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Aberrant PI3K/AKT/mTOR/ pathway have been considered one of the starting points of various types of human cancer, including the oral squamous cell carcinoma (OSCC). The important role played by this signaling pathway in oncogenesis and cancer evolution, oriented the researchers’ attention toward studies of AKT and the PI3K/AKT/mTOR axis in the context of malignant transformation of oral precancerous lesions. Consequently, this article’s aim is an update of the possible key role played by the PI3K /AKT/mTOR axis on the oral lesions’ malignant transformation stage. Oral potentially malignant disorders are defined as lesions that will most probably progress to malignant lesions of the oral cavity. These lesions are mainly represented by leukoplakia, erythroplakia, actinic cheilitis and lichen planus. PI3K/AKT/mTOR signaling cascade should be regarded as a crucial subject for additional research, focusing not only on the early identification of malignant transformations of oral lesions, but also on opening new therapeutic ways in order to prevent malignant transformation and OSCC evolution.

Aim of the study In this study, we aimed to provide more experimental data regarding the possible cytotoxic effects of two types of PMMA-based resin samples (CAD/CAM milled and 3D-printed) on human oral squamous carcinoma cells. Furthermore, we have also explored the possible alterations of the Akt pathway and its downstream target, apoptosis, in the exposed cells to the two types of resin samples. During the last few years, PMMA-based materials have been extensively explored and modified in order to obtain the desired and ideal properties for dentistry applications. However, there are certain unsolved issues regarding the PMMA-based obturators, including possible cytotoxicity due to the residual monomers. As far as we know there are no studies targeting the Akt/mTOR signalling pathway in the human oral squamous carcinoma cells, exposed to PMMA-based resins used for maxillary obturator manufacturing. Material and methods 25 samples of PMMA- based resin were printed with SHERAeco-print 30 resin using Digital Light Processing (DLP) technique. The resin was layered with a thickness of 50 μm. The Human Oral Squamous Carcinoma Cell Line (OECM-1 cell line) were cultured in a humidified atmosphere at 37 degrees Celsius and 5% carbon dioxide. Results Our results showed that the exposure of OECM-1cells to two types of PMMA-based dental resins induced cytotoxic effects, probably via a residual monomer-induced overproduction of ROS, triggering the decrement of cell viability. Furthermore, exposure to the PMMA-based resins disturbed the Akt/mTOR/GSK-3 signaling pathway compared to the unexposed control cells. Moreover, our results might suggest that the noticed decreased cell viability should be attributed to the activation of apoptosis, via a detouring signaling pathway, possibly orchestrated by Bcl-2. Conclusion Within the limitations of the present in vitro study, our results surprisingly revealed that exposure of OECM-1cells to the two types of PMMA-based dental resins (MA-CAD/CAM and MA-3D printed) induced cytotoxic effects and reduced cell viability probably by activation of apoptosis. Due to the experimental limitations of the present study, our data must be considered preliminary.

Background and Aims: Postoperative recurrence in Crohn’s disease remains a significant clinical challenge, with high recurrence rates despite advancements in medical therapy. This study aims to evaluate the efficacy of various treatments for managing postoperative recurrence following ileocolonic resection in Crohn’s disease. Methods: A comprehensive search of PubMed, Cochrane, and Scopus databases was performed to identify studies reporting on the therapeutic management of postoperative recurrence in Crohn’s disease. Studies encompassing patients with an endoscopic Rutgeerts score of at least I2 were included. Results: Ustekinumab showed promise, achieving significant endoscopic and clinical success in difficult-to-treat patients. Anti-TNF agents demonstrated superior endoscopic and clinical remission rates compared to mesalamine and azathioprine. Retreatment with anti-TNF therapy remained effective even after preoperative failure. Thalidomide showed efficacy in refractory Crohn’s disease, but carries significant toxicity risks, necessitating careful patient selection and monitoring. Combination therapies and non-pharmacologic strategies like enteral nutrition offer additional options, though patient compliance remains challenging. Conclusions: Personalized treatment plans based on individual risk factors and biomarkers are crucial. Infliximab is recommended as the first-line treatment, with ustekinumab and vedolizumab as alternatives in case of anti-TNF failure or intolerance. Early intervention, patient education, and ongoing evaluation are essential for optimizing long-term outcomes in managing postoperative recurrence in Crohn’s disease.

