Search

Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis, and UVB may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is the production of cis-urocanic acid (cis-UCA) by keratinocytes. However, the detailed mechanism is yet to be fully understood. In this study, we found FLG expression and serum cis-UCA levels were significantly lower in patients with psoriasis than in healthy controls. We also noted that cis-UCA application inhibited psoriasiform inflammation through the reduction of Vγ4 + γδT17 cells in murine skin and draining lymph nodes. Meanwhile, CCR6 was downregulated on γδT17 cells, which would suppress the inflammatory reaction at a distal skin site. We revealed that the 5-hydroxytryptamine receptor 2A, the known cis-UCA receptor, was highly expressed on Langerhans cells in the skin. cis-UCA also inhibited IL-23 expression and induced PD-L1 on Langerhans cells, leading to the attenuated proliferation and migration of γδT-cells. Compared to the isotype control, α-PD-L1 treatment in vivo could reverse the antipsoriatic effects of cis-UCA. PD-L1 expression on Langerhans cells was sustained through the cis-UCA-induced mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These findings uncover the cis-UCA-induced PD-L1-mediated immunosuppression on Langerhans cells, which facilitates the resolution of inflammatory dermatoses., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pain and itch are both important manifestations of various disorders, such as herpes zoster, atopic dermatitis, and psoriasis. Growing evidence suggests that both sensations have shared mediators, overlapping neural circuitry, and similarities in sensitization processes. In fact, pain and itch coexist in some disorders. Determining pharmaceutical agents and targets for treating pain and itch concurrently is of scientific and clinical relevance. Here we review the neurobiology of pain and itch and discuss the pharmaceutical targets as well as novel compounds effective for the concurrent treatment of these sensations.

Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), also known as permeability glycoprotein, multidrug-resistant protein 1, or cluster of differentiation 243 (CD243), is a crucial protein for purging foreign substances from cells. The functions of ABCB1 have been investigated extensively for their roles in cancer, stem cells, and drug resistance. Abundant pharmacogenetic studies have been conducted on ABCB1 and its association with treatment responsiveness to various agents, particularly chemotherapeutic and immunomodulatory agents. However, its functions in the skin and implications on dermatotherapeutics are far less reported. In this article, we reviewed the roles of ABCB1 in dermatology. ABCB1 is expressed in the skin and its appendages during drug delivery and transport. It is associated with treatment responsiveness to various agents, including topical steroids, methotrexate, cyclosporine, azathioprine, antihistamines, antifungal agents, colchicine, tacrolimus, ivermectin, tetracycline, retinoid acids, and biologic agents. Moreover, genetic variation in ABCB1 is associated with the pathogenesis of several dermatoses, including psoriasis, atopic dermatitis, melanoma, bullous pemphigoid, Behçet disease, and lichen planus. Further investigation is warranted to elucidate the roles of ABCB1 in dermatology and the possibility of enhancing therapeutic efficacy through ABCB1 manipulation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pruritus, or itch, is a prevalent symptom causing profound health burden in many dermatological and non-dermatological disorders. Several itch questionnaires have been created to assess itch. Particularly, Eppendorf Itch Questionnaire (EIQ) is widely accepted since it encompasses various aspects of itch, including intensity, affects, coping behavior, and motivation to scratch., Methods: In a cross-sectional survey, we examined the validity, reliability and clinical utility of Traditional Chinese EIQ., Results: We administered the consensus version to 128 adults (median: 48.5 years, interquartile range [IQR]: 39-63) with active itch for more than 6 weeks at the Outpatient Clinics of three medical centers in Taiwan. Clinical diagnoses included psoriasis (N = 82), xerosis (N = 34), or other dermatitis (N = 12). Cronbach's alpha for each EIQ scale ranged 0.82-0.98, suggesting good to excellent internal consistency and reliability. Three EIQ scales significantly correlated with visual analogue scale (VAS) for itch intensity (P ≤ 0.001 for median test), supporting for its concurrent validity. None of EIQ scale was statistically correlated with Psoriasis Area Severity Index (PASI) scores in psoriasis patients, confirming its discriminant validity. Moreover, patients of different diagnoses had distinct responses to the multi-scale EIQ index, affording it a better clinical test (area-under-the-ROC curve [AUC]: 0.76, 95% CI: 0.63-0.90) than VAS alone (AUC: 0.42, 95%CI: 0.24-0.59) in distinguishing dermatitis/eczema-related itch from psoriasis or xerosis-related itch., Conclusion: We demonstrated the reliability and validity of Chinese EIQ in adult patients with chronic itch at the outpatient setting. The study also revealed the diversified aspects of itch across patients with various dermatoses., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent signaling reaches percept-forming cortical neurons and can occur due to increased sensory signaling, decreased inhibitory signaling, or a combination of both processes. To treat these symptoms, detailed knowledge of sensory transmission, from innervated end organ to cortex, is required. Molecular, genetic, and behavioral dissection of itch in animals and patients has improved understanding of the receptors, cells, and circuits involved. In this review, we will discuss neuropathic itch with a focus on the itch-specific circuit.

TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Here, we identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Tmem100 is coexpressed and forms a complex with TRPA1 and TRPV1 in DRG neurons. Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. Single-channel recording in a heterologous system reveals that Tmem100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibition of TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect; i.e., it enhances the association of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide (CPP) containing the C-terminal sequence of Tmem100-3Q mimics its effect and inhibits persistent pain. Our study unveils a context-dependent modulation of the TRPA1-V1 complex, and Tmem100-3Q CPP is a promising pain therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This paper proposes a new mixed quantum mechanics (QM)-molecular mechanics (MM) approach, where MM is replaced by quantum Hamilton mechanics (QHM), which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics.

In primates, C-fibre polymodal nociceptors are broadly classified into two groups based on mechanosensitivity. Here we demonstrate that mechanically sensitive polymodal nociceptors that respond either quickly (QC) or slowly (SC) to a heat stimulus differ in responses to a mild burn, heat sensitization, conductive properties and chemosensitivity. Superficially applied capsaicin and intradermal injection of β-alanine, an MrgprD agonist, excite vigorously all QCs. Only 40% of SCs respond to β-alanine, and their response is only half that of QCs. Mechanically insensitive C-fibres (C-MIAs) are β-alanine insensitive but vigorously respond to capsaicin and histamine with distinct discharge patterns. Calcium imaging reveals that β-alanine and histamine activate distinct populations of capsaicin-responsive neurons in primate dorsal root ganglion. We suggest that histamine itch and capsaicin pain are peripherally encoded in C-MIAs, and that primate polymodal nociceptive afferents form three functionally distinct subpopulations with β-alanine responsive QC fibres likely corresponding to murine MrgprD-expressing, non-peptidergic nociceptive afferents.

Itch-specific neurons have been sought for decades. The existence of such neurons has been doubted recently as a result of the observation that itch-mediating neurons also respond to painful stimuli. We genetically labeled and manipulated MrgprA3(+) neurons in the dorsal root ganglion (DRG) and found that they exclusively innervated the epidermis of the skin and responded to multiple pruritogens. Ablation of MrgprA3(+) neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions, whereas pain sensitivity remained intact. Notably, mice in which TRPV1 was exclusively expressed in MrgprA3(+) neurons exhibited itch, but not pain, behavior in response to capsaicin. Although MrgprA3(+) neurons were sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.

