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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This case report delves into the intricacies of a challenging clinical scenario involving deep pelvic endometriosis, which manifested with renal complications. Endometriosis, a complex gynecological condition, is explored in this case, highlighting its multifaceted nature. The patient presented with a complex interplay of symptoms, including chronic pelvic pain, urinary tract issues, and severe deep adenomyosis. The diagnostic journey was protracted, emphasizing the need for early recognition and intervention in such cases. A thorough evaluation, including laparoscopic examination and histopathological analysis, revealed the extensive presence of endometriotic lesions in various pelvic and renal structures, ultimately leading to left hydronephrosis. The report underscores the significance of timely diagnosis and surgical intervention to prevent irreversible renal damage. This case provides valuable insights into the management of deep endometriosis with renal involvement and the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Inflammation in primary teeth (PT) is commonly associated with a lower sensibility to painful stimuli, compared to permanent teeth, and usually leads to late presentation for dental treatment. Data obtained on the molecular assessments of dental pulp and clinical examinations could guide practitioners to conduct precise diagnoses and correct treatments. The aim of our pilot study was to assess the levels of several biomarkers (e.g., mineralization, oxidative stress, and inflammation) in primary teeth. The research included 46 dental pulp specimens collected from the primary teeth of children and adolescents between the ages of 6 and 12. The experimental groups consisted of 18 samples collected from primary teeth with acute pulpitis and 15 samples from chronically inflamed pulp tissues. The control group was represented by 13 specimens acquired from clinically healthy primary teeth. The enzyme-linked immunosorbent assay (ELISA) technique was used to determine the protein expression of tumor necrosis factor-α (TNF-α), superoxide dismutase-3 (SOD-3), osteocalcin, and transforming growth factor-β1 (TGF-β1) in the lysates. Our results revealed that all of the studied parameters presented statistically significant (p ≤ 0.05) increased levels in both experimental groups compared to the control samples. Furthermore, osteocalcin presented statistically significant increased concentrations in chronically- versus acute-inflamed pulp samples (p ≤ 0.05). The studied molecules may have an influential role in acute and chronic pulp inflammation in primary teeth. [ABSTRACT FROM AUTHOR]

Dental pulp inflammation, caused by the evolution of caries, involves numerous interrelated activities at a cellular and molecular level. Cytokines, proteases, growth factors, and other biomarkers of the host response may take part in dental pulp's immune defense. The aim of this pilot study was to determine the levels of inflammation, oxidative stress, and extracellular matrix degradation biomarkers in healthy and symptomatic irreversibly inflamed dental pulp samples from children and adolescents. Twenty-three dental pulp samples were collected from permanent teeth with irreversible inflammation, while nineteen healthy dental pulp samples were obtained from teeth extracted for orthodontic reasons. Pulp lysates were obtained and the levels of IL-2, IL-17, TNF-α, SOD3, TGF-β1, catalase, osteocalcin, MMP-7, and MMP-9 were determined using the enzyme-linked immunosorbent assay (ELISA) technique. We detected significantly higher levels (p < 0.001) of IL-2, IL-17, TNF-α, SOD3, osteocalcin, and TGF-β1 in pulp samples with irreversible inflammation than in controls. Catalase and MMP-7 showed higher levels in the experimental group, while MMP-9 showed slightly increased levels in the control group, but none of these differences were statistically significant (p = 0.064/p = 0.061/p = 0.625). Inflamed dental pulp samples showed an up-regulation of IL-2, IL-17, TNF-α, SOD3, osteocalcin, and TGF-β1. These biomarkers appear to have a powerful role in the inflammation process of human dental pulp. [ABSTRACT FROM AUTHOR]

Cataract is one of the most common diabetes mellitus complication among the adult population worldwide. The purpose of this review is to describe how reactive oxigen species (ROS) are produced, the antioxidant enzymes involved in their neutralization, and the molecular mechanisms associated with hyperglycemia that contributes to cataract development. [ABSTRACT FROM AUTHOR]

According to statistical data published in 2019, breast cancer is among the leading causes of death in women worldwide. The serine/threonine kinase (AKT) or protein kinase B (PkB) signaling pathway is activated by phosphorylation processes, which further is associated with cell growth, proliferation, and survival, but also with activation of glucose metabolism. Mutations of the AKT signaling pathway components (especially PI3KCA and PTEN) have been observed in breast cancer patients, which are associated with resistance to hormonal treatment. Many clinical trials are testing the effect of AKT inhibition in order to block the growth and proliferation of breast cancer cells. The purpose of this review is to present the incidence of this neoplastic disease, to describe AKT signaling pathways activation, mutations that occur at its level, and inhibitors that can block this protein kinase. [ABSTRACT FROM AUTHOR]

