A Prospective Observational Study on the Role of Immunohistochemical Expression of Orphanin in Laryngeal Squamous Cell Carcinoma Recurrence.

To date, histological biomarkers expressed by laryngeal cancer are poorly known. The identification of biomarkers associated with laryngeal squamous cell carcinoma (SCC), would help explain the tumorogenesis and prevent the possible recurrence of the lesion after treatment. For this reason, the aim of this study is to investigate, for the first time, the Orphanin expression in 48 human specimens of laryngeal SCC and evaluate its possible correlation with patients prognosis. We analyzed pathological specimens from 48 patients with laryngeal SCC to detect the presence of Orphanin by using an immunohistochemistry test. We compared the findings with healthy tissue acquired from patients who underwent surgery for mesenchymal benign tumours of the larynx. The specimens were stained with anti-Orphanin monoclonal antibodies. Results were processed through a computerised image analysis system to determine a scale of staining intensity. All the tumoural specimens examined showed a significant immunoreaction for Orphanin when compared with healthy tissues (p < 0.05) but with a different immune reactivity related to clinical-pathological features. A high Orphanin expression was not significantly related to Histological Grading (HG), TNM, and stage (p > 0.05). In the multivariate analysis, the Orphanin expression was significantly related only to the malignant recurrence (p < 0.05). Our study suggests that Orphanin could have a role in tumorigenesis by increasing the recurrence of cancer; therefore, it should be further explored as a possible biomarker for laryngeal cancer.

Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy.

Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools.

Probiotics Can Cure Oral Aphthous-Like Ulcers in Inflammatory Bowel Disease Patients: A Review of the Literature and a Working Hypothesis.

Dysbiosis has been associated with the onset of several chronic autoimmune or inflammatory pathologies (e.g., inflammatory bowel diseases-IBD), because of its primary role in the establishment of a chronic inflammatory process leading to tissue damage. Inflammatory bowel diseases can even involve areas far away from the gut, such as the extraintestinal manifestations involving the oral cavity with the onset of aphthous-like ulcers (ALU). Studies carried out on animal models have shown that intestinal dysbiosis may be related to the development of autoimmune diseases, even if the mechanisms involved are not yet well known. The aim of this paper is to verify the hypothesis that in inflammatory bowel diseases patients, aphthous-like ulcers are the result of the concomitance of intestinal dysbiosis and other events, e.g., the microtraumas, occurring in the oral mucosa, and that ex adiuvantibus therapy with probiotics can be employed to modify the natural course of the aphthous-like ulcers.

Hsp60 as a Novel Target in IBD Management: A Prospect.

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be considered a putatively important driver of events and could play an etiopathogenic role. This possibility is discussed in this review. We also indicate that Hsp60 can be a biomarker useful in disease diagnosing and monitoring and, if found active in pathogenesis, should become a target for developing new therapies. The latter are particularly needed to alleviate patient suffering and to prevent complications, including colon cancer.

Structural Characterization of Polysaccharides of a Productive Strain of the Culinary-Medicinal King Oyster Mushroom, Pleurotus eryngii (Agaricomycetes), from Italy.

A preliminary biological investigation of the dry basidiomata of strain C-142-c of Pleurotus eryngii has shown significant antioxidant activity. Two different polysaccharides (PEPS-A1 and PEPS-A2) were isolated from the cultivated edible mushroom, P. eryngii C-142-c strain. Based on acid hydrolysis, methylation analysis, and nuclear magnetic resonance experiments (1H, 13C, distortionless enhancement by polarization transfer, double quantum filtered correlation spectroscopy, total correlation spectroscopy, nuclear Overhauser effect spectroscopy, heteronuclear single-quantum correlation spectroscopy, and heteronuclear multiple-bond correlation spectroscopy), the structures of the repeating unit of PEPS-A1 and PEPS-A2 were established as follows: (l)PEPS-Al (α-glucan): [→6)-α-D-Glcp-(1→6)-α-D-Glcp-(l→]n; and (2) PEPS-A2 (ß-glucan): [→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(l→]n. The antioxidant activity of PEPS-A1 and PEPS-A2 was evaluated as hydroxyl radical scavenging activity. PEPS-A1 and PEPS-A2 showed SC50 values of 400 µg/mL and 122 µg/mL, respectively, suggesting their possible use as a dietary supplement in functional foods. The polysaccharides were tested for their activity on cell viability using a colorectal adenocarcinoma cell line (HT-29). Both polysaccharides affected cell viability after 48 and 72 hours of treatment, inducing the death of 50% of HT-29 cells between 0.25 and 1 µg/mL and between 0.5 and 1 µg/mL, respectively, for PEPS-A1 and PEPS-A2. These results are promising for future applications of these mushroom-derived polysaccharides as antioxidants and antitumor agents.

Comparative analysis of Hsp10 and Hsp90 expression in healthy mucosa and adenocarcinoma of the large bowel.

