Hidradenitis Suppurativa: An Understanding of Genetic Factors and Treatment.

Hidradenitis suppurativa (HS), recognized as a chronic and debilitating skin disease, presents significant challenges in both diagnosis and treatment. This review explores the clinical manifestations, genetic landscape, and molecular mechanisms underlying HS. The disease's association with a predisposing genetic background, obesity, smoking, and skin occlusion underscores the complexity of its etiology. Genetic heterogeneity manifests in sporadic, familial, and syndromic forms, with a focus on mutations in the γ-secretase complex genes, particularly NCSTN. The dysregulation of immune mediators, including TNF-α, IL-17, IL-1ß, and IL-12/23, plays a crucial role in the chronic inflammatory nature of HS. Recent advancements in genetic research have identified potential therapeutic targets, leading to the development of anti-TNF-α, anti-IL-17, anti-IL-1α, and anti-IL-12/23 therapies and JAK inhibitors. These interventions offer promise in alleviating symptoms and improving the quality of life for HS patients.

Mechanisms of Epigenetic Inheritance in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes debilitating functional impairment in patients. Observations from survivors of traumatic historical events solidify that this disease is not only associated with personal experiences but can also be inherited from familial traumas. Over the past decades, researchers have focused on epigenetic inheritance to understand how responses to adverse experiences can be passed down to future generations. This review aims to present recent findings on epigenetic markers related to PTSD and research in the intergenerational inheritance of trauma. By understanding the information, we hope that epigenetic markers can act as biochemical measurements for future clinical practice.

The effect of papain hydrolysis on tropomyosin levels in shrimp.

Shrimp allergy is a serious public health problem. Epidemiological studies indicated the main cause of food allergy is the ingestion of shrimp and crab. Consequently, reducing the risk of shrimp and crab allergy is a major research focus. Few studies have demonstrated the effect of enzyme hydrolysis on reduction of shrimp allergens in food. In this study, we used papain, a commonly used enzyme in the food industry, as an ingredient to decrease levels of allergen tropomyosin in shrimp. 0-50U of papain was used to treat the shrimp meat, and then heated to measure the levels of tropomyosin, and determined the change of the protein secondary structure. The results showed that 20U of papain decrease the tropomyosin levels up to 80 %, which was further enhanced when combined with 3 min of heating. Furthermore, the result of Fourier-transform infrared spectroscopy (FTIR) showed alteration of secondary protein structure after the processing. The processing developed in this study may be an effective method used to change the levels and structure of tropomyosin.

Molecular Mechanisms of Cutaneous Immune-Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitors.

Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for the treatment of various cancers. These novel treatments effectively target key mediators of immune checkpoint pathways. Currently, ICIs primarily consist of monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite the notable efficacy of ICIs in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present as autoimmune-like or inflammatory conditions. IrAEs have the potential to affect multiple organ systems, with cutaneous toxicities being the most commonly observed. Although cutaneous irAEs are typically of low-grade severity and can usually be managed effectively, there are cases where severe irAEs can become life-threatening. Therefore, early recognition and a comprehensive understanding of the mechanisms underlying cutaneous irAEs are crucial for improving clinical outcomes in cancer patients. However, the precise pathogenesis of cutaneous irAEs remains unclear. This review focuses on the skin manifestations induced by ICIs, the prognosis related to cutaneous irAEs, and the exploration of potential mechanisms involved in cutaneous irAEs.

Female Pattern Hair Loss: An Overview with Focus on the Genetics.

Pattern hair loss can occur in both men and women, and the underlying molecular mechanisms have been continuously studied in recent years. Male androgenetic alopecia (M-AGA), also termed male pattern hair loss, is the most common type of hair loss in men. M-AGA is considered an androgen-dependent trait with a background of genetic predisposition. The interplay between genetic and non-genetic factors leads to the phenotype of follicular miniaturization. Although this similar pattern of phenotypic miniaturization can also be found in female pattern hair loss (FPHL), the corresponding genetic factors in M-AGA do not account for the phenotype in FPHL, indicating that there are different genes contributing to FPHL. Therefore, the role of genetic factors in FPHL is still uncertain. Understanding the genetic mechanism that causes FPHL is crucial for the future development of personalized treatment strategies. This review aims to highlight the differences in the ethnic prevalence and genetic background of FPHL, as well as the current genetic research progress in nutrition, Wnt signaling, and sex hormones related to FPHL.

