Metformin alters peripheral blood mononuclear cells (PBMC) senescence biomarkers gene expression in type 2 diabetic patients.

BACKGROUND: Although there is increasing evidence showing that cell senescence is increased in circulating PBMC in type 2 diabetes mellitus (T2DM), the data are contradictory. This study examined several senescence biomarkers, including LMNA/C transcript variants, p16INK4a, p53, and p21Cip1/WAF, in PBMC of T2DM patients and the effect of Metformin on these senescence markers. METHODS: Blood samples were obtained from 30 lean, 30 obese, 20 newly diagnosed type 2 diabetes mellitus (T2DM), and 30 T2DM on Metformin. PBMC were isolated and mRNA expression of the senescence biomarkers were quantified by RT-qPCR. The effect of ectopic expression of LMNA and LMNC in human monocytic cells lines (THP-1 and U937) on several inflammatory mediators were also examined. RESULTS: LMNA expression was significantly higher in PBMC of obese and T2DM patients. LMNC expression was significantly inhibited in T2DM patients. LMNAΔ10 and Progerin mRNA expression was not detected in PBMC of all groups. Expression of p16INK4a, p21Cip1/WAF and p53 were inhibited significantly in T2DM. Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels. Upregulation of LMNA in monocytic THP-1 and U937 cell lines induced CD68, TNFα, CCL2, IL-6 and NOS2. CONCLUSIONS: These data support the notion that LMNA may mediate senescence in PBMCs of T2DM by upregulating inflammatory pathways. Metformin may exert its anti-inflammatory property by modulation of senescence mediator LMNA.

Middle ear odontoma: A case report and review of the literature.

INTRODUCTION: Odontomas are benign neoplasms originating from odontogenic tissues. Most of these masses are asymptomatic and can only be diagnosed correctly via radiological studies. Treatment of choice for management of odontoma involves surgical excision to prevent secondary complications and result in a favourable prognosis. CASE PRESENTATION: This paper presents a rare case of odontoma of the middle ear in a four-year-old girl. The mass caused unilateral conductive hearing loss and facial nerve entrapment. We shed light on the typically vague clinical presentations of odontomas, as well as the available options in terms of diagnostic imaging modalities and their outcomes. Standard management of odontoma was followed to improve prognosis and avoid relapse. The aim of highlighting this case is to report on unique clinical, radiographical, and histological findings. DISCUSSION: Retrotympanic odontomas are extremely rare. Only five cases in the English-language literature have investigated such an incident. All of the reviewed cases were asymptomatic and discovered only using radiological evidence. Two cases were managed surgically while the remainder were conservatively managed. CONCLUSION: In five of the six cases mentioned in the English-language literature (including this paper), odontomas occurred in the first decade of life, with an obvious female predilection. In one case, odontoma occurred in the third decade of life. Although odontoma is marked by its frequently benign origin, the absence of symptoms, and the necessity of surgical intervention, further studies are needed to analyse the different clinical pictures, and to allow these to add to what is currently known.