Two peptides LLRLTDL and GYALPCDCL inhibit foam cell formation through activating PPAR-γ/LXR-α signaling pathway in oxLDL-treated RAW264.7 macrophages.

Foam cell formation plays a pivotal role in atherosclerosis-associated cardiovascular diseases. Bioactive peptides generated from marine sources have been found to provide multifunctional health advantages. In the present study, we investigated the anti-atherosclerotic effects of LLRLTDL (Bu1) and GYALPCDCL (Bu2) peptides, isolated from ark shell protein hydrolysates by assessing their inhibitory effect on oxidized LDL (oxLDL)-induced foam cell formation. The two peptides showed a promising anti-atherosclerotic effect by inhibiting foam cell formation, which was evidenced by inhibiting lipid accumulation in oxLDL-treated RAW264.7 macrophages and oxLDL-treated primary human aortic smooth muscle cells (HASMC). Two peptides effectively reduced total cholesterol, free cholesterol, cholesterol ester, and triglyceride levels by upregulating cholesterol efflux and downregulating cholesterol influx. Expression of cholesterol influx-related proteins such as SR-A1 and CD36 were reduced, whereas cholesterol efflux-related proteins such as ATP-binding cassette transporter ABCA-1 and ABCG-1 were highly expressed. In addition, Bu1 and Bu2 peptides increased PPAR-γ and LXR-α expression. However, PPAR-γ siRNA transfection reversed the foam cell formation inhibitory activity of Bu1 and Bu2 peptides. Furthermore, the synergistic effect of Bu1 and Bu2 peptides on foam cell formation inhibition was observed with PPAR-γ agonist thiazolidinediones, indicating that PPAR-γ signaling pathway plays a key role in foam cell formation of macrophages. Beyond their impact on foam cell formation, Bu1 and Bu2 peptides demonstrated anti-inflammatory potential by inhibiting the generation of pro-inflammatory cytokines and nitric oxide and NF-κB nuclear activation. Taken together, these results suggest that Bu1 and Bu2 peptides may be useful for atherosclerosis and associated anti-inflammatory therapies.

Multifunctional hydrogel dressing based on fish gelatin/oxidized hyaluronate for promoting diabetic wound healing.

Non-healing chronic diabetic wound treatment remains an unsolved healthcare challenge and still threatens patients' lives. Recently, hydrogel dressings based on natural biomaterials have been widely investigated to accelerate the healing of diabetic wounds. In this study, we introduce a bioactive hydrogel based on fish gelatin (FG) as a candidate for diabetic wound treatments, which is a recently emerged substitute for mammalian derived gelatin. The composite hydrogel simply fabricated with FG and oxidized hyaluronate (OHy) through Schiff base reaction could successfully accelerate wound healing due to their adequate mechanical stability and self-healing ability. In vitro studies showed that the fabricated hydrogels exhibited cytocompatibility and could reduce pro-inflammatory cytokine expression such as NO, IL-1ß, TNF-α, and PGE2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. In addition, the production of reactive oxygen species (ROS), a key marker of free radicals producing oxidative stress, was also reduced by fabricated hydrogels. Furthermore, in vivo experiments demonstrated that the hydrogel could promote wound closure, re-epithelialization, collagen deposition, and protein expression of CD31, CD206, and Arg1 in diabetic mice models. Our study highlights the advanced potential of FG as a promising alternative material and indicates that FOHI can be successfully used for diabetic wound healing applications.

Modulating intestinal health: Impact of chitooligosaccharide molecular weight on suppressing RAGE expression and inflammatory response in methylglyoxal-induced advanced glycation end-products.

