Search

Glucose homeostasis of adipocytes could be regulated by immune-adipose crosstalk. In order to investigate the effects of Lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT) on glucose metabolism, we performed the present study. Our results showed that LIGHT deficiency improved glucose tolerance and enhanced glucose consumption of inguinal white adipose tissue (iWAT) under high fat diet. Consistently, Light overexpression could inhibit glucose uptake during the process of white adipogenesis. Mechanistically, LIGHT interacted with lymphotoxin-β receptor (LTβR) to attenuate AKT pathway leading to downregulation of glucose transporter-4 (GLUT4) expression, which resulted in glucose uptake inhibition. In summary, our findings revealed LIGHT-LTβR-AKT-GLUT4 axis as a regulator of glucose uptake in adipose tissue, which suggested the pivotal role of LIGHT in maintaining glucose homeostasis.

In this work, a new N-halamine precursor with two epoxy groups, 1,3-bis(2,3-epoxypropyl)-s-triazine-2,4,6-trione (BETT), was synthesized and used to enhance the compatibility between poly(lactic acid) (PLA) and poly (butylene adipate-co-terephthalate) (PBAT). The rheological analysis and GPC indicated that chain extension between PLA and PBAT occurred during the melt-blending in the presence of BETT. The PLA/PBAT chain extensions improved the compatibility between PLA and PBAT and hindered the crystallization of PLA. SEM images showed that PLA/PBAT blend gradually changed from the typical sea-island phase without BETT to a co-continuous structure with increase in amount of BETT. This showed that the interfacial compatibility between PLA and PBAT improved significantly on addition of BETT. Moreover, compared to PLA/PBAT blend, the mechanical properties of PLA/PBAT/BETT blends showed great improvement. Furthermore, the chlorinated PLA/PBAT/BETT sheets displayed excellent antibacterial activities against E. coli (CMCC 44103) and S. aureus (ATCC 6538) cultures, wherein the sheets with 17.5 ± 0.8 μg/cm2 of the active chlorine could kill all inoculated bacteria within 30 min.

It is considered that intestinal barrier dysfunction and systemic endotoxemia drive obesity and its related complications. However, what causes barrier dysfunction remains to be elucidated. Here, we showed that the gut microbiota from high-fat diet (HFD)-fed mice had impaired ability to degrade dietary flavonoids, and in correspondence, the microbial-derived flavonoid metabolite desaminotyrosine (DAT) was reduced. Supplementation of DAT in the drinking water was able to counter the HFD-induced body fat mass accumulation and body weight increment. This is correlated with the role of DAT in maintaining mucosal immune homeostasis to protect barrier integrity. DAT could attenuate dextran sodium sulfate (DSS)-induced mucosal inflammation in a type I interferon signal-dependent manner. Furthermore, intraperitoneal injection of DAT-protected mice from bacterial endotoxin-induced septic shock. Together, we identified DAT as a gut microbiota-derived anti-inflammatory metabolite that functions to modulate local and systemic immune homeostasis. Our data support the notion of dysbiosis being an important driving force of mucosal barrier dysfunction and systemic metabolic complications.

Protein-based adhesives have gained considerable interest, due to their unique ecofriendliness and abundant functional groups. However, the presence of polar groups results in poor water resistance...

FTL10 is an early-flowering mutant of rice (Oryza sativa L.) with a premature senescent phenotype. Early leaf senescence can cause negative effects on rice yield. Moreover, rice leaves are damaged under high-light conditions, which promote rice senescence. Artificial shading can reduce the amount of light absorbed by rice leaves. The aim of this study was to investigate the effects of shading at noon (11:30–14:00) on the senescence and yield of FTL10. The results showed that shading improved the total antioxidant capacity of rice leaves, reduced the accumulation of reactive oxygen species (ROS) and reduced the expression of genes related to senescence. In the shaded group, the degradation rate of chlorophyll and Rubisco proteins, which are related to photosynthesis, was relatively slow, and the photosynthetic rate was relatively high. Compared with those under the natural growth conditions, the proportion of photosynthetic electron allocated to photorespiration in the shaded group rice leaves was lower, and the proportion allocated to carbon fixation was higher. The yield data showed that the single-spike weight and yield per plant of rice significantly increased after shading. Therefore, our research shows that shading at noon could delay FTL10 senescence and increase yields.

