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The field of stem cells and regenerative medicine is one of the most attractive foci and research hot spots in the current biology and medicine. The international scientific community has made remarkable breakthroughs in the following issues: 1) The basic regulatory theory of stem cells; 2) iPS cells, targeted reprogramming to functional cells and new types of stem cells; 3) Gene edit technologies; 4) Tissue engineering and translational research, drug development using stem cells, nano-materials research and application in regenerative medicine etc. Scientists in institutes and the biology pharmaceutical industry are actively promoting the clinical translation by discovering new mechanisms, innovating technologies and creating new therapies, leading to a big scale market of the regenerative medicine nowadays. Traditional treatments such as drug therapy and surgery often have little effect on such diseases, and fail to meet the growing medical needs of this age-group. Stem cell-based regenerative medicine is expected to become the third treatment option after drug therapy and surgery. With the increasing financial supports and investments in China recent years, a series of important progress have been made to stem cells and regenerative medicine. In this issue, we investigated the stem cell and regenerative medicine industry in the world and china, such as clinical trial and research institutions distribution.

A one-pot multicomponent approach was established for site selective synthesis of novel 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazine derivatives with high stereoselectivity. The computational studies revealed that the steric hindrances between the 2-hydrogen atoms on the aromatic rings and the carbonyl, as well as the steric repulsions between the hydrogen atoms of the CH group in the benzylidene and the CH2 group in the N-alkylative part might be responsible for the Z/E selectivity. Compound (3Z,6Z)-3h (IC50=11 nM) has a close activity to the positive compound plinabulin (IC50=15 nM) against the cancer cell line HL60.

Immune diseases are a great threat to people’s health. As a crucial component of Chinese medicine, TCM (Traditional Chinese Medicine) has many similarities with modern immune disease treatment in basic thinking and theory. Recently, it is found that TCM treatment has a positive effect on immune diseases treatment. To support the innovation and breakthrough of immune disease treatment, our paper focuses on the analysis of TCM intervention treatment of immune disease patents in China and Guangdong Province, respectively. It makes early warnings about patent risk management. Through the analysis, we figured out that there were three features in common: (1)the quantity of patent application in this area rose swiftly since 2013; (2) the main category of patent technology were concentrated on A61K36 group; (3) corporations and institutions were dominated applicants;(4) In China, the applicants were geographically centralized in Shandong, Beijing, Jiangsu; In Guangdong, the applicants generally assembled in Guangzhou, Dongguan, Foshan. In conclusion, there is a lack of core patents in this field. From the perspective of patent layout, Guangdong needs to increase foreign patent applications and develop more core patents to enhance its competitiveness in TCM intervention treatment of immune diseases.

As1the most revolutionary technology in cell therapy, stem cell technology will give birth to a series of new biotechnology, drive the development of the pharmaceutical industry, and lead the future of biological economy. Guangdong province has a good foundation for stem cell R&D and has set up a project named "Stem Cell and Tissue Engineering Technology" to make breakthroughs in core technologies of stem cell research. In this paper, it is of great significance to compile the industrial technology roadmap and clarify the key points of stem cell and tissue engineering industry through the research to provide reference for the decision-making in Guangdong province.

A series of 3,5-disubstitute-4-alkynylisoxazole derivatives were designed and synthesized through palladium(II)–copper(I) catalyzed Sonogashira cross-coupling reaction of an alkynyl moiety and an isoxazole scaffold as novel HSP90 inhibitors. The resultant compounds displayed moderate to potent binding affinity to HSP90 proteins, and also demonstrated good cell growth inhibitory activity against various cancer cell lines (A549, K562, MCF-7, DU145 and Hela). Some compounds (18d, 18e, 19a, 19d, 20c and 20q) show similar or better binding affinity towards HSP90α and HSP90β comparing to NVP-AUY922. In addition, compounds 18e, 19a and 20q exhibited potent inhibitory activity against various human cancer cell lines.

