The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Soft Tissue Substitutes in Periodontal and Peri-Implant Soft Tissue Augmentation: A Systematic Review

Background: Different extracellular matrix (ECM)-based technologies in periodontal and peri-implant soft tissue augmentation have been proposed in the market. The present review compared the efficacy of soft tissue substitutes (STSs) and autogenous free gingival grafts (FGGs) or connective tissue grafts (CTGs) in mucogingival procedures to increase keratinized tissue (KT) width around teeth and implants. Methods: Two independent examiners performed an electronic search on MEDLINE and the Cochrane Library based on the following PICOS format: (P) adult patients; (I) soft tissue substitutes and FGGs/CTGs; (C) STSs vs. CTGs; STSs vs. FGGs; STSs vs control; (O) KT width gain; (S) systematic reviews, randomized controlled trials. Studies published before November 2023 were included. Results: Around teeth, all biomaterials showed superior performance compared to a coronally advanced flap (CAF) alone for treating gingival recessions. However, when compared to CTGs, acellular dermal matrices (ADMs) yield the most similar outcomes to the gold standard (CTGs), even though in multiple recessions, CTGs continue to be considered the most favorable approach. The use of STSs (acellular matrix or tissue-engineered) in combination with apically positioned flaps (APF) resulted in significantly less gain in KT width compared to that achieved with FGGs and APFs. Around dental implants, free gingival grafts were deemed more effective than soft tissue substitutes in enhancing keratinized mucosa width. Conclusions: Based on the available evidence, questions remain about the alternative use of soft tissue substitutes for conventional grafting procedures using free gingival grafts or connective tissue grafts around teeth and implants