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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 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 correlated both before and after treatment (p < 0.01). In the pretherapeutic group, IL-6 and IL-8 concentrations also correlate with IL-1β and IL-10 serum levels (p < 0.01), while in the posttherapeutic group, IL-4 varies with MIP-1α and TNF-α (p < 0.01). Conclusion: In OSCC patients, serum cytokine levels are significantly higher compared with control, but they are not significantly altered by treatment, therefore implying that they are also influenced by systemic factors. The interactions between all involved cytokines and the various pathways they regulate warrant further studies to clarify their definitive roles.

Collagen is widely used as a biomaterial in the pharmaceutical and cosmetic industries, in the production of hydrogels, wound dressings, bioactive nano/microfibers, controlled drug delivery systems, etc. The collagen isolated from the aquatic source has a higher biological activity and low risk of transmitting genetic diseases. In recent years the sustainable socio-economic and environmental principles promote the full use of natural resources. Thus, fish collagen extracted from fish by-products (skin, scales, bones and fins) can be valorized as a new collagen alternative source. In this work the enzymatic hydrolysis with pepsin of collagen isolation from silver carp (Hypophthalmichthys molitrix) tails fish has been investigated. We successfully isolated type I collagen with 90-95% purity as determined by FTIR, UV-Vis, EDX and SDS-PAGE analyses. The cytotoxicity of obtained collagen was evaluating by MTS assays.

Background: Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide, leading to significant disease-associated social and financial burdens. The investigation of underlying mechanisms involved in carcinogenesis and tumor progression in OSCC might provide new therapeutic perspectives with an impact on disease control and patient survival. Our study aims to investigate the interrelation between metabolic processes, expressed through final catabolism products and clinicopathological characteristics in OSCC. Materials and methods: This is a single cancer comparative retrospective study investigating metabolic byproducts, namely serum urea, creatinine and uric acid, detected at the moment of diagnosis in patients with OSCC, in comparison to healthy controls. Clinical and paraclinical data regarding exposure to risk factors, disease staging and pathological characteristics were collected for all patients. Subjects with co-existing systemic or metabolic diseases, or with a history of malignancy, were excluded from the study. Subsequently, the metabolic byproducts revealing significant changes in OSCC patients were considered for a correlation analysis with the disease clinico-pathological characteristics. Results: Blood levels for urea, creatinine and uric acid were determined in a total of 225 subjects: 145 patients diagnosed with OSCC and 80 healthy control subjects admitted to our hospital between 2016 and 2021. The comparative analysis between groups revealed that the serum urea level was significantly lower in OSCC patients (p = 0.0344). Serum creatinine and uric acid did not reveal significant differences between groups. Furthermore, in advanced stages of the disease (stages III and IV), the blood level of urea was significantly lower compared to incipient OSCC (stages I and II) (p = 0.003). We found a negative correlation of serum urea levels with smoking (p = 0.0004) and cervical lymph node metastasis (p = 0.0070), and a positive correlation with aging (p = 0.0000). We found no significant correlation of serum urea with primary tumor size (p = 0.5061) and patient survival (p = 0.2932). Conclusions: Decreased serum urea levels are detected in patients with advanced OSCC, in correlation with lymph node metastasis. The invasive features of tumor cells in OSCC might be promoted in association with dysregulation of protein catabolism processes, facilitating aggressive behavior in OSCC.

Glioma is the most common primary intracranial tumor and has the greatest prevalence of all brain tumors. Treatment resistance and tumor recurrence in GBM are mostly explained by considerable alterations within the tumor microenvironment, as well as extraordinary cellular and molecular heterogeneity. Soluble factors, extracellular matrix components, tissue-resident cell types, resident or newly recruited immune cells together make up the GBM microenvironment. Regardless of many immune cells, a profound state of tumor immunosuppression is supported and developed, posing a considerable hurdle to cancer cells’ immune-mediated destruction. Several studies have suggested that various GBM subtypes present different modifications in their microenvironment, although the importance of the microenvironment in treatment response has yet to be determined. Understanding the microenvironment and how it changes after therapies is critical because it can influence the remaining invasive GSCs and lead to recurrence. This review article sheds light on the various components of the GBM microenvironment and their roles in tumoral development, as well as immune-related biological processes that support the interconnection/interrelationship between different cell types. Also, we summarize the current understanding of the modulation of soluble factors and highlight the dysregulated inflammatory chemokine/specific receptors cascades/networks and their significance in tumorigenesis, cancer-related inflammation, and metastasis.