BACKGROUND: Heat shock proteins (Hsps) assist other proteins in their folding and drive the degradation of defective proteins. During evolution, these proteins have also acquired other roles. Hsp10 is involved in immunomodulation and tumor progression. Hsp90 stabilizes a range of "client" proteins involved in cell signaling. The present study evaluated the expression levels of Hsp10 and Hsp90 in normal mucosa and adenocarcinoma samples of human large bowel. MATERIALS AND METHODS: Samples of normal mucosa and adenocarcinoma were collected and Reverse transcriptase-polymerase chain reaction RT-PCR, western blotting (WB) analyses, as well as immunohistochemistry were performed to evaluate the expression levels of Hsp10 and Hsp90. RESULTS: RT-PCR showed a higher gene expression of Hsp10 and Hsp90 in adenocarcinoma samples compared to healthy mucosa. WB results confirmed these findings. Immunohistochemistry revealed higher levels of Hsp10 in adenocarcinoma in both the epithelium and the lamina propria, while Hsp90 expression was higher in the adenocarcinoma samples only in the lamina propria. CONCLUSION: Hsp10 and Hsp90 may be involved in large bowel carcinogenesis.

Hsp60 and human aging: Les liaisons dangereuses.

Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly, they are not unique to them. Therefore, it is difficult to determine what is due to aging and what to an associated disease that can occur regardless of age. Does Hsp60 contribute to the pathogenesis? How and when does Hsp60 interact with the immune system and, thus, contributes to the initiation-progression of the generalized chronic inflammation characteristic of aging? These and related issues are discussed here in the light of reports showing the participation of Hsp60 in aging-associated disorders.

Immunohistochemical expression and distribution of orexin, orphanin and leptin in the major salivary glands of some mammals.

The aim of the study was to determine by immunochemistry the expression of leptin, orexin A and orphanin FQ in the major salivary glands (parotid, submandibular and sublingual) of rat, sheep and cow. These peptides, originally synthesized in central nervous system, adipose tissue and peripheral tissues including gastrointestinal tract, play an orexigenic (orphanin and orexin) or anorexigenic (leptin) roles in the intricate neuronal network appointed to the control of nutritional homeostasis. Peptide-specific immunoreactivity was present in the studied salivary glands with various intensities in different species, in the ductal epithelium, sometimes in the acinar epithelium, and in nervous trunks spread in connective tissue stroma. The obtained data show that salivary glands present an unexpected source of orexigenic and anorexigenic peptides which with their autocrine, paracrine, and endocrine mechanisms of action may participate in the control of salivary gland function.

Association between interleukin-10 polymorphisms and Alzheimer's disease: a systematic review and meta-analysis.

It has been hypothesized that polymorphisms of interleukin (IL)-10 genes affect the risk of developing late onset Alzheimer's disease (AD). However, results of different studies are often inconsistent. Our aim was to investigate by meta-analysis the association of the common polymorphisms comprehensively defining the genetic variability of the IL-10 gene with AD risk. Fifteen studies investigating the association between IL-10 polymorphisms (-1082, -819, -592) and AD were found and analyzed. The model-free approach was applied to meta-analyze these case-control genetic association studies. Available data suggested an association between -1082 polymorphism and AD risk with a marginal statistical significance (GG versus AG/AA: pooled odds ratio [OR]: 0.82, 95% confidence interval CI: 0.65-1.02) and evidence of a moderate degree of between-study heterogeneity (χ2 = 27.13, d.f. = 13, p = 0.01, I2 = 52%). For the -819 and -592 polymorphisms, we did not find an association with AD, but significant between-study heterogeneity made genotype data pooling unacceptable. Analysis by IL-10 haplotype showed that the -1082G/-819C/-592C haplotype is associated with a lower risk of AD, although with a marginal statistical significance, probably due to the low number of studies included (GCC versus other genotypes: OR: 0.61, 95% CI: 0.32-1.15; I2: 85%). Current findings suggest a possible association between -1082 A > G polymorphism and the risk of developing AD; this effect is more evident in the oldest patients. The high degree of between-study heterogeneity, due to several underpowered studies and to other methodological problems of individual studies underlies the need for further methodologically adequate studies.

Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study.

Identification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naïve) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins (LDL) were indirectly assessed by determining the triglycerides/high-density lipoproteins (HDL) cholesterol ratio. We also assessed by immunohistochemistry Hsp60 levels in oral mucosa of patients and controls. No difference was found in CRP levels or plasma lipids between the two groups, but subjects with periodontitis showed, in comparison to controls, higher levels of small, dense LDL (p = 0.0355) and circulating Hsp60 concentrations (p < 0.0001). However, levels of mucosal Hsp60 did not change significantly between groups. Correlation analysis revealed that circulating Hsp60 inversely correlated with HDL-cholesterol (r = -0.589, p = 0.0039), and positively with triglycerides (r = +0.877, p < 0.0001), and small, dense LDL (r = +0.925, p < 0.0001). Serum Hsp60 significantly correlated with the degree of periodontal disease (r = +0.403, p = 0.0434). In brief, untreated patients with mild periodontitis had increased small, dense LDL and serum Hsp60 concentrations, in comparison to age- and BMI-matched controls and both parameters showed a strong positive correlation. Our data indicate that atherogenic dyslipidemia and elevated circulating Hsp60 tend to be linked and associated to periodontal pathology. Thus, the road is open to investigate the potential value of elevated levels of circulating Hsp60 as predictor of risk for cardiovascular disease when associated to dyslipidemia in periodontitis patients.