Role of transient receptor potential channels in melanocytes and their related diseases / 中华皮肤科杂志

Transient receptor potential (TRP) channels are a special type of non-selective cationic channel family located on the cell membrane or organelle membrane, and notably expressed in melanocytes. This review summarizes recent research progress in biological functions of TRP channels in melanocytes and their involvement in the pathological process of pigmented skin diseases and melanoma, so as to provide a new theoretical basis for the prevention and treatment of melanin-related diseases.

Role of different melanocyte populations in the reconstitution of pigmented hair follicles / 中华皮肤科杂志

Objective:To observe whether hair follicle cells from mice of different species can integrate to generate new pigmented hair follicles, and to explore the role of different melanocyte populations in pigmented hair follicle reconstruction in mice.Methods:The epidermal cell population, hair follicle epithelial cell population and dermal cell population were isolated from the skin of fetal or neonatal C57BL/6J and BALB/C mice, and epidermal melanocytes were obtained by culture and purification of the epidermal cell population. The experiments were divided into 3 parts: (1) hair follicle reconstruction experiment in neonatal C57BL/6J mice, which included 2 groups: epidermal cells + hair follicle epithelial cells group and dermal cells group; (2) chimeric hair follicle reconstruction experiment, which included 4 groups: dermal cells of neonatal C57BL/6J mice group, dermal cells of neonatal BALB/C mice group, dermal cells of neonatal BALB/C mice + dermal cells of neonatal C57BL/6J mice group, and dermal cells of fetal BALB/C mice + dermal cells of fetal C57BL/6J mice group; (3) pigmented hair follicle reconstruction experiment, which included 3 groups: dermal cells of neonatal BALB/C mice + epidermal cells of neonatal C57BL/6J mice group, dermal cells of neonatal BALB/C mice + hair follicle epithelial cells of neonatal C57BL/6J mice group, and dermal cells of neonatal BALB/C mice + cultured C57BL/6J epidermal melanocytes group. Different cells were implanted into dorsal skin fold chambers of the nude mice, and there were 4 mice in each group. At weeks 4 and 8 after inoculation, hair follicle reconstruction was assessed by gross observation, histological examination and immunofluorescence assay.Results:Among the 8 BALB/C nude mice in the 2 groups in the hair follicle reconstruction experiment, 7 survived and 1 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, no hair growth was observed in the epidermal cells + hair follicle epithelial cells group (3 mice) , while normal hair grew out in the dermal cells group (4 mice) mixed with epithelial components. Among the 16 BALB/C nude mice in the 4 groups in the chimeric hair follicle reconstruction experiment, 14 survived and 2 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, brown-grey hair grew well in the dermal cells of neonatal BALB/C mice + dermal cells of neonatal C57BL/6J mice group (4 mice) , and dermal cells of fetal BALB/C mice + dermal cells of fetal C57BL/6J mice group (3 mice) . Among the 12 BALB/C nude mice in the 3 groups in the pigmented hair follicle reconstruction experiment, 10 survived and 2 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, only white hair grew out in the dermal cells of neonatal BALB/C mice + cultured C57BL/6J epidermal melanocytes group (3 mice) , and no hair follicle melanocytes were observed by immunofluorescence assay, while brown-grey hair grew well in the dermal cells of neonatal BALB/C mice + epidermal cells of neonatal C57BL/6J mice group (4 mice) , and dermal cells of neonatal BALB/C mice + hair follicle epithelial cells of neonatal C57BL/6J mice group (3 mice) .Conclusions:The interaction between mesenchymal cells and hair follicle epithelial cells is a necessary condition for hair follicle reconstruction. The hair follicle cells from different species of mice can integrate to generate new pigmented hair follicles. Both hair follicle melanocytes and epidermal melanocytes can participate in the formation of pigmented hair follicles, but differentiated melanocytes have no such ability.

