ABSTRACT Due to its advantages of a short production cycle, wide market demand, and profitability, decapod crustacean aquaculture has become one of the fastest‐growing food production systems. However, disease outbreaks have become one of the most important factors limiting the sustainability of decapod crustaceans. This review synthesizes current advancements in the understanding of emerging viral pathogens in decapod crustacean aquaculture, with emphasis on their genomic‐based taxonomical classification, susceptible hosts, global distribution, clinical manifestations, pathogenic mechanisms, diagnostic developments, and management strategies. This paper summarizes details of emerging viruses with confirmed pathogenicity (such as decapod iridescent virus 1), as well as viruses with uncertain or yet‐unconfirmed pathogenic roles. In addition, we highlight the role of next‐generation sequencing in virus discovery and examine the challenges posed by coinfection with other microorganisms. This review provides information to help the decapod crustacean aquaculture industry in setting up early warning systems to prevent the introduction of emerging pathogens into the production systems.

Astaxanthin (AST), a carotenoid pigment, has garnered significant interest due to its potent antioxidant, anti-inflammatory, and antibacterial properties, indicating that it is a valuable natural additive in the aquaculture, nutraceutical, and cosmetic industries. To date, Paracoccus spp., a known astaxanthin-producing bacteria, has emerged as a potential microbial source of substantial AST production yield and biosynthetic capabilities. This study reports the biochemical and genomic characterization of two Paracoccus isolates, GCUPA1 and GCUPA3, focusing on their potential as sources of natural carotenoids. Both strains were characterized by distinctive red-orange pigmentation and identified as P. marcusii based on 16S rRNA analysis. Spectroscopic and chromatographic analyses were performed to identify the predominant carotenoids, and the results established AST as the predominant carotenoid in both strains. The extracted pigments exhibited significant antioxidant activity in the 2,2 '-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, indicating their potential to reduce oxidative stress. Genome phylogeny revealed that both strains were closely related to the carotenoid-producing strain, P. marcusii CP157, confirming their taxonomic position within the species. Notably, the complete genome sequences revealed intact carotenoid biosynthetic gene clusters (BGCs) that encode all essential enzymes (crtWZYIBE) required for astaxanthin synthesis from isoprenoid precursors, with high nucleotide identity between strains. These findings establish P. marcusii GCUPA1 and GCUPA3 as a potential cell factory for sustainable astaxanthin production and suggest significant advantages in terms of processing efficiency and production economics compared to existing microbial systems.

Acute hepatopancreatic necrosis disease (AHPND) is an economically devastating shrimp disease caused by Vibrio species that are temperature-sensitive. To elucidate the temperature-dependent pathogenicity of AHPND strains, in vivo (bioassay) and in vitro (bacterial growth kinetics and virulence gene expression quantification) analyses were performed using four different AHPND-associated Vibrio strains. In the bioassay, shrimp challenged with AHPND-causing V. parahaemolyticus (AHPNDVP) and AHPND-causing V. campbellii (AHPNDVC) showed significantly higher mortalities (67.6% and 47.1%, respectively) and severe hepatopancreatic necrosis (G4) at the lowest temperature (20–22°C). In contrast, regardless of temperature, shrimp challenged with AHPND mutant strains with complete or partial pirAB gene deletions exhibited significantly lower mortality (0–5.9%) and mild hepatopancreatic degeneration (G1–G2). In vitro analyses were additionally conducted with pathogenic strains, AHPNDVP and AHPNDVC. AHPNDVP and AHPNDVC were more active at high temperatures (32°C), exhibiting the shortest generation times (16.9 and 17.1 min, respectively) and the highest pirA toxin gene expression (1.34×107 and 4.43×106 copies/μL, respectively). The results revealed that shrimp are more vulnerable to AHPND at low temperatures, while the bacterial growth efficiency and toxin gene expression are enhanced at high temperatures. These results indicate that the pathogenicity of AHPNDVP and AHPNDVC is driven by a complex interplay among temperature, pathogen, and the host. Therefore, to mitigate the impact of AHPND, implementing temperature-dependent strict management strategies is essential. In summer, environmental improvements are necessary to suppress bacterial proliferation, whereas in winter or transitional seasons, maintaining optimal temperature is crucial to protect shrimp from AHPND.

