Search

Acute kidney injury (AKI), a medical condition associated with increased hospitalization rates which requires interdisciplinary management, is a major health concern because of the burden it places on the health systems of different countries. Biomarkers represent the focus of recent years in furthering the early diagnosis of AKI, providing new opportunities for correct prophylaxis or early therapeutic intervention so that the evolution of patients with this pathology is favorable and the risk of life-threatening complications is negligible.

Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity.

Worldwide, diabetes mellitus (DM) and cardiovascular diseases (CVDs) represent serious health problems associated with unhealthy diet and sedentarism. Metabolic syndrome (MetS) is characterized by obesity, dyslipidemia, hyperglycemia, insulin resistance (IR) and hypertension. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase with key roles in glucose and lipid metabolism, cell growth, survival and proliferation. mTOR hyperactivation disturbs glucose metabolism, leading to hyperglycemia and further to IR, with a higher incidence in the Western population. Metformin is one of the most used hypoglycemic drugs, with anti-inflammatory, antioxidant and antitumoral properties, having also the capacity to inhibit mTOR. mTOR inhibitors such as rapamycin and its analogs everolimus and temsirolimus block mTOR activity, decrease the levels of glucose and triglycerides, and reduce body weight. The link between mTOR dysregulation, IR, hypertension and mTOR inhibitors has not been fully described. Therefore, the main aim of this narrative review is to present the mechanism by which nutrients, proinflammatory cytokines, increased salt intake and renin-angiotensin-aldosterone system (RAAS) dysregulation induce mTOR overactivation, associated further with IR and hypertension development, and also mTOR inhibitors with higher potential to block the activity of this protein kinase.

Burns generate every year an important burden of morbidity, being a major global public health problem through prolonged hospitalization, complications, and increased mortality. This study's purpose was to evaluate the serum levels of three adipokines and to establish significant correlations with other circulating molecules and with some clinical parameters. We evaluated 32 children with severe burns (over 25% total burned surface area-TBSA) at 48 h, day 10, and day 21 post burn, and 21 controls. The serum levels of adiponectin, resistin, leptin, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) (among nine other biochemical parameters) were detected by Multiplex technique. Significant statistical differences were obtained for resistin and leptin compared to the control group, in different moments of measurements. Adiponectin serum levels presented statistically significant correlations with hot liquid mechanism of burn, the Revised Baux score, TBSA, resistin, PAI-1, CRP, TNF-α, and triglycerides (TGLs) serum levels. Resistin serum levels presented statistically significant correlations with adiponectin, CRP, PAI-1, leptin, and TNF-α. Additionally, we found statistically significant correlations between leptin serum levels and length of hospitalization, TNF-α, resistin, adiponectin, and PAI-1 serum levels. In severely burned children, adiponectin, resistin, and leptin specifically correlate with clinical parameters and with proteins involved in the systemic inflammatory response and the hypermetabolic response.

Background : Burns represent a serious health problem, associated with multiple-organ failure, prolonged hospitalization, septic complications, and increased rate of mortality. The main aim of our study was to evaluate the levels of various circulating molecules in children with severe burns (more than 25% TBSA), in three different moments: 48 h, day 10, and day 21 post-burn. Materials and Methods : This study included 32 children with burns produced by flame, hot liquid, and electric arc and 21 controls. Serum plasminogen activator inhibitor-1 (PAI-1), α 1-acid glycoprotein (AGP), C-reactive protein (CRP), and platelet factor 4 (PF4) were detected using the Multiplex technique. Several parameters, such as fibrinogen, leucocyte count, thrombocyte count, triiodothyronine, thyroxine, and thyroid-stimulating hormone were also determined for each patient during hospitalization. Results : Significant statistical differences were obtained for CRP, AGP, and PF4 compared to the control group, in different moments of measurements. Negative correlations between CRP, AGP, and PF4 serum levels and burned body surface, and also the hospitalization period, were observed. Discussions: CRP levels increased in the first 10 days after burn trauma and then decreased after day 21. Serum PAI-1 levels were higher immediately after the burn and started decreasing only after day 10 post-burn. AGP had elevated levels 48 h after the burn, then decreased at 7-10 days afterwards, and once again increased levels after 21 days. PF4 serum levels increased after day 10 since the burning event. Conclusions: Serum CRP, AGP, PAI-1, and PF4 seem to be promising molecules in monitoring patients with a burn within the first 21 days.

