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Olive flounder (Paralichthys olivaceus) muscle satellite cells (OFMCs) were obtained by enzymatic primary cell isolation and the explant method. Enzymatic isolation yielded cells that reached 80% confluence within 8 days, compared to 15 days for the explant method. Optimal OFMC growth was observed in 20% fetal bovine serum at 28 °C with 0.8 mM CaCl2 and the basic fibroblast growth factor (BFGF) to enhance cell growth. OFMCs have become permanent cell lines through the spontaneous immortalization crisis at the 20th passage. Olive flounder skeletal muscle myoblasts were induced into a mitogen-poor medium containing 2% horse serum for differentiation; they fused to form multinucleate myotubes. The results indicated complete differentiation of myoblasts into myotubes; we also detected the expression of the myogenic regulatory factors myoD, myogenin, and desmin. Upregulation (Myogenin, desmin) and downregulation (MyoD) of muscle regulation factors confirmed the differentiation in OFMCs.

Wound healing is widely recognized as a critical issue impacting the healthcare sector in numerous countries. The application of wound dressings multiple times in such instances can result in tissue damage, thereby increasing the complexity of wound healing. With the aim of tackling this necessity, in the present study, we have formulated a hydrogel using natural polysaccharide κ-carrageenan and phycobiliprotein R-phycoerythrin from Pyropia yezoensis. The formulated hydrogel κ-Carrageenan-R-Phycoerythrin (κ-CRG-R-PE) was analyzed for its antioxidant and antimicrobial activity. The wound healing potential of the κ-CRG-R-PE was evaluated in Hs27 cells by the wound scratch assay method. The hydrogel showed dose-dependent antioxidant activity and significant antimicrobial activity at 100 μg/mL concentration. κ-CRG-R-PE hydrogels promoted more rapid and complete wound closure than κ-Carrageenan (κ-CRG) hydrogel at 24 and 48 h. κ-CRG-R-PE hydrogels also filled the wound within 48 h of incubation, indicating that they positively affect fibroblast migration and wound healing.

Oysters are saltwater bivalves with high nutritional and medicinal value that are consumed widely around the world. As well as being highly nutritious, oysters are a low-calorie, low-cholesterol source of protein and an exceptional source of zinc, which strengthens the immune system; and a rich source of bioactive compounds, which comprise various biological activities. The present review summarizes the biological applications and bioactive compounds from oyster shells, whole tissue, gill tissue, and mantle tissue. The various biological compounds present in an oyster shell, and their chemical constituents, have applications in the food, pharmaceutical, and medical industries. Bioactive peptides and proteins obtained from the whole, mantle, and gill tissues of oysters exhibit antioxidant, antimicrobial, antihypertensive, anticancer, antifatigue, anticoagulant, and anti-wrinkle effects, as well as enhance osteoblast differentiation. This review clearly shows that oysters have great potential for functional food production and that various compounds therein can have pharmaceutical applications.

The development of dual-stimuli-responsive hydrogels attracts much research interest owing to its unique stimuli-responsive characteristics. In this study, a poly-N-isopropyl acrylamide-co-glycidyl methacrylate-based copolymer was synthesized by incorporating N-isopropyl acrylamide (NIPAm) and a glycidyl methacrylate (GMA) monomer. The synthesized copolymer, pNIPAm-co-GMA was further modified with L-lysine (Lys) functional units and further conjugated with fluorescent isothiocyanate (FITC) to produce a fluorescent copolymer pNIPAAm-co-GMA-Lys hydrogel (HG). The in vitro drug loading and dual pH- and temperature-stimuli-responsive drug release behavior of the pNIPAAm-co-GMA-Lys HG was investigated at different pH (pH 7.4, 6.2, and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions, respectively, using curcumin (Cur) as a model anticancer drug. The Cur drug-loaded pNIPAAm-co-GMA-Lys/Cur HG showed a relatively slow drug release behavior at a physiological pH (pH 7.4) and low temperature (25 °C) condition, whereas enhanced drug release was achieved at acidic pH (pH 6.2 and 4.0) and higher temperature (37 °C and 45 °C) conditions. Furthermore, the in vitro biocompatibility and intracellular fluorescence imaging were examined using the MDA-MB-231 cell line. Therefore, we demonstrate that the synthesized pNIPAAm-co-GMA-Lys HG system with temperature- and pH-stimuli-responsive features could be promising for various applications in biomedical fields, including drug delivery, gene delivery, tissue engineering, diagnosis, antibacterial/antifouling material, and implantable devices.