The accumulation of methylglyoxal (MGO) produced in high-temperature processed foods and excessive production in the body contributes to intestinal barrier dysfunction. In this study, we investigated the effects of chitooligosaccharides (COSs) of different molecular weights (<1 kDa, 1-3 kDa, 3-5 kDa, 5-10 kDa, and >10 kDa) on MGO-induced intestinal barrier dysfunction. We investigated the effect of COSs on inhibiting intracellular MGO accumulation/MGO-derived AGEs production and regulating the receptor for AGE (RAGE)-mediated downstream protein expression, including proteins related to apoptosis and inflammation, intestinal barrier integrity, and paracellular permeability. Pretreatment with COSs ameliorated MGO-induced increased RAGE protein expression, activation of apoptotic cascade/inflammatory response, loss of intestinal epithelial barrier integrity, and increased paracellular permeability, ameliorating intestinal dysfunction through MGO scavenging. 1-3 kDa COSs most effectively ameliorated MGO-induced intestinal dysfunction. Our results suggest the potential of COSs in improving intestinal health by ameliorating intestinal barrier dysfunction by acting as an MGO scavenger and highlighting the need for the optimization of the molecular weight of COSs to optimize its protective effects.

Brown Algae Dictyopteris divaricata Attenuates Adipogenesis by Modulating Adipocyte Differentiation and Promoting Lipolysis through Heme Oxygenase-1 Activation in 3T3-L1 Cells.

The present study aims to explore the probable anti-adipogenesis effect of Dictyopteris divaricata (D. divaricata) in 3T3-L1 preadipocytes by regulating heme oxygenase-1 (HO-1). The extract of D. divaricata retarded lipid accretion and decreased triglyceride (TG) content in 3T3-L1 adipocytes but increased free glycerol levels. Treatment with the extract inhibited lipogenesis by inhibiting protein expressions of fatty acid synthase (FAS) and lipoprotein lipase (LPL), whereas lipolysis increased by activating phosphorylation of hormone-sensitive lipase (p-HSL) and AMP-activated protein kinase (p-AMPK). The extract inhibited adipocyte differentiation of 3T3-L1 preadipocytes through down-regulating adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). This is attributed to the triggering of Wnt/ß-catenin signaling. In addition, this study found that treatment with the extract activated HO-1 expression. Pharmacological approaches revealed that treatment with Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, resulted in an increase in lipid accumulation and a decrease in free glycerol levels. Finally, three adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP1, restored their expression in the presence of ZnPP. Analysis of chemical constituents revealed that the extract of D. divaricata is rich in 1,4-benzenediol, 7-tetradecenal, fucosterol, and n-hexadecanoic acid, which are known to have multiple pharmacological properties.

A literature review of bioactive substances for the treatment of periodontitis: In vitro, in vivo and clinical studies.

Periodontitis is a common chronic inflammatory disease of the supporting tissues of the tooth that involves a complex interaction of microorganisms and various cell lines around the infected site. To prevent and treat this disease, several options are available, such as scaling, root planning, antibiotic treatment, and dental surgeries, depending on the stage of the disease. However, these treatments can have various side effects, including additional inflammatory responses, chronic wounds, and the need for secondary surgery. Consequently, numerous studies have focused on developing new therapeutic agents for more effective periodontitis treatment. This review explores the latest trends in bioactive substances with therapeutic effects for periodontitis using various search engines. Therefore, this study aimed to suggest effective directions for therapeutic approaches. Additionally, we provide a summary of the current applications and underlying mechanisms of bioactive substances, which can serve as a reference for the development of periodontitis treatments.

Ishophloroglucin A-based multifunctional oxidized alginate/gelatin hydrogel for accelerating wound healing.

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.

Phloroglucinol possesses anti-inflammatory activities by regulating AMPK/Nrf2/HO-1 signaling pathway in LPS-stimulated RAW264.7 murine macrophages.

