Engineered CpG-Loaded Nanorobots Drive Autophagy-Mediated Immunity for TLR9-Positive Cancer Therapy.

Smart nanorobots have emerged as novel drug delivery platforms in nanomedicine, potentially improving anti-cancer efficacy and reducing side effects. In this study, an intelligent tumor microenvironment-responsive nanorobot is developed that effectively delivers CpG payloads to Toll-like receptor 9 (TLR9)-positive tumors to induce autophagy-mediated cell death for immunotherapy. The nanorobots are fabricated by co-self-assembly of two amphiphilic triblock polymer peptides: one containing the matrix metallopeptidase 2 (MMP2)-cleaved GPLGVRGS motif to control the mechanical opening of the nanorobots and provide targeting capability for TLR-9-positive tumors and the other consisting of an arginine-rich GRRRDRGRS sequence that can condense nuclear acid payloads through electrostatic interactions. Using multiple tumor-bearing mouse models, it is investigated whether the intravenous injection of CpG-loaded nanorobots could effectively deliver CpG payloads to TLR-9-positive tumors and elicit anti-tumor immunity through TLR9 signaling and autophagy. Therefore, besides being a commonly used adjuvant for tumor vaccination, CpG-loaded nanorobots can effectively reprogram the tumor immunosuppressive microenvironment and suppress tumor growth and recurrence. This nanorobot-based CpG immunotherapy can be considered a feasible approach to induce anti-tumor immunity, showing great therapeutic potential for the future treatment of TLR9-positive cancers.

The clinical progress and challenges of mRNA vaccines.

Owing to the breakthroughs in the prevention and control of the COVID-19 pandemic, messenger RNA (mRNA)-based vaccines have emerged as promising alternatives to conventional vaccine approaches for infectious disease prevention and anticancer treatments. Advantages of mRNA vaccines include flexibility in designing and manipulating antigens of interest, scalability in rapid response to new variants, ability to induce both humoral and cell-mediated immune responses, and ease of industrialization. This review article presents the latest advances and innovations in mRNA-based vaccines and their clinical translations in the prevention and treatment of infectious diseases or cancers. We also highlight various nanoparticle delivery platforms that contribute to their success in clinical translation. Current challenges related to mRNA immunogenicity, stability, and in vivo delivery and the strategies for addressing them are also discussed. Finally, we provide our perspectives on future considerations and opportunities for applying mRNA vaccines to fight against major infectious diseases and cancers. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

B7-H3 but not PD-L1 is involved in the antitumor effects of Dihydroartemisinin in non-small cell lung cancer.

Dihydroartemisinin (DHA), an active antimalaria metabolite derived from artemisinin, has received increasing attention for its anticancer activities. However, little is known about the anticancer mechanisms of DHA, although the existing data define its antimalaria effects by producing excessive reactive oxygen species (ROS). In this study, we showed that DHA effectively suppresses in vitro and in vivo tumor growth of non-small cell lung cancer (NSCLC) without perceptible toxicity on heart, liver, spleen, lung, and kidney tissues. Of note, DHA inhibited the expression of B7-H3 rather than PD-L1, whereas overexpression of B7-H3 completely rescued DHA's inhibition on cell proliferation and migration of NSCLC A549 and HCC827 cells. B7-H3 overexpression also largely inhibited DHA's induction on the apoptosis of the two cell lines. Furthermore, DHA treatment led to increased infiltration of CD8+ T Lymphocytes in the xenografts as compared with that of negative controls. Taken together, our results suggest that B7-H3 but not PD-L1 is involved in the antitumor effects of DHA in NSCLC, which may be indicative of an effective B7-H3 blockade and further combination with anti-PD-L1/PD-1 immunotherapy.

Research Progress of PARP Inhibitor Monotherapy and Combination Therapy for Endometrial Cancer.