(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected 1855 patients from the Bucharest Acute Pancreatitis Index (BUC-API) who presented with acute pancreatitis. We investigated correlations between Alcoholic Acute Pancreatitis (AAP) and the rate of complications, cost, length of hospitalization and rate of recurrence. (3) Results: We found a moderately strong association between AAP and recurrence (p < 0.01) and observed that the disease is likelier to evolve with pseudocysts and walled-off necrosis than other forms of AP. Patients with AAP are less likely to have a morphologically normal pancreas than patients suffering from AP of other causes (p < 0.01), but a low probability of requiring intensive care unit admission (p < 0.01) significantly lowers daily cost (Md = 154.7 EUR compared to Md = 204.4 EUR) (p < 0.01). (4) Conclusions: This study’s data show that patients with AAP have a greater rate of pseudocyst occurrence, lower intensive care unit admittance rate and lower cost of hospitalization than patients with AP of other causes. Typical Sketch: A middle-aged male tobacco smoker with recurrent AP, lower risk of in-hospital mortality and complications such as pseudocysts; treated in a gastroenterological ward and discharged at-will.

(1) Background: Hypertriglyceridemia (HTG) is a well-known metabolic condition associated with an increased risk of acute pancreatitis. In this study, we tried to establish whether there are any significant disparities concerning recurrence rate, intensive care unit (ICU) admission, hospital (ICU and total) length of stay (LoS), morphology, severity and age between HTG-induced acute pancreatitis and any other known cause of pancreatitis (OAP). (2) Methods: The research was a retrospective unicentric cohort study, using information from the Bucharest Acute Pancreatitis Index (BUC-API) registry, a database of 1855 consecutive cases of acute pancreatitis. (3) Results: We found a weak association between HTG-AP and recurrence. The HTG-AP patients were younger, with a median of 44.5 years, and had a longer ICU stay than the OAP patients. In addition, we identified that the HTG-AP patients were more likely to develop acute peripancreatic fluid collection (APFC), to be admitted in ICU, to have a more severe course of disease and to be cared for in a gastroenterology ward. (4) Conclusions: Hypertriglyceridemia-induced APs have a more severe course. The typical patient with HTG-AP is a middle-aged male, with previous episodes of AP, admitted in the gastroenterology ward, with a longer ICU stay and longer length of hospitalization, more likely to evolve in a severe acute pancreatitis (SAP) and with a higher probability of developing APFC.

A γ-ray spectroscopic study of 10B is reported. Excited states in 10B were populated in inelastic proton scattering and their γ-decays were measured with the ELIFANT array, a state-of-the-art spectrometer with large volume LaBr3:Ce and CeBr3 detectors placed in anti-Compton shields and having unprecedented efficiency for high-energy γ rays. A few weak transitions were observed in the experiment, namely M3 transition between Jπ, T = 0+1, 1 isobaric analog state to the Jπ, T = 3+1,0 ground state and E2 transition between the Jπ, T = 2+1,0 state and the isobaric analog state. The results are compared to a new set of ab initio no-core shell model calculation using the newest version of the local position-space chiral N3LO nucleon-nucleon interaction, which correctly reproduces the spectrum of the excited states in 10B, a problem of the theory in previous years.

In this article, we present a method to obtain equations of non-degenerate conics in an initial Cartesian frame (xOy), starting from their canonical expressions in another Cartesian frame (x′′Cy′′).

Cotinus coggygria Scop. (smoketree) and Fragaria × ananassa Duch. (strawberry) are two industrially important species due to their composition in bioactive compounds. In this study, we investigated the effects of acute low-dose gamma irradiation (15, 20, 25, 30, 35 and 40 Gy) on two red callus cultures established in smoketree and strawberry. The biomass production, dry weight, content of phenols, flavonoids, monomeric anthocyanins’, index of anthocyanins polymerization and antioxidant activity were evaluated. For the smoketree callus, a negative correlation between irradiation doses and callus biomass accumulation was observed. For the strawberry callus, irradiation did not significantly affect the accumulation of the biomass. An increased dry weight was observed in irradiated smoketree callus, while for treated strawberry callus, a decrease was recorded. Irradiation with 30 Gy was stimulative for polyphenols’ accumulation in both cultures; however, the increase was significant only in the strawberry callus. The flavonoids increased in the 30 Gy strawberry variants, while it significantly decreased in smoketree callus irradiated with 35 and 40 Gy. In irradiated strawberry callus, except for the 25 Gy variant (1.65 ± 0.4 mg C-3-GE/g DW), all treatments caused an increase in anthocyanins’ accumulation. In smoketree, except for the 15 Gy variant (2.14 ± 0.66 mg C-3-GE/g DW), the irradiation determined an increase in anthocyanins synthesis, with the highest value being seen in the 20 Gy variant (2.8 ± 0.94 mg C-3-GE/g DW). According to UPLC-HRMS investigations, an unidentified compound increased by 99% at the 30 Gy dose in strawberry callus, while in smoketree, maslinic acid increased by 51% after irradiation with 40 Gy. The results of this study showed, for the first time, the differential response of two performant callus cultures to low-dose gamma irradiation, a biotechnological method that can be used to stimulate the synthesis of important flavonoids and triterpenes.

Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood–brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications. Mainly, we review the latest developments of brain-on-a-chip, BBB-on-a-chip, and NVU-on-a-chip devices and their use as testing platforms for high-throughput pharmacological screening. In particular, we analyze the most important contributions of these studies in the field of neurodegenerative diseases and their relevance in translational personalized medicine.

Abstract Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional characterization in mouse brain endothelium is lacking. Here, we show that all muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells. The mRNA expression of M2, M3, and M5 correlates with their respective protein abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels. Acetylcholine activates calcium transients in brain endothelium via muscarinic, but not nicotinic, receptors. Moreover, although M1 and M3 are the most abundant receptors, only a small fraction of M1 is present in the plasma membrane and functions in ACh-induced Ca2+ signaling. Bioinformatic analyses performed on eukaryotic muscarinic receptors demonstrate a high degree of conservation of the orthosteric binding site and a great variability of the allosteric site. In line with previous studies, this result indicates muscarinic acetylcholine receptors as potential pharmacological targets in future translational studies. We argue that research on drug development should especially focus on the allosteric binding sites of the M1 and M3 receptors.

Air transport is an essential part of the international society, constituting a liaison between people and continents and an important contributor to the world economy and globalization. Aircraft operation has grown in complexity needing for a safety level to be maintained and constantly grown. Along with the development of the aviation industry, the legal system in the aviation field has registered significant challenges, one of them being the claims related to air crashes which are contested. The investigation process of an accident or incident has become not only important for the safety of operations but also to the establishment of legal fault and blame. The article proposes to present the principles of conducting and accident and incident investigation, the value of the report and new developments in relation to the recent case law on the use of the accident investigation report in Court.

Antimicrobial peptides (AMPs) are a class of molecules widely used in applications on eukaryotic and prokaryotic cells. Independent of the peptide target, all of them need to first pass or interact with the plasma membrane of the cells. In order to have a better image of the peptide action mechanism with respect to the particular features of the membrane it is necessary to better understand the changes induced by AMPs in the membranes. Laurdan, a lipid membrane probe sensitive to polarity changes in the environment, is used in this study for assessing changes induced by melittin, a well-known peptide, both in model and natural lipid membranes. More importantly, we showed that generalized polarization (GP) values are not always efficient or sufficient to properly characterize the changes in the membrane. We proved that a better method to investigate these changes is to use the previously described log-normal deconvolution allowing us to infer other parameters: the difference between the relative areas of elementary peak (ΔSr), and the ratio of elementary peaks areas (Rs). Melittin induced a slight decrease in local membrane fluidity in homogeneous lipid membranes. The addition of cholesterol stabilizes the membrane more in the presence of melittin. An opposite response was observed in the case of heterogeneous lipid membranes in cells, the local order of lipids being diminished. RS proved to be the most sensitive parameter characterizing the local membrane order, allowing us to distinguish among the responses to melittin of both classes of membrane we investigated (liposomes and cellular membranes). Molecular simulation of the melittin pore in homogeneous lipid bilayer suggests that lipids are more closely packed in the proximity of the melittin pore (a smaller area per lipid), supporting the experimental observation.

Background and objectives: In the last few years, graphene oxide has attracted much attention in biomedical applications due to its unique physico-chemical properties and can be used as a carrier for both hydrophilic and/or hydrophobic biomolecules. The purpose of this paper was to synthesize graphene oxide and to obtain multifunctional platforms based on graphene oxide as a nanocarrier loaded with few biologically active substances with anticancer, antimicrobial or anti-inflammatory properties such as gallic acid, caffeic acid, limonene and nutmeg and cembra pine essential oils. Materials and Methods: Graphene oxide was obtained according to the method developed by Hummers and further loaded with biologically active agents. The obtained platforms were characterized using FTIR, HPLC, TGA, SEM, TEM and Raman spectroscopy. Results: Gallic acid released 80% within 10 days but all the other biologically active agents did not release because their affinity for the graphene oxide support was higher than that of the phosphate buffer solution. SEM characterization showed the formation of nanosheets and a slight increase in the degree of agglomeration of the particles. The ratio I2D/IG for all samples was between 0.18 for GO-cembra pine and 0.27 for GO-limonene, indicating that the GO materials were in the form of multilayers. The individual GO sheets were found to have less than 20 µm, the thickness of GO was estimated to be ~4 nm and an interlayer spacing of about 2.12 Å. Raman spectroscopy indicated that the bioactive substances were adsorbed on the surface and no degradation occurred during loading. Conclusions: These findings encourage this research to further explore, both in vitro and in vivo, the biological activities of bioactive agents for their use in medicine.

