Search

Background Liver biopsy is the gold standard to assess pathological features (eg inflammation grades) for hepatitis B virus-infected patients although it is invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B ( CHB) have been separately described in relatively small hepatitis B virus ( HBV)-infected samples. We aimed to analyse correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase and HBV- DNA) in large-scale CHB samples and to predict inflammation grades by using clinical parameters and/or gene expressions. Methods We analysed gene expressions with three clinical parameters in 122 CHB samples by an improved regression model. Principal component analysis and machine-learning methods including Random Forest, K-nearest neighbour and support vector machine were used for analysis and further diagnosis models. Six normal samples were conducted to validate the predictive model. Results Significant genes related to clinical parameters were found enriching in the immune system, interferon-stimulated, regulation of cytokine production, anti-apoptosis, and etc. A panel of these genes with clinical parameters can effectively predict binary classifications of inflammation grade (area under the ROC curve [ AUC]: 0.88, 95% confidence interval [ CI]: 0.77-0.93), validated by normal samples. A panel with only clinical parameters was also valuable ( AUC: 0.78, 95% CI: 0.65-0.86), indicating that liquid biopsy method for detecting the pathology of CHB is possible. Conclusions This is the first study to systematically elucidate the relationships among gene expressions, clinical parameters and pathological inflammation grades in CHB, and to build models predicting inflammation grades by gene expressions and/or clinical parameters as well. [ABSTRACT FROM AUTHOR]

The present study investigated the regulatory effects of fish oil and chitosan on the signals of hepatic lipid metabolism and the postulated mechanism in high-fat diet-induced obese rats. Diet supplementation of chitosan and fish oil efficiently suppressed the increased weights in body and livers of high-fat diet-fed rats. Supplementation of chitosan and fish oil significantly decreased the activities of hepatic lipid biosynthesis-related enzymes and efficiently regulated plasma lipoprotein homeostasis. Both chitosan and fish oil significantly ameliorated the alterations in the protein expressions of hepatic lipogenic transcription factors (LXRα and PPARα), and could also significantly regulate the downstream hepatic lipogenic genes (FAS, HMGCR, CYP7A1, FATP, FABP, AOX, and ABCA) expressions in high-fat diet-fed rats. These results suggest that both fish oil and chitosan exerts downregulative effects on hepatic lipid metabolism in high-fat diet-induced obese rats via the LXRα inhibition and PPARα activation, which further affect the expressions of hepatic lipogenesis-associated genes. [ABSTRACT FROM AUTHOR]

Objective: Human cytochrome P450 2C9 (CYP2C9), CYP2C19, and CYP2D6 (corresponding to rat CYP2C11, CYP2C6V, and CYP2D3, respectively) are the major enzymes responsible for the metabolism of a wide range of drugs and chemicals. Changes in CYP efficiency are associated with disease susceptibility that can lead to drug toxicity or ineffective therapy. We aimed to examine the effects of lipopolysaccharide (LPS)-induced endotoxemia on gene expressions of hepatic microsomal CYP enzymes in rats. Material and Methods: Male Wistar albino rats were allocated into two subgroups of control and LPS. Saline or LPS (10 mg/kg) of same volume (1 mL/kg) was intraperitoneally (i.p.) injected into rats. After 4 hours, liver tissues were removed. Hepatic mRNA expressions of the CYP enzymes were quantitatively analyzed using real-time polymerase chain reaction (PCR). Results: Hepatic gene expressions of CYP2C11 and CYP2C6V decreased (3.35 and 2.25 fold, respectively) in the endotoxemic rats; however, CYP2D3 expression did not change. Conclusion: Our results revealed that endotoxemia changes CYP2C11- and CYP2C6V-mediated drug metabolism. Therefore, drug dosage must be cautiously ad- justed in the patients with endotoxemia and sepsis. [ABSTRACT FROM AUTHOR]

We investigated whether maternal over-nutrition during pregnancy and lactation affects the offspring's lipid metabolism at weaning by assessing liver lipid metabolic gene expressions and analysing its mechanisms on the development of metabolic abnormalities. Female Sprague-Dawley rats were fed with standard chow diet (CON) or high-fat diet (HFD) for 8 weeks, and then continued feeding during gestation and lactation. The offspring whose dams were fed with HFD had a lower birth weight but an increased body weight with impaired glucose tolerance, higher serum cholesterol, and hepatic steatosis at weaning. Microarray analyses showed that there were 120 genes differently expressed between the two groups. We further verified the results by qRT-PCR. Significant increase of the lipogenesis ( Me1, Scd1) gene expression was found in HFD ( P<0.05), and up-regulated expression of genes ( PPAR-α, Cpt1α, Ehhadh) involved in β-oxidation was also observed ( P<0.05), but the Acsl3 gene was down-regulated ( P<0.05). Maternal over-nutrition could not only primarily induce lipogenesis, but also promote lipolysis through an oxidation pathway as compensation, eventually leading to an increased body weight, impaired glucose tolerance, elevated serum cholesterol and hepatic steatosis at weaning. This finding may provide some evidence for a healthy maternal diet in order to reduce the risk of metabolic diseases in the early life of the offspring. [ABSTRACT FROM AUTHOR]