Patient Blood Management (PBM) as a multidisciplinary practice and a standard of care for the anemic surgical patient is playing an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. The success of PBM implementation depends on staff awareness and involvement in this approach. The main objective of our study was to explore physicians' perceptions of the conditions for implementing PBM in hospitals and the main obstacles they face in detecting and treating anemic patients undergoing elective surgery. This cross-sectional descriptive study includes 113 Romanian health units, representing 23% of health units with surgical wards nationwide. A 12-item questionnaire was distributed to the participants in electronic format. A total of 413 questionnaires representing the perceptions of 347 surgeons and 66 anesthesia and intensive-care specialists were analyzed. Although a lack of human resources was indicated by 23.70% of respondents as the main reason for not adhering the guidelines, the receptiveness of medical staff to implementing the PBM standard was almost 90%. In order to increase adherence to the standard, additional involvement of anesthesia and intensive-care physicians would be necessary from the perception of 35.70% of the responders: 23.60% of surgeons and 18.40% of hematologists.

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA , TP53 , ARID1A , CDH1 , Ras , Raf , and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori , growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

(1) Background: Patient blood management (PBM) program as a multidisciplinary practice and a standard of care for the anemic surgical patient has an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. Documented success of PBM implementation is not sufficient for implementation of recommendations and correct use at hospital level. The primary objective of our study was to define a composite patient blood management process safety index-Safety Index in PBM (SIPBM)-that measures the impact of screening and treating anemic patients on the efficiency and effectiveness of the patient care process undergoing elective surgery. (2) Methods: We conducted a retrospective comparative study in a tertiary hospital by collecting data and analyzing the Safety Index in PBM (SIPBM) in patients undergoing major elective surgical procedures. (3) Results: The percentage of patients from the total of 354 patients (178 in 2019 and 176 in 2022) included in the study who benefited from preoperative iron treatment increased in 2022 compared to 2019 from 27.40% to 36.71%. The median value of the SIPBM was 1.00 in both periods analyzed, although there is a significant difference between the two periods ( p < 0.005), in favor of 2022. (4) Conclusions: Measuring the effectiveness of PBM implementation and providing ongoing feedback through the Safety Index in PBM (SIPBM) increases the degree to which opportunities to improve the PBM process are identified. The study represents a first step for future actions and baselines to develop tools to measure the safety and impact of the patient blood management process in the surgical field.

Renal cell carcinoma (RCC) represents 85-95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.

Due to the nature of their activity, anesthesia and critical care have generally well-developed patient safety cultures, which are linked to a greater level of incident awareness and reporting during clinical activity. In order to determine the status quo and identify and adopt, where appropriate, techniques and instruments for further improving patient safety, it is necessary to evaluate the culture and barriers in these departments. The main objective of our study was to assess patient safety culture in Romanian anesthesia and intensive care departments (AICDs), to pinpoint the areas that may need improvement, and to examine the correlation between the prevalence of adverse event reporting, as well as the level of self-reported patient safety culture. To determine how anesthesia and intensive care department staff perceived patient safety, the Hospital Survey on Patient Safety Culture (HSOPSC) was used in a translated Romanian version. In total, 1200 employees from 36 anesthesiology and intensive care departments across 32 hospitals in Romania received the questionnaire, representing 42.66% of all anesthesia and intensive care departments in the country. In 7 of the 12 examined dimensions, significant differences between tertiary and secondary hospitals were observed. Among all dimensions, the highest positive score was for "organizational learning and continuous development". In general, our study revealed a positive view on patient safety in anesthesia and intensive care departments. Further studies are required to determine a threshold of the level of culture development.

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.

A provisionalization sequence is essential for obtaining a predictable final prosthetic outcome. An assessment of the mechanical behavior of interim prosthetic materials could orient clinicians towards selecting an appropriate material for each clinical case. The aim of this study was to comparatively evaluate the mechanical behavior-with compressive and three-point flexural tests-of certain 3D-printed and conventional resins used to obtain interim fixed dental prostheses. Four interim resin materials were investigated: two 3D-printed resins and two conventional resins (an auto-polymerized resin and a pressure/heat-cured acrylic resin). Cylindrically shaped samples (25 × 25 mm/diameter × height) were obtained for the compression tests and bar-shaped samples (80 × 20 × 5 mm/length × width × thickness) were produced for the flexural tests, observing the producers' recommendations. The resulting 40 resin samples were subjected to mechanical tests using a universal testing machine. Additionally, a fractographic analysis of failed samples in bending was performed. The results showed that the additive manufactured samples exhibited higher elastic moduli (2.4 ± 0.02 GPa and 2.6 ± 0.18 GPa) than the conventional samples (1.3 ± 0.19 GPa and 1.3 ± 0.38 GPa), as well as a higher average bending strength (141 ± 17 MPa and 143 ± 15 MPa) when compared to the conventional samples (88 ± 10 MPa and 76 ± 7 MPa); the results also suggested that the materials were more homogenous when produced via additive manufacturing.