Aim: To extend nursing knowledge of distress experienced by family caregivers of children with rare genetic disorders, by exploring the perspectives of caregivers of children with Russell-Silver Syndrome in Taiwan., Background: Caring for a child with a rare genetic disorder often has profound effects on families, especially when diagnosis and treatment is complex or not yet well developed, such as that in Russell-Silver Syndrome (or Silver-Russell syndrome). This disorder causes dwarfism and developmental difficulties, requiring long-term care planning. Previous research has focused mostly on medical care, but little is known about families' perspectives of caring difficulties, the help they need and nursing care required., Design: An exploratory qualitative approach was used to inform this study., Methods: Family caregivers, whose children were undergoing medical care in a leading Taiwan medical centre, were invited to participate in face-to-face, in-depth interviews. Data were analysed by content analysis., Results: Fifteen caregivers including 11 mothers, two fathers and two grandmothers participated. Five major themes and 13 sub-themes of care-giving distress were identified: endless psychological worries; the lengthy process to confirm a medical diagnosis; adjustment efforts in modifying family roles; dilemmas in deciding between Western or Chinese traditional medicine; and negative responses to society's concerns. Their primary sources of support were spouses, parents and health professionals, accordingly., Conclusion: Complex physio-psycho-social and decision-making distress in caring for children with a rare genetic disorder were systematically revealed from the perspectives of ethnic-Chinese family caregivers., Relevance to Clinical Practice: Long-term care plans for children with a rare genetic disorder such as Russell-Silver Syndrome need to focus on positive dynamic family interactions, life-stage development and family caregiver support. Research on care-giving in rare genetic disorders is also warranted across cultures and countries to develop a substantial knowledge basis for nursing practice., (© 2011 Blackwell Publishing Ltd.)

Itch has been defined as an unpleasant skin sensation that triggers the urge to scratch. Primary sensory dorsal root ganglia neurons detect itch stimuli through peripheral axons in the skin, playing an important role in generating itch. Itch is broadly categorized as histaminergic (sensitive to antihistamines) or nonhistaminergic. The peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL) is an itch-inducing agent widely used to study histamine-independent itch. Here, we show that Mrgprs (Mas-related G protein-coupled receptors), particularly MrgprC11, rather than PAR2 (protease-activated receptor 2) as previously thought, mediate this type of itch. A shorter peptide, SLIGR, which specifically activates PAR2 but not MrgprC11, induced thermal pain hypersensitivity in mice but not a scratch response. Therefore, although both Mrgpr and PAR2 are SLIGRL-responsive G protein-coupled receptors present in dorsal root ganglia, each plays a specific role in mediating itch and pain.

The cellular and molecular mechanisms mediating histamine-independent itch in primary sensory neurons are largely unknown. Itch induced by chloroquine (CQ) is a common side effect of this widely used antimalarial drug. Here, we show that Mrgprs, a family of G protein-coupled receptors expressed exclusively in peripheral sensory neurons, function as itch receptors. Mice lacking a cluster of Mrgpr genes display significant deficits in itch induced by CQ but not histamine. CQ directly excites sensory neurons in an Mrgpr-dependent manner. CQ specifically activates mouse MrgprA3 and human MrgprX1. Loss- and gain-of-function studies demonstrate that MrgprA3 is required for CQ responsiveness in mice. Furthermore, MrgprA3-expressing neurons respond to histamine and coexpress gastrin-releasing peptide, a peptide involved in itch sensation, and MrgprC11. Activation of these neurons with the MrgprC11-specific agonist BAM8-22 induces itch in wild-type but not mutant mice. Therefore, Mrgprs may provide molecular access to itch-selective neurons and constitute novel targets for itch therapeutics., (Copyright 2009 Elsevier Inc. All rights reserved.)

Objective: This study aimed to compare the perspectives of leading ethical issues related to organ transplantation as perceived by health professionals (HP), legal professionals (LP), and religious experts (RE) from Taiwan (TW) and Mainland China (MC)., Materials and Methods: A purposive sample including TW's organ transplant health professionals (OTHP), LP, and RE and MC's HP was obtained in this qualitative research. Data were analyzed by content analysis., Results: A total of 127 subjects participated in this project (n = 119 in TW, 8 in MC). They were HP (n = 92), RE (n = 25 TW), and LP (n = 10 TW). Seven ethical dilemmas were reported: (1) difficulties in touching the hearts of the public (HP 100%, LP 100%, RE 100%); (2) challenges in helping donors and their families (HP 96%, RE 80%, LP 50%); (3) competence and availability of HP (HP 93%, RE 72%, LP 50%); (4) questionable social farewell (HP 92%, RE 20%, LP 100%); (5) questionable legitimacy of prisoners' motivations (LP 90%, RE 64%, HP 60%); (6) worry about public discrimination (LP 90%, HP 50%, RE 20%); and (7) challenges to families in taking care of the recipients (HP 87%, LP 70%, RE 52%)., Conclusions: To provide holistic care, HP need to invite RE to provide spiritual support for the donors of cadaveric organs, recipients, and their families. Reliable LP can help them to complete the sophisticated legal procedures. With help from this triangulated collaborative team, the value of organ transplantation will be appreciated by the public.

