Publisher Summary This chapter presents a classification of pituitary tumors based on their functionality, invasiveness, and aggressiveness. Pituitary tumors, often called adenomas, are among the most frequent intracranial tumors after... more
Publisher Summary This chapter presents a classification of pituitary tumors based on their functionality, invasiveness, and aggressiveness. Pituitary tumors, often called adenomas, are among the most frequent intracranial tumors after meningiomas and gliomas. From their epidemiology to their molecular aspects, pituitary adenomas represent a broad spectrum of disorders that can be analyzed and classified according to autonomous secretion, clinical aspects in diagnosis and treatment, pathology in terms of light microscopy (LM) and electron microscopy (EM) features, and special issues such as the clinical impact of aggressive pituitary adenomas or rare pituitary carcinoma cases. Pituitary adenomas can be classified as secreting tumors (such as growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL) in women, or the rare thyroid-stimulating hormone (TSH)-secreting adenomas) or clinically nonfunctional adenomas. The remaining pituitary adenomas, representing approximately a third, are clinically silent and are known as nonfunctioning pituitary adenomas (NFPAs), meaning that they only cause symptoms due to tumor growth. GH-producing adenomas represent 20% of pituitary tumors in surgical material, and they show no sex predilection. Corticotroph adenomas are the most frequent form (two-thirds) of the Cushing syndrome in adults, leading to the clinical and biochemical features known as Cushing's disease.
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Publisher Summary This chapter outlines various therapeutic approaches for treatment of pituitary adenomas. Future perspectives and therapeutic implications in pituitary adenomas are also explored in this chapter. Despite being considered... more
Publisher Summary This chapter outlines various therapeutic approaches for treatment of pituitary adenomas. Future perspectives and therapeutic implications in pituitary adenomas are also explored in this chapter. Despite being considered as benign, excess hormone secretion or hypopituitarism implies a major impact upon health, with increased cardiovascular events and mortality. With the exception of pituitary incidentalomas, increasing incidence of pituitary adenomas (secreting or nonfunctional) requires specific intervention. Main therapeutic approaches for treatment of pituitary adenomas include drug, surgical, and radiotherapy. The main principles regarding the surgical indication in pituitary adenomas recommend surgical resection as the primary treatment in tumors that are endocrinologically active as well as in tumors accompanied by pituitary insufficiency. In prolactinomas and GH-PRL secreting adenomas, dopamine agonists are the first line therapy, with improvement/normalization of PRL levels and restore of pituitary function. Temozolomide, drugs targeting angiogenesis, or gene therapy are in the front line research and treatment in trials involving patients with pituitary adenomas. Radiotherapy is generally regarded as the last treatment resource for pituitary adenomas.
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Publisher Summary This chapter introduces genomics and proteomics as the new generic tools for diagnosis of pituitary adenomas. The development of tumor-associated serum protein biomarkers over the past few decades has not been much... more
Publisher Summary This chapter introduces genomics and proteomics as the new generic tools for diagnosis of pituitary adenomas. The development of tumor-associated serum protein biomarkers over the past few decades has not been much effective for diagnosing primary neoplasia. There is a considerable pressure to discover new disease-related biomarkers. These markers are quantitative measures of biological effects that provide informative links between the mechanism of action and clinical effectiveness. They can provide new insights into a drug's mechanism of action, metabolism, efficacy, and safety, and into disease mechanisms and disease course. Protein biomarkers show a high potential of conversion into paraclinical diagnostic tests. Genomic analysis is one of the most intensively exploited “instrument” in biomarker discovery. Large-scale sequencing of candidate genes provides new biomarkers for tumor diagnosis and prognosis. Somatic DNA sequence analysis has expanded to genome-wide high-performance DNA sequencing leading to whole genome analysis of DNA sequence variations in tumors.
