Background/objectives: Bile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown.

<strong class="sub-title"> Methods: </strong> Plasma BA, <em>fibroblast</em> <em>growth</em> <em>factor</em> 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = <em>22</em>).

Results: Fasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects.

Conclusion: Altered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release.

The earliest clinical manifestation of SSc is usually Raynaud's phenomenon, a small-arteries vasospasm driven by vascular tone dysregulation and microcirculatory abnormalities, resulting in digital ulcers (DU) in up to 50% of patients. Many cytokines as well as <em>growth</em> <em>factors</em> have been shown to play a role in promoting vascular smooth muscle cell proliferation and <em>fibroblast</em> activation, leading to ischemic damage as well as skin fibrosis. We aim to investigate a possible difference in venous and arterial blood levels of many cytokines (Th1- and Th17-related), GM-CSF, and endothelin-1 (ET1) in patients with and without DU. In the same patients, the correlations between capillary damage, evaluated by nailfold videocapillaroscopy (NVC), extension of skin fibrosis, calculated by modified Rodnan skin score (mRSS), and cytokines, ET-1, and GM-CSF levels were also measured. Patients with DU showed venous levels of IL-1<i>β</i> (<i>p</i>=0.024), IL-6 (<i>p</i>=0.012), IL-<em>22</em>(<i>p</i>=0.006), and TGF-<i>β</i> (<i>p</i>=0.046) significantly higher compared to arterial levels and arterial levels of GM-CSF and TNF-alpha significantly higher compared to venous levels (<i>p</i> < 0.001). NVC abnormalities were correlated with arterial TNFa and venous IL<em>22</em>, IL23, and IL17 levels and negatively correlated with venous ET-1 levels, whereas mRSS showed a negative correlation with IL-21(<i>ρ</i> = -0.427, <i>p</i>=0.050). The increased Th17-cytokine levels in venous compared to arterial blood of patients with DU suggest local cytokine production on ulcer site. The higher TNFa and GM-CSF levels in arterial blood of DU patients support the attempt to mitigate the hypoxic damage, and the correlation between Th17-cytokines, mRSS, NVC, and ET1 agrees with the potent profibrotic stimulus at the onset of the disease, which decreases as the SSc progresses.

<AbstractText>Although surgical ventricular restoration for ischemic cardiomyopathy is expected as an alternative or bridge to heart transplantation, post-operative remodeling of left ventricle (LV) needs to be addressed. This study aimed to examine the effect of basic <em>fibroblast</em> <em>growth</em> <em>factor</em> (bFGF), which induces angiogenesis and tissue regeneration in ischemic myocardium, to prevent remodeling after surgical ventricular restoration (SVR) using a rat ischemic cardiomyopathy model.</AbstractText><AbstractText>Four weeks after coronary artery ligation, rats were divided into two groups: rats treated with SVR alone (SVR; n = 21), and rats treated with SVR and local sustained release of bFGF using gelatin hydrogel sheet (SVR + bFGF; n = <em>22</em>). Cardiac function was assessed by serial echocardiography and cardiac catheterization. Cardiac tissue sections were histologically examined for vascular density and fibrosis.</AbstractText><p><div><b>RESULTS</b></div>Higher systolic function and lower LV end-diastolic pressure (LVEDP) were observed in rats treated with SVR + bFGF (SVR vs SVR + bFGF; Ees: 0.<em>22</em> ± 0.11 vs 0.33 ± 0.<em>22</em> mmHg/μL, p = 0.0328; LVEDP: 12.7 ± 7.0 vs 8.5 ± 4.3 mmHg, p = 0.0230). LV area tended to be lower in rats treated with SVR + bFGF compared to rats treated with SVR alone (left-ventricular end-diastolic area: 0.66 ± 0.07 vs 0.62 ± 0.07 cm², p = 0.071). Vascular density tended to be higher in rats treated with SVR + bFGF than those without bFGF (23.3 ± 8.1 vs 28.8 ± 9.5/mm², p = 0.0509).</p><AbstractText>BFGF induced angiogenesis and attenuated remodeling after SVR which secured the efficacy of SVR in a rat ischemic cardiomyopathy model.</AbstractText>

Essential muscular organ that provides the whole body with oxygen and nutrients, the heart is the first organ to function during embryonic development. Cardiovascular diseases, including acquired and congenital heart defects, are the leading cause of mortality in industrialized countries. <em>Fibroblast</em> <em>Growth</em> <em>Factors</em> (FGFs) are involved in a variety of cellular responses including proliferation, differentiation, and migration. Among the <em>22</em> human/mouse FGFs, the secreted FGF10 ligand through the binding of its specific receptors (FGFR1b and FGFR2b) and subsequent activation of downstream signaling is known to play essential role in cardiac development, homeostasis and disease. FGF10 is one of the major marker of the early cardiac progenitor cells and a crucial regulator of differentiated cardiomyocyte proliferation in the developing embryo. Increasing evidence support the hypothesis that a detailed understanding of developmental processes is essential to identify targets for cardiac repair and regeneration. Indeed the activation of resident cardiomyocyte proliferation together with the injection of cardiac progenitors represent the most promising therapeutical strategies for cardiac regenerative medicine. The recent findings showing that FGF10 promotes adult cardiomyocyte cell cycle reentry and directs stem cell differentiation and cell reprogramming toward the cardiogenic lineage provide new insights into therapeutical strategies for cardiac regeneration and repair.

