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Simple Summary: Body composition assessment in athletes is closely related to sports performance. In sports where alternating aerobic and anaerobic metabolism is required, muscle mass can affect the achievable result. Therefore, the assessment of muscle mass is a field of interest in the sports sciences. Bioimpedance analysis is a method for assessing body composition. Currently, bioimpedance evaluates muscle mass through predictive equations that could provide estimation errors. These errors could be reduced by an evaluation of the raw bioelectrical parameters. Therefore, in this study, we propose a new parameter for assessing the muscle mass in athletes. The evaluation of muscle mass in athletes correlates with sports performance directly. Bioimpedance vector analysis is a growing method of assessing body composition in athletes because it is independent of predictive formulas containing variables such as body weight, ethnicity, age, and sex. The study aims to propose a new parameter (Levi's Muscle Index, LMI) that evaluates muscle mass through raw bioelectrical data. A total of 664 male footballers underwent bioimpedance assessment during the regular season. LMI was correlated with body cell mass (BCM) and phase angle (PA) to establish efficacy. The footballers were 24.5 ± 5.8 years old, 180.7 ± 5.9 cm tall and weighed 76.3 ± 7.1 kg. The relationships were: LMI-BMI: r = 0.908, r2 = 0.824, p < 0.001; LMI-PA: r = 0.704, r2 = 0.495, p = 0.009 and PA-BCM: r = 0.491, r2 = 0.241, p < 0.001. The results obtained confirm that LMI could be considered a new parameter that provides reliable information to evaluate the muscle mass of athletes. Furthermore, the higher LMI-BCM relationship than PA-BCM demonstrates specificity for muscle mass evaluation in athletes regardless of body weight, ethnicity, age, and sex. [ABSTRACT FROM AUTHOR]

• The intestinal epithelial barrier is critical to maintain health. • Aging affects all the components of the intestinal barrier. • The intestinal barrier is a potential strategic target to improve health during aging. The intestinal epithelial barrier protects the mucosa of the gastrointestinal (GI)-tract and plays a key role in maintaining the host homeostasis. It encompasses several elements that include the intestinal epithelium and biochemical and immunological products, such as the mucus layer, antimicrobial peptides (AMPs) and secretory immunologlobulin A (sIgA). These components are interlinked with the large microbial community inhabiting the gut to form a highly sophisticated biological system that plays an important role on many aspects of human health both locally and systemically. Like any other organ and tissue, the intestinal epithelial barrier is affected by the ageing process. New insights have surfaced showing that critical functions, including intestinal stem cell regeneration and regulation of the intestinal crypt homeostasis, barrier integrity, production of regulatory cytokines, and epithelial innate immunity to pathogenic antigens change across life. Here we review the age-associated changes of the various components of the intestinal epithelial barrier and we highlight the necessity to elucidate further the mechanisms underlying these changes. Expanding our knowledge in this area is a goal of high medical relevance and it will help to define intervention strategies to ameliorate the quality of life of the ever-expanding elderly population. [ABSTRACT FROM AUTHOR]

All allergic responses to food indicate the failure of immunological tolerance, but it is unclear why cow's milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and responses to cognate and non-cognate food antigens. Children with confirmed allergy to CME (n = 6) and PN (n = 18) and non-allergic (NA) (n = 8) controls were studied. Constitutive secretion of cytokines was tested in plasma and unstimulated mononuclear cell (PBMNC) cultures. Blood dendritic cell (DC) subsets were analyzed alongside changes in phenotypes and soluble molecules in allergen-stimulated MNC cultures with or without cytokine neutralization. We observed that in allergic children, constitutively high plasma levels IL-1β, IL-2, IL-4, IL-5 and IL-10 but less IL-12p70 than in non-allergic children was accompanied by the spontaneous secretion of sCD23, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IFN-γ and TNF-α in MNC cultures. Furthermore, blood DC subset counts differed in food allergy. Antigen-presenting cell phenotypic abnormalities were accompanied by higher B and T cell percentages with more Bcl-2 within CD69+ subsets. Cells were generally refractory to antigenic stimulation in vitro, but IL-4 neutralization led to CD152 downregulation by CD4+ T cells from PN allergic children responding to PN allergens. Canonical discriminant analyses segregated non-allergic and allergic children by their cytokine secretion patterns, revealing differences and areas of overlap between PN and CME allergies. Despite an absence of recent allergen exposure, indication of in vivo activation, in vitro responses independent of challenging antigen and the presence of unusual costimulatory molecules suggest dysregulated immunity in food allergy. Most importantly, higher Bcl-2 content within key effector cells implies survival advantage with the potential to mount abnormal responses that may give rise to the manifestations of allergy. Here, we put forward the hypothesis that the lack of apoptosis of key immune cell types might be central to the development of food allergic reactions. [ABSTRACT FROM AUTHOR]

The study of the relationships between the different structures of the human locomotor system still to date raises great interest. In fact, the human body networks and in particular the myofascial system "myofascial system network" underlie posture and movement and new knowledge could be useful and applied to many fields such as medicine and prosthetics. The hypothesis of this study was to verify the possibility of creating a structural network representing the human locomotor system as well as to study and describe the relationship between the different structures considered. The graph theory was applied to a network of 2339 body parts (nodes) and 7310 links, representing the locomotor system. The open source platform software Cytoscape was used for data entry (nodes and links) as well as for debugging. In addition, the "Network Analyzer" plugin was used for the descriptive statistics of the network obtained. In order to achieve a better rendering, the results of the network parameters gained were then imported into Gephi (www.Gephi.org). At the end of this procedure, we obtained a image of a human being in an orthostatic position with a precise distribution of the nodes and links. By simulating the common amputations at the level of the foot and leg (as for necrotic complications of diabetes) the balance between the parts and the whole structure of the graph are profoundly modified. [ABSTRACT FROM AUTHOR]

