Neuroprotective Effects of gH625-lipoPACAP in an In Vitro Fluid Dynamic Model of Parkinson's Disease.

Parkinson's disease (PD) is an aggressive and devastating age-related disorder. Although the causes are still unclear, several factors, including genetic and environmental, are involved. Except for symptomatic drugs, there are not, to date, any real cures for PD.

gH625-liposomes deliver PACAP through a dynamic model of the blood-brain barrier.

The blood-brain barrier (BBB) selectively protects the central nervous system (CNS) from external insults, but its function can represent a limit for the passage of therapeutic molecules. Numerous models of the BBB have been realized in order to study the passage of drugs for neurodegenerative diseases, but these models are not very representative of the physiological conditions because of a limited supply of oxygen and nutrients due to static conditions. To avoid this phenomenon, we used a millifluidic bioreactor model that ensures a circulation of the medium and, therefore, of the nutrients, thanks to the continuous laminar flow.

Valproic Acid Synergizes With Cisplatin and Cetuximab and in Head and Neck Cancer by Targeting the Mechanisms of Resistance.

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus cetuximab (CX) is one of the standard first-line treatments in this disease. However, this therapeutic regimen is often associated with high toxicity and resistance, suggesting that new combinatorial strategies are needed to improve its therapeutic index.

Spermatogenesis and regulatory factors in the wall lizard Podarcis sicula.

Spermatogenesis is an extraordinarily complex process, regulated by several factors, which leads to the differentiation of spermatogonia into spermatozoa. Among vertebrates, several reports have been focused on the lizard Podarcis sicula, a seasonal breeder and a good model for the study of reproductive processes. The goal of this review is to resume all the available data about systemic and above all local control factors involved in the control of P.

Adrenal gland response to endocrine disrupting chemicals in fishes, amphibians and reptiles: A comparative overview.

The adrenal gland is an essential component of the body stress response; it is formed by two portions: a steroidogenic and a chromaffin tissue. Despite the anatomy of adrenal gland is different among classes of vertebrates, the hormones produced are almost the same. During stress, these hormones contribute to body homeostasis and maintenance of ion balance.

Pituitary adenylate cyclase-activating peptide (PACAP) and its receptors in Mus musculus testis.

To enlighten the involvement of PACAP/receptors system in the control of mammal testis, we investigated the expression of PACAP and the localization of PACAP and its receptors PAC1, VPAC1, and VPAC2 in the testis of Mus musculus. By molecular and immunohistochemical investigations, we highlighted that PACAP and its receptors are widely represented in germ cells of Mus testis, particularly in spermatocytes I, spermatids, and spermatozoa, strongly suggesting their involvement in spermatogenesis process. Moreover, for the first time in the adult mouse testis we highlighted that PACAP is present within Leydig cells, as PACAP receptors, confirming its involvement in the control of steroidogenesis in mouse.

gH625-liposomes as tool for pituitary adenylate cyclase-activating polypeptide brain delivery.

The blood-brain barrier (BBB) regulates the traffic of molecules into the central nervous system (CNS) and also limits the drug delivery. Due to their flexible properties, liposomes are an attractive tool to deliver drugs across the BBB. We previously characterized gH625, a peptide derived from Herpes simplex virus 1.

Pituitary adenylate cyclase-activating polypeptide in the testis of the quail Coturnix coturnix: Expression, localization, and phylogenetic analysis.

To evaluate the involvement of pituitary adenylate cyclase-activating polypeptide (PACAP)/receptors system in the control of testis activity, we have investigated the expression and localization of PACAP and the distribution of its receptors in the testis of mature samples of quail Coturnix coturnix, and we have performed a phylogenetic analysis of PACAP in birds. Using histological, molecular, and bioinformatics tools, we demonstrated that (a) PACAP messenger RNA shows a high sequence identity with that reported in other birds studied so far and in other vertebrates. Furthermore, we showed that purifying selection acts on PACAP; (b) the PACAP peptide is present only in Leydig cells, whereas its receptors are localized within both Leydig and germ cells; (c) the synthesis of PACAP does not take place in seminiferous tubules.

Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo: characterization of the mechanism by an in vitro model and implications for delivery.

We have investigated the crossing of the blood brain barrier (BBB) by the peptide gH625 and compared to the uptake by liver in vivo. We clearly observed that in vivo administration of gH625 allows the crossing of the BBB, although part of the peptide is sequestered by the liver. Furthermore, we used a combination of biophysical techniques to gain insight into the mechanism of interaction with model membranes mimicking the BBB and the liver.

Interference of dibutylphthalate on human prostate cell viability.

Dibutylphthalate (DBP) is an environmental pollutant widely used as plasticizer in a variety of industrial applications worldwide. This agent can be found in personal-care products, children's toy, pharmaceuticals, food products. Exposure to DBP can occur via ingestion and inhalation as well as intravenous or skin contact.

Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625.

gH625 constitutes a promising delivery vehicle for the transport of therapeutic biomacromolecules across membrane barriers. We report an application of multivalency to create a complex nanosystem for delivery and to elucidate the mechanism of peptide-lipid bilayer interactions. Multivalency may offer a route to enhance gH625 cellular uptake as demonstrated by results obtained on dimers of gH625 by fluorescence spectroscopy, circular dichroism, and surface plasmon resonance.

Nonylphenol effects on human prostate non tumorigenic cells.

