ELL associated factor 2 is a potential diagnostic and prognostic indicator: evidence from the in silico and in vitro experiments.

Due to the lack of sensitive biomarkers, cancer disease kill 9.6 million individuals each year around the globe. The present study aimed to explore the association between ELL Associated Factor 2 (EAF2) expression and its diagnostic and prognostic landscape across different human cancers using an in silico and in vitro approach. To achieve the defined goals of this study, we used the following online sources: UALCAN, KM plotter, TNMplot, cBioPortal, STRING, DAVID, MuTarget, Cytoscape, and CTD. In addition to this, we also used additional The Cancer Genome Atlas (TCGA) datasets via TIMER2, GENT2, and GEPIA to confirm the expression of EAF2 on additional cohorts. Finally, we performed RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques-based analysis using A549, ABC-1, EBC-1, LK-2 lung cancer cell lines, and MRC-9 normal control lung cell line for further validation of the results. On balance, EAF2 was elevated in 19 types of human cancers and its up-regulation was significantly correlated with shorter overall survival (OS), relapse-free survival (RFS), and metastasis in Liver Hepatocellular Carcinoma (LIHC) and Lung Squamous Cell Carcinoma (LUSC) patients. We further evaluated that EAF2 expression was also elevated across LIHC and LUSC patients belonging to different clinicopathological features. Through pathway analysis, EAF2 associations were observed with four important pathways. Moreover, some worth noticing correlations were also documented between EAF2 expression and its promoter methylation level, genetic alterations, other mutant genes, tumor purity, and different immune cells infiltration. The higher EAF2 expression contributes significantly to the tumorigenesis and metastasis of LIHC and LUSC. Therefore, it can be used as a common biomarker in these cancers.

De novo assembly and characterization of the complete chloroplast genome of Elymus magellanicus (É.Desv.) Á.Löve, 1984 (Poaceae, Pooideae).

Elymus magellanicus (É.Desv.) Á.Löve is a foliage accent plant that originated in South America. In this study, the complete chloroplast genome of E. magellanicus is reported. It was found to have a total size of 133,249 bp. The chloroplast genome was found to consist of two inverted repeats (IRA and IRB) of 21,421 bp each, a small single-copy region of 12,709 bp, and a large single-copy region (77,698 bp). The annotation results show the GC content of the chloroplast genome to be 38.47%, including 40 tRNA genes, 82 protein-coding genes, and 8 rRNA genes. Phylogenetic analysis of 29 species revealed that E. magellanicus is closely related to E. arenarius.

Sequencing and characterization of the complete mitochondrial genome of Thinopyrum obtusiflorum (DC.) Banfi, 2018 (Poaceae).

In this study, the mitochondrial genome of Thinopyrum obtusiflorum was sequenced, assembled, and annotated. The complete circular mitogenome of Th. obtusiflorum is 390,725 bp in length and the overall A + T content of mitogenome is 55.61%. It harbors 33 protein-coding genes (PCGs), 21 transfer RNA genes (tRNAs), six ribosomal RNA genes (rRNAs), and 20 simple sequence repeats (SSRs). Phylogenetic analysis indicates that Th. obtusiflorum is a sister to the clade including Aegilops speltoides, Triticum aestivum, and Triticum aestivum cultivar Chinese Yumai in the Triticeae.

The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity.

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.

Development and evaluation of poly adenosine 5'-diphosphate-ribose polymerase 1 immobilization-based receptor chromatography.

Yanghe decoction is a traditional Chinese medicine prescription and has been used for breast cancer treatment for many years. However, the effective ingredients in the decoction have not been identified. The expression of poly(ADP-ribose) polymerase-1 is highly related to breast cancer. Using poly(ADP-ribose) polymerase-1 as a probe, we expressed the haloalkane dehalogenase-tagged protein in BL21(DE3) E. coli, immobilized it on hexachlorocaproic acid-modified macroporous silica gel, and established a poly(ADP-ribose) polymerase-1 chromatographic model. The feasibility of the model was verified by testing the retention behaviors of five drugs on the protein column. We applied the model in screening the bioactive components in yanghe decoction. Rutin, liquiritin, and a compound ([M-H]- 681.7) were identified to be the potential bioactive ingredients. We studied the binding property between rutin and poly(ADP-ribose) polymerase-1 by injection amount dependent method, competitive studies, and molecular docking. We found that rutin can bind to the protein through the typical inhibitor binding site of the protein. Therefore, the chromatographic model is a useful tool to screen bioactive compounds from traditional Chinese medicine. The method is fast, reliable, and applicable to other functional proteins that can screen the potential lead compounds for the treatment of the related diseases.

