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1. Bimetallic hybrid nanoflowers containing l-aspartic acid were synthesized by a one-pot method for successful immobilizing snailase.2. Asp@ZIF-ZnCo-Sna has excellent enzyme loading capacity, activity and better catalytic efficiency.

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@CelINS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@CelINS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@CelINS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@CelINS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

Noncompressible hemorrhage caused by gunshots and sharp objects leads to higher trauma mortality, and cryogels have great potential in controlling noncompressible hemorrhage applications owing to their shape-memory properties. However, the use of non-toxic crosslinkers to prepare cryogels for noncompressible hemorrhage remains a challenge. In this study, a series of cryogels were prepared using oxidized dextran (ODex) as a biocompatible crosslinker, combined with the good hemostatic properties of chitosan (CS) and human-like collagen (HLC), and polydopamine nanoparticles (PDA-NPs) were also introduced to strengthen the shape recovery speed of the cryogels and further enhance their hemostatic performance. The CS/HLC/ODex/PDA-NPs (CHOP) cryogels presented a highly interconnected macroporous structure, powerful water/blood absorption capacity, robust mechanical performance, and rapid water/blood-triggered shape recovery. In vitro coagulation and coagulation mechanism tests showed that CHOP exhibited strong procoagulant ability, high adhesion to blood cells and fibrinogen, and the capacity to activate platelets and intrinsic pathways. In vivo hemostatic tests indicated that CHOP could effectively shorten the bleeding time and reduce the bleeding volume of liver incision bleeding and liver noncompressible hemorrhage. Meanwhile, CHOP exhibited good biocompatibility and biodegradability, and could promote wound healing. These results suggest that CHOP cryogels will be a promising hemostatic dressing.

Hypoxia, excessive reactive oxygen species (ROS), impaired angiogenesis, lasting inflammation, and bacterial infection, are key problems impeding diabetic wound healing. Particularly, controllable oxygen release and ROS scavenging capacities are critical during the wound healing process. Here, an injectable hydrogel based on hyaluronic acid

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world. Recently, suppression of glutamine metabolism has become one of the hottest therapy targets for cancer treatment. There is a growing amount of research that indicates that ginsenosides possess good anti-tumor activity. However, the effect of ginsenoside Rk1 on glutamine metabolism in HCC is unclear. In this study, Rk1 was demonstrated to be effective at inhibiting the proliferation of HCC through the induction of cell cycle arrest and apoptosis. Especially, Rk1 was shown for the first time to inhibit glutamine metabolism in HCC. Rk1 downregulates GLS1 expression, and consequently decreases the GSH production, stimulating ROS accumulation to induce apoptosis. In addition, transcriptomic results showed that the ERK/c-Myc signaling pathway was enriched in HepG2. Rk1 exerts an inhibitory effect on glutamine metabolism in HCC by regulating the ERK/c-Myc signaling pathway, and inducing apoptosis

Sialic acid, a common terminal monosaccharide on many glycoconjugates, plays essential roles in many biological processes such as immune responses, pathogen recognition, and cancer development. For various purposes, sialic acids may need to be removed from glycopeptides or glycans, mainly using enzymatical or chemical approaches. In this study, we found that most commonly used chemical methods couldn't completely remove sialic acids from glycopeptides. Although the de-sialylation efficiency could be further enhanced by increasing the treatment time or acid concentration, the undesirable side reactions on the peptide portion would decrease glycopeptide identification. By adding the deamidation on carbamidomethyl-cysteine (C), asparagine (N), and glutamine (Q) residues as a variable modification during database search, most of the unidentified spectra could be recovered. This optional acid-treatment and database search method for the complete removal of sialic acids without losing much spectral identification should be quite useful for many glycomic and glycoproteomic studies.

Ginsenoside CK alleviated non-alcoholic fatty liver disease through the LKB1/AMPK pathway.

Ginsenoside Rh4 inhibited inflammation, oxidative stress and apoptosis in mice with gastric ulcers through modulation of MAPK/NF-κB and PGE2-Cox pathways, thereby ameliorating gastric injury.