Two new prenylated phenols vaccinol H (1) and vaccinol I (2), together with three known phenols derivatives 3–5, one glyceride derivative 6, and ergosterol 7 were isolated from endogenous Pestalotiopsis vaccinii (cgmcc3.9199) of mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae). The new structures of 1 and 2 were determined by spectroscopic analyses and circular dichroism (CD) spectra. Most of the isolated compounds (2–6) were tested for their antiviral (EV71), cytotoxic, anti-tuberculosis, and anti-inflammatory effects. Among these compounds, compound 2 exhibited potent COX-2 inhibitory activity with an IC50 value of 16.8 μM.

A new xanthone named sydoxanthone C (1) and a new alkaloid named acremolin B (2), together with 10 known compounds (3-12) were isolated from a deep-sea-derived fungus Aspergillus sp. SCSIO Ind09F01. The structures of compounds (1-12) were determined by the extensive 1D, 2D-NMR, High resolution mass spectra (HRESIMS) data. Compounds 7, 8, 11 and 12 showed significant selective cytotoxicities against HeLa, DU145 and U937 cell lines. In addition, compounds 7, 8 and 11 also exhibited COX-2 inhibitory activities with the prominent IC50 values of 2.4, 7.1 and 10.6 μM, respectively.

Three new indolyl diketopiperazine derivatives, penillines A and B (1 and 3), isopenilline A (2), together with seven known alkaloid compounds (E)-3-(1H-imidazole-4-yimethylene)-6-(1H-indl-3-ylmethyl)-2,5-piperazinediol (4), penilloid A (5), meleagrin (6), neoxaline (7), questiomycin A (8), N-(2-hydroxyphenyl)-acetamide (9), 2-benzoxazolinone (10), were isolated from the Antarctic soil-derived fungus Penicillium sp. SCSIO 05705. The new structures of 1–3 were elucidated on the basis of 1D and 2D NMR, mass spectra, CD spectra, and quantum chemical calculations. All the isolated compounds were tested for their antiviral (H1N1 and H3N2), antituberculosis, antibacterial, and cytotoxic activities. Among them, compounds 6–8 had significant in vitro cytotoxicities against the K562, MCF-7, A549, U937, Hela, DU145, HL60, and HT29 cell lines, with IC50 values ranging from 2.73 to 17.7 μM. In addition, compound 8 showed potent antituberculosis activity with an MIC value of 3.91 μM, and the inhibition effect was close to the positive control INH (isoniazid, MIC 2.04 μM). A possible biogenesis pathway for compounds 1–7 was proposed.

Two new anthraquinones, 1,3-dihydroxy-5-methoxy-6-methoxymethyl-2-methyl-9,10-anthraquinone ( 1 ) and 1,3-dihydroxy-5-methoxy-2,6-bismethoxymethyl-9,10-anthraquinone ( 2 ), together with ten known anthraquinone derivatives ( 3 – 12 ), three coumarin derivatives ( 13 – 15 ), and 6-gingerol ( 16 ) were isolated from the barks of Morinda citrifolia (Noni) collected in the Yongxing island of Xisha. The structures of compounds ( 1–16 ) were determined on the basis of extensive spectroscopic analyses, as well as by comparison with literature reports. The new compounds 1 and 2 were tested for their antiviral, cytotoxic, and antibacterial activities. In the primary bioassays, compounds 1 and 2 displayed weak anti-H1N1 activity with IC 50 values of 66.1 and 10.5 μM, respectively. In addition, compound 2 showed weak anti-H3N2 activity with IC 50 value of 11.5 μM, and had weak antimicrobial activity against Staphylococcus aureus with MIC value of 24.5 μM.

Eleven diketopiperazine and fumiquinazoline alkaloids (1–11) together with a tetracyclic triterpenoid helvolic acid (12) were obtained from the cultures of a deep-sea derived fungus Aspergillus sp. SCSIO Ind09F01. The structures of these compounds (1–12) were determined mainly by the extensive NMR, ESIMS spectra data and by comparison with previously described compounds. Besides, anti-tuberculosis, cytotoxic, antibacterial, COX-2 inhibitory and antiviral activities of these compounds were evaluated. Gliotoxin (3), 12,13-dihydroxy-fumitremorgin C (11) and helvolic acid (12) exhibited very strong anti-tuberculosis activity towards Mycobacterium tuberculosis with the prominent MIC50 values of 50 values of 0.191, 0.015 and 95.4 μM, respectively.