Efficient capture of radioactive iodine (129I, 131I) is of great significance in spent fuel treatment. In this paper, a new adsorbent named Catechin@ACF was successfully prepared through interface assembly of specific recognition gripper with plant polyphenols (catechin) on activated collagen fiber (ACF), and the catechin membrane with specific grip on iodine was successfully constructed on the surface of ACF. The results showed that the adsorbent assembled catechin membrane was rich in aromatic rings, hydroxyl groups and imine adsorption sites, and possessed specific recognition and capture characteristics of iodine. Moreover, the as-prepared Catechin@ACF showed excellent capture capacity for iodine vapor and iodine in organic solution with the maximum capture capacity of 2122.68 mg/g and 258.29 mg/g, respectively. In iodine-cyclohexane solution, the adsorption process was in according with the Pseudo first order kinetic and Langmuir isothermal model. In addition, the specific recognition and capture mechanism analysis indicated that the aromatic rings, phenolic hydroxyl groups and imine groups in the catechin membrane were the specific and effective grippers for iodine, and finally iodine formed a stable conjugated system with the adsorbent in the form of I- and I3-. Therefore, the as-prepared specific iodine capturer Catechin@ACF was expected to play a vital role in the capture of radioactive iodine in spent fuel off-gas because of its specific recognition, high capture capacity, large-scale preparation, and environment-friendly.

Extraction uranium from complicated aqueous solutions (seawater and nuclear wastewater) has been promoting the development of multi-functional adsorbents with high adsorption capacities and high selectivity. Here, we proposed a co-immobilization approach to preparing uranium adsorbents. Due to specific recognition and binding between functional groups, bayberry tannin (BT) and hydrous titanium oxide (HTO) were co-immobilized onto nano collagen fibrils (NCFs). The adsorption performances of NCFs-HTO-BT to uranium were systematically investigated in two aqueous systems, including nuclear wastewater and seawater. Results proved that NCFs-HTO-BT possessed the remarkable adsorption capacities and affinities for uranium in wastewater (393.186 mg g−1) and spiked seawater (14.878 mg g−1) with the uranium concentration of 320 mg g−1 and 8 mg g−1, respectively. Based on characteristic analysis of the adsorbent before and after uranium adsorption, the hydroxyl groups of HTO, the adjacent phenolic hydroxyl groups of BT, and nitrogen-containing and oxygen-containing functional groups of NCFs were active sites for uranium adsorption.

Immune and nervous system sensing are two important ways of detecting inner and outer environmental changes. Immune cell activation in the gut can promote metabolic disorders. However, whether enteric nervous system sensing and activities are also important in metabolic syndromes is not clear. Enteric glial cells (EGCs) are thought to have sensing ability, but little is known about the potential connections between EGC and metabolic disorders. Consuming a modern Western-type high-fat low-fiber diet increases the risk of obesity. Here, we reported that dietary shift from a normal chow diet to a high-fat diet in wild-type (WT) C57BL/6 mice induced a transient emergence of glial fibrillary acidic protein (GFAP)-positive EGC network in the ileal lamina propria, accompanied by an increase of glial-derived neurotrophic factors production. Inhibition of EGC metabolic activity via gliotoxin fluorocitrate or glial-intrinsic deletion of myeloid differentiation factor 88 (Myd88) in mice blocked this dietary change-induced activity. Furthermore, we found a different role of MYD88 in glial cells versus adipocyte in diet-induced obesity. The glial Myd88 knockout mice gained less body weight after HFD feeding compared to the littermate controls. In contrast, adipocyte deletion of Myd88 in mice had no impact on the weight gain but had exacerbated glucose metabolic disorders. Pharmacological interventions of glial activities by fluorocitrate prevented body weight gain in a dietary type- and glial MYD88-independent manner. Collectively, our data reveal a previously unappreciated function of EGC in sensing a dietary shift-induced perturbation and glial activities as a whole may play roles in diet-induced obesity.New & NoteworthyIt is known that obesity and its related metabolic syndrome can damage the neuronal system. However, whether the neuronal system also participates in the development of obesity is unclear. Diet is an important contributing factor to obesity. Our study reveals that consuming a high-fat diet can induce a transient enteric glial cell response via its intrinsic sensing molecule(s). Inhibiting overall glial cell activities may have an impact on the development of the metabolic syndrome.

