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Simple Summary: In this article, we analyze the current state of research on nitric oxide biosynthesis metabolites in clear cell renal cell carcinoma and the metabolic pathways that amplify nitric oxide production in the tumour microenvironment. Special attention is given to nitric oxide homeostasis disruption, mechanisms of nitric oxide biosynthesis and signalling, analysis of nitric oxide bimodal effects, quantitative analysis of nitric oxide, metabolites ureagenic cycle and glutamine metabolism, arginine metabolism and depletion, hyperammonemia, branched-chain amino acids catabolism and nitric oxide-based therapy for cancer. Clarifying these issues will contribute to the development of personalized medicine for patients with clear cell renal carcinoma. 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. [ABSTRACT FROM AUTHOR]

The article entitled "Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials" that belongs to the Special Issue, " Personalized medicine in the field of inflammatory skin diseases", a collection of articles addressing the current critical issues in the pathogenesis and management of chronic inflammatory skin disorders, represents a valuable work that has contributed to elucidating the role of Janus kinase (JAK) inhibitors as a treatment option for atopic dermatitis (AD), as well as their safety profiles. Atopic dermatitis (AD) is a chronic inflammatory condition with a complex pathogenesis based on the interplay between genetic factors, the alteration of the epidermal barrier, abnormalities of the immune response, neuroinflammation, and microbial imbalance [[9], [11]]. In conclusion, JAK inhibitors have revolutionized the treatment of AD patients and also offer fresh perspectives on the pathophysiology of the disease. The results of the study confirmed the effectiveness of JAK inhibitors in AD therapy and indicated that upadacitinib 30 mg is the most effective among all included JAK inhibitors; additionally, delgocitinib 3% b.i.d. is more effective compared to other topical JAK inhibitors [[20]]. [Extracted from the article]

Chronic inflammation is related to regulatory T cells, Th2 cells, and mediators of inflammation such as transforming growth factor beta (TGF)- , interleukin (IL)-4, IL-6, IL-10, and IL-13. Although the five cardinal signs of inflammation (calor, dolor, rubor, tumor and functio laesa) have been described since ancient times, there are still many questions surrounding the inflammatory process. Understanding the mechanisms underlying the pathogenesis of chronic ISDs has led to the development of biological therapies that have dramatically changed the management of conditions such as psoriasis and atopic dermatitis, considerably improving patients' quality of life. The skin provides more than a simple mechanical barrier against external aggressors; it is an array of effector cells and molecules that constitute the skin's immune system, as defined by Bos and Kapsenberg in 1986 [[1]]. [Extracted from the article]

We present the case of a 39-year old male patient with various comorbidities including spastic paraparesis due to peripartum hypoxia subsequent to a gemellary pregnancy, coexisting with seizures (under treatment with sodium valproate), intravenous drug abuse since childhood, chronic hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection. Numerous hospitalizations and continuously monitored combined antiretroviral therapy were required for HIV infection. His immunocompromised status led to an infection started in 2013 with multi-drug resistant Mycobacterium tuberculosis, debuted in a lymph node and further extended to the lungs, brain and spleen, remitted after 2015. Since 2018, a different clinical entity appeared and the patient presented multiple condylomas in the genital and inguinal regions. The lesions progressed rapidly despite the self-administered treatment with 5mg/ml podophyllotoxinum cutaneous solution. During the most recent admissions the clinical picture consisted of extensive exophytic cauliflowerlike protrusions as well as plane brown-violaceous tumour masses located in the genital area, completely covering the inguinal folds, penian basis and scrotum bilaterally, without tendency to spontaneous remission. During hospitalization, multiple cryotherapy sessions combined with podophyllin cream 25% were performed. Due to a deficiency and asymmetry in walking, with the left lower limb more adducted than the right one, leading to relative closure of the right inguinal fold, lack of ventilation and a tendency to moisture formation and tissue maceration, the healing was slower on this side. The patient was discharged with an indication for home treatment with an ointment containing Camellia sinensis dry leaf extract, remaining under observation with monthly controls for some persisting lesions. [ABSTRACT FROM AUTHOR]

