Dysbiotic signatures and diagnostic potential of gut microbial markers for inflammatory bowel disease in Korean population.

Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H2S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD.

Gut microbiome therapy: fecal microbiota transplantation vs live biotherapeutic products.

The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.

Self-Assembled Skin-Penetrating Peptides with Controlled Supramolecular Properties for Enhanced Transdermal Delivery.

The use of nanocarriers decorated with penetration-enhancing agents (PEAs) is considered to be a promising approach for efficient transdermal delivery. In this study, we developed short amphiphilic skin-penetrating peptides (17 amino acids) that functioned not only as PEAs but also as building blocks of nanocarriers without the incorporation of additional macromolecules for self-assembly and guest molecule encapsulation. Interestingly, varying only two amino acids in the hydrophobic moiety of the peptides resulted in significantly different self-assembly behavior, thermal stability, protease resistance, and skin-penetration efficiency in a human skin model. The analysis of the peptide secondary structure revealed that such characteristic changes arose due to the sequence variation-mediated conformational change in the hydrophobic block. These findings hold significant promise for the development of simple and effective delivery systems exhibiting controllable supramolecular properties.

The influence of microbial dysbiosis on immunochemotherapy-related efficacy and safety in diffuse large B-cell lymphoma.

The gut microbiome influences cancer development and the efficacy and safety of chemotherapy but little is known about its effects on lymphoma. We obtained stool samples from treatment-naive, newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) (n = 189). We first performed 16S ribosomal RNA gene sequencing (n = 158) and then conducted whole-genome shotgun sequencing on additional samples (n = 106). We compared the microbiome data from these patients with data from healthy controls and assessed whether microbiome characteristics were associated with treatment outcomes. The alpha diversity was significantly lower in patients with DLBCL than in healthy controls (P < .001), and the microbial composition differed significantly between the groups (P < .001). The abundance of the Enterobacteriaceae family belonging to the Proteobacteria phylum was markedly higher in patients than in healthy controls. Functional analysis of the microbiome revealed an association with opportunistic pathogenesis through type 1 pili, biofilm formation, and antibiotics resistance. Enterobacteriaceae members were significantly enriched in patients who experienced febrile neutropenia and in those who experienced relapse or progression (P < .001). Interestingly, greater abundance of Enterobacteriaceae correlated with shorter progression-free survival (P = .007). The cytokine profiles of patients whose microbiome was enriched with Enterobacteriaceae were significantly associated with interleukin 6 (P = .035) and interferon gamma (P = .045) levels. In summary, patients with DLBCL exhibited gut microbial dysbiosis. The abundance of Enterobacteriaceae correlated with treatment outcomes and febrile neutropenia. Further study is required to elucidate the origin and role of gut dysbiosis in DLBCL.

Description of Deefgea piscis sp. nov., and Deefgea tanakiae sp. nov., isolated from the gut of Korean indigenous fish.

Three novel strains, (D17T, D13, and D25T) isolated from the gut of the Korean dark sleeper (Odontobutis platycephala), Kumgang fat minnow (Rhynchocypris kumgangensis), and the Korean oily bitterling (Tanakia koreensis) were identified as two novel species. Strains D17T and D13 showed the highest similarities in 16S rRNA gene and complete genome sequences to Deefgea rivuli WB 3.4-79T (98.0% and 97.9%, respectively, of 16S rRNA gene sequence similarity, 77.8% and 77.7%, respectively, of orthologous average nucleotide identity, OrthoANI, and 21.9% and 21.9%, respectively, of digital DNA-DNA hybridization, dDDH). Strain D17T showed the highest similarities in 16S rRNA gene and complete genome sequences to D13 (99.9% of 16S rRNA gene sequence similarity, 91.8% of OrthoANI, and 45.1% of dDDH); therefore, strains D17T and D13 were assigned as the same species. Strain D25T showed the highest similarities in 16S rRNA gene and complete genome sequences to D. chitinilytica Nsw-4T (98.2% of 16S rRNA gene sequence similarity, 82.4% of OrthoANI, and 25.1% of dDDH). Strains D17T and D13 were Gram-stain-negative, facultative anaerobes, rod-shaped, non-motile, and non-flagellated. Strain D25T was Gram-stain-negative, facultative anaerobe, rod-shaped, and motile by a single polar flagellum. These strains had C16:0 and summed feature 3 (C16:1ω7c and/or C16:1ω6c) as the major cellular fatty acids and possessed Q-8 as a major respiratory ubiquinone. All three strains contained phosphatidylethanolamine and phosphatidylglycerol as the major polar lipids. Based on polyphasic taxonomic data, strains D17T, D13, and D25T represent two novel species of the genus Deefgea. We propose the name Deefgea piscis sp. nov. for strains D17T (= KCTC 82958T = JCM 34941T) and D13 (= KCTC 92368), and Deefgea tanakiae sp. nov. for strain D25T (= KCTC 82959T = JCM 34942T).