Endometrial cancer is one of the three most common malignant tumors in the female reproductive system. Advanced and recurrent endometrial cancers have poor prognoses and lack effective treatments. Poly (ADP-ribose) polymerase (PARP) inhibitors have been applied to many different types of tumors, and they can selectively kill tumor cells that are defective in homologous recombination repair. Endometrial cancer is characterized by mutations in homologous recombination repair genes; accordingly, PARP inhibitors have achieved positive results in off-label treatments of endometrial cancer cases. Clinical trials of PARP inhibitors as monotherapies and within combination therapies for endometrial cancer are ongoing. For this review, we searched PubMed with "endometrial cancer" and "PARP inhibitor" as keywords, and we used "olaparib", "rucaparib", "niraparib" and "talazoparib" as search terms in clinicaltrials.gov for ongoing trials. The literature search ended in October 2020, and only English-language publications were selected. Multiple studies confirm that PARP inhibitors play an important role in killing tumor cells with defects in homologous recombination repair. Its combination with immune checkpoint inhibitors, PI3K/AKT/mTOR pathway inhibitors, cell cycle checkpoint inhibitors, and other drugs can improve the treatment of endometrial cancer.

Formation and Antioxidant Activity of Maillard Reaction Products Derived from Different Sugar-amino Acid Aqueous Model Systems of Sesame Roasting.

This investigation was carried out to offer insight into the formation and antioxidant activity of Maillard reaction products (MRPs) derived from various sugar-amino acid model systems active in the roasting of sesame seeds. Reducing sugars (glucose, fructose, and xylose) and amino acids (serine, cystine, arginine, and lysine) present in sesame seeds were used to prepare the MRPs at various reaction times, and then the effect of reaction time on the MRPs derived from the various model systems was investigated. Within the first 15 min, the amounts of free amino groups decreased around 40% remaining amino groups of Lys-sugar model and around 75% remaining amino groups of Arg-sugar model. Results indicated that reducing sugar and free amino groups decreased obviously in Lys- and Arg-model systems. Based on correlation coefficient of antioxidant activities assessment and MRP formation in the Lys- and Arg-model systems above 0.978 and an extremely significant correlation in Pearson test exists, a conclusion could be made that these model systems are critical contributing factors in MRP formation during the roasting of sesame seeds. These findings offer insight into the formation and antioxidation of MRPs during the sesame seeds roasting.

Improvement of the oxidative stability of cold-pressed sesame oil using products from the Maillard reaction of sesame enzymatically hydrolyzed protein and reducing sugars.

BACKGROUND: In recent years, cold-pressed oils have become more and more popular with consumers. However, their oxidative stability is low. Improving the oxidative stability of cold-pressed oils will increase their shelf life. Maillard reaction products (MRPs) have been shown to promote the oxidative stability of lipids. In this study, products from the Maillard reaction of reducing sugars and sesame enzymatically hydrolyzed protein (SEHP) were added to cold-pressed sesame oils to improve their oxidative stability. RESULTS: Three types of MRPs from reducing sugars (xylose, fructose, and glucose) and SEHP were prepared. Xylose-SEHP MRPs prepared under optimum conditions had the highest antioxidant activities among the three. The optimum conditions for xylose-SEHP were as follows: reaction temperature, 130 °C; reaction time, 180 min; pH, 6.5; and sugar/protein ratio, 10:1. The addition of xylose-SEHP MRPs at a level of 20 g kg-1 could significantly improve the oxidative stability of cold-pressed sesame oil. Besides, the addition of MRPs reduced the loss of tocopherol. The interaction of MRPs with endogenous antioxidants in the sesame oil (sesamol and tocopherol) was proved by comparison with lard. There was a synergistic increase in antioxidant activity for the combination of MRPs and sesamol and the combination of MRPs and tocopherol. CONCLUSIONS: The results provide evidence that adding certain MRPs can improve the oxidative stability of cold-pressed sesame oil. © 2019 Society of Chemical Industry.

Salinibius halmophilus gen. nov., sp. nov., isolated from a marine solar saltern.

