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Nutraceuticals have for several years aroused the interest of researchers for their countless properties, including the management of viral infections. In the context of the COVID-19 pandemic, studies and research on the antiviral properties of nutraceuticals have greatly increased. More specifically, over the past two years, researchers have focused on analyzing the possible role of nutraceuticals in reducing the risk of SARS-CoV-2 infection or mitigating the symptoms of COVID-19. Among nutraceuticals, turmeric, extracted from the rhizome of the Curcuma Longa plant, and spirulina, commercial name of the cyanobacterium Arthrospira platensis, have assumed considerable importance in recent years. The purpose of this review is to collect, through a search of the most recent articles on Pubmed, the scientific evidence on the role of these two compounds in the fight against COVID-19. In the last two years many hypotheses, some confirmed by clinical and experimental studies, have been made on the possible use of turmeric against COVID-19, while on spirulina and its possible role against SARS-CoV-2 infection information is much less. The demonstrated antiviral properties of spirulina and the fact that these cyanobacteria may modulate or modify some mechanisms also involved in the onset of COVID-19, lead us to think that it may have the same importance as curcumin in fighting this disease and to speculate on the possible combined use of these two substances to obtain a synergistic effect.

Background: Postural stability and plantar pressure parameters can be assessed by baropodometry; nevertheless, they are often affected by low repeatability. The aim of the study was to test the accuracy and repeatability of a novel resistive sensor pressure plate and to establish the most reliable baropodometric parameters. Methods: Accuracy and repeatability of the FM12050 BTS-Bioengineering plate measurements were assessed by using different weights in static conditions across three sessions. Subsequently, 20 healthy subjects were assessed by 30-s stabilometric analysis in bipedal standing with open eyes across four trials in two sessions, morning and afternoon. Results: Pressure plate repeatability in measuring the static weights was very high, and plate measurements were correlated to the scale measurements (Pearson’s coefficient = 0.99). Percentage of load distribution between left and right foot and in rearfoot and forefoot regions showed the largest repeatability (coefficient of variation < 5%) across trials. Eventually, median and percentiles (25–75%) were reported for each parameter. Conclusions: This study helped to assess the accuracy and repeatability of a novel pressure plate in static conditions and to define the most reliable parameters for the assessment of postural stability and foot morphology. The present healthy-subject stabilometric dataset may be used as reference data in the evaluation of pathological populations.

Background: Asymmetrical posture maintained over long training periods may affect phenotypic plasticity, resulting functional to sporting goal but negative to the locomotor system. Aim of this study was to quantitatively evaluate these long-term effects in competitive boxers. Methods: Baropodometric analysis was used to assess 20 competitive boxers and 20 non-sportsmen in upright bipedal posture for 5 s and for 51.2 s with open (OE) and closed (CE) eyes. Results: The boxers' group (BOX) showed a larger total foot load (TFL) (p=0.022) on the right foot and a larger rearfoot load (RfL) (P=0.011) on the left foot compared to non-sport controls (CTR). Moreover, a larger forefoot load (FfL) (P=0.001) on the right foot respect to left one was found in the BOX group, with the inversion of the RfL to FfL ratio (P=0.001) between two feet, while no significant differences were found in the CTR group. These findings, associated to a significantly larger center of foot angle (COF) in the BOX group, may indicate an anticlockwise rotation of the anatomical structures above the ankle joint of the right hemisoma respect to the left one, that appears to be consistent with the orthodox stance. Eventually, the BOX group showed a larger centre-of-pressure sway area (COPsa) in the OE condition than what measured in the CE and a significant difference in Romberg Index (BOX< CTR). Conclusions: The results of this study seem to confirm the theory of neuromuscular plasticity imprinted by the repetitive movements and long-lasting postures. Moreover, competitive boxers show an increase of proprioceptive function and a decrease of visual dependence on the postural control.

Previous studies have demonstrated that different curcumin extracts are able to influence cell metabolic activity vitality in human papillary thyroid carcinoma TPC-1 cells. We continued the study using the most effective extract and adding other nutraceuticals such as piperine and vitamin E, in order to define the possible role of these in modulating the genetic expression of cell markers and to understand the effectiveness in modulating the regression of cancer phenotype. Cells were treated with one extract of curcumin (Naturex® Ultimate Botanical Benefits), with Piperine (Piper Longum, A.C.E.F.) and Vitamin E (Dry Vitamin E-Acetate 50% DC, BASF) alone and in combination, dissolved in the culture medium, for 48 h. Treatment with the different nutraceuticals is able to influence cell cycle regulators (cyclin D1, β-catenin, p21, p53) and activators or inhibitors of apoptosis (BAX, pro-caspase3, Bcl-2). They are able to influence cell cycle distribution and metabolic activity vitality. The inhibitory effect of curcumin, piperine and vitamin E on cell proliferation involves different markers, and in particular inhibits β-catenin, cyclinD1 and p53, making them candidates for a possible use in alternative therapies although further studies are needed.