Absolute cross sections for the 86Sr(α,n)89Zr reaction at energies close to the Gamow window are reported. Three thin SrF2 targets were irradiated using the 9 MV Tandem facility in IFIN-HH Bucharest that delivered α beams for the activation process. Two high-purity Germanium detectors were used to measure the induced activity of 89Zr in a low background environment. The experimental results are in very good agreement with Hauser-Feshbach statistical model calculations performed with the TALYS code.

Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU) has been recently proposed. In particular, the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB), two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.

(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected 1855 patients from the Bucharest Acute Pancreatitis Index (BUC-API) who presented with acute pancreatitis. We investigated correlations between Alcoholic Acute Pancreatitis (AAP) and the rate of complications, cost, length of hospitalization and rate of recurrence. (3) Results: We found a moderately strong association between AAP and recurrence (p < 0.01) and observed that the disease is likelier to evolve with pseudocysts and walled-off necrosis than other forms of AP. Patients with AAP are less likely to have a morphologically normal pancreas than patients suffering from AP of other causes (p < 0.01), but a low probability of requiring intensive care unit admission (p < 0.01) significantly lowers daily cost (Md = 154.7 EUR compared to Md = 204.4 EUR) (p < 0.01). (4) Conclusions: This study's data show that patients with AAP have a greater rate of pseudocyst occurrence, lower intensive care unit admittance rate and lower cost of hospitalization than patients with AP of other causes. Typical Sketch: A middle-aged male tobacco smoker with recurrent AP, lower risk of in-hospital mortality and complications such as pseudocysts; treated in a gastroenterological ward and discharged at-will. [ABSTRACT FROM AUTHOR]

This article, published in the Romanian Journal of Oral Rehabilitation, explores the role of the PI3K/AKT/MTOR signaling pathway in the malignant transformation of oral lesions. The authors emphasize the importance of studying this pathway in the context of oral potentially malignant disorders, such as leukoplakia, erythroplakia, actinic cheilitis, and lichen planus. They call for further research to identify early signs of malignant transformation and develop new therapeutic approaches. The article provides an overview of different types of oral potentially malignant disorders and their association with oral cancer. The authors also discuss the potential precancerous nature of oral lichen planus and other oral conditions. The PI3K/AKT/mTOR signaling pathway is highlighted as a key player in malignant transformation, and its abnormal activation has been observed in various oral lesions. The article emphasizes the need for more research on this signaling cascade to identify early malignant transformations and improve treatment strategies for oral potentially malignant disorders. The document is a compilation of various articles and studies on oral diseases and conditions, including oral erythroplakia, oral squamous cell carcinoma, oral lichen planus, actinic cheilitis, and chronic graft-versus-host disease. It discusses the clinical features, prognosis, risk factors, and potential molecular mechanisms associated with these conditions. The phosphatidylinositol 3-kinase/Akt signaling pathway is highlighted as a potential target for cancer therapy. The document also explores the role of aut [Extracted from the article]

This article, published in the Romanian Journal of Oral Rehabilitation, examines the cytotoxicity of milled and 3D-printed PMMA-based resins on oral squamous cancer cells. The study finds that exposure to these resins leads to cytotoxic effects and reduced cell viability, potentially through the activation of apoptosis. The article emphasizes the need for further research in this area and acknowledges the limitations of the study. It also suggests the development of resin-based maxillary obturators to inhibit the growth of residual malignant cells after tumor resection. [Extracted from the article]

Lay Summary: Surgical technique is essential to ensure safe minimally invasive adrenalectomy. Due to the relative rarity of adrenal surgery, it is challenging to ensure adequate exposure in surgical training. Surgical video analysis supports auto-evaluation, expert assessment and could be a target for automatization. The developed ontology was validated by a European expert consensus and is applicable across the surgical techniques encountered in all participating centres, with an exemplary demonstration in bi-centric recordings. Standardization of adrenalectomy video analysis may foster surgical training and enable machine learning training for automated safety alerts. [ABSTRACT FROM AUTHOR]