Apoptosis of pro-B lymphocytes induced by NR4A1 activation in the presence of gingival fibroblast exosomes and TNFα, caspase 8, STAT3, and Akt pathways modulators.

There is a lack of data in the mainstream literature regarding the interactions between gingival fibroblasts, as a component of the local niche, and tumor precursors of B-lymphocytes. Although it is known that the development of tumors and tumor precursors depends on the local environment's characteristics. In order to experimentally evaluate the apoptosis of pro-B type lymphocytes, induced as a result of the known activation of orphan nuclear receptor 4A1 (NR4A1), through Cytosporone B (Csn-B, 10 µM), in the presence or absence of exosomes derived from gingival fibroblasts, we administered as a treatment: 1 µM R-7050 [functional inhibitor of tumor necrosis factor alpha (TNFα)], 1 µM Z-IETD-FMK (functional inhibitor of caspase 8), 1 µM GSK690693 (functional inhibitor of Akt 1∕2∕3 pathways) and, last but not least, 1 µM scutellarin [functional inhibitor of receptor activator of nuclear factor-kappa B ligand (RANKL)] and therefore of the signal transducer and activator of transcription 3 (STAT3) pathway. Firstly, it is really clear that the presence of exosomes in the pro-B lymphocytes culture medium amplified the apoptotic effects of 10 µM Csn-B. The inhibition of tumoral precursors development, namely the pro-B type, might be highly dependent on the inhibition of Akt 1∕2∕3 pathways, the first and most important consequence being apoptosis induced by the activation of NR4A1 orphan nuclear receptors.

New Smart Bioactive and Biomimetic Chitosan-Based Hydrogels for Wounds Care Management.

Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels' structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs.

Clinical Assessment of Acute Organophosphorus Pesticide Poisoning in Pediatric Patients Admitted to the Toxicology Emergency Department.

Pesticide poisoning in pediatric patients is still an important reason for presenting to the emergency department in Romania. In this context, the present study aims to raise awareness of the toxicological impact of pesticides on human health in pediatrics. For this purpose, the demographic characteristics, clinical assessment, and outcome of pediatric patients with acute pesticide poisoning admitted to the toxicology department of "Saint Mary" Emergency Children's Hospital from Iasi, were analyzed. This retrospective study focused on the clinical and laboratory data of patients aged under 18 years diagnosed with acute pesticide poisoning between 2010-2020. The statistical analysis was performed using the Statistica 10 package. A total of 49 patients presented with manifestations of acute pesticide poisoning, and the most common pesticide involved was diazinon. The most frequent exposure route was accidentally ingesting pesticide products (95%). The primary clinical manifestations were toxic encephalopathy, coma, depressive disorder, gastric disorders, and respiratory failure. Changes in the glycemic status, liver, and kidney damage were also present. Treatment included decontamination, administration of antidote, supportive care, and recommendations to be closely monitored to avoid a new incident. These results highlight the toxic potential of pesticides on human health and their biological consequences, which require an increase in consciousness of the precautions imposed on their use, especially when children are nearby.

The Impact of the Storage Conditions and Type of Clearomizers on the Increase of Heavy Metal Levels in Electronic Cigarette Liquids Retailed in Romania.

The growing popularity of electronic cigarettes has raised several public health concerns, including the risks associated with heavy metals exposure via e-liquids and vapors. The purpose of this study was to determine, using atomic absorption spectrometry, the concentrations of Pb, Ni, Zn, and Co in some commercially available e-liquid samples from Romania immediately after purchase and after storage in clearomizers. Lead and zinc were found in all investigated samples before storage. The initial concentrations of Pb ranged from 0.13 to 0.26 mg L-1, while Zn concentrations were between 0.04 and 0.07 mg L-1. Traces of nickel appeared in all investigated e-liquids before storage but in very small amounts (0.01-0.02 mg L-1). Co was below the detection limits. We investigated the influence of the storage period (1, 3, and 5 days), storage temperature (22 °C and 40 °C), and type of clearomizer. In most cases, the temperature rise and storage period increase were associated with higher concentrations of heavy metals. This confirms that storage conditions can affect metal transfer and suggests that the temperature of storage is another parameter that can influence this phenomenon.

Apiaceae Essential Oils: Boosters of Terbinafine Activity against Dermatophytes and Potent Anti-Inflammatory Effectors.