Sobolev et al. found a differential expression of six estrogen-controlled genes (HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2) in the skin of female patients with psoriasis compared to male patients with psoriasis and concluded that these proteins may be involved in the defense of skin cells against inflammation damage. Inflammatory skin diseases occur after the onset of abnormal immune cell responses and the activation of various immune signaling pathways in the skin [[1]]. In the treatment of atopic dermatitis, important advances are being made, and Janus kinase inhibitors (JAK) represent new treatment options. Personalized medicine stratifies patients based on molecular markers and allows the identification of the best possible solution for the patient. [Extracted from the article]

Psoriasis is a highly prevalent dermatological disease associated with an increased systemic inflammatory response. In addition, joint involvement is also present in around 20% of patients. Therefore, treatment modalities used in this condition should be simultaneously effective at improving skin manifestations, reducing inflammation, and addressing psoriatic arthritis when present. Twenty years ago, the introduction of biologic treatments for psoriasis was a turning point in the management of this condition, offering an effective and reasonably safe option for patients whose disease could not be adequately controlled with conventional therapies. At the moment, Janus Kinase inhibitors (JAKis) are a new class of promising molecules in the management of psoriasis. They are orally administered and can show benefits in patients who failed biologic therapy. We conducted a scoping review in order to identify randomized-controlled trials that investigated different JAKis in patients with plaque psoriasis and psoriatic arthritis, with an emphasis on molecules that have been approved by the European Medicines Agency and the Food and Drug Administration. The added value of this study is that it collected information about JAKis approved for two different indications, plaque psoriasis and psoriatic arthritis, in order to provide an integrated understanding of the range of effects that JAKis have on the whole spectrum of psoriasis manifestations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer with a complex but not fully understood pathogenesis. Recent research suggests the role of beta human papillomavirus (HPV) types and HPV-associated inflammatory processes in cSCC development. Beta HPV types are components of the normal flora; however, under the influence of certain cofactors, the virus may trigger a malignant process. Dysregulation of the immune system (chronic inflammation and immunosuppression), environmental factors (ultraviolet radiation), and genetic factors are the most important cofactors involved in beta HPV-related carcinogenesis. In addition, the oncoproteins E6 and E7 of beta HPV types differ biochemically from their counterparts in the structure of alpha HPV types, resulting in different mechanisms of action in carcinogenesis. The aim of our manuscript is to present an updated point of view on the involvement of beta HPV types in cSCC pathogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a modern, non-invasive therapeutic method used for the destruction of various cells and tissues. It requires the simultaneous presence of three components: a photosensitizer (PS), a light source and oxygen. Precancerous skin lesions are conditions associated with a high likelihood of malignant transformation to squamous cell carcinoma. Data available so far indicate that PDT is a promising treatment method which can be successfully employed in several medical fields including dermatology, urology, ophthalmology, pneumology, cardiology, dentistry and immunology. Numerous authors therefore have studied this technique in order to improve its efficacy. As a result, significant advancement has been achieved with regard to PSs and drug delivery systems. Substantial progress was also obtained with respect to PDT for the treatment of precancerous skin lesions, several authors focusing their efforts on the study of daylight-PDT and on identifying methods of decreasing technique-related pain. This review reports on the most recent findings in PDT, with emphasis on cutaneous precancerous lesions. [ABSTRACT FROM AUTHOR]

Lichen planus (LP) is an immune-mediated inflammatory disease that particularly affects the skin and mucous membranes. Its etiology remains elusive, however some trigger factors, including viral or bacterial antigens, drugs and metals, have been postulated. There is a higher prevalence of hepatitis C virus (HCV) infection among patients with LP, with some geographical variations. HCV is an enveloped RNA virus that belongs to the Flaviviridae family and in most instances causes chronic liver infections. It has been hypothesized that HCV may contribute to LP development, but the link between the two disorders is not fully understood. It is still debatable whether HCV leads to the occurrence of LP lesions directly by replication inside the infected cells or indirectly by activating immunological pathways. Molecular studies have revealed HCV RNA in specimens collected from patients with LP. The autoimmune theory was also suggested given that several studies have revealed viral replication and immune response activation associated with autoantibody synthesis. The aim of this review is to summarize the main potential mechanisms involved in the association between LP and HCV infection. Understanding the link between the two disorders may shed some light on the pathogenesis of LP, which is a challenging issue. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Psoriasis is a common disease affecting people worldwide. Although many researchers have tried to understand, throughout history, the mechanisms involved in the pathogenesis of the disease and despite considerable progress that has been made, a plethora of key aspects are still waiting to be discovered. In the last 2,000 years, the treatment evolved from an empirical stage to the modern therapy oriented to targeting molecules shown to be involved in the occurrence of the disease. In this paper we are reviewing the great discoveries that have marked the history of psoriasis, as well as the latest advances in the treatment of the disease. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common tumour of the oral cavity, associated with significant morbidity and mortality. It is a multifactorial condition, both genetic and environmental factors being involved in its development and progression. Its pathogenesis is not fully elucidated, but a pivotal role has been attributed to inflammation, strong evidence supporting the association between chronic inflammation and carcinogenesis. Moreover, an increasing number of studies have investigated the role of different mediators of inflammation in the early detection of OSCC. In this review, we have summarized the main markers of inflammation that could be useful in diagnosis and shed some light in OSCC pathogenesis. [ABSTRACT FROM AUTHOR]