Human Bone Marrow Stromal Cells (hBMSCs) can migrate from bone marrow to injured tissues, where they may differentiate into different types of new cells for replacement of dysfunctional cells. CD44 plays an important role in stem cell movement. The expression distribution of CD44 standard form (CD44S) and CD44 variants (CD44V) is closely related to cell movement and tissue migration. The aim of this study was to evaluate the expressions of CD44S and CD44V in hBMSCs. The hBMSCs from four human subjects were cultured in vitro. Phenotypic properties were analyzed by flow cytometry, and adipocyte and osteoblast differentiations were evaluated at passage 4. The expressions of CD44S and CD44V were examined using quantitative real-time polymerase chain reaction (q-PCR). Results showed that hBMSCs were successfully cultured, with positive expressions of markers of mesenchymal cells (CD90, CD73, CD105), and negative expressions of markers of hematopoietic cells (CD34, CD45). The cultured hBMSCs can be induced to differentiate into adipocytes and osteoblasts. Q-PCR results showed that the expression of CD44S was significantly higher than the expressions of different CD44V isoforms in different samples. These results revealed significant differences in the distributions of CD44S and CD44V gene expressions, demonstrating a dominant CD44S expression in hBMCSs. [ABSTRACT FROM AUTHOR]

Toxicity of Cd was tested with the hemocytes of the freshwater crab, Sinopotamon henanense , which were exposed to concentrations of 0, 0.725, 1.450, and 2.900 mg L −1 Cd for 7, 14 and 21 d. We investigated the effects of Cd on the total antioxidant capacity (TAC), and oxidative damage of biomarkers, such as malondialdehyde (MDA), protein carbonyl derivates (PCO), and DNA–protein crosslink (DPC). Transmission electron microscopy (TEM) was applied to assess ultrastructural changes of hemocytes. The mRNA expression levels of prophenoloxidase ( proPO ), lysozyme ( LSZ ), metallothionein ( MT ), and the activity of phenoloxidase (PO) were also determined. Our results showed that TAC was inhibited by Cd, resulting in an increase of MDA contents, PCO contents, and DPC levels in hemocytes, respectively. Ultrastructural observations revealed that chromatin condensation, nucleus deformation, mitochondrial dilation, rough endoplasmatic reticulum (rER) degranulation and secondary or tertiary lysosomes were observed in hemocytes of crabs exposed to Cd. Meanwhile, the expression levels of proPO were down-regulated, while the activity of PO was up-regulated in hemocytes. The expression levels of LSZ and MT were up-regulated to some extent. Our findings suggest these parameters could be used as biomarkers in the monitoring of heavy metal pollution and quantitative risk assessments of pollutant exposure. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ultrasonic-assisted hypochlorite activation effectively enhanced VFAs yield. • Solubilization and hydrolysis steps were improved by synergetic pretreatment. • The content and bioavailability of organic substrates were remarkably enhanced. • The functional anaerobes (e.g., Proteiniclasticum and Fonticella) were enriched. • The microbial metabolic activities for VFAs biosynthesis were up-regulated. The effective disruption of extracellular polymeric substances using appropriate pretreatment is critical to achieving resource recovery from sewage sludge (SS) by anaerobic fermentation. This work proposed an ultrasonic-assisted hypochlorite activation strategy for enhanced production of volatile fatty acids (VFAs) during SS fermentation. The results demonstrated that after individual ultrasonic and hypochlorite pretreatment, the maximum VFAs yield improved by 8 and 107% with that in control, respectively, while a combination of both techniques led to an improvement of 119%, indicating their synergistic effects on SS fermentation. This method enhanced the solubilization and hydrolysis efficiencies and contributed to the increased biodegradable substrates, which would be beneficial in enhancing microbial activity for VFAs production. The functional anaerobes, metabolic pathways, and gene expressions involved in VFAs biosynthesis were effectively improved. This work would bring a novel insight into the disposal of municipal solid waste for resource recovery. [ABSTRACT FROM AUTHOR]

We investigated the effects of α-tocopherol on oxidative stress-caused damage caused by copper II oxide nanoparticles (CuO NPs) on Oncorhynchus mykiss gonadal cells (RTG-2) for 24 and 48 h. α-Tocopherol reversed the cell death and alterations in the expressions of genes such as sod1, gpx1a, gpx4b, and igf2 caused by CuO NPs; it also supported the expressions of cat, igf1, and gapdh genes caused by CuO NPs for 24 h and promoted alterations in the expressions of the sod2, gh1 , and igf1 genes for 48 h. Additionally, α-tocopherol reversed the caspase 3/7 activity increased by CuO NPs for 24 h and supported it's decrease for 48 h. α-Tocopherol supported the increase in tail DNA (%) affected by CuO NPs for 24 h and reversed it for 48 h. Therefore, α-tocopherol may have the potential to protect against cellular alterations induced by CuO NPs in a time-dependent manner. • CuO NPs caused cytotoxicity, caspase 3/7 activity and tail DNA in the RTG-2 cells. • Tocopherol reduced cytotoxicity, caspase 3/7 activity induced by CuO NPs. • Tocopherol did not make a significant impact on antioxidant enzyme genes at 48 h. • Tocopherol supported the expressions of growth genes (gh1, igf1) changed by CuO NPs. • Tocopherol decreased the expression of the glycolytic gene compared to CuO NPs. [ABSTRACT FROM AUTHOR]