A novel Gram-stain-negative, facultatively anaerobic, flagellated and spiral-shaped bacterium, designated WDS2A16AT was isolated from a marine solar saltern in Weihai, PR China. Growth was observed at 20-40 °C (optimal 33-37 °C), 1-15 % (w/v) NaCl (optimal 3-4 %) and pH 6.0-9.0 (optimal pH 7.5). Major cellular fatty acids (>10 %) were C18 : 1ω7c and C16 : 0. Phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid were detected as the predominant polar lipids. The sole respiratory quinone was Q-8. The DNA G+C content of strain WDS2A16AT was 48.5 mol%. The 16S rRNA gene sequence similarities of WDS2A16AT with other species were less than 91 %. The average nucleotide identity, in silico DNA-DNA hybridization and amino acid identity of strain WDS2A16AT with the most related strain Gynuella sunshinyii YC6258 T were 66.1, 19.3 and 48.1 %, respectively. Comparative analysis of 16S rRNA gene sequences and phenotypic characterization indicated that strain WDS2A16AT represents a novel species in a new genus, for which the name Salinibius halmophilus gen. nov., sp. nov. is proposed. The type strain is WDS2A16AT (=KCTC 52225T=MCCC 1H00139T).

Oceaniglobus ichthyenteri sp. nov., isolated from the gut microflora of sea bass (Dicentrarchus labrax L.) and emended description of the genus Oceaniglobus.

A Gram-stain-negative, non-flagellated, catalase-positive, oxidase-positive bacterial strain, designated YLY08T, was isolated from the gut microflora of sea bass (Dicentrarchus labrax L.) collected from the coast of Yuanyao Wharf, Weihai, PR China, and subjected to a polyphasic taxonomic study. Strain YLY08T grew optimally at 28-30 °C, at pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. Poly-ß-hydroxybutyrate granules were produced. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences revealed that strain YLY08T clustered with the type strain of Oceaniglobus indicus, with which it exhibited 95.3 % sequence similarity, while the similarity to other genera was below 95.0 %. Genomic analyses, including average nucleotide identity and the digital DNA-DNA hybridization, clearly separated YLY08T from O. indicus MCCC 1A11863T with values below the thresholds for species delineation. The major cellular fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The sole respiratory quinone detected was Q-10. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidyldimethylethanolamine, diphosphatidylglycerol, one unidentified aminolipid and one unidentified phospholipid. The genome of strain YLY08T, with 38 assembled contigs, was 3.9 Mb long with a G+C content of 59.0 mol%. The results of the phenotypical, phylogenetic and biochemical analyses between the strain YLY08T and the related type strain indicated that this strain represents a novel species in genus Oceaniglobus within the family Rhodobacteraceae, for which the name Oceaniglobus ichthyenteri sp. nov. is proposed. The type strain is YLY08T (=MCCC 1H00318T=KCTC 62182T).

A rare solitary duodenum plasmacytoma.

Multiple myeloma (MM) is typical of uncontrolled and clonal growth of malignant plasma cells in the bone marrow, then leads to primary symptoms related to bone narrow infiltration and destruction bone lesion. The term of extramedullary plasmacytoma is used to defined malignant plasma cells are found out of the bone marrow. In this study, we reported a rare duodenum plasmacytoma accompanied by gastrointestinal symptoms.

Bioinformatics analysis suggests that COL4A1 may play an important role in gastric carcinoma recurrence.

OBJECTIVE: Cancer recurrence is a complicated problem for clinicians that contributes to poor prognosis. This study aimed to use advanced gastric carcinoma genes profiles to predict increased risk of cancer recurrence in order to identify patients in need of adjuvant therapy for prognosis improvement. METHODS: Differentially expressed genes were identified for advanced gastric carcinoma by analyzing the GSE2685 from the Gene Expression Omnibus database (GEO) using R package. The candidate genes were then obtained by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction analysis and survival analysis. Logistic regression analysis was performed to determine the relationship between candidate genes and the recurrence of gastric carcinoma. RESULTS: Collagen type IV alpha 1 (COL4A1) was overexpressed in gastric carcinoma tissue by analyzing the GSE2685 gene expression profiles from the Gene Expression Omnibus database. COL4A1 was also overexpressed in gastric carcinoma tissue from the Cancer Genome Atlas dataset and further determined that higher COL4A1 expression led to poorer overall survival. A univariate analysis suggested that COL4A1 was strongly correlated with T stage and gastric carcinoma recurrence (P = 0.014 and 0.041, respectively). Moreover, a multiple logistic regression analysis indicated that COL4A1 was significantly associated with gastric carcinoma recurrence (hazard ratio 1.605, 95% confidence interval 1.063-2.677, P = 0.008). CONCLUSIONS: COL4A1 may promote gastric carcinoma recurrence and could be used as a therapeutic target for gastric carcinoma recurrence.

