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Objective: Prostate tumors, if prostate cancer or adenoma, represent a major public health challenge. Progress in research on inflammation has revealed a connection between inflammation, immunity, and cancer. In this context, this study aimed to find IL-6 signaling systemic abnormalities in the inflammatory tumor microenvironment., Material and Methods: This study was case-controlled, multicentered, and included 86 patients, 43 diagnosed with BPH and 43 diagnosed with PCa, between January 2019 and January 2020. The study group was homogenous and the studied parameters were IL-6 complex (IL-6, soluble receptor IL-6R, soluble glycoprotein gp130), acute phase proteins (C reactive protein-CRP, acid alpha1 glycoprotein-AGPA, ferritin, albumin, transferrin), and oxidative stress-associated variables (malondialdehyde-MDA, carbonylated protein-PCO, 8-hydroxy-deoxy guanosine-8-OHdG, total antioxidant status-bTAS)., Results: The inflammatory microenvironment determined IL-6 signaling alterations (over-regulation of sIL-6R and suppression of sgp130 in PCa versus BPH), changes in acute phase reaction markers (increased serum levels of CRP, AGPA, ferritin, and decreased serum levels of albumin, transferrin) that were much more evident in PCa compared to BPH, an imbalance between macromolecular oxidative damage (MDA, PCO, 8-OHdG) and endogenous antioxidants (TAS) that was more accentuated in PCa compared with BPH, and a representative association between the sIL-6R/sgp130 ratio and inflammatory/oxidative stress-related factors only in PCa patients., Conclusions: Our study reconfirms the anterior concept that IL-6 promotes prostatic tumorigenesis. In this study, we first demonstrated that a high sIL-6R/sgp130 ratio facilitates prostate malignancy.

Introduction: Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) metabolites. In this study, we aimed to investigate the role of NO metabolites and hypoxia in HPV infection., Materials and Methods: We included 36 patients with palmoplantar warts and 36 healthy subjects and performed serum determinations of NO metabolites (direct nitrite, total nitrite, nitrate, and 3-nitrotyrosine) and HIF1α, a marker of hypoxia., Results: We found elevated serum levels in NO metabolites and HIF1α, and decreased direct nitrite/nitrate ratios in patients with warts versus controls. Additionally, we identified statistically significant positive correlations between NO metabolites and HIF1α levels, except for 3-nitrotyrosine., Conclusions: Our findings show that HPV infection causes hypoxia and alterations in NO metabolism and suggest a link between wart development and cellular stress. Our research could provide new insights for a comprehensive understanding of the pathogenesis of cutaneous HPV infections.

The carcinomas originating from the renal cortex are the most aggressive renal malignancies, with a high tendency for metastasis. Understanding the incidence of cutaneous manifestations caused by renal carcinomas is a challenge. In the first part, this article summarizes a series of factors that promote oncogenesis, invasiveness, and the ability of renal cell carcinoma (RCC) to develop secondary cutaneous manifestations. It is postulated that the cellular stress response is one of the leading causes of developing dermatological events induced by cancers located at distant sites. Furthermore, the paper provides an overview of cutaneous complications associated with renal cancer, categorized as malignant manifestations (metastases, synchronous or metachronous cutaneous malignancies associated with renal cancer), non-malignant indirect cutaneous manifestations associated with renal cancer, and treatment consequences. The data presented in this article suggest that recognizing certain cutaneous disorders could assist the physician in the early identification of renal neoplasms and could lead to a better prognosis.

Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce., Methods: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers-direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis., Results: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP., Conclusion: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense.

Introduction: During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the management of patients with lower urinary tract symptoms (LUTS) underwent dynamic adjustments in response to an evolving understanding of the virus's impact on different patient populations. Healthcare practitioners reevaluated therapeutic approaches for conditions like benign prostatic hyperplasia (BPH), considering the potential implications of this condition on the severity and progression of coronavirus disease 2019 (COVID-19). This study aims to investigate potential correlations between SARS-CoV-2 infection severity, exacerbation of LUTS, and BPH progression., Material and Methods: This retrospective study includes patients hospitalized in our Urology Department between January 2021 and January 2023, presenting with both SARS-CoV-2 and BPH. Their ages ranged from 57 to 88 years, with a mean age of 65.4 years. The diagnosis of BPH relied on a diagnostic triad consisting of digital rectal examination, biological markers (including prostate-specific antigen (PSA) and free PSA, and ultrasound examination, with both conditions confirmed based on test results. Transurethral resection of the prostate (TURP) procedures utilized monopolar Karl Storz resection equipment, using sorbitol and bipolar Olympus devices for transurethral resection of the prostate in saline (TURPis). Haemostasia was performed using roller balls. Anticoagulation followed a prescribed scheme by cardiologists and infectious disease specialists. Statistical analysis was conducted using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp., Results: Among the 138 hospitalized patients affected by both BPH and COVID-19, 18 required emergency endoscopic procedures (specifically TURP or TURPis) to achieve hemostasis (Figures 1, 2). These individuals presented persistent hematuria despite conservative treatments. The mean duration of surgery was 57.9 minutes. Patients who underwent surgery had a longer average hospital stay compared to those who did not, with durations of 10.5 days versus 7.5 days, respectively. Additionally, urethrovesical catheter insertion was necessary in 29 cases due to acute urinary retention or worsening voiding symptoms during hospitalization. These patients are scheduled for further urological evaluation following the resolution of the COVID-19 episode. In a cohort of 53 patients for whom data were accessible, comparisons were made between the pre-COVID status and the levels of the International Prostate Symptom Score (IPSS), post-voiding residue (PVR), and quality of life (QoL). The findings revealed a mean pre-COVID IPSS value of 11.6 and a COVID-related value of 14.2, with a statistically significant difference noted (p < 0.05). The mean pre-COVID PVR was 42.3 cm 2 , whereas during the COVID-19 period, it measured 62.5 cm 2 , also exhibiting a significant difference (p < 0.05). Additionally, the QoL showed a mean pre-COVID-19 score of 2.4 and a COVID-19-associated score of 2.9, again demonstrating statistical significance (p < 0.05)., Conclusion: The onset of the SARS-CoV-2 pandemic posed novel challenges in the medical realm, impacting the approach to BPH management. A common practice was delaying treatment for chronic BPH until viral infection remission to reduce associated risks. Additionally, our study revealed a worse evolution in LUTS among individuals with severe COVID-19 symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Balacescu et al.)

Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)-nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case-control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1.73 mp, and a group of 37 healthy subjects. The laboratory determinations were the serum level of arginine, the enzymatic activity of arginase 2 and inducible nitric oxide synthase, the serum levels of the stable metabolites of nitric oxide (nitrate, direct nitrite, and total nitrite), and the endogenous inhibitors of nitric oxide synthesis (asymmetric dimethylarginine and symmetric dimethylarginine). In the ADPKD group, the levels of the arginine and nitric oxide metabolites were low, while the levels of the metabolization enzymes were higher compared to the control group. Statistical analysis of the correlations showed a positive association between the serum levels of Arg and the eGFR and a negative association between Arg and albuminuria. ADPKD is a metabolic kidney disease that is auxotrophic for arginine. Exploring arginine reprogramming and L-Arg-NO pathways could be an important element in the understanding of the pathogenesis and progression of ADPKD.

Introduction: Research regarding the role of the IL-12 cytokine family in modulating immune and inflammatory responses is continuously evolving. In this study, the contribution of the p35 and p40 subunits as monomers (noted as IL-12p35 and IL-12p40) and heterodimers (noted as IL-12p70 or IL-12p35/p40) was analysed in the pathophysiology and progression of chronic spontaneous urticaria (CSU)., Materials and Methods: We conducted a longitudinal, case-control study involving 42 CSU cases and 40 control cases comprising adults without associated conditions. Serial measurements were performed to assess the serum levels of IL-12p70, IL-12p35, and IL-12p40 at the onset of the disease (pre-therapy phase) and 6 weeks after the initiation of the treatment (post-therapy phase)., Results: During the pre-therapeutic phase of CSU, elevated serum levels of IL-12 cytokine subtypes were detected compared to the control group. The relationship between IL-12 profiles and the course of CSU highlighted the pro-inflammatory role of IL-12p70 and the anti-inflammatory role of IL-12p35. Significant correlations were observed between IL-12p70 levels and the duration of the disease, as well as between IL-12 and the effectiveness of H1-antihistamines., Conclusions: The molecular background for the pleiotropic activities mediated by IL-12-derived cytokines in patients with CSU lies in the strict regulation of the production, signalling pathways, and cytokine-specific influences on the same pathophysiological events. The results of the present study suggest that the superficial layers of the skin serve as a cellular source of IL-12, a cytokine produced through antigenic stimulation. In patients with CSU, we identified independent, additive, or divergent functions of IL-12p70, IL-12p35, and IL-12p40, all relevant to systemic inflammation. These findings prove that the prototype programming of IL-12 is abnormal in CSU.

Cutaneous squamous cell carcinoma (cSCC) arising from the malignant proliferation of epidermal keratinocytes is the second most common skin cancer. Actinic keratosis (AK), which is considered cSCC in situ, may progress into invasive tumors. Currently, there are no serum markers that can differentiate cSCC from AK. The aim of our study was to assess angiogenesis and oxidative stress in patients with cSCC and patients with AK and find reliable serum markers useful in the diagnosis of cSCC. We have determined the serum levels of a group of proangiogenic factors (MMP-2, MMP-9, VEGF, FGF2), the total antioxidative status/capacity (TAS/TAC), ImAnOx, a marker of oxidative stress, and HIF-1 alpha, an indicator of hypoxia. We have identified higher serum levels of MMP-2. MMP-9, VEGF, FGF2 and HIF-1 alpha and lower levels of ImAnOx in cSCC patients compared to AK patients and controls. There were no statistically significant differences between AK patients and controls. We have found positive correlations between proangiogenic markers and HIF-1 alpha and negative correlations between proangiogenic markers and ImAnOx. Our results suggest that MMP-2, MMP-9, VEGF, FGF2, ImAnOx and HIF-1 may be promising markers for differentiating AK from cSCC, and there is a link between angiogenesis, oxidative stress and hypoxia., Competing Interests: The authors declare no conflicts of interest.

It is important to note that maintaining adequate levels of nitric oxide (NO), the turnover, and the oxidation level of nitrogen are essential for the optimal progression of cellular processes, and alterations in the NO cycle indicate a crucial step in the onset and progression of multiple diseases. Cellular accumulation of NO and reactive nitrogen species in many types of tumour cells is expressed by an increased susceptibility to oxidative stress in the tumour microenvironment. Clear cell renal cell carcinoma (ccRCC) is a progressive metabolic disease in which tumour cells can adapt to metabolic reprogramming to enhance NO production in the tumour space. Understanding the factors governing NO biosynthesis metabolites in ccRCC represents a relevant, valuable approach to studying NO-based anticancer therapy. Exploring the molecular processes mediated by NO, related disturbances in molecular pathways, and NO-mediated signalling pathways in ccRCC could have significant therapeutic implications in managing and treating this condition.

Lynch syndrome, characterized by DNA mismatch repair deficiency, represents a significant paradigm among cancer predisposition syndromes and is notably associated with heightened susceptibility to various cancers, particularly colorectal and endometrial malignancies. The primary aim of this research paper is to scrutinize specific associations and delve into the underlying molecular mechanisms of Lynch syndrome. Genetic alterations in MMR genes, including MLH1, MSH2, MSH6, PMS2, and EPCAM, compromise DNA repair mechanisms, predisposing affected individuals to a spectrum of malignancies. This paper comprehensively investigates current screening methodologies and preventive measures tailored for individuals identified or at risk of Lynch syndrome. The integration of advanced sequencing technologies and refined bioinformatics tools has significantly improved mutation detection accuracy, facilitating precise identification of mutation carriers and their at-risk relatives. Moreover, this review emphasizes the evolving diagnostic landscape, which have revolutionized the identification of potential mutation carriers. The structured diagnostic algorithm, incorporating clinical criteria, tumor testing, and genetic analysis, plays a pivotal role in systematically identifying and managing individuals with Lynch syndrome. While the well-established association of Lynch syndrome with colorectal and endometrial cancers is recognized, emerging evidence suggests an increased risk for other types of malignancies. A crucial aspect of this literature review is to extensively analyze the less commonly acknowledged correlation between Lynch syndrome and prostate or testicular malignancies. Understanding these correlations holds significant importance in guiding tailored screening protocols and preventive strategies for individuals carrying Lynch syndrome-associated genetic mutations. The comprehensive assessment of this diverse spectrum of cancers underscores the necessity for tailored surveillance strategies and multidisciplinary approaches to effectively manage and mitigate risks in individuals harboring Lynch syndrome-associated genetic alterations., (Celsius.)