O 2 deprivation induces stress in living cells linked to free-radical accumulation and oxidative stress (OS) development. Hypoxia is established when the overall oxygen pressure is less than 40 mmHg in cells or tissues. However, tissues and cells have different degrees of hypoxia. Hypoxia or low O 2 tension may be present in both physiological (during embryonic development) and pathological circumstances (ischemia, wound healing, and cancer). Meanwhile, the kidneys are major energy-consuming organs, being second only to the heart, with an increased mitochondrial content and O 2 consumption. Furthermore, hypoxia-inducible factors (HIFs) are the key players that orchestrate the mammalian response to hypoxia. HIFs adapt cells to low oxygen concentrations by regulating transcriptional programs involved in erythropoiesis, angiogenesis, and metabolism. On the other hand, one of the life-threatening complications of severe burns is acute kidney injury (AKI). The dreaded functional consequence of AKI is an acute decline in renal function. Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of HIFs in the development of AKI in patients with severe burns, because kidney hypoxia is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia.

Burn healing should be regarded as a dynamic process consisting of two main, interrelated phases: (a) the inflammatory phase when neutrophils and monocytes infiltrate the injury site, through localized vasodilation and fluid extravasation, and (b) the proliferative-remodeling phase, which represents a key event in wound healing. In the skin, both canonical autophagy (induced by starvation, oxidative stress, and environmental aggressions) and non-canonical or selective autophagy have evolved to play a discrete, but, essential, "housekeeping" role, for homeostasis, immune tolerance, and survival. Experimental data supporting the pro-survival roles of autophagy, highlighting its Yang, luminous and positive feature of this complex but insufficient explored molecular pathway, have been reported. Autophagic cell death describes an "excessive" degradation of important cellular components that are necessary for normal cell function. This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy. Autophagy seems to perform dual, conflicting roles in the angiogenesis context, revealing once again, its Yin-Yang features. Autophagy with its Yin-Yang features remains the shadow player, able to decide quietly whether the cell survives or dies.

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC., Competing Interests: The authors declare no conflict of interest.

It has become widely accepted that insulin resistance and glucose hypermetabolism can be linked to acute pathologies, such as burn injury, severe trauma, or sepsis. Severe burns can determine a significant increase in catabolism, having an important effect on glucose metabolism and on muscle protein metabolism. It is imperative to acknowledge that these alterations can lead to increased mortality through organ failure, even when the patients survive the initial trauma caused by the burn. By limiting the peripheral use of glucose with consequent hyperglycemia, insulin resistance determines compensatory increased levels of insulin in plasma. However, the significant alterations in cellular metabolism lead to a lack of response to insulin's anabolic functions, as well as to a decrease in its cytoprotective role. In the end, via pathological insulin signaling associated with increased liver gluconeogenesis, elevated levels of glucose are detected in the blood. Several cellular mechanisms have been incriminated in the development of insulin resistance in burns. In this context, the main aim of this review article is to summarize some of the drugs that might interfere with insulin resistance in burns, taking into consideration that such an approach can significantly improve the prognosis of the burned patient.

Burns can be caused by various factors and have an increased risk of infection that can seriously delay the wound healing process. Chronic wounds caused by burns represent a major health problem. Wound healing is a complex process, orchestrated by cytokines, growth factors, prostaglandins, free radicals, clotting factors, and nitric oxide. Growth factors released during this process are involved in cell growth, proliferation, migration, and differentiation. Reactive oxygen species are released in acute and chronic burn injuries and play key roles in healing and regeneration. The main aim of this review is to present the roles of growth factors, reactive oxygen species, and metformin in the healing process of burn injuries.

