Biosynthesis and bioactivities of microbial genotoxin colibactins.

Covering: up to 2021Colibactin(s), a group of secondary metabolites produced by the pks island (clb cluster) of Escherichia coli, shows genotoxicity relevant to colorectal cancer and thus significantly affects human health. Over the last 15 years, substantial efforts have been exerted to reveal the molecular structure of colibactin, but progress is slow owing to its instability, low titer, and elusive and complex biosynthesis logic. Fortunately, benefiting from the discovery of the prodrug mechanism, over 40 precursors of colibactin have been reported. Some key biosynthesis genes located on the pks island have also been characterised. Using an integrated bioinformatics, metabolomics, and chemical synthesis approach, researchers have recently characterised the structure and possible biosynthesis processes of colibactin, thereby providing new insights into the unique biosynthesis logic and the underlying mechanism of the biological activity of colibactin. Early developments in the study of colibactin have been summarised in several previous reviews covering various study periods, whereas the two most recent reviews have focused primarily on the chemical synthesis of colibactin. The present review aims to provide an update on the biosynthesis and bioactivities of colibactin.

Discovery of ent-kaurane diterpenoids, characteristic metabolites of Isodon species, from an endophytic fungal strain Geopyxis sp. XY93 inhabiting Isodon parvifolia.

Isogeopyxins A-C (1-3), three new diterpenoids with ent-kaurane, ent-pimarane, and ent-abietane scaffolds, respectively, along with six known ent-kauranoids, were isolated from the fermentation culture of Geopyxis sp. XY93 inhabiting the leaves of Isodon parvifolia. Their structures were elucidated by interpretation of spectroscopic data, and single crystal X-ray diffraction. It marks the first time that ent-kauranoids, characteristic metabolites of Isodon species, have been isolated from an associated endophytic fungus.

Nomograms for predicting survival in early-onset esophageal cancer.

Background: This study aimed to develop nomograms predicting the overall survival (OS) of patients younger than 50 years old with esophageal cancer.Methods: We selected patients included 2004-2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed using significant variables from multivariable Cox analyses. The discrimination and calibration power of the models were evaluated using concordance indexes (C-indexes) and calibration curves. Decision curve analysis was used to assess the clinical net benefits of the nomograms.Results: Of 1,997 selected patients, 53.2% had advanced-stage tumor. Race, grade, T stage, N stage, and treatment were independent factors affecting OS in early-stage patients. The C-indexes of the corresponding nomogram were 0.710 (95% CI = 0.684-0.736) and 0.681 (95% CI = 0.640-0.722) in training and validation sets, respectively. Grade, marital status, and treatment were independent factors affecting OS in advanced-stage patients. The C-indexes of the corresponding nomogram were 0.677 (95% CI = 0.653-0.701) and 0.675 (95% CI = 0.638-0.712) in training and validation sets, respectively. Calibration curves demonstrated high consistency between predicted and actual survival.Conclusion: We constructed and verified nomograms that could accurately predict the survival rate of esophageal cancer in patients younger than 50 years old. This may help clinicians better understand prognostic factors.

Serum microRNA expression profiling revealing potential diagnostic biomarkers for lung adenocarcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis. METHODS: The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays. RESULTS: Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs. CONCLUSION: The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

Discovery of isopenicin A, a meroterpenoid as a novel inhibitor of tubulin polymerization.

Microtubules are involved in celluar processes of movement, intracellular trafficking and mitosis, thus microtubule-targeting agents have been widely used in cancer therapy. Herein, we report isopenicin A, a novel meroterpenoid isolated from the plant endophytic fungus of Penicillium sp. sh18, as a novel microtubule binding molecule that efficiently depolymerizes microtubule polymerization to evoke G2/M cell cycle arrest and subsequent cell apoptosis, contributing to proliferation inhibition of human tumor cell lines. The discovery of isopenicin A provides a new chemotype for discovery and development of promising microtubule inhibitors.

Isopenicins A-C: Two Types of Antitumor Meroterpenoids from the Plant Endophytic Fungus Penicillium sp. sh18.

Isopenicins A-C (1-3), three novel meroterpenoids possessing two types of unprecedented terpenoid-polyketide hybrid skeletons, were isolated from the cultures of Penicillium sp. sh18. Their structures were determined through synergetic use of extensive spectroscopic analysis, quantum-chemical calculation with ANN-PRA analysis, and X-ray crystallographic analysis. Additionally, the inhibitory activities of these compounds on the Wnt/ß-catenin signaling pathway were evaluated, and 1 was identified as a potent inhibitor of the Wnt signaling pathway.

Secondary Metabolites from the Endophytic Fungus Xylaria sp. hg1009.

A detailed chemical investigation of the secondary metabolites produced by the endophytic fungus Xylaria sp. isolated from the stems of Isodon sculponeatus afforded six new compounds, xylariahgins A-F (1-6), two new natural products (7 and 8), along with two known compounds (9 and 10) (Fig. 1). The structures of all compounds were unambiguously established by analyzing their spectroscopic data or referring to pertinent literature. Compounds 1-8 were tested for their cytotoxic activity against five human tumor cell lines.

Hepatic resection combined with radiofrequency ablation versus hepatic resection alone for multifocal hepatocellular carcinomas: A meta-analysis.

