Dysregulation of Amphiregulin stimulates the pathogenesis of cystic lymphangioma.

Along with blood vessels, lymphatic vessels play an important role in the circulation of body fluid and recruitment of immune cells. Postnatal lymphangiogenesis commonly occurs from preexisting lymphatic vessels by sprouting, which is induced by lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C). However, the key signals and cell types that stimulate pathological lymphangiogenesis, such as human cystic lymphangioma, are less well known. Here, we found that mouse dermal fibroblasts that infiltrate to sponges subcutaneously implanted express VEGF-D and sushi, Von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) in response to PDGFRß signal. In vitro, Pdgfrb knockout (ß-KO) fibroblasts had reduced expression of VEGF-D and SVEP1 and overproduced Amphiregulin. Dysregulation of these three factors was involved in the cyst-like and uneven distribution of lymphatic vessels observed in the ß-KO mice. Similarly, in human cystic lymphangioma, which is one of the intractable diseases and mostly occurs in childhood, fibroblasts surrounding cystic lymphatics highly expressed Amphiregulin. Moreover, fibroblast-derived Amphiregulin could induce the expression of Amphiregulin in lymphatic endothelial cells. The dual source of Amphiregulin activated EGFR expressed on the lymphatic endothelial cells. This exacerbation cascade induced proliferation of lymphatic endothelial cells to form cystic lymphangioma. Ultimately, excessive Amphiregulin produced by fibroblasts surrounding lymphatics and by lymphatic endothelial cells per se results in pathogenesis of cystic lymphangioma and will be a fascinating therapeutic target of cystic lymphangioma.

Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice.

Blood-brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, imatinib-induced HT only when administrated in the subacute phase of MCAO, but not in the acute phase. Secondly, we generated genetically mutated mice (C-KO mice) that showed decreased expression of perivascular PDGFRα. Additionally, transient MCAO experiments were performed in these mice. We found that the ischemic lesion size was not affected; however, the recruitment of PDGFRα/type I collagen-expressing perivascular cells was significantly downregulated, and HT and IgG leakage was augmented only in the subacute phase of stroke in C-KO mice. In both experiments, we found that the expression of tight junction proteins and PDGFRß-expressing pericyte coverage was not significantly affected in imatinib-treated mice and in C-KO mice. The specific implication of PDGFRα signaling was suggestive of protective effects against BBB dysfunction during the subacute phase of stroke. Vascular TGF-ß1 expression was downregulated in both imatinib-treated and C-KO mice, along with sustained levels of MMP9. Therefore, PDGFRα effects may be mediated by TGF-ß1 which exerts potent protective effects in the BBB.

Estimation of the standardized ileal digestible lysine requirement and optimal sulphur amino acids to lysine ratio for 30-50 kg pigs.

Two experiments were conducted to determine the standardized ileal digestible (SID) lysine (Lys) requirement and the ideal SID sulphur amino acids (SAA) to Lys ratio for 30-50 kg crossbred pigs. In experiment 1, a total of 72 crossbred pigs with an average initial body weight (BW) of 28.9 kg were allotted to one of six dietary treatments in a randomized complete block design. Each diet was assigned to six pens containing two pigs each. Six diets were obtained by supplementing graded levels of L-Lysine∙HCl to create six dietary levels of SID Lys (0.70%, 0.80%, 0.90%, 1.00%, 1.10% and 1.20%). Responses of weight gain (ADG) and gain:feed (G:F) to increasing the SID Lys content of the diet fitted well with the curvilinear-plateau model; whereas, for plasma urea nitrogen (PUN) two-slope linear broken-line model was well fitted. The optimal SID Lys requirement for the pigs of this period was 1.10%. Experiment 2 was a dose-response study using SID Met+Cys to Lys ratios of 50%, 55%, 60%, 65%, 70% and 64%. A total of 72 crossbred pigs with initial BW of 32.9 kg were randomly allotted to receive one of the six diets. Diets 1-5 were formulated to contain 1.0% SID Lys to be second limiting in Lys and diet 6 contained 1.11% SID Lys to be adequate in Lys. The average optimal SID SAA:Lys ratio for maximal ADG and G:F and minimal PUN was 65.2% using curvilinear-plateau and linear broken-line models.

Impact of the individualized risks of end-stage renal disease on living kidney donor selection.

