Miscellaneous by Sebastian Yu
Food Chemistry, 2019
In Taiwan, crab is one of the main causes for food allergy. Several proteins are recognized as cr... more In Taiwan, crab is one of the main causes for food allergy. Several proteins are recognized as crustacean allergens, and tropomyosin is known to be the major one. However, sensitization patterns of Taiwanese patients to crustacean allergens remain unclear. Therefore, we analyzed the specific-IgE binding ability of crucifix crab (Charybdis feriatus) allergens by western blot using patients’ sera. In particular, we found a 56 kDa protein in crucifix crab reacted with specific-IgEs in patients’ sera, and we further identified the protein as a novel crab allergen pyruvate kinase 2. Additionally, little is known about tropomyosin contents in crabs consumed in Taiwan. Thus, we also quantified the levels of tropomyosin by using enzyme-linked immunosorbent assay (ELISA) among raw and cooked crab species. Our results showed tropomyosin levels varied depending on crab species. In summary, these findings improve the understanding of crustacean allergens and contribute to the clinical diagnosis of crustacean allergies.
Journal of Investigative Dermatology, 2019
Clinical Hemorheology and Microcirculation, 2019
Background: Skin physiology measurement is receiving more attention for detecting vasculopathy in... more Background: Skin physiology measurement is receiving more attention for detecting vasculopathy in systemic sclerosis (SSc). Laser Doppler flowmetry (LDF) is a widely used physiological measurement to assess cutaneous microcirculation. However, findings of LDF may be subtle during early stage of microangiopathy in SSc.
Objective: We hypothesized that cold stress test combined with LDF could detect early-stage microangiopathy in patients with SSc.
Methods: A 67-year-old male came with multiple ulcerations on his fingers for one year. After excluding diseases such as diabetes mellitus-related peripheral arterial occlusive disease and smoking-related Buerger’s disease, the diagnosis of SSc was made according to the 2013 ACR/EULAR criteria. We performed LDF and angiography for a patient with SSc and compared the results.
Results: Although occlusions of right ulnar and digital arteries were obvious in angiography, the baseline skin temperature and perfusion unit on right fingers remained within normal limits. While the microcirculatory abnormalities measured by LDF alone are subtle, LDF combined with cold stress test detected a significant slow recovery of skin blood flow 40 minutes after cold immersion.
Conclusions: In conclusion, there may be discordance between macrovasculopathy and baseline microcirculatory blood flow in SSc. In such a case, cold immersion test is essential to measure the dynamic change and slow recovery of blood flow.
Food Chemistry, 2018
Food allergy is one of the most important health issues worldwide. In Taiwan, current literature ... more Food allergy is one of the most important health issues worldwide. In Taiwan, current literature suggests shrimps and crabs are the most common causes of food allergy, and are frequently associated with acute allergic reactions such as urticaria, atopic dermatitis, and asthma. However, knowledge regarding the shrimp allergens remains limited. Thus, there is an urgent need to establish comprehensive information for elucidating underlying triggers for food allergy. In this study, whiteleg shrimp (Litopenaeus vannamei) was used to evaluate the IgE binding properties of various shrimp proteins to 7 allergic patients’ sera by western blot. A 63 kDa protein was found in raw and cooked shrimp bound to specific-IgEs in 7 and 4 patients’ sera, respectively. This protein was further identified as pyruvate kinase based on the proteomic mass spectrometry. This study identifies an important shrimp allergen unique to Taiwan and further testing and prevention measures might be implemented in the allergen analysis.
Dermatologica Sinica, 2014
Herein we report a rare case of classical Dowling-Degos disease (DDD) in a Taiwanese woman. A 23-... more Herein we report a rare case of classical Dowling-Degos disease (DDD) in a Taiwanese woman. A 23-year-old Taiwanese woman presented with generalized hyperpigmentation in irregular and reticulated shapes that she had had since junior high school. Her mother and two sisters had also developed similar pigmentations, starting during their teenage years. The patient did not have previous skin lesions or a history of trauma. She did not have any nail or hair abnormalities. Viewed through a microscope, the hyperpigmented area was found to have elongated rete ridges, the tips of which were found to have a concentration of melanin. Based on the disease onset, family history, clinical and histopathological manifestations, the patient was diagnosed as having DDD. We performed an electron microscopic study revealing a greater number of mature melanosomes in the keratinocytes in the pigmented skin than in those in the nonpigmented skin. The numbers of melanosomes in the melanocytes were similar in both types of skin. This is the first direct comparison of ultrastructural features in pigmented and uninvolved skin in Taiwanese with DDD. We follow the discussion of the case with the differential diagnosis and genetic abnormalities of diseases with reticulate pigmentations. This case report reminds us that keratin 5/14 plays a role in both keratinocyte integrity and melanin transfer.
