circular dichroism (ECD) analysis. Anti-inflammatory activity evaluation revealed that compounds 1-7 inhibit the production of nitric oxide with IC50 values of 79.4, 49.7, 81.3, 40.2, 86.7, 90.1, and 54.4 µM, respectively, and decrease the levels of tumor necrosis factor-α, interleukin-6 contents in lipopolysaccharide-induced RAW264.7 macrophages.

[Correlation between Gut Microbiota and Lung Cancer].

Gene-environment interactions underlie cancer susceptibility and progression. The human body is exposed to and affected by the microenvironment seiscasts of various microorganisms and their metabolites, such as the microenvironment of gut microbiota. The relative abundance of some intestinal microbes in lung cancer patients was significantly different from that in the control group. These studies suggest that gut microbiota may be associated with lung cancer through some ways. At the same time, gut microbiota is relatively manageable environmental variables compared to the external environment we are exposed to, as they are highly quantifiable and relatively stable in the individual. Just as some measures of diagnosis, intervention and treatment of lung cancer targeting gut microbiota have achieved some results in clinical practice. In this review, we mainly discuss the role of gut microbiota and its metabolites in the progression and treatment of lung cancer through certain ways, such as regulation of metabolism, inflammation, and immune response. Finally, based on current research progress, it is inferred that research on gut microbiota may be an effective approach to the precise and personalized medical treatment of lung cancer.
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Inaccuracy of Thyroid to Background Uptake Ratio in Evaluating Technetium-99m-pertechnetate Thyroid Uptake and Establishing an Improved Algorithm.

OBJECTIVES: The aim of this study was to explore the accuracy of thyroid to background uptake ratio (UR) in the evaluation of 99mTc-pertechnetate thyroid uptake (TcTU) and establishment of an improved algorithm. METHODS: This study was conducted on the thyroid images of 322 patients with thyroid diseases and 67 controls. For the purpose of the study, URs of the images were calculated, and then corrected by standardized thyroid area size to establish a corrected uptake ratio (CUR). Subsequently, the accuracy between UR and CUR was compared. RESULTS: The results of linear regression using weighted least squares (using TcTU as a dependent variable and CUR, UR, or thyroid area size as independent variables) showed that CUR (t=105.5, P=0.000), UR (t=31.9, P=0.000), and thyroid area size (t=15.9, P=0.000) are influential factors of TcTU. Furthermore, the standardized coefficient of CUR (ß=0.983) was obviously higher than those of UR (ß=0.851) and thyroid area size (ß=0.629). The linear goodness-of-fit between CUR and TcTU (R=0.983) was better than that between UR and TcTU (R=0.851). In addition, the total concordance rate between CUR and TcTU (96.7%) was significantly higher than that between UR and TcTU (83.0%; χ2=42.9, P=0.000). Discordance rates of CUR in large thyroid area (1.4% vs. 13.4%, χ2=17.0, P=0.000) and small thyroid area (3.3% vs. 42.2 %, χ2=44.3, P=0.000), were significantly lower than that of UR. In the abnormal thyroid areas, the discordance rates of UR obviously increased as compared to those of CUR. The UR overestimated the thyroid uptake in small thyroid areas and underestimated it in large thyroid areas. CONCLUSION: Based on the findings, CUR is more accurate than UR in measuring 99mTcO4- thyroid uptake; accordingly, it is more significant in the diagnosis of thyroid disease.

Phylogeography and conservation genetics of the endangered Tugarinovia mongolica (Asteraceae) from Inner Mongolia, Northwest China.

Tugarinovia (Family Asteraceae) is a monotypic genus. It's sole species, Tugarinovia mongolica Iljin, is distributed in the northern part of Inner Mongolia, with one additional variety, Tugarinovia mongolica var ovatifolia, which is distributed in the southern part of Inner Mongolia. The species has a limited geographical range and declining populations. To understand the phylogeographic structure of T. mongolica, we sequenced two chloroplast DNA regions (psbA-trnH and psbK-psbI) from 219 individuals of 16 populations, and investigated the genetic variation and phylogeographic patterns of T. mongolica. The results identified a total of 17 (H1-H17) chloroplast haplotypes. There were no haplotypes shared between the northern (T. mongolica) and southern groups (T. mongolica var. ovatifolia), and they formed two distinct lineages. The regional split was also supported by AMOVA and BEAST analyses. AMOVA showed the main variation that occurred between the two geographic groups. The time of divergence of the two groups can be dated to the early Pleistocene epoch, when climate fluctuations most likely resulted in the allopatric divergence of T. mongolica. The formation of the desert blocked genetic flow and enhanced the divergence of the northern and southern groups. Our results indicate that the genetic differences between T. mongolica and T. mongolica var. ovatifolia are consistent with previously proposed morphological differences. We speculate that the dry, cold climate and the expansion of the desert during the Quaternary resulted in the currently observed distribution of extant populations of T. mongolica. In the northern group, the populations Chuanjinsumu, Wuliji and Yingen displayed the highest genetic diversity and should be given priority protection. The southern group showed a higher genetic drift (FST = 1, GST = 1), and the inbreeding load (HS = 0) required protection for each population. Our results propose that the protection of T. mongolica should be implemented through in situ and ex situ conservation practices to increase the effective population size and genetic diversity.