Root hairs are tubular outgrowths that originate from epidermal cells. Exposure of Arabidopsis to cadmium (Cd) and arsenic [arsenite, As(III)] increases root hair density and length. To examine the underlying mechanism, we measured the expression of genes involved in fate determination and morphogenesis of root hairs. Cd and As(III) downregulated TTG1 and GL2 (negative regulators of fate determination) and upregulated GEM (positive regulator), suggesting that root hair fate determination is stimulated by Cd and As(III). Cd and As(III) increased the transcript levels of genes involved in root hair initiation (RHD6 and AXR2) and root hair elongation (AUX1, AXR1, ETR1, and EIN2) except CTR1. DR5::GUS transgenic Arabidopsis showed a higher DR5 expression in the root tip, suggesting that Cd and As(III) increased the auxin content in the root tip. Knockdown of TTG1 in Arabidopsis resulted in increased root hair density and decreased root hair length compared with the control (Col-0) on 1/2 MS media. This phenotype may be attributed to the downregulation of GL2 and CTR1 and upregulation of RHD6. By contrast, gem mutant plants displayed a decrease in root hair density and length with reduced expression of RHD6, AXR2, AUX1, AXR1, ETR1, CTR1, and EIN2. Taken together, our results indicate that fate determination, initiation, and elongation of root hairs are stimulated in response to Cd and As(III) through the modulation of the expression of genes involved in these processes in Arabidopsis.

Aeromonas hydrophila can pose a great threat to fish survival. In this study, we investigated the differential immune and redox response in gut-liver axis of hybrid fish (WR) undergoing gut infection. WR anally intubated with A. hydrophila showed severe midgut injury with decreased length-to-width ratios of villi along with GC hyperplasia and enhanced antioxidant activities, but expression profiles of cytokines, chemokines, antibacterial molecules, redox sensors and tight junction proteins decreased dramatically. In contrast, immune-related gene expressions and antioxidant activities increased significantly in liver of WR following gut infection with A. hydrophila. These results highlighted the differential immune regulation and redox balance in gut-liver axis response to bacterial infection. [Display omitted] • Severe midgut injury with GC hyperplasia was observed in WR anally intubated with A. hydrophila. • Suppressions of tight junction molecules were observed in midgut of WR following gut infection. • WR receiving gut infection with A. hydrophila exhibited differential immune and redox response in gut-liver axis. [ABSTRACT FROM AUTHOR]

This study aims to elucidate the underlying molecular mechanisms of artemisinin accumulation induced by Cd. The effects of different Cd concentrations (0, 20, 60, and 120 μmol/L) on the biosynthesis of Artemisia annua L. were examined. Intermediate and end products were quantified by HPLC-ESI-MS/MS analysis. The expression of key biosynthesis enzymes was also determined by qRT-PCR. The results showed that the application of treatment with 60 and 120 μmol/L Cd for 3 days significantly improved the biosynthesis of artemisinic acid, arteannuin B, and artemisinin. The concentrations of artemisinic acid, arteannuin B, and artemisinin in the 120 μmol/L Cd-treated group were 2.26, 102.08, and 33.63 times higher than those in the control group, respectively. The concentrations of arteannuin B and artemisinin in 60 μmol/L Cd-treated leaves were 61.10 and 26.40 times higher than those in the control group, respectively. The relative expression levels of HMGR, FPS, ADS, CYP71AV1, DBR2, ALDH1, and DXR were up-regulated in the 120 μmol/L Cd-treated group because of increased contents of artemisinic metabolites after 3 days of treatment. Hence, appropriate doses of Cd can increase the concentrations of artemisinic metabolites at a certain time point by up-regulating the relative expression levels of key enzyme genes involved in artemisinin biosynthesis. [ABSTRACT FROM AUTHOR]

An experiment was conducted to investigate the effect of dietary non-phytate phosphorus (NPP) level on growth performance, bone characteristics and phosphorus metabolism-related gene expressions, so as to evaluate the dietary NPP requirement of broiler chicks fed a conventional corn-soybean meal diet from 1 to 21 d of age. A total of 540 day-old Arbor Acres male chicks were randomly allocated to one of nine treatments with six replicate cages of 10 birds per cage in a completely randomized design, and fed a basal corn-soybean meal diet (containing 0.08% of NPP) supplemented with 0.10, 0.15, 0.25, 0.30, 0.35, 0.40, 0.45, or 0.50% of inorganic phosphorus in the form of CaHPO4·2H2O, respectively. Each diet contained the constant calcium content of about 1.0%. The results showed that daily weight gain, serum inorganic P, tibia bone strength, tibia ash percentage, tibia bone mineral content (BMC) and density (BMD), middle toe ash percentage, middle toe BMC and BMD were affected (P < 0.0001) by dietary NPP level, and increased linearly (P < 0.0001) and quadraticly (P < 0.004) as dietary NPP levels increased. The gene expression of type IIb sodium-phosphate cotransporter (NaPi-IIb) in the duodenum was affected (P < 0.03) and decreased linearly (P < 0.002) as dietary NPP levels increased. Dietary NPP requirements estimated based on fitted broken-line models (P < 0.0001) of the sensitive indices including daily weight gain, tibia bone strength, tibia ash percentage, tibia BMC and BMD as well as middle toe ash percentage were 0.34-0.39%. The results from this study indicate that tibia BMC and BMD might be new, sensitive, and noninvasive criteria to evaluate the dietary NPP requirements of broilers, and the dietary NPP requirement is 0.39% for broiler chicks fed a conventional corn-soybean meal diet from 1 to 21 d of age. [ABSTRACT FROM AUTHOR]