Psoriasis is a common disease affecting people worldwide. although many researchers have tried to understand, throughout history, the mechanisms involved in the pathogenesis of the disease and despite considerable progress that has been made, a plethora of key aspects are still waiting to be discovered. in the last 2,000 years, the treatment evolved from an empirical stage to the modern therapy oriented to targeting molecules shown to be involved in the occurrence of the disease. in this paper we are reviewing the great discoveries that have marked the history of psoriasis, as well as the latest advances in the treatment of the disease. [ABSTRACT FROM AUTHOR]

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with significant impact on patients’ quality of life. Malignant transformation into oral squamous cell carcinoma (OSCC) is considered as one of the most serious complications of the disease; nevertheless, controversy still persists. Various factors seem to be involved in the progression of malignant transformation; however, the mechanism of this process is not fully understood yet. Molecular alterations detected in OLP samples might represent useful biomarkers for predicting and monitoring the malignant progression. In this review, we discuss various studies which highlight different molecules as ominous predictors of OLP malignant transformation. [ABSTRACT FROM AUTHOR]

Psoriasis is a physically, emotionally, and socially invalidating multifactorial disorder, with a significant impact on the patients’ quality of life. Stress is one of the leading triggers for psoriasis and has been associated with disease onset and subsequent flare-ups, while the flare-ups by themselves often lead to psychological discomfort. The treatment of psoriasis is individualized, depending on the patients’ measurable severity of illness, as well as the impact the skin condition has on patients’ quality of life, as assessed by standardized questionnaires. The clinical scales used nowadays for measuring the severity of psoriasis are characterized by low reproducibility and high variability between examiners. Hence, there is a real need to identify objectively measurable biomarkers to standardize the assessment of the severity of psoriasis. We aim to review the pathophysiological mechanisms involved in psoriasis, focusing on the most critical advances in psoriasis biomarker discovery, pointing out those biomarkers which have also been studied in other stress-related conditions, thus emphasizing the relationship between psoriasis and stress. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, immune-mediated disorder characterized by well demarcated, erythematous plaques covered by thick, silvery-white scales, most often located on the knees, elbows, sacral area and scalp. It has a significant impact on the patient's quality of life. Biological therapies revolutionized the treatment of psoriasis vulgaris but there has been concern regarding the use of those agents due to severe adverse reactions reported in patients receiving TNF-α inhibitors for various inflammatory diseases. The aim of this paper is to review the most important adverse reactions reported in patients receiving biological treatments. The most common and severe side effects associated with biologicals are infections, cardiac adverse reactions, neurologic adverse reactions, lymphomas, non-melanoma skin cancers and hepatobiliary disease. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is the inability to achieve and maintain an erection sufficient for satisfactory sexual intercourse. It is the most frequent sexual dysfunction in elderly men and its prevalence increases with age. Ever since ED was recognized as a real health problem, several treatment options became available and some of them proved to be very efficient. PDE5 inhibitors are the mainstay treatment of ED. However, other treatment options such as intracorporal injections, surgery, vacuum devices and prosthesis are also available for patients who are unresponsive to PDE5 inhibitors. Since none of the treatment options available so far has proven ideal, research in the field of sexual medicine continues. The aim of this paper is to review the most advances in the treatment of ED. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is a modern treatment with applications in several medical specialties, which has been intensely studied in the last years. The main indications in dermatology are actinic keratosis, superficial basal cell carcinoma and Bowen's disease-common skin disorders in which photodynamic therapy proved its efficacy. At present, the use of photodynamic therapy for the treatment of other skin disorders is profoundly researched. Pain is the most common and redoubtable adverse effect of photodynamic therapy and it is the most important factor affecting the patient's adherence to treatment. The aim of this article is to look over the most recent medical studies regarding pain in PDT, with emphasis on the factors affecting the occurrence of pain and the most recent strategies for controlling photodynamic therapy-related pain. [ABSTRACT FROM AUTHOR]