Autoimmune enteropathy (AIE) is a rare disease characterized by prolonged diarrhea, vomiting and weight loss; although it is mainly a rare pediatric disease, over the years a number of adults have also been found to be affected. In this study, we present a case report of a 73-year-old woman with a history of autoimmune hepatitis, antinuclear (ANA) and positive anti-enterocyte antibodies (AEA), who has suffered two months of intractable diarrhea, nausea, anorexia and severe weight loss. The histological examination of the endoscopic duodenal mucosa biopsies revealed severe shortening and flattening of the villi, resulting in mucosal atrophy. The immunohistochemical study revealed a polymorphic lymphoid population, exhibiting a B cell (CD20+) phenotype in follicles and a T cell phenotype (CD3+) in the diffuse component within the lamina propria. Our patient had a complete recovery after two weeks of taking prednisone and following a gluten-rich diet. To our knowledge this is the first case of autoimmune enteropathy in adults with ANA and AEA 7 years after a diagnosis of autoimmune hepatitis. To date, the patient is still in clinical remission on a low dose of orally administered predinisone without any additional immunosuppression.

The placenta, a temporary organ that forms during pregnancy, is the largest fetal organ and the first to develop. It is recognized as an organ that plays a vital role as a metabolic and physical barrier in the fetoplacental unit; throughout fetal development it acts as the lungs, gut, kidneys, and liver of the fetus. When its two components, the fetal and the maternal one, successfully interact, pregnancy proceeds healthily. However, in some cases there may be pregnancy disorders, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), which can lead to a different outcome for the mother and the newborn. In recent years, several studies have been conducted to try to understand how the expression of factors involved in the development of the placenta varies under pathological conditions compared with normal conditions. The purpose of this review is to summarize recent discoveries in this field.

There are many factors contributing to the development of gastrointestinal diseases, grouped into genetic, environmental, and lifestyle factors. In recent years attention has fallen on pathogens; in particular,Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli (E. coli) and Helicobacter pylori have been studied. Several points remain to be clarified, and above all, as regards the adherent-invasive E. coli strains of E. coli, one wonders if they are a cause or a consequence of the disease. In this review, we have tried to clarify some points by examining a series of recent publications regarding the involvement of the bacterium in the pathology, even if other studies are necessary.

Hoverboards are always more popular among children. Hoverboards are to them like a game or a mean of transport, but they could be used as a valid and useful instrument in children’s training programs to improve their performance. In this study, we compared the athletic performance of two groups of 12 children. A total of 24 children aged between 8 and 11 years followed a similar training program for five months, but the first group used a hoverboard (Hb+ group: Age: Standard Deviation (SD) = 1.15 Mean = 9.66; Weight: SD = 5.90 Mean = 32; Height: SD = 7.64 Mean = 135.08) for some of the training time, differently from the second group (Hb- group: Age: SD = 1.15 Mean = 9.66; Weight: SD = 5.82 Mean = 31.16; Height: SD = 7.66 Mean = 136.16), which never used it. All of the children were asked to complete three tests (one leg test, stork test and balance beam walking test) before starting their own training program and after five months, to evaluate how their performances changed in terms of time. Comparing the recorded time difference between T0 and T1 of the Hb+ group with the same difference measured in Hb- group, it was found that there was a statistically significant difference (p value < 0.05) between these data for all three tests. Children who used the hoverboard in their training program achieved better result than children who did not use it. In the future, the hoverboard could help athletes to improve their performances, possibly applying it not only in football training, but even in other sports.