The physiologic signals that regulate beige adipogenesis remain incompletely understood, especially those that limit browning and prevent overexpenditure of energy. In this study, the TNF family member cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT), also known as TNF super family protein 14 (TNFSF14), can inhibit adipose precursor differentiation into beige adipocytes. In acute cold stress, LIGHT deficiency in mice accelerated browning in the subcutaneous white adipose tissue (scWAT). Further experiments showed that LIGHT interacting with lymphotoxin-β receptor (LTβR) on adipose precursors blocked beige fat biogenesis. LTβR signals attenuated the JNK pathway, which contributed to their antibeiging effect. Blocking JNK activation using a small molecular inhibitor prevented cold-induced scWAT beiging. Furthermore, LIGHT/LTβR signals acted as an attenuator of white adipogenesis. LIGHT deficiency in mice promoted obesity during high-fat diet feeding. These findings identify the LIGHT axis as a regulator of adipose tissue homeostasis and suggest that LIGHT signaling functions as a mechanism to divert energy in favor of immune activation.-Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., Wang, Y. LIGHT/TNFSF14 signaling attenuates beige fat biogenesis.

The efficient capture of radioactive iodine (I-129, I-131) and radon (Rn-222) is crucial to the development of nuclear energy in spent fuel treatment. Herein, we successfully synthesized a new type of three-dimensional hydrolyzed collagen aerogel immobilized with catechin (Catechin@3DCF aerogel) as an effective adsorbent to remove iodine and radon through enzymatic hydrolysis, dialysis, freeze-drying, immobilization, and cross-linking. The as-prepared adsorbent was systematically characterized by FE-SEM, EDX, FT–IR, and XPS, showing that the adsorbent possesses ultra-high porosity, high content flake structure, and abundant adsorption sites on the surface of adsorbent. The results show that Catechin@3DCF aerogel exhibited excellent capture capacity for iodine and radon, with the maximum capture capacity of 222.67 wt% (88.5 wt% for 3DCF aerogel) and 44,877.9 Bq/Kg, respectively. Through the active group-shielding experiment analysis, the phenolic hydroxyl groups on the surface of adsorbent played a major role in iodine capture, followed by the -NHR group. In addition, mechanism studies have shown that the capture of iodine is mainly by chemical adsorption, while the capture of radon is mainly through physical adsorption, which is related to the numerous mesopores and flake structure of the adsorbent. Furthermore, Catechin@3DCF aerogel still maintains excellent adsorption capacity for iodine and radon under 60Co γ-ray irradiation at a total dose ranging from 10 to 350 kGy, indicating that it has excellent radiation resistance stability. Advantages such as novelty, ultra-high porosity, high-radiation stability, ultra-high capture capacity, environment-friendly, and low-cost indicate that biomass-derived Catechin@3DCF aerogel plays a role in the capture of radioactive iodine and radon from airborne effluents.

Bifidobacterium inhabiting the human and animal intestinal tract is known for its health-promoting effect. Tolerance to acid stress is crucial for bifidobacteria to survive and then exert their beneficial effects in the gut. A long-term adaptation in successive batch cultures was used as evolutionary engineering strategy to improve acid stress tolerance in an industrial probiotic strain, B. longum JDM301. Its derivative, JDM301AR showed higher resistance to several stress conditions, including acid stress than the parental strain, JDM301. To better understand bifidobacterial acid stress response, the changes of fatty acid (FA) in cell membrane of these two strains were determined. A shift in the production of FA in cell membrane, characterized by increased C14:0 was found, when JDM301AR was exposed to low-pH environment. It was implied that the increased production of C14:0 is associated with the acquisition of acid-tolerant phenotype for JDM301AR. High-throughput RNA-sequencing was performed to analyze the changes of gene expression profile after acid-exposure. The transcriptional profiles of JDM301AR and JDM301 under normal condition and acid stress were compared to reveal the different acid response between them. A total of 5 genes involved in FA metabolism were upregulated and no downregulated genes were found in response to acid stress in JDM301AR. The up-regulated BLJ_0565 and BLJ_1105 may play important roles in the modification of membrane FA composition of JDM301AR after acid exposure. Overall, these results suggested that successive batch cultures induced the acid stress tolerance of B. longum involved in transcriptional and physiological responses, including modification of cell wall and cell membrane, metabolism of amino acid and neutralization of internal pH by strengthening NH3 production and transport.

