Basic Fibroblast Growth Factor Levels Research Articles

Hyperglycaemia perturbs blood-brain barrier integrity through its effects on endothelial cell characteristics and function

ABSTRACT Breakdown of blood-brain barrier (BBB) represents a key pathology in hyperglycemia-mediated cerebrovascular damage after an ischemic stroke. As changes in the level and nature of vasoactive agents released by endothelial cells (ECs) may contribute to BBB dysfunction, this study first explored the specific impact of hyperglycemia on EC characteristics and secretome. It then assessed whether secretome obtained from ECs subjected to normoglycaemia or hyperglycemia might regulate pericytic cytokine profile differently. Using a triple cell culture model of human BBB, composed of brain microvascular EC (BMEC), astrocytes and pericytes, this study showed that exposure to hyperglycemia (25 mM D-glucose) for 72 h impaired the BBB integrity and function as evidenced by decreases in transendothelial electrical resistance and increases in paracellular flux of sodium fluorescein. Dissolution of zonula occludens-1, a tight junction protein, and appearance of stress fibers appeared to play a key role in this pathology. Despite elevations in angiogenin, endothelin-1, interleukin-8 and basic fibroblast growth factor levels and a decrease in placental growth factor levels in BMEC subjected to hyperglycemia vs normoglycaemia (5.5 mM D-glucose), tubulogenic capacity of BMECs remained similar in both settings. Similarly, pericytes subjected to secretome obtained from hyperglycemic BMEC released higher quantities of macrophage migration inhibitory factor and serpin and lower quantities of monocyte chemoattractant protein-1, intercellular adhesion molecule, interleukin-6 and interleukin-8. Taken together these findings indicate the complexity of the mechanisms leading to BBB disruption in hyperglycemic settings and emphasize the importance of endothelial cell-pericyte axis in the development of novel therapeutic strategies.

Morphological peculiarities of regeneration phases and dynamics of growth factor levels at using 2-ethyl-6-methyl-3-hydroxypyridinium n-acetyl-6-aminohexanoate for rat skin burns repairation

BACKGROUND: It was found that new derivatives of acexamic acid — N-acetyl-6-aminohexanoate of silver and 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate stimulate regeneration and mineralization of bone tissues in osteoporosis. However, to date, the effect of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate on the features of reparative histogenesis and the relationship of its stages with the levels of growth factors in regenerating tissues during skin restoration after thermal burn has not been studied.
 AIM: To estimate the morphology dynamics of skin burn healing and its relationship with the levels of vascular endothelial growth factor and basic fibroblast growth factor growth factors in rat regenerating tissues to characterize the reparative properties of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate.
 MATERIALS AND METHODS: 63 nonlinear rats were used to establish thermal burn wound model according to standard methodics. Burn wounds of the experimental group animals were treated with 2% ointment of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate daily, control group 1 — the burns were not treated, control group 2 — ointment base was applied daily. Morphological examinations of regenerating tissues from the burn area were carried out on days 7, 14 and 21 of the experiment after standard sample preparation. The concentrations of growth factors in homogenates of regenerating tissues were determined by Enzyme Immunoassay.
 RESULTS: The inflammation phase is characterized by vascular endothelial growth factor active production and release from cells and morphologically accompanied by early neovasculogenesis in granulation tissue and significant differences in its thickness in rats of the experimental group. During the proliferation phase, activation of fibroblast reproduction and differentiation was associated with an increase in basic fibroblast growth factor levels and the maintenance of elevated vascular endothelial growth factor levels in all groups, especially high in experimental group rats. The epithelialization phase was accompanied by a statistically significant decrease in the content of basic fibroblast growth factor and vascular endothelial growth factor in regenerating skin tissues by 1.9 and 1.8 times, respectively, in comparison with the control groups.
 CONCLUSIONS: The obtained experimental data indicate 2% ointment with 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate has a reparative potential, as evidenced by the accelerated reduction both the area of burn defects and the average time for their healing in the experimental group compared to the control groups.

Human Fibroblast-Derived Matrix Hydrogel Accelerates Regenerative Wound Remodeling Through the Interactions with Macrophages.

