Identification of novel immune-related signatures for keloid diagnosis and treatment: insights from integrated bulk RNA-seq and scRNA-seq analysis.

BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.

Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN), causing bradykinesia and rest tremors. Although the molecular mechanism of PD is still not fully understood, neuroinflammation has a key role in the damage of dopaminergic neurons. Herein, we found that kurarinone, a unique natural product from Sophora flavescens, alleviated the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic neurotoxicity, including the losses of neurotransmitters and tyrosine hydroxylase (TH)-positive cells (SN and striatum [STR]). Furthermore, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia involved in the nuclear factor kappa B signaling pathway. The proteomics result of the solvent-induced protein precipitation and thermal proteome profiling suggest that the soluble epoxide hydrolase (sEH) enzyme, which is associated with the neuroinflammation of PD, is a promising target of kurarinone. This is supported by the increase of plasma epoxyeicosatrienoic acids (sEH substrates) and the decrease of dihydroxyeicosatrienoic acids (sEH products), and the results of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH revealed that this natural compound is an uncompetitive inhibitor. In addition, sEH knockout (KO) attenuated the progression of PD, and sEH KO plus kurarinone did not further reduce the protection of PD in MPTP-induced PD mice. These findings suggest that kurarinone could be a potential natural candidate for the treatment of PD, possibly through sEH inhibition.

Acceleration of Stepwise Carbon-Polygold Bonding Cleavage in Hypercoordinated Carbon-Centered Gold(I) Clusters.

Hypercoordinated carbon-centered organometallic clusters extensively exist in polymetallic and metal surface catalysis. The investigation on their electronic structures and transformations is crucial for mechanistic studies. Herein, we try to clarify the reactivity difference between a hypercoordinated tetrametalated species [PA-C-Au4]+ and a classical trimetalated one [(PA-C-Au3) + H]+ based on experimental and theoretical studies. Under a protonolysis condition, the hypercoordinated carbon species [PA-C-Au4]+ experiences a sequential cleavage process of carbon-polymetal bonding through the trinuclear [(PA-C-Au3) + H]+ intermediate to end up with a methyl group. Theoretical studies indicate that the high symmetry of five-center bonding in [PA-C-Au4]+ promotes the delocalization of negative charges, finally resulting in less nucleophilicity of the central hypercarbon atom. In contrast, the low C3V triangular arrangement of gold atoms in the [(PA-C-Au3) + H]+ structure causes the decrease in orbital interaction between the Aun moiety and the central carbon atom and the increase in the negative charge on the central carbon atom. Along with the gradual cleavage of the carbon-polymetal bonding, the accumulation of negative charges and the reduction of steric hindrance around the central carbon atom jointly contribute to the synergistic multi-step protodeauration process. This work not only illustrates the reactivity difference of RC-Mn species in different degrees of metalation but also provides an essential structural basis for the design of synergistic polymetallic catalysts.

Sediminihaliea albiluteola gen. nov., sp. nov., a new member of the family Halieaceae, isolated from marine sediment.