The conformation and stability of zein in solution are closely associated with its solvation process and influence the mechanical properties of the related zein-based materials. In this work, a common solvent dimethyl sulfoxide (DMSO) was used to dissolve zein, rather than solvents frequently used such as aqueous ethanol and acetic acid. It was found that DMSO could dissolve zein readily and the solution was stable for at least 2 weeks. Rheological analysis and small-angle X-ray scattering (SAXS) were employed to characterize the zein DMSO solution. Results of rheological analysis suggested a Huggins coefficient of 0.24, indicating DMSO to be a good solvent for zein. SAXS results revealed that zein adopted an elongated conformation and had dimensions of 2.8 nm × 2.8 nm × 14.8 nm in DMSO solution. Moreover, robust zein films were fabricated from zein DMSO solutions. The content of residual DMSO in the films was determined to be approximately 15 wt % by thermogravimetric analysis, in consistence with the value obtained by other two methods. The film showed a large breaking strain of 320.6% with a considerable breaking stress of 1.9 MPa, yielding a breaking energy of 376.2 MJ/m3. Therefore, the ease of dissolution and good mechanical performance of the final zein-based material make DMSO a potential solvent for fabrication of zein materials, thereby improving the scope of practical applications of zein.

Injury to the biliary epithelium triggers cholangiopathies. However, factors involved in regulating the pathogenesis remains incompletely understood. Here, we report that the gut microbiota is important in regulating hepatobiliary fibroproliferative regenerative process. In helminth Clonorchis sinensis-induced bile duct injury model, wild-type mice showed more extensive peribiliary fibroproliferative responses than non-littermate IL-33-deficient mice. However, these reactions could be attenuated by co-housing of the animals together. In the meantime, the relatively fibroproliferative-resistant IL-33-deficient mice could become fibroproliferative-responsive especially in large intrahepatic bile duct by antibiotics treatment. Furthermore, microbiota-derived metabolite butyrate was able to inhibit biliary organoid expansion in vitro and temper 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced biliary fibrosis in vivo. Together, our data implies a potential way of management of hepatobiliary diseases by modulating gut microbiota.

Nano-scale zero-valent iron (NZVI) is easy to be agglomerated and passivated in the process of U(VI) reduction and fixation. Herein, a facile one-step process for titanium modified beaded segments like nano-zero-valent iron nanoparticles (FTNP) was designed and prepared for U(VI) adsorption-reduction from aqueous solution. The as-prepared NZVI, FTNP were characterized by Fourier transform infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), X-Ray photoelectron spectra (XPS), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and Energy dispersive X-ray spectrum (EDS). Results indicated that the beaded segments like FTNP were successful prepared. Furthermore, the uranium removal performance of FTNP with the effect of adsorption and reduction were investigated and showed excellent adsorption and reducibility for U(VI) from aqueous solution. Batch adsorption for U(VI) shown the U(VI) adsorption capacity of FTNP reached 734.4 mg g–1 (pH = 5.0). In the Fe-U reaction system, Fe2+ was generated as the primary reducing agent to reduce U(VI) from Fe0. Therefore, part of U(VI) was removed and reduced to U(IV), while others was precipitation hydrolyzed to schoepite, which also reduced to U(IV) and precipitated. This study may provide a novel and significant method for using nano-zero-valent iron to develop for wastewater decontamination.

In this study, the structural characterization of Sphallerocarpus gracilis polysaccharide (SGP) and its hypoglycaemic activities are reported for the first time. SGP, which has a weight average molar mass (Mw) of 7.413×105, was isolated from Sphallerocarpus gracilis and purified by ion-exchange chromatography. The polysaccharide is composed of rhamnose, arabinose, mannose, glucose and galactose, with the molar ratio of 4.12: 8.99: 5.45: 65.94: 15.50. The mechanism underlying the hypoglycaemic effect of SGP was evaluated. Experimental results showed that SGP protected pancreatic β-cells from alloxan damage by several possible mechanisms, including: (1) repairing free radical damage; (2) reducing the apoptosis of pancreatic β-cells by inhibiting the activities of caspase-3 and bax, and enhancing the activity of bcl-2; (3) stimulating insulin secretion and upregulating the pancreatic and duodenal homeobox 1 gene and the insulin gene and the pancreatic in pancreatic β-cells. The results obtained in this study suggest that SGP may be a promising therapeutic agent in the treatment of diabetes mellitus.