Association between liver cirrhosis and estimated glomerular filtration rates in patients with chronic HBV infection.

To investigate the estimated glomerular filtration rates of chronic hepatitis B (CHB) patients with or without liver cirrhosis, and to explore the related risk factors.A total of 559 CHB patients were enrolled. Liver cirrhosis was diagnosed with ultrasound. The Child-Pugh scoring system was used to stage patients with liver cirrhosis. The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the estimated glomerular filtration rate (eGFR).A total of 296 patients were involved. The results showed that the incidence of renal impairment in patients with liver cirrhosis was 8.45% (25/296). The incidence of renal impairment in Child-Pugh C patients was significantly higher than that in Child-Pugh B and Child-Pugh Grade A patients (i.e., 17.2% [17/99] vs 6.67% [7/105] vs 1.09% [1/92], respectively, P < .001); age, hyperuricemia, and Child-Pugh score are all risk factors for impaired renal function.With the deterioration of liver function in patients with cirrhosis, the incidence of impaired renal function has increased significantly, and renal function should be closely monitored to guide patients in clinical medication.

Efficacy and safety of telbivudine treatment for the prevention of HBV perinatal transmission.

To observe the efficacy of telbivudine in chronic hepatitis B (CHB) women with high viral load during pregnancy and the long-term effects on intelligence, growth, and development of the newborns.A total of 87 patients were included. Forty-two patients received telbivudine orally 600 mg per day and treatment initiated from 12 weeks after gestation until the 12th postpartum week. Forty-five patients were untreated according to principle of informed consent. All infants received injection of hepatitis B immune globulin (HBIG; 200 IU) and were vaccinated with recombinant HBV vaccine. Wechsler preschool intelligence scale was used to assess mental and neuropsychological developments of these children till they were 6 years old. Data including serum HBV DNA viral load, Apgar score, and scores of Wechsler preschool intelligence scale were analyzed and compared.Levels of both serum HBV DNA and ALT in patients who received telbivudine were significantly decreased at the 12th week after delivery, compared with baseline levels (P < .01). No significant changes were observed in patients not receiving telbivudine (P > .05). Serum HBV DNA and ALT levels at the 12th week after delivery in the telbivudine group were significantly lower than those of patients without telbivudine (P < .01). The serum HBsAg-positive rate in neonates 7 months of age was 0%, which was significantly lower than that in control group (11.11%) (P < .05). No statistical differences were observed between the 2 groups regarding maternal cesarean section rate, adverse pregnancy rate, postpartum bleeding rate, neonatal body mass, Apgar score, neonatal malformation incidence, or intelligence development of newborn.Telbivudine is effective to reduce the viral load in CHB mothers with high viral load and could lower the perinatal transmission rate. Both mental and physical development in neonates with exposure to telbivudine during perinatal period were similar to those without telbivudine exposure.

Yin-yang effect of tumour cells in breast cancer: from mechanism of crosstalk between tumour-associated macrophages and cancer-associated adipocytes.

Currently, adipocytes and macrophages are considered to be key cell types of breast cancer (BC) tissues. With the emergence of crown-like structures (CLS), cancer-associated adipocytes (CAAs) and tumour-associated macrophages (TAMs) are formed respectively in tumor microenvironment (TME). Both of them affect the progress of breast cancer, while forming crosstalk in the tumour tissue. CAAs play an important role, which produces hypoxia and inflammation environment and aggravates this environment. The formation and secretion of TAMs with M2 phenotypic characteristics, such as HIF-1α, and TNF-α, affect the progress of cancer cells by interfering with the secretion of MCP-1 by CAAs. Therefore, the interaction between CAAs and TAMs may be an effective therapeutic target for breast cancer. In this review, we focus on the biological effects of two types of cells in breast cancer, in order to better explain the crosstalk between them and provide new ideas for the future treatment of breast cancer.

