Adiponectin is an abundant adipocytokine secreted by adipocytes. It exists in the plasma in its trimeric, hexameric, high-molecular-weight (HMW), and globular (a proteolytic product) isoforms. Adiponectin’s anti-inflammatory effects on macrophages remain controversial. We have previously reported a simple and effective method for purifying native HMW adiponectin from human plasma. Here, we investigated whether native HMW adiponectin from human plasma has anti-inflammatory effects on macrophages. Pretreatment with human native HMW adiponectin inhibited lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) gene expression, but not tumor necrosis factor (TNF)-α expression. However, simultaneous treatment with HMW adiponectin and LPS did not inhibit IL-1β expression. Further, HMW adiponectin pretreatment decreases glycogen synthase kinase-3β (GSK-3β) inactivation by abrogating LPS-induced Akt (Ser473) phosphorylation, which subsequently suppresses LPS-induced CCAAT/enhancer binding protein β (C/EBPβ) protein translation and nuclear translocation. However, HMW adiponectin pretreatment did not affect LPS-induced nuclear factor-kappaB (NF-κB) activation. These results suggest that HMW adiponectin mediates potent anti-inflammatory activities in macrophages by inhibiting its Akt–C/EBPβ signaling pathway, thereby suppressing IL-1β gene expression.

Human cytomegalovirus (HCMV) is associated with epithelial–mesenchymal transition (EMT) in glioma cells; however, its underlying action mechanism remain ambiguous. In this study, we investigated the effects of receptor-interacting protein 2 (RIP2) and nuclear factor (NF)-κB on EMT in HCMV-infected glioma LN-18 cells. Wound healing and invasion assays were used to evaluate the migration and invasion of cells. Western blotting and immunofluorescence microscopy were used to determine the protein expression levels. We found that HCMV induced enhanced migration and invasion of LN-18 cells, activation of the RIP2/NF-κB signaling pathway, downregulation of epithelial cell marker (E-cadherin) expression, and upregulation of mesenchymal cell marker (N-cadherin and vimentin) expression. Moreover, inhibition of RIP2 or NF-κB inhibited the induction of HCMV in LN-18 cells. Therefore, HCMV induces EMT in glioma cells by promoting the activation of NF-κB signaling pathway via the upregulation of RIP2 expression.

Vascular endothelial cells sustain vascular health through barrier and endocrine functions. Insufficient oxygen supply induces endothelial dysfunction in the pathology of various diseases. In addition, oxygen deprivation reportedly induces endothelial dysfunction via autophagy. Ras guanyl-releasing protein 2 (RasGRP2) has guanosine 5′-diphosphate (GDP)/guanosine 5′-triphosphate (GTP) exchange factor activity and activates Rap1 and R-Ras which belong to the small GTPases. RasGRP2 exerts protective effects against vascular endothelial dysfunction. However, the effect of RasGRP2 on hypoxic stress in vascular endothelial cells has not yet been investigated. We examined the protein expression of hypoxia-inducible factor (HIF)-1α, BCL2 interacting protein 3 (BNIP3), and microtubule-associated protein light chain 3β (LC3β). We observed that oxygen deprivation increased the expression of HIF-1α, BNIP3 and LC3β II. RasGRP2 suppressed the induction of HIF-1α and the subsequent increase in LC3β II. These findings suggest the possibility that RasGRP2 plays a protective role against endothelial dysfunction by suppressing oxygen deprivation-induced autophagy.

Isoflavones and their derivatives possess neuroprotective activities against neurological disorders. Recently, the active compound SPA1413 (dehydroequol) derived from S-equol, an isoflavone-derived metabolite produced by human intestinal bacteria, was identified as a potent anti-amyloidogenic and neuroinflammatory candidate against Alzheimer’s disease. However, its detailed modes of action, associated signaling pathways, and comparison with potential isoflavone derivatives have not yet been studied. Hence, the current study aimed to identify signaling pathways associated with SPA1413 using lipopolysaccharides (LPS)-stimulated BV2 cells as the experimental model via biological assays, Western blotting, and quantitative (q)RT-PCR. The results indicate that the SPA1413 anti-neuroinflammatory effect arises due to suppression of the nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and mitogen-activated protein kinase (MAPK) signaling networks, including those of p38 and c-Jun N-terminal kinase (JNK). Interestingly, SPA1413 inhibited IL-11 through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. In addition, SPA1413 inhibited neuronal cell death by reducing LPS-activated microglia in neuronal N2a cells. Our findings suggest that SPA1413 may act as a strong anti-neuroinflammatory candidate by suppressing the MAPK and JAK/STAT signaling pathways.

