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Objectives: The presence of prostate‐specific antigen (PSA) in saliva and salivary glands has been reported. Nevertheless, its release pathway in these glands remains to be elucidated. Here, we showed PSA subcellular distribution focusing on its plausible route in human salivary parenchyma. Materials and Methods: Sections of parotid and submandibular glands were subjected to the immunohistochemical demonstration of PSA by the streptavidin–biotin method revealed by alkaline phosphatase. Moreover, ultrathin sections were collected on nickel grids and processed for immunocytochemical analysis, to visualize the intracellular distribution pattern of PSA through the observation by transmission electron microscopy. Results: By immunohistochemistry, in both parotid and submandibular glands PSA expression was detected in serous secretory acini and striated ducts. By immunocytochemistry, immunoreactivity was retrieved in the cytoplasmic compartment of acinar and ductal cells, often associated with small cytoplasmic vesicles. PSA labeling appeared also on rough endoplasmic reticulum and in the acini's lumen. A negligible PSA labeling appeared in most of the secretory granules of both glands. Conclusions: Our findings clearly support that human parotid and submandibular glands are involved in PSA secretion. Moreover, based on the immunoreactivity pattern, its release in oral cavity would probably occur by minor regulated secretory or constitutive‐like secretory pathways. [ABSTRACT FROM AUTHOR]

Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has been focused on Insulin-like Growth Factor 2 (IGF-2), mainly detected in embryonic and fetal somatic tissues, which regulate metabolic and mitogenic functions. The binding between IGF-2 and its receptor Insulin-like Growth Factor 1 Receptor (IGF-1R) activates the PI3K-AKT pathway, which leads to the regulation of cell growth, differentiation, and the expression of specific genes. Since IGF2 is regulated by parental imprinting, in different human tumors, the IGF2 Loss of Imprinting (LOI) results in IGF-2- and IGF2-derived intronic miR-483 overexpression. Based on these activities, the purpose of this study was to investigate the overexpression of IGF-2, IGF-1R, and miR-483. Using an immunohistochemical approach, we demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher's exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively). Therefore, IGF-2/IGF-1R co-expression could suggest their interplay through the two different paracrine/autocrine IGF-2 routes for signaling transfer, which would activate the PI3K/AKT signaling pathway. In this scenario, miR-483 gene family transcription might synergically reinforce IGF-2 oncogenic function through its boosting pro-proliferative and antiapoptotic activity. [ABSTRACT FROM AUTHOR]

Abstract Background Cervical cancer ranks as the first most frequent cancer among women in Benin. The major cause of cervical cancer now recognized is persistent infection of Human Papillomavirus (HPV). In Benin there is a lack of screening programs for prevention of cervical cancer and little information exists regarding HPV genotype distribution. Methods Cervical cells from 725 women were examined for the presence of viral DNA by means of a polymerase chain reaction (PCR) multiplex-based assay with the amplification of a fragment of L1 region and of E6/E7 region of the HPV genome, and of abnormal cytology by Papanicolaou method. The association between HPV status and Pap test reports was evaluated. Socio-demographic and reproductive characteristics were also related. Results A total of 18 different HPV types were identified, with a prevalence of 33.2% overall, and 52% and 26.7% among women with and without cervical lesions, respectively. Multiple HPV infections were observed in 40.2% of HPV-infected women. In the HPV-testing group, the odds ratio for the detection of abnormal cytology was 2.98 (95% CI, 1.83-4.84) for HPV positive in comparison to HPV negative women. High risk types were involved in 88% of infections, most notably HPV-59, HPV-35, HPV-16, HPV-18, HPV-58 and HPV-45. In multiple infections of women with cytological abnormalities HPV-45 predominated. Conclusions This study provides the first estimates of the prevalence of HPV and type-specific distribution among women from Benin and demonstrates that the epidemiology of HPV infection in Benin is different from that of other world regions. Specific area vaccinations may be needed to prevent cervical cancer and the other HPV-related diseases.

Objective: The purpose of the study was to examine whether the insertion (I) and/or deletion (D) polymorphism of ACE confers susceptibility to primary pterygium in Sardinian patients in a case-control study. Methods and results: Polymorphism genotyping was performed by nested PCR using genomic DNA extracted from the whole peripheral blood of participants with (n=251) and without (n=260) pterygium. DD, ID and II genotype frequencies were: 48%, 39% and 13%, respectively, for patients with pterygium, and 15%, 40% and 44%, respectively, for the control group. A statistically significant difference was found between the pterygium and control groups for the ACE I/D polymorphism (p<0.001). Moreover, a statistically significant difference was found between the DD and II groups (p<0.01; OR=10.49; 95% CI 6.18 to 17.79), DD+ID versus II group (p<0.01; OR=5.23; 95% CI 3.37 to 8.13) and DD versus ID groups (p<0.01; OR=3.21; 95% CI 2.04 to 5.04). Conclusions: Statistical analysis showed that the DD genotype is associated with an increased risk of developing pterygium, and with a good chance that the D allele may play an important role in the development of disease. [ABSTRACT FROM AUTHOR]

