Automated Machine Learning to Develop Predictive Models of Metabolic Syndrome in Patients with Periodontal Disease.

Metabolic syndrome is experiencing a concerning and escalating rise in prevalence today. The link between metabolic syndrome and periodontal disease is a highly relevant area of research. Some studies have suggested a bidirectional relationship between metabolic syndrome and periodontal disease, where one condition may exacerbate the other. Furthermore, the existence of periodontal disease among these individuals significantly impacts overall health management. This research focuses on the relationship between periodontal disease and metabolic syndrome, while also incorporating data on general health status and overall well-being. We aimed to develop advanced machine learning models that efficiently identify key predictors of metabolic syndrome, a significant emphasis being placed on thoroughly explaining the predictions generated by the models. We studied a group of 296 patients, hospitalized in SCJU Sibiu, aged between 45-79 years, of which 57% had metabolic syndrome. The patients underwent dental consultations and subsequently responded to a dedicated questionnaire, along with a standard EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire. The following data were recorded: DMFT (Decayed, Missing due to caries, and Filled Teeth), CPI (Community Periodontal Index), periodontal pockets depth, loss of epithelial insertion, bleeding after probing, frequency of tooth brushing, regular dental control, cardiovascular risk, carotid atherosclerosis, and EQ-5D-5L score. We used Automated Machine Learning (AutoML) frameworks to build predictive models in order to determine which of these risk factors exhibits the most robust association with metabolic syndrome. To gain confidence in the results provided by the machine learning models provided by the AutoML pipelines, we used SHapley Additive exPlanations (SHAP) values for the interpretability of these models, from a global and local perspective. The obtained results confirm that the severity of periodontal disease, high cardiovascular risk, and low EQ-5D-5L score have the greatest impact in the occurrence of metabolic syndrome.

Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant.

The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical Candida albicans strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of C. albicans in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.

Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action.

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative.

Molecular markers associated with potentially malignant oral lesions (Review).

According to literature data, potentially premalignant oral lesions are the basis of over 85% of cell carcinomas. Despite multiple advances achieved during the last few decades in the diagnosis and treatment of oral squamous cell carcinomas, there has not been a significant change in the prognosis and 5-year survival rate. The prevention of malignant transformation of these tumors by diagnosis and targeted treatment would be the ideal scenario. These potentially premalignant oral lesions represent an important subject for either the clinical or the research field, due to the higher malignant transformation observed in the last few years at different ages. To date, histopathological examination based on TNM criteria is considered the 'golden standard'. However, this type of examination has its limitation due to staining procedures and photonic microscope examination. Identification of cellular and molecular markers specific to these oral lesions with potentially malignant transformation could lead to early detection, accurate diagnosis, prevention of the development of oral squamous cell carcinoma (OSCC) and facilitate a targeted therapeutic approach. In this review, we focused on a series of molecules that are implicated in the malignant transformation of these lesions and considered potential biomarkers.

Effects of poling and crystallinity on the dielectric properties of Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 at cryogenic temperatures.

The mechanisms underlying the anomalously large, room temperature piezoelectric activity of relaxor-PbTiO3 type single crystals have previously been linked to low temperature relaxations in the piezoelectric and dielectric properties. We investigate the properties of Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 between 10 and 300 K using dielectric permittivity measurements. We compare results on single crystal plates measured in the [001] and [111] directions with a polycrystalline ceramic of the same composition. Poled crystals have very different behaviour to unpoled crystals, whereas the dielectric spectrum of the polycrystalline ceramic changes very little on poling. A large, frequency dependent dielectric relaxation is seen in the poled [001] crystal around 100 K. The relaxation is much less prominent in the [111] cut crystal, and is not present in the polycrystalline ceramic. The unique presence of the large relaxation in poled, [001] oriented crystals indicates that the phenomenon is not due their relaxor nature alone. We propose that heterophase dynamics such as the motion of phase domain boundaries are responsible for both the anomalous electromechanical and dielectric behaviour.

Correlations between morphological changes induced by curcumin and its biological activities.