Vibrio parahaemolyticus harboring the pVA1 plasmid (VpAHPND) causes acute hepatopancreatic necrosis disease (AHPND), a major threat to global shrimp aquaculture. Although bacteriophage (phage)-based biocontrol has emerged as a promising alternative to antimicrobial agents for controlling VpAHPND, most studies have focused on disease prevention in culturing shrimp rather than post-harvest applications. In this study, a KVP40-like jumbo phage, designated vB_VpM-pA3B5, was isolated and characterized, and its biocontrol potential was evaluated in both VpAHPND-contaminated shrimp products and shrimp bioassay. Phage vB_VpM-pA3B5 exhibited a broad host range, infecting globally distributed VpAHPND strains, an AHPND-causing V. campbellii strain, and three additional Vibrio species. The phage demonstrated strong lytic activity, efficient replication, and high environmental stability. Genome analysis revealed a 243,570-bp linear dsDNA genome encoding 382 predicted ORFs and 28 tRNAs, with no virulence or antimicrobial resistance genes detected. Comparative genomic analysis indicated high synteny with the Schizotequatrovirus phages KVP40 and PVA8 and identified a unique tail fiber protein (ORF115) that may contribute to its broad host range. In VpAHPND-contaminated shrimp products, the phage efficiently reduced bacterial loads and actively replicated during storage. In the shrimp bioassay, although cumulative mortality was not reduced, phage-treated shrimp exhibited alleviated hepatopancreatic lesions and lower pirA gene loads than the VpAHPND-challenged group. These findings highlight the potential of phage vB_VpM-pA3B5 as a biocontrol agent for mitigating AHPND-associated risks in shrimp aquaculture and reducing the dissemination of VpAHPND through shrimp products.

Background and Aim:Growth retardation syndrome in cultured Penaeus vannamei has been associated with Enterocytozoon hepatopenaei (EHP) and a recently identified decapod hepanhamaparvovirus (DHPV) genotype V. However, data on its prevalence, pathogenicity, and interaction with the shrimp hepatopancreatic microbiome in Thailand remain limited. This study aimed to determine the incidence and co-infection rate of DHPV genotype V with EHP, evaluate its pathogenic potential, and explore microbiome alterations associated with infection. Materials and Methods:Between 2022 and 2023, 1,270 shrimp from 127 grow-out ponds across 46 farms in eastern Thailand and post-larvae 12 from five hatcheries in the south were screened for DHPV and EHP by polymerase chain reaction. Six representative isolates underwent phylogenetic analysis based on non-structural protein 1 (NS1) and NS2 genes. Pathogenicity was evaluated by immersion challenge bioassays in specific pathogen-free P. vannamei. Hepatopancreatic microbiomes of naturally infected and healthy shrimp were compared using 16S ribosomal RNA gene sequencing and Quantitative Insights Into Microbial Ecology 2-based analysis. Results:DHPV was detected in 54.33% (69/127) of ponds and 4% (1/25) of hatchery tanks. Co-infection with EHP occurred in 40.16% of ponds. Phylogenetic analysis showed 97.99%-98.82% similarity with DHPV genotype V from South Korea, confirming transboundary genetic relatedness. Experimental infection caused low mortality (20%) but resulted in viral replication (101-103 copies/μL) and characteristic intranuclear inclusion bodies in hepatopancreatic cells. DHPV-infected shrimp exhibited distinct microbiome profiles with elevated Firmicutes, Planctomycetota, and Actinobacteriota abundances, supporting a pathobiome shift during infection. Conclusion:This is the first report of DHPV genotype V in P. vannamei from Thailand and its frequent co-infection with EHP. Despite its low experimental virulence, the widespread occurrence and microbiome dysbiosis suggest that it may have subclinical impacts that could exacerbate growth retardation. Routine molecular screening in hatcheries and farms, coupled with integrated viral-microbiome surveillance, is essential for sustainable aquaculture biosecurity and aligns with the United Nations Sustainable Development Goal 14 (Life Below Water) by promoting resilient aquatic food systems.

