Syringin alleviates hepatic fibrosis by enhancing autophagic flux and attenuating ER stress-TRIB3/SMAD3 in diabetic mice.

Type 2 diabetes mellitus (T2DM) is a key risk factor for the developing of metabolic liver injury and easily evolving to advanced fibrosis. Syringin (SYR), isolated from Acanthopanax senticosus, has anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, its hepatoprotective effects and mechanisms in T2DM-induced liver fibrosis remain unclear. Here, we investigated whether syringin (SYR) could serve as a therapeutic agent for liver fibrosis and its mechanism in high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic mice. C57BL/6 mice were induced with T2DM via HFD and STZ injection and treated with different doses of SYR. Serum lipid parameters and liver function indicators were measured, and hepatic histology and fibrosis were examined. The mechanism of SYR was explored through molecular analyses Results demonstrated SYR improved oral glucose tolerance, decreased the levels of ALT, AST, and AKP, and reduced hepatic lipid deposition in diabetic mice. Moreover, SYR ameliorated epithelial-to-mesenchymal transition to reverse hepatic fibrosis via suppressing TRIB3-SMAD3 interaction to restrain nuclear localization of SMAD3. Strikingly, SYR reversed hyperglycemia-induced deficiency in autophagic flux by regulation of Raptor/mTORC1, triggering nuclear translocation of TFEB to improve autophagosome-lysosomal fusion. In brief, SYR potentially ameliorates hepatic injury and fibrosis by enhancing autophagic flux and inhibing TRIB3 activation in diabetic mice.

Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the therapeutic potential for cancer by modulating multiple cellular signaling pathways. However, the effect and mechanism of cordycepin on anti-SCLC BM remain unknown. PURPOSE: In this study, we focused on the anti-SCLC BM effect of cordycepin in the zebrafish model and its potential mechanism. STUDY DESIGN AND METHODS: A SCLC xenograft model based on zebrafish embryos and in vitro cell migration assay were established. Cordycepin was administrated by soaking and microinjection in the zebrafish model. RNA-seq assay was performed to analyze transcriptomes of different groups. Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to reveal the underlying mechanism. Real-time qPCR was used to verify the effects of cordycepin on the key genes. RESULTS: Cordycepin showed lower cytotoxicity in vitro compared with cisplatin, anlotinib and etoposide, but showed comparable anti-proliferation and anti-BM effects in zebrafish SCLC xenograft model. Cordycepin showed significant anti-SCLC BM effects when administrated by both soaking and microinjection. RNA-seq demonstrated that cordycepin was involved in vitamin D metabolism, lipid transport, and proteolysis in cellular protein catabolic process pathways in SCLC BM microenvironment in zebrafish, and was involved in regulating the expressions of key genes such as cyp24a1, apoa1a, ctsl. The anti-BM effect of cordycepin in SCLC was mediated by reversing the expression of these genes. CONCLUSION: Our work is the first to describe the mechanism of cordycepin against SCLC BM from the perspective of regulating the brain microenvironment, providing new evidence for the anti-tumor effect of cordycepin.

Increased Water-Soluble Yellow Monascus Pigment Productivity via Dual Mutagenesis and Submerged Repeated-Batch Fermentation of Monascus purpureus.

Monascus pigments (MPs) have been used in the food industry for more than 2,000 years and are known for their safety, bold coloring, and physiological activity. MPs are mainly yellow (YMPs), orange (OMPs), and red (RMPs). In this study, a mutant strain Monascus purpureus H14 with high production of water-soluble YMPs (WSYMPs, λ max at 370 nm) was generated instead of primary YMPs (λ max at 420 nm), OMPs (λ max at 470 nm), and RMPs (λ max at 510 nm) produced by the parent strain M. purpureus LQ-6 through dual mutagenesis of atmospheric and room-temperature plasma and heavy ion beam irradiation (HIBI), producing 22.68 U/ml extracellular YMPs and 10.67 U/ml intracellular YMPs. WSYMP production was increased by 289.51% in optimal conditions after response surface methodology was applied in submerged fermentation. Application of combined immobilized fermentation and extractive fermentation improved productivity to 16.89 U/ml/day, 6.70 times greater than with conservative submerged fermentation. The produced WSYMPs exhibited good tone stability to environmental factors, but their pigment values were unstable to pH, light, and high concentrations of Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+. Furtherly, the produced exYMPs were identified as two yellow monascus pigment components (monascusone B and C21H27NO7S) by UHPLC-ESI-MS. This strategy may be extended to industrial production of premium WSYMPs using Monascus.