2,6,8-trioxypurine known as uric acid represents a heterocyclic derivative of purine, with a molecular weight of 158 Da. In contrast to primates and humans, in the other animals uric acid is further oxidized by the uricase enzyme (urate oxidase) to allantoin, 100 times more water-soluble than uric acid and, consequently, more efficient excreted in the urine. Humans and higher pri¬mates lack a functional uricase gene. The uricase activity loss in higher primates and humans occurred about 15 million years ago, re¬sulting in a relatively higher plasma uric acid level than that in lower ani¬mals. This was an impressive and very important evolutionary event, providing essential survival advantages for humans. Uric acid represents a powerful antioxidant capable of scavenging singlet oxygen molecules, oxygen radicals, and peroxynitrite (ONOO−) molecules. However, in vivo and cellular research studies are interestingly illustrating that, depending on its chemical microenvironment, the uric acid molecule plays a duplicate role, being also a pro-oxidant. Uric acid represents the most important salivary antioxidant, in the circumstances of very low salivary thiols concentrations. Uric acid plays an important role in oral pathology and may be regarded as a very useful future salivary biomarker. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The use of saliva as a diagnostic fluid is a relatively recent trend. Saliva is a mixed oral fluid derived from major and minor salivary glands. Oral fluid, often called the mirror of the body's health, is a perfect medium to be explored for health and disease surveillance. Saliva is considered to be the first line of defense against oxidative stress (OS), the main cause for many systemic and oral diseases. Important sources of oral free radicals and reactive oxygen species (ROS) are tobacco smoke, periodontitis and other oral diseases. Saliva is rich in antioxidants: uric acid, albumin, ascorbate and enzymes which constitute the antioxidant potential of saliva. Aim of the study: To test possible correlations between several salivary biomarkers and oral diseases associated with OS. Material and methods: We have determined the salivary antioxidant potential in patients with periodontitis (20), oral lichen planus (OLP) (20) smokers (20) versus controls (20). The following salivary biomarkers were evaluated: uric acid, albumin and total antioxidant capacity (TAC). Salivary biomarkers were performed using analysis kits on automatic analyzer. Analysis kits were provided by Biosystems Diagnostics (Spain) and by Randox (UK). Results: Analysis revealed statistically significant changes of the mentioned parameters in patients' saliva versus controls. Conclusions: Our results illustrate that OS caused a depletion of antioxidant status in the oral cavity. Uric acid, albumin and TAC are very important and promising salivary biomarkers for monitoring the oral OS. [ABSTRACT FROM AUTHOR]

O2 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 O2 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 O2 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Saliva is the first line of defense against oxidative stress. The salivary antioxidant system includes different categories of molecules, the most important of these being the uric acid molecule and the salivary peroxidase system, both hydrosoluble. Our experimental data revealed significant reductions in salivary uric acid levels in the context of severe oral conditions, such as periodontal disease, oral lichen, oral cancer, compared to controls. The analysis of our results led us to the conclusion that chronic inflammation, as well as premalignant and/or malignant lesions, can significantly reduce the salivary antioxidant potential, supported primarily by uric acid, thus causing the oral environment to become more vulnerable to oxidative stress, which explains the progression of oral affections and the emergence of resistance to treatment. [ABSTRACT FROM AUTHOR]

Regardless of whether the articles they examined were ultimately published, the editors would like to express their appreciation and thank the following reviewers for the time and dedication that they have shown I Cells i : those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). I Cells i was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. Thanks to the efforts of our reviewers in 2022, the median time to first decision was 16 days and the median time to publication was 42 days. [Extracted from the article]