Nonylphenol (NP) is an industrial chemical with estrogenic activity both in vivo and in vitro; estrogens play a critical role in the development of prostate and may be the cause of some pathological states, including cancer. In this study we examined the effects of NP on human prostate non tumorigenic epithelial cells (PNT1A) investigating on cell proliferation, interaction with estrogen receptors (ERs) and gene expression of genes involved in prostate diseases. We found that NP affects cell proliferation at 10(-6)M, promoting a cytoplasm-nucleus translocation of ERα and not ERβ, like the natural estrogen 17β-estradiol (E2).

Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells.

The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44 nm (NP44) and 100 nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway.

Role of PACAP on testosterone and 17β-estradiol production in the testis of wall lizard Podarcis sicula.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that in mammalian testis is involved in the control of testosterone and 17β-estradiol synthesis. A similar involvement was recently postulated in the testis of a nonmammalian vertebrate, the wall lizard Podarcis sicula. Indeed, we reported the presence of PACAP and its receptors throughout the reproductive cycle within both germ and somatic cells.

Pituitary adenylate cyclase-activating peptide (PACAP) and PAC1 receptor in the testis of cartilaginous fish Torpedo marmorata: A molecular and phylogenetic study.

The role of PACAP in spermatogenesis and steroidogenesis has been largely investigated in last years in mammals; conversely, a few studies have been performed in non mammalian vertebrates. In this paper we investigated the sequence, expression and localization of PACAP and its PAC1 receptor in the testis of the benthic elasmobranch Torpedo marmorata, the marbled electric ray. Cloning a partial PACAP cDNA, we demonstrated for the first time in elasmobranches that PACAP shows a highly conserved sequence, compared with the PACAP of other chordates (tunicates and vertebrates).

Sex steroid hormone secretion in the wall lizard Podarcis sicula testis: The involvement of VIP.

Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide involved in different functions, including testosterone synthesis. Recently, we reported the presence of VIP in the testis of Podarcis sicula, throughout the reproductive cycle. Now, we investigated the effects of the VIP on steroidogenesis in significant periods of the Podarcis reproductive cycle: winter stasis, reproductive period, and summer stasis.

Expression and potential role of the peptide orexin-A in prostate cancer.

The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed.

Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood-brain barrier in rats.

Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood-brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines.

PACAP and PAC₁ receptor in the reproductive cycle of male lizard Podarcis sicula.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide involved in multiple functions, including vertebrate reproduction. Recently, we reported the presence of PACAP in the testis of Italian wall lizard Podarcis sicula during reproductive period (May-June). Herein we investigated the PACAP mRNA expression and the localization of PACAP/PACAP receptor system, in the other periods of the Podarcis reproductive cycle, namely in summer stasis, early autumnal resumption, mid-autumnal resumption, winter stasis, and spring resumption.

Molecular cloning of VIP and distribution of VIP/VPACR system in the testis of Podarcis sicula.

Using molecular, biochemical, and cytological tools, we studied the nucleotide and the deduced amino acid sequence of PHI/VIP and the distribution of VIP/VPAC receptor system in the testis of the Italian wall lizard Podarcis sicula to evaluate the involvement of such a neuropeptide in the spermatogenesis control. We demonstrated that (1) Podarcis sicula VIP had a high identity with other vertebrate VIP sequences, (2) differently from mammals, VIP was synthesized directly in the testis, and (3) VIP and its receptor VPAC2 were widely distributed in germ and somatic cells, while the VPAC1 R had a distribution limited to Leydig cells. Our results demonstrated that in Podarcis sicula the VIP sequence is highly preserved and that this neuropeptide is involved in lizard spermatogenesis and steroidogenesis.

The VIP/VPACR system in the reproductive cycle of male lizard Podarcis sicula.

Starting from the knowledge that in the reproductive period the Vasoactive Intestinal Peptide (VIP) is widely distributed in Podarcis sicula testis, we studied VIP expression and the localization of the neuropeptide and its receptors in the testis of the Italian wall lizard P. sicula in the other phases of its reproductive cycle (summer stasis, autumnal resumption, winter stasis, spring resumption). By Real Time-PCR, we demonstrated that testicular VIP mRNA levels change during the reproductive cycle, showing a cyclic trend with two peaks, one in the mid-autumnal resumption and the other in the reproductive period.

Nonylphenol effects on the HPA axis of the bioindicator vertebrate, Podarcis sicula lizard.

Nonylphenol (NP) is an endocrine disruptor widely distributed in the environment. It accumulates in the lipids of living organisms and enters the human food chain. The main source of human exposure is expected to be food, drinking water and foodstuff contaminated through leaching from packaging or pesticide formulation applications.

Adipose tissue remodeling in rats exhibiting fructose-induced obesity.

Purpose: To explore the effect of a fructose-rich diet on morphological and functional changes in white adipose tissue (WAT) that could contribute to the development of insulin resistance.

Methods: Adult sedentary rats were fed a fructose-rich diet for 8 weeks. Glucose tolerance test was carried out together with measurement of plasma triglycerides, non-esterified fatty acids and lipid peroxidation.

Expression of orexin A and its receptor 1 in the human prostate.

The peptides orexin A (OXA) and orexin B, deriving from the cleavage of the precursor molecule prepro-orexin, bind two G-coupled transmembrane receptors, named as receptor 1 (OX1R) and receptor 2 for orexin, showing different affinity-binding properties. First discovered in the rat hypothalamus, orexins and their receptors have been also found in many peripheral tissues where they exert neuroendocrine, autocrine and paracrine functions. Because inconclusive data on their localization in the mammalian prostate are reported, the aim of this study was to investigate the presence of prepro-orexin, OXA and OX1R in the human normal and hyperplastic gland.