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Background: Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex and heterogeneous diseases driven by uncontrolled cell growth and proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them a promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value in HNSCC through comprehensive bioinformatics analysis, with a particular focus on the therapeutic potential of placental growth factor (PIGF). Methods: Transcriptome data for HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed genes (DEGs) were identified and analyzed for their prognostic significance. Exercise-related gene sets were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, were conducted. The biological functions and clinical implications of key genes were further explored through single-gene expression analysis, immune infiltration analysis, and in vitro cellular experiments. Results: The study identified exercise-related genes associated with survival prognosis in HNSCC. GO and KEGG pathway analyses highlighted the biological functions of these genes, and Kaplan-Meier survival curves confirmed their prognostic value. PIGF expression analysis using TCGA data showed its diagnostic potential, with higher expression linked to advanced tumor stages. Single-cell sequencing revealed PIGF's role in the tumor microenvironment. In vitro experiments demonstrated that PIGF plays a pivotal role in enhancing cell proliferation and colony formation in HNSCC, with PIGF knockdown significantly impairing these functions, highlighting its importance in tumor growth regulation. Additionally, PIGF's predictive performance in drug sensitivity across cancer datasets suggests its potential as a pharmacological target, offering opportunities to modulate the immune microenvironment and improve therapeutic outcomes in cancer treatment. Conclusion: This study provides new insights into the molecular mechanisms underlying HNSCC and identifies exercise-related genes, particularly PIGF, as promising biomarkers for clinical treatment and personalized medicine. By focusing on PTMs and their role in cancer progression, our findings suggest that targeting PIGF may offer innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex and heterogeneous diseases driven by uncontrolled cell growth and proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them a promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value in HNSCC through comprehensive bioinformatics analysis, with a particular focus on the therapeutic potential of placental growth factor (PIGF). Methods: Transcriptome data for HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed genes (DEGs) were identified and analyzed for their prognostic significance. Exercise-related gene sets were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, were conducted. The biological functions and clinical implications of key genes were further explored through single-gene expression analysis, immune infiltration analysis, and in vitro cellular experiments. Results: The study identified exercise-related genes associated with survival prognosis in HNSCC. GO and KEGG pathway analyses highlighted the biological functions of these genes, and Kaplan-Meier survival curves confirmed their prognostic value. PIGF expression analysis using TCGA data showed its diagnostic potential, with higher expression linked to advanced tumor stages. Single-cell sequencing revealed PIGF's role in the tumor microenvironment. In vitro experiments demonstrated that PIGF plays a pivotal role in enhancing cell proliferation and colony formation in HNSCC, with PIGF knockdown significantly impairing these functions, highlighting its importance in tumor growth regulation. Additionally, PIGF's predictive performance in drug sensitivity across cancer datasets suggests its potential as a pharmacological target, offering opportunities to modulate the immune microenvironment and improve therapeutic outcomes in cancer treatment. Conclusion: This study provides new insights into the molecular mechanisms underlying HNSCC and identifies exercise-related genes, particularly PIGF, as promising biomarkers for clinical treatment and personalized medicine. By focusing on PTMs and their role in cancer progression, our findings suggest that targeting PIGF may offer innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

• We found an association between physical activity and soluble fms-like tyrosine kinase 1 (sFlt-1). • Physical activity is associated with lower first trimester levels of sFlt-1. • Physical activity may be a risk modifier of preeclampsia. Physical activity during pregnancy has long been investigated for its role in preeclampsia prevention. The mechanism of this relationship is unknown, although some studies suggest physical activity may affect placental analytes throughout pregnancy. The objective of this study was to determine the effect of physical activity on preeclampsia-associated placental analytes using a prospective cohort of pregnant nulliparous patients. This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be. Frequency and duration of up to three leisure activities was reported in the first and second trimesters and was analyzed, with participants either meeting or not meeting the recommended exercise of 150 min per week. Levels of the following placental analytes, placental growth factor, soluble endoglin, and soluble fms-like tyrosine kinase-1 (sFLT1), were analyzed stratified by the physical activity level. A total of 1,956 participants were included in the analysis. The level of sFLT1 in the first trimester was lower in the group that had ≥ 150 min per week of physical activity, compared to the group that had < 150 min (846.3 [821.6, 871,8] versus 893.0 [864.5,922.5], p = 0.017). There were no significant sFLT1 changes in the second trimester based on physical activity. After controlling for maternal demographic and clinical factors, sFLT1 levels in the second trimester were significantly lower (p = 0.049) in participants that had ≥ 150 min of physical activity per week. Our findings of decreased sFLT1 levels suggest this could be the mechanism explaining the association between PA in pregnancy and lower risk of preeclampsia. [ABSTRACT FROM AUTHOR]