Introduction. Crushing syndrome can affect all structures of a limb and can cause unique or complex injuries. The clinical picture of the injuries is nonspecific and extremely varied, and is not characteristic of the mechanism that generated it. The aim of our study was to correlate the changes of ALD A (aldolase A) and CAIII (carbonic anhydrase III) in the appearance and evolution of the crushing syndrome. Material and methods. The present study included 22 patients with crushing syndrome. The control group consisted of 20 healthy subjects. IL-6 (interleukin-6), CK (creatine kinase), ALD A and CAIII blood levels were determined simultaneously from all the participants to the study. Statistical analysis was performed using IBM SPSS Statistics 25 and Microsoft Office Excel / Word 2013. Results. Our results showed significantly increased levels of ALD A, CAIII, IL-6 and CK in patients with crushing syndrome. However, no statistically significant correlations could be found between the studied biomarkers. Discussions. So far, in the medical literature, very few studies focused on the correlation between the occurrence of crushing syndrome and changes in ALD A and CA III levels. Conclusions. Our study showed that ALD A and CAIII may become important biomarkers for the rapid diagnosis of crushing syndrome in the future. [ABSTRACT FROM AUTHOR]

Introduction. Polytrauma patients are expected to have a higher risk of mortality than that obtained by the summation of expected mortality owing to their individual injuries. Subsequent life-threatening posttraumatic complications are associated with overproduction of proinflammatory mediators (e.g. cytokines, chemokines) and the critical imbalance of cell-regulated innate immunity. Material and methods. The present study is aimed to identify a possible relationship between NT-proBNP, hs-CRP and OXSR1 biochemical markers in polytrauma patients, both by bibliographic research and quantitative analysis and statistics of some parameters of interest in lot of 46 patients. Results and discussions. The correlation between hsCRP and the inflammatory response after trauma is well-known and well documented in literature, so the negative correlation between hsCRP and OXSR1 that resulted from our analysis is of great significance resulting in a potentially new biomarker to be further studied and used in determining the possible outcome of polytrauma patients. Conclusion. Although OXSR1 is a new in the field of polytrauma patients, because is negatively correlated with hsCRP and the clinical evolution of the patients we think that OXSR1 is a good biomarker to further in investigate and may be used in determining the clinical progress of the polytrauma patients. [ABSTRACT FROM AUTHOR]

Introduction. The implications of oxidative stress and inflammation are unanimously accepted in thyroid disease. Objective. The aim of our study was to find correlations between serum antioxidant markers: glutathione peroxidase-3 (GPx-3), thioredoxin (Trx), total antioxidant capacity (TAC), inflammatory marker IL-8 and thyroid hormones, TSH and anti-thyroperoxidase antibodies (ATPO antibodies). Patients with different thyroid disorders were compared. Materials and methods. The study included 57 patients (men and women), divided into three groups: 26 patients with hyperthyroidism, 19 patients with hypothyroidism and 12 patients with autoimmune thyroiditis. The control group was represented by 33 healthy subjects. All the participants provided the informed consent for this study. Results. Our results showed that the patients with autoimmune thyroiditis had the highest level of Il-8 and the lowest TAC. Both Trx and GPx-3 were negatively correlated with TAC and IL-8 was positively correlated with the free T4 level, the ATPO antibodies titers, GPx-3 activity and negatively with serum TAC values. Conclusions. Systemic oxidative stress and inflammation are present in thyroid disorders, act in cluster and potentiate each other The presence of autoimmune antibodies worsens the biological picture. [ABSTRACT FROM AUTHOR]

Worldwide breast cancer (BC) represents one of the most common type of cancer. Mortality from this disease is declining due to new therapies, but many patients face the side effects of cancer and treatment. The most common side effect is the lymphedema of the upper extremity. Although the incidence of lymphedema secondary to breast cancer is 63.4%, there are few studies on the immune mechanisms responsible for lymphedema and healing. Extensive research of the development, structure and function of the lymphatic system must be performed to identify the role of lymphatic vessels in breast cancer. All this can lead to discovery of new potential biomarkers in lymph in order to improve early detection and treatment of lymphedema and the current strategies for controlling tumor metastasis. [ABSTRACT FROM AUTHOR]

Uric acid is a potential metabolite that serves as a danger‐associated molecular pattern (DAMP) and induces inflammatory responses in sterile environments. Porphyromonas gingivalis is a keystone periodontopathogen, and its gingipain proteases play a critical role in the pathogenesis of periodontitis. In this study, we demonstrate that P. gingivalis gingipains play a role in THP‐1 macrophage uric acid production by increasing the expression and activity of xanthine oxidoreductase (XOR). Uric acid sodium salt induces caspase‐1 activation, cell death, and the expression of proinflammatory cytokines, including IL‐1α, IL‐6, and IL‐8, in the human keratinocyte HOK‐16B cell line. Our results suggest that gingipain‐induced uric acid can mediate inflammation in periodontal tissue cells. [ABSTRACT FROM AUTHOR]