Oral hairy leukoplakia is a lesion of the oral mucosa caused by infection with the Epstein-Barr virus. It was first described in 1984 in homosexual men infected with the human immunodeficiency virus (HIV) but it was later associated also with other forms of immunosuppression. In HIV infected patients this lesion proved to be associated with progression to acquired immunodeficiency syndrome (AIDS). We report the case of a 32 year-old patient that presented for acneiform lesions on the face and thorax. Apart from acne vulgaris lesions, the clinical examination revealed irregular, adherent, undetachable and corrugated white plaques located on the tongue and oral mucosa. The presumptive diagnosis was oral hairy leukoplakia. Testing for HIV was recommended and the result was positive. CD4 cell count at the time of treatment initiation was 7 cells/mm3. After three months of antiretroviral therapy, the lesions resolved completely. The particularity of the case resides in the peculiar distribution and extent of the lesions and the late diagnosis of HIV/AIDS. In this case, oral hairy leukoplakia was the single marker of immunosuppression. [ABSTRACT FROM AUTHOR]

Buschke-Löwenstein tumor (BLT) is a rare premalignant disorder, with a considerable potential of malignant transformation into squamous cell carcinoma; HPV infection (especially HPV 6 and HPV 11) have an important role in the ethiopathogeny of the disease, along with immunosuppression- usually caused by HIV virus, a frequently encountered association. We report on the case of a 47 year old male patient who addresses our clinic for the occurrence of a giant tumoral lesion located in the intergluteal cleft, which had rapidly evolved despite the repeatedly negative HIV testing. The histopathologic examination confirms the clinical diagnosis of BLT; wide surgical excision of the tumor with safety margins was not followed by recurrence, during a follow-up period that exceeded 12 months. The case is distinguished through the large dimensions of the tumor, the extremely rare anatomical situation and the rapid evolution, despite the absence of HIV immunosuppression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common skin malignancy, which rarely metastasizes but has a great ability to infiltrate and invade the surrounding tissues. One of the molecular players involved in the metastatic process are matrix metalloproteinases (MMPs). MMPs are enzymes that can degrade various components of the extracellular matrix. In the skin, the expression of MMPs is increased in response to various stimuli, including ultraviolet (UV) radiation, one of the main factors involved in the development of BCC. By modulating various processes that are linked to tumor growth, such as invasion and angiogenesis, MMPs have been associated with UV-related carcinogenesis. The sources of MMPs are multiple, as they can be released by both neoplastic and tumor microenvironment cells. Inhibiting the action of MMPs could be a useful therapeutic option in BCC management. In this review that reunites the latest advances in this domain, we discuss the role of MMPs in the pathogenesis and evolution of BCC, as molecules involved in tumor aggressiveness and risk of recurrence, in order to offer a fresh and updated perspective on this field. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common malignant skin tumor. BCC displays a different behavior compared with other neoplasms, has a slow evolution, and metastasizes very rarely, but sometimes it causes an important local destruction. Chronic ultraviolet exposure along with genetic factors are the most important risk factors involved in BCC development. Mutations in the PTCH1 gene are associated with Gorlin syndrome, an autosomal dominant disorder characterized by the occurrence of multiple BCCs, but are also the most frequent mutations observed in sporadic BCCs. PTCH1 encodes for PTCH1 protein, the most important negative regulator of the Hedgehog (Hh) pathway. There are numerous studies confirming Hh pathway involvement in BCC pathogenesis. Although Hh pathway has been intensively investigated, it remains incompletely elucidated. Recent studies on BCC tumorigenesis have shown that in addition to Hh pathway, there are other signaling pathways involved in BCC development. In this review, we present recent advances in BCC carcinogenesis. [ABSTRACT FROM AUTHOR]

Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis. The pathogenic model leading to the formation of psoriatic plaques has however evolved a lot over the years. There is now enough evidence to support the role of interleukin (IL) -23, IL-17, IL-22, T helper (Th) -17 cells, Th-22 cells, T regulatory cells, transforming growth factor (TGF)-β1 and IL-10 in the pathogenesis of the disease. Moreover, several inflammatory and anti-inflammatory molecules are currently being investigated, some of them showing promising results. The aim of this paper is to look over the most recent advances in the immunological pathways involved in the pathogenesis of psoriasis vulgaris. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) is an esthetic condition with varying psycho-social implications, easily accepted by some patients and tolerated only with difficulty by others. Modern therapeutic options such as 5α-reductase inhibitors have significant outcomes, but also exert significant side effects in a subset of patients. The literature describes three distinct situations regarding finasteride administration, a compound largely used for AGA. Some studies show finasteride to be very safe with minimal or no side effects. Other studies take a more cautious approach, recognizing such side effects but, at the same time, considering the putative relationship between finasteride and adverse effects to be disputable, given that placebo administration in AGA is associated with relatively similar or even more severe side effects. Finally, some authors/studies are concerned that, when compared to placebo, finasteride administration may result in side effects with greater frequency and severity, and sometimes that persist even after treatment cessation in the form of post-finasteride syndrome. Several factors presented in this paper appear to explain finasteride inconsistency regarding its therapeutic and side effects. Such factors should be further investigated and used to categorize subjects into distinct subgroups, either predisposed to adverse reactions or more tolerant of the finasteride administration. [ABSTRACT FROM AUTHOR]

Capsaicin is a natural protoalkaloid recognized as the main pungent component in hot peppers (Capsicum annuum L.). The capsaicin receptor is highly expressed in the unmyelinated type C nerve fibers originating from small diameter sensory neurons in dorsal root ganglia and cranial nerve ganglia correspondents. Capsaicin and related vanilloids have a variety of effects on primary sensory neurons function, from sensory neuron excitation characterized by local burning sensation and neurogenic inflammation, followed by conduction blockage accompanied by reversible ultrastructural changes of peripheral nociceptive endings (desensitization), going as far as irreversible degenerative changes (neurotoxicity). The main role in capsaicin-induced neurogenic inflammation relies on the capsaicin sensitive, small diameter primary sensory neurons, therefore its evaluation could be used as a diagnostic instrument in functional alterations of cutaneous sensory nerve fibers. Moreover, capsaicin-induced desensitization and neurotoxicity explain the analgesic/anti-nociceptive and anti-inflammatory effects of topical capsaicin and its potential use in the management of painful and inflammatory conditions. In this study, we describe the effects of capsaicin on neurogenic inflammation and nociception, as well as its potential diagnostic value and therapeutic impact in various conditions involving impairment of sensory nerve fibers. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit. Its pathogenesis is multifactorial and involves the overlap between four main processes: alteration of the keratinization, increased sebum production, colonization with Cutibacterium acnes, and inflammation. The role of oxidative stress (OS) has been intensively studied in inflammatory skin conditions such as psoriasis, vitiligo, or atopic dermatitis. However, the involvement of OS in the pathogenesis of acne is less known. The evidence accumulated over the last decade suggests that in the case of acne patients, there is an imbalance between oxidants and antioxidants. In this review, we analyzed studies that evaluated markers of OS in patients with acne, published in the last ten years, with the aim of providing new insights into the pathogenesis of acne. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are infamous for their role in potentially fatal anaphylaxis reactions. In the last two decades, a more complex picture has emerged, as it has become obvious that MCs are much more than just IgE effectors of anaphylaxis. MCs are defenders against a host of infectious and toxic aggressions (their interactions with other components of the immune system are not yet fully understood) and after the insult has ended, MCs continue to play a role in inflammation regulation and tissue repair. Unfortunately, MC involvement in pathology is also significant. Apart from their role in allergies, MCs can proliferate clonally to produce systemic mastocytosis. They have also been implicated in excessive fibrosis, keloid scaring, graft rejection and chronic inflammation, especially at the level of the skin and gut. In recent years, the term MC activation syndrome (MCAS) was proposed to account for symptoms caused by MC activation, and clear diagnostic criteria have been defined. However, not all authors agree with these criteria, as some find them too restrictive, potentially leaving much of the MC-related pathology unaccounted for. Here, we review the current knowledge on the physiological and pathological roles of MCs, with a dermatological emphasis, and discuss the MCAS classification. [ABSTRACT FROM AUTHOR]