Store-operated Ca2+ entry (SOCE) provides a major Ca2+ entry route in cancer cells. SOCE is mediated by the assembly of Stim and Orai proteins at endoplasmic reticulum (ER)-plasma membrane junctions upon depletion of the ER Ca2+ store. Additionally, Stim and Orai proteins underpin constitutive Ca2+ entry in a growing number of cancer cell types due to the partial depletion of their ER Ca2+ reservoir. Herein, we investigated for the first time the structure and function of SOCE in primary cultures of colorectal carcinoma (CRC) established from primary tumor (pCRC) and metastatic lesions (mCRC) of human subjects. Stim1-2 and Orai1-3 transcripts were equally expressed in pCRC and mCRC cells, although Stim1 and Orai3 proteins were up-regulated in mCRC cells. The Mn2+-quenching technique revealed that constitutive Ca2+ entry was significantly enhanced in pCRC cells and was inhibited by the pharmacological and genetic blockade of Stim1, Stim2, Orai1 and Orai3. The larger resting Ca2+ influx in pCRC was associated to their lower ER Ca2+ content as compared to mCRC cells. Pharmacological and genetic blockade of Stim1, Stim2, Orai1 and Orai3 prevented ER-dependent Ca2+ release, thereby suggesting that constitutive SOCE maintains ER Ca2+ levels. Nevertheless, pharmacological and genetic blockade of Stim1, Stim2, Orai1 and Orai3 did not affect CRC cell proliferation and migration. These data provide the first evidence that Stim and Orai proteins mediate constitutive Ca2+ entry and replenish ER with Ca2+ in primary cultures of CRC cells. However, SOCE is not a promising target to design alternative therapies for CRC.

Several lines of evidence suggest that adherent-invasive Escherichia coli (AIEC) strains play an important role in Crohn's disease (CD). The objective of this study was to investigate the pathogenic role of two AIEC strains, LF82 and O83:H1, in CD patients. Organ cultures of colonic biopsies from patients were set up to assess the effects of LF82 and O83:H1 on the expression of CEACAM6, LAMP1, HLA-DR, ICAM1 by immunohistochemistry and of IL-8, IFNʏ, and TNF-α genes by RT-PCR. Moreover, on Caco2 cells, we analyzed the cell cycle, the expression of MGMT and DNMT1 genes, and DNA damage induced by LF82 and O83:H1, by FACS, RT-PCR, and DAPI staining, respectively. Epithelial and lamina propria mononuclear cells (LPMNC) expression of CEACAM6 and LAMP1 were higher in biopsies cultured in the presence of both O83:H1 and LF82 than in biopsies cultured with non-pathogenic E. coli. Both AIEC strains induced increased expression of ICAM-1 on blood vessels and HLA-DR on LPMNC. We observed higher levels of TNF-α, IFN-γ, and IL-8 transcripts in biopsies cultured with both AIEC strains than in those cultured with NP. Both LF82 and O83:H1, block the cell cycle into S phase, inducing DNA damage, and modulate the expression of DNMT1 and MGMT genes. Our data suggest that LF82 and 083:H1 strains of E. coli are able to increase in CD colonic biopsies the expression of all the pro-inflammatory cytokines and all the mucosal immune markers investigated. J. Cell. Physiol. 232: 2860-2868, 2017. © 2016 Wiley Periodicals, Inc.

A nutraceutical product can be defined as a substance that has a physiological benefit or provides protection against chronic diseases. The term nutraceutical is a hybrid term derived from the union of “nutrition” and “pharmaceutical”. The list of studied nutraceuticals is constantly changing and reflects ongoing market developments, research and consumer interest. Spices, in addition to giving color and taste to foods, are also important nutraceutical. Spices have been an integral part of human diets and commerce for millennia but recently, the recognition of the link between health and nutrition has strengthened their importance in the food sector and sparked the interest of researchers who increasingly engage in trying to determine the mechanisms of action of spices and the countless beneficial properties attributed to them. Among the many existing spices, turmeric is one of the most studied for its antioxidant, anti-inflammatory, antibacterial and anticancer properties. The purpose of this review is to briefly summarize the fundamental characteristics of turmeric and give an overview of the use of this spice in several diseases.

Wilms tumor (WT) occurs in 1:10.000 live births and affects mainly the unilateral kidney. The National Wilms Tumor Study Group registered 6832 patients with WT from 1969 to January 1993, out of whom only 11 patients (0.16%) were newborns. Since 1969, 14 cases of prenatal diagnosis of WT have been reported in literature, two of which were bilateral WT. Currently, the patients’ survival rate is greater than 90%, owing to a combination of surgery, chemotherapy, and radiotherapy for high-risk patients. We report a case of bilateral WT, undiagnosed during the prenatal period due to the incomplete evaluation of the abdomen with ultrasonography. The newborn was vaginally delivered at 40 weeks’ gestational age with a good perinatal adaptation. Suddenly, during the night the newborn showed respiratory distress, bradycardia and then respiratory arrest. For this reason, he was ventilated, intubated and subjected to conventional mechanical ventilation. Despite the normal cardiac ultrasonography, the health care providers suspected a cyanotic congenital heart disease with duct dependency. After a gradual resumption of the oximetry and blood pressure, the infant was transported by the neonatal emergency transport system to the Cardiac Pediatric Surgery Department of a level III hospital. There, the clinical condition became extremely serious and the infant died of asystole. During autopsy, two large tumoral masses were found in both kidneys, also the characterization of the tumors was done through histological exam, which confirmed the diagnosis of WT. A prenatal diagnosis of WT is very important because the families can take advantage of prenatal counseling to understand the risks of continuing the pregnancy and to evaluate the need for abortion, while health care providers can prepare to face a difficult delivery. The review of the literature suggests that prenatal diagnosis of bilateral WT is possible. During prenatal age, the complete assessment of the abdomen with ultrasonography and Eco-Color-Doppler can reveal kidney anomalies and raise suspicion of diseases with urinary malformations.