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Healthcare professionals face an ongoing challenge in managing both acute and chronic wounds, given the potential impact on patients’ quality of life and the limited availability of expensive treatment options. Hydrogel wound dressings... more
Healthcare professionals face an ongoing challenge in managing both acute and chronic wounds, given the potential impact on patients’ quality of life and the limited availability of expensive treatment options. Hydrogel wound dressings offer a promising solution for effective wound care due to their affordability, ease of use, and ability to incorporate bioactive substances that enhance the wound healing process. Our study aimed to develop and evaluate hybrid hydrogel membranes enriched with bioactive components such as collagen and hyaluronic acid. We utilized both natural and synthetic polymers and employed a scalable, non-toxic, and environmentally friendly production process. We conducted extensive testing, including an in vitro assessment of moisture content, moisture uptake, swelling rate, gel fraction, biodegradation, water vapor transmission rate, protein denaturation, and protein adsorption. We evaluated the biocompatibility of the hydrogel membranes through cellular assays...
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Biocompatibility of several implantable materials - silica wafers (used for implantable probes for measurements of electrical activities of living tissue) and titanium implants was tested in vitro. The testing strategy comprised 2... more
Biocompatibility of several implantable materials - silica wafers (used for implantable probes for measurements of electrical activities of living tissue) and titanium implants was tested in vitro. The testing strategy comprised 2 approaches, derived from the recommendations of the ISO 10993 standard. Thus, a first set of tests was carried with potential extractable components in Balb/c 3T3 cells in culture. A second set of tests was performed in human monocytes for the assessment of cell activation and secretion of proinflammatory cytokines (IL1b and TNF a), measured by an immunoenzymatic method in culture supernatants. Parallel negative control and specific positive controls were run. 24 hrs exposures of 70% confluent cultures were applied in the experiments. Additional assays for 3T3 cells sensitivity tests to TNFa were performed. All assays demonstrated the lack of cytotoxic and proinflammatory effects of silica wafers and titanium implants. Only on uncoated titanium a statis...
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Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to... more
Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to introduce a reliable technological recipe for coating fairly complex 3D-shaped implants (e.g. dental screws) with uniform and mechanical resistant bioactive glass films by the radio-frequency magnetron sputtering method. The mechanical reliability of the bioactive glass films applied to real Ti dental implant fixtures has been evaluated by a procedure comprised of "cold" implantation in pig mandibular bone from a dead animal, followed by immediate tension-free extraction tests. The effects of the complex mechanical strains occurring during implantation were analysed by scanning electron microscopy coupled with electron dispersive spectroscopy. Extensive biocompatibility assays (MTS, immunofluorescence, Western blot) revealed that the bioactive ...
Research Interests: Materials Engineering, Mechanical Engineering, Materials Science, Biomedical Engineering, Hydroxyapatite, and 15 moreHeat Treatment, Dental Implants, Medicine, Adhesion, Biocompatibility, Ceramics, Cell Differentiation, Humans, Bone, Animals, Implant, Magnetic Fields, Bioactive Glass, Dental Implant, and Biocompatible Materials
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Although superficial wounds are often easy to treat for healthy individuals, there are some more severe types of wounds (burns, ulcers, diabetic wounds, etc.) that are a challenge for clinicians. A good therapeutic result is based on the... more
Although superficial wounds are often easy to treat for healthy individuals, there are some more severe types of wounds (burns, ulcers, diabetic wounds, etc.) that are a challenge for clinicians. A good therapeutic result is based on the delivery of a treatment at the right time, for the right patient. Our goal was to sum up useful knowledge regarding wound healing and wound treatments, based on creams and hydrogels with various active ingredients. We concluded that both preparations have application in preventing infections and promoting healing, but their efficacy is clearly conditioned by the type, depth, severity of the wound and patient profile. However, due to their superior versatility and capability of maintaining the integrity and functionality of the active ingredient, as well as it is controlled release at site, hydrogels are more suited for incorporating different active ingredients. New wound healing devices can combine smart hydrogel dressings with physical therapies t...