Vibrio albus sp. nov., isolated from marine sediment.

A Gram-stain-negative, facultative anaerobic, motile, slightly bent rod-shaped bacterium, designated strain E4404T, was isolated from coastal sediment sampled Weihai, China. According to phylogenetic analysis based on its 16S rRNA gene sequence, strain E4404T shared the highest similarity with the type strain of Vibriovariabilis (97.0 %), followed by the type strains of Vibriomaritimus (96.1 %) and Vibrioeuropaeus (96.0 %). Multilocus sequence analysis based on the 16S rRNA gene and eight housekeeping genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA) showed that strain E4404T formed a unique clade in the genus Vibrio. The average nucleotide identity and digital DNA-DNA hybridization values between strain E4404T and some other species in the genus Vibrio were 71.0-72.7 % and 20.4-22.4 %, respectively. Cells grew at 15-37 °C and pH 6.0-8.5 in the presence of 1.0-6.0 % (w/v) NaCl, with optimal growth at 33 °C and pH 7.0-7.5 in the presence of 3.0-3.5 % (w/v) NaCl. No growth was observed on thiosulfate citrate bile salts sucrose medium. The major fatty acids of strain E4404T were summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), C16 : 0 and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The genomic DNA G+C content of strain E4404T was 46.1 mol%. Based on the phylogenetic, genotypic, phenotypic, biochemical and chemotaxonomic characteristics, strain E4404T represented a novel species of the genus Vibrio, for which the name Vibrioalbus sp. nov. is proposed. The type strain is E4404T (=MCCC 1H00197T=KCTC 52890T).

Coraliomargarita sinensis sp. nov., isolated from a marine solar saltern.

A Gram-stain negative, spherical, obligately aerobic bacterium, designated strain WN38T, was isolated from a marine solar saltern on the coast of Weihai, China. Optimal growth occurred at 33 °C, pH 7.0-7.5 and in the presence of 3-4 % (w/v) NaCl. The genome of strain WN38T was found to contain the genes necessary for arsenate reductase and related proteins, indicating that it may have potential in bioremediation of heavy metal polluted environments. Comparative 16S rRNA gene sequence analysis showed that strain WN38T represented a member of the genus Coraliomargarita, and was related most closely to Coraliomargarita akajimensis KCTC 12865T (95.7 %). Pairwise sequence similarities to all other type strains of species were below 90 %. Genome-based calculations (average nucleotide identity, genome-to-genome distance and DNA G+C percentage) and results of pairwise amino acid identity (AAI >60 %) and percentage of conserved proteins (POCP >50 %) also indicated clearly that strain WN38T represents a novel species within this genus. Different phenotypic analyses, such as the detection of a quinone system composed of the sole respiratory quinone was menaquinone-7 (MK-7) and a fatty acid profile with iso-C14 : 0, C18 : 0 and C18 : 1ω9c as major components, supported this finding at the same time as contributing to a comprehensive characterization of strain WN38T. On the basis of its phenotypic and genotypic properties, strain WN38T represents a novel species of the genus Coraliomargarita, for which the name Coraliomargaritasinensis sp. nov. is proposed. The type strain is WN38T (=KCTC 62602T=MCCC 1H00313T).

Primorskyibacter marinus sp. nov., isolated from coastal sediment.

