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Αλέξανδρος Γ. Σφακιανάκης

Wednesday, January 18, 2023

Prediction and validation of microbial community function from normal pulp to pulpitis caused by deep dentinal caries

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

Microbial function changes may be responsible for dental pulp transformation from normal to diseased. However, studies on the prediction and verification of the function of the microbial community in the deep dentine and pulp of caries-induced pulpitis are lacking.

Methods

This study included 171 cases of deep dentinal caries divided into normal pulp (NP), reversible pulpitis (RP), and irreversible pulpitis (IRP). In Experiment I, the microbial-community composition was identified in 111 samples using 16S ribosomal DNA. Function prediction was performed through phylogenetic investigation of communities by PICRUSt prediction and qPCR. In Experiment II, different microbiome functions were confirmed in 60 samples using liquid chromatography-tandem mass spectrometry.

Results

In Experiment I, microbial abundance significantly differed in the IRP group compared to the other two groups. The RP and NP groups had the same microbiome composition, but the predicted functional difference between the RP and NP groups pertained to membrane transport (P<0.010). The predicted functional difference between the IRP and NP groups pertained to amino-acid, co-factor, and vitamin metabolism (P<0.010). In Experiment II, Kyoto Encyclopedia of Genes and Genomes functional annotation revealed that the differential metabolites between the RP and NP groups did not participate in membrane transport; however, the differential metabolites between the IRP and NP groups participated in amino-acid metabolism.

Conclusions

The near-pulp microbiome in RP and NP with deep dentinal caries had the same differential function. However, amino acid metabolism in near the pulp microbial community differed between IRP and NP with deep dentinal caries.

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Βeta‐glucan suppresses high‐fat‐diet‐induced obesity by attenuating dyslipidemia and modulating obesogenic marker expressions in rats

alexandrossfakianakis shared this article with you from Inoreader

Abstract

The current study was designed to evaluate the therapeutic potential of Βeta-glucan (BG) which is a key bioactive compound predominantly present in mushrooms and cereals against high-fat-diet (HFD)-induced obesity, and to understand its mechanism of action. Obesity was induced in rats by supplementing the diet with HFD and BG (40mg/kg bodyweight) for a period of 6 weeks. At the end of the experimental period, the body weight, as well as hyperglycemic, dyslipidemia and obesogenic marker expressions were assessed in the control group and in the experimental obese rats. Administration of BG to obese rats significantly reduced body weight gain and attenuated hyperglycemia which was confirmed by the decreased blood glucose and insulin resistance. At the same time, BG mitigated dyslipidemia by altering expressions of PPAR-γ, SREBP-1c, FAS, HMG-CoA reductase, and Fab-4 in HFD-induced obese rats. In conclusion, this study revealed that BG is a potential candidate to ameliorate HFD-induc ed obesity by modulating obesogenic marker expressions, especially by regulating the master regulator PPAR-γ.

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Impact of peri‐implant soft tissue characteristics on health and esthetics

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objective

To review the impact of key peri-implant soft tissue characteristics on health and esthetics.

Main Considerations

The keratinized mucosa width (KMW), the mucosal thickness (MT), and the supracrestal tissue height (STH) are essential components of the peri-implant soft tissue phenotype. An inadequate KMW (<2 mm) has been associated with local discomfort upon oral hygiene performance and increased risk for the onset of peri-implant diseases. A minimum buccal MT (≥2 mm) is generally required to prevent esthetic issues related to the effect of transmucosal prosthetic elements on the color of the mucosa and can also contribute to long-term mucosal stability. STH is directly related to marginal bone remodeling patterns during the early healing process that follows the connection of transmucosal prosthetic components. Short STH, generally defined as <3 mm, has been consistently associated with marginal bone loss resulting from the physiologic establishment of the mucosal seal. Insufficient STH may also derive into the fabrication of unfavorable transmucosal prosthetic contours, which f requently results in unpleasing esthetic outcomes and predisposes to submarginal biofilm accumulation. Peri-implant soft tissue dehiscences (PISTDs) are a type of peri-implant deformity that are associated with esthetic issues and often occur in sites presenting KMW, MT, and/or STH deficiencies. PISTDs should be correctly diagnosed and treated accordingly, usually by means of multidisciplinary therapy.

Conclusion

Understanding the impact of different dimensional and morphologic features of the peri-implant mucosa on health and esthetic outcomes is fundamental to make appropriate clinical decisions in the context of tooth replacement therapy with implant-supported prostheses.