Recent events in prisons during the COVID-19 pandemic showed how the health situation and overcrowding in prisons are a source of high risk to the health and physical and mental well-being of the prison population and how this has become an important medical problem. The original purpose of this study, which was initially planned to last 6 months, was to examine the effects of a training program on cardio-respiratory capacity, resistance to dynamic strength of the upper and lower body and muscle mass. Following the COVID-19 pandemic, the purpose was subsequently modified by highlighting whether and which deficiencies occurred as a result of the absence of physical activity. Forty adult men between 35 and 55 years of age with more than 1 year of detention were selected and randomly divided into two groups: the experimental group and control group. The fitness training protocol of the experimental group consisted of three weekly sessions lasting 90 min, while control group subjects followed a walk of 30–60 min three days a week without running or resistance training. The unpaired and paired t-tests revealed significant effects of both health status and fitness level (p &lt, 0.05, p &lt, 0.01) on group training. The results of this research show that prisoners can improve their fitness and health through participation in physical education programs. This conclusion is especially important for prisoners who have to serve very long prison sentences and who are at great risk of showing poor physical condition levels.

Background: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+-dependent manner throughout peripheral vasculature. Methods: We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca2+ signaling in NVC. Results: We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca2+-activated K+ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH. Conclusions: It is possible to conclude that endothelial Ca2+ signaling is an emerging pathway in the control of NVC.

Endothelial progenitor cells (EPCs) are a sub-population of bone marrow-derived mononuclear cells that are released in circulation to restore damaged endothelium during its physiological turnover or rescue blood perfusion after an ischemic insult. Additionally, they may be mobilized from perivascular niches located within larger arteries' wall in response to hypoxic conditions. For this reason, EPCs have been regarded as an effective tool to promote revascularization and functional recovery of ischemic hearts, but clinical application failed to exploit the full potential of patients-derived cells. Indeed, the frequency and biological activity of EPCs are compromised in aging individuals or in subjects suffering from severe cardiovascular risk factors. Rejuvenating the reparative phenotype of autologous EPCs through a gene transfer approach has, therefore, been put forward as an alternative approach to enhance their therapeutic potential in cardiovascular patients. An increase in intracellular Ca2+ concentration constitutes a pivotal signal for the activation of the so-called endothelial colony forming cells (ECFCs), the only known truly endothelial EPC subset. Studies from our group showed that the Ca2+ toolkit differs between peripheral blood- and umbilical cord blood (UCB)-derived ECFCs. In the present article, we first discuss how VEGF uses repetitive Ca2+ spikes to regulate angiogenesis in ECFCs and outline how VEGF-induced intracellular Ca2+ oscillations differ between the two ECFC subtypes. We then hypothesize about the possibility to rejuvenate the biological activity of autologous ECFCs by transfecting the cell with the Ca2+ -permeable channel Transient Receptor Potential Canonical 3, which selectively drives the Ca2+ response to VEGF in UCB-derived ECFCs.

Recently increasing emphasis is placed on preventive health and management of chronic comorbidities avoiding long-term toxicities of antiretroviral therapy (ART). Drawing from this background we decided to use the Saos-2, osteosarcoma cell line, as a cellular model, to evaluate the effects of some antiretroviral drugs such as abacavir (ABC), tenofovir (TDF), efavirenz (EFV), etravirine (ETR), and darunavir (DRV), on bone differentiation related pathways. According to our observation, treatment with TDF and ABC affects the ability of the cells to produce calcium deposits with a reduced expression of type I collagen gene and p21 mRNA, also increasing the activity of Wnt3a related pathway. On the other hand treatment with EFV and DRV was not related to any significant reduction of calcium deposits but displayed a decrease in the expression of Wnt3a at day 14 and Type I Collagen at day 7 compared with untreated cells, even if this last down regulation was not confirmed at day 14. Instead ETR administration to Saos-2 cells increases the calcium deposits collagen type I production, as a result of Wnt3a mRNA overexpression, and of an upregulation of collagen type I expression, being also the only drug able to increase the expression of p21 cdk inhibitor as further marker of terminal differentiation. In summary these data suggest the potential negative interference of TDF and ABC on bone differentiation. DRV and EFV partially affect collagen type I production, instead ETR facilitates a positive bone balance as a result of an increased osteoblasts terminal differentiation.