A Gram-stain-negative, rod-shaped and facultatively aerobic bacterial strain, designated F7430T, was isolated from coastal sediment collected at Jingzi Wharf in Weihai, PR China. Cells of strain F7430T were 0.3-0.4 µm wide, 2.0-2.6 µm long, non-flagellated, non-motile and formed pale-beige colonies. Growth was observed at 4-40 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.5-8.0) and at NaCl concentrations of 1.0-10.0 % (w/v; optimum, 1.0 %). The sole respiratory quinone of strain F7430T was ubiquinone 8 and the predominant cellular fatty acids were summed feature 8 (C18 : 1 ω7c / C18 : 1 ω6c; 60.7 %), summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c; 30.2 %) and C15 : 0 iso (13.9 %). The polar lipids of strain F7430T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid and three unidentified lipids. Results of 16S rRNA gene sequences analyses indicated that this strain belonged to the family Halieaceae and had high sequence similarities to Parahaliea aestuarii JCM 51547T (95.3 %) and Halioglobus pacificus DSM 27932T (95.2 %) followed by 92.9-95.0 % sequence similarities to other type species within the aforementioned family. The rpoB gene sequences analyses indicated that the novel strain had the highest sequence similarities to Parahaliea aestuarii JCM 51547T (82.2 %) and Parahaliea mediterranea DSM 21924T (82.2 %) followed by 75.2-80.5 % sequence similarities to other type species within this family. Phylogenetic analyses showed that strain F7430T constituted a monophyletic branch clearly separated from the other genera of family Halieaceae. Whole-genome sequencing of strain F7430T revealed a 3.3 Mbp genome size with a DNA G+C content of 52.6 mol%. The genome encoded diverse metabolic pathways including the Entner-Doudoroff pathway, assimilatory sulphate reduction and biosynthesis of dTDP-l-rhamnose. Based on results from the current polyphasic study, strain F7430T is proposed to represent a novel species of a new genus within the family Halieaceae, for which the name Sediminihaliea albiluteola gen. nov., sp. nov. is proposed. The type strain of the type species is F7430T (=KCTC 72873T=MCCC 1H00420T).

Stappia albiluteola sp. nov., isolated from marine sediment.

A Gram-stain negative, rod-shaped, facultatively aerobic, pale-beige-coloured bacterial strain, designated F7233T, was isolated from coastal sediment sampled at Jingzi Bay, Weihai, PR China. Cells of strain F7233T were 0.3-0.4 µm wide, 1.2-1.4 µm wide long, non-spore-forming and motile with one flagellum. Optimum growth occurred at 30 °C, with 1.0 % (w/v) NaCl and at pH 6.5-7.0. Positive for nitrate reduction, hydrolysis of Tweens and oxidase activity. The sole respiratory quinone of strain F7233T was ubiquinone-10 and the predominant cellular fatty acid was summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and one unidentified aminophospholipid. The G+C content of the chromosomal DNA was 63.3 mol%. Phylogenetic analysis of the 16S rRNA gene sequence revealed that the newly isolate belonged to the genus Stappia, with 96.8 % sequence similarity to Stappia indica MCCC 1A01226T, 96.1 % similarity to Stappia stellulata JCM 20692T and 95.5% similarity to Stappia taiwanensis CC-SPIO-10-1T. On the basis of phylogenetic, phenotypic and chemotaxonomic data, it is considered that strain F7233T should represent a novel species within the genus Stappia, for which the name Stappia albiluteola sp. nov. is proposed. The type strain is F7233T (=MCCC 1H00419T=KCTC 72859T).

Alisma genus: Phytochemical constituents, biosynthesis, and biological activities.

The genus Alisma contains 11 species distributed worldwide, of which at least two species (A. orientale [Sam.] Juzep. and A. plantago-aquatica Linn.) have been used as common herbal medicines. Secondary metabolites obtained from the genus Alisma are considered to be the material basis for the various biological functions and medicinal applications. In this review, we mainly focused on the recent investigations of secondary metabolites from plants of the genus Alisma and their biological activities, with the highlighting on the diversity of the chemical structures, the biosynthesis of interesting secondary metabolites, the biological activities, and the relationships between structures and bioactivities.

Inula japonica ameliorated bleomycin-induced pulmonary fibrosis via inhibiting soluble epoxide hydrolase.

