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Type 2 diabetes mellitus (T2DM) is a common metabolic syndrome that decreases insulin sensitivity and mitochondrial biogenesis in the liver. Our previous study demonstrated that ginsenoside Rg5 (Rg5) could attenuate renal injury in diabetic mice but its underlying mechanism in mitochondrial biogenesis and insulin sensitivity remains poorly understood. In this study, we found that Rg5 intervention significantly inhibited blood glucose increases in db/db mice, improved liver function damage and hepatocyte apoptosis, and activated the IRS-1/phosphatidylinositol 3-kinase/AKT insulin metabolism signaling pathway. Rg5 treatment also increased the level of glycogen synthesis and activated sirtuin1 (Sirt1) to increase glucose uptake and insulin sensitivity in insulin-resistant HepG2 (IR-HepG2) cells. Rg5 intervention also effectively improved liver oxidative stress and inflammation in db/db mice and increased mitochondrial biogenesis caused by T2DM. Additionally, the Rg5 treatment increased the mitochondrial mass in IR-HepG2 cells and activated Sirt1 to regulate the Sirt1/PGC-1α/mitofusin-2 mitochondrial biosynthesis pathway. Our findings demonstrated that Rg5 enhanced liver mitochondrial biogenesis and insulin sensitivity in db/db mice by activating the Sirt1/PGC-1α signaling pathway, suggesting the potential of Rg5 as a natural product for T2DM interventions.

Bacterial infection, tissue hypoxia and inflammatory response can hinder the infected wound repair process. To mitigate the above issues, tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets (MoS2@TA/Fe NSs) with dual enzyme activities were developed and anchored to a multifunctional hydrogel. The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy (PTT), glutathione (GSH) loss, and the peroxidase (POD)-like activity (catalyse H2O2 into ·OH under acid condition) of MoS2@TA/Fe NSs. Benefitting from the catalase (CAT)-like activity, the hydrogel could decompose H2O2 into O2 at neutral pH to relieve hypoxia and supply adequate O2. POD-like activity was mainly attributed to MoS2 NSs, while CAT-like activity was primarily due to TA/Fe complex. Moreover, MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species (ROS) and reactive nitrogen species (RNS) under neutral environment to maintain the balance of antioxidant systems and prevent inflammation. In addition, the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA. TA retained partial phenolic hydroxyl groups, which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels. Due to the dynamic boron ester bonds between polyvinyl alcohol (PVA), dextran (Dex), MoS2@TA/Fe, and borax, the hydrogel demonstrated fast self-healing and rapid shape adaptability. This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound, ensuring that it achieved its functions with maximum efficiency. The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing., Graphical abstract Image 1, Highlights • MoS2@TA/Fe NSs presents POD- and CAT-like activities. • MoS2@TA/Fe NSs shows anti-oxidant and anti-inflammation abilities. • The hydrogel shows fast self-healing, adhesiveness, and rapid shape-adaptivity. • MoS2@TA/Fe NSs-based hydrogel exhibits large potential in infected wound healing.

Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure, metabolism and immune function. Following the technological advances in isolation, purification and mass production, their mechanisms of action are gradually elucidated, providing solid basis for clinical applications. Ginseng extracts (total ginsenosides) and ginsenoside Rg3, CK, Rd have been marketed or entered clinical trials as drugs or dietary supplements. Despite the proven safety and efficacy of some ginsenosides, their applications are hindered by inferior pharmacokinetics such as low solubility, poor membrane permeability and metabolic instability. Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility, providing protection, facilitating intracellular transport, and enabling sustained and controlled release. This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes, micelles, albumin-based nanoparticles, and inorganic nanoparticles, as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.

Surface modification of biomaterials for rapid endothelialization is a promising approach for improving long-term patency of artificial vascular grafts (e.g. polytetrafluoroethylene, PTFE) with small-caliber vascular (

The pH diversification has been proved as an important factor affecting the self-assembly of spidroin. Herein, we constructed a novel spider silk protein (NT-MaSp1s-CT) with the pH-dependent secondary structures, containing pH-sensitive N-terminal, C-terminal domains and a repeated core region with merely 191 amino acids. Then pH sensitivity of NT-MaSp1s-CT was detected at different pH conditions and NT-MaSp1s-CT displayed pH-dependent conformational transitions consistent with rational designed objective. Besides, the micelles theory was employed to inquiry the assembly mechanism of NT-MaSp1s-CT in high concentration spinning dope. As expected, NT-MaSp1s-CT protein can be spun into continuous and uniform fibers with the pH ranging from 2 to 11, which is the largest pH boundary for artificial spider silk formation, simplifying the assembly conditions and paving a broad path for spinning process. Moreover, the hemolysis and cytotoxicity of NT-MaSp1s-CT fibers were also determined and the novel fibers exhibit excellent biocompatibility, providing wider potential applications in the biomedical and pharmaceutical fields.

In situ injectable hydrogels, which have great potential in tissue engineering, are characterized by simple preparation, minimal invasiveness and adaptation to complex shapes. However, injectable hydrogels have higher requirements for biocompatibility and safety due to their use in vivo implantation. Therefore, in this study, a human-like collagen (HLC)-based in situ gel-forming injectable HLC-HPA hydrogel was synthesized by combining the amino group of HLC with the carboxyl group of HPA activated using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), followed by crosslinking by horseradish peroxidase (HRP) and H2O2, and used as scaffold material for tissue engineering. The hydrogel stiffness, gel time and biodegradation rate could be easily and independently adjusted by varying the H2O2 and HRP concentrations. Scanning electron microscope (SEM) clarified the homogeneous porous and interconnected internal structures of the hydrogel. In vitro cell viability and in vivo degradation experiments confirmed that the HLC-HPA hydrogel had good biodegradability and excellent biocompatibility. Interestingly, in cultured macrophages, the HLC-HPA hydrogel showed anti-inflammatory activity by reducing the amount of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and increasing the secretion of the anti-inflammatory cytokine interleukin-10 (IL-10) induced by lipopolysaccharide (LPS). Meanwhile, in animal experiments, HLC-HPA hydrogels exhibit excellent biocompatibility and have properties of hemostasis and reduction of inflammatory response. Therefore, the HLC-HPA hydrogel prepared in this study has great potential for development for use in the biomedical field.