Helicobacter pylori infects 50% of mankind. The vast majority of H. pylori infection occurs in the developing countries where up to 80% of the middle-aged adults may be infected. Bacterial infection causes an inflammatory response that proceeds through a series of intermediated stages of precancerous lesions (gastritis, atrophy, intestinal metaplasia, and dysplasia). Among infected individuals, approximately 10% develops severe gastric lesions such as peptic ulcer disease, 1-3% progresses to gastric cancer (GC) with a low 5-year survival rate, and 0.1% develops mucosa-associated lymphoid tissue (MALT). GC is one of the most common cancer and the third leading cause of cancer-related deaths worldwide. In this review, we have summarized the most recent papers about molecular mechanisms of H. pylori pathogenesis. The main important steps of H. pylori infection such as adhesion, entry in epithelial gastric cells, activation of intracellular pathways until epigenetic modifications have been described.

Endothelial progenitor cells (EPCs) are a sub-population of bone marrow-derived mononuclear cells that are released in circulation to restore damaged endothelium during its physiological turnover or rescue blood perfusion after an ischemic insult. Additionally, they may be mobilized from perivascular niches located within larger arteries' wall in response to hypoxic conditions. For this reason, EPCs have been regarded as an effective tool to promote revascularization and functional recovery of ischemic hearts, but clinical application failed to exploit the full potential of patients-derived cells. Indeed, the frequency and biological activity of EPCs are compromised in aging individuals or in subjects suffering from severe cardiovascular risk factors. Rejuvenating the reparative phenotype of autologous EPCs through a gene transfer approach has, therefore, been put forward as an alternative approach to enhance their therapeutic potential in cardiovascular patients. An increase in intracellular Ca

Background Lipofilling is a cosmetic surgical procedure that consists in the withdrawal of a small quantity of fat tissue from a suitable anatomic area and the reimplantation of this tissue in another corporeal district in the same individual, so as to obtain a filling effect. Recently, adipose-derived stem cells (ADSCs) have been isolated in the aspirates. These are pluripotent mesenchymal stem cells that are able to differentiate in mature adipose cells or other adult mesenchymal cells after paracrine or autocrine hormonal stimulations, thus favoring a longer survival of the implanted tissues. Methods In this article, we have defined a new method for liposuction (Prolipostem®), where the ADSCs are recovered and mixed with the suctioned adipose tissue derived from the abdominal fat, before the reimplantation. Results We have demonstrated by immunocytochemistry the presence of ADSCs in the adipose tissue taken with Prolipostem® from the abdominal fat and the ability of these ADSCs to differentiate in mature adipose cells in vitro. Conclusions The possibility to enrich the tissue to be implanted with ADSCs would assure a longer survival of the cells implanted and a regeneration of the host tissue thanks to growth and angiogenic stimuli induced by the ADSCs.

Antiretroviral drugs used for the treatment of human immunodeficiency virus (HIV) have proven to be effective even against cancer. Drawing from this background, the aim of our research project was to evaluate the effects of anti-HIV drugs that belong to the nucleoside and nucleotide reverse transcriptase inhibitor [NRTI; abacavir (ABC) and tenofovir (TDF)], nonnucleoside reverse transcriptase inhibitor [NNRTI; efavirenz (EFV) and etravirine (ETR)], and protease inhibitor [PI; darunavir (DRV)] categories on ovarian adenocarcinoma cell line SKOV-3. Using FACS analysis, we observed that treatment with NRTIs and NNRTIs showed a block in the G0/G1phase. In particular, ETR displayed a relevant block in the progression of the G0/G1phase of the cell cycle compared with the other examined drugs, and it also induced differentiation of SKOV-3 cells. In contrast, FACS analysis demonstrated that ABC and the PI inhibitor DRV showed no effect on the proliferation of cancer cells. DAPI (4′,6-diamidino-2-phenylindole) staining demonstrated that cells treated with NNRTIs (EFV and ETR) presented more DNA damage compared with other treatments. Immunoblotting analysis demonstrated that TDF, EFV, and ETR were able to obtain a reduction in the expression of cyclin D1 and Rb hypophosphorylation, and an increase in p21 concentration. Finally, we observed that ETR also induced differentiation, as demonstrated by Western blot, with high levels of E-cadherin expression. Therefore, our study provides additional evidence supporting the in vitro cytotoxic effects of ETR and EFV. Furthermore, it promotes the hypothesis for their potential use as therapeutic agents in ovarian cancer.