Oral cancer represents one of the most common types of cancer worldwide, with oral squamous cell carcinoma (OSCC) being the most frequently diagnosed. Cytokines play a crucial role in inflammation, apoptosis and metastasis. Interleukin (IL)-8 promotes the direct migration of inflammatory cells. IL-6 induces tumor cell proliferation, increases expression of invasiveness and angiogenetic factors or matrix metalloproteinases (MMPs), promoting metastasis. Tissue inhibitor of metalloproteinases (TIMPs) blocks the action of MMPs controlling extracellular matrix degradation and inhibiting metastasis. The aim of our study was to analyze the existence of correlations between inflammation markers (IL-6 and IL-8) and extracellular degradation protection markers such as TIMP-1 in OSCC tumors. Our study included 20 patients (12 females and 8 males) diagnosed with OSCC, recruited from January to April, 2020. IL-8, IL-6 and TIMP-1 levels were measured in the tumor cell lysates by ELISA technique, using relevant assay kits. Our results showed a positive and significant correlation between IL-6 and IL-8 (P=0.005, R=0.517) indicating that high IL-8 levels can be associated with high IL-6 levels. We also found a significant and high negative correlation (P<0.001, R=-0.673) between IL-6 and TIMP-1 and a significant and high negative correlation (P<0.001, R=-0.684) between IL-8 and TIMP-1 indicating that high levels of IL-8 and IL-6 are significantly associated with lower levels of TIMP-1. In conclusion, our study confirms the available literature data on IL-6 and IL-8 as potential markers for oral cancers such as OSCC and affect the tumor microenvironment by decreasing TIMPs. All three biomarkers included in this study have the potential to be used as detection or prognostic factors for oral cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Radulescu et al.)

A wide range of mediators are released from the pulp tissue because of bacterial invasion which causes inflammation. Interleukins (ILs) and matrix metalloproteinases (MMPs) have a leading role in initiating and spreading of inflammation because of their synergic action. Biomarkers such as ILs and MMPs can be identified via several methods, establishing the inflammatory response of the dental pulp. The aim of this systematic review is to evaluate the levels of ILs and/or MMPs in human dental pulp. PubMed, OVID, Cochrane, Scopus, Web of Science and Wiley online library databases were searched for original clinical studies. After applying inclusion and exclusion criteria, a quality assessment of studies was performed based on a modified Newcastle-Ottawa scale. In the review were included articles that evaluated the presence of ILs and/or MMPs in pulp tissue using enzyme-linked immunosorbent assay (ELISA) or western blot or multiplex assay. Six articles were included in the present synthesis. Although various diagnostic methods were used, statistically significant higher levels of ILs and/or MMPs were mostly found in the experimental groups compared to healthy pulp samples. The biomarkers studied can be a promising tool to evaluate pulp tissue health or even in pulpitis treatment.

Carotenoids loaded in nanoparticles should be regarded as a promising way to increase the availability in healthy cells and to induce apoptosis in cancer. Lutein is a carotenoid that, in contrast to beta-carotene, has no known toxicities. Oral cancer represents one of the most frequent types of cancer world-wide with an incidence rate of about 9% of all types of cancer. Almost 95% of all oral cancers are represented by squamous cell carcinomas (OSCC). The aim of this study was to review and analyse the effects of lutein and Poly(d,l-lactide-co-glycolide) (PLGA) Nps containing lutein (Lut Nps) on oxidative stress biomarkers (OXSR-1, FOXO-3, TAC) and collagen degradation biomarker-MMP-9, in human cells BICR10 of buccal mucosa squamous carcinoma. Lut Nps were prepared by the emulsion-solvent evaporation method. MMP, OXSR-1, TAC, FOXO-3 and MMP-9 were measured in tumour cell lysates by the ELISA technique. Our results have shown that in Lut 100 cells and Lut Nps the OXSR1 ( p < 0.001, p < 0.001) and TAC ( p < 0.001, p < 0.001) values were significantly higher than in control cells. The Lut 100 and Lut Nps FOXO-3 levels revealed no significant differences versus the control. MMP-9 levels were significantly reduced ( p < 0.001) in the Lut Nps cells versus control cells. In our study conditions, lutein and lutein Nps did not trigger an oxidative stress by ROS induction. However, lutein Nps treatment seemed to have a positive effect, by downregulating the MMP-9 levels. Loaded in Nps, lutein could be regarded as a protective factor against local invasiveness, in whose molecular landscape MMPs, and especially MMP-9 are the main actors.

Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient's health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel "ready to use" by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.

