Improvement of retinoids production in recombinant E. coli using glyoxylic acid

Isoprenoids are the most chemically diverse compounds found in nature. They are present in all organisms and have essential roles in membrane structure, redox chemistry, reproductive cycles, growth regulation, signal transduction and defense mechanisms. In spite of their diversity of functions and structures, all isoprenoids are derived from the common building blocks of isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). Optimization of IPP synthesis pathway is of benefit to mass production of various isoprenoids. There are two pathways of 2-C-Methyl-D-erythritol-4-phosphate (MEP) and mevalonate (MVA) for IPP synthesis. Prokaryotes including E. coli generally use MEP pathway whereas MVA pathway is used in eukaryotes. To improve isoprenoid production, it was performed the deletion of genes in E. coli, which are involved in both formation of fermentation by-products such as organic acids and alcohols, and consumption of precursors of MEP and MVA pathways, pyruvate and acetyl-CoA. As a result, we were able to develop a strain with improved fermentation productivity and carbon source utilization efficiency, the mutant strain was called AceCo. Higher lycopene production was achieved in the AceCo strain compared to the wild type MG1655 strain due to no formation of the inhibitory by-products. However, retinoids production of AceCo strain decreased to a half of that of MG1655 strain. Please click Additional Files below to see the full abstract

Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20 μM suppressed the LPS-induced IL-8 production through the TLR4 activation, inhibiting eotaxin-1 induction. The in vivo study explored the demoting effects of kaempferol on asthmatic inflammation in BALB/c mice sensitized with ovalbumin (OVA). Mouse macrophage inflammatory protein-2 production and CXCR2 expression were upregulated in OVA-challenged mice, which was attenuated by oral administration of ≥10 mg/kg kaempferol. Kaempferol allayed the airway tissue levels of eotaxin-1 and eotaxin receptor CCR3 enhanced by OVA challenge. This study further explored the blockade of Tyk-STAT signaling by kaempferol in both LPS-stimulated BEAS-2B cells and OVA-challenged mice. LPS activated Tyk2 responsible for eotaxin-1 induction, while kaempferol dose-dependently inhibited LPS- or IL-8-inflamed Tyk2 activation. Similar inhibition of Tyk2 activation by kaempferol was observed in OVA-induced mice. Additionally, LPS stimulated the activation of STAT1/3 signaling concomitant with downregulated expression of Tyk-inhibiting SOCS3. In contrast, kaempferol encumbered STAT1/3 signaling with restoration of SOCS3 expression. Consistently, oral administration of kaempferol blocked STAT3 transactivation elevated by OVA challenge. These results demonstrate that kaempferol alleviated airway inflammation through modulating Tyk2-STAT1/3 signaling responsive to IL-8 in endotoxin-exposed airway epithelium and in asthmatic mice. Therefore, kaempferol may be a therapeutic agent targeting asthmatic diseases

Esophageal Thermal Injury by Hot Adlay Tea

Reversible thermal injury to the esophagus as the result of drinking hot liquids has been reported to generate alternating white and red linear mucosal bands, somewhat reminiscent of a candy cane. This phenomenon is associated with chest pain, dysphagia, odynophagia, and epigastric pain

Angiotensin {II}-induced redox-sensitive {SGLT}1 and 2 expression promotes high glucose-induced endothelial cell senescence

High glucose (HG)-induced endothelial senescence and dysfunction contribute to the increased cardiovascular risk in diabetes. Empagliflozin, a selective sodium glucose co-transporter2 (SGLT2) inhibitor, reduced the risk of cardiovascular mortality in type 2 diabetic patients but the protective mechanism remains unclear. This study examines the role of SGLT2 in HG-induced endothelial senescence and dysfunction. Porcine coronary artery cultured endothelial cells (ECs) or segments were exposed to HG (25 mmol/L) before determination of senescence-associated beta-galactosidase activity, protein level by Western blot and immunofluorescence staining, mRNA by RT-PCR, nitric oxide (NO) by electron paramagnetic resonance, oxidative stress using dihydroethidium and glucose uptake using 2-NBD-glucose. HG increased ECs senescence markers and oxidative stress, down-regulated eNOS expression and NO formation, and induced the expression of VCAM-1, tissue factor, and the local angiotensin system, all these effects were prevented by empagliflozin. Empagliflozin and LX-4211 (dual SGLT1/2 inhibitor) reduced glucose uptake stimulated by HG and H2O2 in ECs. HG increased SGLT1 and 2 protein levels in cultured ECs and native endothelium. Inhibition of the angiotensin system prevented HG-induced ECs senescence and SGLT1 and 2 expression. Thus, HG-induced ECs ageing is driven by the local angiotensin system via the redox-sensitive up-regulation of SGLT1 and 2, and, in turn, enhanced glucotoxicity

Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach

© 2020, The Author(s).Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.