Enhanced Migration of Bone Marrow-Derived Mesenchymal Stem Cells with Tetramethylpyrazine and Its Synergistic Effect on Angiogenesis and Neurogenesis After Cerebral Ischemia in Rats.

Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for treating ischemic stroke owing to their capacity to secrete various trophic factors with potent angiogenic and neurogenic potentials. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limits effective therapies for the treatment of stroke. The combination of BMSCs and pharmacological agent can promote the migration of BMSCs toward infarcted regions and improve the therapeutic effects after stroke. In this study, we aimed to investigate whether BMSCs combined with tetramethylpyrazine (TMP) enhanced BMSC migration into the ischemic brain, which had better therapeutic effect in the treatment of stroke. In a rat stroke model, we found that combination treatment significantly upregulated ischemic brain stromal-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) expressions, and promoted BMSCs homing toward the ischemic regions than BMSC monotherapy. Moreover, BMSCs combined with TMP synergistically increased the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, promoted angiogenesis and neurogenesis, and improved functional outcome after stroke. These results suggest that combination treatment could not only enhance the migration of BMSCs into the ischemic brain but also act in a synergistic way to potentiate endogenous repair processes and functional recovery after ischemic stroke.

Typhae pollen polysaccharides ameliorate diabetic retinal injury in a streptozotocin-induced diabetic rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: According to ancient traditional Chinese medicine, Typhae Pollen (TP) is commonly used to treat fundus haemorrhage because it improves blood circulation. AIMS OF THE STUDY: This study evaluated the role of the main TP component, polysaccharides (TPP), on diabetic retinopathy (DR) and its possible mechanisms of inhibiting inflammation and improving blood circulation. MATERIALS AND METHODS: After successful establishment of a diabetic rat model, TPP was administered to diabetic rats for treatment, and the rats were sacrificed at 12 weeks. Retinal electrophysiology and ultrastructures were observed, and serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels were also measured. Changes in the retinal expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were examined by immunofluorescence. A mouse model of acute blood stasis was then established, and the effects of TPP on haemorheology were observed. The anti-inflammatory effect of TPP was analysed based on the changes in abdominal capillary permeability and the degree of auricle swelling in the mice. RESULTS: In streptozotocin (STZ)-induced DR rats, TPP (0.4 g/kg) treatment restored electrophysiology indexes and retinal ultrastructures, reduced serum IL-6 and TNF-α levels, decreased VEGF and bFGF expression in retinal tissues, and improved haemorheology indexes. Moreover, TPP reduced abdominal capillary permeability and relieved auricle swelling in a dose-dependent manner. CONCLUSIONS: TPP treatment ameliorated DR by inhibiting inflammation and improving blood circulation.

Protective effects of the Chinese herbal medicine prescription Zhujing pill on retina of streptozotocin-induced diabetic rats.

OBJECTIVE: In this study, we investigate the protective effects of the Chinese herbal medicine prescription Zhujing pill (ZJP) on the development of diabetic retinopathy (DR) and explore the potential mechanisms. MATERIALS AND METHODS: Zhujing pill extract (ZJPE) was prepared, and the main components were identified by high-performance liquid chromatography (HPLC). Several serum and tissue (retina) parameters were measured, such as levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), advanced glycation end products (AGEs), and high sensitivity C-reactive protein (hsCRP). Aldose reductase (AR) activity and blood-retinal barrier (BRB) breakdown were determined. Finally, retinal electrophysiology and morphological changes were assayed. RESULTS: In STZ-induced DM rats, ZJPE treatment restored the body weight decrease. DM rats showed decreased levels of SOD and GSH-Px and increased levels of IL-6, TNF-α, hsCRP, and MDA, whereas all these changes were significantly reversed by ZJPE administration. ZJPE alleviated BRB breakdown. Furthermore, ZJPE also alleviated the retinal electrophysiology changes and impaired morphology of the retina and lowered the high levels of TNF-α, IL-1ß, ICAM-1, VEGF, AGEs, and AR in the retina. CONCLUSIONS: ZJPE treatment attenuated the progression of DR in STZ-induced diabetic rats.

Molecular cytogenetic identification of a novel wheat-Agropyron elongatum chromosome translocation line with powdery mildew resistance.