Background: It is recommended to determine the risks of end-stage renal disease (ESRD) in living donor candidates. The aim of this study was to determine how many candidates would have been cleared for donation according to different thresholds of risks. Methods: Four pre-donation and post-donation risks of ESRD were calculated retrospectively using online tools (http://www.transplantmodels.com/) and the calculator of the University of Minnesota for 151 living kidney donors and 27 patients disqualified for living donation based on a glomerular filtration rate (GFR) <80 mL/min/1.73 m2. Results: A complete overlap of the pre-donation 15-year ESRD risk, pre-donation projected lifetime ESRD risk, post-donation 15-year ESRD risk and the Minnesota post-donation 15-year risk of ESRD or GFR <30 mL/min/1.73 m2 was observed for the living kidney donors and the disqualified candidates. We next defined different thresholds of pre- and post-donation risks of ESRD that could be used for clearing living donation. In candidates over 61 years of age, the use of a pre-donation 15-year ESRD risk of 0.25% and/or a post-donation 15-year ESRD risk of 50 per 10 000 would increase the percentage of donors by 28.6% and 26.3%, respectively. Conversely, only 22.3% of donors aged 18-35 years would have been selected by using a pre-donation projected lifetime ESRD risk <0.5%. Conclusions: The use of these ESRD risks would significantly modify donor selection by increasing the percentage of donors ≥61 years of age with GFR <80 mL/min/1.73 m2 and by decreasing the percentage of donors aged 18-35 years with a high GFR.

Protective Effect of Willow (Salix babylonica L.) on Fish Resistance to Vibrio parahaemolyticus and Vibrio alginolyticus.

Vibrio spp. cause vibriosis in many saltwater and freshwater aquatic species, such as fish, crustaceans, and mollusks. Vibrio parahaemolyticus and Vibrio alginolyticus are among the few Vibrio species commonly found in infections in fish. This study aimed at investigating the chemical composition and evaluating the antibacterial activities of Salix babylonica L. The ethyl acetate (LL2) and methanolic (LL3) extracts were used to evaluate the resistance of strains as V. parahaemolyticus LBT6 and VTCC 12233, and two strains of V. alginolyticus, NG20 and ATCC 17749, and compared their efficacy with cefotaxime in order to find an alternative to antibiotics in the treatment of vibriosis. The obtained results show that the LL2 extract, with its major components identified as chrysoeriol, luteolin, and ß-sitosterol, exhibited a bacteriostatic effect against all the tested strains. In parallel, the LL3 extract, with the four major compounds luteolin-7-O-ß-D-glucopyranoside, salicin, p-hydroxy benzoic acid, and ß-sitosterol-3-O-ß-D-glucopyranoside, showed significant bactericidal activity against these four strains; the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) varied from 2.0 to 3.0 µg/mL and from 3.5 to 5.0 µg/mL, respectively. Moreover, the LL3 extract could effectively increase the survival rate of the challenged fish at a dose of 5% (w/w) for the zebrafish (Danio rerio) and 3% (w/w) for the sea bass (Lates calcarifer). The LL3 extract showed a potential application of S. babylonica L. in the prevention and treatment of vibriosis in fish.

A Portable Band-shaped Bioimpedance System to Monitor the Body Fat and Fasting Glucose Level.

With better quality of life, obesity is becoming a worldwide disease due to over-eating and sedentary lifestyle. Therefore, daily monitoring of the glucose and body fat percentage (%) is vital to keep track of one's health. Currently, separated devices are required to monitor each parameter at home and some are still invasive to measure the glucose level. In this study, a portable band-shaped bioimpedance system is proposed to measure both parameters. The system is battery run with two main modules: the current source and the voltage recording, with minimal design to fit into a band of 150 mm x 40 mm in dimension. The impedance is measured at the frequency of 1 kHz at 30 kHz sampling frequency and in 1000 signal cycles to flatten noises. The final average impedance is calculated and evaluated in correlation with the body fat and the fasting glucose. The system was tested on 21 volunteers and 4 locations were picked for the impedance measurement: the arm under the triceps, the side of the belly, the back on one side and the thigh under the bicep femoris. The results show promising results with the arm being the best location for predicting the body fat (correlation coefficient: 0.89, 95% CI: 0.73-0.95), while the thigh impedance best correlated with the fasting glucose (correlation coefficient: 0.92, 95% CI: 0.81-0.97). These preliminary results indicate the feasibility and capacity of the proposed system as a home-based, portable and convenient system in monitoring the body fat and glucose. The system's performance will be verified and replicated in a future larger study.

Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain.

Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin+ immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

Influence of different diets on growth performance, meat quality, and disease resistance in pig crossbreeds (PIE x MC-local) and PIE (LW x MC-local).

The present study evaluated the effect of different dietary formulations on the growth rate in pigs and their resistance to infection with hog cholera. Results indicate that growth rates can be enhanced by certain formulations and that there is a correlation between this increased growth rate and increased resistance to infection with hog cholera.