Objectives: Nonylphenol (NP) is present ubiquitously in both aquatic and terrestrial environments. This compound is considered an important endocrine disruptor and its toxic/oestrogenic activity has been investigated in a number of in vitro and in vivo studies. Human exposure to NP may occur by cutaneous absorption, ingestion of contaminated food or water and inhalation. Moreover, while the cytotoxic effects of NP are known and studied, its effects on cell death and related mechanisms are not known. Our group decided to investigate NP effects on a gastric epithelial cell line (AGS), in particular NP effects on AGS cell cycle and apoptosis. Materials and methods: Cell cycle was analysed by flow cytometry, p21 and p27 induction, and apoptosis was analysed by flow cytometry and annexin-V assays, Fas, Fas-L, caspase 8 and caspase 3 activation. Results: We have demonstrated that NP affected cell cycle and apoptosis in a time- and dose-dependent manner, reaching the most notable effect at concentration of 10−7 m, for 48 h. Flow cytometry revealed that treatment with 10−7 m NP led to accumulation of cells at G2/M transition and increased percentage population of apoptotic cells. Results have shown that NP at concentration 10−7 m induced marked increase in Fas and Fas-L expression. Moreover, 107 m NP induced activation of caspases 8 and 3, but not activation of caspase 9. Conclusions: The results reported suggest that gastric cells can be useful as screening population for appropriate study of developmental toxicity.

Formyl-peptide receptors (FPRs) are expressed in several tissues and cell types. The identification of markers involved in cell growth may further allow for molecular profiling of lung cancer. We investigated the possible role of FPRs as molecular markers in several types of lung carcinomas which is the main cause of cancer death worldwide.Tumor tissue samples were collected from six patients affected by lung cancer. Biopsies were analyzed for expression of FPR isoforms both in tumoral and peritumoral tissue by real-time polymerase chain reaction (PCR), western blot and immunofluorescence.Real-time PCR, western blot and immunofluorescence analyses showed that FPR expression is lower in types of human lung cancer tissues when compared to the surrounding peritumoral tissues.The study of the mechanistic basis for the control of FPR expression in normal peritumoral versus tumoral tissues could provide the basis for new diagnostic and therapeutic interventions.

During the woman's fertile period, the non-pregnant uterus is subject to constant cyclic changes. The complex mechanisms that control the balance among proliferation, differentiation, cell death and the structural remodeling of the extracellular matrix can contribute to the benign or malignant endometrial pathological state. The small leucine-rich proteoglycans (SLRPs) are important components of cell surface and extracellular matrices.Using immunohistochemistry, we showed that the distribution patterns of SLRPs were completely modified in the pathological compared to normal endometrium.The expression of SLRPs was low/absent in all endometrial pathologies examined compared to normal endometrium. We observed an increase of lumican from proliferative to secretory phase of the endometrium and a decrease of fibromodulin, biglycan and decorin. In menopause endometrial tissue, the level of expression of fibromodulin, biglycan, decorin and lumican dramatically decreased.The results revealed the prominence and importance of proteoglycans in the tissue architecture and extracellular matrix organization.

After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated following several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis. Drawing from these background we decided to evaluate the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while the expression of p53 was reduced. Treatment with Maraviroc was also able to block the accumulation of fibrillar collagens and extracellular matrix proteins (ECM), as demonstrated by the decrease of specific markers as Collagen type I, α-SMA and TGF-β1. In addition we observed a down regulation of both metalloproteins (MMP-2, MMP-9), used for the degradation of the extracellular matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound that may modulate the dynamic of liver fibrosis could be crucial in all chronic liver diseases. Maraviroc could play an important role because, in addition to its own anti-HIV activity, it could reduce the release of pro-inflammatory citokynes implicated in liver fibrogenesis. This article is protected by copyright. All rights reserved.

Historically, in severe trauma, such as extensive burns and large loss of substance of the soft tissues, increased emphasis is given to the survival of the traumatized person and less attention is placed on the recovery of the actual traumatized organ. Today, recovery of complete functionality of the injured part and the possibility of minimizing scars in order to make them as acceptable and invisible as possible are also important. The present study analyzed morphologically the events occurring in the wounds of patients in which a dermal substitute was used in combination with a cleansing process. Pre-treatment of the lesion by cleansing followed by the application of a biomaterial showed that in the tissue that forms, a reduced number of cells are present, the collagen is more undulating with interstitial spaces, and Langerhans cells are evident. In addition, these cells participate in the growth and turnover of keratinocytes. The mediating role of these elements would also be strongly dependent on the components of the extracellular matrix of the dermis.