Regulation of melanocyte chemokine expression by folliculin protein in vitiligo patients / 中华医学美学美容杂志

Objective:To investigate the effect of human tumor suppressor folliculin (FLCN) on the expression of melanocyte chemokines (MC) mediated by immune factors in vitiligo.Methods:The MC of vitiligo patients that received autologous melanocyte transplantation in the Department of Dermatology, Hangzhou Third People′s Hospital from January to April 2019 were collected. The blister fluid of the white spot and the normal part was taken. Western blot was used to analyze the expression difference of MC and FLCN protein in normal, vitiligo patients and that induced by immune factors; FLCN shRNA lentivirus was constructed by shRNA and transfected into normal MC (FLCN shRNA MC) to interfere with the expression of silenced FLCN gene. The effect of immune factors on chemokines in FLCN shRNA MC was detected by ELISA.Results:The results of Western blot showed that FLCN protein was highly expressed in melanocytes of vitiligo patients, immune factors stimulated FLCN protein expression in normal melanocytes significantly increased ( t=1.27; P<0.001), chemokine CXCL10 and CCL20 also significantly increased ( t=104.53 and 60.21, respectively; P<0.001). The expression of FLCN in FLCN shRNA MC was significantly decreased ( F=1.95, P<0.001); and the high expression of CXCL10 and CCL20 induced by immune factors was significantly inhibited ( F=93.676 and 74.096, all P<0.001). Conclusions:Immune factors can stimulate the expression of CXCL10 and CCL20, which are closely related to vitiligo, while FLCN is a key protein involved in immune factors inducing melanocyte chemokine expression.

Correlations of α-melanocyte stimulating hormone levels in serum and synovial fluid with progression of primary knee osteoarthritis / 中华创伤骨科杂志

Objective:To explore the correlations of α-melanocyte stimulating hormone ( α-MSH) levels in serum and synovial fluid with progression of primary knee osteoarthritis (KOA). Methods:A retrospective analysis was conducted of the 96 patients who had been diagnosed as primary KOA at Department of Orthopedics, The First Hospital of Huizhou from October 2018 to October 2019. Radiographic severity of KOA was determined by Kellgren-Lawrence (K-L) grades; α-MSH levels were measured by enzyme-linked immunosorbent assay (ELISA). Levels of pro-inflammatory cytokine interleukin-1 β (IL-1 β) and matrix metalloproteinase-3 (MMP-3) were also detected. Another 64 patients with patellar dislocation, matched in age and gender, were enrolled as controls. The Numeric Pain Scale (NPS) and revised Oxford Knee Score (OKS) were employed to evaluate their symptomatic severity. Receiver operating characteristics (ROC) curve was used to compare α-MSH, IL-1 β and MMP-3 with regard to their diagnostic values in the K-L grading. Results:There were no statistically significant difference in age, gender and body mass index between the 2 groups, showing they were comparable ( P> 0.05). The α-MSH levels in synovial fluid were significantly lower in the KOA patients than in the controls [(16.9±3.8) pg/mL versus (18.8±2.7) pg/mL] ( P<0.001); there were no significant differences between the KOA patients and the controls in the serum α-MSH levels [(24.9±1.8) pg/mL versus (24.8±1.7) pg/mL] ( P>0.05). The α-MSH levels in synovial fluid were negatively correlated with K-L grades ( r=-0.382, P<0.001) and negatively correlated with NPS ( r=-0.382, P<0.001) but positively correlated with OKS ( r=0.339, P<0.001). Moreover, the α-MSH levels in synovial fluid were negatively correlated with the IL-1 β levels in synovial fluid ( r=-0.483, P<0.001) and with the MMP-3 levels in synovial fluid ( r=-0.336, P< 0.001). Conclusions:The level of serum α-MSH may not be correlated with the progression of KOA but the synovial fluid α-MSH is negatively correlated with the progression of KOA. Therefore, the expression level of α-MSH in joint synovial fluid can be used as a potential biomarker for assessment of severity of knee osteoarthritis.