Objective. The impairment of glycemic control can induce limited joint mobility even in young type 1 diabetic (T1DM) patients. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in young T1DM subjects and define a mathematical model of diabetes mellitus long-term effects on AJM. Methods. AJM was evaluated using an inclinometer in 37 patients and 53 healthy, sex- BMI- and age-matched controls. To set up the mathematical model, we assumed that reduced metabolic control affects AJM according to a lognormal function: requiring some time for development of a reduction of joint mobility, which then persists for a long period, before fading out over time (if glycemic control has been recovered). A non-linear optimization determined the model parameters to achieve the best fit for a series of patients. Results. Both plantar and dorsiflexion AJM was significantly lower in diabetic subjects than in controls (plantarflexion: 28.5°±7.5 vs 35.2°±6.5; dorsiflexion: 93.9°±16.0 vs 104.7±12.8; p<0.01). The defined model approximates the experimental data with good accuracy; after optimization, the lognormal curve obtained is in line with empirical estimates: lack of glycemic control needs to persist for at least a few months before producing a significant effect, that lasts up until one year. The fitting procedure indicated the optimal solution is p = (37; 30; 3:5; 6:7; 137); thus, the optimal _im(t) corresponds to the curve reported. Conclusion. AJM was significantly reduced in young T1DM patients. The mathematical model represents the experimental data accurately. [ABSTRACT FROM AUTHOR]

Intestinal macrophages expressing the fraktalkine receptor (CX 3 CR1 + ) represent a cell population that plays a variety of roles ranging from maintaining intestinal immune homeostasis at steady state to controlling antigen access by extending transepithelial dendrites (TEDs) to capture luminal microbes and shuttle them across the epithelium to initiate immune responses. However, recent evidence shows that very early during infection, pathogen-capturing CX 3 CR1 + macrophages migrate to the lumen of the small intestine, therefore preventing pathogens from traversing the epithelium. Here we discuss the complexity of the at-times seemingly opposing roles played by these cells and propose that CX 3 CR1-mediated pathogen exclusion is part of a defensive strategy against infections that includes multiple effector mechanisms acting synergistically at the intestinal mucosa. [ABSTRACT FROM AUTHOR]

The article focuses on studying the blood-brain barrier (BBB) and the crucial role of astrocytes in its formation and function, highlighting their influence on the expression and correct distribution of tight junction proteins like claudin 5 in brain endothelial cells.

With the recent advances in medicine, human life expectancy is increasing; however, the extra years of life are not necessarily spent in good health or free from disability, resulting in a significantly higher incidence of age-associated pathologies. Among these disorders, neurodegenerative diseases have a significant impact. To this end, the presence of the protective blood–brain barrier (BBB) represents a formidable obstacle to the delivery of therapeutics. Thus, this makes it imperative to define strategies to bypass the BBB in order to successfully target the brain with the appropriate drugs. It has been demonstrated that targeting the BBB by ultrasound (US) can transiently make this anatomical barrier permeable and in so doing, allow the delivery of therapeutics. Thus, our aim was to carry out an in depth in vitro molecular and morphological study on the effects of US treatment on the BBB. The rat brain endothelial (RBE4) cell line was challenged with exposure to 12 MHz diagnostic US treatment for 10, 20, and 30 min. Cell viability assays, Western blotting analysis on the endoplasmic reticulum (ER), and oxidative stress marker evaluation were then performed, along with cytological and immunofluorescence staining, in order to evaluate the effects of US on the intercellular spaces and tight junction distribution of the brain endothelial cells. We observed that the US treatment exerted no toxic effects on either RBE4 cell viability or the upregulation/dislocation of the ER and oxidative stress marker (GRP78 and cytochrome C, respectively). Further, we observed that the application of US induced an increase in the intercellular spaces, as shown by Papanicolaou staining, mainly due to the altered distribution of the tight junction protein zonula occludens-1 (ZO-1). This latter US-dependent effect was transient and disappeared 20 min after the removal of the stimulus. In conclusion, our results show that US induces a transient alteration of the BBB, without altering the intracellular signaling pathways such as the ER and oxidative stress that could potentially be toxic for endothelial cells. These results suggested that US treatment could represent a potential strategy for improving drug delivery to the brain. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a well-known occupational and environmental pollutant worldwide, and its toxicity is widely recognised. Cd is reported to increase the permeability of the blood–brain barrier (BBB) and to penetrate and accumulate in the brain. Although many lines of evidence show that Cd toxicity is induced by different mechanisms, one of the best known is the Cd-dependent production of reactive oxygen species (ROS). Zinc is a trace element known as coenzyme and cofactor for many antioxidant proteins, such as metallothioneins and superoxide dismutase enzymes. To date, very little is known about the role of Zn in preventing Cd-induced blood–brain barrier (BBB) alterations. The goal of this study was to test the Zn antioxidant capacity against Cd-dependent alterations in a rat brain endothelial cell line (RBE4), as an in vitro model for BBB. In order to mimic acute Cd poisoning, RBE4 cells were treated with CdCl2 30 µM for 24 h. The protective role of ZnCl2 (50 µM) was revealed by evaluating the cell viability, reactive oxygen species (ROS) quantification, cytochrome C distribution, and the superoxide dismutase (SOD) protein activity. Additionally, the effectiveness of Zn in counteracting the Cd-induced damage was investigated by evaluating the expression levels of proteins already known to be involved in the Cd signalling pathway, such as GRP78 (an endoplasmic reticulum (ER) stress protein), caspase3 pro- and cleaved forms, and BAX. Finally, we evaluated if Zn was able to attenuate the alterations of zonula occludens-1 (ZO-1), one of the tight-junction (TJ) proteins involved in the formation of the BBB. Our data clearly demonstrate that Zn, by protecting from the SOD activity impairment induced by Cd, is able to prevent the triggering of the Cd-dependent signalling pathway that leads to ZO-1 dislocation and downregulation, and BBB damage. [ABSTRACT FROM AUTHOR]

Aims Evaluation of how ankle joint mobility (AJM) can be useful in the identification of patients with diabetes at risk of foot ulcer (FU). Methods Plantar and dorsal flexion of foot were evaluated using an inclinometer in 87 patients (54 type 2 and 33 type 1), and 35 healthy sex- and age-matched control subjects. Patients with diabetes were followed up for diagnosis of FU over the next 8 years and subsequently, patients were subdivided into: those without a history of FU (18 type 1 and 33 type 2), those who had a history of FU detected before baseline evaluation (14 type 2) and those who had history of first ulceration detected by the 8th year of the evaluation period (7 type 2). Results Aging and diabetes caused a significant reduction in mobility of each of the movements investigated ( p < 0.001), whereas after adjusting for the confounding effect of age, diabetes specifically reduced plantar flexion ( p < 0.0001). AJM was significantly lower in those with history of previous FU compared to all the other groups ( p < 0.001). The first ulceration was detected in the same foot presenting lower AJM in 17 of the 22 subjects with diabetes with history of ulcer (77.27%). Conclusions Diabetes and aging reduce AJM although diabetes seems to reduce plantar flexion to a more specific extent. Reduced AJM is mostly associated with a previous history of FU. The evaluation of AJM is a valid and reliable ulcer risk scale that indicates which foot is at higher ulcer risk. [ABSTRACT FROM AUTHOR]