Objectives: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in both males and females. Considering the growing impact of NSCLC on public health, there is an urgent need for additional treatment strategies. Veratramine, a natural steroidal alkaloid extracted from the roots of plants in the lily family, has recently garnered attention regarding its potential anti-cancer effects. However, to the best of our knowledge, the role of veratramine in the progression of lung cancer is unclear. Methods : The various concentration of veratramine were applied to the NSCLC cell lines (A549, NCI-H358 and NCI-H1299). The cell viability, apoptosis, and the cell cycle were evaluated using CCK-8 and flow cytometry assays. Phenotype of NSCLC cells were examined using an optical microscope and ImageJ software. Protein expression in veratramine-treated NSCLC cells was measured using immunoblotting. Results : Veratramine-treated NSCLC cells exhibited significantly reduced cell viability and migration ability. Flow cytometry (i.e., fluorescence-activated cell sorting) revealed that treatment with veratramine increased apoptosis and cell cycle delay. Immunoblotting indicated that the Hedgehog (Hh) signaling pathway was significantly downregulated via inhibiting gli1 expression. Cell cycle-related proteins in NSCLC cells were decreased by veratramine treatment. Conclusion : Veratramine suppresses lung cancer cell growth by inhibiting the Hh signaling pathway, suggesting its potential applicability in the treatment of NSCLC.

Polystyrene-derived microplastics (PS-MP) are one of the most important environmental problems in modern society and are associated with various chronic disorders. Previous studies have shown that PS-MP exerts estrogenic effects on aquatic organisms. This research indicates that PS-MP may function as an endocrine-disrupting chemical and a risk factor for estrogen-related diseases, such as breast cancer. However, the carcinogenic potential of PS-MPs in breast cancer has not been studied extensively. Therefore, in the present study, we aimed to elucidate the effects of PS-MP on human breast cancer cells. Estrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cells were exposed to low and high concentrations of PS-MP for 4 weeks. MCF-7 cells exposed to PS-MP exhibited significantly increased cell viability, whereas MDA-MB-231 cells showed no change. Subsequent in vitro and in vivo experiments demonstrated that PS-MP-stimulated MCF-7 cells significantly increased non-genomic ER signaling pathways and tumor growth in mice. Moreover, the ER-knockdown MCF-7 cells were not affected by PS-MP simulation. Our results demonstrate that PS-MP stimulation promotes the malignant transformation of human breast cancer cells via the ER signaling pathway. Considering the emerging concerns regarding PS-MP pollution worldwide, these data provide novel insights into the potential carcinogenic risk of PS-MP to human breast cancer.

This study investigated Macrobrachium rosenbergii imported from India (15 batches, N = 180) and Vietnam (7 batches, N = 84) between 2023 and 2024, for Enterocytozoon hepatopenaei (EHP) monitoring and genetic analysis. Polymerase chain reaction assays detected EHP in 13.3% (2/15) and 71.4% (5/7) samples from India and Vietnam, respectively. The sequence of the small subunit ribosomal ribonucleic acid region of the EHPs isolated from M. rosenbergii showed no significant differences from those available in GenBank. Interestingly, spore wall protein (SWP) 1 region analysis revealed that M. rosenbergii EHPs could be divided into three groups, some of which were closely related to Penaeus vannamei EHPs. Similarly, the internal transcribed spacer-1 (ITS-1) region analysis divided M. rosenbergii EHPs into two groups, with some showing close relationships with P. vannamei EHPs. Phylogenetic analyses based on the SWP 1 and ITS-1 regions suggested that EHPs infecting M. rosenbergii exhibited greater genetic diversity than those infecting P. vannamei. This study provides the first report of EHP detection in M. rosenbergii imported from India and Vietnam to South Korea. Further genome-based analyses are necessary for a comprehensive genetic characterization of EHPs infecting M. rosenbergii from various geographical regions.

Background:Platelet hyperactivation is a major factor in thrombotic complications such as myocardial infarction and ischemic stroke. Ginsenoside Rg5 is a minor ginsenoside, and among its various beneficial pharmacological effects, its antithrombotic potential has not been extensively studied. Methods:Human platelets were isolated and treated with Rg5 (35-100 μM) before stimulation with agonists such as collagen, thrombin, and U46619. Platelet aggregation, granule secretion, calcium mobilization, thromboxane A2 production, fibrinogen binding, and clot retraction were evaluated. The effects of Rg5 on signaling pathways were determined via Western blot analysis of key proteins. In vivo, the antithrombotic efficacy was assessed using ferric chloride (FeCl3)-induced thrombosis in mice. Results:Rg5 dose-dependently inhibited collagen-induced platelet aggregation (IC50 = 42.5 μM) and selectively inhibited GPVI-mediated signaling compared to thrombin and U46619. Rg5 suppressed intracellular calcium mobilization, granule secretion, and thromboxane A2 production, with no cytotoxicity observed. Rg5 downregulated key signaling proteins (p-PI3K, p-AKT, p-cPLA2, and p-p38) while upregulating p-VASP (S157 and S239), suggesting its role in elevating cyclic nucleotide signaling. Additionally, Rg5 inhibited CD162 expression that was induced in the presence of collagen and oxidized low-density lipoprotein. It also prevented fibrinogen and fibronectin binding and significantly reduced clot retraction. In vivo, Rg5 (20 mg/kg) significantly prolonged the carotid artery occlusion time and prevented thrombus formation, outperforming aspirin (100 mg/kg). Conclusion:Ginsenoside Rg5 exhibits potent antiplatelet activity by selectively targeting GPVI-mediated platelet activation and modulating key intracellular signaling pathways. These results suggest that Rg5 could be utilized to develop safer and natural antiplatelet therapies.