Agropyron elongatum (Host.) Neviski (synonym, Thinopyrum ponticum Podp., 2n = 70) has been used extensively as a valuable source for wheat breeding. Numerous chromosome fragments containing valuable genes have been successfully translocated into wheat from A. elongatum. However, reports on the transfer of powdery mildew resistance from A. elongatum to wheat are rare. In this study, a novel wheat-A. elongatum translocation line, 11-20-1, developed and selected from the progenies of a sequential cross between wheat varieties (Lankaoaizaoba, Keyu 818 and BainongAK 58) and A. elongatum, was evaluated for disease resistance and characterized using molecular cytogenetic methods. Cytological observations indicated that 11-20-1 had 42 chromosomes and formed 21 bivalents at meiotic metaphase I. Genomic in situ hybridization analysis using whole genomic DNA from A. elongatum as a probe showed that the short arms of a pair of wheat chromosomes were replaced by a pair of A. elongatum chromosome arms. Fluorescence in situ hybridization, using wheat D chromosome specific sequence pAs1 as a probe, suggested that the replaced chromosome arms of 11-20-1 were 5DS. This was further confirmed by wheat SSR markers specific for 5DS. EST-SSR and EST-STS multiple loci markers confirmed that the introduced A. elongatum chromosome arms belonged to homoeologous group 5. Therefore, it was deduced that 11-20-1 was a wheat-A. elongatum T5DL∙5AgS translocation line. Both resistance observation and molecular marker analyses using two specific markers (BE443538 and CD452608) of A. elongatum in a F2 population from a cross between line 11-20-1 and a susceptible cultivar Yannong 19 verified that the A. elongatum chromosomes were responsible for the powdery mildew resistance. This work suggests that 11-20-1 likely contains a novel resistance gene against powdery mildew. We expect this line to be useful for the genetic improvement of wheat.

[Ligustrazine Promoted the Migration of Bone Marrow Mesenchymal Stem Cells by Up-regulating MMP-2 and MMP-9 Expressions].

OBJECTIVE: To explore the effect of ligustrazine on the migration of bone marrow mesenchymal stem cells (BMSCs) and protein expressions of matrix metalloproteinase-2 and-9 (MMP-2 and MMP-9) in vitro. METHODS: BMSCs were in vitro isolated and cultured using whole bone marrow adherent method, and phenotypes [surface positive antigens (CD29 and CD90) and negative antigens (CD34 and CD45)] identified using flow cytometry. BMSCs were divided into the blank control group, 25, 50, 100 µmol/L ligustrazine group, and the GM6001 group (100 µmol/L ligustrazine +MMPs inhibitor GM6001 ). The migration of BMSCs was tested by Transwell chamber test and wound healing assay after treated with ligustrazine for 24 h. The protein expressions of MMP-2 and MMP-9 were detected by Western blot. RESULTS: The third passage BMSCs grew well in uniform morphology. The expression rate of CD29, CD90, CD34, and CD45 was 96.9%, 97.3%, 0.2%, and 3.0%, respectively. Compared with the blank control group, the number of migrated cells and relative distance of cell invasion increased, and the protein expressions of MMP-2 and MMP-9 were elevated in each ligustrazine group (P < 0.05, P < 0.01). Compared with 100 µmol/L ligustrazine group, the number of migrated cells and relative distance of cell invasion decreased in 25 and 50 µmol/L ligustrazine groups and the GM6001 group (P < 0.01). Protein expression of MMP-2 decreased in 25 and 50 µmol/L ligustrazine groups (P < 0.01). CONCLUSION: Ligustrazine could promote the migration of BMSCs in vitro, and its mechanism might be related to up-regulating expression levels of MMP-2 and MMP-9 protein.

Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells.

