Intersecting Pathways: Nonalcoholic Fatty Liver Disease and Psoriasis Duet-A Comprehensive Review.

Psoriasis is a chronic, immune-mediated, inflammatory disease that has a major impact on patients' quality of life. Common psoriasis-associated comorbidities include cardiovascular diseases, psoriatic arthritis, inflammatory bowel syndromes, type-2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is affecting a substantial portion of the population and is closely linked with psoriasis. The interplay involves low-grade chronic inflammation, insulin resistance, and genetic factors. The review presents the pathophysiological connections between psoriasis and nonalcoholic fatty liver disease, emphasizing the role of cytokines, adipokines, and inflammatory cascades. The "hepato-dermal axis" is introduced, highlighting how psoriatic inflammation potentiates hepatic inflammation and vice versa. According to the new guidelines, the preliminary examination for individuals with psoriasis should encompass evaluations of transaminase levels and ultrasound scans as part of the initial assessment for this cohort. Considering the interplay, recent guidelines recommend screening for NAFLD in moderate-to-severe psoriasis cases. Treatment implications arise, particularly with medications impacting liver function. Understanding the intricate relationship between psoriasis and NAFLD provides valuable insights into shared pathogenetic mechanisms. This knowledge has significant clinical implications, guiding screening practices, treatment decisions, and the development of future therapeutic approaches for these chronic conditions.

Hidradenitis suppurativa: Detangling phenotypes and identifying common denominators.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a severe impact on patients' quality of life through its recurrent and painful nature, as well as its comorbidity burden. The shift in the pathogenic paradigm from a condition of the apocrine glands to an autoinflammatory disease associated with follicular destruction has rendered its understanding difficult, as there are still large gaps in pinpointing the underlying mechanisms, which cannot currently explain the existing clinical variation and as a result, translate into suboptimal therapy. Multifactorial involvement is hypothesized, with an implication of genetic mutations, microbiome dysbiosis, cytokine upregulation and environmental factors. Clinical observation is fundamental for diagnosis, however, the marked heterogeneity in presentation leads to delays in detection and challenges in treatment selection, showcasing clear limits in defining the link between genetic aspects of HS, the role of epigenetic factors and its pathogenic pathways. There have been attempts to formulate phenotypes that could aid in prognostication and management, however, current classification schemata show significant overlap and no validation through longitudinal studies. In this context, nomenclature poses a great challenge due to the lack of global agreement in the definition of lesions, which should be addressed by future research to enable simplified recognition and allow for more precise severity scoring. This could be complemented by the addition of extra dermatologic findings or paraclinical assessment in constructing phenotypes. The development of valid, predictive and reliable classifications of HS may lead to an improvement in comprehending its pathophysiology, favouring a more personalized approach in management. This could be achieved through consensus in the characterization of clinical features and data gathering, as well as validation attempts for described phenotypes. Ultimately, the genotype-endotype-phenotype correlation in HS requires targeted, systematic inquiries and should be addressed more largely to broaden the perspective on this debilitating entity.

Skin Cancer Correlations in Psoriatic Patients.

Psoriasis is a common chronic, immune-mediated, inflammatory disease with associated comorbidities. Common psoriasis-associated comorbidities include psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory digestive syndromes, and depression. A less studied association is between psoriasis and specific-site cancers. A key cell in the pathophysiology of psoriasis is the myeloid dendritic cell, which links the innate and adaptive immune systems, and therefore is involved in the control of cancer-prevention mechanisms. The relationship between cancer and inflammation is not new, with inflammation being recognized as a key element in the development of neoplastic foci. Infection leads to the development of local chronic inflammation, which further leads to the accumulation of inflammatory cells. Various phagocytes produce reactive oxygen species that cause mutations in cellular DNA and lead to the perpetuation of cells with altered genomes. Therefore, in inflammatory sites, there will be a multiplication of cells with damaged DNA, leading to tumor cells. Over the years, scientists have tried to assess the extent to which psoriasis can increase the risk of developing skin cancer. Our aim is to review the available data and present some information that might help both the patients and the care providers in properly managing psoriatic patients to prevent skin cancer development.

Kaempferol: Antimicrobial Properties, Sources, Clinical, and Traditional Applications.

Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.

Cutaneous Adverse Reactions Associated with Monoclonal Antibodies Treatment in Multiple Sclerosis: Case Reports and Short Literature Review.

BACKGROUND AND AIMS: Multiple sclerosis is a disease of the central nervous system, whose treatment often involves the use of monoclonal antibodies. This can lead to a series of complications that the clinician should pay attention to and accordingly adjust the therapy. We aim to emphasize real-life experiences with adverse cutaneous reactions to monoclonal antibodies by presenting a series of two cases from our clinic. METHODS: In the first case, a female patient was treated with natalizumab for eight years and developed relapsing-remitting cutaneous lesions following the monthly administration of the treatment. The second case is of a male patient treated with ocrelizumab, who developed plaque-like lesions following the fifth administration. We analyzed the biological parameters and performed investigations, dermatological evaluation and skin biopsies. RESULTS: The result of the skin biopsy for the natalizumab patient showed a chronic spongiotic dermatitis, with the anti-natalizumab antibodies being negative. The patient who received ocrelizumab developed nummular eczema, disseminated on his trunk and limbs. CONCLUSIONS: Given the fact that these therapies are frequently used in multiple sclerosis patients, and their skin adverse reactions are known, we described some particularities and a brief review of the literature with practical implications. Further studies need to be conducted to establish a firm association between monoclonal antibodies therapy and adverse cutaneous reactions, but the clinician should be aware of their existence.