Dermatophyte infections represent an important public health concern, affecting up to 25% of the world's population. Trichophyton rubrum and T. mentagrophytes are the predominant dermatophytes in cutaneous infections, with a prevalence accounting for 70% of dermatophytoses. Although terbinafine represents the preferred treatment, its clinical use is hampered by side effects, drug-drug interactions, and the emergence of resistant clinical isolates. Combination therapy, associating terbinafine and essential oils (EOs), represents a promising strategy in the treatment of dermatophytosis. In this study, we screened the potential of selected Apiaceae EOs (ajowan, coriander, caraway, and anise) to improve the antifungal activity of terbinafine against T. rubrum ATCC 28188 and T. mentagrophytes ATCC 9533. The chemical profile of EOs was analyzed by gas chromatography. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of EOs/main compounds were determined according to EUCAST-AFST guidelines, with minor modifications. The checkerboard microtiter method was used to identify putative synergistic combinations of EOs/main constituents with terbinafine. The influence of EOs on the viability and pro-inflammatory cytokine production (IL-1ß, IL-8 and TNF-α) was determined using an ex vivo human neutrophils model. The binary associations of tested EOs with terbinafine were found to be synergistic against T. rubrum, with FICI values of 0.26-0.31. At the tested concentrations (6.25-25 mg/L), EOs did not exert cytotoxic effects towards human neutrophils. Anise EO was the most potent inhibitor of IL-1ß release (46.49% inhibition at 25 mg/L), while coriander EO displayed the highest inhibition towards IL-8 and TNF-α production (54.15% and 54.91%, respectively). In conclusion, the synergistic combinations of terbinafine and investigated Apiaceae EOs could be a starting point in the development of novel topical therapies against T. rubrum-related dermatophytosis.

Experimental EDX analysis of different periodontal splinting systems.

Physiological/normal tooth mobility may be defined as the slight displacement of the clinical crown of a tooth, which is allowed by the resilience of an intact and healthy periodontium, under the application of a moderate force. The factors influencing the success and longevity of dental splinting are the type of material used for the splint, the type of composite resin, the number and location of the dental units included for splinting (maxillary or mandibular arch). In periodontology, the term 'splint' is defined as the joining of two or more teeth into a rigid unit through restorations or fixed or removable devices. The purpose of using periodontal splints for tooth immobilization is to provide a period of rest in the areas where the healing process has begun and to allow normal functioning there where the tissues alone would not be able to withstand occlusal forces. The aim of the present study was to evaluate comparatively, by means of energy dispersive electron spectrometry (EDX), the chemical composition in the case of in vitro samples that structurally reproduce direct periodontal immobilization systems using fiberglass strips and fluid composite resins. The differences in the chemical composition of the investigated materials can influence their physiochemical properties, but also their biological and toxicological reliability. Elements such as C, O, Al, Si and Ba were identified as common elements among the resins tested in the present study. The only difference in terms of the component elements was found in the case of the fluid composite Clearfil Majesty ES Flow, which, apart from the elements mentioned, also presented Co in its structure.

Unravelling the potential of seaweeds from the Black Sea coast of Romania as bioactive compounds sources. Part I: Cystoseira barbata (Stackhouse) C. Agardh.

The Romanian coastlines of the Black Sea have abundant seaweed resources, but little effort has been done to investigate their biological potential. The aim of the present study was to assess the in vitro antioxidant and anti-proliferative effects of Cystoseira barbata (Stackhouse) C. Agardh (Sargassaceae), a brown alga inhabiting the Black Sea coast of Romania. The 70% acetone, methanol and water extracts of C. barbata were evaluated for their total phenolic content, antioxidant activity and anti-proliferative potential against human tumor cell lines (pulmonary A549, colon HT-29, mammary MCF-7) and the non-tumor mammary epithelial MCF-10A cell line. C. barbata 70% acetone extract (CBAE) displayed the highest antioxidant and cytotoxic activities. The mechanism of CBAE anti-proliferative activity involved initially increased intracellular ROS accumulation, followed by increased DNA content in the subG1 phase and DNA fragmentation leading to excessive apoptosis. Thus, our study provides a theoretical basis for the use of CBAE as a tumor preventive agent. Furthermore, UHPLC-DAD-QTOF-MS analysis of CBAE tentatively identified 18 phlorotannins as fucophlorethol and eckol derivatives, containing three up to seven phloroglucinol units. In conclusion, C. barbata represents a valuable source for the development of macroalgal-based products with putative use as nutraceuticals and pharmaceuticals.