Breast cancer is a serious health problem worldwide, representing the second cause of death through malignancies among women in developed countries. Population, endogenous and exogenous hormones, and physiological, genetic and breast-related factors are involved in breast cancer pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is a signaling pathway involved in cell proliferation, survival, invasion, migration, apoptosis, glucose metabolism and DNA repair. In breast tumors, PIK3CA somatic mutations have been reported, located in exon 9 and exon 20. Up to 40% of PIK3CA mutations are estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) -negative in primary and metastatic breast cancer. HER2 is overexpressed in 20-30% of breast cancers. HER1, HER2, HER3 and HER4 are membrane receptor tyrosine kinases involved in HER signaling to which various ligands can be attached, leading to PI3K/AKT activation. Currently, clinical studies evaluate inhibitors of the PI3K/AKT/mTOR axis. The main purpose of this review is to present general aspects of breast cancer, the components of the AKT signaling pathway, the factors that activate this protein kinase B, PI3K/AKT-breast cancer mutations, PI3K/AKT/mTOR-inhibitors, and the relationship between everolimus, temsirolimus and endocrine therapy.

Periodontitis represents a complex inflammatory disease that compromises the integrity of the tooth-supporting tissue through the interaction of specific periodontal pathogens and the host's immune system. Experimental data help to outline the idea that the molecular way towards periodontitis initiation and progression presents four key steps: bacterial infection, inflammation, oxidative stress, and autophagy. The aim of this review is to outline the autophagy involvement in the pathogenesis and evolution of periodontitis from at least three points of view: periodontal pathogen invasion control, innate immune signaling pathways regulation and apoptosis inhibition in periodontal cells. The exact roles played by reactive oxygen species (ROS) inside the molecular mechanisms for autophagy initiation in periodontitis still require further investigation. However, clarifying the role and the mechanism of redox regulation of autophagy in the periodontitis context may be particularly beneficial for the elaboration of new therapeutic strategies.

This paper's primary aim is to outline relevant aspects regarding the biocompatibility of PMMA (poly(methyl methacrylate))-based materials used for obtaining interim prosthetic restorations, such as the interaction with oral epithelial cells, fibroblasts or dental pulp cells, the salivary oxidative stress response, and monomer release. Additionally, the oral environment's biochemical response to modern interim dental materials containing PMMA (obtained via subtractive or additive methods) is highlighted in this review. The studies included in this paper confirmed that PMMA-based materials interact in a complex way with the oral environment, and therefore, different concerns about the possible adverse oral effects caused by these materials were analyzed. Adjacent to these aspects, the present work describes several advantages of PMMA-based dental materials. Moreover, the paper underlines that recent scientific studies ascertain that the modern techniques used for obtaining interim prosthetic materials, milled PMMA, and 3D (three-dimensional) printed resins, have distinctive advantages compared to the conventional ones. However, considering the limited number of studies focusing on the chemical composition and biocompatibility of these modern interim prosthetic materials, especially for the 3D printed ones, more aspects regarding their interaction with the oral environment need to be further investigated., Competing Interests: The authors declare no conflict of interest.

This paper aims to investigate the composition, surface, and microstructural characteristics, and bioactivity of two commercially available pulp capping materials known as TheraCal LC and BIO MTA+. The materials were prepared as cylindrical samples and assessed by X-ray diffraction (XRD) and complex thermal analysis for mineralogical characterization, and by scanning electron microscopy (SEM) coupled with energy dispersive of X-ray (EDX), Fourier-Transformed Infrared Spectroscopy (FT-IR), and atomic force microscopy (AFM) for microstructural and surface characteristics. The in vitro bioactivity was highlighted by surface mineralization throughout SEM coupled with EDX and FT-IR analysis. XRD analysis performed on both materials showed calcium silicate phases and different radiopacifying compounds. AFM measurements indicated a smoother and more homogenous surface with a lower average roughness for TheraCal LC due to the resin matrix from its composition. FT-IR analysis displayed bands for several compounds in both materials. Both materials exhibited bioactive properties showing surface mineralization after being immersed in solution similar to the human physiological environment. However, the MTA cement showed a better mineralization due to the anhydrous and hydrated phases.