Herein, a novel extracellular matrix (ECM) hydrogel is proposed fabricated solely from decellularized, human fibroblast-derived matrix (FDM) toward advanced wound healing. This FDM-gel is physically very stable and viscoelastic, while preserving the natural ECM diversity and various bioactive factors. Subcutaneously transplanted FDM-gel provided a permissive environment for innate immune cells infiltration. Compared to collagen hydrogel, excellent wound healing indications of FDM-gel treated in the full-thickness wounds are noticed, particularly hair follicle formation via highly upregulated β-catenin. Sequential analysis of the regenerated wound tissues disclosed that FDM-gel significantly alleviated pro-inflammatory cytokine and promoted M2-like macrophages, along with significantly elevated vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) level. A mechanistic study demonstrated that macrophages-FDM interactions through cell surface integrins α5β1 and α1β1 resulted in significant production of VEGF and bFGF, increased Akt phosphorylation, and upregulated matrix metalloproteinase-9 activity. Interestingly, blocking such interactions using specific inhibitors (ATN161 for α5β1 and obtustatin for α1β1) negatively affected those pro-healing growth factors secretion. Macrophages depletion animal model significantly attenuated the healing effect of FDM-gel. This study demonstrates that the FDM-gel is an excellent immunomodulatory material that is permissive for host cells infiltration, resorbable with time, and interactive with macrophages, where it thus enables regenerative matrix remodeling toward a complete wound healing.

Predictors of fibrogenesis in children with JIA: a single-center pilot study

BackgroundPatients with rheumatological diseases are at high risk of developing irreversible fibrotic changes, both articular and extra-articular, as a result of tissue damage caused by the chronic phase of persistent inflammation. Thus, our purpose was to study early markers of fibrosis formation in children with juvenile idiopathic arthritis (JIA).MethodsSeventy patients with juvenile idiopathic arthritis, namely, polyarthritis (64.29%) and oligoarthritis (35.71%) variant JIA (mean age 13.3 years, 64.29% girls, 35.71% boys), were included in this 4-year prospective study. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were determined by ELISA kits.ResultsWe evaluated bFGF (mean: 7478.21 pg/ml; min: 4171.56 pg/ml; max: 18,011.25 pg/ml) and VEGF (mean: 342.47 pg/ml; min: 23.68 pg/ml; max: 2158.91 pg/ml) levels in children with JIA. Children with JIA had a higher VEGF level when JIA onset occurred after 15 years of age and they had a high disease activity; additionally, a higher bFGF level was observed in children older than 14 years and in those with a JIA onset after 15 years of age, the oligoarticular variant, a moderate disease activity and regardless of MTX administration but more often when MTX was administered at a dosage from 10 to 12.5 mg/m2/week.ConclusionsLaboratory screening of fibrosis formation predictors could help identify patients who may be at greater risk of adverse outcomes. Children with JIA had higher bFGF and VEGF levels when JIA onset occurred after 15 years of age, depending on disease activity.

BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

Serum basic fibroblast growth factor and interleukin-1β predict the effect of first-line chemotherapy in patients with advanced gastric cancer.

The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1β levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.

Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair.

Mechanically processed stromal vascular fraction (mSVF) is a highly interesting cell source for regenerative purposes, including wound healing, and a practical alternative to enzymatically isolated SVF. In the clinical context, SVF benefits from scaffolds that facilitate viability and other cellular properties. In the present work, the feasibility of methacrylated gelatin (GelMA), a stiffness-tunable, light-inducible hydrogel with high biocompatibility is investigated as a scaffold for SVF in an in vitro setting. Lipoaspirates from elective surgical procedures were collected and processed to mSVF and mixed with GelMA precursor solutions. Non-encapsulated mSVF served as a control. Viability was measured over 21 days. Secreted basic fibroblast growth factor (bFGF) levels were measured on days 1, 7 and 21 by ELISA. IHC was performed to detect VEGF-A, perilipin-2, and CD73 expression on days 7 and 21. The impact of GelMA-mSVF on human dermal fibroblasts was measured in a co-culture assay by the same viability assay. The viability of cultured GelMA-mSVF was significantly higher after 21 days (p < 0.01) when compared to mSVF alone. Also, GelMA-mSVF secreted stable levels of bFGF over 21 days. While VEGF-A was primarily expressed on day 21, perilipin-2 and CD73-positive cells were observed on days 7 and 21. Finally, GelMA-mSVF significantly improved fibroblast viability as compared with GelMA alone (p < 0.01). GelMA may be a promising scaffold for mSVF as it maintains cell viability and proliferation with the release of growth factors while facilitating adipogenic differentiation, stromal cell marker expression and fibroblast proliferation.

Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, double-blind, crossover study

BackgroundChronic inflammation has been described in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) despite viral suppression. Inflammation associated non-communicable diseases, including atherosclerosis, are becoming recognized complication of HIV infection. We studied the effect of pitavastatin on atherosclerotic-associated inflammatory biomarkers in PLHIV receiving ART.MethodsA randomized, double-blind, crossover study was conducted in HIV-infected persons with dyslipidemia and receiving atazanavir/ritonavir (ATV/r) to evaluate the effect of 2 mg/day pitavastatin treatment versus placebo. High-sensitivity CRP (hs-CRP), cytokines, and cellular markers in PLHIV receiving 12 weeks of pitavastatin or placebo were investigated.ResultsA total of 24 HIV-infected individuals with a median (interquartile range) age of 46 (41–54) years were recruited, and the median CD4 T cell count was 662 (559-827) cells/mm3. The median duration of ATV/r use was 36 (24–48) months. Significant change in levels of basic fibroblast growth factor (FGF) between pitavastatin treatment and placebo at week 12 from baseline was observed (27.1 vs. 20.5 pg/mL; p=0.023). However, there were no significant changes from baseline of hs-CRP and other plasma cytokine levels at week 12 of pitavastatin or placebo. Regarding cellular markers, percentages of HLA-DR+CD38-CD4+ T cells and PD1+CD4+ T cells significantly decreased from baseline in PLHIV receiving pitavastatin for 12 weeks, as compared to placebo (− 0.27 vs. 0.02%; p=0.049 and − 0.23 vs. 0.23%; p=0.022, respectively).ConclusionsPitavastatin treatment increases basic FGF levels, and lowers HLA-DR+CD38-CD4+ T cells, and PD1+CD4+ T cells. Further study on the effects of pitavastatin on preventing cardiovascular diseases in PLHIV should be pursued.

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264-0.892, p = 0.020; OR = 0.323, 95% CI = 0.107-0.972, p = 0.044; OR = 1.492, 95% CI = 1.111-2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.

Elevated Angiogenic Factor Levels After Transarterial Radioembolization for Colorectal Cancer Liver Metastases May Predict a Poor Prognosis.

Objectives:To analyze the change in circulating angiogenic factor levels after transarterial radioembolization (TARE) for colorectal cancer liver metastases (CRCLMs) and its prognostic significanceMethods:Blood samples immediately before TARE and on 1 day, 1 week and 6 weeks after were collected for angiogenic factor analysis in 23 patients.Results:Patients with elevated serum basic fibroblast growth factor and platelet-derived growth factor levels in the 1st week and vascular endothelial growth factor (VEGF) levels in the 6th week after TARE had significantly shorter median overall survival (OS) times.Conclusion:Some early increases in serum angiogenic factor levels and in serum VEGF in the 6th week after TARE for CRCLMs are related to short OS and progression-free survival.

Correlation of CT Perfusion Parameters and Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (BFGF) in Patients with Primary Liver Cancer.

Objective To investigate the correlation of CT perfusion-related parameters with serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) in patients with primary liver cancer. Methods A total of 100 patients with primary liver cancer who were treated in our hospital from June 2019 to June 2021 were selected as the observation group, and 90 patients with benign liver lesions during the same period were selected as the control group. The CT perfusion-related parameters (perfusion volume and perfusion index) and serum VEGF and BFGF levels were compared between the two groups. Pearson correlation was used to analyze the correlation between CT perfusion-related parameters and serum VEGF and BFGF levels. Results Compared to the control group, significantly higher HAP and lower HPP and TLP were observed in the observation group. The perfusion volume indexes of patients with different stages of liver cancer in the observation group were statistically different (P < 0.05). Compared to the control group, the observation group witnessed significantly higher HAPI and lower HPPI. There were statistically significant differences in the perfusion index of patients with different stages of primary liver cancer in the observation group (P < 0.05). The serum VEGF and BFGF levels in the observation group were significantly higher than those in the control group, and the serum VEGF and BFGF levels in patients with different stages of primary liver cancer in the observation group were statistically different (P < 0.05). Pearson correlation analysis showed that HAP and HAPI were positively correlated with VEGF and BFGF (r = 0.986, P ≤ 0.001; r = 0.983, P ≤ 0.001), and HPP, TLP, and HPPI were negatively correlated with VEGF and BFGF (r = −0.992, P ≤ 0.001; r = -0.993, P ≤ 0.001; r = −0.995, P ≤ 0.001). Conclusion CT perfusion-related parameters and serum VEGF and BFGF levels in patients with primary liver cancer are abnormally expressed, and there is a strong correlation between the two, which might aid clinical diagnosis and treatment.