Pulmonary fibrosis is a progressive, irreversible, and fatal fibrotic lung disease with a high mortality and morbidity, and commonly nonresponsive to conventional therapy. Inula japonica Thunb. is a traditional Chinese medicine, known as "Xuan Fu Hua" in Chinese, and has been widely applied to relieve cough and dyspnea and eliminate retained phlegm with a long history. In this study, we aimed to evaluate the anti-fibrosis effect and action mechanism of I. japonica extract (IJE) for the treatment of bleomycin (BLM)-induced pulmonary fibrosis in mice. IJE treatment significantly restored BLM-induced alterations in body weight loss and lung function decline, decreased the collagen deposition induced by BLM in lung tissues, and inhibited fibrotic and inflammatory factors, such as α-SMA, TGF-ß1, TNF-α, IL-6, COX-2, NF-κB, and GSK3ß, in a dose-dependent manner. We found that IJE could enhance the concentration of 8,9-epoxyeicosatrienoic acid (8,9-EET) and decrease concentrations of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET), 11,12-DHET, and 14,15-DHET in BLM-induced mice. Meanwhile, IJE suppressed protein and mRNA expression levels of soluble epoxide hydrolase (sEH), and significantly displayed the inhibition of sEH activity with an IC50 value of 0.98 µg/mL. Our results indicated that IJE exerted remarkable anti-fibrosis effect on BLM-induced pulmonary fibrosis in mice via inhibiting sEH activity, resulting in the regulation of GSK3ß signaling pathway. Our findings revealed the underlying action mechanism of I. japonica, and suggested that I. japonica could be regarded as a candidate resource for the treatment of pulmonary fibrosis.

Aquiflexum aquatile sp. nov., isolated from lake water.

A Gram-stain-negative, facultative anaerobic, red-coloured, rod-shaped, non-flagellated, non-motile and non-gliding bacterium, designated strain Z0201T, was isolated from lake water in Yunnan, China (26° 16' N, 99° 94' E). Cells of strain Z0201T were 0.2-0.4 µm wide and 1.4-2.5 µm long, catalase-positive and oxidase-negative. Strain Z0201T was found to grow at 4-37 °C (optimum, 30 °C) and pH 6.5-8.5 (pH 7.5) in the presence of 0-2.0 % (w/v) NaCl (0-0.5 %). The sole respiratory quinone of strain Z0201T was MK-7 and the DNA G+C content was 41.2 mol%. The major fatty acid was iso-C15 : 0 (49.4 %). The polar lipid profile of strain Z0201T consisted of aminophospholipid, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, two unidentified phospholipids and five unidentified lipids. Based on the 16S rRNA gene sequence analysis, strain Z0201T was a member of the genus Aquiflexum, appearing to be closely related to Aquiflexum balticum (95.4 %). On the basis of phenotypic distinctiveness and phylogenetic divergence, strain Z0201T is considered to represent a novel species of the genus Aquiflexum, for which the name Aquiflexumaquatile sp. nov. is proposed. The type strain is Z0201T (=KCTC 62450T=MCCC 1H00328T).

Aliidiomarina celeris sp. nov., isolated from coastal sediment.

A Gram-stain-negative, heterotrophic, facultative anaerobic, gliding and motile bacterium, approximately 0.6-0.9 µm wide and 1.5-2.6 µm long, designated F3105T, was isolated from a marine sediment sample collected along the coast of Rongcheng, China . The growth of strain F3105T occurred on media with 1.0-8.0 % (w/v) NaCl (optimum, 2.0-3.0 %) and a pH of 6.5-9.5 (optimum, pH 7.5) at 4-45 °C (optimum, 37 °C). The phylogenetic analysis of the 16S rRNA gene and chemotaxonomic data revealed that the isolate belonged to the genus Aliidiomarina, and is closely related to Aliidiomarina shirensis (95.9 % sequence similarity). The sole isoprenoid quinone was Q-8. The major cellular fatty acids of the isolate were iso-C15 : 0, iso-C17 : 1ω9c and iso-C17 : 0, and its polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminolipid, two unidentified lipids and two unidentified aminophospholipids. The DNA G+C content of strain F3105T was 49.5 mol%. On the basis of phenotypic distinctiveness and phylogenetic divergence, strain F3105T is considered to represent a novel species of the genus Aliidiomarina, for which the name Aliidiomarinaceleris sp. nov. is proposed. The type strain is F3105T (=MCCC 1H00223T=KCTC 52891T).

