miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease

IntroductionAlpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3′UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease.MethodsFirstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions.ResultsOverexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation.ConclusionOur findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.     

Nodular Fasciitis of the Oral Cavity with Partial Spontaneous Regression (Nodular Fasciitis)

Nodular fasciitis is a lesion found in the subcutaneous fascia that micoscopically presents as a benign proliferation of fibroblasts and myofibroblasts, which may be mistaken for a sarcoma due to clinically rapid growth. Diagnosis is by histopathology and of the immunohistochemical profile. We describe a case of nodular fasciitis in the oral cavity that demonstrated partial spontaneous regression. The patient was a 32-year-old man with a buccal mucosal mass, which had grown rapidly for 45 days. On microscopic examination, the lesion displayed a well-delineated but not encapsulated proliferation of spindle cells, with a nodular growth pattern. Immunohistochemical analysis showed positivity of the spindle cells for the antibodies against smooth muscle actin and muscle-specific actin (HHF-35). Treatment of such lesions typically involves complete conservative excision, but the lesion may regress eventually in the absence of definitive treatment.     

Evidence of psychosomatic influences in compensated and decompensated tinnitus

The purpose of this study was to evaluate the role and interaction of individual factors on decompensated tinnitus. Subjects consisted of 53 adult patients with chronic tinnitus. They were selected and assigned to two groups, compensated (n?=?28) and decompensated (n?=?25), according to the results of an established tinnitus questionnaire. Both groups were evaluated and compared. The patients with decompensated tinnitus suffered from more pronounced social disabilities, were more prone to depression, and used less effective techniques to cope with their illness. They showed a higher degree of somatic multimorbidity, with particularly strong correlations between tinnitus and the incidence of cardiovascular diseases and hypoacusis. As a consequence, in the psychosomatic tinnitus therapy, greater attention should be given to the treatment of the somatic complaints in addition to psychological and psychosocial aspects.     

MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy

ABSTRACT: OBJECTIVE: Explore the role of Major Vault Protein (MVP) in oral cavity squamous cell carcinoma patients.Subjects and Methods131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 [PLUS-MINUS SIGN] 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 [PLUS-MINUS SIGN] 7.74 Gy in 1.8--2 Gy/fraction). MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. RESULTS: MVP expression was positive in 112 patients (85.5 %) and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein) was related to insulin-like growth factor receptor-1 (IGF-1R) expression (P = 0.014). Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp(B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis. CONCLUSIONS: MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.