Saliva is currently used as a reliable diagnostic fluid in a wide range of local and systemic diseases. However, the link between salivary diagnosis and the inflammatory process in autoimmune diseases has not yet been explored. The aim of our study is to assess possible correlations between salivary inflammatory markers and systemic lupus erythematosus (SLE). Patients fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) diagnosis criteria were included. Salivary and serum levels of interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were determined using stochastic sensors. Serum leptin and IL-6 had significantly higher levels in SLE patients compared to non-SLE. Also, salivary IL-6 levels highly correlated with the serum IL-6 levels. A positive correlation was found between salivary and serum levels of IL-6, signaling salivary IL-6 as a reliable marker for assessing the inflammation process in SLE., (Copyright © 2018. Published by Elsevier GmbH.)

Background: The aim of the present study is to analyze the behavior of selected populations of oral keratinocytes and T-lymphocytes, responsible for re-constructing and maintaining the oral epithelial tissue architecture, following augmentation of the keratinized oral mucosa using a 3D-collagen matrix., Methods: Different groups of oral keratinocytes were isolated from biopsies harvested from 3 patients before the surgical procedure, as well as 7 and 14 days after the augmentation procedure. T-lymphocytes were isolated from peripheral blood at same timepoints. Keratinocytes were characterized for stem and differentiation markers, such as p63, cytokeratin 10 and 14, and in vitro parameters, such as cell viability, cell size and colony-forming efficiency. T-lymphocytes were analyzed for viability and the expression of various cluster of differentiation markers. The methods included magnetic separation of cell populations, immunofluorescence, flow cytometry, and histology of oral biopsies., Results: Both at 7 and 14 days, the majority of cells that repopulate the matrix were actively proliferating/progenitor oral keratinocytes with the phenotype integrin alfa6beta4 + CD71+. These cells display in vitro characteristics similar to the progenitor cells analyzed before the matrix placement. T-lymphocytes expressed CD8 and CD69 markers, while CD25 was absent., Conclusion: The study shows that two weeks after the collagen membrane placement, the healing process appeared to be histologically complete, with no abnormal immune response induced by the matrix, however, with a higher than usual content of active proliferating cells, the majority of keratinocytes being characterized as transit amplifying cells.

There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for several advantages of using natural or synthetic organic nanostructures in a wide variety of dental fields, from implantology, endodontics, and periodontics, to regenerative dentistry and wound healing. Most of the research is concentrated on nanoforms of chitosan, silk fibroin, synthetic polymers or their combinations, but new nanocomposites are constantly being developed. The present work reviews in detail current research on organic nanoparticles and their potential applications in the dental field.

In the past years, biomedical research has recognized hydrogen sulfide (H₂S) not only as an environmental pollutant but also, along with nitric oxide and carbon monoxide, as an important biological gastransmitter with paramount roles in health and disease. Current research focuses on several aspects of H₂S biology such as the biochemical pathways that generate the compound and its functions in human pathology or drug synthesis that block or stimulate its biosynthesis. The present work addresses the knowledge we have to date on H₂S production and its biological roles in the general human environment with a special focus on the oral cavity and its involvement in the initiation and development of periodontal diseases.

Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.

Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Oxidative stress is implicated in the pathogenesis of many systemic and oral diseases such as periodontal disease. The main aim of this study is to explore a possible association between salivary markers of OS and alveolar bone loss., Materials and Methods: The study included 20 patients with chronic periodontitis and 20 controls. Salivary OS biomarkers 8-hidroxy-desoxguanosine (8-HOdG), malondialdehyde (MDA), uric acid, total antioxidant capacity (TAC) and glutathione peroxidase (GPx) were evaluated. Bone loss markers such as C-terminal telopeptide of type I collagen (CTX I), matrix metalloproteinases-8 (MMP-8), osteocalcin and 25-hydroxy vitamin D3 (25- OH D) were detected in this study. The methods included general biochemical tests and ELISA., Results: Salivary 8-OHdG, MDA levels were significantly higher in the chronic periodontitis group compared with controls (p < 0.05). Salivary activities for uric acid, TAC and GPx were significantly decreased in patients with chronic periodontitis vs controls (p < 0.05). Salivary levels for CTX I, MMP-8, 25-OH D and Osteocalcin were significantly higher in the chronic periodontitis group compared to the controls (p < 0.05). A significant positive correlation was observed between salivary levels of MDA and CTX I. Significant negative correlations between uric acid and CTX I and between MMP-8 and uric acid have been found. Significant positive correlations were observed between CTX I, MMP-8, 25-OH D, osteocalcin and clinical parameters of periodontal disease., Conclusions: Important oxidative stress associated with alveolar bone loss biomarkers can be detected in saliva of patients with periodontal disease.