The aim of the present study was to investigate the effects of rapamycin and its underlying mechanisms on acute lymphoblastic leukemia (ALL) cells. We found that the p14, p15, and p57 genes were not expressed in ALL cell lines (Molt-4 and Nalm-6) and adult ALL patients, whereas mTOR, 4E-BP1, and p70S6K were highly expressed. In Molt-4 and Nalm-6 cells exposed to rapamycin, cell viability decreased and the cell cycle was arrested at the G1/S phase. Rapamycin restored p14, p15, and p57 gene expression through demethylation of the promoters of these genes. As expected, rapamycin also increased p14 and p15 protein expression in both Molt-4 and Nalm-6 cells, as well as p57 protein expression in Nalm-6 cells. Rapamycin additionally decreased mTOR and p70S6K mRNA levels, as well as p70S6K and p-p70S6K protein levels. However, depletion of mTOR by siRNA did not alter the expression and promoter methylation states of p14, p15, and p57. These results indicate that the inhibitory effect of rapamycin may be due mainly to increased p14, p15, and p57 expression via promoter demethylation and decreased mTOR and p70S6K expression in ALL cell lines. These results suggest a potential role for rapamycin in the treatment of adult ALL.

[Buyang Huanwu decoction promotes neuroblast migration from subventricular zone via inducing angiogenesis after ischemia].

OBJECTIVE: To study the effect of Buyang Huanwu decoction (BYHWD) inducing angiogenesis on the neuroblast migration from the subventricular zone and its mechanisms after focal cerebral ischemia. METHOD: The middle cerebral artery occlusion (MCAO) was performed to mice for 30 minutes to establish the model. The rats were divided into sham group, model group, BYHWD group and endostatin group. BYHWD (20 g x kg(-1), ig) and endostatin (10 µg, sc) were administered 24 h after ischemia once a day for consecutively 14 days. At 14 d after ischemia, the density of micro-vessel and the number of neuroblasts in the ischemia border zone were determined by immunofluorescence staining. The mRNA and protein expression of cell-derived factor-1 (SDF-1) and brain-derived neurotrophic (BDNF) were examined by real-time PCR and Western blot. RESULT: Compared with the model group, BYHWD significantly increased the density of micro-vessel and the number of DCX positive cells in the ischemia border zone (P < 0.01), and significantly increased the SDF-1 and BDNF mRNA and protein expression (P < 0.01). Compared with BYHWD group, endostatin significantly reduced the density of micro-vessel and the number of DCX positive cells in the ischemia border zone (P < 0.01), as well as the SDF-1, BDNF mRNA and protein expression (P < 0.01). CONCLUSION: BYHWD could promote the neuroblast migration from the subventricular zone via inducing angiogenesis after cerebral ischemia, the mechanism may be correlated with up-regulating the expression of SDF-1 and BDNF.

Expression and clinical significance of miRNA-34a in colorectal cancer.

BACKGROUND: The aim of this study was to investigate differences of miRNA-34a expression in benign and malignant colorectal lesions. MATERIALS AND METHODS: Samples of cancer, paraneoplastic tissues and polyps were selected and total RNA was extracted by conventional methods for real-time PCR to detect the miRNA- 34a expression. In addition, the LOVO colorectal cancer cell line was cultured, treated with the demethylating agent 5-azacytidine and screened for differentially expressed miRNA-34a. RESULTS: After the drug treatment, the miRNA-34a expression of colorectal cancer cell line LOVO was increased and real-time PCR showed that levels of expression in both cell line and colorectal cancer tissues were low, as compared to paraneoplastic tissue (p<0.05). Polyps tissues had significantly higher expression than paraneoplastic and colorectal cancer samples (p<0.05). CONCLUSIONS: miRNA-34a-5p may play a role as a tumor suppressor gene in colorectal cancer, with involvement of DNA methylation.

Potential biosorbent based on sugarcane bagasse modified with tetraethylenepentamine for removal of eosin Y.

Tetraethylenepentamine (TEPA) modified sugarcane bagasse (SB), a novel biosorbent (TEPA-MSB), was proved to be an effective adsorbent for anionic dyes due to the introduced functional amino groups. FTIR, TG and DSC analysis were employed to characterize the sorbent. The effects of pH, temperature, contact time and initial concentration of dye on the adsorption of eosin Y were investigated. The experimental data fit very well to the Langmuir model, giving a maximum sorption capacity of 399.04 mg/g at 25 °C. And the kinetic data were well described by the pseudo-second-order kinetic model. pH 6 was the optimal pH for eosin Y adsorption, and the maximum adsorption capacity of TEPA-MSB calculated by Langmuir model was 18 times higher than that of SB.