A hopeful spinal cord repairing strategy involves the activation of neural precursor cells. Unfortunately, their ability to generate neurons after injury appears limited. Another process promoting functional recovery is synaptic plasticity. We have previously studied some mechanisms of spinal plasticity involving BDNF, Shh, Notch-1, Numb, and Noggin, by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin. TDP-43 is a nuclear RNA/DNA binding protein involved in amyotrophic lateral sclerosis. Interestingly, TDP-43 could be localized at the synapse and affect synaptic strength. Here, we would like to deepen the investigation of this model of spinal plasticity. After lesion, we observed a glial reaction and an activity-dependent modification of Shh, Noggin, and Numb proteins. By using multivariate regression models, we found that Shh and Noggin could affect motor performance and that these proteins could be associated with both TDP-43 and Numb. Our data suggest that TDP-43 is likely an important regulator of synaptic plasticity, probably in collaboration with other proteins involved in both neurogenesis and synaptic plasticity. Moreover, given the rapidly increasing knowledge about spinal cord plasticity, we believe that further efforts to achieve spinal cord repair by stimulating the intrinsic potential of spinal cord will produce interesting results. [ABSTRACT FROM AUTHOR]

The confinement and lockdown imposed by the COVID-19 pandemic have produced restrictions in the lifestyle of Italian citizens with variations in their psychological well-being. The aim of the study was to identify changes and relationship with socio-demographic parameters. An online survey was administered to 1383 subjects (1007 females and 307 males) working in the University of Florence, Italy. Three validated questionnaires were used for the survey: the Global Physical Activity Questionnaire, the Med Diet Score and the Psychological General Well-Being Index-A. All the subjects were asked to complete the questionnaires twice, in order to attain a picture of the habits before and a later time point during confinement. Our results show that work-related physical activity was decreased, along with an increase in sedentary behaviour (from 07:22±03:20 to 08:49±03:41 h:min; p<0.001, ES = 0.38), whereas recreational physical activity was increased (vigorous exercise varied from 568.5 ± 838.6 to 833.7 ± 1263.0 METs; p<0.002, ES = 0.25). Eating habits changed according to the place where meals were eaten, with an increased habit for breakfast and snacks and a slight increase in alcohol consumption. Psychological well-being decreased (Index from 21.4±3.9 to 18.0±5.3; p<0.001, ES = 0.723), especially in terms of vitality and positive thinking. The socio-demographic variables affecting these variations were mostly represented by age, gender and working conditions: young age and self-employment conditions can be considered factors for the changes in daily habits induced by confinement that may affect psychological well-being. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to characterize the skin deterministic damage due to the effect of proton beam irradiation in mice occurred during a long-term observational experiment. This study was initially defined to evaluate the insurgence of myelopathy irradiating spinal cords with the distal part of a Spread-out Bragg peak (SOBP). To the best of our knowledge, no study has been conducted highlighting high grades of skin injury at the dose used in this paper. Nevertheless these effects occurred. In this regard, the experimental evidence of significant insurgence of skin injury induced by protons using a SOBP configuration will be shown. Skin damages were classified into six scores (from 0 to 5) according to the severity of the injuries and correlated to ED50 (i.e. the radiation dose at which 50% of animals show a specific score) at 40 days post-irradiation (d.p.i.). The effects of radiation on the overall animal wellbeing have been also monitored and the severity of radiation-induced skin injuries was observed and quantified up to 40 d.p.i. [ABSTRACT FROM AUTHOR]

Plastic changes have been reported in the SOD1‐G93A mouse model of amyotrophic lateral sclerosis, a disorder characterized by progressive motoneuronal loss; however, whether these changes related with the onset and development of motor impairments is still unclear. Here, the functional and anatomical changes taking place in SOD1‐G93A mice and their time course were investigated during ongoing motoneuronal degeneration. Starting from about 4 postnatal weeks, SOD1‐G93A and wild‐type (WT) mice were evaluated in the rotarod test, to be sacrificed at about 12–13 or 19 weeks of age, and their lumbar spinal cords were processed for histo‐ and immunohistochemistry. Compared to age‐matched WT controls, 12 weeks‐old SOD1‐G93A mice exhibited relatively mild or no motor impairments in the rotarod test, in spite of a dramatic (≈60%, as estimated by stereology) loss of choline acetyl‐transferase (ChAT)‐immunoreactive motoneurons which remained virtually unchanged in SOD1‐G93A mice surviving up to 19 weeks. Notably, the functional sparing in SOD1‐G93A mice at 12 weeks was paralleled by a marked ≈50% increase in motoneuron volume and a near‐normal density of acetylcholinesterase‐positive process arborization, which was significantly increased when analyzed as ratio to the decreased number of ChAT‐positive motoneurons. By contrast, at 19 weeks, when motor deficits had become dramatically evident, both measures were found reverted to about 50–60% of control values. Thus, at specific stages during the progression of the disease, robust compensatory events take place in surviving motoneurons of SOD1‐G93A mice, which sustain motor performance, and whose full understanding may highlight a valuable therapeutic opportunity window. [ABSTRACT FROM AUTHOR]

Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Although motoneuronal loss is the critical hallmark of ALS given their specific vulnerability, other cell populations, including muscle and glial cells, are involved in disease onset and progression, but unraveling their specific role and crosstalk requires further investigation. In particular, little is known about the plastic changes of the degenerating motor system. These spontaneous compensatory processes are unable to halt the disease progression, but their elucidation and possible use as a therapeutic target represents an important aim of ALS research. Genetic animal models of disease represent useful tools to validate proven hypotheses or to test potential therapies, and the conception of novel hypotheses about ALS causes or the study of pathogenic mechanisms may be advantaged by the use of relatively simple in vivo models recapitulating specific aspects of the disease, thus avoiding the inclusion of too many confounding factors in an experimental setting. Here, we used a neurotoxic model of spinal motoneuron depletion induced by injection of cholera toxin-B saporin in the gastrocnemius muscle to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord. The results showed that, following the lesion, the skeletal muscle became atrophic and displayed electromyographic activity similar to that observed in ALS patients. Moreover, the changes in muscle fiber morphology were different from that observed in ALS models, thus suggesting that some muscular effects of disease may be primary effects instead of being simply caused by denervation. Notably, we found plastic changes in the surviving motoneurons that can produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be at least partially driven by glutamatergic signaling, and astrocytes contacting the surviving motoneurons may support this process. [ABSTRACT FROM AUTHOR]