Ginsenoside compound K (CK) with a wide range of pharmacological activities has been widely used in the healthcare product industry. However, the application of CK is limited by low productivity and difficult separation. The purpose of this study is to convert ginsenoside Rb1 into CK by improving conversion efficiency in novel “green” reaction medium-deep eutectic solvent (DES). Talaromyces purpureogenus was selected from ginseng rhizosphere soil to produce β-glucosidase with high activity and purity to transform ginsenosides, and Mn2+ was found to be an enzyme promoter. Among the DES based on choline chloride as hydrogen-bond receptor, choline chloride:ethylene glycol (ChCl:EG = 2:1) was the most promising solvent in maintaining enzyme activity and stability. In the presence of 30% v/v ChCl:EG = 2:1, the half-life of β-glucosidase was increased by 96%, the solubility of F2 was increased by 120%, and CK yield was increased by 54% compared with those in the buffer. Fourier transform infrared, circular dichroism, and fluorescence spectroscopy confirmed that DES did not destroy the structure and conformation of β-glucosidase. In addition, 80.6% CK conversion was obtained at 60 °C, pH 4.5, 48 h and 8 mM Rb1, which provided a feasible method for efficiently producing CK.

Ginsenosides have been proven to be potential beneficial in treatment of osteoporosis. To investigate the potential of ginsenosides in osteoporosis, ginsenoside compound K (GCK) was selected to explore the potential therapy targets and mechanism based on network pharmacology (NP). 206 and 6590 targets were obtained for GCK and osteoporosis, respectively, in which 138 targets were identified as co-targets of GCK and osteoporosis based on intersection analysis. Five central gene clusters and hub genes (STAT3, PIK3R1, VEGFA, JAK2 and MAP2K1) were identified through protein-protein interaction network analysis. Gene Ontology (GO) enrichment implied that phosphatidylinositol-related biological process, molecular modification and function may play an important role for GCK in treatment and prevention of osteoporosis. Functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that 16 targets were enriched in the osteoclast differentiation. Also, except for being identified as hub targets, MAPK and phosphatidylinositol-related proteins were enriched in the downstream signaling of c-Fms in the osteoclast differentiation pathway. Molecular docking further confirmed that GCK could interact with active cavity on the surface of c-Fms (osteoclast differentiation-related membrane receptor), and their complex could be stabilized by three H-bonds with residues including Glu 664 (3.19 Å), Glu 664 (2.62 Å) and Cys 666 (2.78 Å). Summarily, GCK could interfere the occurrence and progress of osteoporosis through c-Fms-mediated MAPK and phosphatidylinositol-related signaling regulating osteoclast differentiation.

Worldwide, drug-induced acute liver failure is associated with a high rate of morbidity and mortality. Acetaminophen (APAP), a widely used analgesic, is one of the most common causes of acute liver injury. The purpose of this study was to determine the protective effect of protopanaxatriol-type saponin (PTS) against APAP-induced liver injury and to elucidate the mechanisms underlying this effect. Mice were pretreated with PTS via gavage for 7 days prior to receiving APAP. The results indicated that PTS was highly effective in preventing hepatotoxicity caused by APAP. Meanwhile, pretreatment with PTS resulted in a decrease in inflammation and oxidative stress. Furthermore, PTS reversed the histological change and reduced hepatic injury. Additionally, PTS inhibited the expression of proteins associated with APAP induced hepatic apoptosis in the liver. Taken together, our findings indicated that PTS protected against liver injury caused by APAP by alleviating oxidative stress, inflammation, and apoptosis via the ROS-mediated JNK pathway. Our findings suggest that PTS may have the potential as a novel therapeutic agent for APAP-induced liver injury.

Ginseng is a widely cultivated perennial plant in China and Korea. Ginsenoside Rk3 is one of the major active components of ginseng and is a promising candidate to regulate skin pigments and exert anti-photoaging effects on skin physiology. Ginsenoside Rk3 was mixed with a cream (G-Rk3 cream) and smeared on the skin of mice. Then, the mice were exposed to ultraviolet (UV) A (340 nm and 40 W) and UVB (313 nm and 40 W) radiation. Special attention was given to the anti-photoaging and anti-inflammatory effects of ginsenoside Rk3 on the mouse skin. Macroscopic evaluation indicated that the mouse dorsal skin looked smooth and plump even under UV irradiation for 12 weeks. Pathological analysis indicated that there was no obvious photoaging or inflammation in the mouse skin that was treated with the G-Rk3 cream. More healthy, intact, and neat collagen fibers were observed in mice treated with the G-Rk3 cream than in untreated mice. Further analysis proved that ginsenoside Rk3 could inhibit the decrease in water and hydroxyproline levels in skin tissues and the loss of superoxide dismutase and glutathione peroxidase activities in the blood. Moreover, ginsenoside Rk3 slowed or halted increases in malondialdehyde, matrix metalloproteinase (MMP)-1, and MMP-3 levels in the blood and levels of interleukin 1, interleukin 6, and tumor necrosis factor α in skin tissues. In conclusion, ginsenoside Rk3 plays a significant role in inhibiting photoaging and inflammation to protect skin health.

Preventing bacterial infection in situ and accelerating skin generation simultaneously are essentially important for wound healing. Herein, a mussel-inspired Ag nanozyme-based bilayer hydrogel is constructed to address the above concerns. The bilayer hydrogel is composed of a layer with large pores absorbing the wound exudate and allowing oxygen exchange and a layer with small pores keeping the wound moist and preventing bacterial invasion. Benefitting from the polydopamine (PDA) coating-reduced Ag nanoparticles (AgNPs), the hydrogel exhibits high near infrared (NIR) absorption at 808 nm to generate hyperthermia and NIR-enhanced peroxidase (POD-like) activity to produce hydroxyl radicals (•OH), which endows the hydrogel with excellent antibacterial properties when combined with the released Ag+. In addition, the hydrogel presents adhesiveness due to the catechol group on a PDA molecule. The in vivo test results demonstrate that the bilayer hydrogel can accelerate infected skin generation by facilitating collagen deposition, decreasing tumour necrosis factor-α secretion, and promoting vascular endothelial growth factor expression.