Intraspecific divergences and phylogeography of Panzerina lanata (Lamiaceae) in northwest China.

Climatic fluctuations during the Quaternary significantly affect many species in their intraspecific divergence and population structure across northwest China. In order to investigate the impact of climate change on herbaceous plants, we studied Panzerina lanata (Lamiaceae), a widely distributed species. Sequences of two chloroplast DNA (cpDNA) intergenic spacers (trnH-psbA and rpoB-trnC) and a nuclear ribosomal region (nrDNA, ITS) were generated from 27 populations of Panzerina lanata and resulted in the identification of seven chloroplast haplotypes and thirty-two nuclear haplotypes. We applied AMOVA, neutrality test and mismatch distribution analysis to estimate genetic differentiation and demographic characteristics. The divergence times of the seven cpDNA haplotypes were estimated using BEAST. Our results revealed high levels of genetic diversity (cpDNA: Hcp = 0.6691, H T = 0.673; nrDNA: Hnr = 0.5668, H T = 0.577). High level of genetic differentiation (G ST = 0.950) among populations was observed in the cpDNA sequences, while the genetic differentiation values (G ST = 0.348) were low in nuclear sequences. AMOVA results revealed major genetic variation among the three groups: northern, central, and eastern group. However, the genetic differentiation in ITS data was not found. The species distribution modeling and demographic analysis indicated that P. lanata had not experienced recent range expansion. The occurrence of divergence between seven cpDNA haplotypes, probably during Pleistocene, coincides with aridification and expansion of the desert across northwest China that resulted in species diversification and habitat fragmentation. In addition, we discovered that the deserts and the Helan Mountains acted as effective geographic barriers that promoting the intraspecific diversity of P. lanata.

Effect of arotinolol on left ventricular function in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS: Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol. The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only beta-blocker. Left ventricular function was assessed with the New York Heart Association functional class and two-dimensional echocardiography. RESULTS: After 12-month arotinolol treatment, there was a significant improvement in left ventricular systolic function. Left ventricular end-systolic dimension significantly decreased from 59.52 +/- 8.83 mm to 50.89 +/- 8.17 mm (P < 0.001). Left ventricular ejection fraction significantly increased from 27.39% +/- 7.94% to 41.13% +/- 9.45% ( P < 0.001). Left ventricular mass index decreased from 150.47 +/- 42.42 g/m2 to 141.58 +/- 34.36 g/m2 (P < 0.01). No adverse events leading to premature discontinuation of study drug occurred. CONCLUSION: In this preliminary study, 12-month arotinolol treatment has a favorable effect on left ventricular function in patients with IDCM, and it is safe and well tolerated.

Changes of the proportion and mortality of pulmonary thromboembolism in hospitalized patients from 1974 to 2005.

BACKGROUND: Pulmonary thromboembolism (PTE) has become a common disease that severely endangers people's health. This study analysed the changes in proportion and mortality of PTE in hospitalized patients to provide data for prevention and management of the disease. METHODS: The data of 763 hospitalized patients with PTE from 1974 to 2005 in Fuwai Hospital were analysed. RESULTS: During the 1970s, 0.27% of patients in a cardiovascular hospital had PTE (< 5 cases per year); while so far this century the proportion is 0.94% (48 to 113 per year). The mortality of hospitalized PTE patients fell from 20.00% in the 1970s to 4.10% this century. Prior to 1990, the mortality of hospitalized PTE patients was 12.50%, and in the years after 1990 only 3.40%. The difference was statistically significant (P < 0.005). People with this disease were mostly between the ages of 30 and 69 years. Men were most susceptible between the ages of 30 and 69 years, while women between the ages of 40 and 69 years. Men contracted PTE 10 years earlier than women. The mortality of male PTE patients was 4.70%, not significantly different from female patients, 5.06% (0.50 < P < 0.75). There were not any significant differences between the mortality of patients in the different age groups overall (< or = 39, 40 - 49, 50 - 59, and > or = 60 years, P > 0.1). More people contracted the disease in winter than in other seasons (P < 0.05). There was no obvious difference between the mortality in different seasons overall (0.75 < P < 0.90). CONCLUSION: PTE is an increasingly significant disease and deserves adequate attention.