HPV infection affects a significant number of individuals in the general population. HPV is a DNA virus with tropism for skin and mucous membranes; up to date, more than 200 types have beeen identified. HPV infection causes various disorders, cutaneous and anogenital warts accounting for a large number of cases. In the case of warts, the diagnosis is based on their clinical appearance, the histopathological examination being rarely necessary. Many therapeutic modalities, with variable efficacy, are available. Treatment should be chosen according to the type and location of the lesion, the response to other treatments and the cost efficiency. In addition to conventional therapies (keratolytic agents, cryotherapy), modern therapies such as photodynamic therapy and immunotherapy have been developed, the results being encouraging. [ABSTRACT FROM AUTHOR]

Lichen planus (LP) is an autoimmune, inflammatory skin disorder commonly associated with hepatitis C virus (HCV) infection. Gamma-glutamyl transpeptidase (GGT) plays an important role in modulating the skin response to various internal or external injuries. In order to evaluate the effects of HCV on GGT pro-oxidative activities, we performed a comparative study between LP patients without viral infections and patients with asymptomatic HCV infection (HCV carriers). Our conclusion is that asymptomatic HCV infection induces a functional GGT deficiency, resulting in the alteration of the enzyme’s ability to reduce the toxic effects of free radicals, neutralize unstable oxygen species and prevent the oxidation of certain molecules in the infected tissue. [ABSTRACT FROM AUTHOR]

Introduction. Many epidemiological, clinical and experimental studies have sugested a possible role of infectious agents in the etiopathogenesis of lichen planus. In this paper, the authors performed a retrospective analysis for the presence of hepatitis B (HBV) and C (HCV) viruses in patients with lichen planus, between 2004-2016. Material & Method. The serological screening was realised for 157 patients with lichen planus in order to detect anti-HCV antibodies and HBs antigen. In the case of a positive result for anti-HCV antibodies, confirmatory tests were performed. Results. Among patients with lichen planus diagnosed based on clinical and histopathological aspects, it was found that 12 patients were infected with HCV (7.6%), 4 patients were infected with HBV (2.6%) and 1 patient with HBV/HCV coinfection (0.6%). Conclusions. Based on these results, the authors do not consider that hepatitis viruses play an essential role in the pathophysiology of lichen planus. However it should be noticed the high percentage of cases of HCV infection among these patients. Early identification and treatment of these infections in patients with lichen planus could influence in a positive way the course of the cutaneous disease. [ABSTRACT FROM AUTHOR]

Seborrheic dermatitis (SD) is a relapsing inflammatory skin disorder that affects the seborrheic areas of the body. Its etiology is not completely elucidated; however, the link between disease exacerbations and the proliferation of Malassezia spp., along with the good response to antifungal agents, indicate the role of fungi in its pathophysiology. Sertaconazole nitrate is a relatively new imidazole antifungal agent with a particular structure, consisting in a benzothiophene ring similar to the indole ring of tryptophan, and it acts mainly through the inhibition of ergosterol synthesis and the formation of pores in the fungal cell membrane. The aim of our study was to evaluate the efficiency of sertaconazole 2% cream compared with other topical treatments in patients with SD. We performed an extensive literature search by browsing the PubMed database with the keyword combination "sertaconazole AND seborrheic dermatitis AND clinical trial", which retrieved eight controlled clinical trials evaluating the effects of sertaconazole in SD. All of the clinical trials included a standard scoring index (SI). At 28 days since the beginning of the treatment, the sertaconazole regimen was associated with a significantly higher percentage of patients with mild SI and a lower percentage of patients with moderate or severe SI (odds ratio 0.51) than the other investigated treatments—hydrocortisone, ketoconazole, clotrimazole, metronidazole, pimecrolimus, and tacrolimus (odds ratio 1.95). In conclusion, treatment with sertaconazole 2% cream may represent an efficient alternative therapy for patients with SD. [ABSTRACT FROM AUTHOR]

The incidence of melanoma, a very aggressive skin cancer, has increased over the past few decades. Although there are well-established clinical, dermoscopic and histopathological criteria, the diagnosis is often performed late, which has important implications on the patient's clinical outcome. Unfortunately, melanoma is one of the most challenging tumors to diagnose because it is a heterogeneous neoplasm at the clinical, histopathological, and molecular level. The use of reliable biomarkers for the diagnosis and monitoring of disease progression is becoming a standard of care in modern medicine. In this review, we discuss the latest studies, which highlight findings from the genomics, epitranscriptomics, proteomics and metabolomics areas, pointing out different genes, molecules and cells as potential diagnostic and prognostic biomarkers in cutaneous melanoma. [ABSTRACT FROM AUTHOR]