BACKGROUND: Inflammation is closely related to the pathogenesis of chronic illnesses. Secondary metabolites of marine seaweeds are recognized as reliable sources of bioactive compounds due to their health benefits besides their nutritional value. The objective of this study was to determine the potential anti-inflammatory effect of phloroglucinol (Phl) in RAW264.7 murine macrophages after lipopolysaccharides (LPS) stimulation. METHODS: MTT, nitric oxide (NO), and DCFH-DA assays were conducted to determine cell viability, NO production, and reactive oxygen species (ROS) generation respectively. Pro-inflammatory cytokines and prostaglandin E2 (PGE2) levels were measured using ELISA assay kits. Protein expression levels were determined by western blot analysis. RESULTS: Phl treatment showed a promising anti-inflammatory effect by reducing NO production, secretion of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), PGE2 production, protein expression levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), and ROS generation in LPS-stimulated RAW264.7 murine macrophages. Phl treatment upregulated heme oxygenase-1 (HO-1) expression by inducing nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activating AMPK. However, Zinc protoporphyrin (ZnPP), an inhibitor of HO-1, partially reversed these effects, including NO production, pro-inflammatory cytokine secretion, iNOS, COX-2 and HO-1 expression, and ROS generation. CONCLUSION: Phl has potential anti-inflammatory activities by regulating AMPK/Nrf2/HO-1 pathway in LPS-stimulated RAW264.7 murine macrophages.

Anti-inflammatory action of ark shell (Scapharca subcrenata) protein hydrolysate in LPS-stimulated RAW264.7 murine macrophages.

Potential anti-inflammatory effects of ark shell (Scapharca subcrenata) protein hydrolysates were investigated. Ark shell protein hydrolysates were prepared using Alcalase® and pepsin and were designated ASAH and ASPH, respectively. The nitric oxide (NO) inhibitory activity of ASAH and ASPH was determined in lipopolysaccharides (LPS)-stimulated RAW264.7 murine macrophages, and the results showed that ASAH inhibited better NO inhibitory activity than ASPH. ASAH suppressed inflammatory mediator, a prostaglandin E2, secretion of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), and production of reactive oxygen species (ROS) dose dependently. It inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and simulated heme oxygenase-1 (HO-1) protein expression. However, the pharmacological approach revealed that pretreatment with zinc protoporphyrin ІX (ZnPP), an inhibitor of HO-1, reversed the anti-inflammatory effect of ASAH. Moreover, ASAH upregulated phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2, JNK1/2, and p38 MAPK. To find out the role of MAPKs phosphorylation, MAPKs inhibitors were used, and the results showed that ASAH-mediated HO-1 protein expression and Nrf2 nuclear translocation were abolished. Taken all together, this study revealed that ASAH has a potential anti-inflammatory activity through regulation of the MAPK-dependent HO-1/Nrf2 pathway. PRACTICAL APPLICATIONS: Food-derived marine bioactive peptides, due to their pivotal role in biological activities, are gaining much attention recently. However, the anti-inflammatory activities of ark shell protein hydrolysates still remain to be investigated. This study investigated that ASAH shows potential anti-inflammatory activities through regulation of the MAPK-dependent HO-1/Nrf2 pathway in RAW264.7 murine macrophages. These findings indicated that ASAH may be used as a dietary supplement, functional food, and medicinal drug for the management of inflammation and inflammation-associated diseases.

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.

Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.

Heme oxygenase-1 induction by gallic acid-g-chitosan is an important event in modulating adipocyte differentiation.

Obesity, one of the common worldwide chronic health diseases co-relates with adipogenesis. Adipogenesis is a complex biological action of the emergence of mature adipocytes from the differentiation of pre-adipocytes and the disfunction of this process leads to the development of metabolic issues in obesity. Recently, much attention has been paid to utilizing natural compounds to discover their biological activities. This study focused on investigating the probable anti-adipogenic effects of gallic acid-g-chitosan (GAC) and plain chitosan (PC) through regulating the heme oxygenase-1 (HO-1)/Nrf2 pathway on mesenchymal stem cells. Gallic acid is grafted onto the PC backbone to improve its specific physical and biological properties. GAC showed promising anti-adipogenic effects by enhancing HO-1 expression and lipolysis and as well as suppressing lipid accumulation, reactive oxygen species, and pro-inflammatory cytokines production, transcription factor expression compared to the PC treatment. On the contrary, zinc protoporphyrin ІX (ZnPP), a HO-1 inhibitor reversed these effects of GAC on adipogenesis. Taken all together, this study revealed that grafting GA onto the chitosan improved potential anti-adipogenic activity by induction of the HO-1/Nrf2 pathway on mesenchymal stem cells (MSCs). PRACTICAL APPLICATIONS: GAC is a well-known copolymer with versatile bioactivities such as antimicrobial, antioxidant, and anti-diabetic activity. However, the anti-adipogenic effect of GAC has not been explored in MSCs. This study demonstrated that GAC inhibited adipocyte differentiation in MSCs through HO-1 activation. These findings suggest that GAC can be applied practically from different perspectives. GAC can be applied in the pharmacological industry to the development of anti-obesity drugs, medicinal perspectives for the treatment of obesity and obesity-related diseases, and in the food industry as a functional food to promote health and decrease the risk of diseases.

