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Adult acne is a chronic inflammatory disease of the pilosebaceous unit characterized by the excessive production of abnormal sebum favoring an imbalance of the skin microbiota and the hyperproliferation of Cutibacterium acnes and other virulent microbial strains, leading to an inflammatory environment, innate immunity overactivation, and keratinocyte hyperproliferation in hair follicles pores. Degraded keratinocytes plug the pores, consequently forming microcomedons, which can later evolve to papules, nodules, pustules and scars. Distinct from juvenile acne, in adult female acne (AFA) the symptomatology occurs or persists in postadolescence (after age 25). Although hyperandrogenism or the excessive sensitivity of androgen receptors are the main causes, AFA can be triggered by multiple factors, either including or not including androgen disturbances. The prevalence in adult women is 15–20%. Hyperandrogenism is present in 50% of cases; 70% of hyperandrogenism cases feature polycystic ovary syndrome (PCOS), a complex endocrine and metabolic condition. Genetic susceptibility occurs in 80% of acne cases, often with familial inheritance. Beyond classical stepwise therapeutic protocols (topical agents, isotretinoin, antibiotics, hormonal therapy with estrogens, progestins, spironolactone), novel approaches include the highly effective topical antiandrogen clascoterone, the management of insulin resistance by diet, exercise, stress avoidance, and adjuvant therapies such as berberine. Vaccines against the pathogenic proinflammatory C. acnes hyaluronidase A are in development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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]

Introduction. Psoriasis is a chronic inflammatory skin disease and is the result of the interaction between numerous external and internal factors. Psoriasis presents a wide range of skin manifestations encompassing individual lesions varying from pinpoint to large plaques that can evolve into generalised forms. The lesions mirror the pathophysiological mechanisms involved in psoriasis pathogenesis, such as inflammation, dysregulation of immune response, uncontrolled proliferation of keratinocytes and angiogenesis. In this article, we present the latest advances achieved regarding markers that correlate with psoriasis severity. Material and method. We have performed a narrative review on markers of psoriasis severity, including articles published between March 2018–March 2023. Results. We have identified four categories of markers: inflammation markers, oxidative stress markers, hormonal markers and cancer-related markers. The main focus was on inflammation biomarkers, including immunomodulatory molecules, haematological parameters, inflammatory cells and costimulatory molecules. Conclusions. The analysed data indicate that markers associated with inflammation, oxidative stress and hormones, and cancer-related markers could be useful in assessing the severity of psoriasis. Nevertheless, additional research is required to ascertain the practical importance of these biomarkers in clinical settings. [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]

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]

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]

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]

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]

There is growing evidence that oxidative stress is involved in the pathogenesis of numerous conditions, including dermatological diseases. Various markers are available to assess oxidative stress, but none of these can be considered the ideal marker. Recent studies have shown that ischemia-modified albumin (IMA) is not only an indicator of ischemia, but also a marker of oxidative stress. We have conducted a narrative review to evaluate the role of IMA in dermatological diseases. We have identified 24 original articles that evaluated IMA in skin disorders (psoriasis, acne vulgaris, hidradenitis suppurativa, urticaria, vitiligo and Behcet's disease) and hair disorders (alopecia areata, androgenetic alopecia and telogen effluvium). The results of the studies analyzed reveal that IMA may be considered a new marker of oxidative stress in dermatological diseases and offer new insights into the pathogenesis of these disorders and the theoretical basis for the development of new, effective, targeted therapies. To the best of our knowledge, this is the first review that gathers up data on the role of IMA in dermatological diseases. [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]

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]

Since ancient times, people have tattooed their skin for various reasons. In the past, tattoos were associated with low social status; nowadays, tattoos are very popular and are considered a form of art. However, tattoos are associated with various clinical problems, including immune reactions, inflammatory disorders, infections, and even skin cancer. Epidemiological and clinical data of infections on tattoos are scarce. Tattoo-related infections are mostly bacterial; only a few localized viral infections have been reported so far and are caused by molluscum contagiosum virus (MCV), human papillomavirus (HPV), and herpes simplex virus (HSV). In most cases, the lesions were strictly confined to the area of the tattoo. In this review, we have analysed reported cases of viral infections localized on tattoos and discussed the possible mechanisms involved in the occurrence of these infections. [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]