Acetaminophen (APAP)-induced acute liver injury (AIALI) is one of the most common causes of acute liver failure. Owing to the limitations of N-acetylcysteine (NAC), which is the only antidote currently used in clinical practice for APAP, there is a need to develop new therapies that can provide extensive protection against AIALI. Ginsenoside Rk3 is a rare ginsenoside extracted from Panax notoginseng and a previous study has reported its excellent hepatoprotective function. In this study, we explored the therapeutic potential of ginsenoside Rk3 in APAP-induced acute liver injury. We found that ginsenoside Rk3 could reduce APAP-induced hepatotoxicity by reducing serum alanine aminotransferase and aspartate aminotransferase activity and pathological damage to the liver. Moreover, ginsenoside Rk3 could inhibit APAP-induced liver inflammation and oxidative stress by inhibiting the production of oxidative molecules, increasing the production of antioxidant molecules, and reducing the infiltration of inflammatory cells and the production of pro-inflammatory cytokines. Further mechanistic investigations revealed that the therapeutic effect of ginsenoside Rk3 was mainly dependent on the continuous activation of autophagy. Chloroquine, an autophagy inhibitor, was found to inhibit these protective effects. Therefore, ginsenoside Rk3 shows potential as a novel hepatoprotective agent to prevent drug-induced liver injury.

Fuzhuan brick tea (FBT) is a Chinese dark tea that is famous for its significant health benefits, in which Eurotium cristatum (E. cristatum) strains play a vital role in its postfermentation process. In this study, eurocristatine with hypoglycemic activity was discovered for the first time and purified from the spores of E. cristatum growing in FBT. Eurocristatine (98%) was obtained by D-101 macroporous resin-based column chromatography and preparative high performance liquid chromatography (HPLC) with a C18 column as the stationary phase and 35% acetonitrile in ultrapure water as the mobile phase. Hypoglycemic activity in a Hep-G2 cell hypoglycemic model was used as a screening indicator during purification. The chemical structure of eurocristatine was characterized by ESI/MS, 1H NMR and 13C NMR analyses. The antidiabetic effects of eurocristatine were verified in high-fat diet/streptozocin-induced type 2 diabetes mellitus (T2DM) rats. The results showed that eurocristatine significantly reduced fasting blood glucose. Our study demonstrated that eurocristatine, as a newly discovered hypoglycemic active substance, could be considered a potential candidate for the treatment of diabetes and its complications.

Microencapsulation of bacteria is an alternative technology to enhance viability during processing and application. Different from drug microcapsules, controlled release of the dynamic target bacteria and its metabolites from capsules to the rhizosphere is becoming an important issue for the success of microencapsulated PGPR. This work describes in detail the diffusion permeability coefficient (DPC) of rhizobacteria-loaded microcapsules and their relationship to growth metabolite release and bacterial survival rate. Results showed that the DPC value increased with the decrease of the molecular weight of the model probes, and also the increase of sodium alginate and bentonite concentrations. Importantly, the DPC value was negatively correlated with the survival rate of Rs-198. For storage features, the microencapsulation had no effect on the abilities of IAA production (65 μg mL−1), ammonia nitrogen production (43 mg mL−1), or phosphate dissolved (53 mg L−1) after storing for 90 days. A pot experiment revealed that total nitrogen and phosphorus content of cotton plants in the microcapsules with Rs-198 treatment was increased by 43.48% and 46.51%; soil available phosphorus, ammonium nitrogen, alkali-hydrolysis nitrogen, and nitrate nitrogen contents also increased by 45.43%, 31.48%, 17.13% and 55.69%, respectively due to the synergistic effects of Pseudomonas putida Rs-198 and alginate–bentonite microcapsules. In conclusion, the DPC shows that microcapsules have appropriate permeability to control the bacterial growth metabolism and thus show a beneficial effect on cotton growth. This paper reports the release profile of the bacterial growth metabolism from live rhizobacteria-loaded microcapsules, and will provide valuable guidance on living microcapsule application.

As the most common sleep disorder, insomnia seriously affects people's everyday lives. Phytochemicals have been shown to have excellent sleep-promoting effects. Therefore, this study was designed to investigate whether Rg5 and Rk1 extracted from ginseng had sleep-promoting effects and to explore their potential mechanisms. The results showed that Rg5 and Rk1 could significantly lessen the locomotor activity of mice and promote the sleep quality index, including increasing the amount of sleep in a pentobarbital sodium experiment with a threshold dose. In parallel, Rg5 and Rk1 could significantly shorten the sleep latency of mice and prolong the sleep time of mice. Furthermore, Rg5 and Rk1 augmented the GABA/Glu ratio, up-regulating the expression of the GABAA receptor and the GABAB receptor, whereas the GABAA receptor antagonist picrotoxin could antagonize the sleep quality of Rg5/Rk1. In addition, 5-HTP, the precursor of 5-HT, could enhance the sleep effect of Rg5 and Rk1 in mice, and both Rg5 and Rk1 could up-regulate the expression of 5-HT1A. These results were also confirmed by the detection of GABA and 5-HT in mouse cecum content. In conclusion, ginsenoside Rg5/Rk1 can exert sedative and hypnotic effects by affecting the GABA nervous system and the serotonin nervous system.

Mild stir-assisted membrane dispersion extraction (MDE) method was employed to enhance propionic acid (HA) extraction and compared to the mechanical stirred extraction (MSE) method. Triocylamine (TOA) and tributyl phosphate (TBP) were chosen as model extractant to extract HA. Firstly, droplet size and the size distribution of organic phase were analyzed, and then the effects of phase ratio, extractant and HA concentration on extraction performance were investigated. Comparing the two extraction methods, the results show mild stir-assisted MDE method reduced the mass transfer equilibrium time compared to MSE method. The mass transfer mechanism was explored by analyzing mass transfer resistance. Mild stir-assisted MDE had less total mass transfer resistance than MSE. When the extractant concentration was 40%, the extraction process was controlled by organic phase mass transfer process with HA volume fraction was 1% and controlled by both of reaction process and organic phase mass transfer process when HA concentration increased to 5%. This work may provide a new type of extraction method for the recovery of organic carboxylic acid.