Osmundacetone (DHBAc) is an antioxidant compound that has been shown to have neuroprotective and immunomodulatory activities. However, few studies have estimated its effect on cerebral ischemia–reperfusion (I/R) injury. In this study, we investigated the protective effect of DHBAc on the brain tissue of rats with cerebral I/R injury. Rats were respectively given nimodipine (NI), low dose (L-DHBAc) and high dose (H-DHBAc) Osmundacetone, and they were killed under anesthesia after 24 h of reperfusion. And neurological impairment scores, cerebral infarct size and cerebral pathological changes were respectively detected, and mRNA expression of recombinant kelch like ECH associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression levels of caspase 3, cleaved caspase 3, heme oxygenase-1 (HO-1) and quinone oxidoreductase1 (NQO1) in ischemic brain tissue were measured. Compared with the I/R group, neurological impairment scores of the DHBAc groups were significantly decreased, and their infarct sizes were significantly smaller. DHBAc could improve the pathological status of brain tissue with cerebral I/R injury, including reducing number of inflammatory cells and area of vacuoles and restoring number of normal neurons. Expression levels of Keap1 mRNA and proteins of cleaved caspase3 were significantly decreased in the DHBAc groups than those of the I/R group, while expression levels of Nrf2 mRNA, HO-1 and NQO1 proteins were remarkably increased. The effect of H-DHBAc was similar to those of NI. These results suggest that DHBAc could mitigate damage to brain tissue in rats with cerebral I/R injury.

The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

The use of lipid-modifying agents (LMAs) other than statins has rarely been reported in real clinical settings. We aimed to compare the initiation and subsequent use of LMA classes for prevention of cardiovascular diseases. Using the national claims database, this retrospective cohort study was conducted on patients aged ≥55 years who initiated to use statins, ezetimibe, or fibrates between Fiscal Years (FYs) 2014 and 2017 as the first pharmacotherapy for dyslipidemia in Japan. A permissible gap for defining persistence was set as the median days of supply of a class to an individual. Kaplan–Meier estimates were calculated for rates. Cohorts for primary prevention without/with risk and secondary prevention comprised 1307438, 908378, and 503059 initiators for statins; 44116, 34206, and 11373 for ezetimibe; and 124511, 96380, and 27751 for fibrates. The persistence rates declined shortly after the therapy initiation regardless of the classes, which was approximately 50% at 1 year for any class for primary prevention without risk. A notable sex difference in terms of persistence rates was observed only for statins of secondary prevention. The restarting rates were similar between prevention settings: approximately 50–60% for statins and 30–40% for ezetimibe and fibrates 1 year after first discontinuation. For ezetimibe and fibrates, approximately 10% of initiators were added or switched to statins within 1 year of initiation. Collectively, any class tended to be discontinued early and some restarted; however, there were some unique classes. The findings are useful for improvement of dyslipidemia therapy.

This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.

Ovarian cancer (OC) is one of the most common and high mortality type of cancer among women worldwide. The majority of patients with OC respond to chemotherapy initially; however, most of them become resistant to chemotherapy and results in a high level of treatment failure in OC. Therefore, novel agents for the treatment of OC are urgently required. Benzimidazole anthelmintics might have the promising efficacy for cancer therapy as their selectively binding activity to β-tubulin. Recent study has shown that one of the benzimidazole anthelmintics oxfendazole inhibited cell growth of non-small cell lung cancer cells, revealing its anti-cancer activity; however, the pharmacological action and detailed mechanism underlying the effects of oxfendazole on OC cells remain unclear. Therefore, the present study investigated the cytotoxic effects of oxfendazole on OC cells. Our results demonstrated that oxfendazole significantly decreased the viability of OC cells. Oxfendazole inhibited the proliferation, induced G2/M phase arrest and apoptotic cell death in A2780 cells. The c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway was activated and reactive oxygen species (ROS) generation was increased in OC cells treated with oxfendazole; oxfendazole-induced apoptosis was notably abrogated when co-treated with JNK inhibitor SP600125 and ROS scavenger N-acetyl-L-cysteine (NAC), indicating that JNK/MAPK pathway activation and ROS accumulation was associated with the oxfendazole-induced apoptosis of OC cells. Moreover, oxfendazole could also induce the proliferation inhibition and apoptosis of cisplatin resistant cells. Collectively, these results revealed that oxfendazole may serve as a potential therapeutic agent for the treatment of OC.