Description of Flavobacterium cyclinae sp. nov. and Flavobacterium channae sp. nov., isolated from the intestines of Cyclina sinensis (Corb shell) and Channa argus (Northern snakehead).

Two novel bacterial strains, KSM-R2A25T and KSM-R2A30T, were isolated from intestines of Cyclina sinensis (corb shell) and Channa argus (northern snakehead), respectively. Both specimens were collected in Korea. The strains were Gramstain-negative, non-motile, and strictly aerobic. According to phylogenetic analyses based on 16S rRNA gene sequences, strains belonged to the genus Flavobacterium within the family Flavobacteriaceae. 16S rRNA gene sequences of strains KSM-R2A25T and KSM-R2A30T were closely related to Flavobacterium cucumis DSM 18830T and Flavobacterium aquaticum JC164T with sequence similarities of 97.77% and 98.54%, respectively. Further genomic analyses including reconstruction of the UBCG tree and overall genome-related indices suggested them as novel species of the genus Flavobacterium. Both strains contained menaquinone with six isoprene units (MK-6) as a major isoprenoid quinone and iso-C15:1 G, iso-C15:0 and iso-C16:0 as major cellular fatty acids. The major polar lipid in both strains was phosphatidylethanolamine. The genomic G + C contents of strains KSM-R2A25T and KSM-R2A30T were 31.7 and 31.9%, respectively. Based on the polyphasic taxonomic study presented here, strains KSM-R2A25T and KSM-R2A30T represent novel species of the genus Flavobacterium, for which the names Flavobacterium cyclinae sp. nov and Flavobacterium channae sp. nov are proposed. The type strains of F. cyclinae sp. nov and F. channae sp. nov are KSM-R2A25T (= KCTC 82978T = JCM 34997T) and KSM-R2A30T (= KCTC 82979T = JCM 34998T), respectively.

Anaerostipes hominis sp. nov., a novel butyrate-producing bacteria isolated from faeces of a patient with Crohn's disease.

Cultivation and isolation of gut bacteria are necessary for understanding their role in the intestinal ecosystem. We isolated a novel bacterium, designated strain BG01T, from the faeces of a patient with Crohn's disease. Strain BG01T was a strictly anaerobic, rod-shaped, Gram-variable and endospore-forming bacterium. Strain BG01T possessed C12 : 0, C18 : 0 dimethyl aldehyde (DMA) and C18 : 1 ω9c DMA as predominant cellular fatty acids and meso-diaminopimelic acid as a diagnostic diamino acid. Strain BG01T grew at 15-45 °C (optimum, 37 °C), with 0-4 % (w/v) NaCl (optimum, 0-1 %), at pH 6-10 (optimum, pH 7) and was resistant to bile salt, but not to ampicillin, metronidazole, vancomycin and cefoperazone. Butyrate, propionate, oxalacetate and fumarate were produced as fermentation end products from Gifu anaerobic medium broth. Strain BG01T showed 97.7 % 16S rRNA gene sequence similarity, and 92.0 and 48.5 % of average nucleotide identity and digital DNA-DNA hybridization values, respectively, with Anaerostipes caccae KCTC 15019T. Genomic analysis indicated that strain BG01T had a butyrate-producing pathway. The genomic G+C content of the strain was 43.5 mol%. Results of the phenotypic, phylogenetic and genotypic analyses indicated that strain BG01T represents a novel butyrate-producing species of the genus Anaerostipes, for which the name Anaerostipes hominis sp. nov. is proposed. The type strain is BG01T (=KCTC 15617T=JCM 32275T).

