The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

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

The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

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

PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects

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

Growth Factors, Reactive Oxygen Species, and Metformin—Promoters of the Wound Healing Process in Burns?

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

CHRONIC MARGINAL STRESS AND PERIODONTITIS

Objectives. The aim of our study was to evaluate salivary cortisol levels and the scores of nicotinic social dependence, as markers of stress, in a group of patients with moderate and profound chronic periodontitis but systemically healthy. Material and method. Our study, of pretreatment cross-sectional design, included 28 adult patients with moderate and severe chronic marginal periodontitis and no systemic diseases. They were recruited from a particular clinic in Bucharest. The questionnaire used gathered questions from the Kano test to assess nicotine dependence. The salivary cortisol was determined using a DSNOV20 kit (NovaTec Immundiagnostica GmbH). Results and discussions. The average Kano total score was 13.28 (+ 4.38; range 4-23). The smoker group recorded an average of 16.2 (range 11-23). There were no statistically significant differences between the scores of the three groups. From the 28 patients who completed the questionnaires, 22 were evaluated for salivary cortisol levels. Of these, 3 were smokers, 6 were former smokers and 13 were non-smokers. The mean salivary cortisol level was 6.65 ng/ml (+ 1.47; range 4.12-9.38). The mean salivary cortisol level was higher in smokers compared to non-smokers and ex-smokers (p> 0.05). Conclusions. Stress, expressed by the average level of salivary cortisol, was higher among smokers compared to the other groups, the highest variability being registered among ex-smokers. In patients with moderate and severe chronic marginal periodontitis, there was a positive, albeit insignificant, association between salivary cortisol levels and nicotinic psychological dependence

Hydrogen Sulfide, Oxidative Stress and Periodontal Diseases: A Concise Review

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

ADIPOSE TISSUE BIOMARKERS AND SYSTEMIC HEALTH

Adipose tissue consists primarily of adipocytes, being responsible for storing the body's energy reserves. Adipokines secreted by adipose tissue play important roles in the human body. The purpose of this review is to present the most important adipokines and their involvement in the physiological processes but also in the pathogenesis of numerous systemic diseases commonly associated with obesity

HYPERLEPTINEMIA AND CARDIOVASCULAR SYSTEM

Leptin is the satiety hormone, synthesized in the adipose tissue that reduces food intake, being involved in glucose and lipid metabolism. Hyperleptinemia correlates with obesity and represents a risk factor in the pathology of the cardiovascular system. Increased concentrations of leptin have been observed in patients with hypertension or atherosclerosis. In vitro studies suggest the angiogenic role of leptin. The purpose of this review is to present the metabolic effects of hyperleptinemia in the cardiovascular system

OBESITY INDUCES DNA DAMAGE

A diet rich in saturated lipids, refined carbohydrates associated with a sedentary lifestyle leads to obesity in both adults and children. Obesity is associated with the existence of a chronic inflammatory process, that will further lead to systemic oxidative stress and DNA oxidative damage. There is currently a positive correlation between obesity and cancer due to nuclear but also mitochondrial DNA injury. Obesity is a risk factor for the development of several types of cancer such as breast, prostate or colorectal. The purpose of this review is to present the effects of obesity on human body, by describing the chronic inflammatory process, oxidative stress, and the molecular mechanisms involved in cancer progression

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