Genetics of Generalized Pustular Psoriasis: Current Understanding and Implications for Future Therapeutics.

Psoriasis is a chronic inflammatory skin disease characterized by the appearance of clearly demarcated erythematous and scaly plaques. It can be divided into various types, including plaque, nail, guttate, inverse, and pustular psoriasis. Plaque psoriasis is the most commonly occurring type, though there is another rare but severe pustular autoinflammatory skin disease called generalized pustular psoriasis (GPP), which manifests with acute episodes of pustulation and systemic symptoms. Though the etiopathogenesis of psoriasis is not yet fully understood, a growing body of literature has demonstrated that both genetic and environmental factors play a role. The discovery of genetic mutations associated with GPP has shed light on our comprehension of the mechanisms of the disease, promoting the development of targeted therapies. This review will summarize genetic determinants as known and provide an update on the current and potential treatments for GPP. The pathogenesis and clinical presentation of the disease are also included for a comprehensive discussion.

Inherited Reticulate Pigmentary Disorders.

Reticulate pigmentary disorders (RPDs) are a group of inherited and acquired skin conditions characterized by hyperpigmented and/or hypopigmented macules. Inherited RPDs include dyschromatosis symmetrica hereditaria (DSH), dyschromatosis universalis hereditaria (DUH), reticulate acropigmentation of Kitamura (RAK), Dowling-Degos disease (DDD), dyskeratosis congenita (DKC), Naegeli-Franceschetti-Jadassohn syndrome (NFJS), dermatopathia pigmentosa reticularis (DPR), and X-linked reticulate pigmentary disorder. Although reticulate pattern of pigmentation is a common characteristic of this spectrum of disorders, the distribution of pigmentation varies among these disorders, and there may be clinical manifestations beyond pigmentation. DSH, DUH, and RAK are mostly reported in East Asian ethnicities. DDD is more common in Caucasians, although it is also reported in Asian countries. Other RPDs show no racial predilection. This article reviews the clinical, histological, and genetic variations of inherited RPDs.

The Genomic Landscape of Melanoma and Its Therapeutic Implications.

Melanoma is one of the most aggressive malignancies of the skin. The genetic composition of melanoma is complex and varies among different subtypes. With the aid of recent technologies such as next generation sequencing and single-cell sequencing, our understanding of the genomic landscape of melanoma and its tumor microenvironment has become increasingly clear. These advances may provide explanation to the heterogenic treatment outcomes of melanoma patients under current therapeutic guidelines and provide further insights to the development of potential new therapeutic targets. Here, we provide a comprehensive review on the genetics related to melanoma tumorigenesis, metastasis, and prognosis. We also review the genetics affecting the melanoma tumor microenvironment and its relation to tumor progression and treatment.

Early detection of the initial stages of LED light-triggered non-alcoholic fatty liver disease by wax physisorption kinetics-Fourier transform infrared imaging.

Light-emitting diodes (LEDs), particularly in the blue waveform range, are regarded as a major source of circadian rhythm dysregulation. A circadian rhythm dysregulation induced by blue LEDs is associated with non-alcoholic fatty liver disease (NAFLD). Hepatocellular accumulation of lipids is a key event in the early stages of NAFLD. Kupffer cells (KCs) have been reported to be lost in the early onset of NAFLD followed by an inflammatory reaction that alters the liver response to lipid overload. This study focused on the detection of the initial stages (subpathological stages) of LED light-triggered NAFLD. Mice were exposed to either blue or white LED irradiation for 44 weeks. Synchrotron radiation-based Fourier-transform infrared microspectroscopy (SR-FTIRM) and wax physisorption kinetic-Fourier transform infrared (WPK-FTIR) imaging were used to evaluate the ratio of lipid to protein and the glycosylation of glycoprotein, respectively. Immunohistopathological studies on KCs and circadian-related proteins were performed. Although liver biopsy showed normal pathology, an SR-FTIRM study revealed a high hepatic lipid-to-protein ratio after receiving LED illumination. The results of WPK-FTIR demonstrated that a high inflammation index was found in the high irradiance of the blue LED illumnation group. These groups showed a decrease in KC number and an increase in Bmal1 and Reverbα circadian protein expression. These findings provide explanations for the reduction of KCs without subsequent inflammation. A significant reduction of Per2 and Cry1 expression is correlated with the findings of WPK-FTIR imaging. WPK-FTIR is a sensitive method for detecting initiative stages of NAFLD induced by long-term blue LED illumination.