A novel Gram-stain-negative, whitish-yellow, rod-shaped, non-pigmented, aerobic, oxidase-positive and catalase-positive bacterium, designated PX7T, was isolated from coastal sediment of Xiaoshi Island, Weihai, China (37° 31' 36″ N, 122° 00' 58″ E). Strain PX7T grew optimally at 30 °C, at pH 7.0-7.5 and in the presence of 3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain PX7T formed a robust clade with members of the genus Primorskyibacter and was closely related to Primorskyibacter sedentarius, Primorskyibacter aestuariivivens and Primorskyibacter insulae with 96.5, 96.2 and 95.1 % sequence similarities, respectively. The sole respiratory quinone of strain PX7T was ubiquinone-10, and the dominant fatty acid was C18 : 1ω7c (80.2 %). The major polar lipids were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid, one unidentified phospholipid and one unidentified lipid. The DNA G+C content of strain PX7T was 60.2 mol%. Based on the combination of phylogenetic analyses, phenotypic and chemotaxonomic data, strain PX7T is considered to represent a novel species within the genus Primorskyibacter in the family Rhodobacteraceae, for which the name Primorskyibacter marinus sp. nov. is proposed. The type strain of the new species is PX7T (=KCTC 42952T=MCCC 1H00196T).

Aquimarina sediminis sp. nov., isolated from coastal sediment.

A strictly aerobic, Gram-stain negative, long rod-shaped, motile by gliding and yellow pigmented bacterium, designated strain w01T, was isolated from marine sediment. The strain was characterised to determine its taxonomic position by using a polyphasic approach. Strain w01T was observed to grow optimally in the presence of 3.0% (w/v) NaCl, at 30 °C and to hydrolyse Tweens 20, 40 and 80, starch, casein and alginate. Carotenoid pigments were found to be produced but not flexirubin-type pigments. On the basis of 16S rRNA gene sequence similarities, strain w01T is phylogenetically affiliated with the genus Aquimarina and is closely related to Aquimarina macrocephali JCM 15542T (97.4% sequence similarity) and Aquimarina muelleri KCTC 12285T (97.0%). Lower sequence similarities (< 97.0%) were found with the other currently recognised members of the genus Aquimarina. The predominant fatty acids were identified as iso-C15:0 (33.7%), C18:0 3-OH (16.8%) and C17:1ω7c (10.6%). The polar lipid profile was found to contain phosphatidylethanolamine, an unidentified aminolipid and two unidentified polar lipids. MK-6 was identified as the sole respiratory quinone. The G + C content of the genomic DNA was determined to be 33.3 mol%. Strain w01T can be differentiated genotypically and phenotypically from recognised species of the genus Aquimarina. The isolate is therefore concluded to represent a novel species, for which the name Aquimarina sediminis sp. nov. is proposed, with the type strain w01T (= KCTC 62350T = MCCC 1H00287T).

Roseovarius salinarum sp. nov., isolated from a marine solar saltern.

A Gram-stain-negative, rod-shaped, non-motile and halophilic bacterium, designated N53T, was isolated from a marine solar saltern in Wendeng, China. Cells of strain N53T were 0.3-0.4 µm wide and 2.0-5.5 µm long, catalase-positive and oxidase-positive. The bacterium grew optimally at 33 °C, at pH 7.0-8.0 and in the presence of 6.0 % (w/v) NaCl. Bacteriochlorophyll a was not found. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain N53T formed a phylogenetic lineage with members of the genus Roseovarius. Strain N53T exhibited the highest levels of similarity to Roseovarius pacificus (94.6 %) and Roseovarius confluentis (94.6 %), with a lower level to Roseovarius tolerans was 94.0 %. The percentage of conserved proteins and average nucleotide identity values between N53T and the type strain of the type species, Roseovarius tolerans, were 66.1 and 76.4 %, respectively. The genomic DNA G+C content was 68.1 mol%. The sole respiratory quinone was ubiquinone-10. The predominant cellular fatty acids (>10 %) were C18 : 1ω7c (54.0 %) and C16 : 0 (17.9 %). The polar lipids of strain N53T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, two unidentified phospholipids and two unidentified glycolipids. The differential phenotypic properties, together with the chemotaxonomic and genomic distinctiveness, revealed that strain N53T was separate from other recognized species of the genus Roseovarius. On the basis of the data presented here, strain N53T represents a novel species of the genus Roseovarius, for which the name Roseovariussalinarum sp. nov. is proposed. The type strain is N53T (=MCCC 1H00200T=KCTC 52886T).