The present paper aimed to investigate the altered angiogenetic mechanisms in hypoxic conditions in patients with prostate tumours, in correlation with common clinicopathologic variables. A case-control study was developed and included 87 patients with prostate tumours [40 diagnosed with benign prostatic hyperplasia (BPH) and 47 diagnosed with prostate cancer (PCa), using prostate transrectal biopsy] and 40 healthy subjects. The following parameters were evaluated in the serum of volunteers: Hypoxia-inducible factor (HIF)-1α, fibroblast growth factor (FGF)-2, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and -9, thrombospondin (TSP)-1 and soluble VEGF-1 receptor. Experimental data analysis demonstrated increasing amounts of inflammation in patients with PCa (IL-6, 18.1±4.7 ng/ml) and BPH (IL-6, 16.3±5.1 ng/ml) vs. control (IL-6, 4.1±1.2 ng/ml); overregulation of HIF1α in patients with PCa (129.3±21.8 ng/ml) compared with patients with BPH (65.6±18.2 ng/ml) and control (61.3±12.7 ng/ml); angiogenesis abnormalities in patients with PCa (upregulation of FGF-2, VEGF, MMP-2 and -9, suppression of TSP-1 and soluble VEGR-1) and BPH (upregulation FGF-2 and VEGF) compared with the control group. In conclusion, a greater understanding of the biological mechanism, the pathological roles and the clinical significance of various proangiogenic parameters and angiogenic-suppressor proteins seem useful in clinical practice for establishing an early diagnosis of prostate pathology and finding an individualized therapeutic approach., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

Two new families of zinc/cobalt/aluminum-based pigments, with a unique composition, were obtained through the polyol method. The hydrolysis process of a mixture of Co(CH 3 COO) 2 , Zn(acac) 2 and Al(acac) 3 (acac - = acetylacetonate ion) in 1,4-butanediol afforded dark blue gels (wPZnxCo1-xAl), in the presence of a supplementary amount of water, and light green powders (PZnxCo1-xAl), respectively, for the water-free procedure ( x = 0, 0.2, 0.4). The calcination of the precursors yielded dark green (wZnxCo1-xAl) and blue (ZnxCo1-xAl) products. XRD measurements and Rietveld refinement indicate the co-existence of three spinel phases, in different proportions: Zn x Co 1- x Al 2 O 4 , Co 3 O 4 and the defect spinel, γ-Al 2.67 O 4 . The Raman scattering and XPS spectra are in agreement with the compositions of the samples. The morphology of wZnxCo1-xAl consists of large and irregular spherical particle aggregates ( ca . 5-100 mm). Smaller agglomerates ( ca . 1-5 mm) with a unique silkworm cocoon-like hierarchical morphology composed of cobalt aluminate cores covered with flake-like alumina shells are formed for ZnxCo1-xAl. TEM and HR-TEM analyses revealed the formation of crystalline, polyhedral particles of 7-43 nm sizes for wZnxCo1-xAl, while for ZnxCo1-xAl, a duplex-type morphology, with small (7-13 nm) and larger (30-40 nm) particles, was found. BET assessment showed that both series of oxides are mesoporous materials, with different pore structures, with the water-free samples exhibiting the largest surface areas due, most likely, to the high percent of aluminum oxide. A chemical mechanism is proposed to highlight the role of the water amount and the nature of the starting compounds in the hydrolysis reaction products and, further, in the morpho-structural features and composition of the resulting spinel oxides. The CIE L * a * b * and C * colorimetric parameters indicate that the pigments are bright, with a moderate degree of luminosity, presenting an outstanding high blueness.

(1) Background: The pathogenesis of systemic lupus erythematosus (SLE) involves complicated and multifactorial interactions. Inducible nitric oxide synthase overactivation (iNOS or NOS2) could be involved in SLE pathogenesis and progression. This study explored the relationship between NOS2-associated inflammation profiles and SLE phenotypes. (2) Methods: We developed a prospective, case control study that included a group of 86 SLE subjects, a group of 73 subjects with lupus nephritis, and a control group of 60 people. Laboratory determinations included serum C reactive protein (CRP-mg/L), enzymatic activity of NOS2 (U/L), serum levels of inducible factors of hypoxia 1 and 2 (HIF1a-ng/mL, HIF2a-ng/mL), vascular endothelial growth factor VEGF (pg/mL), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9-ng/mL), thrombospondin 1 (TSP-1-ng/mL), and soluble receptor of VEGF (sVEGFR-ng/mL). (3) Results: CRP, NOS2, HIF-1a, HIF-2a, VEGF, MMP-2, and MMP-9 were significantly increased, while TSP-1 and sVEGFR were decreased in the SLE and lupus nephritis groups compared with the control group. The variations in these biomarkers were strongly associated with the decrease in eGFR and increase in albuminuria. (4) Conclusions: The inflammatory phenotype of SLE patients, with or without LN, is defined by NOS2 and hypoxia over-expression, angiogenesis stimulation, and inactivation of factors that induce resolution of inflammation in relation with eGFR decline.