3,6-Diazaphenothiazines were obtained in cyclization of 3-amino-3′-nitro-2,4′-dipyridinyl sulfide and the reaction of sodium 3-amino-2-pyridinethiolate with 4-chloro-3-nitropyridine followed by alkylation and heteroarylation. The thiazine ring formation ran via the Smiles rearrangement. The structure elucidation was based on 2D NMR and X-ray analysis ofN-methylated product. 3,6-Diazaphenothiazines were investigated for antitumor activity using glioblastoma SNB-19, melanoma C-32 and breast cancer MCF-7 cells. 10H-3,6-diazaphenothiazine was 10 times more active (IC50 < 0.72 μg/mL) than cisplatin. Two diazaphenothiazines with the 2-pyrimidinyl and dimethylaminopropyl substituents were selectively active against MCF-7 and C-32 cells. The expressions ofH3(proliferation marker),TP53, CDKN1A(cell cycle regulators), BAXandBCL-2(proapoptopic and antiapoptopic genes) were detected by RT-QPCR method. The expression analysis suggests the cell cycle arrest and the mitochondrial apoptosis pathway activation in MCF-7 and SNB-19 cells. [ABSTRACT FROM PUBLISHER]

Root hairs are tubular outgrowths that originate from epidermal cells. Exposure of Arabidopsis to cadmium (Cd) and arsenic [arsenite, As(III)] increases root hair density and length. To examine the underlying mechanism, we measured the expression of genes involved in fate determination and morphogenesis of root hairs. Cd and As(III) downregulated TTG1 and GL2 (negative regulators of fate determination) and upregulated GEM (positive regulator), suggesting that root hair fate determination is stimulated by Cd and As(III). Cd and As(III) increased the transcript levels of genes involved in root hair initiation (RHD6 and AXR2) and root hair elongation (AUX1, AXR1, ETR1, and EIN2) except CTR1. DR5::GUS transgenic Arabidopsis showed a higher DR5 expression in the root tip, suggesting that Cd and As(III) increased the auxin content in the root tip. Knockdown of TTG1 in Arabidopsis resulted in increased root hair density and decreased root hair length compared with the control (Col-0) on 1/2 MS media. This phenotype may be attributed to the downregulation of GL2 and CTR1 and upregulation of RHD6. By contrast, gem mutant plants displayed a decrease in root hair density and length with reduced expression of RHD6, AXR2, AUX1, AXR1, ETR1, CTR1, and EIN2. Taken together, our results indicate that fate determination, initiation, and elongation of root hairs are stimulated in response to Cd and As(III) through the modulation of the expression of genes involved in these processes in Arabidopsis. [ABSTRACT FROM AUTHOR]

Terpenoids were isolated using chromatographic purification through solvent purification technique and identified as Azadirone ( 1 ), Epoxyazadiradione ( 2 ) Azadiradione ( 3 ) Gedunin ( 4 ) Nimbin ( 5 ) Salannin ( 6 ) Azadirachtin A ( 7 ) and Azadirachtin B ( 8 ) from Azadirachta indica . Out of eight compounds, only three compounds had osteogenic activity and enhanced osteoblast proliferation, differentiation and mineralization in osteoblast cells. Active compounds stimulated osteogenic genes ALP, RunX-2 and OCN expressions in vitro, but Azadirachtin A had a maximum ability to stimulate osteoblast differentiation and mineralization compared to other two active compounds. For in vivo study, Azadirachtin A injected subcutaneously in pups, which enhanced osteogenic gene expressions and promoted bone formation rate significantly. Here, we conclude that active compounds of Azadirachta indica have osteogenic activity and Azadirachtin A has a beneficial effects on bone. [ABSTRACT FROM AUTHOR]