Cordycepin, a major bioactive component of Cordyceps militaris, ameliorates diabetes-induced testicular damage through the Sirt1/Foxo3a pathway.

Diabetes-induced male dysfunction is considered as a worldwide challenge, and testicular damage mainly caused by oxidative stress is its most common manifestation. Cordycepin, a natural antioxidant, has been used in the treatment of diabetic complications. However, the protective action and underlying mechanism of cordycepin on hyperglycaemia-induced testicular damage are unclear. This study aimed to investigate the protective effects and molecular mechanisms of cordycepin against diabetes-induced testicular damage. The type 2 diabetes model was established in C57BL/6 male mice via high-fat diet for 4 weeks and injected intraperitoneally with 50 mg/kg/day streptozotocin for five consecutive days. Then mice were treated with cordycepin (10 and 20 mg/kg, respectively) for 8 weeks. At the end of experiment, biochemical indicators, microstructure of testicular tissue, sperm morphology, TUNEL staining and protein expressions were evaluated. In the present study, cordycepin alleviated the testicular damage, restored disruption of the blood-testis barrier, and improved spermatogenic function via the antiapoptotic and antioxidant capacity. Mechanistically, cordycepin significantly enhanced SIRT1 expression and triggered the activity of Foxo3a, further to induce the expression of its downstream antioxidant enzymes, including Mn-SOD and CAT. These findings indicated that cordycepin could improve hyperglycaemia-induced testicular damage by regulating downstream antioxidant enzymes activity through the SIRT1/Foxo3a signalling pathway.

Novel Mesoporous Lignin-Calcium for Efficiently Scavenging Cationic Dyes from Dyestuff Effluent.

A novel adsorbent lignin-calcium was fabricated by a simple flocculation-sedimentation approach to remove methylene blue. The structure and morphology of the well-prepared sample were analyzed by multiple characterization methods. Lignin-calcium microspheres demonstrated a mesoporous and inserted layer structure with a coarse surface. Methylene blue (MB) adsorption by lignin-calcium complied with the Langmuir model, showing a maximum adsorption amount of 803.9 mg/g, exceeding that reported in the literature by 3-22-fold. The adsorption kinetics matched the pseudo-second-order model well. The pore volume diffusion model was technically applied to evaluate the mass transfer mechanisms. The effective pore volume diffusion coefficient was 6.28 × 10-12 m2/s. Furthermore, lignin-calcium exhibited excellent adsorbability for methylene blue across a pH range from 3 to 11 and could be regenerated by hydrochloric acid with an elution efficiency of 62.44%. Multiple mechanisms may support the adsorption. Altogether, the tailor-made lignin-calcium is promising as an efficient and sustainable adsorbent for scavenging cationic dyes from dyestuff effluent.

Cost-effective pigment production by Monascus purpureus using rice straw hydrolysate as substrate in submerged fermentation.

Monascus pigments (MPs), the secondary metabolites produced by the fungal strains of Monascus spp., hold commercial importance in not only the food and meat industries, but also therapeutic, cosmetic, and textile industries. To reduce the cost of MPs production, the utilization of rice straw hydrolysate as a substrate in submerged fermentation was investigated. The atmospheric and room temperature plasma (ARTP) mutation system was employed to develop a mutant strain Monascus purpureus M630, with high total extracellular Monascus pigments (exMPs) production of 34.12 U/mL in submerged fermentation with glucose-based medium. The results revealed that M. purpureus M630 produces 8.61 U/mL and 20.86 U/mL of exMPs in rice straw hydrolysate alone or in combination with glucose fermentation medium, respectively. Furfural (Fur) and 5'-hydroxymethyl furfural (5'-HMF), produced during pretreatment and hydrolysis of rice straw; are generally inhibitory for microbial growth and fermentation. Our findings revealed that M. purpureus M630 develops the tolerance and adaptation mechanisms in response to 5'-HMF and Fur during growth and MPs biosynthesis in rice straw hydrolysate. In conclusion, we report that rice straw hydrolysate can serve as an efficient and low-cost substitute for the MP production through submerged fermentation by Monascus spp.