The pH-sensitive hydrogels composed of sodium caseinate (SC) and N,O-carboxymethyl chitosan (NOCC) were prepared and a new method to characterize the gelation process was presented in this work. Reological tests suggested that RSC/NOCC=3/7 (the weight ratio of SC and NOCC) was the best ratio of hydrogel. The well-developed three-dimensional network structures in the hydrogel were confirmed by AFM. Two structural parameters, tIS and tCS, denoted as the initial and critical structure formation time, respectively, were used to provide an exact determination of the start of structure formation and description of gelation process. The gelation process strongly depended on temperature changes, a high temperature resulted in an early start of gelation. The non-kinetic model suggested the higher activation energy in the higher temperatures was disadvantageous to structure formation, and vice versa. Due to the smart gel reported here was very stable at room temperature, we believed that the gel is required for applications in drug delivery or could be exploited in the development of potential application as molecular switches in the future.

Sphallerocarpus gracilis (S. gracilis) is a little-investigated edible plant and used as traditional Chinese medicine. In this study, polysaccharide extracted from S. gracilis,deproteined and purified. The polysaccharide (SGP) was chemically modified to obtain its sulfated derivatives (S-SGP) using the method of chlorosulfonic acid/pyridine (CSA/Pyr). In order to acquire the derivative with the highest degree of substitution (DS), the optimum conditions of the sulfation were obtained based on response surface design (RSD), and the structural characterizations and antioxidant properties of the S-SGP were comparatively investigated by Fourier transform infrared spectrometry (FT-IR), GC-MS analysis, size exclusion chromatography (SEC), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay, and reducing power assay, respectively. Results showed that the modification was successful, and obtained the optimum combination of conditions. Compared with SGP, the sulfated polysaccharide with relatively the decreased degree of molecular weight (Mw) but the same composition of monosaccharides exhibited better antioxidant activities in DPPH, hydroxyl, superoxide radical and reducing power assay. These results indicated that the antioxidant activities in vitro of the S-SGP from S. gracilis may be related to combined effects of Mw, monosaccharide composition, and sulfate content.

To discover the potential functionalities of fenugreek gum (FG) in food applications and pharmaceutical industry, steady-shear flow, thixotropy and dynamical viscoelasticity tests were systemically carried out under a range of FG concentration (0.05–2.0%, w/v) and temperature (0–80 °C). The results showed that FG aqueous solutions exhibited Newtonian plateaus followed by shear-thinning regions which were found to be well correlated to the Carreau model. It was also found that the pseudoplastic behaviors of the FG aqueous solutions exhibited a concentration dependence. When the concentration of FG was above 1%, the system exhibited a gel-like behavior. Dynamical viscoelastic properties also showed a solid, elastic-like viscoelastic behavior. While solution with FG concentration of 0.05% exhibited a transition from a fluid-like to gel-like structure. The variation of the thixotropic index α as a function of FG concentration showed a stronger thixotropic behavior as the polymer concentration increased, which indicated a typical elastic behavior of FG solutions with high concentration. Multiwave temperature ramp test for 1.0% (w/v) FG aqueous solution showed that the solid-like behavior had a strong dependence on frequency rather than temperature, which was consistent with the results of oscillatory frequency sweep test. These results could provide a useful indicator for the applications of FG in food industry and other fields.