Description of Ornithinimicrobium ciconiae sp. nov., and Ornithinimicrobium avium sp. nov., isolated from the faeces of the endangered and near-threatened birds.

Phenotypic and genomic analyses were performed to characterize two novel species, H23M54T and AMA3305T, isolated from the faeces of the Oriental stork (Ciconia boyciana) and the cinereous vulture (Aegypius monachus), respectively. Strains H23M54T and AMA3305T showed the highest similarities of 16S rRNA gene sequences and complete genome sequences with Ornithinimicrobium cavernae CFH 30183T (98.5% of 16S rRNA gene sequence similarity and 82.1% of average nucleotide identity, ANI) and O. pekingense DSM 21552T (98.5% of 16S rRNA gene sequence similarity and 82.3% of ANI), respectively. Both strains were Gram-stain-positive, obligate aerobes, non-motile, non-spore-forming, and coccoid- and rodshaped. Strain H23M54T grew optimally at 25-30°C and pH 8.0 and in the presence of 1.5-2% (wt/vol) NaCl, while strain AMA3305T grew optimally at 30°C and pH 7.0 and in the presence of 1-3% (wt/vol) NaCl. Both strains had iso-C15:0, iso-C16:0, and summed feature 9 (iso-C17:1ω9c and/or C16:0 10-methyl) as major cellular fatty acids. MK-8 (H4) was identified as the primary respiratory quinone in both strains. Strains H23M54T and AMA3305T possessed diphosphatidylglycerol and phosphatidylglycerol as major polar lipids. Moreover, strains H23M54T and AMA3305T commonly contained ribose and glucose as major sugars and L-ornithine, L-alanine, glycine, and aspartic acid as major amino acids. The polyphasic taxonomic data indicate that strains H23M54T and AMA3305T represent novel species of the genus Ornithinimicrobium. We propose the names Ornithinimicrobium ciconiae sp. nov. and Ornithinimicrobium avium sp. nov. for strains H23M54T (= KCTC 49151T = JCM 33221T) and AMA3305T (= KCTC 49180T = JCM 32873T), respectively.

Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.

Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.

Description of Nocardioides piscis sp. nov., Sphingomonas piscis sp. nov. and Sphingomonas sinipercae sp. nov., isolated from the intestine of fish species Odontobutis interrupta (Korean spotted sleeper) and Siniperca scherzeri (leopard mandarin fish).

A polyphasic taxonomic approach was used to characterize three novel bacterial strains, designated as HDW12AT, HDW-15BT, and HDW15CT, isolated from the intestine of fish species Odontobutis interrupta or Siniperca scherzeri. All isolates were obligate aerobic, non-motile bacteria, and grew optimally at 30°C. Phylogenetic analysis based on 16S rRNA sequences revealed that strain HDW12AT was a member of the genus Nocardioides, and closely related to Nocardioides allogilvus CFH 30205T (98.9% sequence identities). Furthermore, strains HDW15BT and HDW15CT were members of the genus Sphingomonas, and closely related to Sphingomonas lutea JS5T and Sphingomonas sediminicola Dae 20T (97.1% and 97.9% sequence identities), respectively. Strain HDW12AT contained MK-8 (H4), and strains HDW15BT and HDW15CT contained Q-10 as the respiratory quinone. Major polar lipid components of strain HDW12AT were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylinositol, and those of strains HDW15BT and HDW15CT were sphingoglycolipid, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine. The G + C content of strains HDW12AT, HDW15BT, and HDW15CT were 69.7, 63.3, and 65.5%, respectively. The results of phylogenetic, phenotypic, chemotaxonomic, and genotypic analyses suggest that strain HDW12AT represents a novel species within the genus Nocardioides, and strains HDW15BT and HDW15CT represent two novel species within the genus Sphingomonas. We propose the names Nocardioides piscis for strain HDW12AT (= KACC 21336T = KCTC 49321T = JCM 33670T), Sphingomonas piscis for strain HDW15BT (= KACC 21341T = KCTC 72588T = JCM 33738T), and Sphingomonas sinipercae for strain HDW15CT (= KACC 21342T = KCTC 72589T = JCM 33739T).