BACKGROUND Chronic kidney disease (CKD) is one of risk <em>factors</em> for dementia and cognitive decline. Cardiovascular and dialysis-related <em>factors</em> might also be involved in the mechanism of cognitive impairment in hemodialysis patients. The objective of this study was to investigate whether cardiovascular risk <em>factors</em> including intracranial artery calcification and dialysis-related <em>factors</em> such as <em>fibroblast</em> <em>growth</em> <em>factor</em> 23 (FGF23) might be associated with cognitive impairment in hemodialysis patients. MATERIAL AND METHODS A cross-sectional observational study included patients receiving in-center hemodialysis over 6 months at our hospital. All patients underwent non-contrast computed tomography (CT) examinations. Internal carotid artery (ICA) calcium scores were measured using the Agatston method. The Korean version of the Montreal Cognitive Assessment was used for measurement of cognitive function at each study visit. Serum concentrations of FGF23, osteoprotegerin, and klotho were analyzed using commercial enzyme-linked immunosorbent assay kits. RESULTS This study included 69 patients. Cognitive impairment was observed in <em>22</em> patients (31.9%), including 3 patients with dementia. ICA calcium score in patients with cognitive impairment was higher than that in those without cognitive impairment (177.3 versus 87.6, P=0.0<em>22</em>). Intracranial artery calcification was significantly associated with cognitive impairment after adjusting for FGF23 and 25-OH vitamin D, but not significant after adjusting for age, FGF23, and 25-OH vitamin D. Low level of FGF23 was associated with cognitive impairment. CONCLUSIONS Intracranial artery calcification and low FGF23 could be associated with cognitive impairment in hemodialysis patients. Longitudinal studies are needed to investigate whether intracranial artery calcification and FGF23 could affect cognitive function of hemodialysis patients.

<AbstractText>To analyse the effects of the alternatively spliced fibronectin (FN) gene and its isoforms on osteoclastogenesis in radicular cysts.</AbstractText><AbstractText>Specimens of radicular cysts were collected surgically from <em>22</em> patients whose radiolucent periapical areas were measured on digital panoramic radiographs before surgery. The associations between the radiolucent areas and FN isoforms, Vascular Endothelial <em>Growth</em> <em>Factor</em> (VEGF) expression or micro-vessel density, as well as the relationships among them, were analysed by immunohistochemical staining using the antibodies IST-9, BC-1, P1F11, VEGF, and CD34. <em>Fibroblasts</em> isolated from those specimens were used to induce Trap+MNCs, and the effects of induction were assessed by blocking FN containing extra domain A (EDA+FN), COX-2, or VEGF in vitro. The effects of EDA exon knockout using CRISPR/Cas system was also assessed. Quantitative PCR was used to analyse relative expression of FN isoforms and osteoclastogenic genes. Data were analysed using Linear regression, Spearman's rank correlation analysis, Chi-square test and Student's t-test; P < 0.05 was considered significant.</AbstractText><p><div><b>RESULTS</b></div>Micro-vessel density and EDA+FN staining were positively associated with the size of radiolucent periapical areas (mm² ) (P<0.05), consistent with a positive association between Trap+MNCs and VEGF expression in <em>fibroblasts</em> (P<0.05). Blocking the interaction between EDA+FN and <em>fibroblasts</em> inhibited Trap+MNC formation. In addition, EDA exon knockout decreased VEGF expression, and inhibited Trap+MNC formation to the extent of blocking VEGF by bevacizumab, but osteoclastogenic induction was restored by recombinant VEGF. Using retrospective clinicopathological data, VEGF staining was shown to be positively associated with EDA+FN staining, micro-vessel density, and the size of radiolucent areas (P<0.05).</p><AbstractText>In fibrous capsules of radicular cysts, the alternatively spliced isoform EDA+FN generated by <em>fibroblasts</em> stimulated VEGF expression via an autocrine effect, and then facilitated osteoclastogenesis. Both blockage of VEGF and EDA exon knockout could be used to inhibit bone destruction.</AbstractText>