Long-term exposure to ultraviolet (UV) irradiation, especially UVB, can trigger destructive intracellular effects, including various types of DNA damage, oxidative stress, and inflammatory responses, leading to accelerated skin aging. Ginsenoside Rk1, a rare ginsenoside pertaining to panaxadiol saponins, has been certified to possess underlying anti-inflammatory effects. Nevertheless, the efficiency of Rk1 against the photoaging of human skin and the latent molecular mechanisms are still unclear. Here, UVB-irradiated HaCaT keratinocytes were used as an

Whitlockite (WH, Ca18Mg2(HPO4)2(PO4)12) is an important inorganic phase in human bones and has positive significance for participating in the bone reconstruction process. In this paper, we report different doping strategies to prepare WH and WH-Ln (Eu/Tb) nanocrystals, and have successfully synthesized WH-Ln (Eu/Tb) nanoparticles (NPs) with bright red or green fluorescence based on ions exchange doping by two-step hydrothermal reaction. WH-5%Ln (Eu/Tb) NPs with the best fluorescence properties were successfully applied to live cell imaging, and WH-5%Eu NPs were implanted into the bone defect site in rabbit femoral condyles to visually observe its degradation process. The related results would help us understand WH nanocrystals and further expand their potential applications in tissue engineering and related fields.

Recombinant collagen, as an alternative to natural collagen, has the potential to be widely used in biomaterials, biomedicine, etc. Diverse recombinant collagens and their variants can be industrially produced in a variety of expression systems, which lays a foundation for exploring and expanding the clinical application of recombinant collagens. We reviewed different expression systems for recombinant collagens, such as prokaryotic expression systems, yeast expression systems, as well as plant, insect, mammal, and human cell expression systems, and introduced the advantages, potential applications, and limitations of recombinant collagen. In particularly, we focused on the current progress in the recombinant collagen production, including recombinant expression system construction and hydroxylation strategies of recombinant collagen, and summarized the current biomedical applications of recombinant collagen.

Flexible electronics are playing an increasingly important role in human health monitoring and healthcare diagnosis. Strong adhesion on human tissue would be ideal for reducing interface resistance and motion artifacts, but arising problems such as skin irritation, rubefaction, and pain upon device removal have hampered their utility. Here, inspired by the temperature reversibility of hydrogen bonding, a skin-friendly conductive hydrogel with multiple-hydrogen bonds was designed by using biocompatible poly(vinyl alcohol) (PVA), phytic acid (PA), and gelatin (Gel). The obtained PVA/PA/Gel (PPG) hydrogel with temperature-triggered tunable mechanic could reliably adhere to skin and detect electrophysiological signals under a hot compress while be readily removed under a cool compress. Furthermore, the additional advantages of transparency, breathability, and antimicrobial activity of the PPG hydrogel ensure its long-time wearable value on the skin. It is both environmentally friendly and cost saving for the waste PPG hydrogel during production can be recycled based on their reversible physical bonding. The PPG hydrogel sensor is expected to have good application prospects to record electrophysiological signals in human health monitoring.

Ginsenoside Compound K (CK) has high pharmacological activity for being widely used in the treatment and prevention of diseases. However, the content of CK in ginseng is very low or almost non-existent. In the present study, ginsenoside Rb1 was converted into ginsenoside F2 and CK by using the extracellular protein isolated from Aspergillus niger Wu-16. The results show that the crude enzymes produced by Wu-16 can catalyze the conversion of the substrate Rb1 to ginsenoside F2 and CK. The reaction time, pH, temperature, and ratio of enzyme to substrate for preparing ginsenoside F2 and CK were used as optimization factors. A reaction time of 48 h, pH=3, temperature of 55°C, and enzyme-to-substrate ratio of 0.8 were obtained. Furthermore, response surface optimization experiment was carried out to further obtain the maximum conversion rates of ginsenoside F2 and CK with 50.11% and 33.50% for 48 h, respectively. On this basis, the effect of metal ions on the enzymatic reaction showed that the conversion rate of ginsenoside Rb1 was increased remarkably by Co2+ with concentrations of 0.5 mM, and the highest conversion rate into rare ginsenoside CK reached 56.10%. Therefore, the advantage of enzymes catalysis from A. Niger Wu-16 could be a simple, convenient, and rapid method to produce rare saponin F2 and CK, this method provides a certain reference value for the production of rare ginsenosides.

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.

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.

Depression is a neuropsychiatric disease that threatens the physical and mental health of humans worldwide. This study explored the potential anti-depressant effects of ginsenoside Rh4 and its mechanisms of action. The results showed that Rh4 could significantly inhibit depression-like behavior in the depression mouse model and alleviate neuronal damage and hypothalamic-pituitary-adrenal axis disorder. Concurrently, Rh4 inhibits hippocampal neuronal apoptosis and synaptic structural damage due to the overexpression of proinflammatory cytokines and overactivation of microglia and astrocytes by inhibiting the immune-inflammatory response and signaling molecular interaction pathways. Rh4 can also improve intestinal flora and increase the short-chain fatty-acids content. The correlation analysis indicated that the Rh4-inhibited LPS/NLRP3/caspase-1/IL-1β signaling pathway plays a key role in ameliorating depression. Therefore, this study provides valuable insights into the mode of action of Rh4 on the brain-gut axis in depression, suggesting that Rh4 may be a promising clinical drug for the treatment of depression.