Helicobacter pylori infects 50% of mankind. The vast majority of H. pylori infection occurs in the developing countries where up to 80% of the middle-aged adults may be infected. Bacterial infection causes an inflammatory response that proceeds through a series of intermediated stages of precancerous lesions (gastritis, atrophy, intestinal metaplasia, and dysplasia). Among infected individuals, approximately 10% develops severe gastric lesions such as peptic ulcer disease, 1-3% progresses to gastric cancer (GC) with a low 5-year survival rate, and 0.1% develops mucosa-associated lymphoid tissue (MALT). GC is one of the most common cancer and the third leading cause of cancer-related deaths worldwide. In this review, we have summarized the most recent papers about molecular mechanisms of H. pylori pathogenesis. The main important steps of H. pylori infection such as adhesion, entry in epithelial gastric cells, activation of intracellular pathways until epigenetic modifications have been described.

TheWFS1gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of theWFS1gene in mice causes progressiveβ-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ.

Background/aim: Oral candidiasis is the most common fungal infection in dental practice, and is caused by yeasts that are normally present in the endogenous flora. Methods: To evaluate a rapid diagnostic method for identification of Candida oral isolates, a multiplex polymerase chain reaction (PCR) was carried out on colonies and on oral rinse solutions from 95 subjects with suspected oral candidiasis and results were compared with those from seven commonly used phenotypic identification systems. Results: Between four and nine species were characterized in the samples by the phenotypic methods. PCR identified the same species in 60 (74%) samples from both colony and oral rinse solutions. Statistical analysis, carried out only for the three most frequently isolated species (Candida albicans, Candida glabrata, and Candida tropicalis), showed good concordance in the comparison of multiplex PCR with API 20C AUX and with the Rapid Yeast Identification Panel; conversely, significant differences were registered in the comparison between the molecular method and other phenotypic systems, including four chromogenic media and the automated system Vitek2. Discussion: Multiplex PCR was rapid and effective in the identification of Candida species and allowed the detection of more than one species in the same sample.

During cartilage regeneration, proliferation and differentiation of new chondrocytes are required and towards this goal, in humans electromagnetic stimulation has been used in order to increase the spontaneous regenerative capacity of bone and cartilage tissue. In vivo tissue engineering has pointed out that the absence of an abundant source of cells accelerating the healing process is a limiting factor in the ability to repair articular cartilage. Considering that the umbilical cord is a viable alternative source of mesenchymal stem cells (MSC), our study evaluated the possibility of a combined use of Wharton's jelly - mesenchymal stem cells (WJ-MSCs) and pulsed electromagnetic field (PMEF). The first effect observed was that compared with the untreated cells, when the WJ-MSCs were treated with PMEF, there was an increase in the division of cells and a rapid increase in cell density and the morphological and biochemical data showed that the treatment with PMEF reduced the time to obtain chondrocyte cell differentiation and deposition of extracellular matrix. Taken together these data indicate the capacity of PEMF to induce early differentiation of WJ-MSCs cells towards cartilaginous tissue.

Neural precursor cell-expressed, developmentally down-regulated-8 (NEDD8) is a 76-amino-acid ubiquitin-like polypeptide. NEDD8 affects the signaling of various molecules but the major cellular target proteins are cullins. The neddylation process is correlated closely with apoptosis, cell-cycle regulation, embryogenesis and development.The purpose of the present work was to investigate NEDD8 distribution and expression in the human placenta during gestation.A total of 30 samples, 15 chorionic villous samples from first trimester and 15 from full-term placentae, were used for the immunohistochemical analysis of NEDD8 expression. The gestation period ranged from 5 to 40 weeks.NEDD8 was highly expressed in the cytotrophoblast of the first trimester of gestation, whereas in the third trimester, it was localized in the endothelial cells and stroma of placental villi.Our results suggest that NEDD8 may play an important role in the control of proliferation and differentiation of human placenta throughout pregnancy.