Cytoprotective Peptides from Blue Mussel Protein Hydrolysates: Identification and Mechanism Investigation in Human Umbilical Vein Endothelial Cells Injury.

Cardiovascular disease represents a leading cause of mortality and is often characterized by the emergence of endothelial dysfunction (ED), a physiologic condition that takes place in the early progress of atherosclerosis. In this study, two cytoprotective peptides derived from blue mussel chymotrypsin hydrolysates with the sequence of EPTF and FTVN were purified and identified. Molecular mechanisms underlying the cytoprotective effects against oxidative stress which lead to human umbilical vein endothelial cells (HUVEC) injury were investigated. The results showed that pretreatment of EPTF, FTVN and their combination (1:1) in 0.1 mg/mL significantly reduced HUVEC death due to H2O2 exposure. The cytoprotective mechanism of these peptides involves an improvement in the cellular antioxidant defense system, as indicated by the suppression of the intracellular ROS generation through upregulation of the cytoprotective enzyme heme oxygenase-1. In addition, H2O2 exposure triggers HUVEC damage through the apoptosis process, as evidenced by increased cytochrome C release, Bax protein expression, and the elevated amount of activated caspase-3, however in HUVEC pretreated with peptides and their combination, the presence of those apoptotic stimuli was significantly decreased. Each peptide showed similar cytoprotective effect but no synergistic effect. Taken together, these peptides may be especially important in protecting against oxidative stress-mediated ED.

Insertion of gallic acid onto chitosan promotes the differentiation of osteoblasts from murine bone marrow-derived mesenchymal stem cells.

Chitosan, a naturally occurring biodegradable and biocompatible polymer, has found use as a food additive, nutraceuticals, and functional foods in recent years. In this study, gallic acid-g-chitosan (GAC) was prepared by the insertion of GA onto plain chitosan (PC) via free radical-mediated grafting and its osteogenic effects were investigated in murine bone marrow-derived mesenchymal stem cells (mBMMSCs). Structural characterization of PC and GAC was performed using 1H NMR and FT-IR spectroscopy. The amount of GA successfully grafted onto PC was 111 mg GA/g GAC via the Folin-Ciocalteu's method. While PC and GAC promoted the increase in alkaline phosphatase activity and mineralization, GAC increased these factors significantly more than PC, indicating that the grafting of GA onto chitosan increased its osteogenic potential. Mechanistic study revealed that GAC activated Wnt1 and Wnt3a mRNA and protein expression as well as increased the translocation of ß-catenin into the nucleus and upregulated the expression of ß-catenin targeted genes including Runx2, osterix, type I collagen and cyclin D1. In addition, DKK-1, a Wnt antagonist, decreased GAC-mediated osteoblast differentiation in mBMMSCs through blocking the Wnt/ß-catenin signaling pathway.

Cytoprotective Role of Edible Seahorse (Hippocampus abdominalis)-Derived Peptides in H2O2-Induced Oxidative Stress in Human Umbilical Vein Endothelial Cells.