Uncarialins A-I, Monoterpenoid Indole Alkaloids from Uncaria rhynchophylla as Natural Agonists of the 5-HT1A Receptor.

Nine new monoterpenoid indole alkaloids, uncarialins A-I (1-9), were isolated from Uncaria rhynchophylla as well as 14 known analogues (10-23). Their structures were determined by HRESIMS, 1D and 2D NMR, and experimental and calculated electronic circular dichroism data. Compounds 5, 7, 15, and 22 displayed significant agonistic effects against the 5-HT1A receptor with EC50 values of 2.2 ± 0.1, 0.1 ± 0.1, 1.6 ± 0.3, and 2.0 ± 0.5 µM, respectively. The mechanisms of action of these four compounds with the 5-HT1A receptor were investigated by molecular docking, and the results suggested that amino acid residues Asp116, Thr196, Asn386, and Tyr390 played critical roles in the observed activity of the above-mentioned compounds.

Demethylbellidifolin isolated from Swertia bimaculate against human carboxylesterase 2: Kinetics and interaction mechanism merged with docking simulations.

In this study, forty-nine kinds of traditional Chinese medicines (TCMs) were evaluated for their inhibitory activities against human carboxylesterase 2 (HCE 2) using a human liver microsome (HLM) system. Swertia bimaculata showed significant inhibition on HCE 2 at 10 µg/mL among forty-nine kinds of TCMs. The extract of Swertia bimaculata was separated by preparative HPLC to afford demethylbellidifolin (1) identified by MS, 1H NMR, and 13C NMR spectra. Demethylbellidifolin (1) was assayed for its inhibitory HCE 2 effect by HCE 2-mediated DDAB hydrolysis, and its potential IC50 value was 3.12 ±â€¯0.64 µM. Demethylbellidifolin (1) was assigned as a mixed-type competitive inhibitor with the inhibiton constant Ki value of 6.87 µM by Lineweaver-Burk and slope plots. Living cell imaging was conducted to corroborate its inhibitory HCE 2 activity. Molecular docking indicated potential interactions of demethylbellidifolin (1) with HCE 2 through two hydrogen bonds of the C-3 and C-5 hydroxy groups with amino acid residues Glu227 and Ser228 in the catalytic cavity, respectively.

Afatinib Decreases P-Glycoprotein Expression to Promote Adriamycin Toxicity of A549T Cells.

We investigated the reversal effect of afatinib (AFT) on activity of adriamycin (ADR) in A549T cells and clarified the related molecular mechanisms. A549T cells overexpressing P-glycoprotein (P-gp) were resistant to anticancer drug ADR. AFT significantly increased the antitumor activity of ADR in A549T cells. AFT increased the intracellular concentration of ADR by inhibiting the function and expression of P-gp at mRNA and protein levels in A549T cells. Additionally, the reversal effect of AFT on P-gp mediated multidrug resistance (MDR) might be related to the inhibition of PI3K/Akt pathway. Cotreatment with AFT and ADR could enhance ADR-induced apoptosis and autophagy in A549T cells. Meanwhile, the co-treatment significantly induced cell apoptosis and autophagy accompanied by increased expression of cleaved caspase-3, PARP, LC3B-II, and beclin 1. Apoptosis inhibitors had no significant effect on cell activity, while autophagy inhibitors decreased cell viability, suggesting that autophagy may be a self protective mechanism of cell survival in the absence of chemotherapy drugs. Interestingly, when combined with AFT and ADR, inhibition of apoptosis and/or autophagy could enhance cell viability. These results indicated that in addition to inhibit P-gp, ADR-induced apoptosis, and autophagy promoted by AFT contributed to the antiproliferation effect of combined AFT and ADR on A549T cells. These findings provide evidence that AFT combined ADR may achieve a better therapeutic effect to lung cancer in clinic. J. Cell. Biochem. 119: 414-423, 2018. © 2017 Wiley Periodicals, Inc.