Pyropia yezoensis (P. yezoensis) is a popular species of red algae that are commercially cultivated and consumed in East Asia, China, Japan, and Korea. The high protein content of P. yezoensis provides a source of multiple bioactive peptides exhibiting antioxidant, anti-inflammatory, antihypertensive, anticancer, tissue healing, immunomodulatory, and anticoagulant properties. Furthermore, many other biologically active substances in P. yezoensis, including carbohydrates, lipids, dietary fibers, and polyphenols, have shown potential health benefits and are important in both the food and agriculture industries. This review provides a detailed summary of researches over the last decade on the biological and medicinal properties of bioactive peptides. The information was extracted from various electronic resources, including Google Scholar, PubMed, MEDLINE, and Google Patents.

A mesoporous silica-based drug delivery system (MS@PNIPAm-PAAm NPs) was synthesized by conjugating the PNIPAm-PAAm copolymer onto the mesoporous silica (MS) surface as a gatekeeper that responds to temperature and pH changes. The drug delivery studies are carried out in vitro at different pH (7.4, 6.5, and 5.0) and temperatures (such as 25 °C and 42 °C, respectively). The surface conjugated copolymer (PNIPAm-PAAm) acts as a gatekeeper below the lower critical solution temperature (LCST) (32 °C), resulting in controlled drug delivery from the MS@PNIPAm-PAAm system. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cellular internalization results support the prepared MS@PNIPAm-PAAm NPs being biocompatible and readily taken up by MDA-MB-231 cells. The prepared MS@PNIPAm-PAAm NPs, with their pH-responsive drug release behavior and good biocompatibility, could be used as a drug delivery vehicle where sustained drug release at higher temperatures is required.

This study examined the digestive physiological response of juvenile and growing olive flounder (Paralichthys olivaceus) fed low-fishmeal diets. P. olivaceus (mean initial weight: 7.86 g) were cultured in eight square concrete tanks (10 × 10 m) at a commercial fish farm and fed twice a day with four types of experimental feed (FM70 control, 70% fishmeal content; FM45, 45% fishmeal content; FM35A, 35% fishmeal content; FM35B, 35% fishmeal content + 7% insect meal + 1% insect oil) for 6 months. During feeding experiments, fish growth was observed at 2-month intervals, and digestive organs (stomach, intestine, and liver) were sampled. Organs were stained with hematoxylin/eosin and Alcian blue/periodic acid–Schiff’s solution for each intestinal tissue (pore intestine and pylori), cholecystokinin in the pylori, and pancreatic polypeptide expression in the liver. Trypsin, chymotrypsin, and lipase activities in the intestine were measured. No significant differences in any of the measured variables were observed among the control, FM45, FM35A, and FM35B treatments at any of the sampling intervals. These results suggest that a diet comprising 35% fishmeal with added insects will not affect the digestive physiology of P. olivaceus in commercial fish farming in Korea.