Acta Dermato-Venereologica, Jan 31, 2017
Dermatologica Sinica, 2016
Blaschko lines are manifestations of cutaneous mosaicism, with apparent contrast between normal c... more Blaschko lines are manifestations of cutaneous mosaicism, with apparent contrast between normal cells and abnormal cells, which carry postzygotic mutations. Linear cutaneous lupus erythematosus is a rare subset of cutaneous lupus erythematosus (CLE), characterized by skin lesions along Blaschko lines. In this paper, we presented a 47-year-old female with subacute CLE lesions along Blaschko lines. Although the antinuclear antibody and anti-Ro titers were remarkably high, there were no systemic symptoms. The histopathology showed atrophic epidermis with vacuolization of basal keratinocytes and papillary edema. While no typical linear lupus band was found, the direct immunofluorescence revealed cytoid bodies with immunoglobulin G, immunoglobulin M, C3, and C4 depositions in the papillary dermis. The skin lesions completely resolved after topical tacrolimus treatment, and the clinical course was 10 months without recurrence. We reviewed the literature and summarized that CLE along Blaschko lines supports the functional role of Ro antigens and keratinocytes in the development of CLE.
Oncotarget, 2017
Melanoma, a cancer derived from melanocytes, is one of the most chemoresistant cancers and tends ... more Melanoma, a cancer derived from melanocytes, is one of the most chemoresistant cancers and tends to metastasize. Once it metastasizes, the prognosis is poor. Even with the recent advancement of targeted therapy and immunotherapy, the prognosis remains discouraging. SR-T100, a Solanum incanum extract, shows anticancer effects against several cancers; however, its therapeutic efficacy against melanoma and established metastasis remains unknown. In this study, we showed that SR-T100 induces apoptosis, DNA damage, and G0/G1 cell cycle arrest in murine B16 melanoma cells in vitro. In vivo, intralesional injection of SR-T100 decreased the tumor size of the regional melanoma in the foot pad. Moreover, intraperitoneal injection of SR-T100 inhibited the growth and the number of established melanoma metastases in the lungs. Our study highlights SR-T100 as a potential novel treatment for established tumors from regional and metastatic melanoma.
Photomedicine by Sebastian Yu
Journal of Dermatological Science, 2017
The authors regret that there is a typo in the title of this Letter to the Editor. The word repig... more The authors regret that there is a typo in the title of this Letter to the Editor. The word repigmentation was erroneously spelled as regimentation. The correct title is “Ultraviolet B (UVB) induces development of early melanocytic progenitors via increased oxidative stress in vitro suggesting the use of antioxidants after repigmentation in UVB phototherapy for vitiligo”.
The authors would like to apologise for any inconvenience caused.
Journal of Dermatological Science, 2017
British Journal of Dermatology, 2011
BACKGROUND:
Visible light is a treatment option for segmental vitiligo (SV), and visible light-in... more BACKGROUND:
Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy.
OBJECTIVES:
To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV.
METHODS:
Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period.
RESULTS:
The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes.
CONCLUSIONS:
Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.
Journal of European Academy of Dermatology and Venereology, 2016
Experimental Dermatology, 2019
Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low-level lase... more Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low-level laser light (coherent light) or light-emitting diodes (LEDs; noncoherent light), leading to the modulation of cellular functions, such as proliferation and migration, which result in tissue regeneration. PBM therapy has important clinical applications in regenerative medicine. Vitiligo is an acquired depigmentary disorder resulting from disappearance of functional melanocytes in the involved skin. Vitiligo repigmentation depends on available melanocytes derived from (a) melanocyte stem cells located in the bulge area of hair follicles and (b) the epidermis at the lesional borders, which contains a pool of functional melanocytes. Since follicular melanoblasts (MBs) are derived from the melanocyte stem cells residing at the bulge area of hair follicle,
the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low-energy helium-neon (He-Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He-Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O2 consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He-Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He-Ne laser initiated mitochondrial retrograde signalling via a Ca2+-dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic-AMP response element binding protein)-related cascade, is responsible for the He-Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He-Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.