[Clinical analysis of 8 cases of paradoxical embolism].

OBJECTIVE: To describe the clinical features of paradoxical embolism and therefore to improve its diagnosis. METHODS: Case analysis and literature review. RESULTS: Eight cases of pulmonary embolism complicated with paradoxical embolism were diagnosed, of whom there were six men and two women (mean age, 47.6 years). Patent foramen ovale with right to left shunt was identified in only 3 cases. Cerebral embolism occurred in three patients, kidney artery embolism in 2 patients, left atrial thrombus in 1 patient, lower limb artery and aortic embolism in 1 patients respectively. The diagnosis of paradoxical embolism can only be confirmed when a venous thrombus was detected lodged at arterial-venous communication; otherwise, paradoxical embolism was considered a clinical diagnosis. Of the 8 cases, 7 were clinically diagnosed, while 1 was confirmed. CONCLUSIONS: Paradoxical embolism is not uncommon. The diagnosis should be considered when venous thromboembolism is complicated with systematic embolism or unknown cause of systematic embolism.

[Vicissitudes of proportion and mortality of patients with pulmonary thromboembolism].

OBJECTIVE: To investigate the vicissitudes of the proportion and the mortality of patients with pulmonary thromboembolism (PTE). METHODS: To analyze respectively the data of 442 patients with PTE admitted to the Fuwai Hospital during the period 1974-2002 were analyzed retrospectively. RESULTS: The numbers of PTE in-patients every year during the 1970s and 48-79 cases in the early 2000s. The hospitalization constituent ratio of PTE was 0.1152% in 1970s and was 0.5866% in early 2000s. The age of onset ranged from 30 to 60. The tide age was from 30 to 60 in the male patients and from 40 to 60 in the female patients. The in-hospital mortality of PTE patients was descending from 20.0% in 1970s to 5.8% in early 2000s. The in-hospital mortality was 12.5% before 1990 and was 4.5% after 1990 (P = 0. 005). The in-hospital mortality rates of the male and female patients were 4.6% and 8.6% respectively (P = 0.09). The in-hospital mortality rates of the patients younger than 70 and elder than 70 were 5.5% and 19.0% respectively (P < 0.05). CONCLUSION: PTE The mortality of PTE, which attacks males more frequently than females, and the proportions of the number of PTE in-patients to the number of the whole in-patients increased and the in-hospital mortality increased during the past 3 decades.

Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population.

A mutation in coagulant factor V gene, a substitution in the 3' untranslated region of prothrombin gene, and a variant in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be related to venous thromboembolism in Caucasians, but this relationship remains in debate in other populations. In this case-control study, we aimed to determine the prevalence of these three mutations in the Chinese population and investigate whether they are associated with pulmonary thromboembolism. The subjects consisted of 90 patients with pulmonary thromboembolism and 143 age- and sex-matched healthy controls. Traditional risk factors for venous thrombosis and pulmonary thromboembolism were investigated as well. We found that the frequencies of varicose vein, phlebitis, trauma, and surgery were significantly higher in cases than in controls. Of all subjects, none was a carrier of coagulant factor V gene G1691A mutation or prothrombin gene G 20210A mutation, which are common point mutations in Caucasians, while the frequency of MTHFR gene 677T allele exceeded 55% in cases (56.7%), controls (55.2%), and all subjects (55.8%) studied. The homozygous mutation rate of MTHFR gene was over 30% in both cases (33.3%) and controls (32.2%), but no significant difference was found in genotype distribution (chi(2)=0.100, P=0.951). Model fitting using logistic regression did not find that MTHFR gene C677T mutation was associated with pulmonary thromboembolism, consistent with the results of stratification analysis. In conclusion, coagulant factor V gene G1691A mutation and prothrombin G20210A mutation are very rare, while MTHFR C677T mutation is very common, and all of them are not associated with pulmonary thromboembolism in the Chinese population.

[Pulmonary artery sarcoma misdiagnosed as pulmonary thromboembolism: report of 3 cases and literature review].

OBJECTIVE: To improve the differential diagnosis of pulmonary artery sarcoma from pulmonary embolism. METHOD: Case analysis and literature review. RESULTS: Pulmonary artery sarcoma had similar clinical features as pulmonary thromboembolism. When the radiological features such as unilateral hilar enlargement and massive lumps in main trunk of pulmonary artery were observed and clinical deterioration occurred after thrombolytic and anticoagulant therapy, pulmonary artery sarcoma should be considered seriously in patients with suspected pulmonary thromboembolism. CONCLUSION: Pulmonary artery Sarcoma can be easily misdiagnosed as pulmonary thromboembolism.