Michelangelo's marble sculpture of David is one of the most admired works of art in the world. It is the most iconic symbol of the Florentine Renaissance, and a representation of the idealized human form in its perfection and proportion. The statue was examined in 2004 by two anatomists who observed the apparent absence of a single muscle. Our re-examination of the statue, from our perspective as clinical geneticists, shows unexpected and hitherto unpublished details of variations and disproportions within the overall context of exceptional harmony and beauty. This apparent contradiction raises the question as to what is considered to be morphologically "normal" and what "is not". [ABSTRACT FROM AUTHOR]

Lower extremity ulcers represent the most ominous, feared, and costly complications of diabetes mellitus. The aim of this review is to highlight the role of daily life physical activities (PAs) and continuous movement monitoring (CMM) in the prevention of foot ulcers. Peripheral neuropathy and peripheral vascular disease are the main causes of foot ulceration and contribute, in turn, to the development of additional risk factors such as foot deformities and/or joint and muscular alterations. Moreover, a deficit of balance, posture abnormalities, followed by gait alterations, increases the risk of ulceration. PA can play a key role in the management of patients with diabetes and in the prevention of ulcers; however, even if it has been reported that some of these risk factors significantly improve after a few weeks of exercise therapy (ET), the real preventive role of ET has not yet been demonstrated. These uncertain results can occur due to some limitations in the management of the same relationship between PA and diabetic foot prevention. Technological advances during the last years enable timely management of overall daily PA. The use of these modern technologies and devices allows CMM assessment and description of daily PA even in the long term. The data collected from these devices can be used to properly manage patients' PA and thus contribute to the prevention of foot ulcers. [ABSTRACT FROM AUTHOR]

Variations in the branching pattern of the aortic arch are clinically relevant because of the direct influence that their presence can have on the success of cardio-vascular procedures, neck or thorax surgery, trauma management or intensive care. In most cases these anatomical variations are asymptomatic and considered clinically benign, but some particular aortic branching patterns have been associated with surgical complications or with vascular diseases in non-surgical patients. The main objective of this work was to study the frequency of variation of the aortic arch branching pattern in a wide and varied population on the basis of literature reports. The aortic arch branching pattern of 20,030 cases reported by 40 anatomical or radiological studies were analyzed. 84,52% of the studied population had a three branches pattern and 14,65% had a two branches pattern. The four primary arteries were seen arising directly from the aortic arch in 0,81% of the cases and only 0,02% had them all arising from a common trunk. [ABSTRACT FROM AUTHOR]

The vertical jump is frequently used for the functional evaluation of athletes and non-sporting subjects. The jump height is often used as an indicator of lower limbs strength. The aim of this study was to verify the presence of a relationship between the maximum height reached and muscle parameters expressed during the vertical jump. In 22 healthy males practicing recreational physical activity (age, mean ± standard deviation: 22.5±1.2 years; body mass: 72.8±13.2 kg; body height: 177.1±7.0 cm) and in 15 female volley players (age: 16.5±0.4 years; body mass: 64.4± 8.4 kg; body height: 175.5±7.9 cm), Jump Height (cm), Muscle Strength (N/kg) and Power (W/kg) were recorded during the jump tests. In the healthy males group, jump height was correlated with muscle power: r = 0.33, p>0.05; a higher correlation resulted between muscle strength and power: r = 0.62, p<0.01. In the female volleyball players group, only the muscle strength and power showed a correlation: r = 0.54, p<0.05. It is therefore possible to confirm that the jump height reached during a vertical jump does not provide clear information on the strength of the lower limbs. At the same time, an improvement in muscular strength of the lower limbs does not guarantee an increase in jump height. Several parameters should be evaluated at the same time for a correct functional assessment of athletes and healthy non-sporting subjects. [ABSTRACT FROM AUTHOR]

Even if physical activity plays a key role within diabetic foot treatment its use and the results obtained from this treatment seem to be still limited. Nowadays, new and even more advanced technologies for the long term daily physical activity monitoring are available and they are radically changing some aspects of physical activity such as its amount, features and monitoring. In spite of the past, the several electronic devices that are currently available can be integrated into routine care and provide essential information for management to both the healthcare providers and patients. In particular, since the end of the last century, an increasing number of studies have applied the movement monitoring to patients at risk or with history of ulceration. The questionnaires have been progressively replaced with modern technologies such as accelerometers or complex multisensory devices able to objectively measure the physical activity performed. The data collected through the use of such devices can allow a better assessment of patient's condition and provide useful information for the definition of a more complete treatment protocol. Daily physical activity monitoring devices provide to the Diabetes Units information on the typology, quantity, distribution and intensity of the daily physical activity performed by each patient concurring to the prevention of foot ulcers that represent the most dreadful diabetes complications. The different functions and modes of operation of monitoring devices can be integrated to provide a more comprehensive and intelligent monitoring system that provide valuable information on patients' ongoing health status and the physical activity performed during daily life. These devices can manage in real time or even in remote the physical activity performed in addition to calculate that to be performed in the following hours. As a result, they contribute to improve patients' lifestyle and reduce the costs for the treatment of such complications. The aim of this review is to define and emphasize the role of a long term daily physical activity monitoring in the prevention of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Background/Objective: It is known that patients with diabetes can develop limited joint mobility (LJM) and that this can depend on the metabolic control maintained and the duration of the disease. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in both plantar and dorsiflexion in young type 1 diabetic patients (T1D) considering also the possible role of sport practiced as a further factor, able to modify AJM. Methods: AJM was evaluated by an inclinometer in 82 T1D patients (M/F: 48/34), mean age 12.9 ± 2.6 years, body mass index (BMI) 19.7 ± 3.6 kg/m2, duration of diabetes 5.6 ± 3.3 years, mean HbA1c 7.5 ± 1.0% and in 226 healthy controls (M/F: 146/80), age‐, gender‐, and BMI‐matched practicing different sports (soccer, volleyball, basketball, and dance). Results: The patients’ ankle range of motion was significantly lower than that in controls (132.7 ± 22.3° vs 126.1 ± 17.9°; P < .017). In particular, ankle plantar flexion was significantly lower in the patients group (31.6° ± 7.9° vs 28.5° ± 6.6°; P < .002). Soccer players showed lower AJM in both groups: patients (120.1 ± 15.9° vs 127.3 ± 18.1) and controls (119.4 ± 21.1° vs 142.0 ± 18.1; P < .0001) than subjects practicing other sports or who were sedentary. In both groups, patients and controls, age, sex, duration of disease, hemoglobin 1Ac, and BMI have not been shown to be correlated to the mobility assessed. Conclusions: The results of this study, in addition to confirming the negative effect of diabetes on AJM of young T1D patients, suggest that during these evaluations the sport‐related effect should be considered because it can induce significant changes of AJM. [ABSTRACT FROM AUTHOR]