A combination of two regional flaps for the complex reconstruction after head and neck cancer surgery as an alternative approach during the COVID-19 pandemic: A case report.

Since the COVID-19 pandemic outbreak, the medical systems were challenged by continuously increasing numbers of infections and faced critical issues when trying to find solutions for patients suffering from other diseases, including patients with head and neck cancers. Complex surgeries were delayed due to an acute deficit of specialized intensive care medical staff and equipment, which were redirected towards COVID-19 hospitalized cases, with irreversible consequences for the patients. In the present study, the case of locally advanced head and neck cancer was presented, which was treated radically during the heaviest wave of the COVID-19 pandemic in Romania using an alternative approach for immediate defect reconstruction. The case of locally advanced buccal carcinoma (staged T4aN0Mx) was reported, where radical tumor excision was followed by immediate reconstruction using a combination of two regional flaps, temporal and submental, in order to provide timely and optimal medical care. In the difficult context of the COVID-19 pandemic, the standard reconstructive technique, which is the free vascularized tissue transfer, could not be performed for this patient, due to the acute deficit of anesthetists and associated medical staff, as well as the lack of free beds in intensive care units. Combinations of local and regional flaps, such as temporal muscle flap and submental flap, are simple and accessible surgical techniques that require reduced surgical time, minimal equipment, and basic surgical training, advantages that become crucial in historically challenging times, such as a global pandemic. Individual cases, like elderly patients or patients with severe comorbidities, should be considered for these types of reconstructive techniques: simple solutions, single or in combination, which may be an improved therapeutic option for these patients.

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis.

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism's response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.

Persistent Changes of Peripheral Blood Lymphocyte Subsets in Patients with Oral Squamous Cell Carcinoma.

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

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review).

Chronic obstructive pulmonary disease (COPD) and asthma are chronic respiratory diseases with high prevalence and mortality that significantly alter the quality of life in affected patients. While the cellular and molecular mechanisms engaged in the development and evolution of these two conditions are different, COPD and asthma share a wide array of symptoms and clinical signs that may impede differential diagnosis. However, the distinct signaling pathways regulating cough and airway hyperresponsiveness employ the interaction of different cells, molecules, and receptors. Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a major role in cough and airway inflammation. Consequently, its agonist, capsaicin, is of substantial interest in exploring the cellular effects and regulatory pathways that mediate these respiratory conditions. Increasingly more studies emphasize the use of capsaicin for the inhalation cough challenge, yet the involvement of TRPV1 in cough, bronchoconstriction, and the initiation of inflammation has not been entirely revealed. This review outlines a comparative perspective on the effects of capsaicin and its receptor in the pathophysiology of COPD and asthma, underlying the complex entanglement of molecular signals that bridge the alteration of cellular function with the multitude of clinical effects.

The Effects of Capsaicin on Gastrointestinal Cancers.

Gastrointestinal (GI) cancers are a group of diseases with very high positions in the ranking of cancer incidence and mortality. While they show common features regarding the molecular mechanisms involved in cancer development, organ-specific pathophysiological processes may trigger distinct signaling pathways and intricate interactions with inflammatory cells from the tumoral milieu and mediators involved in tumorigenesis. The treatment of GI cancers is a topic of increasing interest due to the severity of these diseases, their impact on the patients' survivability and quality of life, and the burden they set on the healthcare system. As the efficiency of existing drugs is hindered by chemoresistance and adverse reactions when administered in high doses, new therapies are sought, and emerging drugs, formulations, and substance synergies are the focus of a growing number of studies. A class of chemicals with great potential through anti-inflammatory, anti-oxidant, and anti-tumoral effects is phytochemicals, and capsaicin in particular is the subject of intensive research looking to validate its position in complementing cancer treatment. Our paper thoroughly reviews the available scientific evidence concerning the effects of capsaicin on major GI cancers and its interactions with the molecular pathways involved in the course of these diseases.

Use of prokinetics and other quality factors in capsule endoscopy - old and new insights (Review).

Despite the extensive recent development of different techniques for endoscopic evaluation for both diagnostic and therapeutic reasons, the small bowel remains quite difficult to visualize. Capsule endoscopy and device assisted enteroscopy are presently considered the best diagnostic tools for examination of small bowel disorders, assessing diverse pathologies such as obscure gastrointestinal bleeding, iron deficiency anemia, Crohn disease, small bowel tumors and polyposis syndromes. Like any other imagistic method, it has specific indications, and contraindications, and possibly it is more important to consider limitations. In order to obtain a better result, it is necessary to respect the procedural quality indicators. Among them the use of prokinetics - diverse pharmacological substances increasing the success rate of capsule endoscopy have raised debates. Capsule endoscopy small bowel evaluation is a reliable, non-invasive and safe with many advantages and minimum risks, with a proper selection of patients, and can be used as first line investigation.

Cannabinoids in the Pathophysiology of Skin Inflammation.

Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.