Background: Oral squamous cell carcinoma (OSCC) is a common cancer with high morbidity and mortality. Alterations of antitumor immune responses are involved in the development of this malignancy, and investigation of immune changes in the peripheral blood of OSCC patients has aroused the interest of researchers. Methods: In our study, we assessed the proportions of CD3+ total T lymphocytes, CD3+CD4+ helper T lymphocytes, CD3+CD8+ suppressor/cytotoxic T lymphocytes, CD3−CD19+ total B lymphocytes, and CD3−CD16+CD56+ NK cells in the peripheral blood of OSCC patients. Results: The data obtained both pre- and post-therapy showed a similar level of total CD3+ T lymphocytes in OSCC patients and control subjects, pinpointing the stability of this immune parameter. On the other hand, pre-therapeutic data showed a lower proportion of helper T lymphocytes (CD4+), a significantly higher level of cytotoxic/suppressive T lymphocytes (CD8+), and a much lower CD4+ T lymphocyte/CD8+ T lymphocyte ratio compared to control subjects. Conversely, evaluation of circulating NK (CD16+) cells showed a markedly higher pre-therapeutic level compared to the control group. Conclusions: Our results related to immune changes in the peripheral blood add new information to this complex universe of connections between immuno-inflammatory processes and carcinogenesis.

(1) Background: Oral squamous cell carcinoma (OSCC) is a common malignancy, and the impact of immune and inflammatory mechanisms in its development and progression are of major interest. The aim of our study is to assess the prognostic potential of circulating immune and inflammatory elements determined preoperatively in patients with OSCC, as well as the development of a new compound parameter with predictive value. (2) Methods: We assessed preoperative fibrinogen (Fib) and the platelet-to-lymphocyte ratio (PLR) in 111 OSCC patients. Using a mathematic algorithm, we determined a composite parameter with cumulative information from Fib and PLR, named Fibrinogen-PLR Algorithm (FiPLA). Survival analysis, followed by bivariate and multivariate analyses, was subsequently conducted. (3) Results: Increased preoperative Fib and PLR levels were associated with poor outcome in OSCC (p = 0.0001 and p = 0.0015, respectively). Preoperative FiPLA values were also associated with poor patient survival (p &lt, 0.0001). Multivariate analysis confirmed the independent prognostic role for FiPLA only (CI95% 1.232–67.770, p = 0.03), showing the superior predictive value of FiPLA compared to its individual components. (4) Conclusions: Preoperative assessments of circulating immune and inflammatory elements can provide high-quality prognostic information, and they represent valuable tools in clinical practice, facilitating the early risk stratification of patients with OSCC.

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.

Lead, a high-risk environmental pollutant and extensively used by industry, is one of the most widely outspread toxic metal today. Lead toxicity is a public health problem both for the children and for the adults. Lead does not have any useful functions in the body, instead it produces only harmful effects once it gets into the body. In this study, we investigated the toxicity of lead in an animal model of non-acute exposure. Experimental groups received treatment of aqueous solution lead acetate at different doses and time of administration. Toxic effects of lead were investigated on haematological and behaviour of treated rats. We noticed the disturbances of both haematological parameters and behaviour. Our results indicated that non-acute exposure to lead induced toxic effects in the blood, and central nervous system of adult Wistar rats.