Ginsenoside Rg5, a rare saponin belonging to the family of protopanaxadiol ginsenosides, has been demonstrated to have potential anti-tumor effects in various cancers. However, the effect of Rg5 on human gastric cancer and the underlying molecular mechanisms remain to be elucidated. In this study, Rg5 could suppress cell proliferation by causing G2/M phase arrest. Treatment with Rg5 could induce apoptosis through the extrinsic death receptor and intrinsic mitochondrial pathways. Autophagy induction was demonstrated by the formation of autophagosomes and autophagy-related proteins. Rg5-induced cell death was inhibited by the autophagy inhibitor 3-MA and apoptosis inhibitor Z-VAD-FMK. Moreover, the suppression of apoptosis weakened Rg5-induced autophagy, while the inhibition of autophagy attenuated Rg5-induced apoptosis. Further studies revealed that Rg5 induced ROS production and activated MAPK signaling pathways. The ROS scavenger NAC markedly diminished G2/M arrest, apoptosis, autophagy and activation of MAPK pathways induced by Rg5. The p38 inhibitor SB203580 or knockdown of p38 by siRNA clearly reversed Rg5-induced apoptosis and G2/M arrest. The JNK inhibitor SP600125 or knockdown of JNK by siRNA markedly attenuated Rg5-induced G2/M arrest, apoptosis and autophagy. The inhibition of ERK inhibitor U0126 or knockdown of ERK by siRNA clearly restored Rg5-induced apoptosis and autophagy. Finally, Rg5 significantly suppressed the growth of xenograft gastric tumors with fewer side effects. Overall, the evidence suggested that Rg5 is a novel and promising strategy for the treatment of gastric cancer owing to its high efficacy, multiple mechanisms and fewer side effects.

The basic fibroblast growth factor (bFGF) plays an important role in the wound repair process. However, lacking of better biomaterials to carry bFGF still is a challenge in skin repair and regeneration. In this study, the human-like collagen (HLC) cross-linked with transglutaminase (TG) to fabricate a HLC/TG hydrogel to load bFGF. The physical properties of hydrogel, such as interior structure, mechanical property, were characterized

Background and purpose Ginsenoside Rg5 (Rg5), a triterpene saponin, extracted from the natural herbal plant ginseng, is one of the most potent anticancer drugs against various carcinoma cells. However, the therapeutic potential of Rg5 is limited by its low solubility in water, poor bioavailability, and nontargeted delivery. Therefore, we prepared folic acid (FA)-modified bovine serum albumin (BSA) nanoparticles (FA-Rg5-BSA NPs) to improve the therapeutic efficacy and tumor targetability of Rg5. Methods Various aspects of the FA-Rg5-BSA NPs were characterized, including size, polydispersity, zeta potential, morphology, entrapment efficiency (EE), drug loading (DL), in vitro drug release, thermal stability, in vitro cytotoxicity, cell apoptosis, cellular uptake, in vivo antitumor effects and in vivo biodistribution imaging. Results The FA-Rg5-BSA NPs showed a particle size of 201.4 nm with a polydispersity index of 0.081, uniform spherical shape, and drug loading of 12.64±4.02%. The aqueous solution of FA-Rg5-BSA NPs had favorable stability for 8 weeks at 4°C. The FA-Rg5-BSA NPs dissolved under acidic conditions. Moreover, the Rg5-BSA NPs and FA-Rg5-BSA NPs had advanced anticancer activity compared with Rg5 in MCF-7 cells, while poor cytotoxicity was observed in L929 cells. The FA-Rg5-BSA NPs facilitated cellular uptake and induced apoptosis in MCF-7 cells. In addition, in an MCF-7 xenograft mouse model, the in vivo antitumor evaluation revealed that FA-Rg5-BSA NPs were more effective in inhibiting tumor growth than Rg5 and Rg5-BSA NPs. The in vivo real-time bioimaging study showed that the FA-Rg5-BSA NPs exhibited superior tumor accumulation ability. Conclusion The results suggested that FA-Rg5-BSA NPs could serve as a promising system to improve the antitumor effect of Rg5.

Polyvinyl alcohol (PVA) has good mechanical stability and flexibility. However, PVA hydrogels of low compressive strength and low cell adhesion is still considered difficult to apply to tissue engi...

Ginsenosides have been reported to possess pharmacological effects, such as antioxidative, anti-inflammatory and antitumor effects. Nevertheless, little has been reported about the anti-breast cancer effects of ginsenoside Rk1 (Rk1). In this work, we explored the anti-breast cancer effects of Rk1. The results suggested that Rk1 suppressed cell growth, colony formation, and triggered S phase arrest. Rk1 also triggered ROS overproduction, reduced mitochondrial membrane potential and induced apoptosis. Moreover, the PTEN/PI3K/Akt/mTOR pathway was involved in Rk1-induced apoptosis. Treatment with Z-VAD-FMK, LY294002 and N-acetylcysteine further illustrated that Rk1 induced apoptosis in MCF-7 cells through ROS-mediated PTEN/PI3K/Akt/mTOR signaling pathway. Furthermore, in xenograft nude mice model, Rk1 treatment dramatically suppressed tumor growth and caused no obvious injuries to major organs. Taken together, the results of this study demonstrated, for the first time, the anticancer efficacy and mechanism of Rk1 in MCF-7 cells, providing basic evidence supporting Rk1 as a potential anti-breast cancer agent.

7α- and 7β-hydroxysteroid dehydrogenases (HSDHs) are key biocatalysts for the biotransformation of ursodeoxycholic acid (UDCA) from chenodeoxycholic acid (CDCA). Various researches focused on heterogeneously expressed engineering enzymes to epimerize CDCA for UDCA, however not yet applied to further industrial application. In this work, we present the large-scale production of UDCA from CDCA by 7α- and 7β-HSDH enzymatic synthesis. Engineering enzymes were both successfully heterologous overexpressed in Escherichia coli BL21, and the effect of the enzymatic synthesis was investigated. The mass analysis (MS), IR spectrum, 1H NMR and 13C NMR were used to characterize the product. 500-L fermentor fermentation strategy producing a stable supply of HSDH and large-scale production process of UDCA in dozens kilogram class enabled industrial application.

To improve mechanical strength, polyvinyl alcohol hydrogels were often prepared through freeze-thaw method. However, they usually exhibited micropores limiting their applications. Hence, macroporou...

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.