Curcumin is a phytochemical polyphenol extracted from turmeric rhizome, with multiple biological activities, intensively studied in various therapeutic areas. Its effects covers a wide range of specialties, from the neuroprotective to the antimetastatic properties, influencing pathologies from cardiovascular, neuronal and oncological fields, as a part of its broad spectrum of action. These effects are explained by antioxidant, anti-inflammatory and anticarcinogenic simultaneous roles of curcumin and its derivatives. In this review, we selected the information about morphological evidences correlated with the biological effects on the following organ systems: the central nervous system (including neurological pathology, such as Parkinson's and Alzheimer's disease), the cardiovascular system (including disorders like atherosclerosis, endothelial dysfunction and drug-induced myotoxicity), multiple forms of cancer, and metabolic syndromes including diabetes. The central point of this review was to target a variety of morphological changes at microscopic level induced by curcumin, using different microscopy techniques.

The ultrastructural features of the premalignant oral lesions.

Premalignant oral lesions are among the most important risk factors for the development of oral squamocellular carcinoma. Recent population studies indicate a significant rise in the prevalence of leukoplakia, erythroplakia/erythroleukoplakia, actinic cheilitis, submucous fibrosis and erosive lichen planus. Since standard histopathological examination has numerous limitations regarding the accurate appreciation of potential malignant transformation, the present study aims to aid these evaluations using the transmission electron microscopy (TEM) technique, which emphasizes ultrastructural changes pertaining to this pathology. Oral mucosa fragments collected from 43 patients that were clinically and histopathologically diagnosed with leukoplakia, erosive actinic cheilitis and erosive lichen planus have been processed through the classic technique for the examination using TEM and were examined using a Philips CM100 transmission electron microscope. The electron microscopy study has confirmed the histopathological diagnosis of the tissue samples examined using photonic microscopy and has furthermore revealed a series of ultrastructural details that on the one hand indicate the tendency for malignant transformation, and on the other reveal characteristic features of tumor development. All the details furnished by TEM complete the overall picture of morphological changes, specific to these lesions, indicating the importance of using these techniques in establishing both a correct diagnosis and prognosis.

The molecular mosaic of the premalignant cutaneous lesions.

In the last three decades, the premalignant cutaneous lesions have represented a milestone for the clinicians and the anatomopathologists given the increased risk of malignant transformation not only in the old but also in the young population. Recent research indicates the fact that, though multiple progresses were recorded in the diagnosis and treatment of the cutaneous squamocellular carcinomas, developed in more than 85% of the cases in premalignant lesions, however the prognosis and survival up to five years did not register significant improvements. For the achievement of the diagnosis with certainty, the histopathological examination, considered until recently the "golden standard", principally based on the TNM criterion, has an increased percentage of subjectivity and it is relatively unsure, being known the fact that two apparently identical tumors answer differently to the same therapy. The variability of the morphological aspects from simple dysplasia to in situ carcinomas and the cancers themselves impose the identification of some cellular and molecular markers typical to the premalignant and malignant cutaneous lesions. In this respect, the knowledge and characterization of the molecular mosaic allow the establishment of some clear criterion for an early diagnosis, corresponding monitoring and adequate treatment.

In vitro evaluation of curcumin effects on breast adenocarcinoma 2D and 3D cell cultures.

UNLABELLED: Breast adenocarcinoma cell line MDA-MB-231, even if it expresses low levels of E-cadherin, still readily form multicellular aggregates of cells, namely spheroids. Curcumin is a diarylheptanoid antitumoral drug while it significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. Curcumin photoactivation may enhance antiapoptotic role against cancer cells. AIM: To evaluate the effect of low curcumin concentrations, ranged from 1.9 to 15 µM, with and without photoactivation, using a manufactured 670 nm LED-matrix. A secondary aim was to evaluate the ideal method to produce easy-to-use tumor cell spheroids, comparing two low adherence plate supports. MATERIALS AND METHODS: Breast adenocarcinoma cell line MDA-MB-231 were cultured according to 2D monolayer and 3D spheroid models then submitted to normal and photoactivated curcumin in micromolar concentrations. MTT assay was used to evaluate cell viability following curcumin application on cells. On 2D cell cultures, curcumin inhibits cell tumor development and proliferation at concentrations of 15 µM, with a viability of 65.7% at 48 hours incubation time. A decreased viability up to 25% for a concentration of 15 µM was recorded following photoactivation and cytotoxic action on breast cancer tumor cell line continued at concentrations of 7.5 and 3.75 µM. Curcumin photoactivation increases pro-apoptotic effects in both 2D and 3D tumor cell culture models and also responsiveness to curcumin is slightly reduced in spheroid-like structures. Thus, 3D tumor cell culture systems appear to be the ideal environment for in vitro assays regarding anticancer drug effects on cell viability.