Cancer can take many years to develop from initiation to progression. The long period of development might represent an opportunity to use multi-functional, multi-targeted preventive drugs to block or reverse tumorigenesis. One path to cancer prevention could be to target and reverse the early epigenetic alterations. Unlike genetic mutations, they are potentially reversible and can be restored to their normal state. Epidemiological studies have revealed the close link between rich diets in bioactive compounds and the low incidence of different types of cancer. Thus, the study regarding the impact of bioactive nutrients on the epigenome has become widespread, with focus on the modulation of epigenetic mechanisms of gene expression, such as genomic DNA methylation. Following altered activity and expression of DNA methyl transferases and ten-eleven translocation enzymes, different types of cancers exert local DNA hypermethylation of gene promoters of tumor suppressor genes or of non-coding RNAs (microRNAs and long-noncoding RNAs), as well as global hypomethylation. Recently, the potential of phytochemicals to modulate epigenetic events in human health has become evident, although specific molecular mechanisms are still unclear. Phytochemicals and other bioactive dietary compounds can restore global and gene-specific promoter DNA methylation patterns by reactivating DNA methyltransferases or by providing the provision of methyl groups. Several natural products, such as EGCG, curcumin, sulforaphane, have shown DNMT inhibitory activity, but this property needs more in-depth investigations. This review focuses on the impact of modified DNA methylation pattern on early carcinogenesis and summarizes the effects/mechanism of phytochemical interventions on this type of epigenetic alterations.

Tear composition is a source of information on the health state of the eye. Dry eye syndrome represents nowadays a common disorder that can be associated with other eye diseases, in particular keratoconus. As such, we focussed on the correlation of selected protein levels with ophthalmic parameters and, as a novelty, we explored the possible correlation of these data, classically used in examination, with electron paramagnetic resonance (EPR) spectral parameters of spin probes. Three groups of patients with (i) dry eye syndrome, (ii) dry eye syndrome and keratoconus and (iii) healthy eyes were considered. Tears were collected from the subjects to determine the levels of total protein, lactoferrin, lysozyme and human serum albumin, and to record the EPR spectra of spin probes with fatty acid-like structures: 5-doxyl stearic acid (5-DSA) and 4-(N,N′-dimethyl-N-hexadecyl)ammonium-2,2′,6,6′-tetramethylpiperidine-1-oxyl iodide (CAT16). In tear secretion, the EPR spectra of spin probes showed two components, one with slow dynamics and another one revealing a quasi-isotropic, rapid motion. We analysed in depth the changes observed in the EPR spectra of 5-DSA for the reason that the differences in dynamics between the 5-DSA components are more evident. The challenge of this study was to provide an alternative to biochemical analysis in monitoring the evolution of the health state of patients diagnosed with dry eye syndrome or keratoconus using the information provided by EPR spectra of spin probes. The results indicate a decreased contribution of the EPR component with rapid motion following treatment, and a significant correlation with the Schirmer and/or BUT values.

Past decades demonstrate an increasing interest in herbal remedies in the public eye, with as many as 80% of people worldwide using these remedies as healthcare products, including those for skin health. Sea buckthorn and its derived products (oil, alcoholic extracts), rich in flavonoids and essential fatty acids, are among these healthcare products. Specifically, sea buckthorn and its derivatives are reported to have antioxidant and antitumor activity in dysplastic skin cells. On the other hand, evidence suggests that the alteration of lipid metabolism is related to increased malignant behavior. Given the paradoxical involvement of lipids in health and disease, we investigated how sea-buckthorn seed oil, rich in long-chain fatty acids, modifies the proliferation of normal and dysplastic skin cells in basal conditions, as well as under ultraviolet A (UVA) radiation. Using real-time analysis of normal and dysplastic human keratinocytes, we showed that sea-buckthorn seed oil stimulated the proliferation of dysplastic cells, while it also impaired the ability of both normal and dysplastic cells to migrate over a denuded area. Furthermore, UVA exposure increased the expression of CD36/SR-B2, a long-chain fatty acid translocator that is related to the metastatic behavior of tumor cells.

Inflammation is deeply involved in the development of most types of cancer. Many studies focus on the interaction between immune-inflammatory mechanisms and tumorigenesis in the head and neck squamous cell carcinoma (HNSCC). In this chapter, we emphasize the complexity of processes underlying this interaction and discuss the mechanisms of carcinogenesis in HNSCC with a special focus on metabolic changes, inflammation, and the immune landscape. Unveiling complex connections between immuno-inflammatory processes and tumor initiation, promotion, and progression will open new directions in the reliable identification of predictive factors and therapeutic targets in HNSCC.