Objective: Hand muscle strength assessment is widespread and can be a useful marker in the evaluation and monitoring of subjects at different ages and health conditions. This study aimed at validating and determining the reliability of a new digital device for evaluation of hand pinch strength by comparing it with a well-validated hand strength assessment device, the Jamar hydraulic hand dynamometer. Methods: In 65 healthy subjects, (males / females: 29 / 36), mean age 40.3±18.0 (range: 19.3 - 76.5) years, hand pinch strength and hydraulic hand dynamometer were used to assess hand strength following a testing protocol. Only the dominant hand was tested. Evaluations were performed considering gender, hand dominance, body mass index and age, according to the standardized testing protocol. The mean of three consecutive grip tests and lateral pinch tests was recorded. Results: There was a strong correlation (p<0.0001) between the hydraulic hand dynamometer and hand pinch strength tests. Both mean strengths measured by hydraulic hand dynamometer and hand pinch strength in females were significantly lower than in males (P<0.001), the grip strength being 34.75% and the lateral pinch test 27.83% weaker than in males. Multivariate analysis indicated that the strength expressed by the hand pinch strength pinch test remained significantly associated with the results of hydraulic hand dynamometer (p<0,001), independent of age and body weight. Conclusions: hand pinch strength and hydraulic hand dynamometer have been shown to be significantly correlated with each other in subjects of different ages, sex and body mass index.The hand pinch strength device has been proven to be a reliable tool for measuring maximal isometric strength by lateral pinch test. This device can be used for quick and inexpensive numerical evaluation of muscular strength in cases as the elderly in communities, bedridden patients, and during drug therapies presumed to be strength affecting. [ABSTRACT FROM AUTHOR]

During Salmonella Typhimurium infection, intestinal CX3CR1+ cells can either extend transepithelial cellular processes to sample luminal bacteria or, very early after infection, migrate into the intestinal lumen to capture bacteria. However, until now, the biological relevance of the intraluminal migration of CX3CR1+ cells remained to be determined. We addressed this by using a combination of mouse strains differing in their ability to carry out CX3CR1-mediated sampling and intraluminal migration. We observed that the number of S. Typhimurium traversing the epithelium did not differ between sampling-competent/migrationcompetent C57BL/6 and sampling-deficient/migration-competent BALB/c mice. In contrast, in sampling-deficient/migrationdeficient CX3CR1-/- mice the numbers of S. Typhimurium penetrating the epithelium were significantly higher. However, in these mice the number of invading S. Typhimurium was significantly reduced after the adoptive transfer of CX3CR1+ cells directly into the intestinal lumen, consistent with intraluminal CX3CR1+ cells preventing S. Typhimurium from infecting the host. This interpretation was also supported by a higher bacterial fecal load in CX3CR1+/gfp compared with CX3CR1gfp/gfp mice following oral infection. Furthermore, by using real-time in vivo imaging we observed that CX3CR1+ cells migrated into the lumen moving through paracellular channels within the epithelium. Also, we reported that the absence of CX3CR1-mediated sampling did not affect Ab responses to a noninvasive S. Typhimurium strain that specifically targeted the CX3CR1-mediated entry route. These data showed that the rapidly deployed CX3CR1+ cell-based mechanism of immune exclusion is a defense mechanism against pathogens that complements the mucous and secretory IgA Ab-mediated system in the protection of intestinal mucosal surface. [ABSTRACT FROM AUTHOR]

Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitely in vitro and give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies. [ABSTRACT FROM AUTHOR]

A better understanding of pediatric tumor biology is needed to allow the development of less toxic and more efficient therapies, as well as to provide novel reliable biomarkers for diagnosis and risk stratification. The emerging role of microRNAs in controlling key pathways implicated in tumorigenesis makes their use in diagnostics a powerful novel tool for the early detection, risk assessment and prognosis, as well as for the development of innovative anticancer therapies. This perspective would be more urgent for the clinical management of pediatric cancer. In this review, we focus on the involvement of microRNAs in the biology of the main childhood tumors, describe their clinical significance and discuss their potential use as novel therapeutic tools and targets. [ABSTRACT FROM AUTHOR]

The article offers information on morphological features of rat brain vascular pericytes (RBVP) during toxic insult and their role in blood-brain barrier characterization. Topics include information on pericytes which are fibroblast like cells; information on extensive cytoplasmic elongation; and different cell types of central nervous system.

Carbon-based nanomaterials are nowadays attracting lots of attention, in particular in the biomedical field, where they find a wide spectrum of applications, including, just to name a few, the drug delivery to specific tumor cells and the improvement of non-invasive imaging methods. Nanoparticles inhaled during breathing accumulate in the lung alveoli, where they interact and are covered with lung surfactants. We recently demonstrated that an apparently non-toxic concentration of engineered carbon nanodiamonds (ECNs) is able to induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells. Therefore, the complete understanding of their "real" biosafety, along with their possible combination with other molecules mimicking the in vivo milieu, possibly allowing the modulation of their side effects becomes of utmost importance. Based on the above, the focus of the present work was to investigate whether the cellular alterations induced by an apparently non-toxic concentration of ECNs could be counteracted by their incorporation into a synthetic lung surfactant (DPPC:POPG in 7:3 molar ratio). By using two different cell lines (alveolar (A549) and microglial (BV-2)), we were able to show that the presence of lung surfactant decreased the production of ECNs-induced nitric oxide, total reactive oxygen species, and malondialdehyde, as well as counteracted reduced glutathione depletion (A549 cells only), ameliorated cell energy status (ATP and total pool of nicotinic coenzymes), and improved mitochondrial phosphorylating capacity. Overall, our results on alveolar basal epithelial and microglial cell lines clearly depict the benefits coming from the incorporation of carbon nanoparticles into a lung surfactant (mimicking its in vivo lipid composition), creating the basis for the investigation of this combination in vivo. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted to evaluate in the human cerebellum the presence of an intrinsic serotonergic neuronal subpopulation. The immunoreactions were revealed by streptavidin-biotin-peroxidase and 3,3-diaminobenzidine tetrahydrochloride technique; for positive controls were used duodenum and brainstem fragments of rat subjected to the same experimental protocol.