Effects of losartan on glandular epithelial prostatic hyperplasia in spontaneously hypertensive rats

ABSTRACT Introduction Benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) are common disorders in aging men and cause lower urinary tract symptoms. Hypertension induces atherosclerosis in the blood vessels of the lower urinary tract, subsequently following by the development of BPH and BPE. Clinical study demonstrated that anti-hypertensive drug angiotensin II type 1 receptor blocker (ARB) treatment improved storage and voiding scores in male patients with hypertension, whereas other antihypertensive drugs were not effective. ARB could improve prostatic hyperplasia independent of reducing blood pressure. Spontaneously hypertensive rats (SHRs) are widely used as genetically hypertensive model. SHRs also demonstrate decreased prostatic blood flow and develop glandular epithelial hyperplasia and morphological abnormalities in the ventral prostate. Objective We examined the effects of an ARB, losartan on glandular epithelial prostatic hyperplasia in SHRs. Methods Thirty-six-weeks old male SHRs were orally treated with losartan (3 or 10 mg/kg/day) or vehicle once daily for 18 weeks. Wistar Kyoto rats (WKYs) were treated with vehicle were used as controls (n = 8). After the oral treatment, effects of losartan were evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The tissue levels of malondialdehyde (oxidative stress marker; MDA), interleukin-6 (inflammatory cytokine; IL-6), and basic fibroblast growth factor (bFGF) levels in ventral prostate were measured by colorimetric assay and ELISA assay. Histological analysis for the ventral prostate was performed by hematoxylin and eosin (HE) staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The glandular epithelial area was determined by HE staining. TUNEL assay was performed to quantify the degree of apoptosis. The statistical differences were determined using one-way analysis of variance followed by the Tukey-Kramer test. Histological data were analyzed using the nonparametric Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni's correction for multiple comparison. Results Body weight did not significantly differ among the groups. The vehicle treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow compared to the vehicle treated WKYs. Treatment with losartan significantly decreased PBR and improved prostatic blood flow and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs. Conclusion Chronic losartan treatment could improve glandular epithelial prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might improve not only hypertension but also prostatic hyperplasia in humans. Disclosure Work supported by industry: no.

Exploring the Role and Mechanism of Adipose Derived Mesenchymal Stem Cells on Reversal of Pigmentation Model Effects.

Interventions for extrinsic aging can be implemented, but these must address photoaging, which is the primary cause of extrinsic aging. Pigmentation due to photoaging depends on the duration and intensity of sun exposure. This study investigated the relationship between adipose-derived mesenchymal stem cells (ASCs) and photoaging pigmentation, and the underlying mechanism of action by establishing a photoaging pigmentation model using various treatments and exposure options in a guinea pigs. The energy dose of each UVB irradiation was 120 mJ/cm2 and the total dose of irradiation was 360 mJ/cm2. After successfully establishing the photoaging model, ASCs (1×106) in an balanced salt solution (0.9 ml), balanced salt solution (0.9 ml), and bFGF (9 μg) mixed with an balanced salt solution (0.9 ml) were injected intradermally in ten guinea pigs. ELISA, macroscopic skin and histological observations, and Masson-Fontana staining were done. At 2 and 4 weeks post-injection, noticeable changes were observed. Guinea pigs receiving ASCs injections displayed significantly lower visible skin scores while the melanin content continued to decrease. Somewhat improved histopathological morphology, including epidermal thinning, dermal thickening, and little inflammatory cell infiltration was observedimmediately after and up to 4 weeks of ASCs injection. Melanocortin 1 receptor (MC1R) and alpha-melanocyte test hormone (alpha-MSH) levels reduced significantly, and basic fibroblast growth factor (bFGF) levels increased significantly immediately after and up to 4 weeks of ASCs injection. The MC1R and alpha-MSH levels reduced significantly immediately after and up to 4 weeks of bFGF injection. Briefly, intradermal ASCs injection can notably eliminate pigmentation in a guinea pig photoaging pigmentation model. This may be related to the fact that bFGF secreted by ASCs lowers MC1R and alpha-MSH levels, blocks the cAMP signalling pathway, and inhibits melanin synthesis. This finding may present new options for treating photoaging pigmentation.Level of Evidence: N/A.