Chinese artichoke tuber (Stachys sieboldii Miq.) is used as an herbal medicine as well as edible food. This study examined the effect of the Chinese artichoke extracts on the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway that induces the expression of antioxidant enzymes to explore its novel characteristics. Hot water extracts exhibited relatively high ARE activity. ARE activity was observed in two fractions when the hot water extracts were separated in the presence of trifluoroacetic acid using HPLC. Conversely, the highly active fraction disappeared when the hot water extracts were separated in the absence of trifluoroacetic acid. These results indicate that acidic degradation produces active ingredients. The structural analysis of the two active fractions identified harpagide, which is an iridoid glucoside, and harpagogenin. In vitro experiments revealed that harpagide was converted into harpagogenin under acidic conditions and that harpagogenin, but not harpagide, had potent ARE activity. Therefore, this study identified harpagogenin, which is an acid hydrolysate of harpagide, as an ARE activator and suggests that Nrf2–ARE pathway activation by Chinese artichoke contributes to the antioxidative effect.

Although polymethoxyflavones have been reported to exhibit various pharmacological actions, the effects of polymethoxyflavones sudachitin and demethoxysudachitin from the peel of Citrus sudachi on the cardiovascular system have not been clarified. This study investigated the mechanisms of vasorelaxation induced by sudachitin and demethoxysudachitin in rat aorta. Both compounds inhibited phenylephrine-induced contractions in a concentration-dependent manner. This was also observed in the case of potassium chloride (KCl)-induced contractions although the inhibitory effect was weak. In both contraction types, no differences were found in the inhibitory effects of sudachitin and demethoxysudachitin between endothelium-intact and -denuded aorta. The relaxant effects of sudachitin in endothelium-intact aortas were not affected by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) or the cyclooxygenase inhibitor indomethacin. In endothelium-denuded aorta, propranolol did not affect the relaxant effect of sudachitin. Both the adenylate cyclase activator forskolin- and soluble guanylate cyclase activator sodium nitroprusside-induced relaxant effects were potentiated by preincubation of sudachitin. Furthermore, the relaxant effect of sudachitin was not affected by the adenylate and guanylate cyclase inhibitors SQ22536 and or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), respectively. Finally, we examined the effect of phosphodiesterase inhibition. Phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, cilostamide or sildenafil) alone, sudachitin alone, and a combination of phosphodiesterase inhibitors with sudachitin exhibited relaxant effects, while the lack of any interaction between each phosphodiesterase inhibitor and sudachitin indicated an additive effect between the two substance categories. These results suggest that sudachitin and demethoxysudachitin cause endothelial-independent relaxation, and that the mechanism of vasorelaxation by sudachitin is associated with the enhancement of cAMP- and guanosine 3′,5′-cyclic monophosphate (cGMP)-dependent pathways.

Rheumatoid arthritis has a significant impact on the life quality, but current pharmacological therapies have limitations. As a result, there is growing interest in exploring the potential of natural plant components to intervene in the development of rheumatoid arthritis. Resveratrol, a natural polyphenol and one of the main active components of the Chinese herbal medicine Polygonum cuspidatum, has emerged as a promising candidate for this purpose. In the present study, we investigated the role and mechanism of resveratrol in inhibiting inflammatory response in rat primary fibroblast-like synoviocytes. Tumor necrosis factor (TNF)-α was used to establish a model of inflammation, the Sirtuin1 selective inhibitor Selisistat (EX527) was used to inhibit Sirtuin1 activity, and small interfering RNA was used to silence cortistatin expression. The results showed that pre-treatment with resveratrol could time- and dose-dependently inhibit TNF-α induced cellular interleukin (IL)-1β and IL-6 secretion, and upregulate Sirtuin1 and cortistatin mRNA and protein expression in the range of 48 h, 100 µM. Selisistat (EX527) could attenuate resveratrol inhibited inflammatory response and upregulated cortistatin expression. Silencing cortistatin expression attenuated the effect of resveratrol on inhibiting inflammatory response, but did not affect its effect on upregulating Sirtuin1 expression. In conclusion, resveratrol effectively inhibited the TNF-α induced inflammatory response in fibroblast-like synoviocytes by a mechanism involving the Sirtuin1/cortistatin pathway.

