EphB2 represents an independent prognostic marker in patients with gastric cancer and promotes tumour cell aggressiveness

Dysregulated expression of ephrin type-B receptor 2 (EphB2) has been linked with development and progression of solid tumours. In the current study we attempted to investigate the clinical relevance in GC and the effect of EphB2 expression on gastric cancer (GC) cells. EphB2 protein levels in GC and benign gastric tissues were determined using immunohistochemistry. EphB2 transcript expression in a GC cohort with GC tissue samples (n=171) and paired adjacent normal gastric tissues (n=97) was determined using qPCR. The EphB2 expression was over-activated using a CRISPR activator for the investigation of its cellular function. The expression levels of the EphB2 protein in the tumour tissues of tissue arrays were higher than the benign non-cancerous gastric tissues (P<0.05). EphB2 mRNA expression in GC tissues was also significantly elevated when compared with adjacent non-cancerous tissues (P<0.01). EphB2 activation promoted the migration and invasion abilities of the GC cell lines (P<0.01, respectively). In contrast, EphB2 activation significantly decreased the adhesion in GC cells (P<0.0001, respectively). The enrichment analysis of the correlated genes in a GC cohort indicates that EphB2 may function through mediating the cytokine-cytokine interaction, JAK-STAT and TP53 signaling pathways. In conclusion, EphB2 represents as a novel independent prognostic marker in GC. And activation of the EphB2 gene expression elevated the levels of migration and invasion, but suppressed adhesion of GC cells, indicating that EphB2 may act as a tumour promotor in GC. Our findings thus provide fundamental evidence for the consideration of the therapeutic potential of targeting EphB2 in GC

Novel compounds in fruits of coriander (Coşkuner & Karababa) with anti-inflammatory activity

© 2020 Coriander, Coriandrum Sativum L., is one of the commonest food and medicinal plants in many countries, but its chemical ingredients and pivotal role in anti-inflammatory activity have not been fully explored. The present study aimed to identify new compounds in the fruits of coriander and explore their anti-inflammatory activity. The compounds were isolated by chromatographic seperations and identified using spectroscopic and spectrometric methods. RAW264.7 macrophage cells were used to detect the anti-inflammatory activity of the compounds via Griess assay, western blotting, ELISA, and flow cytometry methods. The study resulted in the discovery of four new compounds, which were identified as: 4α-(furo[2,3-d]pyrimidin-6′-ylmethyl)-9α-propylnonolactone (1), 4-(formyloxy)-4-(6′-methylcyclohex-1-en-1-yl)butanoate(2), (7α,8α)-3α-hydroxyl-12,13α-dimethyl-5(6)-en-bicyclo[5,3,0]caprolactone (3), 7-methoxy-4-methyl-5,6-dihydro-7H-(2-hydroxypropan-2-yl)furo[2,3-f] coumarin (4). Compound 3 showed the highest anti-inflammatory activity with IC50 of 6.25 μM for an inhibitory effect on nitrite oxide (NO) level. In addition, compound 3 decreased the lipopolysaccharides-stimulated generations of ROS and the inflammatory cytokines (IL-6 and TNF-α). Mechanism exploration indicated that compound 3 suppressed inflammatory mediators’ expression, like iNOS and COX-2. Furthermore, the NF-κB and MAPK pathways were involved in the anti-inflammatory process of compound 3

Ergosterol Alleviates Kidney Injury in Streptozotocin-Induced Diabetic Mice

permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ergosterol (ERG) has been widely used in the development of novel drugs due to its unique physiological function. However, little is known about the protective effects of ERG on diabetes. Hence, the current study was designed to evaluate the positive role of ergosterol on streptozotocin- (STZ-) induced diabetes in mice. Oral glucose tolerance test (OGTT) was carried out to assess blood glucose level. Biochemical parameters such as uric acid, creatinine, serum insulin, triglycerides (TG), and total cholesterol (TC) were alsomeasured. Pathological condition of kidney was examined by hematoxylin-eosin (H&amp;E) staining.The expressions of PI3K, p-PI3K, Akt, p-Akt, NF

Podwyższone stężenia lipokaliny-2 w surowicy krwi są związane ze wskaźnikami metabolizmu glukozy i metabolizmu kostnego w przebiegu cukrzycy typu 2

