Synthesis of fucosylated oligosaccharides with α-l-fucosidase from Thermotoga maritima immobilized on Eupergit® CM

Extremophiles - Fucosylated oligosaccharides present in human milk perform various biological functions that benefit infants’ health. These compounds can be also obtained by enzymatic...     

Beta-adrenergic pathway activation enhances aggressiveness and inhibits stemness in head and neck cancer

Chronic stress leads to the activation of the beta-adrenergic pathway. Its activation has been implicated in the progression of different types of cancer but its role on head and neck squamous cell carcinomas (HNSCCs) remains undefined. The aim of this study was to investigate the influence of the beta-adrenergic pathway activation in the progression of HNSCCs and offer a panel of potential treatments for patients with the active beta-adrenergic pathway. Five hundred and twenty TCGA patients with primary HNSCCs were divided in two groups: ADRB2^low / SLC6A2^low and ADRB2^high / SLC6A2^high. Differentially expressed genes (DEGs) were identified through differential expression analysis. The association of clinicopathological and genomic features between the groups was analyzed using a bioinformatic approach. Potential drugs for treatment of HNSCC were identified based on the DEGs. There was association between ADRB2 and SLC6A2 expressions with age, race, tumor site, histologic grade, perineural invasion, and HPV p16 status. It was identified 898 DEGs between the groups. High ADRB2/SLC6A2 expression stimulated HNSCC proliferation, adhesion, invasion, and angiogenesis. On the other hand, genes related to cell stemness were downregulated in patients with activation of the beta- adrenergic pathway. Finally, 56 FDA-approved antineoplastic and immunotherapeutic drugs were identified as potential targets for the personalized treatment.     

Robusta coffee beans post-harvest microflora: Lactobacillus plantarum sp. as potential antagonist of Aspergillus carbonarius

Coffee contamination by ochratoxigenic fungi affects both coffee quality as well as coffee price with harmful consequences on the economy of the coffee exporting countries for whom which is their main source of income. Fungal strains were isolated from coffee beans and identified as black Aspergilli. Ochratoxigenic moulds like Aspergillus carbonarius were screened and selected for detailed studies. Also lactic acid bacteria (LAB) were isolated from silage coffee pulp and their antifungal activity was tested on dual-culture agar plate. Ten of the isolated LAB demonstrated antifungal effect against A. carbonarius. API 50 CH and APIZYM were used to perform phenotypic identification. 16S rDNA sequencing was made to confirm the results.     

Insulin protects against hepatic damage postburn

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes.     

Bioluminescent bioreporter Pseudomonas putida TVA8 as a detector of water pollution. Operational conditions and selectivity of free cells sensor

Conditions influencing bioluminescence output from Pseudomonas putida TVA8 harboring chromosomal tod-luxCDABE fusion were followed. In complex media, cell growth was not influenced by the presence of toluene at 53 mg/L. Bioluminescence induction was tested in minimal medium. At 15 °C the highest bioluminescence induced with toluene (1.325 mg/L) was reached after 6 h. At 25 °C the bioluminescence maximum was approximately 20% lower but this was reached after 3.5 h, and at temperatures of 7 °C, 28 °C, 30 °C and 34 °C, bioluminescence peaked at ≤60% of the maximum. Time courses of bioluminescence were dependent on cell concentrations. The heights of bioluminescence maxima were proportional to toluene concentration in the range 0–26 mg/L. Twenty-three organic pollutants (10³× diluted saturated solutions) were tested as bioluminescent inducers. The bioluminescence maximum decreased in the order: ethylbenzene > toluene > phenol > benzene > 4-ethyltoluene > 4-fluorotoluene > cumene > isobutylbenzene > styrene > trichloroethylene > o-, p-xylene > cresol > m-xylene > 2-methylnaphthalene > benzylchloride > naphthalene > salicylic acid > hexachlorobenzene > 2-chloronaphthalene > biphenyl > 2-bromonaphthalene > 1,3,5-triethylbenzene. Bioluminescence was also induced with ethanol and methanol and the presence of these alcohols in concentrations of ≤1% increased bioluminescence of toluene. The induction of bioluminescence from samples of wastewater and groundwater contaminated with BTEX (benzene, toluene, ethylbenzene and xylene) from 0.5 to 120 mg/L was demonstrated.     

Th2-associated alternative Kupffer cell activation promotes liver fibrosis without inducing local inflammation

Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.     

Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-terminal domain

Background  

The NIMA-related kinases (Neks) are widespread among eukaryotes. In mammalians they represent an evolutionarily conserved family of 11 serine/threonine kinases, with 40-45% amino acid sequence identity to the Aspergillus nidulans mitotic regulator NIMA within their catalytic domains. Neks have cell cycle-related functions and were recently described as related to pathologies, particularly cancer, consisting in potential chemotherapeutic targets. Human Nek6, -7 and -9 are involved in the control of mitotic spindle formation, acting together in a mitotic kinase cascade, but their mechanism of regulation remain elusive.