The involvement of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing in the central nervous system (CNS) has been reported using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the roles of 5-HT receptor family in acute pruriceptive processing have not been fully elucidated in the CNS. In the present study, scratching behavior induced by chloroquine (CQ) was ameliorated by milnacipran or mirtazapine, and these effects were reversed by SB207266, a 5-HT₄ antagonist, or SB258585, a 5-HT₆ antagonist, but not by SB258585, a 5-HT₅ antagonist. Moreover, CQ-induced scratches were mitigated by intrathecal injection of 5-HT₄ agonists, such as BIMU8 and ML10302, and the 5-HT₆ agonist, WAY208466. Conversely, histamine-induced scratches were not affected by the 5-HT₄ agonists or a 5-HT₆ agonist. Similarly, the amelioration of histamine-induced scratches by these antidepressants was not reversed by the 5-HT₄, 5-HT₅, or 5-HT₆ receptor antagonist. Therefore, 5-HT is involved in the amelioration of CQ-induced scratches by milnacipran and mirtazapine, and 5-HT₄, 5-HT₅, and 5-HT₆ receptors play differential roles in acute pruriceptive processing after administration of CQ or histamine.

The modified Cockcroft–Gault (CG) equation, previously developed for an aged-oriented cohort, was validated in a newly obtained dataset. Estimates of creatinine clearance (CCr) using this equation were found to be more accurate than those determined using the conventional CG equation, particularly for patients exceeding 65 years of age. We identified a subset of patients in this cohort whose estimates were inadequate. Using statistical analysis, we found that the deviation from estimates was attributed to a decreased albumin level. In addition, we determined a reduced albumin cutoff value for the modified CG equation to obtain a good estimate. Univariate linear regression analysis was applied to measure the CCr in this cohort and identify parameters related to body composition, and we found that extracellular water (ECW)/total body water (TBW) and body fat (%) were relevant. Using measured values of ECW/TBW and body fat (%), a multivariate linear regression (MLR) estimating equation was developed based on the modified CG equation. This equation was applied to a cohort over 65 years of age, and it was found that a good estimate was obtained for older patients with low albumin levels. Thus, we propose a flow diagram that illustrates conditions for selecting an appropriate estimating equation from among the CG, modified CG, and MLR equations.

The eukaryotic canonical nucleosome has an acidic patch on each H2A/H2B dimer. This acidic patch is also detected in histone variants, such as the H2A.Z (yeast Htz1)/H2B dimer. Here, we screened a comprehensive histone point mutant library and identified 11 histone residues located in four distinct nucleosome domains (Homologous Recombination (HR) Domain I–IV (HRD-I–IV)) with a potential role in HR. H2A-L66, -E93, and -L94 residues in HRD-I are located in the acidic patch region. Equivalent residues (H2A-L66 and Htz1-L73) partly compensate the function of each dimer. A common residue H2B-L109, which is located underneath of the acidic patch in both dimers, also partly compensates the function of each dimer. Upon exposure to DNA double-strand break (DSB)-inducing agents, the fragmented chromosomes of H2A-L66A mutant cells exhibited slow and limited recovery into intact chromosomes, suggesting that the H2A-L66A mutant is partly deficient in DSB repair. Furthermore, strand invasion, one of critical steps of HR, could be less efficient in H2A-L66A cells. All 11 HRD residues, including H2A-L66, are highly conserved in extant eukaryotic cells; therefore, our screening reported in this study will provide a foundation for future studies about the mechanisms underlying eukaryotic HR based on chromatin.

Clostridioides difficile is the major causative pathogen of pseudomembranous colitis, and novel antimicrobial agents are required for treatment. Phage-derived endolysins exhibiting species-specific lytic activity have potential as novel antimicrobial agents. We surveyed the genome of C. difficile strain 630 and identified a gene encoding an endolysin, Ecd18980, which has an amidase_3 domain at the N-terminus but unknown C-terminal domain. The genes encoding Ecd18980 and its catalytic domain (Ecd18980CD) were cloned and expressed in Escherichia coli as N-terminal histidine-tagged proteins. These purified proteins showed lytic activity against C. difficile. Ecd18980CD showed higher lytic activity than the wild-type enzyme and near-specific lytic activity against C. difficile. This species specificity is thought to depend on substrate cleavage activity rather than binding. We also characterized the biochemical properties of Ecd18980CD, including optimal pH, salt concentration, and thermal stability.