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vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin.

Objective

To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies.

Design

Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing.

Results

A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline.

Conclusions

For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin.

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Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double strand break repair and augments efficacy of temozolomide in glioblastoma

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Efficient DNA repair in response to standard chemo and radiation therapies often contribute to GBM therapy resistance. Understanding the mechanisms of therapy resistance and identifying the drugs that enhance the therapeutic efficacy of standard therapies may extend the survival of GBM patients. In this study, we investigated the role of KDM1A/LSD1 in DNA double strand break (DSB) repair and combination of KDM1A inhibitor and TMZ in vitro and in vivo using patient derived GSCs.
Methods
Brain-bioavailability of the KDM1A inhibitor (NCD38) was established using LS-MS/MS. Effect of combination of KDM1A knockdown or inhibition with TMZ was studied using cell viability and self-renewal assays. Mechanistic studies were conducted using CUT&Tag-seq, RNA-seq, RT-qPCR, Western blot, HR and NHEJ reporter, immunofluorescence, and comet assays. Or thotopic murine models were used to study efficacy in vivo.
Results
TCGA analysis showed KDM1A is highly expressed in TMZ treated GBM patients. Knockdown or knockout or inhibition of KDM1A enhanced TMZ efficacy in reducing the viability and selfrenewal of GSCs. Pharmacokinetic studies established that NCD38 readily crosses the BBB. CUT&Tag-seq studies showed that KDM1A is enriched at the promoters of DNA repair genes and RNA-seq studies confirmed that KDM1A inhibition reduced their expression. Knockdown or inhibition of KDM1A attenuated HR and NHEJ-mediated DNA repair capacity and enhanced TMZ mediated DNA damage. Combination of KDM1A knockdown or inhibition and TMZ treatment significantly enhanced survival of tumor bearing mice.
Conclusions
Our results provide evidence that KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA DSB repair pathways.
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Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus

alexandrossfakianakis shared this article with you from Inoreader
AbstractCholinergic signaling shapes sound processing and plasticity in the inferior colliculus (IC), the midbrain hub of the central auditory system, but how cholinergic terminals contact and influence individual neuron types in the IC remains largely unknown. Using pharmacology and electrophysiology, we recently found that acetylcholine strongly excites VIP neurons, a class of glutamatergic principal neurons in the IC, by activating α3β4* nicotinic acetylcholine receptors (nAChRs). Here, we confirm and extend these results using tissue from mice of both sexes. First, we show that mRNA encoding α3 and β4 nAChR subunits is expressed in many neurons throughout the IC, including most VIP neurons, suggesting that these subunits, which are rare in the brain, are important mediators of chol...
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Tuesday, January 17, 2023

Vertical ridge augmentation with Ti‐reinforced dense polytetrafluoroethylene (d‐PTFE) membranes or Ti‐meshes and collagen membranes: 3‐year results of a randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

The present study aimed to evaluate hard and soft tissue parameters around implants placed in augmented posterior mandible, comparing Ti-reinforced d-PTFE membranes with Ti-meshes covered with collagen membranes, after 3 years of follow-up.

Materials and Methods

Forty eligible patients were randomly assigned to group A (Ti-reinforced d-PTFE membrane) or group B (mesh covered with collagen membrane) for vertical ridge augmentation (VRA) and simultaneous implants. Implants were evaluated using specific peri-implant parameters for bone and soft tissues: probing pocket depth (PPD), modified plaque index (mPI), bleeding on probing (BoP), modified gingival index (mGI), thickness of keratinized tissue (tKT), width of keratinized tissue (wKT), fornix depth (FD), peri-implant bone level (PBL), interproximal bone peaks (IBP), marginal bone loss (MBL), interproximal bone loss (IBL).

Results

A total of 28 patients with 79 implants were evaluated after 3 years of follow-up. The mean value of MBL was 0.70 mm (group A = 0.73 mm; group B = 0.71 mm), while mean IBL was 0.54 mm (group A = 0.64 mm; group B = 0.40 mm). The treatment with meshes resulted not inferior to PTFE and their clinical results appeared similar. A strong correlation between PBL and IBP was confirmed. Both study groups showed an increase of tKT and wKT values.

Conclusion

In the posterior mandible, VRA using both techniques provides stable PBLs up to 3 years. A correct soft tissue management and a strict professional oral hygiene protocol play a crucial role on peri-implant health over time.

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