Silver–graphene oxide (Ag–GO) nanocomposites were in situ fabricated rapidly through a green one-pot method by using tryptophan (Trp) as a reducing and stabilizing agent. The morphologies of synthesized Ag–GO nanocomposites were characterized by UV–vis absorption spectroscopy, transmission electron microscopy (TEM), and micro-Raman system. The results indicated silver nanoparticles (Ag NPs) with spherical size were well dispersed on the surface of graphene oxide (GO). The role of pH has been explored to obtain optimum reaction conditions during the growth process. Raman signals of GO were greatly enhanced after Ag NPs loaded on its surface. More importantly, the synthesized Ag–GO nanocomposites exhibited excellent surface-enhanced Raman scattering (SERS) activity as SERS substrates to detect crystal violet (CV) in aqueous solution, and the enhancement factor ( EF ) from the intensity of the vibrational mode at 1621 cm −1 was calculated to be 1.6 × 10 5 .

The latest report from the National Bureau of Statistics, "China's economic and social development in 2016", shows that the number of people aged 60 and above is approximately 230 million (i.e., 16.7% of the population). By 2050, this age-group will increase to 400 million, accounting for more than 30% of the population. In China, this dramatic aging trend has endangered people's health. Major disorders such as tissue and organ damage, cardiovascular and other functional organ failures, degenerative diseases, and cancer are closely related to aging. Traditional treatments such as drug therapy and surgery often have little effect on such diseases, and fail to meet the growing medical needs of this age-group. Stem cell-based regenerative medicine is expected to become the third treatment option after drug therapy and surgery. With the increasing financial supports and investments in China recent years, a series of important progress have been made to stem cells and regenerative medicine. In this issue, we investigated the stem cell and regenerative medicine industry in the world and china, such as research literature and research institutions distribution.

Fifteen compounds, including six quinone/hydroquinone meroterpenoids, purpurogemutantin (1), macrophorin A (2), 4′-oxomacrophorin (3), 7-deacetoxyyanuthone A (4), 2,3-hydro-deacetoxyyanuthone A (5), 22-deacetylyanuthone A (6), anicequol (7), three roquefortine derivatives, roquefortine C (8), (16S)-hydroxyroquefortine C (9), (16R)-hydroxyroquefortine C (10), dihydroresorcylide (11), nectriapyrone (12), together with three fatty acid derivatives, methyl linoleate (13), phospholipase A2 (14), methyl elaidate (15), were isolated from the sponge-derived fungus Gliomastix sp. ZSDS1-F7 isolated from the sponge Phakellia fusca Thiele collected in the Yongxing island of Xisha. Their structures were elucidated mainly by extensive NMR spectroscopic and mass spectrometric analyses. Among these compounds, compounds 1–3 and 5–7 showed significant in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4 and HL60 cell lines, with IC50 values ranging from 0.19 to 35.4 μM. ...

Aspergone, a new chromanone derivative from fungus Aspergillus sp. SCSIO41002 derived of mangrove soil sample

A one-pot multicomponent approach was established for site selective synthesis of novel 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazine derivatives with high stereoselectivity. The computational studies revealed that the steric hindrances between the 2-hydrogen atoms on the aromatic rings and the carbonyl, as well as the steric repulsions between the hydrogen atoms of the CH group in the benzylidene and the CH2 group in the N-alkylative part might be responsible for the Z/E selectivity. Compound (3Z,6Z)-3h (IC50=11 nM) has a close activity to the positive compound plinabulin (IC50=15 nM) against the cancer cell line HL60.

