Fibroblasts Collagen Production and Histological Alterations in Hereditary Gingival Fibromatosis

Hereditary gingival fibromatosis is a disorder for which the etiology remains unknown. We aimed to evaluate the fibroblasts and histological alterations to give new clues. A father and a daughter of a family showing gingival hereditary fibromatosis were treated, and gingival biopsies were obtained. A histological study revealed dense fibrous tissue, basal lamina disruption, and epithelial cell migration into the connective tissue. Fibroblasts were cultured from the father and daughter and compared with those from a healthy control patient. The results of the biochemical analysis showed increased collagen synthesis, reduced antioxidant CoQ10 content, and high levels of lipid peroxidation. Additionally, fibroblasts culture incubation with the oxidant H2O2 increased collagen levels that have been reduced by the addition of the antioxidant CoQ10. We conclude that some fibroblasts metabolic alterations play a significant role in initiating and maintaining persistent fibrotic tissue. Oxidative stress influences the fibroblasts collagen production and could play a particular role in the pathogenesis of hereditary gingival fibromatosis

Incidence of Peri-Implantitis and Relationship with Different Conditions: A Retrospective Study

Articles on the prevalence of peri-implant diseases showed that 90% of peri-implant tissues had some form of inflammatory response and a prevalence of peri-implantitis from 28% to 51% according to various publications. Objective: To provide an overview of how risk factors can be related with peri-implantitis. Methods: A retrospective longitudinal study including 555 implants placed in 132 patients was evaluated based on the presence of peri-implantitis following the criteria of Renvert et al. 2018. Results: In total, 21 patients (15.9%) suffered peri-implantitis (PPG) and 111 patients (84.1%) did not suffer peri-implantitis (NPG). The results reveal that smokers have a high incidence of peri-implantitis (72.7%) compared to non-smokers (27.3%) (p < 0.0005). Another variable with significant results (p < 0.01) was periodontitis: 50% PPG and 23.9% NPG suffered advanced periodontitis. Systemic diseases such as arterial hypertension, diabetes mellitus, osteoporosis, and cardiovascular diseases do not show a statistically significant influence on the incidence of peri-implantitis. Patients who did not attend their maintenance therapy appointment had an incidence of peri-implantitis of 61.4%, compared to 27.3% in those who attend (p < 0.0001). From the results obtained, we can conclude that relevant factors affect peri-implantitis, such as tobacco habits, moderate and severe periodontitis, and attendance in maintenance therapy

Strawberry tree honey in combination with 5-fluorouracil enhances chemosensitivity in human colon adenocarcinoma cells

The authors would like to thank Prof. Gavino Sanna, Department of Chemistry and Pharmacy (University of Sassari, Italy), for providing STH samples. Tamara Y. Forbes-Hernandez is supported by a "Juan de la Cierva-Formacion" post-doctoral contract.Colorectal cancer remains a challenging health burden worldwide. This study aimed to assess the potentiality of Strawberry tree honey (STH), a polyphenol-enriched food, to increase the effectiveness of 5-Fluorouracil (5-FU) in adenocarcinoma (HCT-116) and metastatic (LoVo) colon cancer cell lines. The combined treatment reduced cell viability and caused oxidative stress, by increasing oxidative biomarkers and decreasing antioxidant defence, in a more potent way compared to 5-FU alone. The expression of endoplasmic reticulum (ATF-6, XBP-1) and MAPK (p-p38 MAPK, p-ERK1/2) markers were also elevated after the combined treatment, enhancing the cell cycle arrest through the modulation of regulatory genes (i.e., cyclins and CDKs). Apoptotic gene (i.e., caspases) expressions were also increased after the combined treatment, while those of proliferation (i.e., EGFR), cell migration, invasion (i.e., matrix metallopeptidase) and epithelial–mesenchymal transition (N-cadherin, β-catenin) were suppressed. Finally, the combined treatment led cell metabolism towards a quiescent stage, by reducing mitochondrial respiration and glycolysis. In conclusion, this work represents an initial step to highlight the possibility to use STH in combination with 5-FU in the treatment of colon cancer, even if further in vitro an in vivo studies are strongly needed to confirm the possible chemo-sensitizing effects of STH."Juan de la Cierva-Formacion" post-doctoral contrac

Inhibition of the NLRP3 inflammasome prevents ovarian aging

Inflammation is a hallmark of aging and is negatively affecting female fertility. In this study, we evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in WT mice during reproductive aging. High expression of NLRP3, caspase-1, and IL-1β was also observed in granulosa cells from patients with ovarian insufficiency. Ablation of NLRP3 improved the survival and pregnancy rates and increased anti-Müllerian hormone levels and autophagy rates in ovaries. Deficiency of NLRP3 also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility

Potential role of the mitochondria for the dermatological treatment of Papillon-Lefèvre

The Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS

Potential Role of the Mitochondria for the Dermatological Treatment of Papillon-Lefèvre

The Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS.This research was funded by by a grant from the Andalusian regional government (Grupo de Investigacion Junta de Andalucia CTS113).Ye