Chronic blue light-emitting diode exposure harvests gut dysbiosis related to cholesterol dysregulation.

Night shift workers have been associated with circadian dysregulation and metabolic disorders, which are tightly coevolved with gut microbiota. The chronic impacts of light-emitting diode (LED) lighting at night on gut microbiota and serum lipids were investigated. Male C57BL/6 mice were exposed to blue or white LED lighting at Zeitgeber time 13.5-14 (ZT; ZT0 is the onset of "lights on" and ZT12 is the "lights off" onset under 12-hour light, 12-hour dark schedule). After 33 weeks, only the high irradiance (7.2 J/cm2) of blue LED light reduced the alpha diversity of gut microbiota. The high irradiance of white LED light and the low irradiance (3.6 J/cm2) of both lights did not change microbial alpha diversity. However, the low irradiance, but not the high one, of both blue and white LED illuminations significantly increased serum total cholesterol (TCHO), but not triglyceride (TG). There was no significant difference of microbial abundance between two lights. The ratio of beneficial to harmful bacteria decreased at a low irradiance but increased at a high irradiance of blue light. Notably, this ratio was negatively correlated with serum TCHO but positively correlated with bile acid biosynthesis pathway. Therefore, chronic blue LED lighting at a high irradiance may harvest gut dysbiosis in association with decreased alpha diversity and the ratio of beneficial to harmful bacteria to specifically dysregulates TCHO metabolism in mice. Night shift workers are recommended to be avoid of blue LED lighting for a long and lasting time.

Current and Innovated Managements for Autoimmune Bullous Skin Disorders: An Overview.

Autoimmune bullous skin disorders are a group of disorders characterized by the formation of numerous blisters and erosions on the skin and/or the mucosal membrane, arising from autoantibodies against the intercellular adhesion molecules and the structural proteins. They can be classified into intraepithelial or subepithelial autoimmune bullous dermatoses based on the location of the targeted antigens. These dermatoses are extremely debilitating and fatal in certain cases, depending on the degree of cutaneous and mucosal involvement. Effective treatments should be implemented promptly. Glucocorticoids serve as the first-line approach due to their rapid onset of therapeutic effects and remission of the acute phase. Nonetheless, long-term applications may lead to major adverse effects that outweigh the benefits. Hence, other adjuvant therapies are mandatory to minimize the potential harm and ameliorate the quality of life. Herein, we summarize the current therapeutic strategies and introduce promising therapies for intractable autoimmune bullous diseases.

Cutaneous Adverse Events Associated with Immune Checkpoint Inhibitors: A Review Article.

Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They are monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation of immunologic symptoms and signs, termed immune-related adverse events (irAEs), with the skin being the most commonly involved organ. The dermatologic toxicities are observed in nearly half of the patients treated with ICIs, mainly in the form of maculopapular rash and pruritus. In the majority of cases, these cutaneous irAEs are self-limiting and manageable, and continuation of the ICIs is possible. This review provides an overview of variable ICI-mediated dermatologic reactions and describes the clinical and histopathologic presentation. Early and accurate diagnosis, recognition of severe toxicities, and appropriate management are key goals to achieve the most favorable outcomes and quality of life in cancer patients.

Abnormalities in Cutaneous Microcirculation in Patients with Alzheimer's Disease, Mild Cognitive Impairment, and Chronic Insomnia Disorder.

