VEGF-C attenuates renal damage in salt-sensitive hypertension

Salt-sensitive hypertension is a major risk factor for renal impairment leading to chronic kidney disease. High-salt diet leads to hypertonic skin interstitial volume retention enhancing the activation of the tonicity-responsive enhancer-binding protein (TonEBP) within macrophages leading to vascular endothelial growth factor C (VEGF-C) secretion and NOS3 modulation. This promotes skin lymphangiogenesis and blood pressure regulation. Whether VEGF-C administration enhances renal and skin lymphangiogenesis and attenuates renal damage in salt-sensitive hypertension remains to be elucidated. Hypertension was induced in BALB/c mice by a high-salt diet. VEGF-C was administered subcutaneously to high-salt-treated mice as well as control animals. Analyses of kidney injury, inflammation, fibrosis, and biochemical markers were performed in vivo. VEGF-C reduced plasma inflammatory markers in salt-treated mice. In addition, VEGF-C exhibited a renal anti-inflammatory effect with the induction of macrophage M2 phenotype, followed by reductions in interstitial fibrosis. Antioxidant enzymes within the kidney as well as urinary RNA/DNA damage markers were all revelatory of abolished oxidative stress under VEGF-C. Furthermore, VEGF-C decreased the urinary albumin/creatinine ratio and blood pressure as well as glomerular and tubular damages. These improvements were associated with enhanced TonEBP, NOS3, and lymphangiogenesis within the kidney and skin. Our data show that VEGF-C administration plays a major role in preserving renal histology and reducing blood pressure. VEGF-C might constitute an interesting potential therapeutic target for improving renal remodeling in salt-sensitive hypertension.     

Schwannoma-Derived Growth Factor Interacts with the Epidermal Growth Factor Receptor

Abstract: Schwannoma-derived growth factor (SDGF) is a potent mitogen and neuronal differentiation factor. Because of its relationship to epidermal growth factor (EGF) and the heregulins, it was asked if SDGF interacts with the EGF receptor or HER2/neu. SDGF binds to and causes the phosphorylation on tyrosine of the EGF receptor but not HER2/neu.     

Resistance training-induced muscle hypertrophy is mediated by TGF-β1-Smad signaling pathway in male Wistar rats

The TGF-β1-Smad pathway is a well-known negative regulator of muscle growth; however, its potential role in resistance training-induced muscle hypertrophy is not clear. The present study proposed to determine whether and how this pathway may be involved in resistance training-induced muscle hypertrophy. Skeletal muscle samples were collected from the control, trained (RT), control + SB431542 (CI_TGF), and trained + SB431542 (RTI_TGF) animals following 3, 5, and 8 weeks of resistance training. Inhibition of the TGF-β1-Smad pathway by SB431542 augmented muscle satellite cells activation, upregulated Akt/mTOR/S6K1 pathway, and attenuated FOXO1 and FOXO3a expression in the CI_TGF group (all p < .01), thereby causing significant muscle hypertrophy in animals from the CI_TGF. Resistance training significantly decreased muscle TGF-β1 expression and Smad3 (P-Smad3^S423/425) phosphorylation at COOH-terminal residues, augmented Smad2 (P-Smad2-L^S245/250/255) and Smad3 (P-Smad3-L^Ser208) phosphorylation levels at linker sites (all p < .01), and led to a muscle hypertrophy which was unaffected by SB431542, suggesting that the TGF-β1-Smad signaling pathway is involved in resistance training-induced muscle hypertrophy. The effects of inhibiting the TGF-β1-Smad signaling pathway were not additive to the resistance training effects on FOXO1 and FOXO3a expression, muscle satellite cells activation, and the Akt/mTOR/S6K1 pathway. Resistance training effect of satellite cell differentiation was independent of the TGF-β1-Smad signaling pathway. These results suggested that the effect of the TGF-β1-Smad signaling pathway on resistance training-induced muscle hypertrophy can be attributed mainly to its diminished inhibitory effects on satellite cell activation and protein synthesis. Suppressed P-Smad3^S423/425 and enhanced P-Smad2-L^S245/250/255 and P-Smad3-L^Ser208 are the molecular mechanisms that link the TGF-β1-Smad signaling pathway to resistance training-induced muscle hypertrophy.     