Ginsenoside Rh4, as a bioactive component obtained from Panax notoginseng, has excellent pharmacological properties. However, its role in regulating gut microbiota and intestinal inflammation is still poorly understood. Thus, the aim of this study is to investigate the effect of Rh4 on gut microbiota, especially antibiotic-induced microbiota perturbation, and the underlying mechanisms. C57BL/6 mice were given different doses of Rh4 after the establishment of a gut microbiota disturbance model with antibiotics. Our data revealed that Rh4 administration could greatly improve the pathological phenotype, gut barrier disruption, and intestinal inflammation in mice that had been antibiotic-induced. Notably, it was found that Rh4 significantly inhibited the TLR4-MyD88-MAPK signaling pathway. In addition, Rh4 treatment could significantly increase the number of short chain fatty acids (SCFAs) and bile acids (BAs). These changes were accompanied with beneficial alterations in gut microbiota diversity and composition. In conclusion, Rh4 improves intestinal inflammation and induces potentially beneficial changes in the gut microbiota, which are conducive to revealing host-microbe interactions.

Bacterial infection and oxidative stress remain critical problems for wound closure because they frequently trigger severe complications and delay wound healing. In addition, maintaining a moist microenvironment can promote skin regeneration. In this study, a bilayer hydrogel modified with tannic acid (TA) was constructed to accelerate wound repair. The bilayer hydrogel, composed of a layer with large pores to absorb the fluids and allow gas exchange and small pores to maintain the wound moist and prevent bacterial invasion, was initially developed. Thereafter, TA was introduced into the hydrogel to form a dual crosslinked network and endowed the hydrogel with adhesiveness, antibacterial, and oxidation resistance. In addition, the TA@bilayer hydrogel exhibited shape memory behaviour and self-healing ability due to the hydrogen bonds formed between TA and the bilayer hydrogel. As a result, the TA@bilayer hydrogel significantly promoted wound closure by accelerating collagen deposition, reducing tumour necrosis factor-α (TNF-α) levels, and facilitating the expression of vascular endothelial growth factor (VEGF).

Protein-based hydrogels are important functional materials with many potential applications. However, the relatively small pore size and poor mechanical properties substantially limit their application. Here a superporous bovine serum albumin (BSA) hydrogel is prepared with high porosity and interconnectivity by using BSA and 1,2,7,8-diepoxyoctane (DEO). The equilibrium water contents of hydrogels can reach 76.5%. Moreover, the BSA hydrogels show excellent mechanical properties and excellent deformation recoverability, with a maximum compression modulus of 50 MPa at 75% strain and no residual strain generated after 500 cyclic compression tests. The resulting BSA hydrogel has excellent biocompatibility for cell adherence and is nonbiodegradable for 40 weeks. More importantly, the BSA hydrogel exhibits excellent hemostatic ability, with hemostatic times in a rabbit ear artery and rabbit liver of 33 and 28 s, respectively. Therefore, BSA hydrogels have potential applications as painless nonadherent wound dressings and implant materials for plastic surgery.

For the first time, collagen-based hydrogels were fabricated in the presence of a biocompatible ionic liquid, 1-ethyl-3-methylimidazolium acetate ([EMIM] [Ac]), by a simple biopolymer cross-linking process facilitated by the strong catalytic hydrolysis of microbial transglutaminase (MTGase). Phosphate buffer solution (PBS)-encapsulated human-like collagen (HLC) or fish bone collagen (FBC) for the composite hydrogels was simply prepared by the codissolution of biopolymers in [EMIM] [Ac] or, in the absence of the ionic liquid, by the dispersion of MTGase in the biopolymer solution, leading to the formation of MTGase-aided hydrogels (Gel1 and Gel4) and [EMIM] [Ac]/MTGase-aided hydrogels (Gel2, Gel3, and Gel5). The effects of different contents of [EMIM] [Ac] and collagens of different origins (HLC and FBC) during fabrication on a range of structural and material characteristics, including the synthesis mechanism, three-dimensional structure, swelling behavior, mechanical strength, enzymatic hydrolysis rate, cytotoxicity, fibroblast cell proliferation rate

The excessive inflammation, oxidative stress, and impaired wound angiogenesis are major factors leading to difficulties in chronic wound healing. To simplify the design of wound dressing and eliminate the need for drug loading and develop bioactive materials with intrinsic antioxidant and anti-inflammatory properties, we prepared hydrogels for the first time using paramylon secreted by Euglena gracilis, which is a polysaccharide with prominent antioxidative and anti-inflammatory properties and has been approved by FDA as food additive. The paramylon hydrogel had a through pore structure, suitable mechanical and water retention properties, and excellent hemocompatibility and cytocompatibility (promoting cell proliferation and adhesion). This study showed that the paramylon hydrogel has favourable anti-inflammatory effects and the ability to scavenge reactive oxygen species (ROS) through free radical destruction, deoxygenation, and singlet oxygen quenching, and the paramylon hydrogels could also inhibit ROS production by chelating the metal ions required for the formation of ROS. We constructed an acute full-skin defect model and a chronic deep third-degree burn wound model and found that the paramylon hydrogel could effectively reduce wound inflammation and promote angiogenesis to facilitate wound repair. Furthermore, for the first time, we found that paramylon hydrogel could promote the formation of blood vessels via the HIF-1α-VEGF pathway. These results indicated that the highly bioactive paramylon could be the preferred material for wound healing and tissue engineering.

Treating serious bone trauma with an osteo-inductive agent such as bone morphogenetic proteins (BMPs) has been considered as an optimized option when delivered via a collagen sponge (CS). Previous works have shown that the BMP concentration and release rate from approved CS carriers is difficult to control with precision. Here we presented the fabrication of a recombinant fusion protein from recombinant human-like collagen (HLC) and human BMP-2 (hBMP2). The fusion protein preserved the characteristic of HLC allowing the recombinant protein to be expressed in Yeast (such as Pichia pastoris GS115) and purified rapidly and easily with mass production after methanol induction. It also kept the stable properties of HLC and hBMP2 in the body fluid environment with good biocompatibility and no cytotoxicity. Moreover, the recombinant fusion protein fabricated a vertical through-hole structure with improved mechanical properties, and thus facilitated migration of bone marrow mesenchymal stem cells (MSCs) into the fusion materials. Furthermore, the fusion protein degraded and released hBMP-2 in vivo allowing osteoinductive activity and the enhancement of utilization rate and the precise control of the hBMP2 release. This fusion protein when applied to cranial defects in rats was osteoinductively active and improved bone repairing enhancing the repairing rate 3.5- fold and 4.2- fold when compared to the HLC alone and the control, respectively. There were no visible inflammatory reactions, infections or extrusions around the implantation sites observed. Our data strongly suggests that this novel recombinant fusion protein could be more beneficial in the treatment of bone defects than the simple superposition of the hBMP2/collagen sponge.