In the present study, we investigated the ability of anti-HIV drugs to interfere with normal cell cycle progression and to induce oxidative stress by perturbing the redox environment. Our results provide evidence that anti-HIV drugs have a differential effect on adipocyte cell cycle and differentiation, being able to modify the response to oxidative stress through an increase of reactive oxygen species (ROS) that compromises the induction of phase-2 and antioxidant enzymes. In detail, saquinavir, efavirenz, and stavudine exert antiadipogenic influences on the model 3T3-L1 cell line, perturbing the oxidative response and inducing of apoptosis. When considered together, the effects of anti-HIV drugs on 3T3-L1 pre adipocytes are distinct but commonly antiadipogenic, thus suggesting another additional possible mechanism by which antiretroviral therapies could contribute to lipoatrophy.

Human mesenchymal stem cells (hMSC) have become an important resource in developing strategies for regenerative medicine and tissue engineering, owing to their ability to renew and their potential for differentiation into cells of various types of tissues. Pulsed electromagnetic field (PEMF) stimulation has been used for several years in the treatment of fracture healing, with clinical beneficial effects, and several studies have demonstrated its capacity to increase bone tissue regeneration. In the present study, stromal cells of human bone marrow (BMSC), obtained from healthy donors, were appropriately expanded and underwent PEMF stimulation eight hours a day for fourteen days. Parameters such as proliferation and differentiation ability were evaluated on stimulated cultures. The evaluation of the marker expression was performed by RT-PCR for osteocalcin, by alkaline phosphatase quantitation and by histochemical stains. The results we obtained showed that BMSC treated with PEMF begin differentiation earlier than untreated BMSC, as shown by the markers used. The data show that PEMF is able to increase the osteogenic differentiation potential in adult mesenchymal cells isolated from young patients.

The introduction of highly active antiretroviral therapies (HAART) has significantly changed the clinical course of HIV disease, with prolonged survival and better quality of life for HIV infected patients. However, this successful therapeutic advance has been partially marked by the development of serious long-term side effects including metabolic alterations, cardiovascular disease, kidney impairment, bone alterations and adipose tissue redistribution. This last phenomenon is currently indicated as HIV related lipodystrophy (Barbaro, 2006). Even if some studies suggested an independent role for HIV in the development of lipodystrophic phenotype, there is a widely accepted consensus that the risk to develop fat redistribution in HIV patients has to be mostly related to antiretroviral therapy. In order to investigate new pathways involved in the development of lipodystrophy, our group performed an array screening using two identical filter arrays with cDNAlabeled probes, generated from the adipose tissue of either HIV patients affected or not affected by lipodystrophy. Among the genes selected, we focused our attention on a recently described 48 kDa protein of 417 amino acids named FAP48. Our results suggest, using 3T3-L1-FAP48 stable clone, that FAP48 over-expression results in rapid NFAT dephosphorilatyon by activating CaN and in the increase of aP2 gene transcription, a gene expressed at the last phase of the adipocyte differentiation. These data support the role of Fap48 in the activation of adipocyte differentiation through a pathway involving NFAT. Moreover we evaluated the expression of PPARγ and aP2 in 3T3-L1 FAP48pcDNA stably transfected cells treated with five antiretroviral drugs (Indinavir, Amprenavir, Efavirenz, Stavudine and Saquinavir), belonging to the three main classes of anti-HIV drugs, that were able, in our experimental model, to affect adipocyte differentiation (Esposito et al., 2009). We observed that cells treated with Saquinavir and Efavirenz, using 3T3-L1FAP48 stable clone, are characterized by an increased expression of PPARγ and aP2, during the 6 day time course, compared with the control cells. This evidence supports the hypothesis of a protective mechanism, that in 3T3L1 cells could counteract the toxicity of Efavirenz and Saquinavir or could be activated in presence of these drugs. Drawing from our experimental results it can be then postulated that this mechanism could work trough FAP48/ FBP52/Hsp90 pathway, suggesting this complex as a potential target for novel therapeutic approaches to the HAART related lipodystrophy in patients treated with regimen including Efavirenz and Saquinavir. references

Asthma is currently defined as a chronic inflammatory disease of the airway. Several evidence indicate that vehicle emissions in cities is correlated with the allergic respiratory diseases. In the present study, we evaluated in the A549 cells the production and release of IL-4, IL-5 and IL-13 after treatment with sub-micron PM 1.0 particles (PM 1.0 ), Parietaria officinalis (ALL), and PM 1.0 + ALL together. Our data demonstrated that PM 1.0 + ALL together exhibited the greatest capacity to induce A549 cells to enhance the expression of IL-4 and IL-5 compared with the only PM 1.0 or ALL treatment. Interestingly, IL-13 that is necessary for allergen-induced airway hyper responsiveness, is increased in cells treated with PM 1.0 + ALL together, but is higher expressed when the cells are treated only with the allergen. Our data support the hypothesis that the urban environment damage the acinar lung units and activates cells of the immune system.