Arsenic by Sebastian Yu
Journal of Asian Earth Sciences, 2013
Endemic contamination of artesian water for drinking by arsenic is known to cause several human c... more Endemic contamination of artesian water for drinking by arsenic is known to cause several human cancers, including cancers of the skin, bladder, and lungs. In skin, multiple arsenic-induced Bowen’s disease
(As-BD) can develop into invasive cancers after decades of arsenic exposure. The characteristic histological features of As-BD include full-layer epidermal dysplasia, apoptosis, and abnormal proliferation. Calcium propagation is an essential cellular event contributing to keratinocyte differentiation, proliferation, and apoptosis, all of which occur in As-BD. This study investigated how arsenic interferes calcium propagation of skin keratinocytes through ROS production and whether hydrogen-enriched water would restore arsenic-impaired calcium propagation. Arsenic was found to induce oxidative stress and inhibit
ATP- and thapsigaragin-induced calcium propagation. Pretreatment of arsenic-treated keratinocytes by hydrogen-enriched water or beta-mercaptoethanol with potent anti-oxidative effects partially restored
the propagation of calcium by ATP and by thapsigaragin. It was concluded that arsenic may impair calcium propagation, likely through oxidative stress and interactions with thiol groups in membrane proteins.
Journal of Dermatology, 2018
Exposure to arsenic is a global health issue. Long-term arsenic exposure may associate with vario... more Exposure to arsenic is a global health issue. Long-term arsenic exposure may associate with various cancers and many other pathological effects. Over 100 million people worldwide are exposed to arsenic particularly in countries such as Bangladesh, Chile, China, India, Mexico, Taiwan and the USA. Drinking of water contaminated with arsenic is the major route of human exposure. Skin lesions are considered to be the most common adverse effects associated with chronic arsenic exposure. Skin lesions usually develop with the latency period spanning more than 20 years from first exposure. Arsenic-induced Bowen’s disease, the most frequently encountered carcinoma in situ resulting from chronic arsenic exposure, is characterized by multiple and recrudescent lesions. Long-term arsenic exposure results in impaired immunity in susceptible individuals. In the prenatal stage, enhanced placental inflammatory responses and reduced placental T cells by arsenic may result in decreased thymic size and functions in newborns. In childhood, arsenic exposure may reduce peripheral CD4+ cells and interleukin-2 secretion which leads to susceptibility to opportunistic infections. There was an impairment of macrophage function and oxidative DNA damage of peripheral polymorphonuclear leukocytes in adults with skin lesions. In arsenic-induced Bowen’s disease lesions, a decrease in the number and functions of Langerhans cells and, in parallel, a selective CD4+ cell apoptosis was noticed. These findings provide scientific evidence for understanding the phenomenon of arsenic-induced immune escape in the early stage of carcinogenesis and a reasonable explanation for multiple and recrudescent arsenic cancers in the skin.
Skin-Brain interaction by Sebastian Yu
Dermatologica Sinica, 2017
Background/Objective
The prevalence of selected psychiatric disorders, such as depression and anx... more Background/Objective
The prevalence of selected psychiatric disorders, such as depression and anxiety, is higher in patients with psoriasis. However, the association between psoriasis and schizophrenia is less clear. Here, we investigated whether the prevalence of schizophrenia is higher in patients with psoriasis.
Methods
In this cross-sectional study, we analyzed the 1-million-person cohort enrolled from Taiwan's National Health Insurance Research Database. Psoriasis, schizophrenia, and comorbidities were ascertained by the International Classification of Diseases, 9th revision, Clinical Modification coding. For schizophrenia, the concomitant catastrophic illness certificate was used to verify the diagnosis. The prevalence of schizophrenia in patients with psoriasis was compared with the prevalence of schizophrenia in a comparable population using a generalized linear mixed model.
Results
The prevalence of schizophrenia was significantly higher in patients with psoriasis than in the comparison population [prevalence ratio = 1.77, 95% confidence interval (CI) = 1.48–2.12, p < 0.0001)]. Within the psoriasis cohort, patients aged between 40 years and 59 years had a higher odds ratio (OR) for schizophrenia (OR = 2.49, 95% CI = 1.55–4.00, p = 0.0002). Furthermore, psoriatic patients with comorbid cerebrovascular disease (OR = 2.01, 95% CI = 1.11–3.65, p = 0.0220) and chronic pulmonary disease (OR = 1.64, 95% CI = 1.07–2.49, p = 0.0218) had higher odds for schizophrenia.
Conclusion
Schizophrenia is more prevalent in patients with psoriasis. Although the exact mechanisms remain to be clarified, the finding that psoriatic patients with comorbid cerebrovascular disease or chronic pulmonary disease have higher odds for schizophrenia may imply psoriatic patients with those comorbidities are likely to have higher inflammatory burden, which would contribute to the development of schizophrenia if a disruption of the blood–brain barrier is present. Further investigations are indicated to validate the hypothesis explaining the association between known comorbidies of psoriasis and schizophrenia.