Bifidobacterium longum strain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) system in its chromosome, designated MazE 1 F 1 Bif , MazE 2 F 2 Bif , and RelBE Bif , respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interactions between MazF 1 Bif and MazE 2 Bif or RelB Bif were assessed in B. longum strain JDM301. MazF 1 Bif caused the degradation of tufA Bif mRNA, and its toxicity was inhibited by forming a protein complex with its cognate antitoxin, MazE 1 Bif . Notably, MazF 1 Bif toxicity was also partially neutralized when jointly expressed with noncognate antitoxin MazE 2 Bif or RelB Bif . Our results show that the two noncognate antitoxins also inhibited mRNA degradation caused by MazF 1 Bif toxin. Furthermore, the physical interplay between MazF 1 Bif and its noncognate antitoxins was confirmed by immunoprecipitation. These results suggest that MazF 1 Bif can arrest cell growth and that MazF 1 Bif toxicity can be neutralized by its cognate and noncognate antitoxins. These results imply that JDM301 uses a sophisticated toxin-antitoxin interaction network to alter its physiology when coping with environmental stress. IMPORTANCE Although toxin-antitoxin (TA) systems play an important role in several stress responses, the regulatory mechanisms of multiple TA system homologs in the bacterial genome remain largely unclear. In this study, the relationships between MazE 1 F 1 Bif and the other two TA systems of Bifidobacterium longum strain JDM301 were explored, and the interactions between MazF 1 Bif and MazE 2 Bif or RelB Bif were characterized. In addition, the mRNA degradation activity of MazF 1 Bif was demonstrated. In particular, the interaction of the toxin with noncognate antitoxins was shown, even between different TA families (MazF 1 Bif toxin and RelB Bif antitoxin) in JDM301. This work provides insight into the regulatory mechanisms of TA systems implicated in the stress responses of bifidobacteria.

Core-shell structured multifunctional nanocarriers (NCs) of ZnO quantum dots-conjugated gold nanoparticles (Au NPs) as core and amphiphilic hyperbranched block copolymer as shell were synthesized for targeted anticancer drug delivery. The amphiphilic hyperbranched block copolymer contained poly(l-lactide) (PLA) inner arm and folate (FA)-conjugated a sulfated polysaccharide from Gynostemma pentaphyllum Makino (GPPS-FA) outer arm. The structure and properties of core-shell structured multifunctional nanocarriers were characterized and determined by UV-visible spectra, FT-IR spectra, X-ray diffraction (XRD), fluorescence spectroscopy and TEM analyses. The release results indicated that camptothecin (CPT) release from NCs at pH 7.4 was much greater than that at pH 5.3. The cytotoxicity studies showed that both the blank NCs and the CPT-loaded NCs provided high anticancer activity against Hela cells. Furthermore, nanocarriers gained specificity to target model cancer cells in this study due to the enhanced cell uptake mediated by FA moiety. The results indicated that the NCs not only had great potential as tumor-targeted drug delivery nanocarrier, but also had an assistant role in the treatment of cancer.

The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development.

A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (K562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs.

Sulfated modification of a polysaccharide obtained from Radix hedysari (RHP) was studied. Four sulfated derivatives (RHPS) with variable degrees of substitution (DS) were obtained by the chlorosulfonic acid method with ionic liquids (ILs) as solvent and 4-dimethylaminopyridine (DMAP) as catalyst. The structures of RHPS were characterized by FT-IR spectra and ¹³C NMR spectra, and the results indicated that the sulfated groups were modified mainly at the C-6 position and C-2 position. Four kinds of RHPS showed different DS ranging from 0.63 to 1.45, and different weight-average molecular mass (Mw) ranging from 60.8 to 71.1 kDa with a little degradation. Compared with RHP, all of RHPS exhibited obvious antitumor activity on A549 cells and BGC-823 cells in vitro. However, they had no obvious influence on HEK293 cells, which indicated that they had low toxicity to normal cells. Flow cytometric studies indicated that the treatment of RHPS against A549 cells and BGC-823 cells could mediate the cell-cycle arrest in the G1 phase.

Phosphorylated modification of a polysaccharide obtained from Radix Hedysari (RHP) was studied. Three phosphorylated polysaccharides (RHPP) with variable degrees of substitution (DS(p)) were obtained with 4-dimethylaminopyridine (DMAP) and N, N' Dicyclocarbodiimide (DCC) as catalyst. The structures of RHPP were characterized by FT-IR spectra and (13)C NMR spectra. Depending on different reaction time, RHPP showed different DS(p) ranging from 0.30 to 0.66, and different Mw ranging from 86.6 to 89.7 KDa. Compared with RHP, RHPP exhibited superior antioxidant activities in vitro, which indicated that phosphorylated modification could enhance antioxidant activities of RHP. Furthermore, it was obvious that the DS(p) had a significant effect on the antioxidant activity.