Natural animal collagen and its recombinant collagen are favorable replacements in human tissue engineering due to their remarkable biomedical property. However, this exploitation is largely restricted due to the potential of immunogenicity and virus contamination. Exploring new ways to produce human collagen is a fundamental key to its biomedical and clinical application. All human fibrillar collagen molecules have three polypeptide chains constructed from a repeating Gly-Xaa-Yaa triplet, where Xaa and Yaa represent one random amino acid. Using cDNA techniques to modify several repeat sequences of the cDNA fragment, a novel human collagen named recombinant human-like collagen (HLC), with low immunogenicity and little risk from hidden virus can be engineered and notably tailored to specific applications. HLC was initially used as a coating to modify the tissue engineering scaffold, and then used as the scaffold after cross link agents were added to increase its mechanical strength. Due to its good biocompatibility, low immunogenicity, stabilised property and the ability of mass production, HLC has been widely considered to use in skin injury treatments, vascular scaffolds engineering, cartilage, bone defect repair, skincare, haemostatic sponge, and drug delivery including coating with medical nanoparticles. In this review, we symmetrically reviewed the development, recent advances in design and application of HLC, and other recombinant human collagen-based biomedicine potentials. For comparison and providing basic background information about the techniques, we start with recombinant human collagens. In the end, future improvements in using HLC are also discussed.

Barium sulfate (BaSO4) is a material with high reflectance for preparing bifunctional sheets used in dry reagent chemical tests. In this study, bifunctional BaSO4 sheets with scattering power and high reflectance were prepared with BaSO4 microspheres sized 1.3~1.8 &mu, m and cellulose acetate (CA). Factors such as the BaSO4 morphology, CA dosage, mixing time, surfactant, solid content and wet sheet thickness were investigated. Scanning electron microscopy (SEM), a dynamic contact angle test, light reflection detector and light reflection densitometer were employed to characterize the structure and properties of bifunctional BaSO4 sheets. The optimal conditions for preparing bifunctional BaSO4 sheets under natural drying conditions were as follows: mass ratio of CA to BaSO4 microspheres was 0.03:1, mixing acetone solution was used to form liquid stock puree, 35 &mu, L Tween-80 was used to improve the hydrophilicity of bifunctional sheets, solid content was 54.9%, mixing 2 h then 450 &micro, m thick sheets were cast on a glass plate using a film applicator. The light reflectance value of bifunctional BaSO4 sheets in the range of 400~800 nm was higher than 97%. Serum diffused in bifunctional BaSO4 sheets reacted in reagent sheets and formed uniform colorful spots. Considering the repeatability of spot proportion and light reflectance value, the sheet offered a uniform serum scattering power and good repeatability. Therefore, the bifunctional BaSO4 sheets are regarded as a promising material for dry chemical diagnostic reagents.

In this study, single factor experiments and orthogonal test were designed to fabricate a novel poly(vinyl alcohol) (PVA), human-like collagen (HLC) and sodium alginate (SA) composite hydrogel as w...

Ginsenosides, as major active components of ginseng, possess various pharmacological activities, including anti-tumor, anti-diabetic and hypotensive effects. However, the sedative and hypnotic effect of ginsenosides and the involved mechanism remain unclear. In the present study, the hypnotic effect of rare protopanaxadiol-type (PD) ginsenosides, consisting of Rg3, Rk1, Rg5, and protopanaxatriol-type (PT) ginsenosides, consisting of Rh1, Rk3, Rh4, was investigated and compared in rodent models through behavioral pharmacology methods. Both rare PD and PT ginsenosides decreased spontaneous locomotion activity in normal mice and reduced sleep latency, and extended sleep duration in pentobarbital-treated mice. Moreover, PD and PT ginsenosides attenuated the insomnia induced by caffeine in mice. These hypnotic effects of PD and PT ginsenosides were potentiated by 5-hydroxytryptophan (5-HTP), a precursor of serotonin, and inhibited by p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. Flumazenil (FLU, a specific gamma aminobutyric acid (GABA) antagonist) also impaired the hypnotic effect of both PD and PT ginsenosides. The aforementioned results indicated that PD and PT ginsenosides exhibit sedative and hypnotic activity, and PT ginsenosides show higher activity than PD ginsenosides at high doses (96 mg kg−1). Furthermore, the bioactivity of these two types of ginsenosides might be mediated via the serotonergic and GABAergic systems.

Protopanaxatriol saponin (PPT) has excellent anti-cancer, anti-diabetes, and anti-anemia effects, but its effect on intestinal bacteria has rarely been studied. In this study, we investigated whether PPT has the ability to improve intestinal health in antibiotic-treated mice. Model mice were constructed using a broad-spectrum antibiotic, cephalosporin. The composition of the gut microbiota and relative concentration of short-chain fatty acids (SCFAs), short-chain fatty acid receptor proteins (GPR41, GPR43 and GPR109A), tight junction components (ZO-1 and occludin) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-22 and IFN-γ) were determined. The results showed that PPT improved the composition of the gut microbiota, increased the concentration of SCFAs as well as receptor proteins and tight junction proteins, and decreased the pro-inflammatory cytokines. These findings indicate that PPT has a protective effect on intestinal microbes and enhances the integrity of the intestinal barrier as well as alleviates colonic inflammation in antibiotic-treated mice.

Ginsenoside Rk3 (G-Rk3) is a main active ingredient of ginsenosides. Several recent studies demonstrated that ginsenosides have potential anti-type 2 diabetes mellitus (T2DM) properties. To evaluate the anti-T2DM effect of G-Rk3 and verify its potential mechanism, a high-fat-diet/streptozocin (HFD/STZ) induced model of T2DM in C57BL/6 mice and a high glucose induced insulin resistance model of HepG2 cells were applied in this research. Our analysis indicated that G-Rk3 reduced HFD/STZ induced hyperglycemia, and serum insulin and inflammation levels, and ameliorated glucose tolerance and insulin resistance, and prevented liver histological changes. Furthermore, it also significantly reduced lipid accumulation as shown by lower TG, LDL-C and TC serum concentrations and Oil Red O staining in liver tissues. The hypoglycemic effect of G-Rk3 seemed to be partially mediated via the inhibition of hepatic gluconeogenesis, which was supported by the activated p-Akt, p-FoxO1 and GLUT2 and inhibited FoxO1, PEPCK and G6pase protein expressions in the liver as well as increased glucose uptake in high glucose induced HepG2 cells. The gene expressions of hepatic gluconeogenesis were also down-regulated by G-Rk3 in HFD/STZ induced T2DM mice. In addition, G-Rk3 suppressed HFD/STZ induced lipid accumulation by regulating related gene and protein expressions such as p-ACC, FAS and SREBP-1, which are the downstream targets of AMPK. AMPK and Akt inhibitors significantly reversed G-Rk3 mediated hepatic gluconeogenesis and lipid accumulation. Thus, our study is the first to illustrate that G-Rk3 mediates hepatic gluconeogenesis and lipid accumulation via activating the AMPK/Akt signaling pathway in HFD/STZ induced T2DM mice.