C Cadmium is a toxic heavy metal known as environmental pollutant world-wide distributed. Its toxicity, predominantly due to its long half-life of 15-20 years, affects many organs and tissues including kidney, lung, liver, heart, bone, muscles and the central nervous system (CNS) as well [1]. Our research group previously demonstrated that cadmium is able to alter the blood-brain barrier by modifying the tight junction sealing morphology and to induce oxidative stress, thus leading to neuronal degeneration mainly by oxidative stress [2]. Among the cellular population of the CNS, glial cells own a pivotal role in maintaining the physiological brain homeostasis and their alteration has been demonstrated to indirectly affect neurons [3]. The aim of the present research is to evaluate cadmium toxicity in two glial cell lines (astrocyte DITNC1 and microglia BV-2), at different time and increasing concentration of metal exposure. Cadmium increasing concentrations (0.1-100 µM) were administered in starvation medium for 8, 24 and 48 hours. Cell viability assay, western blotting analysis, and immunofluorescent staining were employed in order to evaluate the molecular and morphological alterations induced by the heavy metal. Our results clearly demonstrated that Cd is able to affect the cell viability even at the lowest concentrations and in a time-dependent manner, by altering the oxidative balance (ROS production, cytochrome C expression) and inducing an endoplasmic reticulum stress (GRP78 upregulation). Moreover, Cd is able to induce glial morphological alterations as well as an overexpression of activation glial markers, such as GFAP, S100ß, CD86, and Iba1. In conclusion, the data obtained clearly demonstrated that Cd toxicity occurs even at low doses and for very short exposure times Further experiments should be performed in order to evaluate the mechanisms underlying the Cd-dependent activation of glial cells and how this, in turn, induces a neuronal homeostasis alteration. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a highly toxic environmental pollutant released from the smelting and refining of metals and cigarette smoking. Oral exposure to cadmium may result in adverse effects on a number of tissues, including the central nervous system (CNS). In fact, its toxicity has been related to neurological disorders, as well as neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Under normal conditions, Cd barely reaches the brain in adults because of the presence of the blood–brain barrier (BBB); however, it has been demonstrated that Cd-dependent BBB alteration contributes to pathogenesis of neurodegeneration. However, the mechanism underlying Cd-dependent BBB alteration remain obscure. Here, we investigated the signaling pathway of Cd-induced tight junction (TJ), F-actin, and vimentin protein disassembly in a rat brain endothelial cell line (RBE4). RBE4 cells treated with 10 μM cadmium chloride (CdCl2) showed a dose- and time-dependent significant increase in reactive oxygen species (ROS) production. This phenomenon was coincident with the alteration of the TJ zonula occludens-1 (ZO-1), F-actin, and vimentin proteins. The Cd-dependent ROS increase elicited the upregulation of GRP78 expression levels, a chaperone involved in endoplasmic reticulum (ER) stress that induces caspase-3 activation. Further signal profiling by the pannexin-1 (PANX1) specific inhibitor 10Panx revealed a PANX1-independent increase in ATP spillage in Cd-treated endothelial cells. Our results point out that a ROS-dependent ER stress-mediated signaling pathway involving caspase-3 activation and ATP release is behind the BBB morphological alterations induced by Cd. [ABSTRACT FROM AUTHOR]

Sonic hedgehog (Shh) signaling is a key pathway within the central nervous system (CNS), during both development and adulthood, and its activation via the 7-transmembrane protein Smoothened (Smo) may promote neuroprotection and restoration during neurodegenerative disorders. Shh signaling may also be activated by selected glucocorticoids such as clobetasol, fluocinonide and fluticasone, which therefore act as Smo agonists and hold potential utility for regenerative medicine. However, despite its potential role in neurodegenerative diseases, the impact of Smo-modulation induced by these glucocorticoids on adult neural stem cells (NSCs) and the underlying signaling mechanisms are not yet fully elucidated. The aim of the present study was to evaluate the effects of Smo agonists (i.e., purmorphamine) and antagonists (i.e., cyclopamine) as well as of glucocorticoids (i.e., clobetasol, fluocinonide and fluticasone) on NSCs in terms of proliferation and clonal expansion. Purmorphamine treatment significantly increased NSC proliferation and clonal expansion via GLI-Kruppel family member 1 (Gli1) nuclear translocation and such effects were prevented by cyclopamine co-treatment. Clobetasol treatment exhibited an equivalent pharmacological effect. Moreover, cellular thermal shift assay suggested that clobetasol induces the canonical Smo-dependent activation of Shh signaling, as confirmed by Gli1 nuclear translocation and also by cyclopamine co-treatment, which abolished these effects. Finally, fluocinonide and fluticasone as well as control glucocorticoids (i.e., prednisone, corticosterone and dexamethasone) showed no significant effects on NSCs proliferation and clonal expansion. In conclusion, our data suggest that Shh may represent a druggable target system to drive neuroprotection and promote restorative therapies. [ABSTRACT FROM AUTHOR]

Interaction between intestinal epithelial cells (IECs) and the underlying immune systems is critical for maintaining intestinal immune homeostasis and mounting appropriate immune responses. We have previously showed that the T helper type 1 (TH1) cytokine IL-12 plays a key role in the delicate immunological balance in the gut and the lack of appropriate levels of IL-12 had important consequences for health and disease, particularly with regard to food allergy. Here we sought to understand the role of IL-12 in the regulation of lympho-epithelial cross talk and how this interaction affects immune responses locally and systemically. Using a combination of microscopy and flow cytometry techniques we observed that freshly isolated IECs expressed an incomplete, yet functional IL-12 receptor (IL-12R) formed solely by the IL-12Rb2 chain that albeit the lack of the complementary IL-12b1 chain responded to ex-vivo challenge with IL-12. Furthermore, the expression of IL-12Rb2 on IECs is strategically located at the interface between epithelial and immune cells of the lamina propria (lp) and using in vitro co-culture models and primary intestinal organoids we showed that immune-derived signals were required for the expression of IL-12Rb2 on IECs. The in vivo biological relevance of the IEC-associated IL-12Rb2 was assessed in vivo in a mouse model of food allergy characterized by allergy-associated diminished intestinal levels of IL-12 and in chimeric mice that lack the IL-12Rb2 chain on IECs. These experimental models enabled us to show that the anti-allergic properties of orally delivered recombinant Lactococcus lactis secreting bioactive IL-12 (rLc- IL12) were reduced in mice lacking the IL-12b2 chain on IECs. Finally, we observed that the oral delivery of IL-12 was accompanied by the down-regulation of the production of the IECderived pro-allergic cytokine thymic stromal lymphopoietin (TSLP). However, further analysis of intestinal levels of TSLP in IL-12Rb2-/- mice suggested that this event was not directly linked to the IEC-associated IL-12Rb2 chain. We interpreted these data as showing that IECassociated IL12Rb2 is a component of the cytokine network operating at the interface between the intestinal epithelium and immune system that plays a role in immune regulation. [ABSTRACT FROM AUTHOR]