Antioxidant Activity of Essential Oil From Carum Carvi L. Cultivated in North-Eastern Romania.

Essential oils have significant antioxidant activity, being used frequently as preservatives in the food and cosmetic industries. Aim: To assess the in vitro antioxidant activity of essential oil from Carum carvi L. (caraway) cultivated in northeastern Romania. Materials and Methods: The essential oil was isolated by hydrodistillation from dried caraway fruits. The chemical composition was investigated by gas chromatography and gas chromatography­mass spectrometry analyses. Antioxidant activity was evaluated by three different in vitro antioxidant assays (DPPH∙ and ABTS•+ scavenging and reducing power assays). Butylhydroxyanisole was used as reference standard. Results and Discussion: Carvone was the major compound of essential oil of caraway fruits (48.53%), followed by limonene (44.42%). Evaluation of the antioxidant activity (DPPH∙and ABTS•+ scavenging activity and reducing power) revealed significant effects, with IC50 values of 46.51 ± 1.61 µg/mL, 5.34 ± 0.07 µg/mL and 7.64 ± 0.22 µg/mL, respectively, as compared to those of the reference standard, butylhydroxyanisole (6.09 ± 0.27 µg/mL, 1.49 ± 0.00 µg/mL and 3.39 ± 0.07 µg/mL, respectively). Conclusions: Essential oil of Carum carvi cultivated in northeastern Romania belongs to carvone chemotype. Due to its high antioxidant activity it might be a potential alternative to conventional preservatives in the food, cosmetic and pharmaceutical industries.

ANTIOXIDANT AND PHYTOBIOLOGICAL STUDIES ON TWO ALLIUM CEPA L. EXTRACTS.

AIM: To investigate the antioxidant potential of two Allium cepa L. extracts. MATERIAL AND METHODS: The antioxidant activity of the two extracts (encoded EC1 and EC2) was assessed using two methods: DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging capacity and determination of their reducing power; phytobiological, studies were performed using grains of Triticum aestivum L., Falmura variety. RESULTS AND DISCUSSIONS: EC1 and EC2 extracts had a particular affinity for binding DPPH radicals. At equivalent concentrations, the reducing power of EClextract was about 2 times higher compared to EC2, increasing with the concentration of the analyzed sample. The phytobiological study demonstrated that the investigated extracts had no cytotoxic and genotoxic potential.

α,ß-DIBROMOCHALCONE DERIVATIVES--SYNTHESIS AND ANTIMICROBIAL ACTIVITY.

AIM: To obtain some chalcones and their dibrominated analogues and to evaluate their antimicrobial potential. MATERIAL AND METHODS: Eight chalcones were synthesized using the Claisen-Schmidt condensation of acetophenone/4-bromo-acetophenone and different benzaldehyde derivatives. These chalcones were further brominated using two different bromination agents: molecular bromine and pyridinium tribromide. The antimicrobial activity was tested using the disk diffusion method. RESULTS AND DISCUSSIONS: The classical bromination technique was compared to the eco-friendly one using pyridinium tribromide. Pyridinium tribromide bromination did not improve the reaction yields (except for one compound), but it had the advantage of being a stable, non-corrosive and non-toxic salt. The results of the antimicrobial assessment indicated that the bromination of the double bond slightly increased the antimicrobial potential in some cases, but the results obtained during the antimicrobial evaluation were modest, some of the derivatives being active especially on Sarcina lutea ATCC 9341 and Bacillus cereus ATCC 14579. CONCLUSIONS: In this study, eight chalcones and their dibrominated analogues were synthesized, four of the α,ß-dibromochalcones being reported for the first time. Pyridinium tribromide was used as an alternative for liquid bromine, the main advantage of this method being related to the reduced toxicity of the reagents. The synthesized compounds did not exhibit a very good antimicrobial potential.

[Antimicrobial activity of some cinnamic acid derivatives]. / Evaluarea actiunii antimicrobiene a unor derivati de acid cinamic.

Due to drug-resistance phenomenon, there is a constant need for discovering new antiinfectious agents. A series of cinnamic acid derivatives was synthesized and then brominated with bromine in the presence of chloroform or acetic acid. The structure of the new compounds was confirmed by elemental and spectral data. Their antimicrobial activity was tested by disc-diffusion method. The tested compounds had mainly antifungal activity and were moderately active against Gram-positive bacteria. Bromination of the double bond determined the enhancement of the antimicrobial activity for all the tested compounds.