The impacts of environmental stressors on polyploid organisms are largely unknown. This study investigated changes in morphometric, molecular, and biochemical parameters in full-sibling diploid and triploid African catfish ( Clarias gariepinus ) in response to chlorpyrifos (CPF) exposures. Juvenile fish were exposed to three concentrations of CPF (mean measured μg/L (SD): 9.71 (2.27), 15.7 (3.69), 31.21 (5.04)) under a static-renewal condition for 21 days. Diploid control groups had higher hepatosomatic index (HSI), plasma testosterone (T), and brain GnRH and cyp19a2 expression levels than triploids. In CPF-exposed groups, changes in HSI, total weight and length were different between the diploid and triploid fish. In contrast, condition factor did not alter in any of the treatments, while visceral-somatic index (VSI) changed only in diploids. In diploid fish, exposure to CPF did not change brain 11β-hsd2 , ftz-f1 , foxl2 , GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group. In contrast, 11β-hsd2 and foxl2 expression levels were changed in triploids following CPF exposures. In diploids, plasma T levels showed a linear dose-response reduction across CPF treatments correlating with liver weight and plasma total cholesterol concentrations. In contrast, no changes in plasma cholesterol and T concentrations were observed in triploids. Plasma cortisol and 17-β estradiol (E 2 ) showed no response to CPF exposure in either ploidy. Results of this first comparison of biomarker responses to pesticide exposure in diploid and polyploid animals showed substantial differences between diploid and triploid C. gariepinus . [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was the verification of the applicability of NPHS2/SYNPO ratio for diagnosis of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) in Czech patients and identification of new markers for distinguishing between MCD and FSGS. Material and methods: Our study was performed on 24 samples from patients with FSGS and MCD. Gene expressions were determined using relative quantitative real-time PCR and TaqMan® Array Micro Fluidic Cards and normalized to the reference gene GAPDH. Results and conclusion: Our results did not find any significant difference in the podocin/synaptopodin ratio and in any other studied genes between FSGS and MCD. [ABSTRACT FROM AUTHOR]

In many practical cases of multiple hypothesis problems, it can be expected that the alternatives are not symmetrically distributed. If it is known a priori that the distributions of the alternatives are skewed, we show that this information yields high power procedures as compared to the procedures based on symmetric alternatives when testing multiple hypotheses. We propose a Bayesian decision theoretic rule for multiple directional hypothesis testing, when the alternatives are distributed as skewed, under a constraint on a mixed directional false discovery rate. We compare the proposed rule with a frequentist's rule of Benjamini and Yekutieli (2005) using simulations. We apply our method to a well-studied HIV dataset. [ABSTRACT FROM AUTHOR]

Twenty-four organic Fe sources were evaluated by polarographic analysis and via solubility in buffers (pH 5 and 2) and deionized water. Organic Fe sources included 6 Fe-Met complexes (Fe-Met), 10 Fe-Gly complexes, 1 Fe-Lys complex, 4 Fe proteinates, and 3 Fe-AA complexes (Fe-AA). Sources varied considerably in chemical characteristics. Chelation strengths (quotient of formation [Qf] values) ranged from weak (Qf = 1.08) to extremely strong strength (Qf = 8,590). A total of 1,170 1-d-old Arbor Acres male broilers were randomly allotted to 6 replicate cages (15 chicks/cage) for each of 13 treatments in a completely randomized design involving a 4 × 3 factorial arrangement of treatments (4 Fe sources × 3 added Fe levels) plus a control with no added Fe. Dietary treatments included a corn-soybean meal basal diet (control; 55.8 mg Fe/kg) and the basal diet supplemented with 20, 40, or 60 mg Fe/ kg as iron sulfate (FeSO4∙7H2O); an Fe-Met with weak chelation strength (Fe-Met W; Qf = 1.37; 14.7% Fe); an iron proteinate with moderate chelation strength (Fe-Prot M; Qf = 43.6; 14.2% Fe); or an iron proteinate with extremely strong chelation strength (Fe-Prot ES; Qf = 8,590; 10.2% Fe). The growth performance, Fe concentrations, hematological indices, and activities and gene expressions of 2 Fe-containing enzymes in tissues of broilers at 7, 14, and 21 d of age were determined in the present study. Transferrin saturation in plasma on 14 d; bone Fe on d 7 and 14; liver Fe on d 7, 14, and 21; kidney Fe on d 14; succinate dehydrogenase activities in the liver on d 21 and in the kidney on d 7 and 21; catalase mRNA levels in the kidney and heart on d 14; and succinate dehydrogenase mRNA levels in the liver and kidney on d 21 linearly increased (P < 0.05) as added Fe levels increased. However, differences in bioavailabilities among Fe sources were detected (P < 0.05) only for the succinate dehydrogenase mRNA levels in the liver and kidney on d 21. Based on slope ratios from the multiple linear regression of succinate dehydrogenase mRNA level in the liver or kidney of broilers on d 21 on daily dietary analyzed Fe intake, the bioavailabilities of Fe-Met W, Fe-Prot M, and Fe-Prot ES relative to iron sulfate (100%) were 129 (P = 0.18), 164 (P < 0.003), and 174% (P < 0.001) or 102 (P = 0.95), 143 (P = 0.09), and 174% (P < 0.004), respectively. These results indicated that the relative bioavailabilities of organic Fe sources were closely related to their Qf values and organic Fe sources with greater Qf values showed higher Fe bioavailabilities. [ABSTRACT FROM AUTHOR]