<AbstractText>Accelerated proliferation of human periodontal ligament stem cells (PDLSCs) is present in periodontitis. It is known that <em>fibroblast</em> <em>growth</em> <em>factor</em> 2 (FGF2) regulates the proliferation of PDLSCs, while the function of FGF2 in myogenic cell differentiation is mediated by Linc-RNA Activator of Myogenesis (Linc-RAM) lncRNA. Therefore, Linc-RAM lncRNA may also participate in periodontitis.</AbstractText><AbstractText>This study included 28 patients with periodontitis (patient group) and <em>22</em> patients without periodontitis but received orthodontic treatment (control group) in the stomatological hospital of Sun Yat-Sen university. Gingival biopsies were obtained from participants. RT-qPCR, cell transfection, cell proliferation assay and western blot were carrying out to analyze the samples.</AbstractText><AbstractText>We found that FGF2 mRNA was upregulated, while Linc-RAM was downregulated in PDLSCs derived from periodontitis-affected teeth than in healthy teeth. FGF2 mRNA and Linc-RAM were inversely correlated in both types of PDLSCs. FGF2 overexpression led to inhibited Linc-RAM expression in PDLSCs derived from periodontitis-affected teeth and promoted the proliferation of PDLSCs. Linc-RAM overexpression failed to significantly affect FGF2 expression but attenuated the enhancing effects of FGF2 overexpression on the proliferation of PDLSCs.</AbstractText><AbstractText>Therefore, downregulation of Linc-RAM lncRNA may participate in FGF-2 mediated- proliferation of human PDLSCs.</AbstractText>

OBJECTIVE

To explore the effect of basic fibroblast growth factor 1 (bFGF1) during embryonic development on hematopoiesis, to study the expression of FGF1, vascular endothelial growth factor receptor (KDR), CD133, CD34 and transcription factors Ihh, SCL, GATA-1, GATA-2 and PU. 1 in the yolk sac, and to learn about the role and relationships of FGF1, hematopoietic cells and transcription factors during embryonic hematopoiesis.

METHODS

10 microm sections and total RNA were prepared from 107 human embryos aged 3-12 weeks. Immunohischemical SP staining and RT-PCR were performed.

RESULTS

The yolk sac blood islands of human 3 approximately 12 weeks embryos consisted of peripheral vascular endothelial cells and central hematopoietic cells. The expression of FGF1 was firstly found in visceral mesoderm around periphery of yolk sac blood island at day 16, while was little inside it. KDR was not or lowly expressed and CD34 and CD133 were not expressed then. The expression increased, gray value decreased and staining enhanced at day 21. Strong staining of CD34+, CD133+ and KDR+ cells were found in blood island and mesoderm at day 30, their gray values changed from 156 +/- 16, 173 +/- 18 and 160 +/- 14 to 53 +/- 7, 52 +/- 6 and 69 +/- 8 respectively. FGF1 expression was strong positive, the gray value declined dramatically from 161 +/- 13 to 40 +/- 5. Some positive cells formed vessel-like structure along the periphery of blood island. Moderate expression of CD34+, CD133+, KDR+ cells increased at day 45, the cells aggregated into mass in blood island and FGF1+ cells did the same in blood island, while little in mesoderm. Its gray valve was increased. After 7 weeks, CD133+, KDR+, CD34+ cells significantly decreased their gray values increased, the staining became week. FGF1 was weakly expressed in yolk sac and its gray value increased to 179 +/- 22. RT-PCR showed Ihh, SCL, GATA-1 and GATA-2 were expressed at different time in yolk sac. PU. 1 were not expressed at day 16, and then expressed.

CONCLUSIONS

The hematopoietic properties of yolk sac may be dependent on signaling through FGF receptors and FGF1 plays an important role in hematopoietic stem cell homeostasis. The FGF pathway regulates primitive hematopoiesis by modulating transcription factors such as Gata1 expression level and activity.

Our previous studies demonstrated that interleukin (IL)-<em>22</em> is involved in cardiovascular diseases such as hypertension, cardiac fibrosis and aortic dissection. The purpose of the present study was to detect IL-<em>22</em> expression in patients with atrial fibrillation (AF). Atrial tissue was collected from donors with sinus rhythm and patients with permanent AF, and the expression level of IL-<em>22</em> and its receptors (IL-<em>22</em>R1 and IL-10R2) in both the left atrium (LA) and right atrium (RA) of each sample was detected. Blood samples were also obtained from donors with paroxysmal, persistent and permanent AF and from donors without AF history, and IL-<em>22</em> levels were measured. In addition, the effects of IL-<em>22</em> on collagen synthesis in TGF-β1-treated cardiac <em>fibroblasts</em> were investigated. IL-<em>22</em>R1, IL-10R2 and IL-<em>22</em> expression was elevated in both the LA and RA in permanent AF patients. Elevated IL-<em>22</em> expression positively correlated with the collagen areas and fibrosis marker levels in the atria of these patients. Plasma IL-<em>22</em> levels were higher in AF patients compared with healthy donors and increased with increasing AF duration (from paroxysmal to persistent to permanent AF). A positive correlation was observed between IL-<em>22</em> levels and TGF-β1 levels in AF patients. <i>In vitro</i>, recombinant mouse IL-<em>22</em> treatment upregulated α-SMA, collagen I and collagen III expression in TGF-β1-treated cardiac <em>fibroblasts</em>. These effects were reversed by SP600125, an inhibitor of the JNK pathway. To conclude, IL-<em>22</em> levels are elevated in patients with AF and may exacerbate collagen synthesis in TGF-β1-induced cardiac <em>fibroblasts</em>. IL-<em>22</em> may also influence AF by activating the JNK pathway.