Brevilactibacter coleopterorum sp. nov., isolated from the intestine of the dark diving beetle Hydrophilus acuminatus, and Weissella coleopterorum sp. nov., isolated from the intestine of the diving beetle Cybister lewisianus.

A polyphasic taxonomic approach was used to characterize two novel bacterial strains, designated as HDW11T and HDW19T, isolated from intestine samples of the dark diving beetle Hydrophilus acuminatus and the diving beetle Cybister lewisianus, respectively. Both isolates were Gram-stain-positive, facultatively anaerobic and non-motile. Strain HDW11T grew optimally at 30 °C, pH 8 and in the presence of 1% (w/v) NaCl. Strain HDW19T grew optimally at 25 °C, pH 7 and in the presence of 0.3% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences and genome sequences revealed that strain HDW11T is a member of the genus Brevilactibacter and is closely related to Brevilactibacter flavus VG341T [with 97.9% 16S rRNA sequence identity and 79.1% average nucleotide identity (ANI)], and that strain HDW19T belongs to the genus Weissella and is closely related to W. koreensis KCTC 3621T (with 98.9% 16S rRNA sequence identity and 79.5% ANI). The major cellular fatty acids of strains HDW11T and HDW19T were C18:1 ω9c and anteiso-C15:0, respectively. The sole respiratory quinone of strain HDW11T was MK-9 (H4). The major polar lipid components of strain HDW11T were diphosphatidylglycerol and phosphatidylglycerol, and the major polar lipid component of strain HDW19T was diphosphatidylglycerol. The genomic DNA G+C content of strains HDW11T and HDW19T were 72.1 and 37.2 mol%, respectively. The results of phylogenetic, phenotypic, chemotaxonomic and genotypic analyses suggest that strain HDW11T represents a novel species within the genus Brevilactibacter, and that strain HDW19T represents a novel species within the genus Weissella. We propose the name Brevilactibacter coleopterorum sp. nov. for strain HDW11T (=KACC 21335T=KCTC 49320T=JCM 33680T) and the name Weissella coleopterorum for strain HDW19T (=KACC 21347T=KCTC 43114T=JCM 33684T).

Tessaracoccus coleopterorum sp. nov., isolated from the intestine of the dark diving beetle, Hydrophilus acuminatus.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated as strain HDW20T, isolated from the intestine of the dark diving beetle Hydrophilus acuminatus. The isolate was Gram-stain-positive, facultatively anaerobic, non-motile, coccus-shaped, and formed pale orange colonies. Phylogenetic analysis based on 16S rRNA gene sequences and genome sequences showed that the isolate belonged to the genus Tessaracoccus in the phylum Actinobacteria and was closely related to T. flavescens SST-39T, T. defluvii JCM 17540T, and T. aquimaris NSG39T, with the highest 16S rRNA gene sequence similarity of 98.5 % and a highest average nucleotide identity (ANI) value of 80.6 %. The major cellular fatty acids were C18 : 1 ω9c and anteiso-C15 : 0. The main respiratory quinone was MK-9 (H4). The major polar lipid components were phosphatidylglycerol and diphosphatidylglycerol. The genomic DNA G+C content was 69.0 %. The isolate contains ʟʟ-diaminopimelic acid, ʟ-alanine, and ʟ-lysine as amino acid components, and ribose, glucose, and galactose as sugar components of the cell wall peptidoglycan. The results of phylogenetic, phenotypic, chemotaxonomic, and genotypic analyses suggested that strain HDW20T represents a novel species within the genus Tessaracoccus. We propose the name Tessaracoccus coleopterorum sp. nov. The type strain is HDW20T (=KACC 21348T=KCTC 49324T=JCM 33674T).