Medical Hypotheses, 2017
The number of elderly patients with chronic pruritus has been gradually increasing in aging count... more The number of elderly patients with chronic pruritus has been gradually increasing in aging countries. Bullous pemphigoid, a common autoimmune blister disease in the elderly, is always heralded by pruritic eczematous dermatitis and is often associated with neurodegenerative diseases. We hypothesized that chronic eczematous dermatitis in patients with neurodegenerative diseases may be an early marker of bullous pemphigoid. By conducting retrospective chart review, we found neurodegenerative diseases are more prevalent in elderly patients with chronic eczematous dermatitis. The mean time delay between the diagnosis of neurodegenerative diseases and onset of skin lesions is 4.17years. In all 6 patients who received skin biopsy, eosinophils in the upper dermis or at the dermo-epidermal junction were obvious, which are remnant of the pathological finding of bullous pemphigoid. Together with the well-known association between bullous pemphigoid and neurodegenerative diseases, the results suggested that unlocalized eczematous dermatitis in the elderly may be an early manifestation of bullous pemphigoid. Inter-discipline communication among neurology, dermatology and geriatrics/gerontology is required to tailor specific managements for elderly patients with pruritus and neurodegenerative diseases.
British Journal of Dermatology, 2012
Background Itch is the cardinal symptom of atopic dermatitis (AD). b-Endorphin, a
neuropeptide, i... more Background Itch is the cardinal symptom of atopic dermatitis (AD). b-Endorphin, a
neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an
itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how
IL-31 and b-endorphin interact in AD skin remains elusive.
Objectives To investigate the mechanistic interaction of IL-31 and b-endorphin in
AD.
Methods This was a prospective cross-sectional study. We recruited adult patients
with AD and controls according to Hanifin’s AD criteria. Serum levels of IL-31
and b-endorphin were measured by enzyme-linked immunosorbent assay.
Expressions of IL-31 receptor A (IL-31RA) and b-endorphin in the skin were
assessed by immunohistochemistry. Their expression in the skin and blood was
compared and correlated in patients with AD and in controls. We also treated
primary keratinocytes with IL-31 and measured calcium influx, b-endorphin
production and signalling pathways to define their mechanistic interactions.
Results b-Endorphin was increased in the supernatant from IL-31-treated keratinocytes.
IL-31 receptor activation resulted in calcium influx and STAT3 activation;
pretreatment with STAT3 inhibitor stopped the increase of b-endorphin. Notably,
either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl
borate, an inhibitor for the store-operated channel, blocked STAT3 activation.
We found higher levels of blood b-endorphin and IL-31, which were
significantly correlated, in patients with AD. Moreover, IL-31RA and b-endorphin
were increased and colocalized both in AD human skin and TPA-painted mouse
skin.
Conclusions IL-31 receptor activation in keratinocytes induces calcium influx and
STAT3-dependent production of b-endorphin. These results might contribute to
an understanding of the regulatory mechanisms underlying peripheral itch.
Journal of European Academy of Dermatology and Venereology, 2017
Background
Schizophrenia is a complex disease which proceeds from an interaction between genetic... more Background
Schizophrenia is a complex disease which proceeds from an interaction between genetic background and environmental factors. Recent studies showed T helper 17 (Th17) signalling, which is the main downstream immune response of psoriasis, is activated in schizophrenia.
Objective
To investigate whether patients with schizophrenia have higher risk of psoriasis. Methods In this nationwide retrospective cohort study, we analysed the 1 million enrollees’ cohort from Taiwan’s National Health Insurance Research Database. Psoriasis and schizophrenia were ascertained by International Classification of Diseases, 9th revision, Clinical Modification coding. The study cohort was comprised of enrollees diagnosed with schizophrenia during the period from 1 January 1996 through 31 December 2010, while the comparison population consisted of enrollees who had not been diagnosed with schizophrenia during the study period. Hazard ratio (HR) and 95%
confidence interval (CI) were calculated for the risk of psoriasis associated with schizophrenia using Cox proportional hazard regression.
Results
The adjusted HR of psoriasis associated with schizophrenia was 2.32 (95% CI = 1.81–2.98). After 15 years, the cumulative incidence of psoriasis in patients with schizophrenia and comparison population was 2.82% and 1.17%, respectively. The Kaplan–Meier curves for the cumulative incidence of psoriasis in individuals with and without
schizophrenia differed significantly (P < 0.0001, log-rank test).
