Brown Algae Ecklonia cava Extract Modulates Adipogenesis and Browning in 3T3-L1 Preadipocytes through HO-1/Nrf2 Signaling.

This study explores the anti-obesity effects of the ethyl acetate extract of Ecklonia cava (EC-ETAC) on 3T3-L1 preadipocytes, focusing on its impact on adipogenesis, lipolysis, and adipose browning via the HO-1/Nrf2 pathway. Western blot analysis revealed that EC-ETAC significantly inhibited adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1) and lipogenesis-related proteins (FAS, LPL). Concurrently, EC-ETAC enhanced lipolytic markers (p-AMPK, p-HSL) and adipose browning-related proteins (UCP-1, PGC-1α), indicating its role in promoting lipolysis and adipose browning. The inhibition of HO-1 by zinc protoporphyrin (ZnPP) significantly reversed these effects, underscoring the critical role of HO-1 in mediating the anti-obesity properties of EC-ETAC. Additionally, fluorescence measurements and Oil Red O staining confirmed the reduction of lipid accumulation and oxidative stress upon EC-ETAC treatment. These findings suggest that EC-ETAC exerts its anti-obesity effects by modulating the HO-1/Nrf2 pathway, which is crucial for regulating adipogenesis, lipolysis, and adipose browning. This study highlights the potential of EC-ETAC as a natural therapeutic agent for obesity management and supports further research into its clinical applications. By targeting the HO-1/Nrf2 pathway, EC-ETAC could offer a novel approach to enhancing energy expenditure and reducing fat mass, thereby improving metabolic health.

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.

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.

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.

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.

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.

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.

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.

Sea Squirt (Halocynthia roretzi) Hydrolysates Induce Apoptosis in Human Colon Cancer HT-29 Cells through Activation of Reactive Oxygen Species.

Recent evidence provides that seafood has a lot of health benefits due to its unique bioactive compounds. Sea squirt is widely cultured and consumed as a foodstuff in Korea; however, seldom reports with reference to bioactivities are available until now. In this study, edible part of sea squirt was hydrolyzed by pepsin and its hydrolysates was evaluated for anticancer effect on human colon cancer HT-29 cells. Sea squirt hydrolysates (SSQ) reduced HT-29 cell viability. Treatment with SSQ resulted in the increase in reactive oxygen species (ROS) generation followed by disruption of mitochondrial membrane potential (MMP). Flow cytometry analysis revealed that SSQ induced G2/M phase arrest and apoptosis evidenced by Hoechst 33342 staining. Levels of mRNA expression by real-time polymerase chain reaction (PCR) showed that treatment with SSQ in HT-29 cells upregulated expression of p53, bax, and caspase-3 genes and downregulated expression of bcl-2 gene. Protein level of cytochrome c into cytosol and caspase-3 by Western blotting were also increased by treatment with SSQ in HT-29 cells. These results suggest that SSQ may be useful for functional food ingredients and/or nutraceuticals.

Amino Acid Composition, Antioxidant, and Cytoprotective Effect of Blue Mussel (Mytilus edulis) Hydrolysate through the Inhibition of Caspase-3 Activation in Oxidative Stress-Mediated Endothelial Cell Injury.

Enhanced oxidative stress plays a central role in promoting endothelial dysfunction, leading to the development of atherosclerosis. In this study, we investigated the protective effects of the hydrolysates derived from blue mussel (Mytilus edulis) against H2O2-mediated oxidative injury in human umbilical vein endothelial cells (HUVECs). The blue mussel hydrolysates were prepared by enzymatic hydrolysis with eight proteases, and blue mussel-α-chymotrypsin hydrolysate (BMCH) showed the highest antioxidant activities in DPPH radical scavenging, ABTS⁺ radical scavenging, and ORAC value compared to those of the other hydrolysates. BMCH also inhibited Cu2+-mediated low density lipoprotein (LDL) oxidation. Treatment of H2O2 resulted in the decreased HUVEC viability whereas pre-treatment with BMCH increased HUVEC viability and reduced reactive oxygen species (ROS) generation. BMCH pre-treatment increased cellular antioxidant capacities, including levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) against H2O2-mediated oxidative stress in HUVECs. Flow cytometry and western blot analysis revealed that BMCH pre-treatment significantly reduced H2O2-mediated HUVEC apoptosis through inhibition of caspase-3 activation. Real-time-qPCR analysis showed that BMCH down-regulated expression of p53 and caspase-3 genes, as well as decreased the bax/bcl-2 ratio. Taken together, these results indicate that BMCH may be useful as functional food ingredients for protecting endothelial dysfunction or related disease.