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Persistent, low-grade inflammation is now considered a hallmark feature of chronic kidney disease (CKD), being involved in the development of all-cause mortality of these patients. Although substantial improvements have been made in... more
Persistent, low-grade inflammation is now considered a hallmark feature of chronic kidney disease (CKD), being involved in the development of all-cause mortality of these patients. Although substantial improvements have been made in clinical care, CKD remains a major public health burden, affecting 10-15% of the population, and its prevalence is constantly growing. Due to its insidious nature, CKD is rarely diagnosed in early stages, and once developed, its progression is unfortunately irreversible. There are many factors that contribute to the setting of the inflammatory status in CKD, including increased production of proinflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, altered metabolism of adipose tissue, and last but not least, gut microbiota dysbiosis, an underestimated source of microinflammation. In this scenario, a huge step forward was made by the increasing progression of omics approaches, specially designed for identification of bio...
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In recent years, natural product's research gained momentum, fueled by technological advancement and open availability of research data. To date, sea buckthorn (Hippophae rhamnoides L. [Elaeagnaceae]) plant parts, especially berries,... more
In recent years, natural product's research gained momentum, fueled by technological advancement and open availability of research data. To date, sea buckthorn (Hippophae rhamnoides L. [Elaeagnaceae]) plant parts, especially berries, are well characterized and repeatedly tested for antioxidant activity and regenerative properties, in various cell types and tissues. However, fatty acids (FA) have been less investigated in term of biological effects, although, they are important bioactive components of the sea buckthorn fruit and oil. The aim of our work was to determine whether sea buckthorn seed oil is a suitable source of FA with regenerative properties on normal skin cells. Using high-performance liquid chromatography (HPLC) and liquid chromatography – mass spectrometry (LC-MS), we purified and characterized four fractions enriched in saturated (palmitic) and non-saturated (linoleic, alfa-linolenic, oleic) FA, which were tested for cytotoxicity, cytokine and growth factor prod...
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Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body’s response to cancer has many parallels with inflammation and repair; the inflammatory cells... more
Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body’s response to cancer has many parallels with inflammation and repair; the inflammatory cells and cytokines present in tumours are more likely to contribute to tumour growth, progression, and immunosuppression, rather than in building an effective antitumour defence. Using new proteomic technology, we have investigated serum profile of pro- (IL-1β, IL-6, IL-8, IL-12, GM-CSF, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF) in order to assess tumoural aggressiveness. Our results indicate significant dysregulation in serum levels of cytokines and angiogenic factors, with over threefold upregulation of IL-6, IL-1β, TNF-α, and IL-10 and up to twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are involved in tumour progression and aggressiveness, and are also involved in...
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Background: The oral squamous cell carcinoma (OSCC) tumor microenvironment (TME) is a complex interweb of cells and mediators balancing carcinogenesis, inflammation, and the immune response. However, cytokines are not only secreted within... more
Background: The oral squamous cell carcinoma (OSCC) tumor microenvironment (TME) is a complex interweb of cells and mediators balancing carcinogenesis, inflammation, and the immune response. However, cytokines are not only secreted within the TME but also released by a variety of other cells that do not comprise the TME; therefore, a thorough assessment of humoral changes in OSCC should include the measurement of serum cytokines. Methods: We assessed the role of various serum cytokines in the evolution of OSCC, before and after treatment, versus a control group. We measured the serum concentrations of MIP-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, and TNF-α. Results: Significantly higher values (p < 0.01) were noted for IL-1β, IL-6, IL-8, IL-10, and TNF-α in the OSCC group before treatment (n = 13) compared with the control group (n = 14), and the increased concentrations persisted after treatment (n = 11). Furthermore, the variations in the values of MIP-1α, IL-1β, IL-10, and TNF-α are...
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Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival... more
Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobul...
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the caused disease - coronavirus. COVID-19 represents an unattended threat for health and life. In the present review we are addressing several hypotheses that may... more
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the caused disease - coronavirus. COVID-19 represents an unattended threat for health and life. In the present review we are addressing several hypotheses that may explain why diabetic patients with SARS-CoV-2 infection are at higher risk of experiencing a severe form COVID-19 disease.