BACKGROUND/AIM:Pre-mRNA processing factor 4 (PRPF4), a core protein of U4/U6 small nuclear ribonucleoproteins (snRNPs), is crucial for maintaining their structure by interacting with PRPF3 and Cyclophilin H. Beyond its role in splicing, PRPF4 has been implicated in cell survival, apoptosis, and oncogenesis. Although PRPF4 mutations have been associated with retinitis pigmentosa, its role in glioblastoma (GBM) remains unclear. This study aimed to investigate the function of PRPF4 in GBM progression and its potential as a therapeutic target. MATERIALS AND METHODS:Gene expression profiling was conducted to compare PRPF4 levels between GBM tumors and normal tissues. PRPF4 expression was also evaluated in various cancer and GBM cell lines. Stable PRPF4 knockdown cell lines were established using A172 and T98G GBM cell lines. Cellular proliferation, apoptosis, migration, and invasion were assessed through gene expression and functional assays. Additionally, molecular pathways affected by PRPF4 knockdown were examined, focusing on the p38 MAPK signaling pathway. Finally, metabolic processes in PRPF4 knockdown cells were estimated through proteomic analysis. RESULTS:PRPF4 expression was elevated in GBM. Knockdown of PRPF4 reduced cell proliferation, induced apoptosis, and suppressed migration and invasion in GBM cells. PRPF4 knockdown also suppressed MKK3/6-p38-ATF2 and RAS-MEK-ERK1/2 signaling pathways. Proteome analysis revealed disruptions in metabolic pathways, including glutathione and carbon metabolisms, which are associated with GBM progression. CONCLUSION:PRPF4 knockdown inhibits GBM progression by reducing p38 MAPK and ERK signaling cascade with metabolic alterations. Targeting PRPF4 may offer novel therapeutic strategies for GBM treatment.

Enterocytozoon hepatopenaei (EHP) is an important shrimp pathogen, causing growth retardation syndrome which leads to substantial economic losses worldwide. In this study, we examined the possibility of EHP transmission between Pacific white shrimp (Penaeus vannamei) and green mud crabs (Scylla paramamosain), a common benthic species in shrimp culture environments. Naturally infected shrimp (with EHP loads ranging from 102 to 106 copies/mu L) were used as donors for EHP transmission to EHP-free crabs and shrimp through water and sediment transfer. The recipient shrimp became EHP-positive 7 days post-exposure (dpe) (with EHP loads ranging from 101 to 104 copies/mu L). Histopathological examination confirmed EHP spores in the hepatopancreatic cells of the recipient shrimp at 7 and 14 dpe. The recipient crabs were EHP-positive after 14 dpe (EHP loads between 101 and 102 copies/mu L) and the crabs could transmit EHP back to the recipient shrimp (EHP loads ranging from 101 to 102 copies/mu L) 14 dpe via the same route. Although the crabs tested positive for EHP through PCR and qPCR, no histopathological change was observed. The present study suggests that green mud crabs may act as a mechanical vector for EHP transmission, providing information to enhance biosecurity protocols in shrimp farms to reduce the risk of EHP contamination.

