Assessment of serum levels and placental bed tissue expression of IGF-1, bFGF, and PLGF in patients with placenta previa complicated with placenta accreta spectrum disorders.

OBJECTIVE: This study aims to detect the serum levels of IGF-1, bFGF, and PLGF and their expressions in placental bed tissues of patients with placenta previa complicated with PAS disorders. METHODS: This case and control study included 40 multiparous pregnant women with complete placenta previa between 34 weeks and 38 weeks of gestation and they were divided into two groups: 25 patients with PAS (case group) and 15 patients without PAS (control group). The venous blood samples were collected 2 h before the cesarean section, and the placental bed tissues were taken intraoperatively at the placental implantation site and then were histologically examined to evaluate the gravity of the myometrial invasion of the placenta. According to FIGO PAS increasing grading, the 25 patients were also divided into three groups: PAS grade I group, PAS grade II group, and PAS grade III group. The concentrations of IGF-1, bFGF, and PLGF in serum were measured using ELISA, and the mean ratio of the relative mRNA expression of each biomarker in placental bed tissues was calculated using qRT-PCR. The staining intensity and the positive cells were quantitatively measured and expressed as means by using Image J software for IHC analysis. RESULTS: IGF-1 had low serum levels and high placental bed expression in placenta previa patients with PAS disorders compared to those without PAS (all p < 0.0001). PLGF had high serum levels (p = 0.0200) and high placental bed expression (p < 0.0001) in placenta previa patients with PAS disorders compared to those without PAS. IGF-1 serum levels decreased up to PAS grade II (means were 24.3 ± 4.03, 21.98 ± 3.29, and 22.03 ± 7.31, respectively for PAS grade I, PAS grade II, PAS grade III groups, p = 0.0006). PLGF serum levels increased up to PAS grade II (means were 12.96 ± 2.74, 14.97 ± 2.56, and 14.89 ± 2.14, respectively for the three groups, p = 0.0392). However, IGF-1 and PLGF mRNA placental bed expression increased up to PAS grade III. The relative expression of mRNA means for the three groups was 3.194 ± 1.40, 3.509 ± 0.63, and 3.872 ± 0.70, respectively for IGF-1; and 2.784 ± 1.14, 2.810 ± 0.71, and 2.869 ± 0.48, respectively for PLGF (all p < 0.0001). Their IHC (immunohistochemical) staining also had increasing trends, but p > 0.05. bFGF was not significantly expressed in placenta previa with PAS disorders in most of the analysis sections (p > 0.05). CONCLUSIONS: Low serum levels and high expression in placental bed tissues of IGF-1, or high serum levels and high expression in placental bed tissues of PLGF, may differentiate placenta previa patients with FIGO PAS grade I and PAS grade II from those without PAS disorders. However, they could not significantly predict the degree of placental invasiveness in FIGO PAS grades II and III.

MAPs/bFGF-PLGA microsphere composite-coated titanium surfaces promote increased adhesion and proliferation of fibroblasts.

Infection and epithelial downgrowth are two major problems with maxillofacial transcutaneous implants, and both are mainly due to lack of stable closure of soft tissues at transcutaneous sites. Fibroblasts have been shown to play a key role in the formation of biological seals. In this work, titanium (Ti) model surfaces were coated with mussel adhesive proteins (MAPs) utilizing its unique adhesion ability on diverse inorganic and organic surfaces in wet environments. Prepared basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid) (PLGA) microspheres can be easily synthesized and combined onto MAPs-coated Ti surfaces, due to the negative surface charges of microspheres in aqueous solution, which is in contrast to the positive charges of MAPs. Titanium model surfaces were divided into three groups. Group A: MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces. Group B: MAPs-coated Ti surfaces. Group C: uncoated Ti surfaces. The effects of coated Ti surfaces on adhesion of fibroblasts, cytoskeletal organization, proliferation, and extracellular matrix (ECM)-related gene expressions were examined. The results revealed increased adhesion (P < 0.05), enhanced actin cytoskeletal organization, and up-regulated ECM-related gene expressions in groups A and B compared with group C. Increased proliferation of fibroblasts during five days of incubation was observed in group A compared with groups B and C (P < 0.05). Collectively, the results from this in vitro study demonstrated that MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces had the ability to increase fibroblast functionality. In addition, MAPs/bFGF-PLGA microsphere composite-coated Ti surfaces should be studied further as a method of promoting formation of stable biological seals around transcutaneous sites.

An experimental and molecular-modeling study of the binding of linked sulfated tetracyclitols to FGF-1 and FGF-2.

The experimental binding affinities of a series of linked sulfated tetracyclitols [Cyc2N-R-NCyc2, where Cyc = C6H6(OSO3Na)3 and R = (CH2)n (n = 2-10), p-xylyl or (C2H4)2-Ncyc] for the fibroblast growth factors FGF-1 and FGF-2 have been measured by using a surface plasmon resonance assay. The KD values range from 7.0 nM to 1.1 microM for the alkyl-linked ligands. The binding affinity is independent of the flexibility of the linker, as replacement of the alkyl linker with a rigid p-xylyl group did not affect the KD. Calculations suggest that binding modes for the p-xylyl-linked ligand are similar to those calculated for the flexible alkyl-linked tetracyclitols. The possible formation of cross-linked FGF:cyclitol complexes was examined by determining KD values at increasing protein concentrations. No changes in KD were observed; this suggesting that only 1:1 complexes are formed under these assay conditions. Monte Carlo multiple-minima calculations of low-energy conformers of the FGF-bound ligands showed that all of the sulfated tetracyclitol ligands can bind effectively in the heparan sulfate-binding sites of FGF-1 and FGF-2. Binding affinities of these complexes were estimated by the Linear Interaction Energy (LIE) method to within a root-mean-square deviation of 1 kcal mol(-1) of the observed values. The effect of incorporating cations to balance the overall charge of the complexes during the LIE calculations was also explored.

Protein NMR recall, precision, and F-measure scores (RPF scores): structure quality assessment measures based on information retrieval statistics.

One of the most important challenges in modern protein NMR is the development of fast and sensitive structure quality assessment measures that can be used to evaluate the "goodness-of-fit" of the 3D structure with NOESY data, to indicate the correctness of the fold and accuracy of the resulting structure. Quality assessment is especially critical for automated NOESY interpretation and structure determination approaches. This paper describes new NMR quality assessment scores, including Recall, Precision, and F-measure scores (referred to here are "NMR RPF" scores), which quickly provide global measures of the goodness-of-fit of the 3D structures with NOESY peak lists using methods from information retrieval statistics. The sensitivity of the F-measure is improved using a scaled Fold Discriminating Power (DP) score. These statistical RPF scores are quite rapid to compute since NOE assignments and complete relaxation matrix calculations are not required. A graphical method for site-specific assessment of structure quality based on the Precision statistic is also described. These statistical measures are demonstrated to be valuable for assessing protein NMR structure accuracy. Their relationships to other proposed NMR "R-factors" and structure quality assessment scores are also discussed.