Three enantiomeric pairs consisting of copper(II) complexes with tridentate Schiff bases have been synthesized for employing in biological assessments: 1∞[Cu 2 ( R / S -salmet) 2 (H 2 O)] (1-R/S·H2O), 1∞[Cu( R / S -3-HOMe-5-Me-salmet)] (2-R/S), and 1∞[Cu( R / S -3-MeO-salmet)] (3-R/S) (where R / S -salmetH 2 , R / S -3-HOMe-5-Me-salmetH 2 , and R / S -3-MeO-salmetH 2 result from the condensation of R / S -methionine with salicylaldehyde, 2-hydroxy-3-(hydroxymethyl)-5-methylbenzaldehyde, and 3-methoxy-salicylaldehyde, respectively, in a 1 : 1 molar ratio). The crystal structures of 1-R·H2O and 2-R/S are reported. Moreover, the 1-R/S·H2O enantiomers have been subjected to a single-crystal-to-single-crystal (SC-SC) transformation by heating at 160 °C to afford their dehydrated forms, 1∞[Cu 2 ( R / S -salmet) 2 ] (1-R/S), whose structures have also been crystallographically determined. The coordination polyhedra of the metal centers, the binding modes of the ligands, and the 1-D double chain assemblies generated by the chiral mononuclear units are comparatively described. The diffuse reflectance UV-Vis and circular dichroism (CD) spectra of compounds 1-R/S·H2O, 1-R/S, and 2-R/S are analysed with respect to their structural peculiarities and compared to those of 3-R/S. The UV-Vis and CD spectra of solutions of 1-R/S, 2-R/S, and 3-R/S point to the collapse of the double chains via dissolution. Biological tests performed on the model eukaryote Saccharomyces cerevisiae indicated low toxicity for 1-R/S, 2-R/S, and 3-R, and moderate toxicity for 3-S. The S -type complexes were accumulated by cells in higher quantity compared to their R -type counterparts due to selective transport via the high-affinity S -methionine transporter, Mup1. A chemogenomic analysis of 3-S toxicity performed on a collection of yeast knockout mutants revealed that most of the deleted genes identified in the screen were involved in the cell response to oxidative stress, calcium-mediated response, or metal homeostasis. Altogether, it was concluded that 3-S accumulation may perturb the redox state of the cell, also interfering with the calcium-mediated response to oxidative stress or metal-related oxidative stress.

Early detection of bladder cancer has a positive impact on prognosis. A variety of biomarkers have been developed to detect bladder tumors in urine early and reduce the need for cystoscopy. To detect bladder cancer, several methods are available, but their accuracy varies according to the sensitivity and specificity of each method. This review aims to highlight the established detection methods for bladder cancer based on the available literature. In addition, we aim to identify the combination of different effective detection methods that provides the highest degree of accuracy. In our study, a keyword retrieval method was used to search for appropriate English-language references. This bibliography has been indexed in PubMed and Scopus or has been found through systematic searches from 2015 to 2022. Based on an analysis of international guidelines, it has been revealed that there are numerous discrepancies and unresolved issues. The discovery of an ideal detection method for urothelial cell carcinoma biomarkers has been the subject of numerous efforts. In recent years, a wide range of off-label, experimental, novel, and combined approaches have been published on this topic. This review can contribute to the identification of accurate methods of detecting bladder cancer and highlight areas for future research that can be improved.

Hypoxia was intensively studied in cancer during the last few decades, being considered a characteristic of the tumor microenvironment. The aim of the study was to evaluate the capacity of tumor cells to adapt to the stress generated by limited oxygen tissue in cutaneous melanoma. We developed a case-control prospective study that included 52 patients with cutaneous melanoma and 35 healthy subjects. We focused on identifying and monitoring hypoxia, the dynamic of nitric oxide (NO) serum metabolites and posttranslational metabolic disorders induced by NO signaling according to the clinical, biological and tumoral characteristics of the melanoma patients. Our study showed high levels of hypoxia-inducible factor-1a (HIF-1a) and hypoxia-inducible factor-2a (HIF-2a) in the melanoma patients. Hypoxia-inducible factors (HIFs) control the capacity of tumor cells to adapt to low levels of oxygen. Hypoxia regulated the nitric oxide synthase (NOS) expression and activity. In the cutaneous melanoma patients, disorders in NO metabolism were detected. The serum levels of the NO metabolites were significantly higher in the melanoma patients. NO signaling influenced the tumor microenvironment by modulating tumoral proliferation and sustaining immune suppression. Maintaining NO homeostasis in the hypoxic tumoral microenvironment could be considered a future therapeutic target in cutaneous melanoma.

Benign prostatic hyperplasia and prostate cancer are tumoral pathologies characterized by the overexpression of inflammatory processes. The exploration of tumor microenvironment and understanding the sequential events that take place in the stromal area of the prostate could help for an early management of these pathologies. This way, it is feasible the hypothesis that normalizing the stromal environment would help to suppress or even to reverse tumor fenotype. A number of immunological and genetic factors, endocrine dysfunctions, metabolic disorders, infectious foci, nutritional deficiencies, and chemical irritants could be involved in prostate tumor development by maintaining inflammation, affecting local microcirculation, and promoting oxidative stress. Inflammatory processes activate hyperproliferative programs that ensure fibromuscular growth of the prostate and a number of extracellular changes. Acute and chronic inflammations cause accumulation of immunocompetent cells in affected prostate tissue (T cells, macrophages, mastocytes, dendritic cells, neutrophils, eosinophils, monocytes). Prostate epithelial and stromal cells, peri-prostatic fat cells, prostatic microvascular endothelial cells, and inflammatory cells produce cytokines, generating a local inflammatory environment. Interleukin-6 (IL-6) proved to be involved in the prostate tumor pathogenesis. IL-6 ability to induce pro- and anti-inflammatory responses by three mechanisms of signal transduction (classical signaling, transsignaling, cluster signaling), to interact with a diversity of target cells, to induce endocrine effects in an autocrine/paracrine manner, and the identification of an IL-6 endogenous antagonist that blocks the transmission of IL-6 mediated intracellular signals could justify current theories on the protective effects of this cytokine or by alleviating inflammatory reactions or by exacerbating tissue damage. This analysis presents recent data about the role of the inflammatory process as a determining factor in the development of benign and malign prostate tumors. The presented findings could bring improvements in the field of physiopathology, diagnosis, and treatment in patients with prostate tumors. Modulation of the expression and activity of interleukin-6 could be a mean of preventing or improving these pathologies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Cosmin-Victor Ene et al.)

Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of the cutaneous epithelium, is the second most common skin cancer after basal cell carcinoma (BCC). Unlike BCC, cSCC exhibits a greater aggressiveness and the ability to metastasize to any organ in the body. Chronic inflammation and immunosuppression are important processes linked to the development of cSCC. The tumor can occur de novo or from the histological transformation of preexisting actinic keratoses (AK). Malignant cells exhibit a higher amount of sialic acid in their membranes than normal cells, and changes in the amount, type, or linkage of sialic acid in malignant cell glycoconjugates are related to tumor progression and metastasis. The aim of our study was to investigate the sialyation in patients with cSCC and patients with AK. We have determined the serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), beta-galactoside 2,6-sialyltransferase I (ST6GalI), and neuraminidase 3 (NEU3) in 40 patients with cSCC, 28 patients with AK, and 40 healthy subjects. Data analysis indicated a significant increase in serum levels of TSA ( p < 0.001), LSA ( p < 0.001), ST6GalI ( p < 0.001), and NEU3 ( p < 0.001) in the cSCC group compared to the control group, whereas in patients with AK only the serum level of TSA was significantly higher compared to the control group ( p < 0.001). When the cSCC and AK groups were compared, significant differences between the serum levels of TSA ( p < 0.001), LSA ( p < 0.001), ST6GalI ( p < 0.001) and NEU3 ( p < 0.001) were found. The rate of synthesis of sialoglycoconjugates and their rate of enzymatic degradation, expressed by the ST6GalI/NEU3 ratio, is 1.64 times lower in the cSCC group compared to the control group ( p < 0.01) and 1.53 times lower compared to the AK group ( p < 0.01). The tumor diameter, depth of invasion, and Ki67 were associated with higher levels of TSA and LSA. These results indicate an aberrant sialylation in cSCC that correlates with tumor aggressiveness.

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

Background: The pathogenesis of chronic spontaneous urticaria involves metabolic, immunological, and psychological factors. The thiol-disulfide exchange reactions could be a mechanism to counteract oxidative stress in patients with chronic spontaneous urticaria., Objective: The assessment of thiol-disulfide homeostasis parameters (TDHPs) according to disease severity and the influence of H1-antihistamine therapy in patients with chronic spontaneous urticaria., Material and Method: We have included 30 patients with chronic spontaneous urticaria in the study and we have determined the levels of native thiol, total thiol, disulfides as well as the disulfide/native thiol ratio, disulfide/total thiol ratio and the native thiol/total thiol ratio, before and after therapy with H1-antihistamines., Results: The results of the study showed altered levels of TDHPs and their normalization after treatment with H1-antihistamines in patients with chronic spontaneous urticaria. We determined a statistically significant increase in the serum levels of total thiol, native thiol, and native thiol/total thiol ratio and a significant reduction in the levels of disulfides, disulfide/native thiol ratio and disulfide/total thiol ratio after treatment with H1-antihistamines. The normalization of the serum levels of TDHPs has been associated with the relief of symptoms and reduction or resolution of pruritus and urticarial plaques., Conclusion: These results suggest the involvement of thiol-disulfide homeostasis in the defense against the harmful effects of reactive oxygen species in patients with chronic spontaneous urticaria and the potential role of TDHPs in monitoring H1-antihistamine therapy. To the best of our knowledge, this is the first study investigating TDHPs in patients with chronic spontaneous urticaria before and after treatment.

We have investigated glycoconjugates sialization profile, endogen synthesis rate of antiganglioside antibodies (AGA), IL-6 signaling pathways correlated with activity disease in systemic lupus erythematous (SLE) and lupus nephritis (LN)., Material and Methods: A case-control study was developed and included 109 patients with SLE with or without renal impairment, 32 patients with IgA nephropathy and 60 healthy volunteers, clinically and paraclinically monitored. The following parameters were evaluated in volunteers serum: total sialic acid (TSA), orosomucoids, lipid bound sialic acid (LSA), interleukin-6 (IL-6), soluble factors IL-6R, gp130, anti -GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b antigangliosides antibodies of IgG and IgM type., Results: Experimental data analysis showed: increase in synthesis rhythm of sialoglyco-conjugated in SLE (TSA increased in SLE and LN compared to control), accelerated catabolism of LSA in LN (LSA/TSA ratio was higher in SLE and LN than in control group), overexpression of IL-6 mediated trans-signaling (sIL-6R/sgp 130 ratio was subunit in SLE and IgA nephropathy and superunit in LN), large AGA profile synthesis of IgM isotype (over 45.1% in SLE and over 20.7% in LN)., Conclusions: Hypersialization, accelerated glycosphingolipids degradation, IL-6 trans-signaling amplify and AGA pattern could represent essential mechanisms in LN pathogenesis.

Lichen planus (LP) is a chronic, immune-mediated inflammatory skin condition that mainly affects the skin (cutaneous LP, CLP) and oral mucosa (oral LP, OLP). However, the mechanisms involved in the pathogenesis of the disease are not fully elucidated. Over time, several theories that could explain the appearance of LP lesions have been postulated. The key players in LP pathogenesis are the inflammatory infiltrate consisting of T cells and the proinflammatory cytokines. The cytokines stimulate the production of reactive oxygen species that induce cell apoptosis, a defining element encountered in LP. The lead inquiry triggered by this revolves around the role of oxidative stress in LP development. There are currently numerous studies showing the involvement of oxidative stress in OLP, but in terms of CLP, data are scarce. In this review, we analyze for the first time the currently existing studies on oxidative stress in CLP and summarize the results in order to assess the role of oxidative stress in skin lesions offering a fresher updated perspective., Competing Interests: The authors declare no conflict of interest.

Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period of three years and included 55 patients with localized renal cell carcinoma and 30 heathy subjects. Glycosylation, nitration and carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation and proteolytic cleavage were evaluated in the serum of the evaluated subjects in the present study. Our results showed some characteristics for early ccRCC: high production of cytokines, substrate hypersialylation, induced nitrosative and carbonylic stress, arginine hypermethylation, thiol/disulfide homeostasis (TDH) alteration, the regulatory role of soluble receptors (sRAGE, sIL-6R) in RAGE and IL-6 signaling, the modulatory effect of TK-1and TuM2-PK in controlling the level of phosphometabolites in neoplastic cells. These data could be the initial point for development of a panel of biomarkers such as total sialic acid, orosomucoids, nitrotyrosine, carbonylic metabolites, ADMA, SDMA, and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease PTM signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis.