Multiple K channel complexes contribute to total K current in numerous cell types and usually subserve different physiological functions. Identifying the complete compliment of functional K channel subunits in cells is a prerequisite to understanding regulatory function. It was the goal of this work to determine the complete K subunit compliment that contribute to functional K currents in rat small mesenteric artery (SMA) myocytes as a prelude to studying channel regulation. Using RNA prepared from freshly dispersed myocytes, high levels of K 1.2, 1.5, and 2.1 and lower levels of K 7.4 α-subunit expressions were demonstrated by quantitative PCR and confirmed by Western blotting. Selective inhibitors correolide ( K 1; COR), stromatoxin ( K 2.1; ScTx), and linopirdine ( K 7.4; LINO) decreased K current at +40 mV in SMA by 46 ± 4, 48 ± 4, and 6.5 ± 2 %, respectively, and K current in SMA was insensitive to α-dendrotoxin. Contractions of SMA segments pretreated with 100 nmol/L phenylephrine were enhanced by 27 ± 3, 30 ± 8, and 7 ± 3 % of the response to 120 mmol/L KCl by COR, ScTX, and LINO, respectively. The presence of K 6.1, 9.3, β1.1, and β1.2 was demonstrated by RT-PCR using myocyte RNA with expressions of Kβ1.2 and K 9.3 about tenfold higher than Kβ1.1 and K 6.1, respectively. Selective inhibitors of K 1.3, 3.4, 4.1, and 4.3 channels also found at the RNA and/or protein level had no significant effect on K current or contraction. These results suggest that K current in rat SMA myocytes are dominated equally by two major components consisting of K 1.2-1.5-β1.2 and K 2.1-9.3 channels along with a smaller contribution from K 7.4 channels but differences in voltage dependence of activation allows all three to provide significant contributions to SMA function at physiological voltages. [ABSTRACT FROM AUTHOR]

Information on the biological responses of polyploid animals towards environmental contaminants is scarce. This study aimed to compare reproductive axis-related gene expressions in the brain, plasma biochemical responses, and the liver and gill histopathological alterations in diploid and triploid full-sibling juvenile African catfish ( Clarias gariepinus ). Fish were exposed for 96 h to one of the two waterborne phenanthrene (Phe) concentrations [mean measured (SD): 6.2 (2.4) and 76 (4.2) μg/L]. In triploids, exposure to 76 μg/L Phe increased mRNA level of f ushi tarazu-factor 1 ( ftz-f1 ). Expression of tryptophan hydroxylase2 ( tph2 ) was also elevated in both ploidies following the exposure to 76 μg/L Phe compared to the solvent control. In triploids, 76 μg/L Phe increased plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels compared to the other Phe-exposed group. It also elevated lactate and glucose contents relative to the other groups. In diploids, however, biochemical biomarkers did not change. Phenanthrene exposures elevated glycogen contents and the prevalence of histopathological lesions in the liver and gills of both ploidies. This study showed substantial differences between diploids and triploids on biochemical and molecular biomarker responses, but similar histopathological alterations following acute Phe exposures. [ABSTRACT FROM AUTHOR]

DNase I hypersensitive sites (DHSs) mark diverse classes of cis-regulatory regions, such as promoters and enhancers. MSB-1 derived from chicken Marek's disease (MD) lymphomas is an MDV-transformed CD4+ T-cell line for MD study. Previously, DNase I HS sites were studied mainly in human cell types for mammalian. To capture the regulatory elements specific to MSB1 cells and explore the molecular mechanisms of T-cell transformation caused by MDV in MD, we generated high-quality of DHSs map and gene expression profile for functional analysis in MSB1 cell line. The total of 21,724 significant peaks of DHSs was identified from around 40 million short reads. DHSs distribution varied between chromosomes and they preferred to enrich in the gene-rich chromosomes. More interesting, DHSs enrichments appeared to be scarce on regions abundant in CpG islands. Besides, we integrated DHSs into the gene expression data and found that DHSs tended to enrich on high expressed genes throughout whole gene regions while DHSs did not show significant changes for low and silent expressed genes. Furthermore, the correlation of DHSs with lincRNAs expression was also calculated and it implied that enhancer-associated lincRNAs probably originated from enhancer-like regions of DHSs. Together, our results indicated that DNase I HS sites highly correlate with active genes expression in MSB1 cells, suggesting DHSs can be considered as markers to identify the cis-regulatory elements associated with chicken Marek’s disease.

We have studied the expression of insulin-like growth factor receptor (IGF1R) and insulin-like growth factor binding protein (IGFBP4 and IGFBP5) genes in U87 glioma cells upon glutamine deprivation condition in relation to inhibition of ERN1 (endoplasmic reticulum to nuclei signaling 1), a sensor and signaling enzyme of endoplasmic reticulum stress, which control cell proliferation. It was shown that exposure control glioma cells upon glutamine deprivation condition leads to up-regulation of IGFBP4 and down-regulation of IGF1R expression at the mRNA level in control glioma cells, but IGFBP5 gene expression in these cells does not depend upon glutamine deprivation. At the same time, inhibition of IRE1 modifies the effect of glutamine deprivation on the expression of IGFBP5 gene because in glioma cells without functional activity of ERN1 glutamine deprivation leads to suppression of this IGFBP. We have also shown that the expression of all studied genes in glioma cells is regulated by ERN1 signaling enzyme at standard condition because ERN1 inhibition significantly enhances the expression of IGFBP4 and IGFBP5 genes. Proteins encoded by these genes are major inhibitors of pro-proliferative activity of insulin-like growth factors IGF1 and IGF2. We have also shown upregulation of the expression level of IGF1R gene in glioma cells with ERN1 knockdown as compared to control glioma cells. Results of this study shown that glutamine deprivation affects the expression of studied genes and that ERN1 inhibition preferentially changes these genes expression. [ABSTRACT FROM AUTHOR]