Identification and Isolation of Glucosytransferases (GT) Expressed Fungi Using a Two-Photon Ratiometric Fluorescent Probe Activated by GT.

As is well-known, fungi are an important biocatalysis model of glucosylation and have been widely applied for bioactive compounds glucosylation mediated by the intracellular glucosytransferases (GTs). However, there is no efficient method for the real-time detection of GTs and the rapid isolation of the target fungi strains with the high expression of GTs. In the present work, we first developed a two-photon ratiometric fluorescent probe N-( n-butyl)-4-hydroxy-1,8-naphthalimide (NHN) for detecting the glucosyltransferases activity and intracellular imaging of GTs. Under UV light (365 nm), the transformed product of NHN mediated by intracellular glucosyltransferase displayed blue emission to guide the rapid isolation of fungal strains possessing overexpression of GTs from complex soil samples. Finally, by using the fluorescent probe, two target fungi were isolated and identified to be Rhizopus oryzae and Mucor circinelloides by molecular analysis, and they exhibited a robust capability for regio- and stereospecific O-glycosylation. Our results fully demonstrated that NHN may be a promising tool for guiding real-time GTs activity in fungal strains and even for developing natural fungal strains with GTs overexpression.

Isolation of γ-Glutamyl-Transferase Rich-Bacteria from Mouse Gut by a Near-Infrared Fluorescent Probe with Large Stokes Shift.

Bacterial γ-glutamyltranspeptidases (γ-GT) is a well-known metabolic enzyme, which could cleave the γ-glutamyl amide bond of γ-glutamyl analogues. As a key metabolic enzyme of bacteria and a virulence factor for the host, bacterial γ-GT was determined to be a novel pharmaceutical target for new antibiotics development. However, there is no efficient method for the sensing of γ-GT activity in bacteria and the recognition of γ-glutamyltransferase rich-bacteria. In the present work, a dicyanoisophorone derivative (ADMG) has been designed and developed to be a sensitive and selective near-infrared fluorescent probe for the sensing of bacterial γ-GT. ADMG not only sensed bacterial γ-GT in vitro, but also imaged intestinal bacteria in vivo. More interesting, the intestinal bacteria existed in the duodenum section of mouse displayed significant fluorescence emission. Under the guidance of the sensing of γ-GT using ADMG, three intestinal bacteria strains K. pneumoniae CAV1042, K. pneumoniae XJRML-1, and E. faecalis were isolated successfully, which expressed the bacterial γ-GT. Therefore, the fluorescent probe ADMG not only sensed the endogenous bacterial γ-GT and imaged the intestinal bacteria but also guided the isolation of intestinal bacteria possessing γ-GT efficiently, which suggested a novel biological tool for the rapid isolation of special bacteria from a mixed sample.

Uncaria rhynchophylla Ameliorates Parkinson's Disease by Inhibiting HSP90 Expression: Insights from Quantitative Proteomics.

BACKGROUND/AIMS: Uncaria rhynchophylla, known as "Gou-teng", is a traditional Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions, and pacify the liver. Although U. rhynchophylla has a long history of being often used to treat central nervous system (CNS) diseases, its efficacy and potential mechanism are still uncertain. This study investigated neuroprotective effect and the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH-SY5Y cells and MPTP-induced mice. METHODS: MPP+-induced SH-SY5Y cells and MPTP-induced mice were used to established Parkinson's disease (PD) models. Quantitative proteomics and bioinformatics were used to uncover proteomics changes of URE. Western blotting was used to validate main differentially expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy-related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay were further used to confirm the effect of URE on MPP+-induced apoptosis in SH-SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP-induced mice. The levels of dopamine (DA) and their metabolites were examined in striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH) was detected by immunohischemical staining and Western blotting. RESULTS: URE dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells. Quantitative proteomics and bioinformatics results confirmed that HSP90 was an important differentially expressed protein of URE. URE inhibited the expression of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K p110α, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38, and LC3-II. URE also markedly decreased the apoptotic ratio and elevated mitochondrial transmembrane potential (DΨm). Furthermore, URE treatment ameliorated behavioral impairments, increased the contents of DA and its metabolites and elevated the positive expressions of TH in SN and STR as well as the TH protein. CONCLUSIONS: URE possessed the neuroprotective effect in vivo and in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD treatment.