<strong class="sub-title"> Keywords: </strong> JNK pathway; atrial fibrillation; atrial fibrosis; interleukin-<em>22</em>.

Since the half-life of most angiogenic <em>growth</em> <em>factors</em> is several hours or less, sustained-release delivery would be optimal for their future clinical use. Two <em>fibroblast</em> <em>growth</em> <em>factors</em>, basic <em>fibroblast</em> <em>growth</em> <em>factor</em> (bFGF) and endothelial cell <em>growth</em> <em>factor</em> (ECGF), were delivered in two sustained-released modalities (poloxamer 407 and a gelatin sponge [Gelfoam]) to attempt to increase soft tissue vascularity. In vitro bioactivity of ECGF-poloxamer formulations was also tested on endothelial cell cultures. Among vascular-compromised skin flaps in rabbits, ECGF-poloxamer (N = 26), bFGF-poloxamer (N = 5), ECGF-poloxamer (N = 9, irradiated), and bFGF-Gelfoam flaps (N = <em>22</em>) did not demonstrate significant differences in viability and vascularity compared to controls (p>> .05). Irradiation had a detrimental effect on both flap vascularity and viability (p = .02). Future efforts for sustained delivery of angiogenic proteins are critical in order to make them clinically useful in wound healing.

<strong class="sub-title"> Background: </strong> The eutherian <em>fibroblast</em> <em>growth</em> <em>factors</em> were implicated as key regulators in developmental processes. However, there were major disagreements in descriptions of comprehensive eutherian <em>fibroblast</em> <em>growth</em> <em>factors</em> gene data sets including either 18 or <em>22</em> homologues. The present analysis attempted to revise and update comprehensive eutherian <em>fibroblast</em> <em>growth</em> <em>factor</em> gene data sets, and address and resolve major discrepancies in their descriptions using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets.

<strong class="sub-title"> Results: </strong> Among 577 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated eutherian third-party data gene data set of <em>fibroblast</em> <em>growth</em> <em>factor</em> genes including 267 complete coding sequences. The present study first described 8 superclusters including <em>22</em> eutherian <em>fibroblast</em> <em>growth</em> <em>factor</em> major gene clusters, proposing their updated classification and nomenclature.

<strong class="sub-title"> Conclusions: </strong> The integrated gene annotations, phylogenetic analysis and protein molecular evolution analysis argued that comprehensive eutherian <em>fibroblast</em> <em>growth</em> <em>factor</em> gene data set classifications included <em>22</em> rather than 18 homologues.

Keywords: Eutheria; Gene annotations; Molecular evolution; Phylogenetic analysis; RRID:SCR_014401.

<em>Fibroblast</em> <em>growth</em> <em>factor</em>-2 (FGF-2) promotes cardiac myocyte proliferation and has been detected in extracellular as well as cytoplasmic and nuclear compartments. As a first step in examining the participation of intracellular FGF-2 in cardiac myocyte cell cycle we have investigated its localization in proliferative chicken cells during interphase and the various stages of mitosis in culture. We have used a previously characterized and affinity-purified anti-FGF-2 antibody preparation which recognizes the 19-<em>22</em> kDa variants of chick FGF-2. By immunofluorescence, bright, punctate anti-FGF-2 labelling was observed in 26% of interphase nuclei from myocytes derived from 5 day embryonic heart ventricles; these nuclei were positive for anti-bromodeoxyuridine staining indicating that they are at the S- or G2 phase of the cell cycle. In prophase and metaphase, bright anti-FGF-2 staining was detected in apparent association with chromosomes. During anaphase, however, anti-FGF-2 staining dissociated from chromosomal locations distinctly remaining in strand-like structures in the area of ensuing cleavage furrow formation. In late telophase and cytokinesis, strong staining persisted in the area of the midbody and reappeared in a small fraction of newly formed daughter nuclei. Absorption of the antibody preparation with immobilized FGF-2 eliminated all staining. This dynamic pattern of anti-FGF-2 staining suggests that chick FGF-2 or immunologically related protein(s) not only increase in DNA-synthesizing nuclei but they may play a role in subsequent stages of mitosis and cytokinesis.