Objective: This study aimed to compare the dilemmas of using organs from prisoners with death penalties (PDP) from the perspectives of organ transplant health professionals (OTHP) from Taiwan (TW) and Mainland China (MC)., Materials and Methods: A purposive sample including TW's OTHP (including transplant surgeons, nurses, researchers, social workers, and medical religious and legal experts), and MC's OTHP (including surgeons and nurses) was obtained in this qualitative research. TW's subjects received face-to-face interviews, and MC's subjects received telephone interviews due to limited communication opportunities. Data were analyzed by content analysis., Results: A total of 105 subjects participated in this project (TW n = 99, MC n = 6). They were surgeons (n = 18: TW n = 14, MC n = 4), registered nurses (n = 42: TW n = 40, MC n = 2), OT coordinating nurses (n = 10 TW), OT researchers (n = 5 TW), social workers (n = 10 TW), medical religious experts (n = 15 TW), and medical legal experts (n = 5 TW). The following 8 ethical dilemmas were reported: (1) questionable legitimacy of PDP motivation (TW 100%, MC 100%); (2) recipients' worries about public discrimination (TW 89%, MC 50%); (3) difficulties in approaching PDP (TW 100%); (4) hesitation of HP and volunteers in helping PDP (TW 37%); (5) questionable social contribution of PDP as donor sources (TW 32%); (6) complex legal details of PDP issues (TW 26%); (7) potential threat from PDP families (TW 23%); and (8) difficulties in helping PDP families cope with post-organ donation syndrome (TW 11%)., Conclusions: Five suggestions were developed in managing these challenges: (1) TW OTHP may empower their basic social science knowledge and empirical competence; (2) TW government may form a task force wherein OTHP leaders are encouraged to foster interdisciplinary collaborations with the public within short-, mid-, and long-term time frames; (3) TW and MC may establish evidence-based center(s) to provide systematic literature reviews for clinical guidance, policy making, and educational resources; (4) TW and MC may try to improve the quality of PDP organ harvesting and donation practice in jails/health institutes; and (5) TW and MC may develop reliable communication systems to share experiences of quality care for PDP, and to evaluate the appraisals both pro and con from multidisciplinary societies and the public, if available.

Previous studies of predictors of atopic dermatitis (AD) in Asia have had limited sample size and small numbers of variables focused primarily on family history or dietary exposures. The purpose of this study was to evaluate the influence of various environmental risk factors for early infantile AD. We used multistage, stratified systematic sampling to recruit 2048 mother-child pairs from the Taiwan national birth registration in 2003. Information on environmental risk factors for infant AD gathered by questionnaire were available from 1760 infants at 6 months of age. Multiple logistic regression was used to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) for risk factors for AD after adjusting for potential confounders. AD was noted in 118 of 1760 (6.7%) of the infants. After adjusting for maternal age and education, family history of atopy, infant gender, and gestational age, fungi on walls of the house [aOR 2.14 (95% CI 1.41-3.22)] and frequent use of microwave oven at home [aOR 1.71 (95% CI 1.13-2.58)] increased the risk of early infantile AD. This study suggests that environmental factors do play a role in early infantile AD. Fungi, a kind of aeroallergen, are especially important in humid climate as in Taiwan and their impacts might be felt at the early infant stage. The hazards of microwave use should be paid more attention.