Effects of Biomaterials for Sustained-Release Growth Factor Biomaterials on Tendon Healing in Rats

To investigate the effect of sustained-release growth factor biomaterials on tendon healing in rats. A total of 45 healthy adult Sprague-Dawley rats were randomly divided into 3 groups viz. blank group, vascular endothelial growth factor group and basic fibroblast growth factor group with 15 rats in each group. The rats in vascular endothelial growth factor group and basic fibroblast growth factor group were injected with 0.2 ml vascular endothelial growth factor (100 ng) and 0.2 ml basic fibroblast growth factor (100 ng) respectively. They were injected again on the 7th d, 14th d and 21st d after operation. At 2, 4 and 6 w after operation, 4 rats in each group were selected for experimental observation. The changes of vascular endothelial growth factor and basic fibroblast growth factor levels in the treated experimental animals and the control rats were compared by the Hematoxylin and Eosin staining and adhesion were observed during the observation period. The expression of both vascular endothelial growth factor and basic fibroblast growth factor in the experimental group was significantly higher than that in the control group. The concentration of the control group at each time phase had no significant change compared with that before operation. Both vascular endothelial growth factor and basic fibroblast growth factor play an important role in the healing process of muscle bonds. Vascular endothelial growth factor is better than basic fibroblast growth factor in promoting micro angiogenesis and cell proliferation in the early stage and basic fibroblast growth factor may be better than vascular endothelial growth factor in promoting collagen synthesis.

Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation

BackgroundSex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR.MethodsIn 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression.ResultsAfter adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h.ConclusionsMen and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.

Molecular Evaluation of Efficacy of Freshwater and Marine Acellular Fish Skin Matrixes in Reconstruction of Ventro- Lateral Hernia in Bucks

The objective of present study is to compare between the effectiveness of freshwater and marine acellularfish skin (AFS) matrices on the reconstruction of large abdominal wall hernias in Iraqi bucks using ofmolecular evaluation depending on Real Time-quantification Polymerase Chain Reaction (RT-qPCR)technique to investigate the levels of basic-fibroblast growth factor (b-FGF) and vascular endothelial growthfactor (VEGF) genes during the healing process of the abdominal wall hernias. Ventral-lateral abdominalwall hernias (7X7cm) were induced experimentally in 18 bucks. Thirty days post-inducing of hernias, theanimals were divided randomly into two main groups (9 Bucks/ group). The hernias in animals of group (A)were treated with onlay implantation of freshwater AFS sheet. While, the hernias in animals of group (B)were treated with onlay implantation of marine AFS sheet. Molecular evaluation was depended at 2, 8, and12 weeks post-treatment of hernias. The results revealed that the significant elevation of the level of b-FGFbetween treatment groups was at week 8th in group B and at week 12th in group A. While, the significantelevation of level of VEGF between treatment groups was recorded in group A, 12 week post-treatment.

The Influence of the Preservation Method and Gamma Irradiation Sterilization on TGF-β and bFGF Levels in Freeze-Dried Amnion Membrane (FD-AM) and Amnion Sponge.

Background Amnion grafts can be preserved as freeze-dried amnion membrane (FD-AM) and amnion sponge. Preserved grafts require to be sterilized by gamma irradiation. However, each step of the process could affect its biological properties. Even so, there are only a few studies that report the influence of the preservation method and gamma irradiation on growth factor levels in preserved amniotic grafts. Methods This was an in vitro experimental study with a pretest-posttest group design using a consecutive sampling technique in one batch of amnion donors at a particular time. The amnion was made into FD-AM and amnion sponge preparations, and they were sterilized with gamma irradiation (15 kGy and 25 kGy). Nonirradiated specimens served as controls, and 20 mg of each specimen was pulverized to evaluate the growth factors levels using ELISA. Results There were significant decreases in amnion sponge compared to the FD-AM, both in transforming growth factor beta (TGF-β) and basic fibroblast growth factor (bFGF) levels and in the preirradiated and 25 kGy postirradiated preparations (p ≤ 0.05). The growth factor levels in the preirradiated and postirradiated FD-AM (both 15 kGy and 25 kGy) showed significant differences (p ≤ 0.05). Likewise, the preirradiated amnion sponge group's growth factor levels compared with the postirradiated amnion sponge group also showed a significant decrease (p ≤ 0.05). Conclusion TGF-β and bFGF levels were lower in amnion sponge than FD-AM. The FD-AM and amnion sponge preparations' growth factors levels were reduced following gamma irradiation sterilization. Although the decrease in growth factor levels is significant, the number of growth factor levels is still sufficient for tissue healing.