OBJECTIVE

To study the distribution and expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the III-IV stage of pressure ulcer wound, and to explore their correlation with ulceration.

METHODS

Forty-one patients hospitalized in the two Affiliated Hospital of Wenzhou Medical College from June 2010 to March 2012 were recruited, including twenty-one patients with 23 pressure ulcer of stage III-IV, 14 acute injury patients, and 6 donors of normal skin. Samples harvested from the 41 patients through surgery were divided into four groups, including pressure ulcer centre group (n = 23), pressure ulcer margin group (n = 23), acute wound group (n = 14), and normal skin group (n = 6). The histological changes in wounds were observed after HE staining. The distribution of collagen fiber in wound was observed with Masson staining. Expressions of VEGF and bFGF in wounds were detected with immunohistochemical staining. Data were processed with independent samples t test and paired samples t test.

RESULTS

(1) In the two pressure ulcer groups, large number of inflammatory cells were found in aggregation; the expression of collagen fiber was decreased or disappeared; the positive expressions of VEGF and bFGF were mainly located in fibroblasts and endothelial cells. The expression levels of VEGF and bFGF were respectively 100 ± 39, 132 ± 46 in pressure ulcer centre group, and 228 ± 48, 299 ± 80 in pressure ulcer margin group. The differences between the two pressure ulcer groups were statistically significant (with t values respectively 13.497 and 13.020, P values below 0.01). (2) In acute wound group, a large number of fibroblasts but a small amount of collagen fibers were observed; the positive expressions of VEGF and bFGF were mainly located in fibroblasts, with respective expression levels of 292 ± 59 and 443 ± 194, which were significantly higher than those of the two pressure ulcer groups (with t values from 2.370 to 11.570, P < 0.05 or P < 0.01). (3) In normal skin group, structure of tissue was appropriate, and abundant collagen fibers were observed; the expression levels of VEGF and bFGF were respectively 45 ± 18 and 54 ± 22, which were significantly lower than those of the other three groups (with t values from 3.983 to 14.087, P values all below 0.01).

CONCLUSIONS

In contrast with those of the acute wounds, the expression levels of VEGF and bFGF are significantly decreased in the pressure ulcer wound at stage III-IV. It may be closely correlated with the decrease or cessation of the synthesis of collagen fiber.

Environmental, genetic, oxidative and biochemical <em>factors</em> play an important role in the atherosclerotic process. We investigated the association of serum <em>fibroblast</em> <em>growth</em> <em>factor</em> (FGF-23), klotho, fetuin-A, osteoprotegerin (OPG), osteopontin (OPN) and high-sensitive-CRP (Hs-CRP) markers with coronary artery disease and whether one was superior to others or not. A study group of 52 patients with coronary artery disease (CAD) and a control group of 30 patients with angiographically normal epicardial coronary arteries were included in the study. Serum FGF-23, klotho, fetuin-A, OPN, OPG and Hs-CRP marker levels were studied. Patients with CAD were classified in two groups as low (SYNTAX ≤<em>22</em>, <i>n</i> = 29) and moderate-high (SYNTAX ≥ 23, <i>n</i> = 23) according to anatomic SYNTAX score. FGF-23 (<i>p</i> = .033), klotho (<i>p</i> < .001), fetuin-A (<i>p</i> = .005) and OPG (<i>p</i> = .001) serum marker levels were significantly lower in CAD patients than the control group. Serum levels of FGF-23 (<i>p</i> = .012), klotho (<i>p</i> = .001), fetuin-A (<i>p</i> = .015) and OPG (<i>p</i> = 0.002) were significantly different between SYNTAX tertiles and control group. Klotho (<i>p</i> = .025, odd ratio (OR) = 0.542, 95% confidence interval (CI): 0.317-0.926) and HT (<i>p</i> = .004, OR = 34.598, 95%CI:1.054-1135.657) were the independent predictors of CAD presence. Serum klotho levels of 91.48 pmol/L predicts the presence of CAD with 60% sensitivity and 96.55% specificity (<i>p</i> < .001, area under curve = 0.864, 95% CI = 0.768, 0.931). We found that serum klotho level is an independent predictor of presence, extent and severity of CAD.