Oxidative stress-induced endothelial dysfunction is strongly linked to the pathogenesis of cardiovascular diseases. A previous study revealed that seahorse hydrolysates ameliorated oxidative stress-mediated human umbilical vein endothelial cells (HUVECs) injury. However, the responsible compounds have not yet been identified. This study aimed to identify cytoprotective peptides and to investigate the molecular mechanism underlying the cytoprotective role in H2O2-induced HUVECs injury. After purification by gel filtration and HPLC, two peptides were sequenced by liquid chromatography-tandem mass spectrometry as HGSH (436.43 Da) and KGPSW (573.65 Da). The synthesized peptides and their combination (1:1 ratio) showed significant HUVECs protection effect at 100 µg/mL against H2O2-induced oxidative damage via significantly reducing intracellular reactive oxygen species (ROS). Two peptides and their combination treatment resulted in the increased heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, through the activation of nuclear transcription factor-erythroid 2-related factor (Nrf2). Additionally, cell cycle and nuclear staining analysis revealed that two peptides and their combination significantly protected H2O2-induced cell death through antiapoptotic action. Two peptides and their combination treatment led to inhibit the expression of proapoptotic Bax, the release of cytochrome C into the cytosol, the activation of caspase 3 by H2O2 treatment in HUVECs, whereas antiapoptotic Bcl-2 expression was increased with concomitant downregulation of Bax/Bcl-2 ratio. Taken together, these results suggest that seahorse-derived peptides may be a promising agent for oxidative stress-related cardiovascular diseases.

Blue Mussel-Derived Peptides PIISVYWK and FSVVPSPK Trigger Wnt/ß-Catenin Signaling-Mediated Osteogenesis in Human Bone Marrow Mesenchymal Stem Cells.

Marine-derived bioactive peptides have shown potential bone health promoting effects. Although various marine-derived bioactive peptides have potential nutraceutical or pharmaceutical properties, only a few of them are commercially available. This study presented an osteogenic mechanism of blue mussel-derived peptides PIISVYWK and FSVVPSPK as potential bone health promoting agents in human bone marrow-derived mesenchymal stem cells (hBMMSCs). Alkaline phosphatase (ALP) activity and mineralization were stimulated using PIISVYWK and FSVVPSPK as early and late markers of osteogenesis in a concentration-dependent manner. Western blot and RT-qPCR results revealed that PIISVYWK and FSVVPSPK increased osteoblast differentiation of hBMMSCs by activating canonical Wnt/ß-catenin signaling-related proteins and mRNAs. Immunofluorescence images confirmed nuclear translocation of ß-catenin in osteogenic differentiation. Treatment with the pharmacological inhibitor DKK-1 blocked PIISVYWK- and FSVVPSPK-induced ALP activity and mineralization, as well as mRNA expression of the canonical Wnt/ß-catenin signaling pathway in hBMMSC differentiation into osteoblasts. These findings suggested that PIISVYWK and FSVVPSPK promoted the canonical Wnt/ß-catenin signaling pathway in osteogenesis of hBMMSCs. Blue mussel-derived PIISVYWK and FSVVPSPK might help develop peptide-based therapeutic agents for bone-related diseases.

Anti-Osteoporotic Effects of Antioxidant Peptides PIISVYWK and FSVVPSPK from Mytilus edulis on Ovariectomized Mice.