Vulvodynia is a chronic condition which affects an increasing number of women; it presents currently an incidence that is higher than had previously been estimated. Regarding pathogenesis, several (hormonal, infectious, inflammatory and psychological) factors have been proposed, but vulvodynia etiology remains still unclear. This disorder is a multifactorial condition with a significant impact on the patient’s quality of life, yet is difficult to diagnose (an under-estimated/ under-recognized affection). Certain medical investigations are required in order to exclude other diseases (the diagnosis of vulvodynia being one of exclusion), but anamnesis and physical examination are essential steps in the diagnosis. Although many therapies have been proposed, both pharmacological and non-pharmacological, a standardized therapy has not yet been established/ generally accepted. Accordingly, many therapeutic options have been studied with varying results. Vulvodynia remains a challenging disease and a multidisciplinary approach is needed to achieve satisfactory outcomes. Further studies are needed to completely understand its pathogenesis and to develop a standardized treatment. [ABSTRACT FROM AUTHOR]

Significant progress has been made in the therapy of hepatitis C, but many things are still unknown about its pathogenesis. The course of hepatitis C is influenced by both host and virus characteristics. More and more studies highlight the role of oxidative stress in the pathogenesis of hepatitis C. Core protein plays a key role in the generation of reactive oxygen species. In addition, the most important complications of the infection, cirrhosis and hepatocellular carcinoma, seem to be related to the presence of oxidative stress. In this context antioxidants could be a useful adjuvant therapy. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory skin disorder, which affects an important segment of the general population. Its etiology is unknown, but the interest of many researchers is directed to the role of microorganisms, especially to Demodex mites and Helicobacter pylori. A higher density of Demodex mites were noticed in patients with rosacea than in the general population. Demodex mites seem to be involved in the initiation of an inflammatory process by destroying the cutaneous barrier. On the other hand, many studies show a higher prevalence of the infection with H. pylori in patients with rosacea than in the control group and the improvement of the skin lesions after the eradication of the infection. Moreover the oxidative stress induced by the microorganism seems to play an important role in the development of the lesions. However, further studies are still needed to understand the role of these microorganisms in the pathogenesis of rosacea. [ABSTRACT FROM AUTHOR]

Cases of multidrug resistant tuberculosis are on the rise in many regions; therefore prevention programs are fundamental to reduce the incidence of tuberculosis. Knowledge of the risk factors and understanding of the mechanisms which underlie the acquired resistance of Mycobacterium tuberculosis strains can contribute to the implementation of prevention and control strategies. This paper reviews the main risk factors and mechanisms involved in the acquisition of resistance to first and second line anti-tuberculosis drugs. [ABSTRACT FROM AUTHOR]

Oxidative stress represents the imbalance between oxidants and antioxidants and has been associated with a wide range of diseases. Thiols are the most important compounds in antioxidant defense. There is an equilibrium between thiols and their oxidized forms, disulfides, known as dynamic thiol-disulfide homeostasis (TDH). In 2014, Erel and Neselioglu developed a novel automated assay to measure thiol and disulfide levels. Subsequently, many researchers have used this simple, inexpensive and fast method for evaluating TDH in various disorders. We have reviewed the literature on the role of TDH in skin diseases. We identified 26 studies that evaluated TDH in inflammatory diseases (psoriasis, seborrheic dermatitis, atopic dermatitis, vitiligo, acne vulgaris and rosacea), allergic diseases (acute and chronic urticaria) and infectious diseases (warts, pityriasis rosea and tinea versicolor). The results are heterogeneous, but in most cases indicate changes in TDH that shifted toward disulfides or toward thiols, depending on the extent of oxidative damage. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) represents a novel therapy tested and is used more and more frequently in dermatology and cosmetic surgery for a variety of conditions, including androgenic alopecia (AGA), a common condition with a complex pathogenesis involving genetic factors, hormonal status and inflammation. We performed an extensive literature search which retrieved 15 clinical trials concerning the use in AGA of PRP therapy, alone or in combination, in male, female or mixed patient groups. A quantitative statistical meta-analysis of n = 17 trial groups proved significant increases in hair density from 141.9 ± 108.2 to 177.5 ± 129.7 hairs/cm2 (mean ± SD) following PRP (p = 0.0004). To the best of our knowledge, this is the first meta-analysis that proved a statistically significant correlation between the number of PRP treatments per month and the percentage change in hair density (r = 0.5, p = 0.03), as well as a negative correlation between the mean age of treatment group and the percentage change in hair density (r = −0.56, p = 0.016). Other factors considered for analysis were the PRP preparation method, amount used per treatment, hair diameter, terminal hairs and pull test. We conclude that PRP represents a valuable and effective therapy for AGA in both males and females if patients are rigorously selected. [ABSTRACT FROM AUTHOR]