Inflammation is deeply involved in the development of most types of cancer. Many studies focus on the interaction between immune-inflammatory mechanisms and tumorigenesis in the head and neck squamous cell carcinoma (HNSCC). In this chapter, we emphasize the complexity of processes underlying this interaction and discuss the mechanisms of carcinogenesis in HNSCC with a special focus on metabolic changes, inflammation, and the immune landscape. Unveiling complex connections between immuno-inflammatory processes and tumor initiation, promotion, and progression will open new directions in the reliable identification of predictive factors and therapeutic targets in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer worldwide. Strong connections have been revealed between immune cells and the pathogenesis of HNSCC. Important differences regarding the levels of immune cell subpopulations in both peripheral circulation and tumor microenvironment were emphasized, with some of them having prognostic significance. In our study, we performed an analysis of immune changes in the tumor tissue and the peripheral blood of untreated HNSCC patients, investigating the proportions of different immune cell populations in these two compartments. The local infiltrating lymphocytes were mainly cytotoxic T cells (CD8+). We have also revealed an increased level of B lymphocytes (CD19+) in the tumor microenvironment. In peripheral blood, the most important lymphocyte subtype was represented by the helper T lymphocytes (CD4+). We also found an increased proportion of circulating NK cells (CD56+). Our results showed significant differences between all investigated lymphocyte subtypes in the peripheral blood and the tumor tissue of untreated HNSCC patients, suggesting that the local and systemic expressions of antitumor immune responses are different and that investigation of immune cell proportions in peripheral circulation has different cues that do not reflect the immune infiltrate pattern within the tumor microenvironment. Further studies are necessary to unveil the complex interplay involving local and systemic events in the immune system’s fight against cancer.

At present, specific therapies for COVID-19 are not well established, being certain only that the immune system plays a decisive role in the initiation and progression of the disease. Plants have given and continue to give compounds with great efficiency and low toxicity, some of them being a starting point for extremely effective synthetic substances. Although herbal remedies are used mainly for preventive purposes, there are also guidelines issued by some countries that indicate the use of traditional remedies for different stages of COVID-19 disease.Europe has a long and strong tradition of using medicinal plants for therapeutic purposes, but clinical trials for this type of approach are scarce, compared to Asia. In this regard, a bridge between tradition and science, would have a strong impact on the capacity for prevention and treatment of COVID-19. The paper reviews compounds of plant origin that have previously proven effective in counteracting some coronaviruses but also some of their major effects - direct action on virus replicative apparatus (viral entry or replication, action on the viral enzymatic system), collateral action of natural compounds on the immune system and also the contribution of herbal medicine as vaccine adjuvants are tackled.

As we are facing one of the major outbreaks of viral infection of the modern history, the SARS-Cov2 pandemic, all the aspects of this new viral infection are explored in an accelerated pace. In all...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the caused disease - coronavirus disease 2019 (COVID-19), has affected so far >6,000,000 people worldwide, with variable grades of severity, and has already inflicted >350,000 deaths. SARS-CoV-2 infection seems severely affected by background diseases such as diabetes mellitus and its related complications, that seem to be favoring the most severe manifestations of SARS-CoV-2 and, therefore, require special attention in clinical care units. The present literature review focus on addressing several hypotheses explaining why diabetic patients could develop multi-organ failure in severe acute respiratory syndrome coronavirus (SARS-CoV) infections. Undoubtedly, as diabetes related complications are present it is expected to emphasize the severity of the COVID-19. Dermatological complications can occur and worsen in diabetic patients, and diseases such as acanthosis nigricans and psoriasis are prone to more severe manifestations of COVID-19. Approaches to treat SARS-CoV-2 infected patients, based on different solutions i.e. plasma therapy, use of antiviral compounds, development of vaccines or new therapeutic agents are ongoing.

Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes&mdash, freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)&mdash, was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p &lt, 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification.

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 immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

Acanthosis nigricans (AN), a skin disorder with high prevalence, represents a dermatological condition with esthetic implications, but otherwise mild symptoms. For any clinician, it is in fact the tip of the iceberg, leading him/her to investigate what lies beneath the surface, since AN points to a systemic problem or disease: metabolic disorder (most frequently), endocrine syndrome, medication side effects, malignancy, and genetic factors. Sometimes, it is the first observed sign of a malignancy or of diabetes mellitus, especially in patients with chronic metabolic disorder; therefore, it is not to be taken lightly. The present review summarizes the information in literature regarding the etiopathogenesis of AN. We propose a new classification that aims to better organize the different types of AN, with implications on the extent and urgency of the investigation plan, as well as various therapeutic algorithms. Therapy options are also presented, both systemic treatments that target the underlying disease, and local ones for esthetic reasons.

Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non‐coding RNAs (lncRNAs) and their main representatives, large intergenic non‐coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem‐like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs‐induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

Cation-substituted hydroxyapatite (HA), standalone or as a composite (blended with polymers or metals), is currently regarded as a noteworthy candidate material for bone repair/regeneration either in the form of powders, porous scaffolds or coatings for endo-osseous dental and orthopaedic implants. As a response to the numerous contradictions reported in literature, this work presents, in one study, the physico-chemical properties and the cytocompatibility response of single cation-doped (Ce, Mg, Sr or Zn) HA nanopowders in a wide concentration range (0.5–5 at.%). The modification of composition, morphology, and structure was multiparametrically monitored via energy dispersive X-ray, X-ray photoelectron, Fourier-transform infrared and micro-Raman spectroscopy methods, as well as by transmission electron microscopy and X-ray diffraction. From a compositional point of view, Ce and Sr were well-incorporated in HA, while slight and pronounced deviations were observed for Mg and Zn, respectively. The change of the lattice parameters, crystallite size, and substituting cation occupation factors either in the Ca(I) or Ca(II) sites were further determined. Sr produced the most important HA structural changes. The in vitro biological performance was evaluated by the (i) determination of leached therapeutic cations (by inductively coupled plasma mass spectrometry) and (ii) assessment of cell behaviour by both conventional assays (e.g., proliferation—3-(4,5-dimethyl thiazol-2-yl) 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, cytotoxicity—lactate dehydrogenase release assay) and, for the first time, real-time cell analysis (RTCA). Three cell lines were employed: fibroblast, osteoblast, and endothelial. When monophasic, the substituted HA supported the cells’ viability and proliferation without signs of toxicity. The RTCA results indicate the excellent adherence of cells. The study strived to offer a perspective on the behaviour of Ce-, Mg-, Sr-, or Zn-substituted HAs and to deliver a well-encompassing viewpoint on their effects. This can be highly important for the future development of such bioceramics, paving the road toward the identification of candidates with highly promising therapeutic effects.

Natural killer cells are the main agents of innate immunity. Since 1970, various studies have repeatedly confirmed their involvement in decreasing local tumor growth and also decreasing the risk of metastasis, due to their cytotoxic effects and also through the release of immunostimulatory cytokines such as IFN-gamma. In the 1990s, several studies demonstrated the existence of certain inhibiting and stimulating receptors of these cells, leading to the concept of “induced self”, thus explaining why tumors with MHC-1 are destroyed and autologous cells without it are saved out. Recognition and destruction of tumor cells by the NK cells are the result of complex interactions between inhibiting and activating factors. This paper, based on extensive research of currently available studies, summarizes the mechanisms employed by the NK cells to destroy the cancer cells, thus highlighting their role in the risk of tumor recurrence as well as their use and handling in certain types of immunotherapy

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 the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene‑related peptide and somatostatin, as well as neurohormones, such as proopiomelanocortin and its derived peptides, α‑melanocyte‑stimulating hormone and adrenocorticotropin. All these factors have been, at least at some point, a subject of debate regarding their precise role in the pathogenesis of NMSC. There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC. Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. Further studies are required in order to elucidate the exact mechanisms through which neuroactive molecules promote or inhibit cutaneous carcinogenesis, as this could lead to the development of more sophisticated and tailored treatment protocols, as well as open new perspectives in skin cancer research.