Numerous amounts of evidence suggest that bioactive peptides with diverse physiological activities can be nutraceuticals or potential drug candidates. In this study, blue mussel-derived antioxidant peptides PIISVYWK and FSVVPSPK were subjected to evaluate their osteogenic effect in mouse bone marrow mesenchymal stem cells (mBMMSCs) followed by an in vivo anti-osteoporotic effect. Treatment of PIISVYWK and FSVVPSPK on mBMMSCs stimulated alkaline phosphatase activity and calcification. Western blot results revealed that PIISVYWK and FSVVPSPK increased the expression of bone morphogenetic protein-2/4 (BMP-2/4) followed by upregulating p-Smad1/5, type I collagen, and transcription factors including Runx2 and osterix in mBMMSCs. Two peptides also activated the phosphorylation of MAPKs (p-p38, p-ERK, and p-JNK). Treatment of MAPK inhibitors significantly inhibited the BMP signaling pathway, indicating that PIISVYWK and FSVVPSPK stimulated osteoblast differentiation of mBMMSCs through the MAPK-dependent BMP signaling pathway. The anti-osteoporotic effect of PIISVYWK and FSVVPSPK in ovariectomized (OVX) mice was investigated. Treatment of PIISVYWK and FSVVPSPK for ten weeks showed a notable anti-osteoporotic effect in OVX mice via increasing bone mineral density and other bone parameters compared to OVX mice without peptides. Serum analysis also showed that treatment of PIISVYWK and FSVVPSPK completely reduced osteocalcin and ALP (alkAline phosphatase) activity. Taken together, these results suggest that PIISVYWK and FSVVPSPK could be health-promoting functional food ingredients against osteoporosis.

Ark shell protein-derived bioactive peptides promote osteoblastic differentiation through upregulation of the canonical Wnt/ß-catenin signaling in human bone marrow-derived mesenchymal stem cells.

In this study, the stimulating effect of ark shell protein-derived peptides AWLNH and PHDL on osteoblast differentiation in human bone marrow-derived mesenchymal stem cells (hBMMSCs) and its molecular mechanism was investigated. The hBMMSCs were cultured with two peptides and osteogenic markers were analyzed. Results showed that enhanced ALP activity and calcification were detected in the presence of AWLNH and PHDL. Based on western blotting, RT-qPCR, and immunostaining analysis, AWLNH and PHDL are specific for osteoblast differentiation of hBMMSCs through activating the canonical Wnt/ß-catenin signaling pathway followed by activating Runx2, osterix, and type I collagen. Loss-of-function assay with DKK-1, a Wnt antagonist, showed that the canonical Wnt/ß-catenin signaling was essential for AWLNH and PHDL-induced osteogenesis in hBMMSCs. These findings suggested that AWLNH and PHDL can stimulate osteoblast differentiation of hBMMSCs via upregulating the canonical Wnt/ß-catenin signaling and may be useful for a potential nutraceuticals or pharmaceuticals to treat osteoporosis. PRACTICAL APPLICATIONS: Ark shell is a popular foodstuff in Korea. However, biological effects of its protein and peptide have not been explored in many ways. This study demonstrated that ark shell protein-derived peptides promoted osteoblast differentiation in hBMMSCs through upregulating the canonical Wnt/ß-catenin signaling. The results of this study could be a basis to promote its application as functional foods and/or nutraceuticals.

Low molecular weight blue mussel hydrolysates inhibit adipogenesis in mouse mesenchymal stem cells through upregulating HO-1/Nrf2 pathway.

Blue mussel proteins are a good source of bioactive peptides. In this study, blue mussel hydrolysate (BMH) with anti-adipogenic effect in mouse mesenchymal stem cells (mMSC) was produced by peptic hydrolysis at 1:500 of pepsin/substrate ratio for 120 min. Additionally, BMH with below 1 kDa (BMH < 1 kDa) showed the highest anti-adipogenic effect in mMSC. BMH < 1 kDa increased lipolysis and down-regulated adipogenic transcription factors including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). Generation of intracellular reactive oxygen species during adipogenesis was markedly decreased by BMH < 1 kDa treatment, which is attributed to the up-regulation of heme oxygenase-1 (HO-1) through Nrf2 translocation into the nucleus. Moreover, ZnPP, HO-1 inhibitor, treatment abolished BMH < 1 kDa-mediated HO-1 expression and anti-adipogenic effect in mMSCs through down-regulating adipogenic transcription factors. Taken together, BMH < 1 kDa may be a potential ingredient of nutraceuticals and/or functional foods in ameliorating obesity.

Characterization of the complete mitochondrial genome of brown barracuda, Sphyraena pinguis (Perciformes: Sphyraenidae).