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 (

Osteochondral defects are most commonly characterized by damages to both cartilage and underlying subchondral bone tissues, thus developing bi-layered scaffold that can concurrently regenerate these two specific lineages becomes challenge. In this study, the highly biomimetic bi-layered scaffolds were successfully prepared using human-like-collagen (HLC), hyaluronan (HA) and nano hydroxyapatite (HAP) particles, combined with “liquid phase synthesis” technology, freeze-drying and chemical cross-linking techniques, which was simulated the composition of natural extracellular matrix to repair osteochondral defects. This novel bilayer osteochondral graft had a seamlessly integrated layer structure, suitable pore size, high levels of porosity, and excellent mechanical properties. In vitro cell experiments of the bilayer scaffold indicated that the scaffold could promote the proliferation and adhesion of human bone marrow mesenchymal stem cells. In vivo osteochondral defects and micro-CT experiment revealed that bilayer scaffolds showed complete closure of the defect. Histology confirmed collagen and glycosaminoglycans were deposited in the new matrix of hyaline cartilage and bone in the bilayer scaffold group. Therefore, the developed bionic bilayer scaffold enhanced the regeneration of hyaline cartilage through subchondral bone formation and lateral host-tissue integration. In conclusion, this bilayer scaffold based on HLC could be used as the desired strategy for osteochondral defects regeneration.

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.

Ginsenoside Compound K (CK) has high pharmacological activity for being widely used in the treatment and prevention of diseases. However, the content of CK in ginseng is very low or almost non-existent. In the present study, ginsenoside Rb1 was converted into ginsenoside F2 and CK by using the extracellular protein isolated from Aspergillus niger Wu-16. The results show that the crude enzymes produced by Wu-16 can catalyze the conversion of the substrate Rb1 to ginsenoside F2 and CK. The reaction time, pH, temperature, and ratio of enzyme to substrate for preparing ginsenoside F2 and CK were used as optimization factors. A reaction time of 48 h, pH = 3, temperature of 55°C, and enzyme-to-substrate ratio of 0.8 were obtained. Furthermore, response surface optimization experiment was carried out to further obtain the maximum conversion rates of ginsenoside F2 and CK with 50.11% and 33.50% for 48 h, respectively. On this basis, the effect of metal ions on the enzymatic reaction showed that the conversion rate of ginsenoside Rb1 was increased remarkably by Co2+ with concentrations of 0.5 mM, and the highest conversion rate into rare ginsenoside CK reached 56.10%. Therefore, the advantage of enzymes catalysis from A. Niger Wu-16 could be a simple, convenient, and rapid method to produce rare saponin F2 and CK, this method provides a certain reference value for the production of rare ginsenosides.

Diabetic wound healing remains challenging owing to the risk for bacterial infection, hypoxia, excessive glucose levels, and oxidative stress. Glucose-activated cascade reactions can consume glucose and eradicate bacteria, avoiding the direct use of hydrogen peroxide (H

It is well known that ginsenosides—major bioactive constituents of Panax ginseng—are attracting more attention due to their beneficial pharmacological activities. Ginsenoside Rd, belonging to protopanaxadiol (PPD)-type ginsenosides, exhibits diverse and powerful pharmacological activities. In recent decades, nearly 300 studies on the pharmacological activities of Rd—as a potential treatment for a variety of diseases—have been published. However, no specific, comprehensive reviews have been documented to date. The present review not only summarizes the in vitro and in vivo studies on the health benefits of Rd, including anti-cancer, anti-diabetic, anti-inflammatory, neuroprotective, cardioprotective, ischemic stroke, immunoregulation, and other pharmacological effects, it also delves into the inclusion of potential molecular mechanisms, providing an overview of future prospects for the use of Rd in the treatment of chronic metabolic diseases and neurodegenerative disorders. Although biotransformation, pharmacokinetics, and clinical studies of Rd have also been reviewed, clinical trial data of Rd are limited; the only data available are for its treatment of acute ischemic stroke. Therefore, clinical evidence of Rd should be considered in future studies.