Abstract In the present study, the protective effects of Hizikia fusiforme and Chlorella sp. extracts on lead acetate-induced hepatotoxicity were investigated. Hepatic damage was induced in rats by intraperitoneal (i.p.) injection of lead acetate and the protective effects of H. fusiforme (HZK) and Chlorella sp. (CHL) extracts on lead acetate-induced hepatic damage in rat liver were examined. The results revealed significantly increased glutamic oxaloacetate and glutamic pyruvic transaminase levels in the group treated with lead acetate only (Pb group); oral administration of HZK and CHL extracts tended to decrease the enzyme levels similar to those observed in the control group. Regarding antioxidant enzymes, superoxide dismutase activity was increased in the Pb group and decreased in a concentration-dependent manner in the HZK- and CHL-treated groups. Glutathione levels were increased in a concentration-dependent manner in the HZK- and CHL-treated groups. There was no significant difference in catalase activity. Western blot analysis showed inflammation-related protein expression in mitogen-activated protein kinase and Nrf2 pathways was affected in the HZK- and CHL-treated groups. Therefore, HZK and CHL extracts exerted antioxidant and anti-inflammatory effects against lead acetate-induced hepatotoxicity. Development of functional health foods containing HZK and CHL extracts, which have hepatoprotective effects against inhaled lead acetate, should be considered.

In olive flounder (Paralichthys olivaceus), growth performance, expression of growth-related factors, digestive physiology, and gut microbiota were assessed under farm conditions in the fish fed diets with low levels of fishmeal. Four experimental diets were prepared, FM70 [control (CON), 70% fishmeal], FM45 (45% fishmeal), FM35A (35% fishmeal), and FM35B (35% fishmeal + insect meal), and fed to the fish for five months. The CON-fed fish had the highest plasma GH, but IGF-1 and hepatic IGF-1 mRNA expression of the olive flounder fed diets with low-fishmeal levels did not significantly differ among diets. The intestinal villus length, muscular thickness, and the number of goblet cells were statistically similar, and ocular examination of hepatopancreas showed no discernable difference in all experimental diets. The chymotrypsin content of FM35B-fed fish is significantly lower, but trypsin and lipase contents are similar. The diversity of gut microbiota did not differ among groups, although the FM35B group had a higher composition of Firmicutes. Thus, a diet with reduced fishmeal content and several alternative protein sources can be used as feed ingredients in feed formulation for olive flounder reared under typical aquaculture farm conditions.

Recently, many manufacturers have been developing or producing imitation crab sticks (ICSs) that are highly similar to real snow crab leg meat (RC). This study evaluated the similarities between commercial ICSs and RC based on the analysis of physicochemical and sensory properties. Normal ICS (NS) and premium ICSs either with real crab leg meat (PS-RC) or without it (PS) were compared with RC. The sensory evaluation results showed that PS and NS had the highest and lowest levels of similarity to RC, respectively. The carbohydrate contents of ICSs (10–23%) were higher than that of RC (0.5%). Among ICSs, PS showed more similarity with RC than NS and PS-RC in terms of gel strength and texture profiles. PS-RC and PS showed a microstructural pattern that slightly imitated the muscle fiber arrangement of RC. The electric tongue analysis of taste compounds, such as sugars, free amino acids, and nucleotides, showed that the taste profile of ICSs is distinctly different from that of RC. The electronic nose analysis identified 32 volatile compounds, while the principal component analysis using electronic nose data successfully distinguished three clusters: PS-RC and PS, RC, and NS. Our results could provide useful information for the development of ICSs with higher similarity to RC.

Fishmeal is an important source of protein in the fish diet, but its supply is unstable due to environmental pollution and overfishing of anchovy and herring. In addition, the disease outbreak of fish has been increased, and the abuse of antibiotics and vaccines has been becoming a problem for residual substances. Therefore, studies that address diets with reduced fishmeal content and additives that can increase efficiency and replace antibiotics are needed. Hence, in this study, the probiotics bacteria Bacillus sp. SJ-10 (BSJ-10) and Lactobacillus plantarum (LP) were heat-killed (HK) used as additives in a low-fishmeal diet. The two bacteria with a 45 % fishmeal diet were added at a concentration of 3.34 × 108 CFU/mL, and both of probiotics bacteria were mixed and added to the same concentration in order to produce the diet for HK BSJ-10 (HKBSJ-10), HK LP (HK-LP), and MIX (HKBSJ-10 + HK-LP) groups. We raised four replicates of juvenile olive flounder for 8 weeks. In the HKBSJ-10 group, the plasma insulin, GH, and IGF-I level were higher than the other groups (P