Effects of alginate and resistant starch on feeding patterns,behaviour and performance in ad libitum-fed growing pigs

This study assessed the long-term effects of feeding diets containing either a gelling fibre (alginate (ALG)), or a fermentable fibre (resistant starch (RS)), or both, on feeding patterns, behaviour and growth performance of growing pigs fed ad libitum for 12 weeks. The experiment was set up as a 2×2 factorial arrangement: inclusion of ALG (yes or no) and inclusion of RS (yes or no) in the control diet, resulting in four dietary treatments, that is, ALG−RS− (control), ALG+RS−, ALG−RS+, and ALG+RS+. Both ALG and RS were exchanged for pregelatinized potato starch. A total of 240 pigs in 40 pens were used. From all visits to an electronic feeding station, feed intake and detailed feeding patterns were calculated. Apparent total tract digestibility of energy, dry matter (DM), and CP was determined in week 6. Pigs’ postures and behaviours were scored from live observations in weeks 7 and 12. Dietary treatments did not affect final BW and average daily gain (ADG). ALG reduced energy and DM digestibility (P<0.01). Moreover, ALG increased average daily DM intake, and reduced backfat thickness and carcass gain : digestible energy (DE) intake (P<0.05). RS increased feed intake per meal, meal duration (P<0.05) and inter-meal intervals (P=0.05), and reduced the number of meals per day (P<0.01), but did not affect daily DM intake. Moreover, RS reduced energy, DM and CP digestibility (P<0.01). Average daily DE intake was reduced (P<0.05), and gain : DE intake tended to be increased (P=0.07), whereas carcass gain : DE intake was not affected by RS. In week 12, ALG+RS− increased standing and walking, aggressive, feeder-directed, and drinking behaviours compared with ALG+RS+ (ALG×RS interaction, P<0.05), with ALG−RS− and ALG−RS+ in between. No other ALG×RS interactions were found. In conclusion, pigs fed ALG compensated for the reduced dietary DE content by increasing their feed intake, achieving similar DE intake and ADG as control pigs. Backfat thickness and carcass efficiency were reduced in pigs fed ALG, which also showed increased physical activity. Pigs fed RS changed feeding patterns, but did not increase their feed intake. Despite a lower DE intake, pigs fed RS achieved similar ADG as control pigs by increasing efficiency in DE use. This indicates that the energy utilization of RS in pigs with ad libitum access to feed is close to that of enzymatically digestible starch.     

Ruptured fission yeast walls

Distributions of rupture sites of fission yeast cells ruptured by glass beads have been related to a new morphometric analysis. As shown previously (Johnson et al.,Cell Biophysics, 1995), ruptures were not randomly distributed nor was their distribution dictated by geometry, rather, ruptures at the extensile end were related to cell length just as the rate of extension is related to cell length. The extension patterns of early log, mid-log, late log, and stationary phase cells from suspension cultures were found to approximate the linear growth patterns of Kubitschek and Clay (1986). The median length of cells was found to decline through the log phase in an unbalanced manner.     

Risk assessment of heavy metal and metalloid toxicity through a contaminated vegetable (Cucurbita maxima) from wastewater irrigated area: A case study for a site-specific risk assessment in Jhang,Pakistan

The present research was conducted in district Jhang, Pakistan, to evaluate the concentration of metals/metalloids in soil and pumpkin (Cucurbita maxima) irrigated with domestic wastewater. Data revealed that the levels of metals and metalloids in soil samples from two different sites were below the safe limits except Cd, whereas, in the vegetable, the concentrations of As, Se, Ni, Mo, Pb, Mn, and Cu were above the safe limits. The levels of 12 metals and metalloids in the soil were ranged between 0.14 to 22.76 mg/kg at site-I and 0.16 to 22.13 mg/kg at site-II. The levels of these metals in the vegetable were found 0.35 to 61.13 mg/kg at site-I and 0.31 to 53.63 mg/kg at site-II. The transfer factor at both sites was highest for As and Co. The pollution load index recorded for Se, Cu, Cd, Mo, Pb, and Co was greater than 1. The daily intake of As, Mn, and Mo was above the oral reference dose, which reflects that the intake of pumpkin is not safe for the inhabitants of the selected sites. The control measures should be taken to phytoextract heavy metals and metalloids from polluted sites so as to reduce the health risks.     

Purification of a fibrolast-inhibitory factor from Actinobacillus actinomycetemcomitans Y4

Abstract A factor showing inhibitory activity against human gingival fibrolasts was extracted from the cytosol fraction of Actinobacillus actinomycetemcomitans Y4. The activity markedly inhibited the proliferation of human gingival fibrolasts, but had no effect on cell viability or gross morphology. No such activity was found in cytosol fractions from either Porphyromonas gingivalis 381 or Escherichia coli HB101. The extract from A. actinomycetemcomitans Y4 was then purified by anion-exchange chromatography, hydroxyapatite chromatography and gel-filtration chromatography to give a single band on SDS-PAGE with an apparent molecular mass of 65 kDa. The purification ratio was 183-fold with a recovery rate of 5% compared with the crude extract (starting material) when the activity was assessed by direct cell counts.     

Linearized Growth Curve,Proper Age and Age at Menarche

A mathematical model of the linearized growth curve and its physiological interpretation by the introduction of proper age, which is proportional to the chronological age, are presented here. In the second phase, but not in the first phase, this constant of proportionality is highly correlated with the age at menarche.