Pulsed electric fields stimulate microglial transmitter release of VEGF, IL-8 and GLP-1 and activate endothelial cells through paracrine signaling.

As action potentials propagate along an axon, pulsed extracellular electric fields (E-fields) are induced. We investigated the role of E-fields in activating microglia cells and affecting capillary function and found that E-fields control human microglia secretions in concert with purinergic factors. We generated E-fields by applying transcranial pulsed electromagnetic fields (T-PEMF) identical to those appearing outside neurons as action potentials propagate.

Finasteride interferes with prostaglandin-induced CatSper signalling in human sperm.

Ca2+ signalling controls human sperm functions necessary for successful fertilization. Multiple endocrine-disrupting chemicals have been found to activate the CatSper Ca2+ channel and thereby interfering with Ca2+ signalling in human sperm. Finasteride is prescribed to men in the fertile age to treat hair loss and its use has been associated with impaired male fertility.

The Calcium-Sensing Receptor Is Essential for Calcium and Bicarbonate Sensitivity in Human Spermatozoa.

Context: The calcium-sensing receptor (CaSR) is essential to maintain a stable calcium concentration in serum. Spermatozoa are exposed to immense changes in concentrations of CaSR ligands such as calcium, magnesium, and spermine during epididymal maturation, in the ejaculate, and in the female reproductive environment. However, the role of CaSR in human spermatozoa is unknown.

Transcranial low-frequency pulsating electromagnetic fields (T-PEMF) as post-concussion syndrome treatment.

Background: Treatment options for the subgroup of people who develop long-lasting symptoms following mild traumatic brain injury are limited. Transcranial pulsating low-frequency electromagnetic stimulation (T-PEMF) in other patient groups has shown promising results in several studies with proposed neuroprotective and anti-inflammatory effects.

Objective: The present pilot study was conducted to access feasibility and tolerability of T-PEMF in treating post-concussion syndrome.

EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner.

Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca influx into human sperm cells via the CatSper Ca-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca influx through CatSper, thus mimicking the effect of progesterone on Ca signaling.

GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries.

We investigated the acute effects of glucagon-like peptide-1 (GLP-1), GLP-1(1-36), and GLP-1(7-36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal l-cells modulates processes related to PLCγ activation, Src, and endothelial NOS (eNOS) signaling, thereby controlling endothelial vessel tone. By using RT-PCR analysis, we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells, and rat arteries.

Chemical UV Filters Mimic the Effect of Progesterone on Ca Signaling in Human Sperm Cells.

Progesterone released by cumulus cells surrounding the egg induces a Ca influx into human sperm cells via the cationic channel of sperm (CatSper) Ca channel and controls multiple Ca-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of progesterone on CatSper, thus affecting Ca signaling in human sperm cells. We examined 29 UV filters allowed in sunscreens in the United States and/or the European Union for their ability to induce Ca signals in human sperm by applying measurements of the intracellular free Ca concentration.

The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages.

Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes.

The Diagnostic Apathia Scale predicts a dose-remission relationship of T-PEMF in treatment-resistant depression.

Objective: The aim of this study was to evaluate the predictive validity of the apathy subsyndrome in patients with therapy-resistant depression in the dose-remission study with transcranial pulsating electromagnetic fields (T-PEMF).

Methods: The apathy subsyndrome consists of the symptoms of fatigue, concentration and memory problems, lack of interests, difficulties in making decisions, and sleep problems. We evaluated 65 patients with therapy-resistant depression.

Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression: a randomized, double-blind controlled study.

Objective: To evaluate to what extent a twice daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was superior to once daily in patients with treatment-resistant depression as to obtaining symptom remission after 8 weeks of augmentation therapy.

Methods: A self-treatment set-up of the T-PEMF device was used allowing self-administration by patients in own homes. All patients were treated for 30 min per T-PEMF session.

TNFR1 mediates TNF-α-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling.

Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-α markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-α-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism.

IL-17A potentiates TNFα-induced secretion from human endothelial cells and alters barrier functions controlling neutrophils rights of passage.

Interleukin-17A (IL-17A) is an important pro-inflammatory cytokine that regulates leukocyte mobilization and recruitment. To better understand how IL-17A controls leukocyte trafficking across capillaries in the peripheral blood circulation, we used primary human dermal microvascular endothelial cells (HDMEC) to investigate their secretory potential and barrier function when activated with IL-17A and TNFα. Activation by TNFα and IL-17A causes phosphorylation of p38 as well as IκBα whereby NFκB subsequently becomes phosphorylated, a mechanism that initiates transcription of adhesion molecules such as E-selectin.

IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression.

Objective: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight into the interplay between the immune system and development of the lymphatic system.

Methods: IL-27-stimulated signal transduction in human dermal lymphatic endothelial cells was measured by western blotting and synthesis of CXCL10 and CXCL11 by use of RT-PCR and ELISA.

Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis.

Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading to widespread pulmonary and lymph-node metastases. Coimplantation of dual factors in the mouse cornea resulted in additive angiogenesis and lymphangiogenesis.

Non-genomic effects of vitamin D in human spermatozoa.

The spectrum for vitamin D (VD) mediated effects has expanded in recent years. Activated VD (1,25(OH)(2)D(3)) binds to the VD receptor (VDR) and mediates non-genomic effects through the alternative ligand binding-pocket (VDR-ap) or regulates gene transcription through the genomic binding-pocket. VDR and VD-metabolizing enzymes are expressed in human testis, male reproductive tract and mature spermatozoa, and VD is considered important for male reproduction.

Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality.

Vitamin D (VD) is important for male reproduction in mammals and the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human spermatozoa. The VD-inactivating enzyme CYP24A1 titrates the cellular responsiveness to VD, is transcriptionally regulated by VD, and has a distinct expression at the sperm annulus. Here, we investigated if CYP24A1 expression serves as a marker for VD metabolism in spermatozoa, and whether CYP24A1 expression was associated with semen quality.

Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa.

Background: The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)(2)D(3)) in human spermatozoa and whether VD serum levels are associated with semen quality.

Methods: Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm motility and acrosome reaction.

Identifying patients with therapy-resistant depression by using factor analysis.

Introduction: Attempts to identify the factor structure in patients with treatment-resistant depression have been very limited.

Methods: Principal component analysis was performed using the baseline datasets from 3 add-on studies [2 with repetitive transcranial magnetic stimulation and one with transcranial pulsed electromagnetic fields (T-PEMF)], in which the relative effect as percentage of improvement during the treatment period was analysed.

Results: We identified 2 major factors, the first of which was a general factor.

IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation.

IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimulation of hTERT-HDLEC with IL-20, we found an increase in the intracellular free calcium concentration, in Akt and eNOS phosphorylations as well as in perinuclear NO production.

Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial.

Background: The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy. We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram. However, because a recent meta-analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients, we decided to make an interim analysis.

IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs.

Successful therapeutic angiogenesis for the treatment of ischemic disorders relies on selection of optimal proangiogenic or arteriogenic agents that are able to promote establishment of functional collateral networks. Here, we show that IL-20, a pleiotropic inflammatory cytokine, displays an imperative effect on vascular remodeling. Stimulation of both large and microvascular endothelial cells with IL-20 leads to activation of receptor-dependent multiple intracellular signaling components, including increased phosphorylation levels of JAK2/STAT5, Erk1/2, and Akt; activation of small GTP-binding proteins Rac and Rho; and intracellular release of calcium.

Treatment of knee osteoarthritis with pulsed electromagnetic fields: a randomized, double-blind, placebo-controlled study.

Objective: The investigation aimed at determining the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee by conducting a randomized, double-blind, placebo-controlled clinical trial.

Design: The trial consisted of 2h daily treatment 5 days per week for 6 weeks in 83 patients with knee OA. Patient evaluations were done at baseline and after 2 and 6 weeks of treatment.

Nerve growth factor activates aorta endothelial cells causing PI3K/Akt- and ERK-dependent migration.

Nerve growth factor (NGF) is a well-known neurotrophin. We determined whether NGF can activate endothelial cell migration and signalling that underlie angiogenic processes. We showed that aorta endothelial cells express mRNA for both the receptor tyrosine kinase TrkA and the p75 neurotrophin receptor (p75NTR) that associates with TrkA when signalling occurs.

A comparative study of the FcepsilonRI molecule on human mast cell and basophil cell lines.

Background: Mast cells and basophils express the high-affinity IgE receptor FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of the basophil cell line KU812 in order to reveal possible differences concerning the FcepsilonRI surface regulation, anti-IgE-triggered activation, FcepsilonRIalpha protein stability and the mRNA level of FcepsilonRIalpha-, beta- and the truncated beta-chain (beta(T)), and thereby determine the utility of these cell lines in investigations of the FcepsilonRI biology.

Methods: The surface expression of FcepsilonRI was assessed by flow cytometry, using the monoclonal antibody CRA1.