Aging is associated with an increased risk of emotional disorders such as depression. In this study, effects of Capsosiphon fulvescens hydrophilic glycoproteins (Cf-hGP) on depressive-like behavior in aged rats were investigated. Oral administration of Cf-hGP (15 mg/kg/day; 4 weeks) attenuated immobility time of aged rats in forced swimming test by increasing expression of mature brain-derived neurotrophic factor (BDNF) in the ventral hippocampus. Cf-hGP-induced BDNF-mediated activation of extracellular signal-regulated kinase (ERK)1/2 increased cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) phosphorylation, which upregulated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 phosphorylation at serine 845. The activation of BDNF-mediated PKA signaling by Cf-hGP also attenuated endoplasmic reticulum (ER) stress in the ventral hippocampus. AMPAR blockade or PKA inhibition abolished the Cf-hGP-induced decrease in immobility time. These findings suggest that BDNF-mediated cAMP/PKA signaling in the ventral hippocampus contributes to antidepressant effects of Cf-hGP by regulating AMPAR GluA1 phosphorylation and ER stress.

Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory activities were analyzed. The C. soldanella ethyl acetate fraction (CsEF) had the strongest antioxidative activity, given its high polyphenol compound content. It also exhibited anti-inflammatory effects, inhibiting the production of inflammatory cytokines such as NO, PGE2, IL-1β, IL-6, and TNF-α in LPS-stimulated mouse macrophages. CsEF activated the nuclear transcription factor Nrf-2, thereby upregulating antioxidant enzymes such as HO-1 and NQO-1 and inhibiting NF-κB expression, which in turn, suppressed the expression of COX-2, iNOS, and inflammatory cytokines, ultimately exerting anti-inflammatory effects. Further, UPLC-Q-TOF-MS/MS was used to analyze the polyphenol compound contents in CsEF. The quercetin glycosides isoquercitrin and quercitrin were the primary flavonoid compounds, while the caffeic acid derivatives, chlorogenic acid and dicaffeoylquinic acid, were the primary phenolic acids. Thus, C. soldanella, which had only a limited use thus far as a medicinal plant, may serve as a natural medicinal resource for treating inflammatory diseases.

Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria that is widely used as a fluorescent probe or as a colorant in the food and cosmetic industries. In this study, phycoerythrin was extracted from the red algae Pyropia yezoensis and purified by ammonium sulfate precipitation and various chromatography methods. The purified phycoerythrin was analyzed by UV-visible and fluorescence spectroscopy. The isolated pigment had the typical spectrum of R-phycoerythrin, with a trimmer state with absorbance maxima at 497, 536, and 565 nm. It was further purified and identified by LC-MS/MS and Mascot search. It showed a 100% sequence similarity with the R-phycoerythrin alpha subunit of Pyropia yezoensis. The molecular mass was 17.97 kDa. The antioxidant activity of the purified R-phycoerythrin alpha subunit was analyzed. It showed significant antioxidant activity in ABTS and FRAP assays and had significant cytotoxicity against HepG2 cells.

Olive flounder (Paralichthys olivaceus) is a commercially important and valuable species for aquaculture in Korea. Due to the unstable supply of fishmeal for farmed fish, an optimum fish-feed formulation should be researched to ensure the sustainability of P. olivaceus aquaculture. This study investigated the effect of three experimental diets: Con (basal diet); FM20 (20% fishmeal replacement of CON); and FM30 (30% fishmeal replacement of CON) on P. olivaceus over 20 weeks at a typical farm by monitoring the growth and factors relating to sexual maturation. The results showed that no differences in growth were observed between the CON and diet-replacement groups. Gonadal oocyte development was similar between the CON and diet-replacement groups. Moreover, sbGnRH and GH expression did not differ between the CON and diet-replacement groups. The levels of Erβ and Vtg expression were significantly higher in the FM20 group than in the CON and FM30 groups after the experimental period. The expression of PSS-I was significantly higher in the FM30 group than in the CON and FM20 groups. Therefore, although growth occurred when 30% of the fishmeal was replaced, such high dietary protein replacement may be ill-advised during the maturation of olive flounder at the commercial fish farm.