In Vitro Antibacterial and Synergistic Effect of Chitosan-Phytochemical Conjugates Against Antibiotic Resistant Fish Pathogenic Bacteria.

Chitosan-phytochemical conjugates exhibited significant antibacterial effect with minimum inhibitory concentration (MIC) ranging from 128 to 2048 µg/ml against antibiotic-resistant fish pathogenic bacteria such as Edwardseilla tarda, Vibrio harveyi and Photobacterium damselaewhich were isolated from Korean cultured fish. Furthermore, the MIC values of old-fashioned antibiotics such as erythromycin and oxytertacycline drastically reduced in combination with chitosan-phytochemical conjugates against the fish pathogenic bacteria. The combination of conjugates with erythromycin and oxytetracycline gave median ∑FIC results ranging from 0.281 to 0.625 and 0.312 to 0.625, respectively. This result indicates the synergistic antibacterial effects and an increased susceptibility against the antibiotics.

Induction of Nrf2-mediated phase II detoxifying/antioxidant enzymes in vitro by chitosan-caffeic acid against hydrogen peroxide-induced hepatotoxicity through JNK/ERK pathway.

Chemical modification of chitosan is a promising method for the improvement of biological activity. In this study, chitosan-caffeic acid (CCA) was prepared and its in vitro hepatoprotective ability against hydrogen peroxide-induced hepatic damage in liver cells was evaluated. Treatment with CCA (50-400 µg/mL) did not show cytotoxicity and also significantly (p < 0.05) recovered cell viability against 650 µM hydrogen peroxide-induced hepatotoxicity. CCA treatment attenuated reactive oxygen species generation and lipid peroxidation in addition to increasing cellular glutathione level in cultured hepatocytes. To validate the underlying mechanism, antioxidant and phase II detoxifying enzyme expressions, which are mediated by NF-E2-related factor 2 (Nrf2) activation, were analyzed and CCA treatment was found to increase the expression of superoxide dismutase-1 (SOD-1), glutathione reductase (GR), heme oxygenase-1 (HO-1), and NAD(P)H:quinine oxidoreductase 1 (NQO1). CCA treatment resulted in increased Nrf2 nuclear translocation. The phosphorylation of extracellular regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) by CCA treatment contributed to Nrf2 activation. Pharmacological blockade of ERK, JNK, and p38 MAPK revealed that SP600125 (JNK inhibitor) and PD98059 (ERK inhibitor) treatment reduced Nrf2 translocation into the nucleus while SB203580 (p38 inhibitor) exhibited weak inhibition. Collectively, CCA protects liver cells against hydrogen peroxide-induced injury and this ability is attributed to the induction of antioxidants and phase II detoxifying enzymes that are mediated by Nrf2 translocation via JNK/ERK signaling.

The mechanism of antibacterial activity of phlorofucofuroeckol-A against methicillin-resistant Staphylococcus aureus.

