Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

Microgravity impairs tissue organization and critical pathways involved in the cell– microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization

Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

<p>Abstract</p> <p>Background</p> <p>The aims of this study were: (1) to show the feasibility of using adipose-derived stromal vascular fraction (SVF) as an alternative to bone marrow mono nuclear cell (BM-MNC) for cell transplantation into chronic ischemic myocardium; and (2) to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI) against left ventricular (LV) remodelling and cardiac dysfunction.</p> <p>Methods</p> <p>Four weeks after left anterior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12) had SVF cell transplantation (6 × 10⁶cells). BM-MNC group (n = 12) received BM-MNCs (6 × 10⁶) and the control (n = 10) had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20.</p> <p>Results</p> <p>At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition.</p> <p>Conclusions</p> <p>Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.</p

Inositols: From established knowledge to novel approaches

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects

Better mental health in children of Vietnamese refugees compared with their Norwegian peers - a matter of cultural difference?

<p>Abstract</p> <p>Background</p> <p>There are conflicting results on whether immigrant children are at a heightened risk of mental health problems compared with native youth in the resettlement country.</p> <p>The objective of the study</p> <p>To compare the mental health of 94 Norwegian-born children from a community cohort of Vietnamese refugees, aged 4 - 18 years, with that of a Norwegian community sample.</p> <p>Methods</p> <p>The SDQ was completed by two types of informants; the children's self-reports, and the parents' reports, for comparison with Norwegian data from the Health Profiles for Children and Youth in the Akershus study.</p> <p>Results</p> <p>The self-perceived mental health of second-generation Vietnamese in Norway was better than that of their Norwegian compatriots, as assessed by the SDQ. In the Norwegian-Vietnamese group, both children and parents reported a higher level of functioning.</p> <p>Conclusion</p> <p>This surprising finding may result from the lower prevalence of mental distress in Norwegian-Vietnamese children compared with their Norwegian peers, or from biased reports and cultural differences in reporting emotional and behavioural problems. These findings may represent the positive results of the children's bi-cultural competencies.</p

Hyaluronic acid and vitamins are effective in reducing vaginal atrophy in women receiving radiotherapy

During the last decades, therapies targeting cervical cancer have been considerably improved. Surgery and radiotherapy (RT) represent the main common therapeutic approach in cervical cancer. In order to minimize the side effects of radiotherapy approach, several protocols have been developed such as brachytherapy (BRT). Among the side effects associated with RT, the vaginal atrophy is the most important and common one. Vaginal atrophy, in turn, leads to additional alterations like inflammation, associated to relevant symptoms such as itching, burning and dyspareunia. All these alterations heavily affect the quality of women's life. The aim of our study was to evaluate the toxicity induced by RT on vaginal mucosa, and the adjuvant action of a product containing LMWHA, vitamin A, and Vitamin E (Santes®, Lo.Li. Pharma, Rome, Italy). The introduction of adjuvant therapies may have likely had a relevant place in providing that result

Molecular biopathology of metaplastic, dysplastic, and neoplastic laryngeal epithelium

In a large series of more than 100 cases of laryngeal carcinomas, the presence of steroid hormone receptors was demonstrated in the cytosol and in the nuclear fraction. Their presence was confirmed by the identification of estrogen receptor isophorms and by the detection of hormone-related proteins such as ER-D5. EGFr, and cathepsin D. These molecules were also variably expressed in normal, hyperplastic, and dysplastic epithelium. These data suggest a possible role of hormone receptors during laryngeal carcinogenesis. Finally, the presence of an Angiotensin II receptor was studied in neoplastic and preneoplastic laryngeal epithelium

Natural products - alpha-lipoic acid and acetyl-L-carnitine - in the treatment of chemotherapy-induced peripheral neuropathy

OBJECTIVE: Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of anticancer agents. Yet, CIPN pathophysiology is poorly understood, and there is a lack of well-tolerated pharmacological remedies helpful to prevent or treat it. Therefore, new safe and effective compounds are highly warranted, namely if based on an adequate understanding of the pathogenic mechanisms.MATERIAL AND METHODS: Herein we reviewed and discussed scientific data related to the beneficial role of some non-conventional treatments able to counteract CIPN, focusing our attention on alpha-lipoic acid (ALA) and L-acetyl-carnitine (LAC), two natural products that have been demonstrated to be promising preventive drugs.RESULTS: Although a growing body of in vitro and in vivo studies support ALA as a molecule able to counteract CIPN symptoms, mostly due to its antioxidant and anti-inflammatory properties, only two randomized clinical trials evaluated ALA usefulness in preventing chemotherapy-related neuropathy. Unfortunately, these studies were inconclusive and clinical outcomes showed to be highly dependent on the route of administration (oral versus or intravenous injection). LAC has demonstrated beneficial effects on both in vitro and in animal studies. Yet, some controversies aroused from randomized clinical trials. Indeed, while CIPN-patients treated with Taxane showed no benefit from LAC treatment, CIPN-patients treated with platinum compounds exhibit significant improvement of CIPN-related symptoms. Therefore, LAC treatment should be used, and thoroughly investigated only in patients treated with chemotherapy protocols Taxanes-free.CONCLUSIONS: Mechanisms of toxicity triggered by each single drug need to be deeply explored to better identify effective compounds to prevent or treat them. Moreover, additional experiments are mandatory to establish effective doses and length of treatment for each clinical situation in order to perform large and long-term randomized studies