Aquimarina celericrescens sp. nov., isolated from seawater.

An orange-coloured, slender rod-shaped, gliding bacterium, designated NS08T, was isolated from coastal water of Xiaoshi Island, Weihai, China (37° 31' 36'' N 122° 00' 58'' E). Cells were Gram-stain-negative, non-spore-forming, non-flagellated, aerobic, catalase-positive and oxidase-negative. Growth occurred at 10-37 °C (optimum 30 °C), in the presence of 1.0-5.0 % (w/v) NaCl (optimum 2.0-3.0 %) and at pH 6.5-9.0 (optimum pH 7.0-7.5). Carotenoid pigments were produced but flexirubin-type pigments were not. The major fatty acids (>10 %) were iso-C15 : 0 and iso-C17 : 0 3-OH. The sole isoprenoid quinone of strain NS08T was menaquinone MK-6 and the DNA G+C content was 39.4 mol%. The polar lipid compositions of strain NS08T and the type strain of the type species of the genus Aquimarina, Aquimarina muelleri KCTC 12285T, were very similar with phosphatidylethanolamine, an unidentified aminolipid and two unknown polar lipids as the major components. A phylogenetic tree based on 16S rRNA gene sequences showed that strain NS08T formed an evolutionary lineage within the genus Aquimarina and shared the highest level of similarity to A. versatilis JCM 19528T (96.0 %) while level to A. muelleri KCTC 12285T was 95.0 %. Phenotypic characteristics distinguished strain NS08T from described members of the genus Aquimarina. On the basis of the evidence presented in this study, strain NS08T represents a novel species of the genus Aquimarina, for which the name Aquimarina celericrescens sp. nov. is proposed. The type strain is NS08T (=KCTC 52897T=MCCC 1H00191T).

Targeting ALDH2 with disulfiram/copper reverses the resistance of cancer cells to microtubule inhibitors.

Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients. Here, we investigated the mechanisms underlying these findings. DSF/Cu reversed the microtubule inhibitor resistance in A549/Taxol and KB/VCR cells in vitro, and had anti-tumor effects in A549/Taxol and KB/VCR xenograft mice. DSF/Cu and DSF reduced the cancer stem cell (CSC) characteristics of drug-resistant A549/Taxol and KB/VCR cells, including sphere formation, colony generation and migration, and DSF/Cu was more effective than DSF alone. DSF/Cu also decreased the aldehyde dehydrogenase (ALDH) activity and the expression of P-gp and stem cell transcription factors in A549/Taxol and KB/VCR cells. Knockdown of ALDH2 attenuated the CSC characteristics of resistant cancer cells and enhanced their sensitivity to Taxol or VCR. Importantly, DSF/Cu treatment inhibited the expression of ALDH2 in vitro and in vivo. Our findings suggest that DSF/Cu reverses microtubule inhibitor resistance in cancer cells by suppressing ALDH2 expression, and Cu improves the activity of DSF.

Lentibacillus sediminis sp. nov., isolated from a marine saltern.

A novel, Gram-stain-positive, moderately halophilic, endospore-forming, motile, facultatively anaerobic and rod-shaped strain, designated 0W14T, was isolated from a marine saltern of Wendeng, China. Optimal growth occurred at 37 °C, pH 7.5 and with 6.0 % (w/v) NaCl. MK-7 was the sole respiratory quinone and the peptidoglycan type of 0W14T was A4ßl-Orn-d-Glu. The major cellular fatty acid (>10.0 %) in strain 0W14T was anteiso-C15 : 0. The polar lipid profile of strain 0W14T consisted of diphosphatidylglycerol, phosphatidylglycerol, two unknown glycolipids and four unknown phospholipids. The genomic DNA G+C content of the strain was 44.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 0W14T forms a phylogenetic lineage with members of the genus Lentibacillus within the family Bacillaceae. Based on data from the current polyphasic study, the isolate is proposed to represent a novel species of genus Lentibacillus, for which the name Lentibacillus sediminis sp. nov. is proposed. The type strain is 0W14T (=KCTC 33835T=MCCC 1H00171T).

Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High-Fat High-Cholesterol Diet in Rats.

The aim of this study was to explore the potential beneficial effects of linarin enriched Flos Chrysanthemi extract (Lin-extract) on nonalcoholic steatohepatitis (NASH) induced by high-fat high-cholesterol (HFHC) diet in rats. SD rats received normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The liver content of triglyceride and total cholesterol markedly increased in HFHC diet-fed model rats while middle and high dose of Lin-extract lowered liver cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1) was upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and inhibited the activation of c-Jun N-terminal kinase (JNK) induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 1 (CXCL1), were suppressed by Lin-extract dose-dependently. Furthermore, pathology evaluation showed that high dose Lin-extract greatly improved lobular inflammation. Our results suggest that Lin-extract could attenuate liver injury and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid metabolism may partially contribute to this protective effect.

Evaluation of the effects of active fractions of chinese medicine formulas on IL-1ß, IL-6, and TNF-α release from ANA-1 murine macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Yaotongning (YTN) is a traditional Chinese Medicine (TCM) that contains ten component medicinal materials (CMMs) and uses Chinese rice wine as a vehicle to enhance its efficacy. YTN has been used for rheumatoid arthritis (RA) treatment in China for decades and has been reported to have anti-inflammatory and analgesic effects, as well as to strengthen the immune system. AIM OF THE STUDY: The present work quantitatively evaluated the in vitro effects of active fractions from the ten CMMs that make up YTN and eight additional herbs commonly used in TCM formulas for RA treatment, as well as different combinations of these active fractions, on cellular immune response; the findings were used to determine which active fractions are responsible for promoting an immune response, and to assess whether YTN is superior to other similar formulas and whether YTN can be improved by simplifying its formula from the point of its cellular immunomodulatory activity. MATERIALS AND METHODS: Using the YTN formulation principles and some concepts in combinatorial chemistry, 27 TCM samples were designed by combining some or all of the active fractions of YTN and other eight herbs used for RA treatment. Release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) from ANA-1 murine macrophages was measured using an enzyme-linked immunosorbent assay (ELISA). The immunoregulatory effects of the TCM samples were evaluated by comparing their half-effective concentrations (EC50) for stimulating the release of these cytokines. RESULTS: Among the investigated active fractions, the flavonoids from Carthamus tinctorius (Fct), Davallia mariesii (Fdm), and Cinnamomum cassia Twig volatile oils (Vca) from the eight selected herbs effectively promoted IL-1ß and IL-6 release from ANA-1 cells. Saponins from the YTN CMM Glycyrrhiza uralensis (Sgu) were the most potent promoters of IL-1ß and TNF-α release. The aqueous extract of YTN CMM Eupolyphaga sinensis (Ves) strongly enhanced the release of IL-1ß, IL-6, and TNF-α from ANA-1 cells. The EC50 values for stimulating the secretion of IL-1ß, IL-6, and TNF-α could be determined for only six samples. The full YTN formula and the sample containing 50% Glycyrrhiza uralensis saponins, 25% of the mixture of alkaloids, and 25% of the mixture of all flavonoids exhibited good comprehensive cellular immunomodulatory activity. The immunomodulatory activity of the complete YTN formula was better than that of the sample containing all active fractions of YTN without Chinese rice wine (the YTN vehicle). CONCLUSIONS: Sgu and Ves are the primary active fractions of YTN involved in stimulating immune responses. The YTN prescription was reasonably effective at promoting cellular immune responses. Chinese rice wine, the YTN vehicle, strengthened the immunoregulatory activity of YTN. The results of this study demonstrate that the YTN recipe could be improved by reducing the number of CMMs and altering some active fractions without reducing its activity to promote cellular immune responses.