Polyketides from the fungus Pochonia chlamydosporia and their bioactivities.

Three previously undescribed griseofulvin derivatives, namely pochonichlamydins A-C, one small polyketide, namely pochonichlamydin D, together with nine known compounds, have been isolated from cultures of the fungus Pochonia chlamydosporia. Their structures with absolute configurations were elucidated on the basis of extensive spectrometric methods and single-crystal X-ray diffraction. Dechlorogriseofulvin and griseofulvin exhibited inhibitory activities against Candida albicans at the concentration of 100 µM, with inhibition rates of 69.1% and 56.3%, respectively. Meanwhile, pochonichlamydin C showed mild cytotoxicity against the human cancer MCF-7 cell line with an IC50 value of 33.1 µM.

Elevated histone demethylase KDM5C increases recurrent miscarriage risk by preventing trophoblast proliferation and invasion.

KDM5C is a histone H3K4-specific demethylase, which has been shown to play a key role in biological disease and development. However, the role of KDM5C in trophoblasts at early pregnancy is currently unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from recurrent miscarriage (RM) patients compared with healthy controls (HCs). Trophoblast proliferation and invasion was inhibited by KDM5C overexpression and was promoted by KDM5C knockdown. Transcriptome sequencing revealed that elevated KDM5C exerted anti-proliferation and anti-invasion effects by repressing the expression of essential regulatory genes. The combination analysis of RNA-seq, ChIP-seq and CUT&Tag assay showed that KDM5C overexpression leads to the reduction of H3K4me3 on the promoters and the corresponding downregulation of expression of several regulatory genes in trophoblasts. Among these genes, TGFß2 and RAGE are essential for the proliferation and invasion of trophoblasts. Importantly, overexpression of KDM5C by a systemically delivered KDM5C adenovirus vector (Ad-KDM5C) promoted embryo resorption rate in mouse. Our results support that KDM5C is an important regulator of the trophoblast function during early pregnancy, and suggesting that KDM5C activity could be responsible for epigenetic alterations seen RM disease.

Reinforced erythroid differentiation inhibits leukemogenic potential of t(8;21) leukemia.

Oncoprotein AML1-ETO (AE) derived from t(8;21)(q22;q22) translocation is typically present in a portion of French-American-British-M2 subtype of acute myeloid leukemia (AML). Although these patients have relatively favorable prognoses, substantial numbers of them would relapse after conventional therapy. Here, we explored whether reinforcing the endogenous differentiation potential of t(8;21) AML cells would diminish the associated malignancy. In doing so, we noticed an expansion of immature erythroid blasts featured in both AML1-ETO9a (AE9a) and AE plus c-KIT (N822K) (AK) murine leukemic models. Interestingly, in the AE9a murine model, a spontaneous step-wise erythroid differentiation path, as characterized by the differential expression of CD43/c-Kit and the upregulation of several key erythroid transcription factors (TFs), accompanied the decline or loss of leukemia-initiating potential. Notably, overexpression of one of the key erythroid TFs, Ldb1, potently disrupted the repopulation of AE9a leukemic cells in vivo, suggesting a new promising intervention strategy of t(8;21) AML through enforcing their erythroid differentiation.

Tetra-, penta-, and hexa-nor-lanostane triterpenes from the medicinal fungus Ganoderma australe.

Chemical investigation on the medicinal fungus Ganoderma australe led to the identification of ten new nor-lanostane triterpenes, namely two hexa-nor ones, ganoaustratetraenones A (1) and B (2), five penta-nor ones, ganoaustraldehydes A-E (3-7), and three tetra-nor ones ganoaustrenoic acids A-C (8-10). The chemical structures along with the absolute configurations were determined by extensive spectroscopic analysis of 1D & 2D NMR and HRESIMS data. The postulated biosynthesis pathways of these compounds were proposed. Ganoaustraldehydes A (3) and B (4) showed moderate inhibition against nitric oxide production in RAW264.7 macrophage cells with the respective IC50 values of 32.5, 34.2 µM (the IC50 of positive control pyrrolidine dithiocarbamate was 20.0 µM).

Four New Highly Oxygenated Eremophilane Sesquiterpenes from an Endophytic Fungus Boeremia exigua Isolated from Fritillaria hupehensis.

Four new eremophilane-type sesquiterpenes, boeremialanes A-D (1-4) were obtained from solid substrate cultures of Boeremia exigua (Didymellaceae), an endophytic fungus isolated from Fritillaria hupehensis (Liliaceae). Boeremialanes A-C (1-3) are highly oxygenated eremophilanes with a benzoate unit attached at the C-13 position and are rarely found in nature. Their structures and absolute configurations were determined by extensive spectroscopic methods, electronic circular dichroism (ECD), and nuclear magnetic resonance (NMR) calculations with DP4+ analysis. Boeremialane D (4) potently inhibited nitric oxide production in lipopolysaccharide-treated RAW264.7 macrophages with an IC50 of 8.62 µM and was more potent than the positive control, pyrrolidinedithiocarbamate (IC50 = 23.1 µM).