To investigate Fe deficiency tolerance in tomato cultivars, quantification of proteins and genes involved in Fe metabolism and antioxidant mechanisms were performed in "Roggusanmaru" and "Super Doterang". Fe deficiency (Moderate, low and -Fe) significantly decreased the biomass, total, and apoplastic Fe concentration of "Roggusanmaru", while a slight variation was observed in "Super Doterang" cultivar. The quantity of important photosynthetic pigments such as total chlorophyll and carotenoid contents significantly decreased in "Roggusanmaru" than "Super Doterang" cultivar. The total protein profile in leaves and roots determines that "Super Doterang" exhibited an optimal tolerance to Fe deficiency compared to "Roggusanmaru" cultivar. A reduction in expression of PSI (photosystem I), PSII (photosystem II) super-complexes and related thylakoid protein contents were detected in "Roggusanmaru" than "Super Doterang" cultivar. Moreover, the relative gene expression of SlPSI and SlPSII were well maintained in "Super Doterang" than "Roggusanmaru" cultivar. The relative expression of genes involved in Fe-transport (SlIRT1 and SlIRT2) and Fe(III) chelates reductase oxidase (SlFRO1) were relatively reduced in "Roggusanmaru", while increased in "Super Doterang" cultivar under Fe deficient conditions. The H+-ATPase relative gene expression (SlAHA1) in roots were maintained in "Super Doterang" compared to "Roggusanmaru". Furthermore, the gene expressions involved in antioxidant defense mechanisms (SlSOD, SlAPX and SlCAT) in leaves and roots showed that these genes were highly increased in "Super Doterang", whereas decreased in "Roggusanmaru" cultivar under Fe deficiency. The present study suggested that "Super Doterang" is better tomato cultivar than "Roggusanmaru" for calcareous soils. [ABSTRACT FROM AUTHOR]

Finding bio-markers for complex disease from gene expression profiles attracts extensive attentions for its potential use in diagnosis, therapy, and drug design. In this paper we propose a network-based method to seek high-confident bio-markers from candidate genes collected in the literature. The algorithm includes three consequent steps. First, one can collect the proposed bio-markers in literature as being the preliminary candidate; Second, a spanning-tree based threshold can be used to reconstruct gene networks for normal and cancer samples; Third, by jointly using of degree changes and distribution of the candidates in communities, one can filter out the low-confident genes. The survival candidates are high-confident genes. Specially, we consider expression profiles for carcinoma of colon. A total of 34 preliminary bio-markers collected from literature are evaluated and a set of 16 genes are proposed as high confident bio-markers, which behave high performance in distinguishing normal and cancer samples. [ABSTRACT FROM AUTHOR]

In this study, chitooligosaccharides (COSs) with varying degrees of acetylation (DAs) were applied to wheat seedlings in order to investigate their effect on the plants’ defence response under salt stress. The results showed that treatment with exogenous COSs that had different DAs could promote the growth of plants, decrease the concentration of malondialdehyde (MDA), improve the photosynthetic efficiency and enhance the activities of antioxidant enzymes. The mRNA expression level examination of several salt stress response genes suggested that COS could protect plants from the damage of salt stress by adjusting intracellular ion concentration and enhancing the activities of antioxidant enzymes. Furthermore, COS with DA 50% was the most effective in alleviating salt stress to wheat seedlings, which indicated that the activity of COS was closely related with its DAs. [ABSTRACT FROM AUTHOR]

This article studied the effects of platelet-rich plasma (PRP) on the potential of synovial fluid mesenchymal stem cells (SF-MSCs) to differentiate. The PRP and SF-MSCs were obtained from the blood and knees of pigs, respectively. The identification of SF-MSCs and their ability to differentiate were studied by histological and surface epitopes, respectively. The SF-MSCs can undergo trilineage mesenchymal differentiation under osteogenic, chondrogenic, and adipocyte induction. The effects of various PRP concentrations (0%, 20% and 50% PRP) on differentiation were evaluated using the SF-MSCs-alginate system, such as gene expression and DNA proliferation. A 50% PRP concentration yielded better differentiation than the 20% PRP concentration. PRP favored the chondrogenesis of SF-MSCs over their osteogenesis in a manner that depended on the ratios of type II collagen/type I collagen and aggrecan/osteopontin. Eventually, PRP promoted the proliferation of SF-MSCs and induced chondrogenic differentiation of SF-MSCs in vitro. Both PRP and SF-MSCs could be feasibly used in regenerative medicine and orthopedic surgeries. [ABSTRACT FROM AUTHOR]