Alopecia Areata (AA) is an autoimmune disease characterized by well-circumscribed patches of hair loss especially from the scalp. Cytotoxic T- lymphocyte antigen 4 ( CTLA4) gene, a negative regulator of T cells, has been associated with predisposition to most autoimmune disorders. We evaluated two CTLA4 functional single-nucleotide polymorphisms (SNPs) for potential association with Alopecia Areata in an Italian population using a case-control approach. We genotyped +49AG (rs231775) and CT60 (rs3087243) variants in 130 AA patients and 189 ethnically matched controls by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. CTLA4 +49AG analysis revealed no statistically significant difference in both the allele and genotype frequencies between patients and controls. As regarding CT60 SNP, we found that AA cases less frequently than healthy subjects carried A/A genotype with a higher prevalence of A/G and G/G genotypes (83.8 and 75.1 %; p = 0.041, OR = 0.58, 95 % CI 0.32-1.03), consistent with a dominant effect of G disease risk allele. In particular, it seemed to exert effects mainly in DQ7-negative patients with a less aggressive form of the disease. Haplotype analysis suggested that the G(+49AG), A(CT60) allelic combination was significantly related to a reduced disease risk ( p = 0.014, OR = 0.28, 95 % 0.09-0.82). Altogether, our findings confirm that only CTLA4 CT60 polymorphism seems to be an important genetic determinant of Alopecia Areata development in Italian subjects. [ABSTRACT FROM AUTHOR]

Stemness and apoptosis may highlight the dichotomy between regeneration and demise in the complex pathway proceeding from ontogenesis to the end of life. In the last few years, the concept has emerged that the same microRNAs (miRNAs) can be concurrently implicated in both apoptosis-related mechanisms and cell differentiation. Whether the differentiation process gives rise to the architecture of brain areas, any long-lasting perturbation of miRNA expression can be related to the occurrence of neurodevelopmental/neuropathological conditions. Moreover, as a consequence of neural stem cell (NSC) transformation to cancer stem cells (CSCs), the fine modulation of distinct miRNAs becomes necessary. This event implies controlling the expression of pro/anti-apoptotic target genes, which is crucial for the management of neural/neural crest-derived CSCs in brain tumors, neuroblastoma, and melanoma. From a translational point of view, the current progress on the emerging miRNA-based neuropathology therapeutic applications and antitumor strategies will be disclosed and their advantages and shortcomings discussed. [ABSTRACT FROM AUTHOR]

Polyphenol oxidase (PPO, E.C. 1.14.18.1) is a nearly ubiquitous enzyme that is widely distributed among organisms. Despite its widespread distribution, the role of PPO in plants has not been thoroughly elucidated. In this study, we report for the absence of PPO in Cynomorium coccineum, a holoparasitic plant adapted to withstand unfavorable climatic conditions, growing in Mediterranean countries and amply used in traditional medicine. The lack of PPO has been demonstrated by the absence of enzymatic activity with various substrates, by the lack of immunohistochemical detection of the enzyme, and by the absence of the PPO gene and, consequently, its expression. The results obtained in our work allow us to exclude the presence of the PPO activity (both latent and mature forms of the enzyme), as well as of one or more genes coding for PPO in C. coccineum. Finally, we discuss the possible significance of PPO deficiency in parasitic plants adapted to abiotic stress. [ABSTRACT FROM AUTHOR]

Histological analysis allows an accurate classification of most melanocytic lesions as benign or malig-nant. However, a challenging diagnosis can be faced when differentiating a nevus from a melanoma, mostly due to the heterogeneous histological appearance of melanomas. It is thus necessary to use immunohistochemistry as a complementary tool. The immunohistochemical expression of tyrosinase, the key melanogenic enzyme in melanocytes, has often been useful in formulating a differential diagnosis thanks to the peculiar staining pattern in nevocytes compared with melanoma cells. The expression pattern of tyrosinase in nevi appears to parallel the cytoarchitectural changes typically observable within the lesion: nevus cells in the epidermis or in the superficial dermis are more likely to be larger and strongly express melanocytic differentiation antigens, such as tyrosinase, compared with deeper nevocytes [1]. Our study aimed to evaluate the immunohistochemical expression pattern of the tyrosinase antigen (clone T311) in different histological types of acquired dysplastic melanocytic nevi, including junctional, compound, and intradermal nevi, as well as in a panel of normal skin tissues. Moreover, to evaluate whether the expression of tyrosinase by nevus cells, pointing out the acquisition of melanin-producing capabilities, was associated with the differentiation state of nevocytes, we likewise investigated the immunohistochemical expression of the two markers of pluripotency, CD34 and nestin. Our results revealed a prominent immunoreactivity for tyrosinase in junctional and superficial dermal nevocytes and a decreasing gradient of staining in dermal nevocytes, up to become negative in the deeper dermis. All junctional and dermal nevocytes were negative for CD34. Nestin immunostaining showed an opposing pattern compared with tyrosinase, leading us to look into the melanocytic nevus as a "histopathological model" to trace the final stages of the differentiation pathway that neural crest-derived melanocyte precursors undertake toward their ultimate anatomical and functional site into the epidermis, consistently with Cramer's dermal precursor model of melanocytic origin and the stem cell-based concept of nevogenesis [2]. Both CD34 and nestin intensely stained the small aggregates of cells, resembling "niches", adjacent to the bulge area of hair follicles, that may represent the reservoir of neural crest-derived melanocyte stem cells residing in the dermis. [ABSTRACT FROM AUTHOR]