<em>Fibroblast</em> <em>growth</em> <em>factors</em> (FGFs) are a group of ligands that play multiple roles during development by transducing signals through FGF receptors (FGFRs) to downstream <em>factors</em>. At least <em>22</em> FGF ligands and 4 receptors have been identified in vertebrates, while six to eight FGF ligands and a single FGFR are present in invertebrate chordates, such as tunicates and amphioxus. The chordate FGFs can be categorized into at least seven subfamilies, and the members of which expanded during the evolution of early vertebrates. In contrast, only one FGF and two FGFRs have been found in sea urchins. Thus, it is unclear whether the FGF subfamilies duplicated in the lineage leading to the chordates, or sea urchins lost several fgf genes. Analyses of the FGF signaling repertoire in hemichordates, which together with echinoderms form the closest group to the chordates, may provide insights into the evolution of FGF signaling in deuterostomes. In this study, we identified five FGFs and three FGFRs from Ptychodera flava, an indirect-developing hemichordate acorn worm. Phylogenetic analyses revealed that hemichordates possess a conserved FGF8/17/18 in addition to several putative hemichordate-specific FGFs. Analyses of sequence similarity and protein domain organizations suggested that the sea urchin and hemichordate FGFRs arose from independent lineage-specific duplications. Furthermore, the acorn worm fgf and fgfr genes were demonstrated to be expressed during P. flava embryogenesis. These results set the foundations for further functional studies of FGF signaling in hemichordates and provided insights into the evolutionary history of the FGF repertoire.

MicroRNAs are ~<em>22</em> nt long small noncoding RNA molecules that silence post-transcription gene expression. It has proven that microRNAs are widely expressed in eukaryotes and play an important role in the regulation of cell differentiation and development, <em>growth</em> metabolism, and many other cell activities. Induced pluripotent stem cells (iPS) are a type of pluripotent stem cells reprogrammed from somatic cells and exhibit the essential characteristics of embryonic stem cells. iPS technology has been widely applied in the biological and medical fields, and the key of it is reprogramming of somatic epigenetic state. Therefore, it is of important theoretical and practical significance to study the mechanisms of somatic reprogramming for establishment of an improved iPS technology. The methods of transfection of defined exogenetic stem <em>factors</em>, such as Oct4, Sox2, Klf4, and c-Myc into somatic cells through viral vectors have been continuously improving, but the genome integration and reactivation of the oncogenic gene increase the tumorigenicity of induced cells. The integration-free ways, such as adenovirus, plasmid, recombinant proteins, and L-myc replacement used in iPS technology significantly reduce the risk of cancer. However, the inducing mechanisms are still unclear. Recent studies showed that microRNA affect the process of somatic cell reprogramming, especially embryonic stem cell regulating (ESCC) family of microRNAs (miR302/367, miR200, miR-34, and miR290/295) enhances the reprogramming of embryonic <em>fibroblasts</em> to iPS. This article reviews the recent progresses of roles of microRNA in iPS.

Basement membrane promotes the reassembly of isolated type II alveolar cells into alveoli-like structures, a process attributable in part to a novel cell adhesion site in the alpha 1-chain of laminin-1 (M. L. Matter and G. W. Laurie. J. Cell Biol. 124: 1083-1090, 1994). The possibility that basement membrane contains other alveolarization activities was probed by subtraction analysis and use of neutralizing antibodies. Deletion of components < 100 kDa, and subsequently < 10 kDa, reduced alveolar cross-sectional area by 70% to <em>22</em>-25 x 10(3) microns2: the approximate size of alveolar-like structures formed on purified laminin-1 alone. The deleted basement membrane material was adhesive for type II alveolar cells but failed to support alveolar formation in the absence of laminin-1. Preincubation of basement membrane with neutralizing anti-epidermal <em>growth</em> <em>factor</em> (EGF), -basic <em>fibroblast</em> <em>growth</em> <em>factor</em> (bFGF), -insulin-like <em>growth</em> <em>factor</em> (IGF)II, or -transforming <em>growth</em> <em>factor</em> (TGF)-beta antibodies had no inhibitory effect. Because both subtracted basement membrane preparations have in common the exclusion of components < 10 kDa, these results are interpreted as pointing to a sub-10-kDa alveolarization activity(s) that plays a key accessory role in laminin-1-dependent alveolar formation.

OBJECTIVE

To analyze growth factor receptor expression in the human fetal brain.

METHODS

Messenger RNA was prepared from six regions of the fetal brain from three 21-22-week abortuses and used as templates for reverse transcription. Polymerase chain reaction (PCR) was used to amplify the complementary DNA for each of the six brain regions. Amplified PCR DNA fragments were analyzed by agarose gel electrophoresis. Restriction endonuclease digestion was used to confirm the identity of the amplified PCR fragments.

RESULTS

Polymerase chain reaction amplified DNA fragments consistent with expression of the insulin, insulin-like growth factors I and II, fibroblast growth factor (FGF), transforming growth factor-beta, and epidermal growth factor receptors were detected in each area of the human fetal brain studied. Of the two known insulin receptor subtype sequences, only the smaller (exon 11-) form was detected. We detected both the intact and the 267 base-deleted alternatively spliced forms of the FGF receptor.