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Despite being a “silent epidemic” disease, chronic kidney disease (CKD) is considered one of the major causes of mortality, together with its main complication, the cardiovascular disease, which contributes to the poor prognosis of these... more
Despite being a “silent epidemic” disease, chronic kidney disease (CKD) is considered one of the major causes of mortality, together with its main complication, the cardiovascular disease, which contributes to the poor prognosis of these patients. Inflammation has been recognized as an essential part of CKD and is closely linked to cardiovascular complications. The identification of novel biomarkers using omics technologies is rapidly advancing and could improve the early detection in renal diseases. Omics approaches, including proteomics, could provide novel insights into disease mechanisms, identifying at the same time accurate inflammatory biomarker panels with an essential role in disease monitoring and follow-up. Recent advances highlight the gut microbiota as an important source of inflammation in kidney diseases. An increasing body of evidence reveals the cross talk between microbiota and host in CKD; in addition, gut dysbiosis may represent an underappreciated cause of infla...
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Objectives. Muscle regeneration after trauma is a complex phenomenon involving several cellular processes, such as angiogenesis, inflammation, fibrosis, activation of satellite cells and their differentiation into myocytes and myotubes.... more
Objectives. Muscle regeneration after trauma is a complex phenomenon involving several cellular processes, such as angiogenesis, inflammation, fibrosis, activation of satellite cells and their differentiation into myocytes and myotubes. Although many studies explored these mechanisms in the last years, there is still an unmet need to find new therapy targets, especially regarding some cellular molecules involved in muscular recovery after mechanical or pathological injury. In the present study we investigated the dynamics of endothelin-1 (ET-1), an important factor that has been shown to be involved in all stages of tissue regeneration, but which is poorly investigated in skeletal muscle. Materials and methods. We used an experimental animal model of acute mechanical trauma on mouse gastrocnemius muscle. ET-1 levels were investigated at different time-points after muscle injury by in situ immunofluorescence, xMAP assay on tissue and serum samples, and Western Blot analysis. Results....
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Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute... more
Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2–4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in rena...
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Non‑melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and... more
Non‑melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun‑protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun‑exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. Aside from the well‑known etiopathogenic factors, studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with the exception of penile SCC, for which a paucity of specific data on their pathogenic role exists. The complex interaction between the peripheral nervous system and target cells in ...
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Chronic kidney disease, despite being a “silent epidemic” disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients.... more
Chronic kidney disease, despite being a “silent epidemic” disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients. The specific objective of our study was to characterize the relationship between the inflammatory status, the bone disorders markers, and kidney failure in chronic kidney disease patient stages 2–4, in order to design a novel biomarker panel that improves early disease diagnosis and therapeutic response, thus being further integrated into clinical applications. A panel of proteomic biomarkers, assessed by xMAP array, which includes mediators of inflammation (IL-6, TNF-α) and mineral and bone disorder biomarkers (OPG, OPN, OCN, FGF-23, and Fetuin-A), was found to be more relevant than a single biomarker to detect early CKD stages. The association between inflammatory cytokines and bone disorders markers, IL-6, TNF-α, OPN, OPG, and FGF-23, reflects the...
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ABSTRACT Cancer Stem Cells (CSC) comprise a concept proposed in the 1990s in hematopoietic cancers. These cells were considered, by similitude to normal stem cells, to constitute a small pool of self-renewing cells able to maintain a... more
ABSTRACT Cancer Stem Cells (CSC) comprise a concept proposed in the 1990s in hematopoietic cancers. These cells were considered, by similitude to normal stem cells, to constitute a small pool of self-renewing cells able to maintain a tumor. Due to their quiescence, CSC would be able to avoid chemotherapeutics targeting fast proliferation rates, or radiotherapy, thus being responsible for tumour relapse. Since CSCs have also been implicated in invasion and metastasis and epithelial to mesenchymal transition (EMT) was proposed as a determinant of malignancy in epithelial cancers, the relationship between EMT and CSC is an important issue, which has been increasingly addressed in recent patents on CSC biology. A thorough search for a more accurate identification of these cells, as well as more effective drug search yielded a number of interesting research patents during the last 5 years, several of which are to be detailed in the present review.