The German National Registry of Primary Immunodeficiencies (2012-2017).

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.

Pseudorhodobacter turbinis sp. nov., isolated from the gut of the Korean turban shell, Turbo cornutus.

A novel Gram-stain-negative, coccus-shaped, aerobic and motile bacterial strain, designated S12M18T, was isolated from the gut of the Korean turban shell, Turbo cornutus. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S12M18T belonged to the genus Pseudorhodobacter and had the highest 16S rRNA gene sequence similarity twith Pseudorhodobacter aquimaris HDW-19T (98.63 %). The phylogenomic tree congruently verified that strain S12M18T occupies a taxonomic position within the genus Pseudorhodobacter. The OrthoANIu value between strain S12M18T and P. aquimaris HDW-19T was 87.22 %. The major cellular fatty acid of strain S12M18T was summed feature 8 (C18 : 1 ω7c or C18 : 1 ω6c). The major components of the polar lipids were phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The predominant isoprenoid quinone was Q-10. The DNA G＋C content was 57.8 mol%. The polyphasic analyses indicated that strain S12M18T represents a novel species of the genus Pseudorhodobacter, for which the name Pseudorhodobacter turbinis sp. nov. is proposed. The type strain is S12M18T (=KCTC 62742T=JCM 33168T).

Synergistic effects of alkylated graphene oxide on the properties of polypropylene-based carbon nanocomposites.

Polypropylene (PP)/carbon black (CB)-alkylated graphene oxide (AGO) hybrid nanocomposites were prepared via solution process and the synergistic effects of AGO on the properties of the PP/CB nanocomposites were investigated. AGO at a content of only 0.2 wt% formed an overlapped network structure in the PP matrix and affected the electrical, thermal and mechanical properties of the PP/CB nanocomposites. Specifically, PP/CB (5 wt%)-AGO (0.2 wt%) nanocomposites exhibited an electrical percolation threshold at lower CB contents than the PP/CB nanocomposites did, and the sheet resistance was decreased to 2.3 x 10(7) omega/sq. The thermal degradation temperature and recrystallization temperature of the PP/CB (10 wt%) nanocomposites were increased by 11.3 and 1.6 degrees C, respectively, by the addition of 0.2 wt% AGO. In addition, the Young's modulus of the PP/CB (10 wt%) nanocomposite was increased from 438.1 to 540.1 MPa.

The immune cell infiltrate populating meningiomas is composed of mature, antigen-experienced T and B cells.

BACKGROUND: Meningiomas often harbor an immune cell infiltrate that can include substantial numbers of T and B cells. However, their phenotype and characteristics remain undefined. To gain a deeper understanding of the T and B cell repertoire in this tumor, we characterized the immune infiltrate of 28 resected meningiomas representing all grades. METHODS: Immunohistochemistry was used to grossly characterize and enumerate infiltrating lymphocytes. A molecular analysis of the immunoglobulin variable region of tumor-infiltrating B cells was used to characterize their antigen experience. Flow cytometry of fresh tissue homogenate and paired peripheral blood lymphocytes was used to identify T cell phenotypes and characterize the T cell repertoire. RESULTS: A conspicuous B and T cell infiltrate, primarily clustered in perivascular spaces, was present in the microenvironment of most tumors examined. Characterization of 294 tumor-infiltrating B cells revealed clear evidence of antigen experience, in that the cardinal features of an antigen-driven B cell response were present. Meningiomas harbored populations of antigen-experienced CD4+ and CD8+ memory/effector T cells, regulatory T cells, and T cells expressing the immune checkpoint molecules PD-1 and Tim-3, indicative of exhaustion. All of these phenotypes were considerably enriched relative to their frequency in the circulation. The T cell repertoire in the tumor microenvironment included populations that were not reflected in paired peripheral blood. CONCLUSION: The tumor microenvironment of meningiomas often includes postgerminal center B cell populations. These tumors invariably include a selected, antigen-experienced, effector T cell population enriched by those that express markers of an exhausted phenotype.