It is known that joint mobility (JM), flexibility, muscle strength and posture can determine the quality of movement and could also adversely affect the body development of young subjects practicing sport. The aim of this study was to investigate how the practice of different sports affects these parameters. We enrolled 109 young subjects practicing different sports: soccer (M/F:22/10), mean age 12,6±1,4 yrs, BMI:18,3±2,3 kg/m2; volleyball (M/F:13/14), mean age 12,0±1,3 yrs, BMI 17,4±2,2 kg/m2; basketball (M/F:20/2), mean age 11,1±0,8 yrs, BMI 20,9±4,4 kg/m2; gymnastics (M/F:0/11), mean age 14,5±1,1 yrs, BMI 18,9±2,1 kg/m2 and dance (M/F:0/17), mean age 11,7±3,1 yrs, BMI 18,3±2,8 kg/m2. In these subjects we evaluated ankle JM (inclinometer), trunk flexibility (sit & reach test), muscle strength (standing long jump, vertical jump and Jamar hand grip), posture (images on the sagittal plane) and lifestyle (IPAQ-C, IPAQ-A). The individual sporting history was investigated by a specific questionnaire. The tests performed showed a significantly higher ankle JM in young dancers (155,8±10,3°) compared to all other groups excluding volleyball players (p<0,001). In particular, the subjects practicing soccer showed a significant reduction of the ankle JM (125,2±22,3°) compared to all the other groups of subjects investigated (p<0,01). Gymnasts showed a greater flexibility of the trunk than that measured in all other groups (18,3±3,5 cm; p<0,001), while basketball players showed lower trunk flexibility (-7.7 ± 7.0 cm). In the muscle-strength tests performed the dancers showed the following results (hand grip: 18.7 ± 6.6 kg, long-jump standing 119.8 ± 29.2 cm) that are significantly reduced compared to the gymnasts (hand grip: 26.0 ± 4, 2 kg: p <0.005, long jump standing 163.8 ± 12.7 cm: p <0.001) and to volleyball players (standing long jump 152.5 ± 27.9 cm: p <0.001). The practice of specific sports can significantly modify the ankle JM and the flexibility of the trunk as well as affect muscle strength even in young subjects. It is not entirely clear whether these effects may induce negative consequences on health and development of the anatomical structures involved; therefore, further studies are needed to verify the conclusions and the possible usefulness of APA programmes in the prevention or recovery of such significant effects. [ABSTRACT FROM AUTHOR]

Exercise is generally recommended for elderly subjects although the effects of the different programmes used in the adapted physical activity (APA) centers are not always properly verified. The aim of this study was to evaluate the response of elderly subjects attending classes of APA to a moderate aerobic physical activity. In 15 subjects (2/13 M/F), mean age 67,8±13,8 yrs, body mass index 23,7±3,5 Kg/m2 attending an APA class we evaluated ankle joint mobility (inclinometer), hand strength (Jamar hand grip), walking speed and step length (10 and 20 meters), aerobic capacity and endurance (6 Minute Walk Test- 6MWT), lower extremity function (SPPB: short physical performance battery), posture (sagittal images), and peripheral microcirculation (Laser doppler flowmetry). The subjects were evaluated in the following 3 stages: at the end of a 8-months APA period, after 4 months of inactivity and 4 months after recommencing of a new period of the same programme. All the subjects included in the study performed a training programme of APA twice a week for 1 hour each. The training programme consisted in 10 minutes of organic activation, 30 minutes of moderate physical activity at 45-65% of VO2 peak and toning, 20 minutes of exercises on the floor: breathing and stretching. After 4 months of inactivity, the subjects investigated showed a significant and widespread reduction of the gait parameters investigated: 6MWT (446.5 ± 91.4 vs 429 ± 89.4 mt, p <0.01); 10 meters (step length: 0.67 ± 0.09 vs 0.63 ± 0.08 mt - time: 7.6 ± 1.7 vs 8.5 ± 1.7''); 20 meters (step length: 0.71 ± 0.08 vs 0.67 ± 0.06 mt - time: 14.0 ± 2.1 vs 15.4 ± 2.0''). After 4 months of training there was a significant, even if partial recovery of the parameters investigated in comparison to the results achieved after the inactivity period,: 6MWT (438.05 ± 92.3 mt, p <0.01); 10 meters (step length: 0.65 ± 0.07 mt - time: 8.0 ± 1.7'', p <0.01); 20 meters (step length: 0.68 ± 0.07 mt, p = 0.15 - time: 14.6 ± 2.1'', p <0.01). The 4 meter walking speed (SPPB) evaluated in the subjects investigated was correlated with 10 mt (r = 0.69, p <0.01) and 20 mt (r = 0.6, p <0, 05). The length of the step measured in the 10 and 20 meters tests was correlated with the ankle mobility (10 mt: r = 0.7, p <0.01; 20 mt: r = 0.62, p <0.5). The results of this study show that in a population of elderly subjects a programme of APA, as scheduled and performed in this study, significantly improves the gait parameters. However, a short interruption of the APA training significantly reduced the walking speed and step length. This study, in addition to underlining the importance of the APA programmes, also shows that it is necessary to reduce or avoid interruptions of these physical activities. [ABSTRACT FROM AUTHOR]