Vision loss due to disease or degeneration of the eye (retina, choroid, retinal veins, or macula) is a leading cause of blindness worldwide. In most cases, vision-threatening ocular diseases are accompanied by abnormal changes in the vasculature of the eye, especially the retina, and these conditions are collectively referred to as retinal vasculopathies. Impaired blood supply or hypoxia stimulates angiogenesis in the vascular and non-vascular sections of the eye, which results in neovascularization, leading to conditions such as diabetic retinopathy or age-related macular degeneration. Studies show that vascular endothelial growth factors: VEGF-A, VEGF-B, and placental growth factor (PlGF) are elevated in these diseases, and hence, these factors could be used as markers for disease prognosis and therapy. In this review, we discuss the function of these growth factors in normal development and disease, with focus on ocular disorders and emphasize the importance of accurately determining their levels in the vitreous and serum of patients for correct diagnosis and therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy of first-trimester markers--pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin β (fhCGβ), alpha-fetoprotein (AFP), placental growth factor (PIGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE). METHODS: During 2005-2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE. RESULTS: PAPPA, fhCGβ, and PIGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR). CONCLUSIONS: First-trimester maternal serum levels of PAPPA, fhCGβ, AFP, PIGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE. [ABSTRACT FROM AUTHOR]

Background & Aims: Development of the portal-hypertensive syndrome is mediated by splanchnic inflammation and neoangiogenesis. Since peroxisome proliferator-activated receptor gamma (PPARγ) agonists like pioglitazone (PIO) regulate inflammatory response and inhibit angiogenesis in endothelial cells, we evaluated PIO as treatment for experimental portal hypertension. Methods: PIO (10mg/kg) or vehicle (VEH) was administered from day 21–28 after bile duct ligation (BDL), from day 0–7 after partial portal vein ligation (PPVL) or sham-operation (SO), respectively. After treatment, systemic hemodynamics, splanchnic blood flow (SMABF), portal pressure (PP), and portosystemic shunting (PSS) were assessed. Splanchnic and hepatic tissues were analyzed for angiogenic and inflammatory markers. Results: BDL and PPVL showed significantly increased PP, SMABF, and PSS compared to SO-VEH rats. While PIO treatment did not decrease PP or SMABF, PSS was significantly reduced both in cirrhotic (BDL-VEH: 71% to BDL-PIO: 41%; p <0.001) and non-cirrhotic (PPVL-VEH: 62% to PPVL-PIO: 40%; p =0.041) rats. PIO (10μM, in vitro) inhibited endothelial cell migration and significantly increased PPARγ activity in vivo. In BDL rats, PIO decreased hepatic mRNA levels of PPARγ (p =0.01) and PlGF (p =0.071), and splanchnic mRNA expression of PPARγ (p =0.017), PDGFβ (p =0.053) and TNFα (p =0.075). Accordingly, splanchnic protein expression of PPARγ (p =0.032), VEGFR2 (p =0.035), CD31 (p =0.060) and PDGFβ (p =0.066) were lower in BDL-PIO vs. BDL-VEH animals. In PPVL rats, PIO treatment decreased splanchnic gene expression of Ang2 (−12.4 fold), eNOS (−9.3 fold), PDGF (−7.0 fold), PlGF (−11.9 fold), TGFb (−8.3 fold), VEGF-A (−11.3 fold), VEGFR1 (−5.9 fold), IL1b (−14.4 fold), and IL6 (−9.6 fold). Conclusions: Pioglitazone treatment decreases portosystemic shunting via modulation of splanchnic inflammation and neoangiogenesis. Pioglitazone should be assessed for potential beneficial effects in patients with portosystemic collaterals due to portal hypertension. [Copyright &y& Elsevier]

A letter to the editor is presented which discusses the relationship of the placental growth factor and fms-like tyrosine kinase 1 with the levels of pregnancy-associated plasma protein A (PAPP-A).