Multifunctional inorganic nanomaterials have opened new avenues for cancer diagnosis and therapy. However, the difficulty to functionalize them has prevented their wider application, owing to the lack of active groups on their surfaces. Here we report a novel method to functionalize manganese whitlockite (Mn-WH) with polydopamine (PDA) and hairpin DNA (hpDNA) to improve the water stability and anti-cancer effects of Mn-WH nanoparticles (Mn-WH NPs). Compared to WH NPs, the Mn-WH@PDA-hpDNA NPs exhibit better water dispersibility, high drug loading capacity, excellent photothermal performance, stable MRI imaging ability, and outstanding chemo-photothermal synergistic therapeutic potential against tumors. After intratumoral injection in nude mice, the Mn-WH@PDA-hpDNA-DOX NPs promote complete tumor ablation upon exposure to 808 laser-irradiation. The nanoparticles showed no major side effects or toxicity. Thus, these results indicate that the Mn-WH@PDA-hpDNA-DOX NPs have excellent potential as anti-cancer agents, along with excellent magnetic resonance imaging (MRI) capabilities and the reported functionalization approach provides a novel and effective strategy for the surface functionalization of inorganic nanomaterials.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease with a complex etiology, and is considered as one of the main causes of hepatocellular carcinoma (HCC). The incidence of NAFLD has presented an increasing trend annually as a result of disequilibrium in the dietary structure. However, no specific treatment has been approved for clinical therapy in NAFLD. Ginsenoside CK has been investigated given its various pharmacological activities, but its effects against NAFLD and the underlying mechanism are still unclear. In this study, fructose was used to simulate hepatic fatty degeneration

Breast cancer (BC) has replaced lung cancer as the most common cancer worldwide. Ginsenoside CK (CK) can effectively inhibit triple-negative breast cancer (TNBC), the occurrence and development of which are associated with glutamine addiction. However, the connection between CK and glutamine metabolism in TNBC proliferation and the mechanism of cell death induction remains unclear. Here, we found that high glutamine-addicted TNBC cells were particularly sensitive to CK treatment. CK exerted antitumour activity against TNBC by suppressing glutamine consumption and glutamate production via downregulation of glutaminase 1 (GLS1) expression. CK treatment further decreased cellular ATP production, reduced the utilisation of amino acids associated with glutamine metabolism, and induced glutathione (GSH) depletion and reactive oxygen species (ROS) accumulation, consequently triggering apoptosis in TNBC. Furthermore, CK decreased GLS1 expression in SUM159 xenograft mouse mammary tumours and significantly inhibited tumour growth with few side effects. Together, our data provide a powerful theoretical basis for the application of CK as a glutamine metabolic inhibitor in TNBC treatment.

In this study, a temperature-sensitive molecularly imprinted polymer was prepared by using the bifunctional monomer with the critical phase transition characteristics. Infrared spectrometry, scanning electron microscopy, and specific surface area testing were used to characterize the polymers. Then, the recognizing properties of the polymers were studied. Based on the prepared smart polymers, an SPE-HPLC analytical method for the determination of quinolizidine alkaloids in the extracts of Sophora flavescens was established and verified. Finally, the smart polymers were applied to the enrichment of quinolizidine alkaloids in plant extracts. By changing the temperature and solvents of the solid phase extraction conditions, the extraction process can increase the concentration of quinolizidine alkaloids by 4.3 to 5.2 folds. The extraction process has mild conditions and less time consumption, avoiding the use of a large number of toxic reagents, which indicate that the extraction process are more efficient and environmentally friendly.

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.

Significance Cancer therapy, such as chemotherapy, induces tumor cell death (“debris”), which can stimulate metastasis. Chemotherapy-generated debris upregulates soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4), which triggers a macrophage-derived storm of proinflammatory and proangiogenic lipid autacoid and cytokine mediators. Although sEH inhibitors and EP4 antagonists are in clinical development for multiple inflammatory diseases, their combined role in cancer is unknown. Here, we show that the synergistic antitumor activity of sEH and EP4 inhibition suppresses hepato-pancreatic tumor growth, without overt toxicity, via macrophage phagocytosis of debris and counterregulation of a debris-stimulated cytokine storm. Thus, stimulating the resolution of inflammation via combined inhibition of sEH and EP4 may be an approach for preventing metastatic progression driven by cancer therapy., Cancer therapy reduces tumor burden via tumor cell death (“debris”), which can accelerate tumor progression via the failure of inflammation resolution. Thus, there is an urgent need to develop treatment modalities that stimulate the clearance or resolution of inflammation-associated debris. Here, we demonstrate that chemotherapy-generated debris stimulates metastasis by up-regulating soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4). Therapy-induced tumor cell debris triggers a storm of proinflammatory and proangiogenic eicosanoid-driven cytokines. Thus, targeting a single eicosanoid or cytokine is unlikely to prevent chemotherapy-induced metastasis. Pharmacological abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth.

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.

C1 gaseous substrates (CH