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury.

Myocardial ischemia and reperfusion injury (MIRI), induced by coronary heart disease (CHD), causes damage to the cardiomyocytes. Furthermore, evidence suggests that thrombolytic therapy or primary percutaneous coronary intervention (PPCI) does not prevent reperfusion injury. There is still no ideal animal model for MIRI. This study aims to improve the MIRI model in rats to make surgery easier and more feasible. A unique method for establishing MIRI is developed by using a soft tube during a key step of the ischemic period. To explore this method, thirty rats were randomly divided into three groups: sham group (n = 10); experimental model group (n = 10); and existing model group (n = 10). Findings of triphenyltetrazolium chloride staining, electrocardiography, and percent survival are compared to determine the accuracies and survival rates of the operations. Based on the study results, it has been concluded that the improved surgery method is associated with a higher survival rate, elevated ST-T segment, and larger infarct size, which is expected to mimic the pathology of MIRI better.

[Meta-analysis for clinical efficacy of traditional Chinese medicine in treating resistant hypertension].

To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating patients with resistant hypertension. CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase and other databases were retrieved by computers to screen out the randomized controlled trial of traditional Chinese medicine in treating resistant hypertension. Cochrane Handbook was used to evaluate the quality of the included literature, RevMan 5.3 and Stata 12.0 was used for Meta-analysis. Finally, 11 literatures meeting the criteria were included, involving 1 023 patients. The results of Meta-analysis showed that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further reduce systolic blood pressure of patients with resistant hypertension(MD=-16.69, 95%CI[-22.21,-11.16], P<0.000 01), reduce diastolic blood pressure(MD=-7.51, 95%CI[-8.26,-6.76], P<0.000 01), improve the effective rate of anti-hypertension(OR=5.16, 95%CI[3.01, 8.84], P<0.000 01), improve the up-to-standard rate of blood pressure(OR=3.01, 95%CI[1.49, 6.09], P=0.002), and improve the effectiveness of clinical symptoms(OR=4.48, 95%CI[2.31, 8.68], P<0.000 01), with no significant effect on creatinine level(MD=-2.51, 95%CI[-6.91, 1.89], P=0.26). The results of this study indicated that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further improve the clinical efficacy in patients with resistant hypertension with a good safety, but more high-quality clinical studies are still needed to verify this conclusion.

KDM5C Represses FASN-Mediated Lipid Metabolism to Exert Tumor Suppressor Activity in Intrahepatic Cholangiocarcinoma.

Background: KDM5C is a histone H3K4-specific demethylase, which has multiple biological functions during development and disease. However, the role of KDM5C in intrahepatic cholangiocarcinoma (ICC) remains unknown. Methods: Expression levels of KDM5C in ICC patients were determined by qRT-PCR, western blotting and immunohistochemical assay. The functions of KDM5C in cell proliferation and invasion were determined in human ICC cells and mouse xenograft model using KDM5C overexpression and knockdown strategies in vivo. RNA-seq analysis was applied to investigate the transcriptional program of KDM5C. In addition, ChIP-qPCR was used to determine the regulation of FASN by KDM5C. Results: Here, we show that KDM5C was downregulated in human ICC, where its diminished expression was associated with poor prognosis. ICC cell proliferation and invasion were inhibited by KDM5C overexpression. Moreover, KDM5C suppressed ICC proliferation and metastasis in vivo. RNA-sequencing showed that KDM5C inhibits key signal pathways of cell proliferation, cell invasion and fatty acid metabolism. ChIP-qPCR revealed that overexpression of KDM5C led to the reduction of H3K4me3 on the promoter and the corresponding downregulation of the expression of FASN, which represents the major target gene of KDM5C to mediate the proliferation and invasion of ICC cells. Conclusions: Our results revealed the role of KDM5C as a novel tumor suppressor in ICC largely by repressing FASN-mediated lipid acid metabolism and thus KDM5C may contribute to the pathogenesis of ICC.

Inhibitory effect of aloe emodin mediated photodynamic therapy on human oral mucosa carcinoma in vitro and in vivo.