This meta-analysis aimed to comprehensively assess the efficacy and safety of hepatic resection combined with radiofrequency ablation versus hepatic resection (HR) alone for the treatment of multifocal hepatocellular carcinomas (HCC). A literature search was conducted from the database including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and China Biology Medicine (CBM) disc. The primary outcomes included the 1-, 3-, 5-year overall survival (OS) and disease-free survival (DFS) rate. The secondary outcomes contained the intraoperative parameters and postoperative adverse events (AEs). These parameters were all analyzed by RevMan 5.3 software. After carefully screening relevant studies, four retrospective studies of high quality involving 466 patients (197 in the combined group and 269 in the HR group) were included in this study. The pooled results showed that the 1-, 3-, 5-year OS rate in the combined group were comparable with those in the HR group (OR=0.77, 0.96, 0.88; P=0.33, 0.88, 0.70, respectively). Similarly, there was no significant difference in 1-, 3-, 5-year DFS rate between the combined group and the HR alone group (OR=0.57, 0.83, 0.72; P=0.17, 0.37, 0.32, respectively). And the intraoperative parameters and postoperative AEs were also comparable between the above two cohorts. However, two included studies reported that tumor often recurred in the ablation site in the combined group. The present meta-analysis indicated that the HR combined with RFA could reach a long-term survival outcome similar to curative HR for multifocal HCC patients. And this therapy may be a promising alternative for these patients with marginal liver function or complicated tumor distribution. Furthermore, high quality randomized controlled trials (RCTs) are imperative to verify this conclusion.

Structurally Diverse Diterpenoids from Isodon scoparius and Their Bioactivity.

Fourteen new diterpenoids (1-14) based on four skeletal types and two known analogues (15 and 16) were isolated from the aerial parts of Isodon scoparius. Compound 2 is the first ent-kaurane diterpenoid featuring a 1,11-ether bridge, and the structures of these new compounds were established mainly by NMR and MS methods. The absolute configurations of 1 and 5 and the relative configuration of 3 were determined using single-crystal X-ray diffraction. The absolute configuration of 14 was determined by comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 4, and 15 were active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and they also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 1.0, 3.1, and 1.8 µM, respectively.

Ent-Abietanoids Isolated from Isodon serra.

Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14ß)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC50 = 1.8 µM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480).

miR-203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver.

Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR-203 adenovirus was administered to induce hepatic miR-203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR-203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non-tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR-203 overexpression further promoted the regeneration of the non-tumorous liver by upregulating Ki67 expression and enhancing IL-6/SOCS3/STAT3 pro-proliferative signals. Importantly, miR-203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR-203 overexpression reversed the epithelial-mesenchymal transition induced by hepatectomy through targeting IL-1ß, Snail1 and Twist1. In conclusion, our results suggested that miR-203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial-mesenchymal transition.

Diversity and aboveground biomass of lianas in the tropical seasonal rain forests of Xishuangbanna, SW China

Lianas are important components of tropical forests and have significant impacts on the diversity, structure and dynamics of tropical forests. The present study documented the liana flora in a Chinese tropical region. Species richness, abundance, size-class distribution and spatial patterns of lianas were investigated in three 1-ha plots in tropical seasonal rain forests in Xishuangbanna, SW China. All lianas with = 2 cm diameter at breast height (dbh) were measured, tagged and identified. A total of 458 liana stems belonging to 95 species (ranging from 38 to 50 species/ha), 59 genera and 32 families were recorded in the three plots. The most well-represented families were Loganiaceae, Annonceae, Papilionaceae, Apocynaceae and Rhamnaceae. Papilionaceae (14 species recorded) was the most important family in the study forests. The population density, basal area and importance value index (IVI) varied greatly across the three plots. Strychnos cathayensis, Byttneria grandifolia and Bousigonia mekongensis were the dominant species in terms of IVI across the three plots. The mean aboveground biomass of lianas (3 396 kg/ha) accounted for 1.4% of the total community aboveground biomass. The abundance, diversity and biomass of lianas in Xishuangbanna tropical seasonal rain forests are lower than those in tropical moist and wet forests, but higher than those in tropical dry forests. This study provides new data on lianas from a geographical region that has been little-studied. Our findings emphasize that other factors beyond the amount and seasonality of precipitation should be included when considering the liana abundance patterns across scales. Rev. Biol. Trop. 57 (1-2): 211-222. Epub 2009 June 30.

Las lianas son componentes importantes de los bosques tropicales y tienen importantes impactos en la diversidad, la estructura y la dinámica de los bosques tropicales. El presente estudio documenta la flora de lianas en una región tropical estacional china. La riqueza de especies, abundancia, clases de tamaño y patrones espaciales de distribución de las lianas fueron investigados en tres parcelas de una hectárea de bosque tropical estacional lluvioso, en Xishuangbanna, SW China. Todas las lianas con = 2 cm de diámetro a la altura del pecho (DAP) fueron medidas, etiquetadas e identificadas. Un total de 458 tallos de lianas pertenecientes a 95 especies (que van de 38 a 50 especies/ha), 59 géneros y 32 familias se registraron en las tres parcelas. Las familias mejor representadas fueron Loganiaceae, Annonceae, Papilionaceae, Apocynaceae y Rhamnaceae. Papilionaceae (14 especies registradas) fue la de mayor importancia. La densidad de población, área basal y el índice de valor de importancia (IVI) varió mucho a través de las tres parcelas. Strychnos cathayensis, Byttneria grandifolia y Bousigonia mekongensis fueron las especies dominantes en términos de IVI en las tres parcelas. La media de la biomasa aérea de lianas (3 396 kg/ha) representó el 1.4% de la biomasa aérea total de la comunidad. La abundancia, biomasa y diversidad de lianas en bosques tropicales estacionales de Xishuangbanna son inferiores a los de zonas tropicales y bosques húmedos, pero superiores a los de los bosques tropicales secos. Este estudio proporciona nuevos datos sobre las lianas de una región geográfica que ha sido poco estudiada. Los resultados enfatizan que otros factores, además de la cantidad y la estacionalidad de la precipitación, deben ser considerados al examinar los patrones de la abundancia de lianas.