Flow synthesis, characterization, anticoagulant activity of xylan sulfate from sugarcane bagasse.

High-value utilization of hemicellulose is critical to improve the append value of integrated biorefineries. In this research, the alkali-soluble sugarcane bagasse hemicellulose was sulfated using chlorosulfonic acid and N,N-dimethylformamide/LiCl under homogeneous conditions. With the aid of flow technique, a rapid, mild, and efficient method for the synthesis of xylan sulfate with high molecular weight and controllable degree of substitution was achieved. The results showed that the reaction time and the degradation of xylan chain were drastically reduced compared to the "in flask" batch conditions. High molecular weight of the product (Mw = 148,217) with a reasonable degree of substitution (DS = 1.49) could be obtained even at room temperature in 10 min under the present flow system. Anticoagulant experiments showed good anticoagulant activity of the resultant xylan sulfate, which could significantly prolong the activated partial thromboplastin time and thrombin time. This work not only provides a novel method for the synthesis of xylan sulfate, but also offers new opportunities for the production of other functional polysaccharide derivatives under the flow reaction conditions.

Hydrazine hydrate and organosolv synergetic pretreatment of corn stover to enhance enzymatic saccharification and co-production of high-quality antioxidant lignin.

Hydrazine hydrate and organosolv synergetic pretreatment of corn stover was developed. With the aid of alkaline and reductive hydrazine hydrate, a high delignification rate (77.94%) and total sugar yield of 90.27% (96.60% glucose, 78.82% xylose) based on the pulp could be obtained using hydrazine hydrate (10 mmol/g corn stover) and aqueous ethanol (60 vt%) as the solvent system. Analysis techniques such as FT-IR, SEM, XRD, and NMR were employed to characterize the structure and property changes of stock before and after pretreatment to evaluate the effect of hydrazine hydrate. A mechanism is proposed for the presented system.

Production of cyclopentanone from furfural over Ru/C with Al11.6PO23.7 and application in the synthesis of diesel range alkanes.

The bio-based platform molecule furfural was converted to the high value chemical cyclopentanone over Ru/C (0.5 wt%) and Al11.6PO23.7 catalysts in good yield (84%) with water as the medium. After screening the reaction conditions, the selectivity for cyclopentanone and cyclopentanol could be controlled by adjusting the hydrogen pressure at the temperature of 433 K. Herein, we propose a new mechanism for the synergistic catalysis of a Bronsted acid and Lewis acid for the conversion of furfural to cyclopentanone through the cyclopentenone route, which is catalyzed by Ru/C and Al11.6PO23.7. In addition, based on cyclopentanone, higher octane number cyclic alkanes (>85% selectivity), which are used as hydrocarbon fuels, were synthesized via a C-C coupling reaction followed by hydrodeoxygenation.

Transcriptome analysis of Clostridium beijerinckii adaptation mechanisms in response to ferulic acid.

Clostridium beijerinckii 4693:int with high ferulic acid (FA) tolerance was engineered and characterized in our lab. In this study, the minimum inhibition concentrations of FA against C. beijerinckii NCIMB 8052 (wild-type) and 4693:int were 1.0 and 1.5g/l, respectively; cell viability was 18.5% and 106.7%, respectively, in the presence of 0.5g/l FA. A comparative transcriptome analysis was carried out at two different growth stages to evaluate sensitivity to FA. Genes that were differentially expressed included those related to redox and associated cofactors, riboflavin metabolism, two-component system, glycolysis and butanoate metabolism, and DNA replication as well as those encoding ATP-binding cassette transporters. Cbei_2134 and Cbei_2135 encoding alkyl hydroperoxide reductases are thought to be involved in antibacterial and adaptation mechanisms in C. beijerinckii in the presence of FA.