We report a study on inhibition of human oral squamous cell carcinoma in vitro and in vivo, using novel photosensitizer (PS) aloe emodin (AE) mediated photodynamic therapy (PDT). Distinct morphology changes of oral mucosa carcinoma KB cells were observed under an optical microscope and cell migrations were inhibited owing to AE-PDT. The cell proliferation was blocked in G1 phase and the apoptosis increase were both caused by massive reactive oxygen species (ROS) generated from photoactivated AE. The upregulation of Caspase-3 and Bax protein levels and downregulation of Bcl-2 protein levels were observed after AE-PDT. The survival time of tumor mouse was prolonged without side effects ascribed to AE-PDT and its inhibitory effect on mice transplantation tumors was significant. It is indicated that AE mediated PDT is an innovative way to oral cancer treatment with the dominances of effectivity, minimal invasion, tissue integrity retention and none side effects on main organs.

[Identification of pathogen of Aquilaria sinensis dieback disease].

OBJECTIVE: The research focused on identification the pathogen of Aquilaria sinensis dieback disease and confirmation the function of inducing agarwood formation by fungi. METHOD: The morphological observation, rDNA ITS sequence analyses, Koch's postulates and pathogenicity test were used to identify the isolates. RESULT: The isolates of the causal agent was Lasiodiplodia theobromae, which induced the plant to produce highly valuable agarwood. CONCLUSION: The first report of dieback disease of Aquilaria sinensis caused by L. theobromae, and our research results laid a theoretical foundation for agarwood production by using fungus.

[Cloning and bioinformatics analysis of chalcone synthase (AsCHS1) gene in Aquilaria sinensis].

OBJECTIVE: The study aimed to clone the open reading frame of chalcone synthase (CHS) from Aquilaria sinensis and analyze the bioinformatics and expression of the gene. METHOD: One unique sequence containing CHS domain was discovered in our previous reported wound transcriptome dataset of A. sinensis. The open reading frame of CHS was cloned by RT-PCR strategy with the template of mixed RNA extracted from A. sinensis stem which treated by different wound time. The bioinformatic analysis of this gene and its corresponding protein was performed. The AsCHS1 expression in calli was analyzed with histone gene as an internal control gene under wound condition by qRT-PCR technique. RESULT: One unique sequence of CHS, named as AsCHS1, was cloned from A. sinensis. The full length of AsCHS1 cDNA was containing a 1 192 bp ORF that encoded 397 amino acids. The result of qRT-PCR displayed that the highest expression level was at 12 h, which indicated that it was possibly involved in early-stage response to wound. CONCLUSION: Cloning and analyzing AsCHS1 gene from A. sinensis provided basic information for study the function and expression regulation of AsCHS1 in the flavonoids biosynthesis.

[The mechanical wound transcriptome of three-year-old Aquilaria sinensis].

Chinese agarwood is formed in the aromatic resinous wood formed in Aquilaria sinensis (Lour.) Gilg (botanical family: Thymelaeaceae). Only when suffering stress of wound, etc, can A. sinensis produce sesquiterpenes etc. compounds of agarwood around wounds. However, little is known about how wound induced the biosynthesis pathway of sesquiterpenes. To reveal the molecular mechanism of wound-induced agarwood formation, RNA sequencing (RNA-seq) technology was used to investigate the profile of gene expression in A. sinensis treated by mechanical wounding and elucidate its functional gene. A total of 40,295 ESTs with an average read length of 305 bp were generated and 22 095 unigenes were formed by initial gene splicing. 61.6% of these unigenes (13 611) were annotated using BLAST searches against the SwissProt, KEGG, Nr and Nt databases. Twenty-six unigenes (encoding 7 enzymes) were found to be involved in sesquiterpene of agarwood biosynthesis by bioinformatic tools of Gene Ontology and KEGG. Novel genes that are potentially involved in sesquiterpenes biosynthesis were identified in A. sinensis, providing data for further sesquiterpenes biosynthesis pathway by molecular methods and the EST data establish a foundation for future studies in the molecular mechanisms of wound-induce agarwood formation in A. sinensis.

Influence of halide ions on the chirality and luminescent property of ionothermally synthesized lanthanide-based metal-organic frameworks.

Four lanthanide-based metal-organic frameworks, [Emim][Ln(1.5)(2,5-tdc)(2)]Cl(1.5-x)Br(x) (Ln = Nd 1, Eu 2) and [Emim][Ln(2,5-tdc)(2)] (Ln = Nd 3, Eu 4) (2,5-tdc = thiophene-2,5-dicarboxylate, Emim = 1-methyl-3-ethylimidazolium), were synthesized under ionothermal conditions. Compounds 1 and 2 crystallize in the polar space group P2(1)2(1)2, while 3 and 4 crystallize in the central symmetry space group P2(1)/c. Luminescence studies revealed a significantly higher quantum yield of 4 than that of 2, with similar lifetimes. It is clear that the coordination of the halide ions has profound effects on the structures and properties of these lanthanide-based metal-organic frameworks.