Impaired wound healing is an encumbering public health issue that increases the demand for developing new therapies in order to minimize health costs and enhance treatment efficacy. Available conventional therapies are still unable to maximize their potential in penetrating the skin at the target site and accelerating the healing process. Nanotechnology exhibits an excellent opportunity to enrich currently available medical treatments, enhance standard care and manage wounds. It is a promising approach, able to address issues such as the permeability and bioavailability of drugs with reduced stability or low water solubility. This paper focuses on nanosized-lipid-based drug delivery systems, describing their numerous applications in managing skin wounds. We also highlight the relationship between the physicochemical characteristics of nanosized, lipid-based drug delivery systems and their impact on the wound-healing process. Different types of nanosized-lipid-based drug delivery systems, such as vesicular systems and lipid nanoparticles, demonstrated better applicability and enhanced skin penetration in wound healing therapy compared with conventional treatments. Moreover, an improved chemically and physically stable drug delivery system, with increased drug loading capacity and enhanced bioavailability, has been shown in drugs encapsulated in lipid nanoparticles. Their applications in wound care show potential for overcoming impediments, such as the inadequate bioavailability of active agents with low solubility. Future research in nanosized-lipid-based drug delivery systems will allow the achievement of increased bioavailability and better control of drug release, providing the clinician with more effective therapies for wound care. [ABSTRACT FROM AUTHOR]

Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma. [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]

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]

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. [ABSTRACT FROM AUTHOR]

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. [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]

Simple Summary: Melanoma is a very aggressive and fatal malignant tumor. While curable if diagnosed in its early stages, advanced melanoma, despite the complex therapeutic approaches, is associated with one of the highest mortality rates. Hence, more and more studies have focused on mechanisms that may contribute to melanoma development and progression. Various studies suggest a role played by neuroendocrine factors which can act directly on tumor cells, modulating their proliferation and metastasis capability, or indirectly through immune or inflammatory processes that impact disease progression. However, there are still multiple areas to explore and numerous unknown features to uncover. A detailed exploration of the mechanisms by which neuroendocrine factors can influence the clinical course of the disease could open up new areas of biomedical research and may lead to the development of new therapeutic approaches in melanoma. Melanoma is one of the most aggressive skin cancers with a sharp rise in incidence in the last decades, especially in young people. Recognized as a significant public health issue, melanoma is studied with increasing interest as new discoveries in molecular signaling and receptor modulation unlock innovative treatment options. Stress exposure is recognized as an important component in the immune-inflammatory interplay that can alter the progression of melanoma by regulating the release of neuroendocrine factors. Various neurotransmitters, such as catecholamines, glutamate, serotonin, or cannabinoids have also been assessed in experimental studies for their involvement in the biology of melanoma. Alpha-MSH and other neurohormones, as well as neuropeptides including substance P, CGRP, enkephalin, beta-endorphin, and even cellular and molecular agents (mast cells and nitric oxide, respectively), have all been implicated as potential factors in the development, growth, invasion, and dissemination of melanoma in a variety of in vitro and in vivo studies. In this review, we provide an overview of current evidence regarding the intricate effects of neuroendocrine factors in melanoma, including data reported in recent clinical trials, exploring the mechanisms involved, signaling pathways, and the recorded range of effects. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis (Ssc) is an autoimmune disease with incomplete known physiopathology. There is a high number of candidate proteomic biomarkers for Ssc that have not yet been confirmed on independent Ssc cohorts. The aim of the study was to confirm circulating S100A6, calumenin, and cytohesin 2 as biomarkers for Ssc. Methods: 53 Ssc patients and 26 age- and gender-matched controls were included. Serum S100A6, calumenin, and cytohesin 2 were evaluated with commercial ELISA kits. Associations between serum expression and clinical Ssc characteristics were evaluated. Results: Serum calumenin, S100A6, and cytohesin 2 were higher in Ssc patients compared to controls. Calumenin associated with extensive cutaneous fibrosis, frequency of Raynaud phenomenon, and low complement level, and had a tendency to be higher in Ssc patients with pulmonary fibrosis. S100A6 correlated with the number of active digital ulcers. Serum cytohesin 2 levels were higher in patients with teleangiectasia and associated with pulmonary artery pressure. Conclusions: Serum calumenin, S100A6, and cytohesin 2 were confirmed as biomarkers on an independent group of Ssc patients. Calumenin had the best predictive capacity for cutaneous Ssc manifestations. Future studies are needed to evaluate the prognostic value of these biomarkers and evaluate them as possible therapeutic targets. [ABSTRACT FROM AUTHOR]

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—soluble receptor for advanced glycation end products, sIL-6R—soluble receptor for Interleukin 6) in RAGE and IL-6 signaling, the modulatory effect of TK1—thymidine kinase 1 and TuM2-PK—tumoral pyruvate-kinase 2 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, Asymmetric Dimethylarginines (ADMA), Symmetric Dimethylarginines (SDMA), and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease posttranslational modification signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis. [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]

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. [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]

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.

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.