Seaweed-derived antioxidative proteins can protect brain against ethanol-induced oxidative stress. This study was to investigate whether Capsosiphon fulvescens crude proteins (Cf-CP) alleviates the impairment in spatial memory by regulating brain-derived neurotrophic factor (BDNF) and endoplasmic reticulum (ER) stress against chronic ethanol exposure. Oral administration of Cf-CP for 14 consecutive days increased mature BDNF (mBDNF) levels and phosphorylation of calcium/calmodulin-dependent protein kinase II in rat dorsal hippocampus. The latency to platform was decreased and an increase in mBDNF was maintained until the withdrawal at 35 days in Cf-CP treatment. In rats treated with ethanol for four weeks, the ethanol-induced impairment in spatial memory was reduced by co-administration of Cf-CP. This treatment prevented the decrease in mBDNF and the increase in both of ER stress response protein, glucose-regulated protein 78, and protein kinase C delta phosphorylation. These findings suggest that Cf-CP administration improve cognitive functions by regulating BDNF-mediated ER stress response in the dorsal hippocampus.

Aging-induced cognitive dysfunction can be regulated by probiotics through bidirectional communication with the brain. This study aimed to investigate whether Capsosiphon fulvescens glycoproteins (Cf-hGP) enhanced probiotic-induced improvement of memory in aged rats and the underlying mechanism in the dorsal hippocampus. Cf-hGP were isolated using lectin resin. Cf-hGP (15 mg/kg/day) and/or Lactobacillus plantarum (L. plantarum) (109 CFU/rat/day) were orally administered once a day for 4 weeks. Co-treatment with Cf-hGP and L. plantarum synergistically improved spatial memory in aged rats, which was overturned by functional blocks of brain-derived neurotrophic factor (BDNF) signaling. Increases in BDNF expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation were accompanied by mono- and/or co-administration in the dorsal hippocampus, while c-Jun N-terminal kinase (JNK) phosphorylation and glucose-regulated protein 78 expression were decreased. These synergistic effects were downregulated by blocks of BDNF/Nrf2-mediated signaling. In particular, co-treatment, not mono-treatment, reduced phosphorylation of eukaryotic elongation factor 2 (eEF2) regulated by eEF2 kinase and protein phosphatase 2A. Additionally, co-treatment downregulated the interaction between eEF2 kinase and JNK. These data demonstrated that cognitive impairment in aged rats was synergistically diminished by co-treatment with Cf-hGP and L. plantarum through BDNF-mediated regulation of Nrf2 and eEF2 signaling pathways in the dorsal hippocampus.

In this study, we examined the protective effects of porphyra-334 against UVA-irradiated cellular damage and elucidated the underlying mechanisms. Porphyra-334 prevented UVA-induced cell death and exhibited scavenging activities against intracellular oxidative stress induced by UVA irradiation in skin fibroblasts. We found that porphyra-334 significantly reduced the secretion and expression of IL-6 and TNF-α, reduced nuclear expression of Nuclear factor-κB (NF-κB), and sustained NF-E2-related factor 2 (Nrf2) activation. Further mechanism research revealed that porphyra-334 promoted the Nrf2 signaling pathway in UVA-irradiated skin fibroblasts. Our results show that the antioxidant effect of porphyra-334 is due to the direct scavenging of oxidative stress and its inhibitory effects on NF-κB-dependent inflammatory genes, such as IL-6 and TNF-κ. Therefore, we hypothesize that boosting the Nrf2- NF-κB-dependent response to counteract environmental stress is a promising strategy for the prevention of UVA-related damage.