Conclusions
Patients with schizophrenia have higher risk of psoriasis, which may be due to common genetic susceptibilities and/or immunologic mechanisms in both diseases. Th17 signalling and pro-inflammatory cytokines may act as a link between these two diseases and are potential therapeutic targets for schizophrenia.
Journal of Psoriasis and Psoriatic Arthritis, 2018
Functional connectivity magnetic resonance imaging (fcMRI), a specific form of MRI imaging, quant... more Functional connectivity magnetic resonance imaging (fcMRI), a specific form of MRI imaging, quantitatively assesses connectivity between brain regions that share functional properties. Functional connectivity magnetic resonance imaging has already provided unique insights into changes in the brain in patients with conditions such as depression and pain and symptoms that have been reported by patients with psoriasis and are known to impact quality of life. To identify the central neurological impact of psoriasiform inflammation of the skin, we applied fcMRI analysis to mice that had been topically treated with the Toll-like receptor agonist, imiquimod (IMQ) to induce psoriasiform dermatitis. Brain insula regions, due to their suggested role in stress, were chosen as seed regions for fcMRI analysis. Mouse ear and head skin developed psoriasiform epidermal thickening (up to 4-fold, P < .05) and dermal inflammation after 4 days of topical treatment with IMQ. After fcMRI analysis, IMQ-treated mice showed significantly increased insula fc with wide areas throughout the brain, including, but not limited to, the somatosensory cortex, anterior cingulate cortex, and caudate putamen (P < .005). This reflects a potential central neurological impact of IMQ-induced psoriasis-like skin inflammation. These data indicate that fcMRI may be valuable tool to quantitatively assess the neurological impact of skin inflammation in patients with psoriasis.
Uploads
Miscellaneous by Sebastian Yu
Objective: We hypothesized that cold stress test combined with LDF could detect early-stage microangiopathy in patients with SSc.
Methods: A 67-year-old male came with multiple ulcerations on his fingers for one year. After excluding diseases such as diabetes mellitus-related peripheral arterial occlusive disease and smoking-related Buerger’s disease, the diagnosis of SSc was made according to the 2013 ACR/EULAR criteria. We performed LDF and angiography for a patient with SSc and compared the results.
Results: Although occlusions of right ulnar and digital arteries were obvious in angiography, the baseline skin temperature and perfusion unit on right fingers remained within normal limits. While the microcirculatory abnormalities measured by LDF alone are subtle, LDF combined with cold stress test detected a significant slow recovery of skin blood flow 40 minutes after cold immersion.
Conclusions: In conclusion, there may be discordance between macrovasculopathy and baseline microcirculatory blood flow in SSc. In such a case, cold immersion test is essential to measure the dynamic change and slow recovery of blood flow.
Photomedicine by Sebastian Yu
The authors would like to apologise for any inconvenience caused.
Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy.
OBJECTIVES:
To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV.
METHODS:
Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period.
RESULTS:
The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes.
CONCLUSIONS:
Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.
the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low-energy helium-neon (He-Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He-Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O2 consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He-Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He-Ne laser initiated mitochondrial retrograde signalling via a Ca2+-dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic-AMP response element binding protein)-related cascade, is responsible for the He-Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He-Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.
Arsenic by Sebastian Yu
(As-BD) can develop into invasive cancers after decades of arsenic exposure. The characteristic histological features of As-BD include full-layer epidermal dysplasia, apoptosis, and abnormal proliferation. Calcium propagation is an essential cellular event contributing to keratinocyte differentiation, proliferation, and apoptosis, all of which occur in As-BD. This study investigated how arsenic interferes calcium propagation of skin keratinocytes through ROS production and whether hydrogen-enriched water would restore arsenic-impaired calcium propagation. Arsenic was found to induce oxidative stress and inhibit
ATP- and thapsigaragin-induced calcium propagation. Pretreatment of arsenic-treated keratinocytes by hydrogen-enriched water or beta-mercaptoethanol with potent anti-oxidative effects partially restored
the propagation of calcium by ATP and by thapsigaragin. It was concluded that arsenic may impair calcium propagation, likely through oxidative stress and interactions with thiol groups in membrane proteins.
Skin-Brain interaction by Sebastian Yu
The prevalence of selected psychiatric disorders, such as depression and anxiety, is higher in patients with psoriasis. However, the association between psoriasis and schizophrenia is less clear. Here, we investigated whether the prevalence of schizophrenia is higher in patients with psoriasis.