Degenerative diseases of the central nervous system are significant causes of mortality among aging population in industrialized countries, as well as expensive for the national health systems and caregivers [1]. Nowadays, pharmacological therapies are still not decisive because they are hindered by the blood brain barrier (BBB) [2]. Although in the last decades many researchers have conducted in vivo experiments to better identify a therapeutic approach of ultrasound (US) in neurodegenerative diseases, little is known about their role in increasing the BBB permeability [3,4]. The present study aims to identify, the effect of focused US on a rat brain endothelial cell line (RBE4). After ultrasound stimulation (10-20-30 min.), MTT and western blotting assay were conducted to demonstrate the non-toxic effects of US. Furthermore, immunostaining of stimulated cells was performed to detect changes in cytoskeletal F-actin fibers and Zonula occludens-1 (ZO1) tight juntion. BBB opening was evaluated by measuring the extent of the intercellular space, in Papanicolaou stained cells. The results evidenced an ultrasonic-dependent mechanical action on F-actin fibers that altered their distribution within the cells showing the formation of numerous stress fibers. F-actin alterations were accompanied by an alteration of the ZO-1 distribution, exhibiting a "zipper-like" staining pattern and holes that became visible between cells. Papanicolaou staining confirm the opening of the BBB evidencing many wider areas of intercellular space. All these structural changes on RBE4 cell line occurred without significant alterations in metabolic activity as well as in absence of apoptotic or endoplasmic reticulum stress markers. In conclusion, these results confirm and highlight the potential role of ultrasound in the permeabilization of the BBB, thus suggesting new ways for drugs administration. [ABSTRACT FROM AUTHOR]

Quality of life into later life is influenced by multiple factors. The physical abilityto perform common everyday activities represents a key factor to maintain a healthy and independent lifestyle. Moreover, aging is a process characterized by physiological alterations resulting in a progressive decline in biological functions, decreased resistance to stress, and increased susceptibility to diseases. Especially in elderly people, alterations such as imbalance between pro and antioxidant activity and/or hormonal dysregulation negatively affect the physical capacity, the emotionalstatus and the overall general health and quality of life [1]. On the other hand, regular physical activity is considered an effective strategy for older adults to prevent and reduce the risk of developing those negative conditions arising from aging. A 24-week regular physical activity program (twice weekly, 1 hour per session) focused on functional fitness exercises was performed by 20 older adults (aged 55 years or more). A set of anthropometric (height, weight, BMI and body fat percentage) and physical measurements (grip strength, chair sit to stand, sit and reach and back scratch) assessing the functional fitness performance [2] were evaluated. Moreover, biochemical markers (d-ROMs and BAP tests as assessment of oxidative stress and antioxidant potential; salivary cortisol levels) were measured before and after the intervention program. The results confirm the benefits of a regular physical activity in older adults resulting in improved physical strength and flexibility in the functional fitness parameters, and in regulating pro and antioxidant activity and cortisol levels. [ABSTRACT FROM AUTHOR]

During infection intestinal CX3CR1+ cells can either extend transepithelial cellular processes to sample luminal bacteria or, very early after infection migrate into the intestinal lumen to capture bacteria. However, up to date, the biological relevance of the intraluminal migration of CX3CR1+ cells remained to be determined. We addressed this by using a combination of mouse strains differing in their ability to carry out CX3CR1-mediated sampling and intraluminal migration. We observed that, the number of S. Typhimurium traversing the epithelium did not differ between sampling-competent/migration-competent C57BL/6 and sampling deficient/migration- competent Balb/c mice. By contrast, in sampling-deficient/migration deficient CX3CR1-/- mice the numbers of S. Typhimurium penetrating the epithelium were significantly higher. However, in these mice the number of invading S. Typhimurium was significantly reduced after the adoptive transfer of CX3CR1+ cells directly into the intestinal lumen, consistent with intraluminal CX3CR1+ cells preventing S. Typhimurium from infecting the host. This interpretation was also supported by a higher bacterial faecal load in CX3CR1+/gfp compared to CX3CR1gfp/gfp mice following oral infection. Furthermore, by using real time in vivo imaging we observed that CX3CR1+ cells migrated into the lumen moving through paracellular channels within the epithelium. Also, we reported that the absence of CX3CR1 mediated sampling did not affect antibody responses to a non-invasive S. Typhimurium strain that specifically targeted the CX3CR1-mediated entry route. These data showed that the rapidly deployed CX3CR1+ cell-based mechanism of immune-exclusion is a defence mechanism against pathogens that complements the mucous and secretory (s)IgA antibodymediated system in the protection of intestinal mucosal surface. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a worldwide occupational and environmental pollutant [1]. Cd toxicity is widely known and studied in many tissues and organs such as testis, kidney, liver, lung and brain [2,3]. On the other hand, zinc (Zn) is a trace element known as coenzyme for many proteins such as methallothionein [4]. To date, very little is known about the role of Cd and Zn in BBB permeability. To study their effects in BBB permeability in vitro, the RBE4 cell line was used and different concentrations of CdCl2 and ZnCl2 were tested. Metabolic activity (MTT assay) was performed to test the protective and preventive role of ZnCl2 on CdCl2 toxicity. Western blotting analysis was used to better investigate the molecular pathway involved in Cd-induced BBB permeability evaluating GRP78 (ER stress marker) and caspase-3 protein expression levels. Furthermore, ZO-1 and F-actin immunofluorescent staining was performed to better understand the morphological alterations and BBB permeability achieved by Cd treatment. Our preliminary data highlight the role of Cd in evoking BBB permeability by F-actin and ZO1 dislocations, triggering the caspase-3 molecular pathway activation induced by GRP78-ER stress increase. Moreover, the data clearly show how Zn is able to counteract the metabolic impairment induced by Cd treatment. Taken together these data point out the possible role of Zn in counteracting the Cd-induced BBB impairment. [ABSTRACT FROM AUTHOR]

Due to its high permeability to blood-brain barrier (BBB), cadmium (Cd) has been regarded as a possible etiological factor for human neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and Huntington's disease [1]. However, the mechanism underlying cadmium-induced BBB permeability remains unclear. In this study, we investigated the effect of Cd in RBE4 cells (rat brain endothelial cells) and delineated the signaling pathway that, triggering endoplasmic reticulum (ER) stress and caspase 3 activation, leads to cytoskeleton disorganization and tight junctions disassembly. Our results demonstrate a possible downstream pathway mediated through the Cd-dependent ER stress, assessed by the cytoplasmic expression of an ER protein GRP78, and the consequent caspase-3 activation that results in an extracellular ATP increase, which in turns induces a dislocation, evaluated by immunofluorescent staining, of Zonula Occludens-1 (ZO-1), a tight junction protein, and F-actin. These findings, whereby Cd-induced permeabilization of BBB through a ER stressdependent pathway on endothelial cells represent a possible novel mechanism of action for Cd that could explain, at least in part, the Cd-related central effects. [ABSTRACT FROM AUTHOR]