Chemical characteristics of the fungus Ganoderma lucidum and their inhibitory effects on acetylcholinesterase.

The chemical characteristic of a well-known folk medicine Ganoderma lucidum has been investigated by a series of chromatographic technologies, which displayed the presences of 45 lanostane type triterpenoids, including two new nor-lanostane triterpenoids (40, 41). Their structures were identified on the basis of spectroscopic data analysis (UV, IR, HRESIMS, 1D, and 2D NMR). Notably, some triterpenoids displayed moderate inhibitory effects against AChE (acetylcholinesterase) by an in vitro screened experiment. Triterpenoid 2 displayed the potent inhibitory effect with IC50 10.8 and Ki 14.95 µM (inhibition kinetic). The preliminary SAR has been discussed by the docking analyses between ganoderic acids (1, 2) and AChE.

Diterpenoids from the roots of Euphorbia fischeriana and their inhibitory effects on α-glucosidase.

Chemical investigation has been performed on the roots of Euphorbia fischeriana, a traditional Chinese medicine. Three diterpenoids were obtained using various chromatographic techniques, and their structures were determined by spectroscopic data including HRESIMS, 1D NMR, 2D NMR, ECD, and calculated ECD, which gave two new diterpenoids, daphnane type (1) and ent-pimarene type (3). Additionally, the isolated compounds (1-3) displayed moderate inhibitory effects against α-glucosidase in an in vitro bioassay.

Biotransformation of furanocoumarins by fungi: preparation of imperation analogs.

Imperation analogs have the furanocoumarin skeleton, with the isopentenyl group, which displayed significant bioactivities. The biotransformation of furanocoumarins imperation, isoimperation and phellopterin (1-3) by fungi has been proved to be an efficient method for the structural modification. Ten transformed furanocoumarin analogs were obtained by fungal biotransformation, including one new highly oxygenated furanocoumarin (4c). Aspergillus niger AS 3.739 displayed selectively transformed capability toward furanocouamrins (1-3) with one or two major products. So, seven hydroxylation and hydrolysis derivatives have been prepared efficiently. Additionally, the biotransformation of phellopterin gave multiple products (4a, 4b, 4c) by Cunninghamella blakesleana AS 3.970. The biotransformation time-courses of furanocoumarins have been established, which suggested the preferred incubation time. The bioactivities of furanocoumarin analogs have been investigated in an in vitro bioassay. And, furanocoumarins 1-3, 2a, and 2c displayed moderate anti-osteoporosis activities using MCET3-E1 cell line at the concentrations of 1, 10, and 100 µM.

Photo-Controlled Reversible Microtubule Assembly Mediated by Paclitaxel-Modified Cyclodextrin.

The design and construction of multi-stimuli-responsive supramolecular nanoassemblies that can mimic and regulate the fundamental biological processes have become a focus of interest in supramolecular chemistry. In this work, a perfect combination has been achieved between naturally occurring microtubules and artificially macrocyclic receptors. The self-assembling morphology of microtubules can be photo-tuned by the host-guest interaction of paclitaxel-modified ß-cyclodextrin (PTX-CD) and photochromic arylazopyrazole (PTX-AAP). Moreover, the supramolecularly aggregated microtubules in a cellular environment can induce a pronounced cell morphological change and cell death. This supramolecular approach based on the secondary PTX-AAP⊂PTX-CD complexation provides us a facile method to reversibly control the intertubular aggregation behaviors of microtubules, which may bring new perspectives in the treatment of diseases related to improper protein aggregation.