Single-step genome-wide association study for social genetic effects and direct genetic effects on growth in Landrace pigs

In livestock social interactions, social genetic effects (SGE) represent associations between phenotype of one individual and genotype of another. Such associations occur when the trait of interest is affected by transmissible phenotypes of social partners. The aim of this study was to estimate SGE and direct genetic effects (DGE, genetic effects of an individual on its own phenotype) on average daily gain (ADG) in Landrace pigs, and to conduct single-step genome-wide association study using SGE and DGE as dependent variables to identify quantitative trait loci (QTLs) and their positional candidate genes. A total of 1,041 Landrace pigs were genotyped using the Porcine SNP 60K BeadChip. Estimates of the two effects were obtained using an extended animal model. The SGE contributed 16% of the total heritable variation of ADG. The total heritability estimated by the extended animal model including both SGE and DGE was 0.52. The single-step genome-wide association study identified a total of 23 QTL windows for the SGE on ADG distributed across three chromosomes (i.e., SSC1, SSC2, and SSC6). Positional candidate genes within these QTL regions included PRDM13, MAP3K7, CNR1, HTR1E, IL4, IL5, IL13, KIF3A, EFHD2, SLC38A7, mTOR, CNOT1, PLCB2, GABRR1, and GABRR2, which have biological roles in neuropsychiatric processes. The results of biological pathway and gene network analyses also support the association of the neuropsychiatric processes with SGE on ADG in pigs. Additionally, a total of 11 QTL windows for DGE on ADG in SSC2, 3, 6, 9, 10, 12, 14, 16, and 17 were detected with positional candidate genes such as ARL15. We found a putative pleotropic QTL for both SGE and DGE on ADG on SSC6. Our results in this study provide important insights that can help facilitate a better understanding of the molecular basis of SGE for socially affected traits.info:eu-repo/semantics/publishedVersio

The positive feedback loop between Nrf2 and phosphogluconate dehydrogenase stimulates proliferation and clonogenicity of human hepatoma cells

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.Recent studies report that nuclear factor-erythroid-2-related factor 2 (Nrf2) facilitates tumor progression through metabolic reprogramming in cancer cells. However, the molecular mechanism underlying the oncogenic functions of Nrf2 is not yet well understood. Some of the pentose phosphate pathway (PPP) enzymes are considered to play a role in the cancer progression. The present study was intended to explore the potential role of phosphogluconate dehydrogenase (PGD), one of the PPP enzymes, in the proliferation and migration of human hepatoma HepG2 cells. Genetic ablation of Nrf2 attenuated the expression of PGD at both transcriptional and translational levels. Notably, Nrf2 regulates the transcription of PGD through direct binding to the antioxidant response element in its promoter region. Nrf2 overexpression in HepG2 cells led to increased proliferation, survival, and migration, and these events were suppressed by silencing PGD. Interestingly, knockdown of the gene encoding this enzyme not only attenuated the proliferation and clonogenicity of HepG2 cells but also downregulated the expression of Nrf2. Thus, there seems to exist a positive feedback loop between Nrf2 and PGD which is exploited by hepatoma cells for their proliferation and survival. Treatment of HepG2 cells with ribulose-5-phosphate, a catalytic product of PGD, gave rise to a concentration-dependent upregulation of Nrf2. Collectively, the current study shows that Nrf2 promotes hepatoma cell growth and progression, partly through induction of PGD transcription.

Klebsiella pneumoniae Orbital Cellulitis with Extensive Vascular Occlusions in a Patient with Type 2 Diabetes

A 39-year-old woman visited the emergency room complaining of right eye pain and swelling over the preceding three days. The ophthalmologist's examination revealed orbital cellulitis and diabetic retinopathy in the right eye, although the patient had no prior diagnosis of diabetes. It was therefore suspected that she had diabetes and orbital cellulitis, and she was started on multiple antibiotic therapies initially. She then underwent computed tomography scans of the orbit and neck and magnetic resonance imaging of the brain. These studies showed an aggravated orbital cellulitis with abscess formation, associated with venous thrombophlebitis, thrombosis of the internal carotid artery, and mucosal thickening of maxillary sinus with multiple paranasal abscesses. Three days later, initial blood culture grew Klebsiella pneumoniae. She recovered after incision and drainage and antibiotic therapy for 37 days

Resveratrol suppresses gastric cancer cell proliferation and survival through inhibition of PIM-1 kinase activity

The proviral integration site for Moloney murine leukemia virus (PIM) family of serine/threonine-specific kinases consist of three isoforms, that regulate proliferation, apoptosis, metabolism, invasion, and metastasis of cancer cells. Among these, abnormally elevated kinase activity of PIM-1 contributes to the progression of gastric cancer and predicts poor prognosis and a low survival rate in gastric cancer patients. In the present study, we found that resveratrol, one of the representative chemopreventive and anticarcinogenic phytochemicals, directly binds to PIM-1 and thereby inhibits its catalytic activity in human gastric cancer SNU-601 cells. This resulted in suppression of phosphorylation of the proapoptotic Bad, a known substrate of PIM-1. Resveratrol, by inactivating PIM-1, also inhibited anchorage-independent growth and proliferation of SNU-601 cells. To understand the molecular interaction between resveratrol and PIM-1, we conducted docking simulation and found that resveratrol directly binds to the PIM-1 at the ATP-binding pocket. In conclusion, the proapototic and anti-proliferative effects of resveratrol in gastric cancer cells are likely to be mediated through suppression of PIM-1 kinase activity, which may represent a novel mechanism underlying its chemopreventive and anticarcinogenic actions.