Objective: The aim: To reduce the frequency and severity of preeclampsia, to improve obstetrical and perinatal outcomes in women with multiple pregnancy after assisted reproduction by the development and implementation of the preventive algorithm with biochemical markers of endothelial dysfunction prospective analysis., Patients and Methods: Materials and methods: Clinical and laboratory prospective analysis of 54 cases of twins in women, treated from infertility with assisted reproductive technologies (ART), using the method of intracytoplasmic sperm injection (ICSI) and frozen embryos transfer, have been made. It was proven, that women with multiple pregnancy are always in a high risk group of placental dysfunction (PD) and preeclampsia (PE). Depending on the treatment algorithm and preventive measures, 2 groups of patients were formed. Group I included 29 pregnant women with twins, managed in accordance with developed recommendations. We didn't find evidence-based European guidelines, that would recommend routine prescription of progesterone to improve chorion invasion and further placentation in such group of patients, but in order to prevent endothelial dysfunction and to decrease the incidence and severity of preeclampsia, placental abnormalities and intrauterine growth restriction (IUGR), we proposed the following algorithm: - micronized progesterone 200 mg vaginally (PV), as soon as pregnancy was diagnosed by positive hCG-test, till 16 weeks of pregnancy, angioprotector diosmin 600 mg once daily orally (PO), 2 courses: from 8 till 12 and from 16 till 20 weeks of gestation, antiaggregant - acetylsalicylic acid 150 mg from 12 till 36 weeks of gestation. Group II included 25 pregnant women with twins after the same ART procedures, who have not received above mentioned treatment. Plasma concentrations of PlGF, sFlt-1 and the ratio of sFlt-1/PlGF in the secondtrimester were investigated in both groups of women in order to assess the effectiveness of proposed preventive measures., Results: Results: Usage of preventive algorithm has shown the reduction of PE incidences in 26%, PD in 28.1%, IUGR in 35%, prematurity by 23% and fetal distress in 18%, that led toimprovement of obstetrical and perinatal outcomes in I group of women with multiple pregnancies after ART-treated infertility, compared with group II (p<0.05). The evaluation of PlGF, sFlt-1 plasma concentrations and the ratio of sFlt-1/PlGF in the second trimester of pregnancy reflected the effectiveness of our method in women with twins after ART. The level of PlGF in the study group was higher (186.5 ± 12 vs 154.2 ± 10.7; p<0.05), and the level of sFlt-1 was lower (1523.1 ± 40.3 vs 1835.3 ± 33.6; p <0.05). Results of sFlt-1/PlGF ratio analysis in the I group also showed effectiveness of the method proposed (20.3 ± 3.1 vs 28.1 ± 2.2; p<0.05)., Conclusion: Conclusions: The observed results suggest, that pregnant women with twins after ART-treated infertility are in a high-risk group of PE, PD and IUGR of one or both fetuses. Implementation of the proposed preventive algorithm allows to reduce the incidence of PE, obstetrical and perinatal complications in this group of patients, and can be widely used in clinical practice. Evaluation and prospective assessment of biochemical markers, such as PlGF, sFlt-1 and sFlt-1/PIGF ratio, in the second trimester of pregnancy in the target groups may likely predict the development of PE and its severity.

Angiogenesis is the process through which new blood vessels are formed, based on preexisting vessels, and is the paradigm of diseases such as cancer and exudative ageassociated macular degeneration (ARMD). Several proangiogenic factors have been identified, such as vascular endothelial growth factor (VEGF), especially VEGF-A, which activates endothelial cells and promotes cell proliferation, migration, and an increase in vascular permeability. VEGF is also involved in the etiopathogenesis of other retinal diseases, such as diabetic macular edema and macular edema secondary to retinal vein occlusion. Likewise, there is increasing evidence that placental growth factor (PIGF) acts recepsynergetically with VEGF in promoting these diseases. Currently, the main treatment for these diseases are the anti-VEGF drugs, aflibercept, ranibizumab and bevacizumab. These agents differ in their molecular structure and mechanism of action., (Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)