Therapeutic effects of losartan on prostatic hyperplasia in spontaneously hypertensive rats

AimsWe investigated the therapeutic effects of losartan, an angiotensin II type 1 receptor blocker, on prostatic hyperplasia in spontaneously hypertensive rats (SHRs). Main methodsMale SHRs (age, 36 weeks) were perorally treated with losartan (3 or 10 mg·kg−1) or vehicle once daily for 18 weeks. Age-matched Wistar Kyoto rats (WKYs) were used as vehicle-treated controls (n = 8). The effects of losartan were evaluated by analyzing prostate weight, blood pressure, and prostatic blood flow. The tissue malondialdehyde (MDA), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) levels were measured. Histological analysis for the ventral prostate involved hematoxylin and eosin staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Key findingsCompared to the vehicle-treated WKYs, the vehicle-treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow. Treatment with losartan caused significant recovery of blood flow and decreased PBR and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs. SignificanceChronic losartan treatment could ameliorate prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might have therapeutic effects on not only hypertension but also prostatic hyperplasia in humans.

Skeletal Muscle Regulatory Markers Responses Following Whole And Egg White Ingestion In Resistance Trained Men

Protein ingestion is recommended to maximize muscular adaptations post resistance training (RT). Eggs are a rich food source commonly consumed post-workout to meet protein requirements. Although removing egg yolk is often promoted for the improvement of body composition (BC), whole-egg (WE) consumption has been shown to cause a greater stimulation of post-exercise muscle protein synthesis than egg-white (EW). However, changes in BC and skeletal muscle regulatory markers to chronic RT coupled with WE or EW consumption have not been evaluated. PURPOSE: To compare the effects of WE vs. EW ingestion after 12 wks of RT on BC and skeletal muscle regulatory markers in RT men. METHODS: Thirty RT men [age (24 ± 2 yrs), were randomized to either a WE (n=15) or EW (n=15) consumption group for 12 wks. The WE group ingested three WE while the EW group ingested six EW immediately post-workout and at the same time on non-training days. RT consisted of 10 exercises/session, 3x wk. Three sets of 3-14 reps (load was progressed) were performed for each exercise. Body weight, fat mass (FM), skeletal muscle mass (SMM) as well as serum follistatin (FOL), myostatin (MYO) and basic fibroblast growth factor (FGF-2) levels were measured at baseline and after 12 wks. RESULTS: Significant main effects of time were observed for body weight, SMM, FOL and FGF-2 which significantly (P < 0.05) increased, and for FM and MYO which significantly (P < 0.05) decreased. However, no significant group × time interactions were noted for any markers. Although non-significant, the WE group had ~1 Kg of extra FM loss than EW group. CONCLUSIONS: There are no differences in the changes achieved in BC and skeletal muscle regulatory factors after 12 wks of RT between WE and EW consumption. Although BC did not differ between groups, the ~1 Kg of extra FM loss seen after WE consumption may be an advantage for fitness enthusiasts with aesthetic goals.

Increased circulating basic fibroblast growth factor levels in acute myeloid leukemia: a meta-analysis

ABSTRACT Background: Basic fibroblast growth factor (bFGF) plays an important role in the pathogenesis of acute myeloid leukemia (AML). Whether the levels of circulating bFGF are increased or not in untreated AML patients is still not clear. In order to acquire a more definite evaluation, a meta-analysis was performed. Material and methods: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases for possible eligible articles. Forest plot was used to present the combined effect values and 95% confidence intervals (CI) through the random-effect model. Subgroup analysis was performed based on sample size, sample type, and region. All statistical analysis was performed in STATA12.0 software. Results: After excluding the articles that did not meet the inclusion criteria, 11 studies that met the inclusion conditions were included in this meta-analysis. Overall, AML patients probably had higher circulating levels of bFGF (SMD = 1.15, 95% CI: 0.35–1.94). The results of sensitivity analysis indicated that the results were stable. Moreover, the trim and fill analysis showed that publication bias had little effect and the results were relatively robust. In addition, AML patients with N < 30 group, serum group, and Asia group (all P < 0.05) had higher circulating bFGF levels, whereas other subgroups showed no significant change. Conclusion: The results of current meta-analysis revealed that AML patients had higher circulating bFGF levels, and it was associated with sample type, sample size, and region. Considering the possible pathogenic role of bFGF in AML, drug development targeting bFGF is very promising for AML patients.