Introduction: Endogenously produced antiganglioside antibodies could affect the evolution of cutaneous melanoma. Epidemiological and experimental evidence suggest "chronic inflammation" to be one of the hallmarks in skin cancers. The aim of the study was to characterize the relation between antiganglioside antibodies and inflammation in cutaneous melanoma focusing on gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, GQ1b. Material and Method . We performed an observational study that included 380 subjects subdivided into three groups: patients with metastatic melanoma (170 cases), patients with primary melanoma (160 cases), and healthy subjects (50 subjects). The assessment of antiganglioside antibodies, IgG, and IgM classes, against -GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b was performed using immunoblot technique (EUROLine kit)., Results: The presence of IgG and IgM antiganglioside antibodies in primary melanoma was (%), as follows: anti-GM1 (5.0 and 13.1), -GM2 (1.8 and 18.1), -GM3 (0.6 and 5.6), -GD1a (0.6 and 15.0), -GD1b (3.7 and 10.7), -GT1b (0.0 and 13.1), -GQ1b (0.0 and 5.0). In metastatic melanoma, the level of antiganglioside antibodies was significantly lower compared with primary melanoma ( p < 0.05), while in the control group they were absent. Antiganglioside antibodies anti-GM1 and -GD1a were positively correlated, while anti-GM3, -GD1b, and -GT1b were negatively associated with the inflammatory markers, interleukin 8 (IL-8), and C reactive protein (CRP)., Conclusions: Tumour ganglioside antigens generate an immune response in patients with primary melanomas. The host's ability to elaborate an early antiganglioside response could be considered as a defence mechanism, directed toward eliminating a danger signal from the tumour microenvironment. Antiganglioside antibodies associated with inflammation markers could be used as diagnostic, monitoring, and treatment tools in patients with cutaneous melanoma., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Corina Daniela Ene et al.)

Background and Objectives: Warts are the most common lesions caused by human papillomavirus (HPV). Recent research suggests that oxidative stress and inflammation are involved in the pathogenesis of HPV-related lesions. It has been shown that the soluble receptor for advanced glycation end products (sRAGE) may act as a protective factor against the deleterious effects of inflammation and oxidative stress, two interconnected processes. However, in HPV infection, the role of sRAGE, constitutively expressed in the skin, has not been investigated in previous studies., Materials and Methods: In order to analyze the role of sRAGE in warts, we investigated the link between sRAGE and the inflammatory response on one hand, and the relationship between sRAGE and the total oxidant/antioxidant status (TOS/TAS) on the other hand, in both patients with palmoplantar warts ( n = 24) and healthy subjects as controls ( n = 28)., Results: Compared to the control group, our results showed that patients with warts had lower levels of sRAGE (1036.50 ± 207.60 pg/mL vs. 1215.32 ± 266.12 pg/mL, p < 0.05), higher serum levels of TOS (3.17 ± 0.27 vs. 2.93 ± 0.22 µmol H2O2 Eq/L, p < 0.01), lower serum levels of TAS (1.85 ± 0.12 vs. 2.03 ± 0.14 µmol Trolox Eq/L, p < 0.01) and minor variations of the inflammation parameters (high sensitivity-CRP, interleukin-6, fibrinogen, and erythrocyte sedimentation rate). Moreover, in patients with warts, sRAGE positively correlated with TAS (r = 0.43, p < 0.05), negatively correlated with TOS (r = -0.90, p < 0.01), and there was no significant correlation with inflammation parameters. There were no significant differences regarding the studied parameters between groups when we stratified the patients according to the number of the lesions and disease duration., Conclusions: Our results suggest that sRAGE acts as a negative regulator of oxidative stress and could represent a mediator involved in the development of warts. However, we consider that the level of sRAGE cannot be used as a biomarker for the severity of warts. To the best of our knowledge, this is the first study to demonstrate that sRAGE could be involved in HPV pathogenesis and represent a marker of oxidative stress in patients with warts.

The constant generation of reactive carbonyl species (RCSs) by lipid peroxidation during aerobic metabolism denotes their involvement in cell homeostasis. Skin represents the largest organ of the body that is exposed to lipid peroxidation. Previous studies have suggested the involvement of oxidative stress in the development of lichen planus (LP), a chronic inflammatory skin condition with a complex pathogenesis. The aim of our study is to investigate a panel of pro-oxidants (4-hydroxy-nonenal (4-HNE), thiobarbituric acid reactive substances (TBARS), and malondialdehyde (MDA)), the total antioxidant status (TAS), and thiol-disulfide homeostasis parameters (TDHP), including total thiol (TT), native thiol (NT), disulfides (DS), DS/NT ratio, DS/TT ratio, and NT/TT ratio. The comparative determinations of serum levels of 4-HNE, TBARS, and MDA in patients with LP ( n = 31) and controls ( n = 26) show significant differences between the two groups (4-HNE: 7.81 ± 1.96 µg/mL vs. 6.15 ± 1.17 µg/mL, p < 0.05, TBARS: 4.23 ± 0.59 µmol/L vs. 1.99 ± 0.23 µmol/L, p < 0.05, MDA: 32.3 ± 6.26 ng/mL vs. 21.26 ± 2.36 ng/mL). The serum levels of TAS are lower in LP patients compared to the control group (269.83 ± 42.63 µmol/L vs. 316.46 ± 28.76 µmol/L, p < 0.05). The serum levels of TDHP are altered in LP patients compared to controls (NT: 388.10 ± 11.32 µmol/L vs. 406.85 ± 9.32., TT: 430.23 ± 9.93 µmol/L vs. 445.88 ± 9.01 µmol/L, DS: 21.06 ± 1.76 µmol/L vs. 19.52 ± 0.77µmol/L). Furthermore, a negative association between pro-oxidants and TAS is identified (4-HNE - rho = -0.83, p < 0.01, TBARS - rho = -0.63, p < 0.01, and MDA - rho = -0.69, p < 0.01). Understanding the mechanisms by which bioactive aldehydes exert their biological effects on the skin could help define effective therapeutical strategies to counteract the cytotoxic effects of these reactive metabolic intermediates.