The aim of this study is to investigate the effect of kiwifruit seed oil (KSO) on inflammation and hepatic fat metabolism in high-fat diet (HFD)-induced C57BL/6 obese mice for 12 consecutive weeks by oral intervention. The results showed that KSO supplementation inhibited the body weight gain, decreased fasting blood glucose and insulin levels, and alleviated glucose and insulin tolerance in obese mice. KSO supplementation reduced the hepatic fat accumulation by inhibiting the levels of triglyceride, total cholesterol and adipose hollow space in HFD-induced mice liver tissues. Additionally, KSO administration down-regulated the expression of inflammation-related cytokines (TNF-α, IL-1β and IL-6) and lipid synthesis related genes (PPAR-γ and FAS), while up-regulated the expression of fatty acid β oxidation-related genes (PPAR-α, CPT1a and CPT1b) and thermogenesis-related gene (UCP2) in liver both in transcriptional and translational levels. Overall, our results implicate that KSO as a potential dietary supplement for the prevention of obesity.

CS–HLC–HA–β-GP (chitosan–human-like collagen–hyaluronic acid–β-sodium glycerophosphate) hydrogels were prepared based on the self-assembly of CS–HLC–HA (CCA) fibers. The effects of the fibers on the synthesis, characteristics and biomedical applications of CS–HLC–HA–β-GP (CCAG) hydrogels were studied for various HA contents. The synthesis mechanism of the novel CCAG hydrogel was explored using Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The hydrogels were characterized by a swelling test, gelling time and enzymatic treatments. The results indicated that a new amide bond (–CONH) and –NRH2+ were formed. The gelling time and swelling behaviors were dependent on the intertwining, overlap and adsorption of the polymer chains at various temperatures and pH. Furthermore, biomedical applications were evaluated by transmission electron microscopy (TEM), immunohistochemical analysis and haematoxylin and eosin (H&E) staining. The effect of the fibers on the histocompatibility of the hydrogels revealed that the fibers inside the hydrogel pores reduced the quantity of macrophages, decreased the degree of inflammation, and improved the anti-degradation of the modified hydrogels. This type of new hydrogel emerges as an interesting injectable filling biomaterial for tissue engineering.

In this study, we designed multifunctionalized hydrogel scaffolds and injectable particles based on high-molecular-weight (MW) pullulan and human-like collagen (HLC) crosslinked with 1,4-butanediol diglycidyl ether (BDDE) for combination therapy tissue restoration. The properties of the pullulan/BDDE (PB) and pullulan/BDDE/human-like collagen (PBH) hydrogels were characterized via swelling ratio measurements, mechanical tests, and enzymatic degradation in vitro and via subcutaneous injections in vivo. The results demonstrate that the dry hydrogels completely returned to their original state in deionized water. The elastic modulus of the PBH53 dry hydrogels is higher than that of the other hydrogels after exposure to bending stress and compression stress with a maximum value of 7858.93 MPa. In addition, the in vitro live/dead staining and cell adhesion of the PBH hydrogels exhibited a superior fibroblast morphology without high levels of cell death, which were considerably better than those of PB hydrogels. In vivo, PB and PBH particles with good biocompatibility and anti-biodegradation were successfully prepared via the granulation of wet PB and PBH hydrogels for efficient subcutaneous injection in Kunming mice and New Zealand rabbits. Therefore, the PB and PBH hydrogels were found to be acceptable, safe, soft materials for use in skin restoration, cartilage treatment, and lacrimal dryness therapy.

Ginsenosides have a variety of pharmacological activities, including immunomodulatory, antitumor and anti-inflammatory activities. However, the effect of Rk3 on ulcerative colitis has rarely been reported. This study evaluated the effect of Rk3 on DSS-induced ulcerative colitis and preliminarily explored the anti-inflammatory mechanisms. Rk3 administration significantly attenuated the weight loss, increased DAI scores, colonic shortening, and increased MPO and iNOS activities caused by DSS in mice. Histological improvement was apparent, tight junctions in the colon were restored, and the levels of short-chain fatty acids (acetic acid, butyric acid and isovaleric acid) were increased. In addition, Rk3 reduced the expression of proinflammatory factors (TNF-α, IL-1β and IL-6), NLRP3, ASC, and Caspase-1, indicating blockade of the NLRP3 inflammasome pathway. These results show that Rk3 can improve DSS-induced ulcerative colitis by protecting intestinal barrier function and inhibiting NLRP3 inflammasome expression, indicating that Rk3 could be used as a potential drug for treating ulcerative colitis.

Cartilage tissue engineering has become the trend of cartilage defect repair owing to the engineered biomimetic tissue that can mimic the structural, biological and functional characteristics of natural cartilage. Biomaterials with high biocompatibility and regeneration capacity are expected to be used in cartilage tissue engineering. Herein, in this study, a dual-network bovine serum albumin/sodium alginate with hydroxyapatite nanowires composite (B-S-H) hydrogel scaffold has been prepared for cartilage repair. The obtained B-S-H hydrogel scaffold exhibits ideal physical properties, such as excellent mechanical strength, high porosity and swelling ratio, as well as the excellent biological activity to promote the human bone marrow derived mesenchymal stem cells (hBMSCs) proliferation and differentiation. The in vivo study further shows that the B-S -H hydrogel scaffold can obviously promote the generation of new cartilage that integrates well with surrounding tissues and is similar to adjacent cartilage in terms of thickness. It is considered that the B-S-H hydrogel scaffold has great potential in the application of cartilage defects repair.