Modulation of multiple protein targets with a single compound is essential for the effective treatment of central nervous system disorders. In our previous G protein-coupled receptor (GPCR) cell-based study, a selective human monoamine oxidase (hMAO)-A inhibitor, eckol, stimulated activity of dopamine D3 and D4 receptors. This result led to our interest in marine phlorotannin-mediated modulation of hMAO enzymes and related GPCRs in neuronal disorders. Here, we evaluate the multi-target effects of phloroglucinol, phlorofucofuroeckol-A (PFF-A), and dieckol by screening their modulatory activity against hMAO-A and -B and various neuronal GPCRs. Among the tested phlorotannins, PFF-A showed the strongest inhibitory activity against both hMAO isoforms, with higher selectivity toward hMAO-B than hMAO-A. Enzyme kinetics and docking data revealed that PFF-A noncompetitively acts on hMAOs into the alternative binding pocket of enzymes with allosteric functions. In a functional assay for GPCR screening, dieckol and PFF-A exhibited a multi-target combination of D3R/D4R agonism and D1/5HT1A/NK1 antagonism. In particular, they effectively stimulated D3R and D4R, compared to other GPCRs. Docking analysis confirmed that dieckol and PFF-A successfully docked into the conserved active sites of D3R and D4R and interacted with aspartyl and serine residues in the orthosteric binding pockets of the respective receptors. Based on our experimental and computational data, we established the structure-activity relationship between tested phlorotannins and target proteins, including hMAOs and GPCRs. Our current findings suggest that hMAO inhibitors dieckol and PFF-A, major phlorotannins of edible brown algae with multi-action on GPCRs, are potential agents for treatment of psychological disorders and Parkinson’s disease.

Dexamethasone (DEX), a synthetic glucocorticoid, causes skeletal muscle atrophy. This study examined the protective effects of Pyropia yezoensis peptide (PYP15) against DEX-induced myotube atrophy and its association with insulin-like growth factor-I (IGF-I) and the Akt/mammalian target of rapamycin (mTOR)-forkhead box O (FoxO) signaling pathway. To elucidate the molecular mechanisms underlying the effects of PYP15 on DEX-induced myotube atrophy, C2C12 myotubes were treated for 24 h with 100 μM DEX in the presence or absence of 500 ng/mL PYP15. Cell viability assays revealed no PYP15 toxicity in C2C12 myotubes. PYP15 activated the insulin-like growth factor-I receptor (IGF-IR) and Akt-mTORC1 signaling pathway in DEX-induced myotube atrophy. In addition, PYP15 markedly downregulated the nuclear translocation of transcription factors FoxO1 and FoxO3a, and inhibited 20S proteasome activity. Furthermore, PYP15 inhibited the autophagy-lysosomal pathway in DEX-stimulated myotube atrophy. Our findings suggest that PYP15 treatment protected against myotube atrophy by regulating IGF-I and the Akt-mTORC1-FoxO signaling pathway in skeletal muscle. Therefore, PYP15 treatment appears to exert protective effects against skeletal muscle atrophy.

Cyclophilin (Cyp) is peptidyl−prolyl isomerase (PPIase), and it has many biological functions, including immune response regulation, antioxidants, etc. Cyp from red algae is known for its antioxidant and antifungal activity. However, the other biological effects of Cyp from Pyropia yezoensis are unclear. In this study, we synthesized Cyp from P. yezoensis (pyCyp) and examined its biological activity on IEC-6 cells. First, the MTS assay showed that pyCyp increased cell proliferation in a dose-dependent manner. pyCyp activated the EGFR signaling pathway that regulates cell growth, proliferation, and survival. It induced intracellular signaling pathways, including the Ras signaling pathway. In addition, we observed cell cycle-related proteins. pyCyp increased the expression of cyclin A, cyclin E, and Cdk2, and decreased the expression of p27 and p21 proteins. These results indicate that pyCyp stimulates cell proliferation via the EGFR signaling pathway and promotes cell cycle progression in intestinal epithelial cells. Therefore, we suggest pyCyp as a potential material to promote the proliferation of intestinal epithelial cells.