Organic amine catalytic organosolv pretreatment of corn stover for enzymatic saccharification and high-quality lignin.

A novel and efficient organic amine and organosolv synergetic pretreatment method was developed to overcome the recalcitrance of lignocellulose to produce fermentable sugars and high-quality salt-free lignin. After optimization of the process parameters, a delignification of 81.7% and total sugar yield of 83.2% (87.1% glucose, 75.4% xylose) could be obtained using n-propylamine (10mmol/g, biomass) as a catalyst and aqueous ethanol (60%, v/v) as a solvent. The susceptibility of the substrates to enzymatic digestibility was explained by their physical and chemical characteristics. The physical structure of extracted lignin showed higher ß-aryl ether bonds content and functionalities, offering the potential for further downstream upgrading. The role of organic amine catalyst and a synergistic mechanism is proposed for the present system.

Efficient immobilization of AGE and NAL enzymes onto functional amino resin as recyclable and high-performance biocatalyst.

N-Acetylglucosamine-2-epimerase (AGE) and N-acetylneuraminic acid lyase (NAL) were immobilized for synthesis of N-acetylneuraminic acid (Neu5Ac) on three resins: Amberzyme oxirane resin (AOR), poly (styrene-co-DVB)-Br resin (PBR) and amino resin (AR). The loading capacity and immobilized enzyme activity showed that AR was the best carrier. Three methods of glutaraldehyde cross-linking were tested and simultaneous cross-linking and immobilization was demonstrated to be the best method. The functional properties of immobilized AGE and NAL were studied and compared to those of the free enzyme. The highest enzyme activities of free and immobilized AGE were obtained in 0.1 M potassium phosphate buffer at pH 7.5 and a temperature of 37 °C. Comparatively, the highest NAL activities were at pH 8.5. Meanwhile, an increase in K m (from 1.14 to 1.31 mg·mL-1 for AGE and from 1.05 to 1.25 mg·mL-1 for NAL) and a decrease in V max (from 177.53 to 106.37 µg·min-1 mL-1 for AGE and from 126.41 to 95.96 µg·min-1 mL-1 for NAL) were recorded after immobilization. The AR-glutaraldehyde-enzyme system exhibited better thermal stability than the free enzyme, and retained 72% of its initial activity even after eight repeated runs. The apparent activation energy (E a) of the free and immobilized AGE (NAL) was 117.14 kJ·mol-1 (124.21 kJ·mol-1) and 78.45 kJ·mol-1 (66.64 kJ·mol-1), respectively, implying that the catalytic efficiency of the immobilized enzyme was restricted by mass-transfer rather than kinetic limit. Subsequently, Neu5Ac production from GlcNAc using immobilized enzymes in one reactor was carried out resulting 101.45 g·L-1 of Neu5Ac and the highest conversion ratio of 82%. This method of enzyme immobilization may have a promising future for Neu5Ac production in industry.

Metallo-deuteroporphyrin as a biomimetic catalyst for the catalytic oxidation of lignin to aromatics.

A series of metallo-deuteroporphyrins derived from hemin were prepared as models of the cytochrome P450 enzyme. With the aid of the highly active Co(II) deuteroporphyrin complex, the catalytic oxidation system was applied for the oxidation of several lignin model compounds, and high yields of monomeric products were obtained under mild reaction conditions. It was found that the modified cobalt deuteroporphyrin that has no substituents at the meso sites but does have the disulfide linkage in the propionate side chains at the ß sites exhibited much higher activity and stability than the synthetic tetraphenylporphyrin. The changes in the propionate side chains can divert the reactivity of cobalt deuteroporphyrins from the typical CC bond cleavage to CO bond cleavage. Furthermore, this novel oxidative system can convert enzymolysis lignin into depolymerized products including a significant portion of well-defined aromatic monomers.