A series of novel N-1-monoallylated 2,5-diketopiperazine derivatives were designed, synthesized, and evaluated as cytotoxic agents against eight cancer cell lines by using CCK8 assay. These derivatives were substituted with methoxyphenyl groups at C-6 position, and various long alkyl side chains at C-3-position of the 2,5-diketopiperazine ring. The cytotoxic results showed that 4-methoxyphenyl group was better than 2-methoxyphenyl group as optimal substitutive group, while 3-methoxyphenyl group was not a suitable one. When the number (n value) of the methylene groups for the long alkyl side chain was 3 (compounds 1c and 3c), the derivatives had the strongest cytotoxicities. Compound 3c substituted with 4-methoxyphenyl group and pentylidene side chain exhibited strong activity (IC50 = 0.36-1.9 μM) against all cancer cell lines, and could obviously induce apoptosis of cancer cell line U937 at 1.0 μM after 48 h treatment.

Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC50 values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC50 value of 3.5 ± 1.3 μM.

Five new highly oxygenated α-pyrone merosesquiterpenoids, ochraceopones A-E (1-5), together with one new double bond isomer of asteltoxin, isoasteltoxin (6), and two known asteltoxin derivatives, asteltoxin (7) and asteltoxin B (8), were isolated from an Antarctic soil-derived fungus, Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were determined through extensive spectroscopic analysis, CD spectra, quantum mechanical calculations, and X-ray single-crystal diffraction. Ochraceopones A-D (1-4) are the first examples of α-pyrone merosesquiterpenoids possessing a linear tetracyclic carbon skeleton, which has not been previously described. All the isolated compounds were tested for their antiviral, cytotoxic, antibacterial, and antitubercular activities. Among these compounds, ochraceopone A (1), isoasteltoxin (6), and asteltoxin (7) exhibited antiviral activities against the H1N1 and H3N2 influenza viruses with IC50 values of >20.0/12.2 ± 4.10, 0.23 ± 0.05/0.66 ± 0.09, and 0.54 ± 0.06/0.84 ± 0.02 μM, respectively. A possible biosynthetic pathway for ochraceopones A-E (1-5) was proposed.

Two new phenyl derivatives (1 and 3), along with two new natural products (4 and 5), and three known compounds (2, 6 and 7), were isolated from an endophytic fungus Botryosphaeria sp. SCSIO KcF6. The structures of these compounds 1–7 were elucidated by the extensive 1D and 2D-NMR and HRESIMS Data analysis, and compared with those of reported data. The absolute configuration of the compounds 1 and 3 were assigned by optical rotation and CD data. The isolated compounds were evaluated for their cytotoxic, anti-inflammatory (COX-2) and antimicrobial activities. Compound 3 exhibited a specific COX-2 inhibitory activity with the IC50 value of 1.12 μM.

Three new 4-hydroxy-2-pyridone alkaloids, arthpyrones A-C (1-3), were isolated from the sponge-derived fungus Arthrinium arundinis ZSDS1-F3. Their structures were elucidated on the basis of spectroscopic analysis, CD spectra, quantum chemical calculation, and X-ray single-crystal diffraction analysis. Compounds 1 and 2 possessed a 2-pyridone core featured with a decalin moiety linked via a carboxide bridge bearing a novel oxabicyclo[3.3.1]nonane ring system rarely discovered in nature. A possible biosynthetic pathway for them was proposed.

Fifteen compounds, including two tetramic acid derivatives, penicillenol A1 (1) and penicillenol A2 (2), six polyphenols containing both phenolic bisabolane sesquiterpenoid and diphenyl ether units, expansols A–F (3–8), together with six phenolic bisabolane sesquiterpenoids (9–14) and diorcinol (15), were isolated from the fermentation broth of the marine-derived fungus ZSDS1-F11 isolated from the sponge Phakellia fusca Thiele collected in the Yongxing island of Xisha. Their structures were elucidated mainly by using extensive NMR spectroscopic and mass spectrometric analyses. Compounds 3–5, 7 and 8 showed potent COX-1 inhibitory activity with IC50 values of 5.3, 16.2, 30.2, 41.0 and 56.8 μM, respectively. Meanwhile, compounds 3–8 showed potent COX-2 inhibitory activity with IC50 values of 3.1, 5.6, 3.0, 5.1, 3.2 and 3.7 μM, respectively. In addition, compound 1 exhibited antituberculosis activity with 96.1% inhibition at concentration of 10 μM.

