Correlation between NT-proBNP, hsCRP and OXSR1: Clinical relevance in evaluating the prognosis of polytrauma patients

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

Biochemical Mapping of the Inflamed Human Dental Pulp

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

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

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

Assessment of Mineralization, Oxidative Stress, and Inflammation Mechanisms in the Pulp of Primary Teeth

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

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

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

Autophagy—A Hidden but Important Actor on Oral Cancer Scene

The duration of denture use, oral hygiene, smoking and male sex were identified as risk factors for oral mucosal lesions. As it is well known, all the oral mucosal lesions associated with risk factors have an important degree of malignity. Chronic mechanical irritation can be another cause of oral cancer and it is produced by the constant action of a deleterious agent from the oral cavity. Autophagy represents a complex evolutionary conserved catabolic process in which cells self-digest intracellular organelles in order to regulate their normal turnover and remove the damaged ones with compromised function to further maintain homeostasis. Autophagy is modulated by mTOR kinase and indirectly by PI3K/AKT survival pathway. Due to its dual capacity to either induce cell death or promote cell survival, important evidence pointed that autophagy has a two-faced role in response to chemotherapy in cancer. In conclusion, understanding how to overcome cytoprotective autophagy and how to take advantage of autophagic cell death is critical in order to enhance the cancer cells sensitivity to particular therapeutic agents

Drugs Interfering with Insulin Resistance and Their Influence on the Associated Hypermetabolic State in Severe Burns: A Narrative Review

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

A Potential Indicator for Assessing Patient Blood Management Standard Implementation

(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

Hypoxia-Inducible Factors and Burn-Associated Acute Kidney Injury&mdash;A New Paradigm?

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

(PI3K)/AKT SIGNALLING PATHWAY – A PANDORA’S BOX IN ORAL SQUAMOUS CELL CARCINOMA

Molecular mechanisms of cancer involve mutations of several genes triggering various pathway alterations. Oral squamous cell carcinoma (OSCC) represents approximately 10% of the head and neck cancers and is one of the leading causes of morbidity and mortality in Central and Eastern Europe. The main aim of this review article is to present an overview of one of the major actors in cellular processes’ regulation that are key features of cancer molecular events - the PI3K/AKT signalling pathway. The altered molecular signalling pathways in OSCC have been discussed, emphasizing the frequent disruption of the PI3K/AKT pathway in cancer. Thus, the aspects presented in this article highlight this pathway as an important target for new therapeutic strategies