Methods
In this cross-sectional study, we analyzed the 1-million-person cohort enrolled from Taiwan's National Health Insurance Research Database. Psoriasis, schizophrenia, and comorbidities were ascertained by the International Classification of Diseases, 9th revision, Clinical Modification coding. For schizophrenia, the concomitant catastrophic illness certificate was used to verify the diagnosis. The prevalence of schizophrenia in patients with psoriasis was compared with the prevalence of schizophrenia in a comparable population using a generalized linear mixed model.
Results
The prevalence of schizophrenia was significantly higher in patients with psoriasis than in the comparison population [prevalence ratio = 1.77, 95% confidence interval (CI) = 1.48–2.12, p < 0.0001)]. Within the psoriasis cohort, patients aged between 40 years and 59 years had a higher odds ratio (OR) for schizophrenia (OR = 2.49, 95% CI = 1.55–4.00, p = 0.0002). Furthermore, psoriatic patients with comorbid cerebrovascular disease (OR = 2.01, 95% CI = 1.11–3.65, p = 0.0220) and chronic pulmonary disease (OR = 1.64, 95% CI = 1.07–2.49, p = 0.0218) had higher odds for schizophrenia.
Conclusion
Schizophrenia is more prevalent in patients with psoriasis. Although the exact mechanisms remain to be clarified, the finding that psoriatic patients with comorbid cerebrovascular disease or chronic pulmonary disease have higher odds for schizophrenia may imply psoriatic patients with those comorbidities are likely to have higher inflammatory burden, which would contribute to the development of schizophrenia if a disruption of the blood–brain barrier is present. Further investigations are indicated to validate the hypothesis explaining the association between known comorbidies of psoriasis and schizophrenia.
neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an
itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how
IL-31 and b-endorphin interact in AD skin remains elusive.
Objectives To investigate the mechanistic interaction of IL-31 and b-endorphin in
AD.
Methods This was a prospective cross-sectional study. We recruited adult patients
with AD and controls according to Hanifin’s AD criteria. Serum levels of IL-31
and b-endorphin were measured by enzyme-linked immunosorbent assay.
Expressions of IL-31 receptor A (IL-31RA) and b-endorphin in the skin were
assessed by immunohistochemistry. Their expression in the skin and blood was
compared and correlated in patients with AD and in controls. We also treated
primary keratinocytes with IL-31 and measured calcium influx, b-endorphin
production and signalling pathways to define their mechanistic interactions.
Results b-Endorphin was increased in the supernatant from IL-31-treated keratinocytes.
IL-31 receptor activation resulted in calcium influx and STAT3 activation;
pretreatment with STAT3 inhibitor stopped the increase of b-endorphin. Notably,
either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl
borate, an inhibitor for the store-operated channel, blocked STAT3 activation.
We found higher levels of blood b-endorphin and IL-31, which were
significantly correlated, in patients with AD. Moreover, IL-31RA and b-endorphin
were increased and colocalized both in AD human skin and TPA-painted mouse
skin.
Conclusions IL-31 receptor activation in keratinocytes induces calcium influx and
STAT3-dependent production of b-endorphin. These results might contribute to
an understanding of the regulatory mechanisms underlying peripheral itch.
Schizophrenia is a complex disease which proceeds from an interaction between genetic background and environmental factors. Recent studies showed T helper 17 (Th17) signalling, which is the main downstream immune response of psoriasis, is activated in schizophrenia.
Objective
To investigate whether patients with schizophrenia have higher risk of psoriasis. Methods In this nationwide retrospective cohort study, we analysed the 1 million enrollees’ cohort from Taiwan’s National Health Insurance Research Database. Psoriasis and schizophrenia were ascertained by International Classification of Diseases, 9th revision, Clinical Modification coding. The study cohort was comprised of enrollees diagnosed with schizophrenia during the period from 1 January 1996 through 31 December 2010, while the comparison population consisted of enrollees who had not been diagnosed with schizophrenia during the study period. Hazard ratio (HR) and 95%
confidence interval (CI) were calculated for the risk of psoriasis associated with schizophrenia using Cox proportional hazard regression.
Results
The adjusted HR of psoriasis associated with schizophrenia was 2.32 (95% CI = 1.81–2.98). After 15 years, the cumulative incidence of psoriasis in patients with schizophrenia and comparison population was 2.82% and 1.17%, respectively. The Kaplan–Meier curves for the cumulative incidence of psoriasis in individuals with and without
schizophrenia differed significantly (P < 0.0001, log-rank test).
Conclusions
Patients with schizophrenia have higher risk of psoriasis, which may be due to common genetic susceptibilities and/or immunologic mechanisms in both diseases. Th17 signalling and pro-inflammatory cytokines may act as a link between these two diseases and are potential therapeutic targets for schizophrenia.