Recent data suggest that severe psoriasis is an independent risk factor for chronic renal disease. In the present study, we investigated the role of related-purine derivatives as predictors of renal dysfunctions in patients with psoriasis. A prospective study was conducted on a group of 45 patients with psoriasis vulgaris and 45 control cases, monitored over a 5-year period. Alterations of renal function, albumin/creatinine ratio (ACR, mg/g) and UA/creatinine ratio (UACR, mg/mg) were determined in spontaneous urine samples. The status of related-purine derivatives was evaluated by quantification of uric acid (UA, mg/dl), adenosine deaminase (ADA, UI/mg protein), xanthine oxidase (XO, UI/mg protein) and 8-hydroxy-deoxy-guanosine levels (8-OHdG, ng/ml) in serum samples. Compared to the controls, in patients with psoriasis there was an increase in related-purine derivatives levels, which was demonstrated by the elevated serum levels of UA (5.1±0.4 vs. 5.4±1.0, P=0.066), ADA (0.14±0.08 vs. 0.29±0.12, P=0.052), XO (0.22±0.11 vs. 0.42±0.21, P=0.011) and 8-OHdG (3.1±0.05 vs. 8.3±4.7, P=0.002). The serum levels of related-purine derivatives were associated with the severity of psoriasis. In addition, there was a link between the serum levels of related-purine derivatives and markers of renal impairment. There were positive correlations between 8-OHdG and ACR (r=0.452, P=0.028) and between ADA, XO, UA, 8-OHdG and UACR (r=0.297 and P=0.032, r=0.301 and P=0.002, r=0.431 and P=0.027, r=0.508 and P=0.002) and negative correlations between UA, 8-OHdG and the estimated glomerular filtration rate (r=-0.301 and P=0.036, r=-0.384 and P=0.002). Thus, severe psoriasis is a risk factor for the development of renal disease.

Two ZnO materials of spherical hierarchical morphologies, with hollow (ZnO HS ) and solid cores (ZnO SS ), were obtained through the hydrolysis of zinc acetylacetonate in 1,4-butanediol. The nature of the defects and surface reactivity for the two ZnO materials were investigated through photoluminescence, X-ray photoelectron spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy proving the coexistence of shallow and deep defects and, also, the presence of polyol byproducts adsorbed on the outer layers of the ZnO samples. The EPR spectroscopy coupled with the spin-trapping technique showed that the surface of the ZnO samples generates reactive oxygen species (ROS) like hydroxyl ( • OH) and singlet oxygen ( 1 O 2 ) as well as carbon-centered radicals. The ZnO materials exhibited a wide spectrum of antimicrobial activity, being active against Gram-positive, Gram-negative, and fungi strains, both in planktonic and, more importantly, adherent growth states. The decrease of antimicrobial efficiency in the presence of a ROS scavenger (mannitol) and the decrease of the cell viability with the ROS level suggest that one of the mechanisms that governs both the antimicrobial and cytotoxic activities on human liver cells is ROS-mediated. However, at active antimicrobial concentrations, the biocompatibility of the tested materials is very good.

The reaction of chiral sodium complexes, 1 ∞ [Na(S-valmetH)]⋅H 2 O (1-S) and 1 ∞ [Na(R-valmetH)]⋅H 2 O (1-R), with copper(II) acetate affords chiral one-dimensional coordination polymers with the formulas 1 ∞ [Cu(S-valmet)(H 2 O)]⋅H 2 O (2-S) and 1 ∞ [Cu(R-valmet)(H 2 O)]⋅H 2 O (2-R) (R/S-valmetH 2 are Schiff base proligands resulting from the condensation reactions between o-vanillin and R/S-methionine). The copper ions are connected by the carboxylato groups belonging to the amino-acid moieties, resulting in infinite chains showing syn-anti out-of-plane bridging mode. The circular dichroism spectra of 1-S, 1-R, 2-S, and 2-R confirm their enantiomeric nature. Compounds 2-S and 2-R undergo a two-step single-crystal-to-single-crystal transformation, with the elimination of the lattice and coordinated water molecules: 1 ∞ [Cu(S-valmet)(H 2 O)]⋅H 2 O (2-S)→ 1 ∞ [Cu(S-valmet)]⋅H 2 O (3-S⋅H 2 O)→ 1 ∞ [Cu(S-valmet)] (3-S) and 1 ∞ [Cu(R-valmet)(H 2 O)]⋅H 2 O (2-R)→ 1 ∞ [Cu(R-valmet)]⋅H 2 O (3-R⋅H 2 O)→ 1 ∞ [Cu(R-valmet)] (3-R), respectively. During these transformations, every pair of face-to-face chains present in 2-S (or 2-R) has been "zipped up" into a chiral double chain through the removal of the aqua ligands and their replacement by the carboxylato oxygen atoms from the neighboring chain. Consequently, each carboxylato group now bridges three copper ions. The conversion of the single chains, 2-S and 2-R, into the double chains, 3-S and 3-R, is accompanied by a change of the strength of the exchange interactions between the copper ions: weak antiferromagnetic couplings are observed in compound 2-S (J/k B =-1.23(5) K, H=-2J ΣS i S i+1 ) and relatively strong in compound 3-S (J/k B =-76.0(8) K). When the racemic mixture of the ligands, R,S-valmetH 2 , is employed, in the same experimental conditions, a racemic mixture of mononuclear compounds, [Cu(R,S-valmet)(H 2 O) 2 ]⋅H 2 O (4-RS), is obtained. Compound 4-RS also undergoes a SCSC transformation with the elimination of the lattice and one of the coordinated water molecules, resulting in a racemic mixture of chiral chains, 1 ∞ [Cu(R-valmet)(H 2 O)]⋅ 1 ∞ [Cu(S-valmet)(H 2 O)] (5-RS). In this compound, the coupling of the copper(II) ions within the chains is weak and ferromagnetic (J/k B =+0.10(2) K). These results prove that the chirality of the valmetH 2 ligands (optically pure or racemic mixture) plays a key role in the self-assembly process of the copper(II) complexes., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin., Material and Method: We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants included clinical examination and laboratory and imaging tests., Results: Compared to the control group (19.82 mg/dl) the level of ascorbic acid was significantly lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP (8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary concentrations of ascorbic acid were significantly lower in patients with LP associated with infections compared to patients with LP without infections., Conclusions: The urinary ascorbic acid level may be a useful parameter in identifying patients with LP who are at risk of developing viral or bacterial infections.

Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid-gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria.

Lanthanides are a group of non-essential elements with important imaging and therapeutic applications. Although trivalent lanthanide ions (Ln³⁺) are used as potent blockers of Ca²⁺ channels, the systematic studies correlating Ln³⁺ accumulation and toxicity to Ca²⁺ channel blocking activity are scarce. In this study, we made use of the eukaryotic model Saccharomyces cerevisiae to investigate the correlation between Ln³⁺ accumulation, their toxicity and their capacity to block the exogenous stress-induced Ca²⁺ influx into the cytosol. It was found that the Ln³⁺ blocked the Ca²⁺ entry into the yeast cells only when present at concentration high enough to allow rapid binding to cell surface. At lower concentrations, Ln³⁺ were taken up by the cell, but Ca²⁺ blockage was no longer achieved. At 1 mM concentration, all ions from the Ln³⁺ series could block Ca²⁺ entry into cytosol with the exception of La³⁺, and to a lesser extent, Pr³⁺ and Nd³⁺. The plasma membrane Ca²⁺-channel Cch1/Mid1 contributed to La³⁺ and Gd³⁺ entry into the cells, with a significant preference for La³⁺. The results open the possibility to obtain cells loaded with controlled amounts and ratios of Ln³⁺.

Unlabelled: The authors' interest was focused on prolactin status in patients with melanocytic lesions and on changes induced by interferon treatment in melanoma patients., Material and Method: The study lasted 5 years and included 128 melanoma patients, 48 dysplastic nevi patients and 48 healthy volunteers. Sixty melanoma cases were selected after surgical removal of tumor and divided into 2 groups: 30 patients with 10 MUmp(-1) interferon alpha2b treatment, three times a week, one year and 30 patients without interferon treatment. Prolactin assessment was made at inclusion in the study, after surgical removal of tumor, when patients started the treatment, after 1, 6, 12 months of treatment and 6 months after treatment end., Results: In melanoma patients, high values of prolactin (10.55 ± 5.94 ng/ml) were detected when compared with dysplastic nevi group (5.94 ± 2.87 ng/ml) and control group (5.74 ± 3.66 ng.ml). Prolactin levels decreased after surgical removal of melanoma, significantly increased during interferon treatment and returned to baseline few months after the immunomodulatory treatment., Conclusions: The treatment with interferon alpha2b stimulated reversible and non-cumulative prolactin production. Evaluating prolactin in melanoma patients could become necessary in the future, both for finding a possible pituitary disorder, but also for a new pharmacological intervention.

Background: There are several circulatory biomarkers that are involved in forecasting the clinical outcome of cutaneous melanoma. Serum/plasma vitamin D status is one of the markers intensively studied in this type of cutaneous cancer. The combination of validated serum biomarkers (like LDH) with new biomarkers such as IL-8, angiogenic factor, and vitamin D is still at the dawn of research. Hence, we are aiming to establish the predictive power of inflammatory biomarkers, such as IL-8, and metabolic ones, such as vitamin D. These candidate biomarkers are intended to aid classical biomarkers, such as LDH, in the prognosis of cutaneous melanoma., Methods: Serum vitamin D and IL-8 were quantified in melanoma patients and in matching healthy controls., Results: Median serum vitamin D concentrations were significantly lower (p = 0.003) in melanoma patients as compared to healthy control subjects, while around 65% of the investigated patients have proven a severe circulatory deficiency of this vitamin. IL-8 was found increased (p = 0.001) in melanoma patients as compared to controls., Conclusion: Upregulation of proangiogenic factors associated with vitamin D deficiency can prove to be potent future biomarkers candidates, enhancing the predictive power of classical LDH.

Superoxide dismutases (SODs) stand in the prime line of enzymatic antioxidant defense in nearly all eukaryotic cells exposed to oxygen, catalyzing the breakdown of the superoxide anionic radical to O(2) and H(2)O(2). Overproduction of superoxide correlates with numerous pathophysiological conditions, and although the native enzyme can be used as a therapeutic agent in superoxide-associated conditions, synthetic low molecular weight mimetics are preferred in terms of cost, administration mode, and bioavailability. In this study we make use of the model eukaryote Saccharomyces cerevisiae to investigate the SOD-mimetic action of a mononuclear mixed-ligand copper(II) complex, [CuCl(acac)(tmed)] (where acac is acetylacetonate anion and tmed is N,N,N',N'-tetramethylethylenediamine). Taking advantage of an easily reproducible phenotype of yeast cells which lack Cu-Zn SOD (Sod1p), we found that the compound could act either as a superoxide scavenger in the absence of native Sod1p or as a Sod1p modulator which behaved differently under various genetic backgrounds.

Pho84p, the protein responsible for the high-affinity uptake and transport of inorganic phosphate across the plasma membrane, is also involved in the low-affinity uptake of heavy metals in the Saccharomyces cerevisiae cells. In the present study, the effect of PHO84 overexpression upon the heavy metal accumulation by yeast cells was investigated. As PHO84 overexpression triggered the Ire1p-dependent unfolded protein response, abundant plasma membrane Pho84p could be achieved only in ire1Δ cells. Under environmental surplus, PHO84 overexpression augmented the metal accumulation by the wild type, accumulation that was exacerbated by the IRE1 deletion. The pmr1Δ cells, lacking the gene that encodes the P-type ATPase ion pump that transports Ca(2+) and Mn(2+) into the Golgi, hyperaccumulated Mn(2+) even from normal medium when overexpressing PHO84, a phenotype which is rather restricted to metal-hyperaccumulating plants.

The self-assembly process involving the dianion of trimesic acid (Htrim(2-)) and {Cu(tmen)}(2+) templating cations (tmen = N,N,N',N'-tetramethylethylenediamine) affords a new metallacalixarene, [Cu(4)(tmen)(4)(Htrim)(4)] x n H(2)O. The packing of the cyclic molecules in the crystal generates channels that are filled by water molecules. The dehydration-rehydration process of the crystals was found to be reversible.