To find more effective ways of overcoming methicillin-resistant Staphylococcus aureus (MRSA), there has been considerable interest in the use of marine-derived constituents as alternatives to control pathogenic microorganisms. In this study, we investigated whether phlorofucofuroeckol-A (PFF) isolated from the edible brown alga Eisenia bicyclis suppressed production or function of penicillin-binding protein 2a (PBP2a). The antimicrobial mode of action of PFF in MRSA was identified by measuring cell membrane integrity and using the time-kill curve method. We attempted to determine the antimicrobial effects of PFF on the expression level of the resistance determinants mecA and its regulatory genes mecI and mecR1 in MRSA by reverse transcriptase polymerase chain reaction. PFF suppressed mecI, mecR1, and mecA gene expression in a dose-dependent manner. In addition, we revealed PFF mediates the suppressive effect of PBP2a expression in MRSA by Western blot analysis. PFF suppressed production of the PBP2a protein, suggesting that PFF probably acts by controlling the methicillin resistance-associated genes involved in the cell wall and production of PBP2a. These results demonstrate that PFF isolated from E. bicyclis significantly suppressed the expression of the methicillin resistance-associated genes and production of PBP2a, which is considered the primary cause of methicillin resistance.

Antibacterial and synergic effects of gallic acid-grafted-chitosan with ß-lactams against methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) is spreading worldwide, emphasizing the need to search for new antibiotics. The anti-MRSA activities of gallic acid-grafted-chitosans (GA-g-chitosans) were investigated against 2 MRSA standards and 10 MRSA clinical isolates by determining the minimum inhibitory concentrations (MICs). GA-g-chitosan (I), which has the highest gallic acid content, exhibited the strongest anti-MRSA activities, with MICs of 32-64 µg/mL. A time-kill investigation revealed that GA-g-chitosan (I) exhibited a bactericidal effect at twice the MIC, also demonstrating good thermal and pH stability. Investigation of cell envelope integrity showed the release of intracellular components with an increasing absorbance value at 260 nm, indicating cell envelope damage caused by the GA-g-chitosan (I), which was further confirmed by transmission electron microscopy. When GA-g-chitosans were combined with ß-lactams, including ampicillin and penicillin, synergistic effects were observed on the 2 standard MRSA strains and on the 10 clinical isolates, with fractional inhibitory indices ranging from 0.125 to 0.625. In the time-kill dynamic confirmation test, synergistic bactericidal effects were observed for the combinations of GA-g-chitosans with ß-lactams, and over 4.0 log CFU/mL reductions were observed after 24 h when combination treatment was used. These results may prove GA-g-chitosans to be a potent agent when combined with ampicillin and penicillin for the elimination of MRSA.

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.

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.

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.

Purple Butter Clam (Saxidomus Purpurata) as a Potential Functional Food Source for Obesity Treatment.

Saxidomus purpurata extract (SPE) is a highly consumable seafood worldwide with known health-related benefits. However, there are no reports of its' anti-obesity effect. This study explores the potential of SPE for anti-obesity effects by modulating adipogenesis and lipolysis. SPE reduced intracellular lipid and triglyceride accumulation while increasing free glycerol release in adipocytes. SPE inhibited lipogenesis protein expressions and increased the phosphorylation of hormone-sensitive lipase and Adenosine monophosphate-activated protein kinase (AMPK) to promote lipolysis. In addition, SPE suppressed adipogenesis by downregulating protein expression of key adipogenic markers, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) via Wnt/ß-catenin signaling. SPE augmented the heme oxygenase-1 (HO-1) expression. Thus, pharmacological intervention with Zinc protoporphyrin (ZnPP-HO-1 antagonist) was employed to validate the HO-1 role. The presence of ZnPP increased the lipid accumulation and reduced the free glycerol release. At the molecular level, adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) expressions were restored in the presence of ZnPP. GC-MS analysis revealed that SPE was comprised of several fatty acids, contributing to its anti-obesity activity. SPE is an effective nutraceutical that can be used to reduce the progression of obesity. HO-1 expression during adipogenesis might be the mechanism of action for the anti-obesity effect of SPE.

Strongylocentrotus intermedius Extract Suppresses Adiposity by Inhibiting Adipogenesis and Promoting Adipocyte Browning via AMPK Activation in 3T3-L1 Cells.

The current study aimed to determine whether Strongylocentrotus intermedius (S. intermedius) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and triglyceride content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 and peroxisome proliferator-activated receptor-γ coactivator 1α. Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

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.