Role of Neurotrophins in Orofacial Pain Modulation: A Review of the Latest Discoveries

Orofacial pain represents a multidisciplinary biomedical challenge involving basic and clinical research for which no satisfactory solution has been found. In this regard, trigeminal pain is described as one of the worst pains perceived, leaving the patient with no hope for the future. The aim of this review is to evaluate the latest discoveries on the involvement of neurotrophins in orofacial nociception, describing their role and expression in peripheral tissues, trigeminal ganglion, and trigeminal nucleus considering their double nature as “supporters” of the nervous system and as “promoters” of nociceptive transmission. In order to scan recent literature (last ten years), three independent researchers referred to databases PubMed, Embase, Google Scholar, Scopus, and Web of Science to find original research articles and clinical trials. The researchers selected 33 papers: 29 original research articles and 4 clinical trials. The results obtained by the screening of the selected articles show an interesting trend, in which the precise modulation of neurotrophin signaling could switch neurotrophins from being a “promoter” of pain to their beneficial neurotrophic role of supporting the nerves in their recovery, especially when a structural alteration is present, as in neuropathic pain. In conclusion, neurotrophins could be interesting targets for orofacial pain modulation but more studies are necessary to clarify their role for future application in clinical practice

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

Red LED light in skin regeneration: an in vitro study on human dermal fibroblasts

The use of noncoherent light (light-emitting diodes, LEDs), in particular the Red LED light, represents an innovative approach to tissue regeneration. In dermatological field, experimental studies on its regenerative effect started about ten years ago but the exact mechanism of its action should be better elucidated. Today, a new treatment, named “Dermodinamica” (Elisor, Milan), uses this approach with a wavelength of 630nm to promote skin regeneration. Dermal fibroblast is a primary cell type responsible for synthesis and remodeling of extracellular matrix in human skin. Several studies have reported cytokine-dependent changes in extracellular matrix composition and in particular transforming growth factor (TGF)-beta1 is a fibroblast stimulating cytokine effective on both type I collagen and hyaluronan production. Moreover, ROS-detoxifying enzymes, such as superoxide dismutases (SOD) and heme-oxygenase 1 (HO-1), have an important role in cutaneous wound repair. The aim of the present in vitro preliminary study was to evaluate the effect of Red LED light (Dermodinamica, Elisor, Milan) on normal human dermal fibroblast (NHDF) at 24h from exposition monitoring: cell viability using MTT assay; TGF-beta1 production using ELISA kit; expression of SOD-1 and HO-1 using immunohistochemical technique. Moreover, short (15 min exposition) and prolonged (30 min exposition) treatments were investigated. The results showed a progressive increase in TGF-beta1 release respectively in the short treatment (15 min exposition) and in the prolonged treatment (30 min exposition). Moreover, the ROS-detoxifying enzymes were modulated by this treatment and the cell viability was maintained. These data support the hypothesis of the positive influence of Red LED light in the biological processes involved in skin regeneration

Effect of long-term treatment with melatonin against obesity related dysfunctions in obese mice.

The increasing incidence of obesity, leading to metabolic complications is now recognized as a major public health problem. The adipocytes are not merely energystoring cells, but they play crucial roles in the development of the so-called metabolic syndrome and cardiovascular diseases due to the adipocyte-derived bioactive factors, such adipokines, cytokines and growth factors [1]. Most of adipokines, which affect whole-body homeostasis, are pro-inflammatory, whereas a small number of anti-inflammatory adipokines, including adiponectin exert beneficial actions on obese complications. The dysregulated production and secretion of adipokines seen in obesity is linked to the pathogenesis of various disease processes [2]. New emerging data showed that melatonin, pineal gland indoleamine, play an important role in body weight regulation and energy metabolism [3]. Lean and obese mice (ob/ob) received melatonin (100 mg/kg/day) or vehicle in drinking water for 8 weeks. In obese mice we observed a significant increase in fat depots and a deregulation of adipokines and cytokines fat expressions. In particular, we observed a significant reduction of adiponectin and an increase of resistin and visfatin at adipose tissue level. Melatonin administration for 8 weeks reduced fat accumulation and restored the correct adipokines expression, modulating in turn the vascular tone and homeostasis. These results indicate that melatonin counteracts some of the disrupting effects of obesity

The First Evidence of Bacterial Foci in the Hair Part and Dermal Papilla of Scalp Hair Follicles: A Pilot Comparative Study in Alopecia Areata

The role of the microbiome in hair follicle (HF) growth represents a growing field of research. Here, we studied the bacterial population in the scalp hair follicles of subjects with alopecia areata (AA). Two Healthy and two AA subjects, respectively (20-60 years old), were enrolled and studied regarding the microbial community in the subepidermal scalp compartments by means of a 4-mm biopsy punch. Samples were examined by 16S sequencing, histochemical staining (Gram's method), and transmission electron microscopy (TEM). Bacterial foci were observed in the AA subjects' follicles with both the two adopted complementary approaches (electron microscopy and Gram staining). Significant (p < 0.05) differences were also found in the three-layer biopsy samples (p < 0.05) regarding the bacterial population. In particular, in the deep epidermis and dermis levels, a significant (p < 0.05) lower abundance of Firmicutes and a higher abundance of Proteobacteria were found in AA samples compared to the healthy control. Firmicutes also showed a significant (p < 0.05) lower abundance in hypodermis in AA subjects. In addition, Enterobacteriaceae and the genera Streptococcus, Gemella, Porphyromonas, and Granulicatella were relatively more abundant in AA groups at the deep epidermis level. The Staphylococcus and Flavobacterium genera were significantly less abundant in AA samples than in controls in all three-layer biopsy samples (p < 0.05). In contrast, Veillonella and Neisseriaceae were relatively more abundant in the healthy control group compared to the AA sample. Therefore, higher alpha diversity was observed in all three-layer biopsy samples of AA patients compared to the control. In conclusion, our data suggest that tAA could be defined as a "hair disease associated with dysregulated microbiome-immunity axis of hair follicles"

Platelet preparations in neuronal cell differentiation.

Concentrated Growth Factors (CGF) is a platelet rich preparation that has the important feature of a tight fibrin network and containing a large number of growth factors possessing great regenerative potentialities [1]. The regeneration of nervous system is one of the mail goal of regenerative medicine. The aim of this study is to test the in vitro CGF effects on both differentiated and undifferentiated SH-SY5Y cells, derived from human neuroblastoma. To induce differentiation, SH-SY5Y cells have been treated with Retinoic Acid (RA) 10μM, in both basal and complete medium and in the presence and absence of CGF. After 72 hours, different parameters have been investigated: the morphological characteristics of the cells, the cell proliferation, the cellular vitality using the MTT test, the CGF and/or RA differentiation property and the immunocytochemical analysis of neuronal specific markers (NeuN, Sinaptophisine, β-III-tubulin, Nestin). Moreover the NGF (Nerve Growth Factor) and BDNF (Brain Derived Growth Factor) release have been assayed by ELISA test. Our results obtained suggest that treatment with CGF, also used alone, positively affects cell differentiation and neuronal phenotype regulating the expression of the neuronal markers and improving the outgrowth of neurites. Taken together these results seems to be promised into new approaches for neuronal regeneration using platelet preparations