Gut-derived Lipopolysaccharide Promotes Alcoholic Hepatosteatosis and Subsequent Hepatocellular Carcinoma by Stimulating Neutrophil Extracellular Traps Through TLR4

BackgroundBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and which increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and activation of neutrophil extracellular traps (NETs). MethodsSerum from both binge drinking and alcohol-avoiding patients was analyzed. Mouse models of chronical plus binge alcohol indued steatosis and HCC models were used. ResultsA marker of NETs formation, lipopolysaccharide, was significantly higher in alcoholic steatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE KO mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and genesis of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product lipopolysaccharide (LPS). When mice lacking TLR4 received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. ConclusionFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol usage leads to increased alcoholic steatosis and subsequent HCC.

Bacterial Product Template Domain: An Evolutionary Intermediate between Dehydratase and Aldol Cyclase of Type I Polyketide Synthases

The product template (PT) domains act as an aldol cyclase to control the regiospecific aldol cyclization of the extremely reactive poly-β-ketone intermediate assembled by an iterative type I polyketide synthases (PKSs). Up to now, only the structure of fungal PksA PT that mediates the first-ring cyclization via C4-C9 aldol cyclization is available. We describe here the structural and computational characterization of a bacteria PT domain that controls C2-C7 cyclization in orsellinic acid (OSA) synthesis. Mutating the catalytic His949 of the PT abolishes production of OSA and results in a tetraacetic acid lactone (TTL) generated by spontaneous O-C cyclization of the acyl carrier protein (ACP)-bound tetraketide intermediate. Crystal structure of the bacterial PT domain closely resembles dehydrase (DH) domains of modular type I PKSs in the overall fold, dimerization interface and catalytic “His-Asp” dyad organization, but is significantly different from PTs of fungal iterative type I PKSs. QM/MM calculation reveals that the catalytic His949 abstracts a proton from C2 and transfers it to C7 carbonyl to mediate the cyclization reaction. According to the structural similarity to DHs and the functional similarity to fungal PTs, we propose that the bacterial PT represents an evolutionary intermediate between the two tailoring domains of type I PKSs.

Formylpeptide receptors in GtoPdb v.2021.2

The formylpeptide receptors (nomenclature agreed by the NC-IUPHAR Subcommittee on the formylpeptide receptor family [196]) respond to exogenous ligands such as the bacterial product fMet-Leu-Phe (fMLP) and endogenous ligands such as lipoxin A4 (LXA4), 15-epi-lipoxin A4, annexin I , cathepsin G, amyloid β42, serum amyloid A and spinorphin, derived from β-haemoglobin. FPR1 also serves as a plague receptor for selective destruction of human immune cells by Y. pestis [135]. The FPR1/2 agonists 'compound 17b' and 'compound 43' have shown cardiac protective functions [149, 64].

Assessing BactoMix 5 efficacy for clubroot control in naturally infested soil

The cultivation of cruciferous crops is threatened by extensive yield losses caused by the soil-borne pathogen Plasmodiophora brassicae Woronin, 1877. The objective of the study was to assess the potential of the bacterial product BactoMix 5 for the control of clubroot on a naturally infested soil in growth chamber trials using a P. brassicae-specific qPCR methodology. The results did not show a significant decrease in the P. brassicae in the soil nor a reduction of the disease symptoms on the plants. The native soil microbiota may have exhibited an antagonistic activity against the bacterial species from BactoMix 5 and evoked the poor effect of the product. Therefore, potential biological control agents should be tested with native soil microbiota and the regional production should be advanced to increase the product efficacy in the environment

Formylpeptide receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The formylpeptide receptors (nomenclature agreed by the NC-IUPHAR Subcommittee on the formylpeptide receptor family [185]) respond to exogenous ligands such as the bacterial product fMet-Leu-Phe (fMLP) and endogenous ligands such as annexin I , cathepsin G, amyloid β42, serum amyloid A and spinorphin, derived from β-haemoglobin.

Karakteristik produk dan efektivitas enkapsulasi bakteri pendegradasi asam sianida (HCN)

ABSTRAK<br /><br />Daun singkong pahit (Manihot esculenta)memiliki kandungan antinutrisi berupa asam sianida (HCN) yang tinggi, namun HCN dapat di degradasi dengan bakteri rumen. Penelitian ini bertujuan untuk mengamati karakteristik produk dan efektivitas enkapsulasi bakteri pendegradasi sianida dengan masa simpan (0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 hari) pada suhu ruang. Peubah yang diamati adalah karakteristik produk dan viabilitas bakteri pendegradasi sianida terenkapsulasi. Data yang diperoleh dianalisa dengan sidik ragam (ANOVA) menggunakan program SPSS 16.0. Hasil penelitian menunjukkan bahwa lama penyimpanan berpengaruh terhadap perubahan warna dan bentuk dari produk hasil enkapsulasi. Penyimpanan produk enkapsulasi bakteri pendegradasi sianida selama 3 hari tidak mempengaruhiviabilitas bakteri dibandingkan kontrol. Namun demikian semakin lama penyimpanan produk enkapsulasi bakteri sampai hari ke 28 nyata menurunkan (P&lt;0.05) viabilitas bakteri.Hasil penelitian dapat disimpulkan bahwa dengan teknik enkapsulasi dapat mempertahankan viabilitas bakteri pendegradasi sianida.<br /><br />Kata kunci: bakteri pendegradasi sianida, karakteristik produk, penyimpanan,viabilitas<br /><br />ABSTRACT<br /><br />Bitter cassava leaves have high antinutrients in the form of cyanide acid (HCN), but HCN can be degraded with rumen bacteria. This research aimed to observe the product characteristics and the effectivity of cyanide degradation bacteria capsulation with different length of storages (0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 days)in the room temperature. The observed variables were product characteristics and viability of cyanide degrading bacteriacapsulation. The data obtained were analyzed by Analysis of variance (ANOVA) using SPSS 16.0 program. The results showed that storages duration affected the color and shape of cyanide degradation bacteria capsulation products. The storage of capsulated HCN degrading bacteria up to 3 days did not affect the viability of bacteria compared to the control treatment. However, the longer storage of capsulated bacteria up to 28 days, significant decreased (P&lt;0.05) the viability of the bacteria. It is concluded that capsulation of cyanide degrading bacteria could maintain the viability of bacteria.<br /><br />Keywords: cyanide degradation bacterial, product characteristics, storage, viability