The extensive distribution of microplastics (MPs) in the environment and their food chain contamination urgently necessitates a deeper understanding of their molecular-level impact on physiological responses. This study employed a mass spectrometry-based proteomics approach to investigate the potential risks, mechanisms of associated cellular processes, and biological reactions to preformed protein-MPs coronation and intact MPs using brain-derived neuronal and glial cells. Our findings indicate that MPs can adsorb proteins and form a heterogeneous corona layer when interacting with biological fluids such as serum. Proteomics analysis revealed that protein-MP coronation notably alters protein expression levels compared to intact MPs, impacting core cellular biological processes, including protein synthesis machinery and RNA processing pathways, lipid metabolism, and nuclear-cytoplasmic compartmentalization and transport. Notably, the heterogeneous protein adsorption onto MP surfaces perturbs a wide range of cellular signaling pathways through cellular recognition mechanisms, potentially contributing to the challenge of MP accumulation in the brain.

This study reports the first confirmed case of Myxobolus koi parasitic infection in koi (Cyprinus carpio koi) imported into Thailand. Infected fish exhibit clinical signs during the quarantine process, including lethargy, tachypnea, flared gill opercula and excessive mucus production in the gills. The gross pathological findings included swollen and pale gills interspersed with white nodules. Microscopic examination of gill biopsies revealed mucus clumps and numerous pyriform myxospores, with no evidence of other parasites. Molecular analysis confirmed the presence of Myxobolus spp. DNA through PCR amplification targeting the 18S SSU rRNA. Phylogenetic analysis of 776 bp sequences from our representative isolates (CU01, CU02 and CU03) revealed 100% nucleotide identity with M. koi sequences from goldfish in China (OM757920) and koi in the USA (FJ841887), which formed a distinct clade with strong bootstrap support. Haematological parameters were compared between infected and healthy fish from the same batch, revealing significantly elevated levels of creatine and ALT (p < 0.05) in the infected group. Histopathological examination revealed severe gill damage, with plasmodia infiltrating and disrupting the lamellar architecture. The well-delineated pink fibrous septa encapsulated mature myxospores and pansporoblasts. Scanning and transmission electron microscopy revealed that the M. koi spores, measuring 5.2 × 2.92 μm, were oval, elongated and pyriform, with coiled polar filaments enclosed within two polar capsules. These findings document the occurrence of M. koi in Thailand, underscore its transboundary transmission via international trade and highlight the need for enhanced biosecurity measures to mitigate the spread of aquatic pathogens.

IntroductionPhotobacterium damselae subsp. damselae (PDD) is an emerging marine bacterial pathogen that infects marine animals and humans, causing fatal necrotizing fasciitis and histamine fish poisoning. Despite its clinical and ecological importance, the microbiological and genomic characteristics of PDD remain largely unknown.MethodsWe report the first case of systemic infection caused by PDD in a free-ranging spotted seal (Phoca largha) stranded in Korea. Histopathological and microbial examinations were performed, followed by genomic analysis of the isolated PDD strain GCUPdd. Histamine production capability and cytotoxic effects on human cells were also evaluated.ResultsPDD was identified as the presumptive cause of systemic infection in the seal. Genomic analysis revealed the presence of pPHDD-like plasmid and major virulence factors including damselysin, phobalysin, and phospholipase. Strain GCUPdd harbored a gene cluster for histamine production (histidyl-tRNA synthetase, histidine decarboxylase, and histidine-histamine antiporter) and exhibited significantly higher histamine-producing ability than the reference PDD strain. The strain also demonstrated cytotoxic effects on human cells.DiscussionAlthough the pathogenic role of PDD in pinnipeds remains unclear, this study highlights its zoonotic potential and the importance of monitoring PDD in marine environments. Our findings contribute to understanding risk factors for histamine fish poisoning and provide insights into microbial diversity in marine mammals, emphasizing the need for further surveillance concerning PDD pathogenicity and role in public health.

Decapod hepandensovirus 1 (DHPV) is a viral pathogen that causes growth retardation and decreased feed conversion efficiency in penaeid shrimp. The virus exhibits high genetic variation between different hosts and geographical locations. It has been primarily reported in cultured Penaeus monodon, P. chinensis, and P. merguiensis, and a new type of DHPV has recently been reported in P. vannamei cultured in Korea and Taiwan. In this study, the genome of a recently reported new type of DHPV was fully sequenced by conventional Sanger sequencing combined with a next-generation sequencing approach. Similar to the other types of DHPVs infecting several shrimp species other than P. vannamei, a new type of DHPV contained a linear, single-stranded DNA genome of 6173 bp comprising three major open reading frames. However, by detailed comparative genome and phylogenetic analysis, the virus was not clustered with the pre-existing genotypes, suggesting the emergence of a possible novel genotype of DHPV in cultured shrimps. This study is the first to report the complete genomic sequence of DHPV identified in P. vannamei.