// Cristiana Pistol Tanase 1,2 , Elena Codrici 1 , Ionela Daniela Popescu 1 , Simona Mihai 1 , Ana-Maria Enciu 1,3 , Laura Georgiana Necula 1,4 , Adrian Preda 5 , Gener Ismail 6,8 and Radu Albulescu 1,7 1 Department of Biochemistry-Proteomics, Victor Babes National Institute of Pathology, Bucharest, Romania 2 Titu Maiorescu University, Faculty of Medicine, Bucharest, Romania 3 Department of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 4 Stefan S Nicolau Institute of Virology, Bucharest, Romania 5 Center for Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania 6 Center of Internal Medicine-Nephrology, Fundeni Clinical Institute, Bucharest, Romania 7 National Institute for Chemical Pharmaceutical R&D, Bucharest, Romania 8 Carol Davila University of Medicine and Pharmacy, Faculty of Medicine, Bucharest, Romania Correspondence to: Cristiana Tanase, email: // Keywords : prostate cancer, biomarkers, proteomics, mass spectrometry, prostasomes Received : July 29, 2016 Accepted : December 27, 2016 Published : January 04, 2017 Abstract The clinical and fundamental research in prostate cancer - the most common urological cancer in men - is currently entering the proteomic and genomic era. The focus has switched from one single marker (PSA) to panels of biomarkers (including proteins involved in ribosomal function and heat shock proteins). Novel genetic markers (such as Transmembrane protease serine 2 (TMPRSS2)-ERG fusion gene mRNA) or prostate cancer gene 3 (PCA3) had already entered the clinical practice, raising the question whether subsequent protein changes impact the evolution of the disease and the response to treatment. Proteomic technologies such as MALDI-MS, SELDI-MS, i-TRAQ allow a qualitative/quantitative analysis of the proteome variations, in both serum and tumor tissue. A new trend in prostate cancer research is proteomic analysis of prostasomes (prostate-specific exosomes), for the discovery of new biomarkers. This paper provides an update of novel clinical tests used in research and clinical diagnostic, as well as of potential tissue or fluid biomarkers provided by extensive proteomic research data.

Ageing is a complex, multi-step process which involves, among others loss of collagen and elastin. Collagen is found in large amounts in the body, especially in the dermis layer. These fibers provide the skin's normal strength, hydration and mechanical properties. Collagen is largely available, as it can be extracted from many animal sources, it can be easily absorbed upon topical administration, hence it is largely used in the cosmetic and pharmaceutical industry for the treatment of premature aging. Bioactive peptides, such as collagen hydrolyzate, are among the most used ingredients for the development of nutraceuticals - food or food ingredients that have defined physiological effects. Numerous studies have demonstrated that peptides resulted from ingestion of hydrolysate collagen and detected in the blood stream have chemotactic properties for skin fibroblasts, helping the skin restoration process. The purpose of this minireview is to present an update on the use of hydrolyzed collagen for skin care.

Recently, a large spectrum of biomaterials emerged, with emphasis on various pure, blended, or doped calcium phosphates (CaPs). Although basic cytocompatibility testing protocols are referred by International Organization for Standardization (ISO) 10993 (parts 1–22), rigorous in vitro testing using cutting-edge technologies should be carried out in order to fully understand the behavior of various biomaterials (whether in bulk or low-dimensional object form) and to better gauge their outcome when implanted. In this review, current molecular techniques are assessed for the in-depth characterization of angiogenic potential, osteogenic capability, and the modulation of oxidative stress and inflammation properties of CaPs and their cation- and/or anion-substituted derivatives. Using such techniques, mechanisms of action of these compounds can be deciphered, highlighting the signaling pathway activation, cross-talk, and modulation by microRNA expression, which in turn can safely pave the road toward a better filtering of the truly functional, application-ready innovative therapeutic bioceramic-based solutions.

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 renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers’ expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

Primary cutaneous amyloidosis (PCA) is a form of localized amyloidosis. It is characterized by the deposition of a fibrillar material in the superficial dermis, without affecting other systems or organs. The diagnosis can be made clinically, but usually a skin biopsy is performed in order to exclude other skin diseases with similar appearance. Reflectance confocal microscopy (RCM) is a novel imaging tool that enables in vivo characterization of various skin changes with a high, quasi-microscopic resolution. This technique might have an important role in the differential diagnosis of cutaneous amyloidosis, by the in vivo assessment of epidermal changes and dermal amyloid deposition. Moreover, it is completely non-invasive and can be safely repeated on the same skin area. However, to date, there is only one published paper presenting the confocal features of primary cutaneous amyloidosis. Hereby, we describe the in vivo RCM features of PCA lesions from a patient with diabetes and correlate them with histologic findings. This strengthens the clinical usefulness of in vivo RCM examination for the non-invasive diagnosis of cutaneous amyloidosis, especially in patients that might associate diseases with impaired wound healing.