Impaired sympathetic response is frequently observed in neurodegenerative diseases, such as Alzheimer's disease (AD). On the other hand, chronic insomnia disorder (CID) is also often accompanied by activation of sympathetic nerves. Considering that cutaneous microcirculation reflects sympathetic tone, we hypothesized that baseline cutaneous microcirculation in fingers, as detected by laser Doppler flowmetry (LDF), differs among patients with mild cognitive impairment (MCI), AD, and CID. As light therapy is one of the adjunctive treatments for AD and CID, we designed a randomized controlled cross-over trial of light therapy through eyes for 12 weeks with red light as treatment and green light as control limb, and examined if light therapy has an impact on cutaneous microcirculation. Before light therapy, patients with AD had significantly lower baseline cutaneous perfusion than those with CID in left and right first to fourth fingers. After red light therapy, however, cutaneous perfusion of fingers in CID patients significantly decreased (right fingers, before vs. after = 227.25 ± 62.00 vs. 162.00 ± 49.34, p = 0.007; left fingers, before vs. after = 228.99 ± 58.80 vs. 177.41 ± 59.41, p = 0.003) while cutaneous perfusion of fingers in CID patients did not significantly change after green light therapy. Light therapy with red light also significantly increased cutaneous finger perfusion in patients with AD (right fingers, before vs. after = 130.13 ± 49.82 vs. 172.38 ± 38.32, p = 0.043). Our results suggest that cutaneous perfusion is a useful tool to detect sympathetic dysfunction in patients with CID and AD, and that light therapy with red light is a potential therapeutic intervention to reverse impaired sympathetic function in patients with CID and patients with AD.

Arsenic leads to autophagy of keratinocytes by increasing aquaporin 3 expression.

Exposure to arsenic, a ubiquitous metalloid on Earth, results in human cancers. Skin cancer is the most common arsenical cancers. Both autophagy and aquaporin pathway are known to promote carcinogenesis. However, the mechanisms by which arsenic regulates aquaporin and autophagy in arsenical skin cancers remain elusive. This study aims to address how arsenic regulates aquaporin-3, the predominant aquaporin in epidermal keratinocytes, and how this process would induce autophagy. Quantitative real-time PCR and immunofluorescence were used to measure the expression of aquaporin 3 in arsenical skin cancers and arsenic-treated keratinocytes. Beclin-1 expression and autophagy were measured. We examined if blocking aquaporin 3 could interfere arsenic-induced autophagy in keratinocytes. Expression of aquaporin 3 is increased in arsenical cancers and in arsenic-treated keratinocytes. Arsenic induced autophagy in primary human keratinocytes. Notably, the arsenic-induced autophagy was inhibited by pretreatment of keratinocytes with aquaporin inhibitors Auphen or AgNO3, or RNA interference against aquaporin 3. The data indicates that the aquaporin 3 is an important cell membrane channel to mediate arsenic uptake and contributes to the arsenic-induced autophagy.

Anti-Inflammatory Effects Induced by Near-Infrared Light Irradiation through M2 Macrophage Polarization.

Near-infrared (NIR) can penetrate the dermis. NIR is able to regulate cutaneous component cells and immune cells and shows significant anti-inflammatory therapeutic effects. However, the mechanisms of these effects are largely unknown. The purpose of this study is to elucidate NIR-induced molecular mechanisms on macrophages because macrophages play initial roles in directing immune responses by their M1 or M2 polarizations. Proteomic analysis revealed that NIR radiation enhanced the expression of mitochondrial respiratory gene citrate synthase. This increased citrate synthase expression was triggered by NIR-induced H3K4 hypermethylation on the citrate synthase gene promoter but not by heat, which led to macrophage M2 polarization and finally resulted in TGFß1 release from CD4+ cells. These cellular effects were validated in human primary macrophages and abdominal NIR-irradiated mouse experiments. In a phorbol 12-myristate 13-acetate‒induced inflammatory model on mouse ear, we confirmed that NIR irradiation induced significant anti-inflammatory effects through decreased M1 counts, reduced TNF-α, and increased CCL22 and/or TGFß1 levels.

Red LED light treatment promotes cognitive learning through up-regulation of trpm4 in zebrafish.

Although light emitting diodes (LEDs) are widely used in our daily lives, there is little research regarding LED light's possible effects on biological functions. We used a zebrafish animal model to investigate the long-term effects of white, blue and red LED lights on cognitive learning and memory recall. Our data suggest that these treatments had not only an impact on learning but also surprisingly long-lasting effects, particularly with regard to individuals treated with red light. The qPCR results revealed that the expression levels of trpm4, trpa1b, grin2aa and dlg4 in the skin were increased after monochromatic light treatment. Furthermore, the up-regulation of trpm4 in the brain may correlate to enhanced learning and memory following red-light treatment. Our results identify a light-based stimulation system for enhancing zebrafish learning, which has the potential to provide important insights into the relationship between LED lighting and animal behaviour.