Effects of carbon black-carbon nanotube complex fillers on the properties of isotactic polypropylene nanocomposites.

In this study, the reinforcing effects of carbon black (CB) and carbon nanotube (CNT) complex fillers on the properties of isotactic polypropylene (iPP) nanocomposites were investigated using various methods. The surface of the CNTs was modified using a linear alkyl chain in order to create a homogeneous CNT dispersion in the iPP matrix. When the CB content that was incorporated in the iPP matrix increased, the thermal and mechanical properties of the iPP/CB nanocomposites were enhanced. Additionally these enhancements in the properties were similarly induced by introducing a small amount of alkylated CNTs (a-CNTs). In contrast, the CB/a-CNT complex filler was more effective for the iPP nanocomposites than the CB or a-CNT single filler in terms of the thermal stability and the electrical properties. However, the mechanical properties of the CB/a-CNT complex filler incorporated iPP nanocomposites were poorer than the only a-CNT incorporated iPP nanocomposites. Additionally, the complex filler did not overcome the nucleation behavior of the a-CNTs in the re-crystallization of iPP.

The Anti-inflammatory Effects of Water Extract from Cordyceps militaris in Murine Macrophage.

The aim of this study was to determine the in vitro anti-inflammatory effect of hot water extract from Cordyceps militaris fruiting bodies (CMWE) on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release in RAW 264.7 cells. The treatment of macrophages with various concentrations of hot CMWE significantly reduced LPS-induced production as well as NO, TNF-α and IL-6 secretion in a concentration-dependent manner. These results suggest that CMWE have potent inhibitory effects on the production of these inflammatory mediators.

Effect of water-soluble proteoglycan isolated from Agaricus blazei on the maturation of murine bone marrow-derived dendritic cells.

Water-soluble proteoglycan (WSPG) of Agaricus blazei Murill has been known to stimulate the non-specific complements and humoral immune functions to act as polyclonal activators of B cells and to inhibit tumor growth and metastasis. However, little is known about its immunomodulating effects on murine bone marrow (BM)-derived dendritic cells (DC). In the present study, we examined the maturation process of murine BM-DC. BM cells were cultured in the presence of IL-4 and GM-CSF and the generated immature DC were stimulated with WSPG or LPS (WSPG-DC and LPS-DC, respectively) for 24 h. WSPG significantly enhanced the expression of co-stimulatory molecules (CD80 and CD86) and major histocompatibility complex (MHC) II, as did LPS. IL-12p70 production in WSPG-DC was also identical to that in LPS-DC. The antigen-uptake capacity of WSPG-DC was determined by FITC-labeled dextran uptake. WSPG-DC lost dextran uptake capacity comparable to LPS-DC. The antigen-presenting capacity of WSPG-DC as analyzed by allogeneic T cell proliferation was significantly increased in comparison with immature DC, was identical to LPS-DC, and induced higher levels of IL-2 in responding T cells. These results indicate the immunomodulatory properties of WSPG, which might be therapeutically useful in the control of cancers and immunodeficient diseases through the up-regulation of DC maturation.

Growth inhibition of U937 leukemia cells by aqueous extract of Cordyceps militaris through induction of apoptosis.

Cordyceps militaris is a traditional herbal ingredient, which has been used for patients suffering from cancer in Oriental medicine. In the present study, we investigated the biochemical mechanisms of anti-proliferative effects by aqueous extract of C. militaris (AECM) in human leukemia U937 cells. It was found that AECM could inhibit cell growth of U937 cells in a dose-dependent manner, which was associated with morphological change and apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. We observed the down-regulation of anti-apoptotic Bcl-2 expression and proteolytic activation of caspase-3 in AECM-treated U937 cells. However, AECM did not affect the pro-apoptotic Bax expression and activity of caspase-9. Furthermore, Western blotting and RT-PCR revealed that AECM treatment caused a dose-dependent inhibition of cyclooxygenase-2 and prostaglandin E2 accumulation. Taken together, these results indicated that the anti-proliferative effects of AECM were associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease activity, and AECM may have therapeutic potential in human leukemia treatment.