Mammary Paget's disease is a rare form of cancer, which involves the nipple-areola complex. In most cases it is associated with an underlying tumor of the breast. Diagnosis is based on clinical appearance and is confirmed by histopathological examination. Imaging tests play an important role in detecting the associated ductal carcinoma. We present the case of a 90-year-old woman, who presented to our clinic for an erythemato-squamous lesion that covers her entire left nipple. The lesion was previously treated as eczema. Histopathological examination revealed features characteristic of Paget's disease. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and affects about 8% of cirrhotic patients, with a recurrence rate of over 50%. There are numerous therapies available for the treatment of HCC, depending on cancer staging and condition of the patient. The complexity of the treatment is also justified by the unique pathogenesis of HCC that involves intricate processes such as chronic inflammation, fibrosis, and multiple molecular carcinogenesis events. During the last three decades, multiple in vivo and in vitro experiments have used somatostatin and its analogs (SSAs) to reduce the proliferative and metastatic potential of hepatoma cells by inducing their apoptosis and reducing angiogenesis and the inflammatory component of HCC. Most experiments have proven successful, revealing several different pathways and mechanisms corresponding to the aforementioned functions. Moreover, a correlation between specific effects and expression of somatostatin receptors (SSTRs) was observed in the studied cells. Clinical trials have tested either somatostatin or an analog, alone or in combination with other drugs, to explore the potential effects on HCC patients, in various stages of the disease. While the majority of these clinical trials exhibited minor to moderate success, some other studies were inconclusive or even reported negative outcomes. A complete evaluation of the efficacy of somatostatin and SSAs is still the matter of intense debate, and, if deemed useful, these substances may play a beneficial role in the management of HCC patients. [ABSTRACT FROM AUTHOR]

Bowenoid papulosis is a disease caused by HPV, affecting mainly young sexually active adults. Its course is unpredictable, it may regress, has a slow evolution or turns into an invasive carcinoma. Histopathologically BP exhibits the features of a cutaneous squamous carcinoma in situ. We present the case of a 36-year-old woman diagnosed with BP. [ABSTRACT FROM AUTHOR]

Syphilis is a sexually transmitted infection caused by Treponema pallidum and has four stages of evolution, primary, secondary, latent and tertiary. The clinical appearance of secondary syphilis may take different aspects, the disease being called the great imitator. It should be taken into account that secondary syphilis does not involve only the skin, but also other organs. We present the case of a 26-year-old male with secondary syphilis associated with bilateral tonsillitis and mild hepatic cytolysis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There is a lack of awareness about the risk of acquiring sexually transmitted infections among people aged over 50 years. It should be noted that they remain sexually active and often do not use protection methods. We report the case of an older patient who presented to our clinic for the occurrence of an ulcerative lesion in the genital region. Following investigations the patient was diagnosed with human immunodeficiency virus (HIV) infection and syphilis. In this population group there are certain peculiarities of diagnosis and treatment regarding HIV infection. [ABSTRACT FROM AUTHOR]

Kaposi Sarcoma (KS) is a rare vascular tum or, locally aggressive, described by Moritz Kaposi in 1872. This tumor presents as a double prolife ratio no fendo the lial cells and vascular spaces, with end the lial cells origin. Etiologically linked to hum an herpesvirus-8 (HHV-8), also know n as KS-associated herpes virus (KSHV), Kaposi Sarcoma is com m only seen in HIV-infected and transplant patients and is the most clinically aggressive form o f the disease, in this subset of patients. Although, the skin touch with multifocal localization is the most prevalent, lymphnodal and visceral involvement is possible. [ABSTRACT FROM AUTHOR]