CONCLUSIONS

All six of the receptor messenger RNAs studied were detected in the second-trimester human fetal brain. In addition, alternative splicing of the messenger RNA was noted for the FGF and insulin receptors. This report demonstrates growth factor receptor expression and alternate splicing in specific regions of the human fetal brain. These data suggest that growth factor influence on fetal brain development may be mediated through specific growth factor receptors.

In vitro <em>growth</em> of hematopoietic cells depends on the presence of hematopoietic cytokines. To date, it is unclear if these cells would be able to respond to non-hematopoietic cytokines. In the present study, we have explored this by culturing human hematopoietic cells in presence of neurogenic cytokines. Lineage-negative (Lin^-) umbilical cord blood (UCB)-derived cells -enriched for hematopoietic stem and progenitor cells- were cultured in presence of different combinations of hematopoietic cytokines, neurotrophins, epidermal <em>growth</em> <em>factor</em>, <em>fibroblast</em> <em>growth</em> <em>factor</em>, and neurogenic culture media, in a 3-phase culture system. A proportion (1-<em>22</em>%) of Lin^- UCB hematopoietic cells normally express neural markers and are capable of responding to neural cytokines. Neural cytokines did not have effects on hematopoietic cell proliferation; however, we observed generation of neural-like cells, assessed by morphology, and a significant increase in the proportion of cells expressing neural markers. Such neural-like cells, however, retained expression of hematopoietic markers. It seems that under our culture conditions, no actual transdifferentiation of hematopoietic cells into neural cells occurred; instead, the cells generated in culture seem to be hematopoietic cells that acquired neural features upon contact with neurogenic <em>factors</em>. The identity of UCB cells that acquired a neural phenotype is still unclear.

Keywords: Cord blood; Hematopoietic cytokines; Hematopoietic progenitors; In vitro cultures; Neurogenic cytokines.

<AbstractText>Nipple fissure and nipple pain are common complaints among breastfeeding mothers. Studies found that mupirocin was effective in preventing and treating infections of damaged nipple and nipple pain. Acidic <em>fibroblast</em> <em>growth</em> <em>factor</em> (aFGF) plays an important role in wound healing. However, current evidence on the efficacy and safety of mupirocin plus aFGF for nipple fissure and nipple pain in breastfeeding women is inconclusive due to the lack of well-designed randomised controlled trials on this topic. The purpose of this study is to test the hypothesis that mupirocin plus aFGF is more effective than mupirocin alone for nipple fissure and nipple pain in breastfeeding women.</AbstractText><AbstractText>This study is a randomised, double-blind, single-centre, parallel-group clinical trial. A total of 120 breastfeeding women with nipple fissure and nipple pain will be randomly assigned to either mupirocin plus aFGF group or mupirocin plus placebo group according to a computer-generated random allocation sequence. The treatment period lasts 14 days. The primary outcome is nipple pain intensity measured by the Visual Analogue Scale on day 14 during the treatment period. Secondary outcome measures include time to complete nipple pain relief, changes in the Nipple Trauma Score, time to complete healing of nipple trauma, quality of life measured by the Maternal Postpartum Quality of Life (MAPP-QOL) Questionnaire, the frequency of breast feeding, the rate of breastfeeding discontinuation, weight change in infants and adverse events.</AbstractText><AbstractText>The study has gained approval from the Ethics Review Committee of Tianjin Central Hospital of Gynaecology Obstetrics on <em>22</em> January 2018 (approval no. 2018KY001). We plan to publish our research findings in a peer-reviewed academic journal and disseminate these findings in international conferences. This study has been registered with the Chinese Clinical Trial Registry.</AbstractText><AbstractText>ChiCTR1800017248.</AbstractText>

OBJECTIVE

Fibroblast growth factor-21 (FGF-21) is a member of fibroblast growth factor family. Both growth hormone (GH) and FGF-21 take place in the regulation of glucose and lipid metabolism. We aimed to investigate FGF-21 levels in acromegaly which is characterized by excess GH levels and is associated with comorbidities and altered body composition.

METHODS

We studied 43 subjects (21 females and 22 males, mean age of 50.0 ± 12.8) with acromegaly. The control group consisted of 40 gender- and age-matched subjects (25 females and 15 males, mean age of 48.8 ± 8.8). Acromegaly patients were classified into two groups; active acromegaly (AA; n = 26) and controlled acromegaly (CA; n = 17). Metabolic, anthropometric and laboratory values of subjects were recorded. FGF-21 level was measured by ELISA assay.