Introduction: The role of lipocalin 2 (LCN2) in type 2 diabetes mellitus (T2DM) needs to be fully elucidated. Moreover, bone has been demonstrated to modulate glucose metabolism via LCN2. We thus performed this study to investigate the associations of LCN2 with indexes of glucose metabolism in T2DM. The associations of LCN2 with bone metabolism were examined concurrently. Material and methods: Total 288 Chinese Han subjects entered in this study including 146 patients with T2DM and 142 subjects with normal glucose tolerance. Insulin resistance was assessed by HOMA-IR andWstęp: Wyjaśnienie roli lipokaliny-2 (lipocalin 2; LCN2) w przebiegu cukrzycy typu 2 jest niezbędne, w szczególności, że zostało dowiedzione, iż kość moduluje metabolizm glukozy za pośrednictwem LCN2. Niniejsze badanie przeprowadzono, aby zbadać, w jaki sposób LCN2 jest powiązana ze wskaźnikami metabolizmu glukozy w przebiegu cukrzycy typu 2. Jednocześnie zbadano powiązania LCN2 z metabolizmem kostnym. Materiał i metody: W badaniu wzięło udział 288 Chińczyków Han, w tym 146 pacjentów z cukrzycą typu 2 i 142 pacjentów z prawidłową tolerancją glukozy. Insulinooporność oceniano za pomocą wskaźnika HOMA-IR, natomiast funkcję komórek beta trzustki za pomocą HOMA-β. W przypadku pacjentów z cukrzycą typu 2 oznaczano również markery obrotu kostnego, N-końcowy propeptyd prokolagenu typu I, C-końcowy usieciowany telopeptyd łańcucha alfa kolagenu typu I, gęstość mineralną kości (bone mineral density; BMD) odcinka lędźwiowego kręgosłupa i szyjki kości udowej. Wyniki: Stężenia LCN2 w surowicy krwi w przebiegu cukrzycy typu 2 były wyższe niż u osób z prawidłową tolerancją glukozy (p = 0,005). Ponadto, LCN2 była dodatnio skorelowana ze stężeniem insuliny w surowicy krwi na czczo (r = 0,262, p = 0,001), wskaźnikiem HOMA-IR (r = 0,185, p = 0,026) i HOMA-β (r = 0,306, p &lt; 0,001), odpowiednio, oraz ujemnie skorelowana z osoczowym stężeniem glukozy na czczo (r = –0,218, p = 0,006). Dodatkowo, BMD szyjki kości udowej (β = –0,176, p = 0,033), N-końcowy propeptyd prokolagenu typu I (β = 0,181, p = 0,026) oraz C-końcowy usieciowany telopeptyd łańcucha alfa kolagenu typu I (β = –0,168, p = 0,037) były niezależnymi czynnikami predykcyjnymi dla LCN2 w przebiegu cukrzycy typu 2. Wnioski: Lipokalina-2 była powiązana ze wskaźnikami metabolizmu glukozy. Ponadto, BMD oraz markery obrotu kostnego były nie­zależnymi czynnikami predykcyjnymi dla LCN2 w przebiegu cukrzycy typu 2. Można sądzić, że LCN2 może odgrywać rolę w procesie wzajemnego wpływu homeostazy kości i homeostazy glukozy

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

Microbial Community Succession and Response to Environmental Variables During Cow Manure and Corn Straw Composting

In composting system, the composition of microbial communities is determined by the constant change in the physicochemical parameters. This study explored the dynamics of bacterial and fungal communities during cow manure and corn straw composting using high throughput sequencing technology. The relationships between physicochemical parameters and microbial community composition and abundance were also evaluated. The sequencing results revealed the major phyla included Proteobacteria, Bacteroidetes, Firmicutes, Chloroflexi and Actinobacteria, Ascomycota, and Basidiomycota. Linear discriminant analysis effect size (LEfSe) illustrated that Actinomycetales and Sordariomycetes were the indicators of bacteria and fungi in the maturation phase, respectively. Mantel test showed that NO3--N, NH4+-N, TN, C/N, temperature and moisture content significantly influenced bacterial community composition while only TN and moisture content had a significant effect on fungal community structure. Structural equation model (SEM) indicated that TN, NH4+-N, NO3--N and pH had a significant effect on fungal abundance while TN and temperature significantly affected bacterial abundance. Our finding increases the understanding of microbial community succession in cow manure and corn straw composting under natural conditions

Improved laccase production by Trametes versicolor using Copper-Glycyl-L-Histidyl-L-Lysine as a novel and high-efficient inducer

A highly efficient strategy using Copper-Glycyl-L-Histidyl-L-Lysine (GHK-Cu) as a novel inducer was developed to enhance laccase production by Trametes versicolor. After medium optimization, laccase activity increased by 12.77-fold compared to that without GHK-Cu. The laccase production of 1113.8 U L−1 was obtained by scaling-up culture in 5-L stirring tank. The laccase production induced by CuSO4 was poorer than that of GHK-Cu at the same mole concentration. GHK-Cu could increase the permeability of cell membrane with less damage, and it facilitated the adsorption, accumulation, and utilization of copper by fungal cells, which was beneficial for laccase synthesis. GHK-Cu induced better expression of laccase related genes than that of CuSO4, resulting in higher laccase production. This study provided a useful method for induced production of laccase by applying GHK chelated metal ion as a non-toxic inducer, which reduced the safety risk of laccase broth and provided the potential application of crude laccase in food industry. In addition, GHK can be used as the carrier of different metal ions to enhance the production of other metalloenzymes