The entire mitochondrial genome sequence of Sphyraena pinguis collected from Korean water was determined by the Next Generation Sequencing (NGS) technology. Its total length was 16,620 bps in length, which possessed the canonical 37 genes in the eukaryotes. Unusual start codon was exclusively found in COX1(GTG), while incomplete stop codons (TA-/T-) were identified in ATP6, COX2, ND3, ND4, and Cyt b. A phylogenetic analysis with currently identified full mitogenomes in Perciformes, S. pinguis was most closely related to S. barracuda (76.87%) and S. jello (76.84%). This mitogenome sequence would explain the evolution of genus Sphyraena.

Two novel peptides from ark shell protein stimulate osteoblast differentiation and rescue ovariectomy-induced bone loss.

Osteoporosis is a common bone disease resulting from imbalance between bone formation and bone resorption. Currently, anti-resorptive agents that inhibit bone resorption are the most available drugs on the market. Biosphosphonates, anti-resorptive drugs most commonly used to treat osteoporosis, are limited by their side effects for long-term continuous treatment. It is important to develop appropriate therapeutic stragegies capable of promoting bone formation to counteract osteoporotic bone loss. Thus, anabolic agents that stimulate bone formation are undoubtedly of interest. Here, we purified and identified two novel osteogenic peptides AWLNH and PHDL from ark shell protein hydrolysates. AWLNH and PHDL stimulated osteoblast differentiation via mitogen-activated protein kinase (MAPK) and bone morphogenetic protein-2 (BMP-2) pathways. The activation of BMP-2 pathway stimulated by AWLNH and PHDL was abolished by treating noggin, BMP antagonist, in bone marrow-derived mesenchymal stem cells (BMMSCs), but not the phosphorylation of JNK1/2, ERK1/2, and p38 MAPK. However, treatment with MAPK inhibitors in BMMSCs downregulated the expression of BMP-2 and p-Smad1/5 and inhibited alkaline phosphatase activity. The dominant inhibitory effects by JNK inhibitor and ERK inhibitor are observed. In ovariectomized (OVX) mice, a reduction of femoral bone mineral density (BMD) was significantly observed, however, AWLNH and PHDL (0.2 mg/kg/per day) injection restored BMD as well as the osteoporotic conditions in OVX mice. Moreover, the increased serum osteocalcin and alkaline phosphatase activity in OVX mice were significantly reduced in AWLNH and PHDL injected-OVX mice. These results suggest that two novel osteogenic peptides AWLNH and PHDL could be attractive therapeutic agents for osteoporosis treatment.

Synergistic combination of chemo­phototherapy based on temozolomide/ICG­loaded iron oxide nanoparticles for brain cancer treatment.

Chemo­photothermal therapy for cancer treatment has received increasing attention due to its selective therapeutic effects. In the present study, the anticancer effects of drug­loaded Fe3O4 magnetic nanoparticles (MNPs) by chemo­photothermal therapy on U­87 MG human glioblastoma cells was investigated. Anticancer drug­loaded Fe3O4 MNPs were prepared by loading temozolomide (TMZ) and indocyanine green (ICG), and were characterized by X­ray diffraction, UV­vis spectroscopy, thermal gravimetric analysis, transmission electron microscope, as well as drug­loading capacity. Following treatment with near­infrared (NIR) light irradiation, the administration of Fe3O4­TMZ­ICG MNPs resulted in the apoptosis of U­87 MG glioblastoma cells through the generation of reactive oxygen species. Western blot analysis and reverse transcription­quantitative polymerase chain reaction revealed that Fe3O4­TMZ­ICG MNPs with NIR laser irradiation lead to significantly enhanced anticancer effects on U­87 MG glioblastoma cells through the modulation of intrinsic and extrinsic apoptosis genes, including Bcl­2­associated X protein, Bcl­2, cytochrome c, caspase­3, Fas associated via death domain and caspase­8. These results suggest that Fe3O4­TMZ­ICG MNPs may be potential candidates when administered as chemo­phototherapy for the treatment of brain cancer.