This work investigated the effect of Escherichia coli K88 and zearalenone contamination on pro-inflammatory gene expression (Toll like receptors, cytokines) and signalling molecules and the protective activity of a mixture of Lactobacilli sp. ( Lactobacillus plantarum , Lactobacillus acidofilus and Lactobacillus paracasei ) in porcine intestinal epithelial cells as part of the local immune system. IPEC-1 cell monolayer was exposed for 1 h to the individual or combined action of E. coli , zearalenone and lactobacilli mixture. Our results showed that TLRs (1–10) and cytokine (IL-1,-6,-8,-10, TNF-α, IFN-γ) genes expressed early (after 1 h of culture) in IPEC-1 cells. E. coli alone increased the TLRs mRNA expression, especially TLR4 and the inflammatory cytokines while ZEA alone showed either no effect or a marginally effect on TLRs, cytokines, and signalling genes when compared to untreated cells. The combined actions of the two contaminants lead to a synergistically up-regulation of key cytokines (IFN-γ, IL-10 and TNF-α) and TLRs (-2,-3,-4,-6, and -10). The live lactobacilli mixture was able to attenuate the pathogen and mycotoxin-induced response by downregulated the majority of inflammatory related genes suggesting that this mixture has an immunomodulatory potential and may be used to lower the inflammatory response. [ABSTRACT FROM AUTHOR]

Lycium chinense is an important medicinal plant in the northwest of China. Flavonoids are the major pharmacological components of L. chinense fruits. However, flavonoid metabolism during fruit development of L. chinense remains to be studied. Here, we analyzed the change of flavonoid contents, enzyme activity, and gene expression during fruit development of L. chinense. We found that flavonoids, anthocyanins, and catechins are the most important components of L. chinense fruits. Flavonoid content was increased with fruit development and was high at the late developmental stage. PAL, CHS, and F3H enzymes played a significant role in flavonoid accumulation in fruits. Transcriptomic analysis showed that anthocyanin pathway, flavonol pathway, flavonoid biosynthesis, and phenylpropanoid synthesis pathway were the major pathways involved in flavonoid metabolism in L. chinense. Gene expression analysis indicated that PAL1 and CHS2 genes were critical for flavonoid metabolism in L. chinense fruits. These discoveries help us understand the dynamic changes in flavonoids during fruit development and enhance the use of L. chinense fruits. [ABSTRACT FROM AUTHOR]

In this study, we introduce an artificial intelligent method for addressing the batch effect of a transcriptome data. The method has several clear advantages in comparison with the alternative methods presently in use. Batch effect refers to the discrepancy in gene expression data series, measured under different conditions. While the data from the same batch (measurements performed under the same conditions) are compatible, combining various batches into 1 data set is problematic because of incompatible measurements. Therefore, it is necessary to perform correction of the combined data (normalization), before performing biological analysis. There are numerous methods attempting to correct data set for batch effect. These methods rely on various assumptions regarding the distribution of the measurements. Forcing the data elements into pre-supposed distribution can severely distort biological signals, thus leading to incorrect results and conclusions. As the discrepancy between the assumptions regarding the data distribution and the actual distribution is wider, the biases introduced by such "correction methods" are greater. We introduce a heuristic method to reduce batch effect. The method does not rely on any assumptions regarding the distribution and the behavior of data elements. Hence, it does not introduce any new biases in the process of correcting the batch effect. It strictly maintains the integrity of measurements within the original batches., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: In the current genomic era, gene expression datasets have become one of the main tools utilized in cancer classification. Both curse of dimensionality and class imbalance problems are inherent characteristics of these datasets. These characteristics have a negative impact on the performance of most classifiers when used to classify cancer using genomic datasets., Results: This paper introduces Reduced Noise-Autoencoder (RN-Autoencoder) for pre-processing imbalanced genomic datasets for precise cancer classification. Firstly, RN-Autoencoder solves the curse of dimensionality problem by utilizing the autoencoder for feature reduction and hence generating new extracted data with lower dimensionality. In the next stage, RN-Autoencoder introduces the extracted data to the well-known Reduced Noise-Synthesis Minority Over Sampling Technique (RN- SMOTE) that efficiently solve the problem of class imbalance in the extracted data. RN-Autoencoder has been evaluated using different classifiers and various imbalanced datasets with different imbalance ratios. The results proved that the performance of the classifiers has been improved with RN-Autoencoder and outperformed the performance with original data and extracted data with percentages based on the classifier, dataset and evaluation metric. Also, the performance of RN-Autoencoder has been compared to the performance of the current state of the art and resulted in an increase up to 18.017, 19.183, 18.58 and 8.87% in terms of test accuracy using colon, leukemia, Diffuse Large B-Cell Lymphoma (DLBCL) and Wisconsin Diagnostic Breast Cancer (WDBC) datasets respectively., Conclusion: RN-Autoencoder is a model for cancer classification using imbalanced gene expression datasets. It utilizes the autoencoder to reduce the high dimensionality of the gene expression datasets and then handles the class imbalance using RN-SMOTE. RN-Autoencoder has been evaluated using many different classifiers and many different imbalanced datasets. The performance of many classifiers has improved and some have succeeded in classifying cancer with 100% performance in terms of all used metrics. In addition, RN-Autoencoder outperformed many recent works using the same datasets., (© 2023. The Author(s).)