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

Endoplasmic reticulum (ER) stress is involved in various neurodegenerative disorders. We previously found that Capsosiphon fulvescens (C. fulvescens) crude proteins enhance spatial memory by increasing the expression of brain-derived neurotrophic factor (BDNF) in rat dorsal hippocampus. The present study investigated whether the chronic oral administration of hydrophilic C. fulvescens glycoproteins (Cf-hGP) reduces aging-induced cognitive dysfunction by regulating ER stress in the dorsal hippocampus. The oral administration of Cf-hGP (15 mg/kg/day) for four weeks attenuated the aging-induced increase in ER stress response protein glucose-regulated protein 78 (GRP78) in the synaptosome of the dorsal hippocampus; this was attenuated by the function-blocking anti-BDNF antibody (1 μg/μL) and a matrix metallopeptidase 9 inhibitor 1 (5 μM). Aging-induced GRP78 expression was associated with glycogen synthase kinase-3 beta (GSK-3β) (Tyr216)-mediated c-Jun N-terminal kinase phosphorylation, which was downregulated upon Cf-hGP administration. The Cf-hGP-induced increase in GSK-3β (Ser9) phosphorylation was downregulated by inhibiting tyrosine receptor kinase B and extracellular signal-regulated kinase (ERK)1/2 with cyclotraxin-B (200 nM) and SL327 (10 μM), respectively. Cf-hGP administration or the inhibition of ER stress with salubrinal (1 mg/kg, i.p.) significantly decreased aging-induced spatial memory impairment. These findings suggest that the activation of the synaptosomal BDNF-ERK1/2 signaling in the dorsal hippocampus by Cf-hGP attenuates age-dependent ER stress-induced cognitive dysfunction.

Wound healing is a dynamic and complex process. The proliferation and migration of dermal fibroblasts are crucial for wound healing. Recent studies have indicated that the extracts from Spirulina platensis have a positive potential for wound healing. However, its underlying mechanism is not fully understood. Our previous study showed that spirulina crude protein (SPCP) promoted the viability of human dermal fibroblast cell line (CCD-986sk cells). In this study, we further investigated the wound healing effect and corresponding mechanisms of SPCP on CCD-986sk cells. Bromodeoxyuridine (BrdU) assay showed that SPCP promoted the proliferation of CCD-986sk cells. The wound healing assay showed that SPCP promoted the migration of CCD-986sk cells. Furthermore, cell cycle analysis demonstrated that SPCP promoted CCD-986sk cells to enter S and G2/M phases from G0/G1 phase. Western blot results showed that SPCP significantly upregulated the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 (Cdk2), cyclin-dependent kinase 4 (Cdk4), and cyclin-dependent kinase 6 (Cdk6), as well as inhibited the expression of CDK inhibitors p21 and p27 in CCD-986sk cells. In the meanwhile, SPCP promoted the phosphorylation and activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). However, the phosphorylation of Akt was significantly blocked by PI3K inhibitor (LY294002), which in turn reduced the SPCP-induced proliferation and migration of CCD-986sk cells. Therefore, the results presenting in this study suggested that SPCP can promote the proliferation and migration of CCD-986sk cells; the PI3K/Akt signaling pathway play a positive and important role in these processes.

Glucocorticoids (GCs), which are endocrine hormones released under stress conditions, can cause skeletal muscle atrophy. This study investigated whether Pyropia yezoensis crude protein (PYCP) inhibits synthetic GCs dexamethasone (DEX)-induced myotube atrophy associated with proteolytic systems. Mouse skeletal muscle C2C12 myotubes were treated with DEX in the presence or absence of PYCP. DEX exposure (100 μM) for 24 h significantly decreased myotube diameter and myogenin expression, which were all increased by treatment with 20 and 40 μg/mL PYCP. Additionally, PYCP significantly reduced the nuclear expression of the forkhead box transcription factors, FoxO1 and FoxO3a, and ubiquitin-proteasome pathway activation. Further mechanistic research revealed that PYCP inhibited the autophagy-lysosome pathway in DEX-induced C2C12 myotubes. These findings indicate that PYCP prevents DEX-induced myotube atrophy through the regulation of FoxO transcription factors, followed by the inhibition of the ubiquitin-proteasome and autophagy-lysosome pathways. Therefore, we suggest that inhibiting these two proteolytic processes with FoxO transcription factors is a promising strategy for preventing DEX-related myotube atrophy.