RESULTS

Median FGF-21 levels were significantly higher in acromegaly group compared to control group (85.5 vs. 59.0 pg/mL, p = 0.02, respectively). In the multiple regression model, FPG, A1c, HOMA-IR, glucose intolerance, BMI, visceral fat, hs-CRP, presence of hypertension, dyslipidemia and acromegaly were included as independent variables to explain variability of plasma FGF-21 levels in whole study group. The presence of acromegaly was the only determinant of increased FGF-21 levels in the whole study group (β coefficient = 0.253, p = 0.006).

CONCLUSIONS

FGF-21 levels were increased significantly in acromegaly group. Increased FGF-21 levels were significantly and independently associated with the state of acromegaly. Acromegaly may also be a FGF-21 resistance state independent from insulin resistance, glucose intolerance, obesity, hypertension and dyslipidemia.

Surgery or interventional therapy has some risks in the treatment of cerebral aneurysm. We established an internal carotid artery aneurysm model by dripping elastase in the crotch of the right internal and external carotid arteries of New Zealand rabbits. Following model induction, lentivirus carrying basic <em>fibroblast</em> <em>growth</em> <em>factor</em> was injected through the ear vein. We found that the longer the action time of the lentivirus, the smaller the aneurysm volume. Moreover, platelet-derived <em>growth</em> <em>factor</em> expression in the aneurysm increased, but smooth muscle <em>22</em> alpha and hypertension-related gene 1 mRNA expression decreased. At 1, 2, 3, and 4 weeks following model establishment, following 1 week of injection of lentivirus carrying basic <em>fibroblast</em> <em>growth</em> <em>factor</em>, the later the intervention time, the more severe the blood vessel damage, and the bigger the aneurysm volume, the lower the smooth muscle <em>22</em> alpha and hypertension-related gene 1 mRNA expression. Simultaneously, platelet-derived <em>growth</em> <em>factor</em> expression decreased. These data suggest that recombinant lentivirus carrying basic <em>fibroblast</em> <em>growth</em> <em>factor</em> can repair damaged cells in the aneurysmal wall and inhibit aneurysm dynamic <em>growth</em>, and that the effect is dependent on therapeutic duration.

The objective of this study was to investigate the effects of different <em>growth</em> <em>factors</em> on the proliferation of Bama mini-pig spermatogonial stem cells (SSCs) in vitro. The <em>growth</em> <em>factors</em> glial cell line-derived neurotrophic <em>factor</em> (GDNF), leukaemia inhibitory <em>factor</em> (LIF), GDNF family receptor alpha-1 (GFRα1), and basic <em>fibroblast</em> <em>growth</em> <em>factor</em> (bFGF) were investigated. The SSCs were seeded on SIM mouse embryo derived thioguanine- and ouabain-resistant (STO) feeder layers. Cultivation of the cells were subjected to a <em>factor</em>ial design of the <em>growth</em> <em>factors</em> GDNF + bFGF, GDNF + bFGF +GFRα1, LIF + bFGF, and LIF + bFGF +GFRα1. The SSCs could propagate for 25 passages in the medium adding GDNF + bFGF +GFRα1, <em>22</em> passages in the medium adding GDNF + bFGF, 6 passages in the medium adding LIF + bFGF, or LIF + bFGF +GFRα1. qRT-PCR analysis showed that the highest mRNA expression levels of NANOG, POU5F, DDX4, GFRα1, and UCHL1 were detected in the group adding GDNF + bFGF +GFRα1. The SSCs from the group adding GDNF + bFGF +GFRα1 also showed UCHL1-, DBA-, and CDH1-positive staining. Moreover, Stra8 and Scp3 expression, and haploid peak were detected after induction of the SSCs from the group adding GDNF + bFGF +GFRα1. In conclusion, pig SSCs could be maintained for long-term in the presence of GDNF, bFGF, and GFRα1.

Basic <em>fibroblast</em> <em>growth</em> <em>factor</em> (bFGF) is a potent mitogen for various cell types. We report here the first study of the effects of bFGF on a digestive tract-derived cell line. The effect of bFGF on the proliferation of AR4-2J cells, tumor cells of acinar pancreatic origin, was investigated together with modulation of ornithine decarboxylase (ODC) activity, an intracellular event involved in cell proliferation. bFGF caused a concentration-dependent stimulation of AR4-2J cell <em>growth</em>, with a half maximal effect (EC50) at <em>22</em> +/- 2 pM. ODC activity, assayed by the CO2-trapping method, was also increased by bFGF in a dose-dependent manner, reaching half-maximal stimulation at 20 pM. We conclude that bFGF is a very potent <em>growth</em> promoting <em>factor</em> for cells of pancreatic origin, already effective at picomolar concentrations. The parallelism between the <em>growth</em> assay and the ODC activity assay implicates the involvement of ODC activity in the pathway of the mitogenic effect of bFGF. The stimulation of ODC activity therefore seems to be a reliable early marker for cell proliferation in this model.