At present, approximately 19–34% of diabetic patients (nearly 450 million) may have complications involving diabetic foot ulcers (DFUs). Wound healing of DFUs still faces huge problems, such as long-term chronic inflammation and impaired angiogenesis. Therefore, an M2 macrophage-polarized anti-inflammatory hydrogel (HTHE-M@D) combined with mild heat stimulation is designed for DFUs treatment. The HTHE-M@D hydrogel is prepared by enzymatic cross-linking of epigallocatechin gallate dimer-grafted hyaluronic acid (HA-EGCG) and tyramine-grafted human-like collagen (HLC-TA) and integrating deferoxamine-loaded mesoporous polydopamine nanoparticles (M@D). The hydrogel exhibits prominent enhancement of angiogenesis, which is attributed to the combination of mild heat stimulation via photothermal effects and the angiogenic drugs (deferoxamine) released from the hydrogel. The hydrogel also promotes the transformation of macrophages from the M1 to M2 phenotype and exhibits good anti-inflammatory, antibacterial, antioxidant, hemostatic properties and biocompatibility. Additionally, the hydrogel has desirable mechanical strength, enhanced tissue adhesion and injectability, thus making it more adaptive to DFUs. The results demonstrate that the combination of the hydrogel and mild thermal stimulation promotes skin regeneration of diabetic wounds and shortens the healing time to 13 days. The combined treatment might offer a promising therapeutic strategy for DFUs.

Plant polyphenols have shown antiviral activity against several human pathogens, but their physicochemical interactions are not well-understood. The objectives of this study were to compare the antiviral activity between monomeric catechin and dimeric procyanidin B2 (PB2) using cultivable human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and to understand their potential antiviral mechanism using virus-like particles (VLPs) and the P domain of human norovirus GII (HNoV GII.4). Surrogate viruses at 5 log PFU/mL were treated with 0.5–5 mg/mL monomeric catechin monohydrate, PB2 or phosphate buffered saline (PBS, pH 7.2; control) at 37 °C over 24 h. Infectivity was determined using plaque assays and data from triplicate experiments were statistically analyzed. PB2 at 0.5 mg/mL and 1 mg/mL reduced FCV-F9 to undetectable levels after 3 h and MNV-1 by 0.21 and 1.23 log PFU after 24 h, respectively. Monomeric catechins at 1 mg/mL reduced FCV-F9 to undetectable levels after 6 h and MNV-1 titers to undetectable levels after 24 h. In addition, PB2 was shown to directly bind the P domain, the main capsid structure of HNoVs in the ratio of 1:1 through spontaneous interactions. Electrostatic interactions played a dominant role between PB2 and the P domain. PB2 significantly altered tertiary but not secondary structures of VLPs. Transmission electron microscopy demonstrated that PB2 aggregated VLPs, further indicating interactions between them. These findings indicate that PB2 causes structural changes of the P domain of VLPs, mainly through direct interaction leading to HNoV inactivation., Highlights • Polymeric procyanidins cause higher reduction of human norovirus surrogate titers than monomers. • Binding of procyanidin to human norovirus-like particles alters capsid structure. • Procyanidin binding to viral capsid results in decreased infectivity.

To enhance the stability of recombinant human collagen α1(I) chains (rhCOL1A1) in production and purification stages, a gene fragment fusing COL1A1 and insulin protein coding domains was synthesized and inserted into the pPIC9K expression vector. The fusion peptide-expressing Pichia pastoris strain was created by transformation. After optimization of shake flask cultures, the ultimate intracellular expression level of the insulin-collagen α1(I) chain fusion protein (INS-COL1A1) reached about 300 mg·L− 1, and no obvious protein degradation was found in the fermentation and purification processes. The His-tagged recombinant fusion protein was detected by western blotting and was effectively purified using Ni2 +-chelating chromatography. A prominent improvement in the stability of INS-COL1A1 was observed compared to rhCOL1A1 in vitro, and the rhCOL1A1 released from the fusion protein was studied by LC–MS/MS and in bioassays. The results showed that the purified rhCOL1A1 was consistent with the native protein in amino acid composition and had a similar biological compatibility. To our knowledge, this is the first study to demonstrate the use of insulin as a fusion protein to improve the stability of easily degradable proteins.

The objective of this study was to assess the effect of a modified human-like collagen calcium complex on osteoporosis mice. BHK ( Baby Hamster Kidney ) cells were used to compare the cytotoxicity of different calcium reagents with the MTT test. Six-week-old male mice (n = 80) were randomly divided into eight groups: a blank group (blank), control group (control), human-like collagen calcium group (HLC-Ca), thiolated human-like collagen calcium group (SH-HLC-Ca), phosphorylated human-like collagen calcium group (Pi-HLC-Ca), gluconate group (Glc-Ca), calcium carbonate group (CaCO 3 ) and D-cal group (B). A systematic analysis of the results available in vivo after 3 months of treatment was presented. The effects of several Ca supplements on osteoporosis mice were investigated by detecting serum calcium, alkaline phosphate activity (ALP), bone hydroxyproline (BHP) and bone mineral density (BMD). The results proved that the BMD and BHP of osteoporosis mice were significantly increased in the Pi-HLC-Ca group, while serum calcium and ALP were decreased. Therefore, Pi-HLC-Ca is likely a good calcium supplement for clinical applications. In this review, the advantage of Pi-HLC-Ca in preventing and delaying osteoporosis is highlighted. In addition to the current progress, further investigations are necessary to reveal the relative influences of collagen and calcium proportions on the long-term clinical effects of osteoporosis.

Human-like collagen(HLC) has an important role in biomedical field, while endotoxin contamination limits it use. In this study, the saturated allantoin as an adsorbent was applied in adsorbing endo...

Developing high-rate anode materials with large capacity for lithium ion batteries (LIBs) is quite necessary for the booming electric vehicles industry. The utilization of stable and conductive hollow structures for electrode composite materials could make the desired performances possible in the future. Thus, in this study, a hollow structured Ni–CoSe2 embedded in N-doped amorphous carbon nanocomposite (Ni–CoSe2@NC) has been successfully synthesized with metal–organic frameworks (MOFs) as precursors. Such strategy integrates both the merits of the multicomponents and the hollow structure; the latter could facilitate both mass and charge transport, and the former (the N-doped carbon) could not only offer plenty of surface defects, improving the surface capacitive contributions, but also stabilize the electrode structure during the charge/discharge processes. As a result, the metal selenide composite delivers outstanding high-rate properties with good stability as the anode for LIBs. The structure and comp...