Objective: We hypothesized that cold stress test combined with LDF could detect early-stage microangiopathy in patients with SSc.
Methods: A 67-year-old male came with multiple ulcerations on his fingers for one year. After excluding diseases such as diabetes mellitus-related peripheral arterial occlusive disease and smoking-related Buerger’s disease, the diagnosis of SSc was made according to the 2013 ACR/EULAR criteria. We performed LDF and angiography for a patient with SSc and compared the results.
Results: Although occlusions of right ulnar and digital arteries were obvious in angiography, the baseline skin temperature and perfusion unit on right fingers remained within normal limits. While the microcirculatory abnormalities measured by LDF alone are subtle, LDF combined with cold stress test detected a significant slow recovery of skin blood flow 40 minutes after cold immersion.
Conclusions: In conclusion, there may be discordance between macrovasculopathy and baseline microcirculatory blood flow in SSc. In such a case, cold immersion test is essential to measure the dynamic change and slow recovery of blood flow.
The authors would like to apologise for any inconvenience caused.
Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy.
OBJECTIVES:
To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV.
METHODS:
Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period.
RESULTS:
The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes.
CONCLUSIONS:
Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.
the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low-energy helium-neon (He-Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He-Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O2 consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He-Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He-Ne laser initiated mitochondrial retrograde signalling via a Ca2+-dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic-AMP response element binding protein)-related cascade, is responsible for the He-Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He-Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.
(As-BD) can develop into invasive cancers after decades of arsenic exposure. The characteristic histological features of As-BD include full-layer epidermal dysplasia, apoptosis, and abnormal proliferation. Calcium propagation is an essential cellular event contributing to keratinocyte differentiation, proliferation, and apoptosis, all of which occur in As-BD. This study investigated how arsenic interferes calcium propagation of skin keratinocytes through ROS production and whether hydrogen-enriched water would restore arsenic-impaired calcium propagation. Arsenic was found to induce oxidative stress and inhibit
ATP- and thapsigaragin-induced calcium propagation. Pretreatment of arsenic-treated keratinocytes by hydrogen-enriched water or beta-mercaptoethanol with potent anti-oxidative effects partially restored
the propagation of calcium by ATP and by thapsigaragin. It was concluded that arsenic may impair calcium propagation, likely through oxidative stress and interactions with thiol groups in membrane proteins.
The prevalence of selected psychiatric disorders, such as depression and anxiety, is higher in patients with psoriasis. However, the association between psoriasis and schizophrenia is less clear. Here, we investigated whether the prevalence of schizophrenia is higher in patients with psoriasis.
Methods
In this cross-sectional study, we analyzed the 1-million-person cohort enrolled from Taiwan's National Health Insurance Research Database. Psoriasis, schizophrenia, and comorbidities were ascertained by the International Classification of Diseases, 9th revision, Clinical Modification coding. For schizophrenia, the concomitant catastrophic illness certificate was used to verify the diagnosis. The prevalence of schizophrenia in patients with psoriasis was compared with the prevalence of schizophrenia in a comparable population using a generalized linear mixed model.
Results
The prevalence of schizophrenia was significantly higher in patients with psoriasis than in the comparison population [prevalence ratio = 1.77, 95% confidence interval (CI) = 1.48–2.12, p < 0.0001)]. Within the psoriasis cohort, patients aged between 40 years and 59 years had a higher odds ratio (OR) for schizophrenia (OR = 2.49, 95% CI = 1.55–4.00, p = 0.0002). Furthermore, psoriatic patients with comorbid cerebrovascular disease (OR = 2.01, 95% CI = 1.11–3.65, p = 0.0220) and chronic pulmonary disease (OR = 1.64, 95% CI = 1.07–2.49, p = 0.0218) had higher odds for schizophrenia.
Conclusion
Schizophrenia is more prevalent in patients with psoriasis. Although the exact mechanisms remain to be clarified, the finding that psoriatic patients with comorbid cerebrovascular disease or chronic pulmonary disease have higher odds for schizophrenia may imply psoriatic patients with those comorbidities are likely to have higher inflammatory burden, which would contribute to the development of schizophrenia if a disruption of the blood–brain barrier is present. Further investigations are indicated to validate the hypothesis explaining the association between known comorbidies of psoriasis and schizophrenia.
neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an
itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how
IL-31 and b-endorphin interact in AD skin remains elusive.
Objectives To investigate the mechanistic interaction of IL-31 and b-endorphin in
AD.