In this study, the primers of different protocols for the detection of White Spot Syndrome Virus (WSSV) were analyzed in silico to evaluate their potential performance in PCR. As with any biological entity, this virus evolves constantly. Thus, this analysis showed that a few primers, including those recommended by the World Organization for Animal Health (WOAH), might mismatch with some isolates of WSSV, specially with isolates more recently sequenced. Furthermore, a set of primers recommended by WOAH, showed the potential to self-dimer and form hairpin loop structures, which could affect the efficiency of PCR, resulting in an inaccurate diagnostic result. From our perspective, and considering the evolutionary trajectory of this virus, it may be time for the WOAH to update the PCR protocols recommended for WSSV detection, which remains as a highly prevalent and lethal virus.

Acute hepatopancreatic necrosis disease (AHPND) is one of the most important diseases in the global shrimp industry. The emergence of mutant AHPND-associated V. parahaemolyticus (VpAHPND) strains has raised concerns regarding potential misdiagnosis and unforeseen pathogenicity. In this study, we report the first emergence of a type II (pirA−, pirB+) natural mutant, VpAHPND (strain 20-082A3), isolated from cultured Penaeus vannamei in Korea. Phenotypic and genetic analyses revealed a close relationship between the mutant strain 20-082A3 and the virulent Korean VpAHPND strain 19-021-D1, which caused an outbreak in 2019. Detailed sequence analysis of AHPND-associated plasmids showed that plasmid pVp_20-082A3B in strain 20-082A3 was almost identical (>99.9%) to that of strain 19-021-D1. Moreover, strains 20-082A3 and 19-021-D1 exhibited the same multilocus sequence type (ST 413) and serotype (O1:Un-typeable K-serogroup), suggesting that the mutant strain is closely related to and may have originated from the virulent strain 19-021-D1. Similar to previous reports on the natural mutant VpAHPND, strain 20-082A3 did not induce AHPND-related symptoms or cause mortality in the shrimp bioassay. The emergence of a mutant strain which is almost identical to the virulent VpAHPND highlights the need for surveillance of the pathogen prevalent in Korea. Further investigations to elucidate the potential relationship between ST 413 and recent Korean VpAHPND isolates are needed.

Vibrio parahaemolyticus is a major seafood-borne zoonotic pathogen that causes gastroenteritis in humans and acute hepatopancreatic necrosis disease (AHPND) in shrimp. In this study, we isolated and characterized Vibrio phage vB_VpM-pA2SJ1, which infects clinical and AHPND-associated strains of V. parahaemolyticus. The phage genome is a linear dsDNA 51,054 bp in length with a G + C content of 43.7

Background: Platelet-leukocyte aggregates (PLAs) play important roles in cardiovascular disease and sepsis. Red ginseng extract (RGE) has been well-studied for its antiplatelet and anti-inflammatory activities. However, the potential inhibitory effects of RGE on PLA have not been investigated. Methods: Six-week-old ICR mice were given oral gavage of RGE for 7 days, followed by an intraperitoneal injection of 15 mg/kg of lipopolysaccharide. Mice were euthanized 24 h later, and blood samples were collected for further analysis. Flow cytometry was utilized to sort populations of PLAs and platelet-neutrophil aggregates (PNAs). By using confocal microscopy, PNAs were validated. Morphological changes in platelets and leukocytes were visualized with scanning electron microscopy. Expressions of tissue factor (TF) and platelet factor 4 (PF4) were investigated using enzyme-linked immunosorbent assay. Results: Populations of activated platelets, PLAs and PNAs, were significantly increased with LPS-induction. Treatment with 200 and 400 mg/kg of RGE decreased platelet activation. Moreover, the populations of PLAs and PNAs were reduced. PNAs were visible in the blood of septic mice, and this was attenuated by treatment with 400 mg/kg of RGE. Morphologically, sepsisinduced platelet activation and fibrin formation in the blood. This was reduced with RGE treatment. Sepsis-induced increase in the plasma levels of TF and PF4 was also reduced with RGE treatment. Conclusion: This study shows that RGE is a potential therapeutic that reduces the activation of platelets and targets PLA and PNA formation. Detailed inhibitory mechanisms of RGE should be studied.