The similarity of drug names is one of the common causes of medication error. In Japan, similarity evaluation is performed prior to approval of new drugs in order to avoid potential confusion. However, existing indices do not take account of the difference between characters that contain voiced or semi-voiced and unvoiced sounds, so it is not clear whether such sounds influence the subjective similarity of drug names. Thus, we performed a cognitive psychological experiment to investigate this issue, using participants who had not received any education in medicine, nursing, or pharmacy. An analogue scale questionnaire was used to evaluate the subjective similarity of the names of drug pairs. Drug pairs for the main analysis were prepared by matching the first 0 to 3 characters, and then varying the difference in the number of voiced and semi-voiced characters from 0 to 3 in these matched characters. By means of this procedure, the drug pairs were classified into a total of 10 groups. Then, a total of 60 drug pairs were created by assigning 6 drugs to each group. The subjective similarity tended to increase with increasing number of common characters among the first three characters. When classified according to the number of these common characters, the subjective similarity was significantly decreased when voiced or semi-voiced sounds were present, as compared with when they were absent. These results indicate that a new drug name similarity index that takes account of voiced and semi-voiced sound differences should be developed to minimize medication errors.

Hyaluronic acid (HA) is a hydrophilic supra-macromolecule, with a molecular weight (MW) 1000000<. HA is recognized as a biomaterial for skin moisturization. HA solution is typically injected into the skin using a needle. However, needle injection is invasive and does not result in homogeneous distribution of HA over a large area of skin. Therefore, non-invasive and effective technologies for homogenous intradermal delivery of HA are needed. Recently, we demonstrated the use of iontophoresis (ItP) for non-invasive intradermal delivery of various macromolecules, such as small interfering RNA (siRNA) (MW: 12000) and antibodies (MW: 150000). Based on our previous studies, we hypothesized that HA can also be delivered non-invasively into the skin by ItP. In this study, we applied ItP to fluorescence-labeled HA (MW: 600000–1120000 and 1200000–1600000) on rat dorsal skin. Following treatment, fluorescence was observed to be widely distributed in the skin, demonstrating successful intradermal delivery of HA via ItP. In addition, the relative moisture content and elasticity of skin treated with ItP/HA was temporarily higher than that of control skin. This is the first report demonstrating successful non-invasive intradermal delivery of HA and improvement of skin conditions by high-molecular weight HA delivered by ItP. In conclusion, ItP would be a useful technology for non-invasive intradermal delivery of high-molecular weight HA for treatment of skin diseases and cosmetology applications.

The oral bioavailability of berberine is quite low due to extensive first-pass metabolism. To increase the bioavailability of berberine (BBR), the efficacy of rectal administration that can avoid intestinal and hepatic first-pass metabolism partly was evaluated using BBR sulfate in rats. BBR sulfate was administered intravenously (1 mg/kg as BBR), orally (10 mg/kg as BBR) and rectally (1, 3, or 10 mg/kg as BBR) using Witepsol^® H15 suppository base to evaluate bioavailability in rats. Concentrations of BBR in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). When BBR sulfate was administered orally, the average oral bioavailability was 0.26%. When BBR sulfate was administered rectally, the average bioavailabilities were 17.0% at 1 mg/kg, 24.3% at 3 mg/kg, and 12.3% at 10 mg/kg as BBR, respectively. Thus, rectal administration of BBR sulfate greatly increased the bioavailability of BBR as compared with oral administration, which would also increase the pharmacological activities of BBR in vivo.

Daily intake of extracellular vesicles (EVs) derived from fish (f-EVs) may contribute to health maintenance by reducing cardiovascular risk. However, their physicochemical and biological properties remain unclear. In this study, we compared the physical characteristics (size, zeta potential, and free fatty acid composition) and biological characteristics (cell proliferation) of f-EVs with those of EVs derived from mammals (m-EVs). In the physical characteristic analysis, f-EVs derived from Pagrus major (PMS-EVs) and Seriola quinqueradiata (SQS-EVs) had a negatively charged and a positively charged group and higher levels of unsaturated fatty acids, unlike m-EVs. In the biological characteristic analysis for f-EVs, SQS-EV enhanced the human umbilical vein endothelial cell proliferation via vascular endothelial growth factor receptor 2, fibroblast growth factor receptor 1, or platelet-derived growth factor β. These data suggest that SQS-EVs have unique functions compared with other EVs. To the best of our knowledge, this is the first study to show that SQS-EVs act positively on human cells.