Methods This was a prospective cross-sectional study. We recruited adult patients
with AD and controls according to Hanifin’s AD criteria. Serum levels of IL-31
and b-endorphin were measured by enzyme-linked immunosorbent assay.
Expressions of IL-31 receptor A (IL-31RA) and b-endorphin in the skin were
assessed by immunohistochemistry. Their expression in the skin and blood was
compared and correlated in patients with AD and in controls. We also treated
primary keratinocytes with IL-31 and measured calcium influx, b-endorphin
production and signalling pathways to define their mechanistic interactions.
Results b-Endorphin was increased in the supernatant from IL-31-treated keratinocytes.
IL-31 receptor activation resulted in calcium influx and STAT3 activation;
pretreatment with STAT3 inhibitor stopped the increase of b-endorphin. Notably,
either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl
borate, an inhibitor for the store-operated channel, blocked STAT3 activation.
We found higher levels of blood b-endorphin and IL-31, which were
significantly correlated, in patients with AD. Moreover, IL-31RA and b-endorphin
were increased and colocalized both in AD human skin and TPA-painted mouse
skin.
Conclusions IL-31 receptor activation in keratinocytes induces calcium influx and
STAT3-dependent production of b-endorphin. These results might contribute to
an understanding of the regulatory mechanisms underlying peripheral itch.
Schizophrenia is a complex disease which proceeds from an interaction between genetic background and environmental factors. Recent studies showed T helper 17 (Th17) signalling, which is the main downstream immune response of psoriasis, is activated in schizophrenia.
Objective
To investigate whether patients with schizophrenia have higher risk of psoriasis. Methods In this nationwide retrospective cohort study, we analysed the 1 million enrollees’ cohort from Taiwan’s National Health Insurance Research Database. Psoriasis and schizophrenia were ascertained by International Classification of Diseases, 9th revision, Clinical Modification coding. The study cohort was comprised of enrollees diagnosed with schizophrenia during the period from 1 January 1996 through 31 December 2010, while the comparison population consisted of enrollees who had not been diagnosed with schizophrenia during the study period. Hazard ratio (HR) and 95%
confidence interval (CI) were calculated for the risk of psoriasis associated with schizophrenia using Cox proportional hazard regression.
Results
The adjusted HR of psoriasis associated with schizophrenia was 2.32 (95% CI = 1.81–2.98). After 15 years, the cumulative incidence of psoriasis in patients with schizophrenia and comparison population was 2.82% and 1.17%, respectively. The Kaplan–Meier curves for the cumulative incidence of psoriasis in individuals with and without
schizophrenia differed significantly (P < 0.0001, log-rank test).
Conclusions
Patients with schizophrenia have higher risk of psoriasis, which may be due to common genetic susceptibilities and/or immunologic mechanisms in both diseases. Th17 signalling and pro-inflammatory cytokines may act as a link between these two diseases and are potential therapeutic targets for schizophrenia.
Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood.
Objective
To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice.
Methods
Following daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions.
Results
Compared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45+ leukocytes, mast cells as well as CD3+ T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice.
Conclusions
In summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.
Psoriasis is a chronic inflammatory disease that affects the skin, joints, and cardiovascular system. Although a potential association of end-stage renal disease (ESRD) with psoriasis has been demonstrated in patients, the potential for the use of cyclosporin in these patients for the modulation of the course of ESRD remains doubted. Furthermore, the association between psoriasis and renal diseases in general remains unclear. This study aimed to investigate the risk of renal disease in psoriatic patients with or without the use of cyclosporin.
Methods
We performed a retrospective cohort study using the National Health Insurance Database of Taiwan from 1996 to 2010 to identify patients with psoriasis, renal disease, chronic renal failure, and ESRD, and the use of cyclosporin. Overall, 3502 psoriatic patients and 10,506 matched population comparisons were identified. The hazard ratios (HRs) for renal events during the follow-up period were computed.
Results
Patients with psoriasis had an increased risk of chronic renal failure [HR = 3.00; 95% confidence interval (CI), 2.30–3.93; p < 0.0001] and ESRD (HR = 2.03; 95% CI, 1.04–3.96; p = 0.0393). Cyclosporin increased the risk of renal disease in patients without psoriasis (HR = 6.34; 95% CI, 3.57–11.26; p < 0.0001), but not in patients with psoriasis (HR = 1.33; 95% CI = 0.66–2.69; p = 0.4299).
Conclusion
Psoriasis is an independent risk factor of chronic renal failure and ESRD. Cyclosporin, a commonly used antipsoriatic agent, does not significantly increase the risk of renal disease in patients with psoriasis. Further studies with larger sample size are indicated to validate this result.