Non-protected 2,5-diketopiperazine derivatives have poor solubility thus with negative impact on their bioavailability. In the present study, twenty-one novel soluble mono-protected, and three non-protected 2,5-diketopiperazine derivatives were designed and synthesized. Their anticancer activity to ten cell lines were evaluated by using CCK8 assay, and the results showed that about half of the mono-protected derivatives had broad-spectrum anticancer activity. Among allyl-protected derivatives, compound 4m had strong activity to all the cell lines (IC50 = 0.5-4.5 mu M), especially to the cancer cell lines U937 (IC50 = 0.5 mu M) and K562 (IC50 = 0.9 mu M). Compound 4m could become a lead compound for further development for anticancer agents. (C) 2014 Elsevier Masson SAS. All rights reserved.

Herein we describe a self-assembly synthesis of graphene oxide/Ag nanoparticles nano-composites (GO/CS/AgNPs) by non-covalent attachment of AgNPs to chitosan (CS) functionalized graphene oxide (GO) sheets. The negatively charged AgNPs are prone to form aggregates on GO/CS via electrostatic interaction, which is extremely beneficial to the surface-enhanced Raman scattering (SERS) detection of aromatic molecules. Taking advantage of the enrichment of target molecules on GO, the obtained hybrids exhibit strong SERS activity to aromatic molecules (trypan blue and methylene blue). Furthermore, SERS signals of a negatively charged molecule (trypan blue) are stronger than signals of a positively charged molecule (methylene blue) due to the different adsorption capacity of GO/CS/AgNPs for the two opposite charged molecules through electrostatic interaction. Moreover, GO/CS/AgNPs remarkably enhance the main peaks of l-phenylalanine, in comparison with the silver nanoparticles, showing great potential for biomedical applications.

The intrinsic Raman signals provide the potential of graphene oxide (GO) for cellular imaging. Herein, novel surface-enhanced Raman scattering (SERS) labels based on GO-Ag nanoparticle (NP) composites are developed for fast cellular probing and imaging. The optimum SERS signals of the hybrids can be well controlled by adjusting the weight ratio between AgNO(3) and GO. Utilizing GO-AgNPs as the highly sensitive optical probes, fast SERS imaging of cancer cells is realized with a very short integration time of about 0.06 s per pixel. Furthermore, folic acid (FA) is covalently conjugated to GO for targeting specific cancer cells with folate receptors (FRs). Targeted SERS images can be acquired after 2 h incubation with FA-GO-AgNPs, which are specifically located on the surface of FR-positive cancer cells. In conclusion, the GO-based Raman probes mentioned here open up exciting opportunities for biomedical imaging.

Nanographene oxide (NGO), a new type of nanomaterial for anticancer drugs delivery and near-infrared (NIR)-mediated photothermal ablation of tumors, has been used in the combination of photothermal therapy and chemotherapy. Herein, targeted chemo-photothermal therapy based on polyvinylpyrrolidone (PVP) functionalized NGO was achieved. Folic acid (FA), a common target molecule to cancer cells, was conjugated to NGO via covalent amide bond. The obtained FA–NGO–PVP was proved to be an ideal pH-responsive nanocarrier for delivery of an anticancer drug doxorubicin (DOX) with the loading ratio more than 100%. In vitro experiments were then performed with the combination of chemotherapy and NIR photothermal therapy. The results demonstrated that the targeted chemo-photothermal therapy could specifically deliver drug and heat to tumor sites and showed excellent efficacy of anticancer therapy. Thus, FA–NGO–PVP could be used as a novel nanomaterial for selective chemo-photothermal therapy.