Fucosterol from edible brown seaweeds has various biological activities, including anti-inflammatory, anti-adipogenic, antiphotoaging, anti-acetylcholinesterase, and anti-beta-secretase 1 activities. However, little is known about its effects on soluble amyloid beta peptide (sAβ)-induced endoplasmic reticulum (ER) stress and cognitive impairment. Fucosterol was isolated from the edible brown seaweed Ecklonia stolonifera, and its neuroprotective effects were analyzed in primary hippocampal neurons and in aging rats. Fucosterol attenuated sAβ1-42-induced decrease in the viability of hippocampal neurons and downregulated sAβ1-42-induced increase in glucose-regulated protein 78 (GRP78) expression in hippocampal neurons via activation of tyrosine receptor kinase B-mediated ERK1/2 signaling. Fucosterol co-infusion attenuated sAβ1-42-induced cognitive impairment in aging rats via downregulation of GRP78 expression and upregulation of mature brain-derived neurotrophic factor expression in the dentate gyrus. Fucosterol might be beneficial for the management of cognitive dysfunction via suppression of aging-induced ER stress.

We investigated the protective effects of Pyropia yezoensis crude protein (PYCP) against dexamethasone (DEX)-induced myotube atrophy and its underlying mechanisms. DEX (3 mg/kg body weight, intraperitoneal injection) and PYCP (150 and 300 mg/kg body weight, oral) were administrated to mice for 18 days, and the effects of PYCP on DEX-induced muscle atrophy were evaluated. Body weight, calf thickness, and gastrocnemius and tibialis anterior muscle weight were significantly decreased by DEX administration (p < 0.05), while PYCP supplementation effectively prevented the DEX-induced decrease in body weight, calf thickness, and muscle weight. PYCP supplementation also attenuated the DEX-induced increase in serum glucose, creatine kinase, and lactate dehydrogenase levels. Additionally, PYCP supplementation reversed DEX-induced muscle atrophy via the regulation of the insulin-like growth factor-I/protein kinase B/rapamycin-sensitive mTOR complex I/forkhead box O signaling pathway. The mechanistic investigation revealed that PYCP inhibited the ubiquitin-proteasome and autophagy-lysosome pathways in DEX-administrated C57BL/6 mice. These findings demonstrated that PYCP increased protein synthesis and decreased protein breakdown to prevent muscle atrophy. Therefore, PYCP supplementation appears to be useful for preventing muscle atrophy.

Perfluorooctane sulfonate (PFOS), a stable fluorosurfactant, causes endoplasmic reticulum (ER) stress in the brain. This study was designed to investigate whether a phycoerythrin-derived peptide of Pyropia yezoensis (PYP) reduces PFOS-induced ER stress associated with calcium dysregulation. The protective effects of PYP were determined by cell viability, immunoblotting for ER stress response protein glucose-regulated protein 78 (GRP78) and calcium-dependent protein kinases in rat frontal cortical neurons. PFOS-induced decrease in cell viability was attenuated by PYP pretreatment (1 µg/mL) for 24 h, which was downregulated by inhibiting tropomyosin-receptor kinase B (TrkB). PYP pretreatment downregulated the increase in intracellular calcium levels and phosphorylation of calcium/calmodulin-dependent protein kinase II and c-Jun N-terminal kinase which are associated with a PFOS-induced increase in GRP78. The PFOS-induced increase in GRP78 was downregulated via activation of TrkB receptor-linked extracellular signal-regulated kinases 1/2 (ERK1/2) by PYP pretreatment. Moreover, PYP microinjections (1 µg/kg, 0.54 nmol) attenuated the GRP78 expression in rat prefrontal cortex caused by PFOS (10 mg/kg) exposure for 2 weeks. These findings demonstrate that PYP enhances frontal cortical neuron viability via activation of TrkB receptor-ERK1/2 signaling and attenuation of ER stress in rat prefrontal cortex against PFOS exposure, suggesting that PYP might prevent neuronal dysfunctions caused by PFOS-induced ER stress.