Updated Molecular Regulation of Hair Growth and Pigmentation by Dermal Papilla Cells / 中国医学科学院学报

There is growing evidence that dermal papilla cells(DPCs)act as the organizing center to induce the cyclic hair regeneration.On one hand,DPCs secrete cytokines or growth factors to regulate the differentiation,proliferation,and migration of epithelial stem cells(EpSCs)and melanocyte stem cells(MeSCs)residing in the bulge region.On the other hand,DPCs manipulate the microenvironment(also termed as niche)for both EpSCs and MeSCs,such as the size of dermal papilla,the distance between dermal papilla and the bulge region,and the lymphatic drainage and sympathetic nerve innervation surrounding the bulge region,thereby orchestrating the cycling hair growth.Recent studies have demonstrated at least four subpopulations existing in dermal papillae,which induce the unilineage transit-amplifying epithelial cells to form the concentric multilayers of hair shafts and sheaths.In addition,emerging study has indicated that sustained psychological stress potentially leads to hyperactivation of the sympathetic nerves that innervate the bulge region.The large amount of norepinephrine released by the nerve endings forces MeSCs to rapidly and abnormally proliferate,resultantly causing the depletion of MeSC pool and the loss of hair pigment.Understanding the molecular regulation of hair growth and pigmentation by DPCs holds substantial promise for the future use of cultured DPCs

Assessment of Acute Phase Protein Serum hs-CRP Levels and its Role in Severity of Disease in Vitiligo Patients – A Hospital Based Case Control Study in M.Y. Hospital, Indore M.P.

Introduction: Vitiligo an acquired pigmentary disorderof the skin and mucous membranes characterized by wellcircumscribed, depigmented macules and patches resultingfrom selective destruction of melanocytes. CRP is an acutephase protein secreted by the liver in response to severalinflammatory cytokines such as IL6. Since inflammatoryand immune factors plays a key role in the pathogenesis ofvitiligo, we aimed to assess the relationship between theserum level of hs-CRP and pathogenesis and severity ofvitiligo.Material and methods: The study was conducted in theDept. of Biochemistry and Dept. of Dermatology andVenereology in MGM Medical College & M Y HospitalIndore after approval from ethical committee on 70Confirmed & diagnosed cases of Vitiligo patients of agegroup 18 to 55 years attending Dermatology OPD in MYHospital Indore during a period of April 2018 to April 2019.Patients were divided into three groups according to thearea of skin affected. Healthy individual without vitiligowere taken as controls. Venous blood sample was analyzedfor serum hs-CRP levels and liver function. Appropriatestatistical tests were applied on Minitab Version 17.0 and pvalues < 0.01was considered significant.Results: In our study the mean serum hs-CRP in case groupwas higher 12.09 ± 11.64 than in control group it was 1.99 ±2.05 with negative but statistically significant correlation withage of onset of disease and positive statistically significantcorrelation with duration of disease thus, serum hs-CRPlevel might be useful for evaluating the disease activity ofvitiligo as Novel biomarker.Conclusion: As high-sensitive C-reactive protein (hs-CRP)is an important sensitive diagnostic and prognostic markerin many systemic inflammatory diseases and very lowconcentrations of hs-CRP can be analyzed in the serum, itsdetection and serial measurements helps to provide a novellink to evaluate the disease activity and severity and responseto treatment

The comprehensive detection of miRNA, lncRNA, and circRNA in regulation of mouse melanocyte and skin development

BACKGROUND: Pigmentation development, is a complex process regulated by many transcription factors during development. With the development of the RNA sequencing (RNA-seq), non-coding RNAs, such as miRNAs, lncRNAs, and circRNAs, are found to play an important role in the function detection of related regulation factors. In this study, we provided the expression profiles and development of ncRNAs related to melanocyte and skin development in mice with black coat color skin and mice with white coat color skin during embryonic day 15 (E15) and postnatal day 7 (P7). The expression profiles of different ncRNAs were detected via RNA-seq and also confirmed by the quantitative real-time PCR (qRT-PCR) method. GO and KEGG used to analyze the function the related target genes. RESULTS: We identified an extensive catalogue of 206 and 183 differently expressed miRNAs, 600 and 800 differently expressed lncRNAs, and 50 and 54 differently expressed circRNAs, respectively. GO terms and pathway analysis showed the target genes of differentially expressed miRNA and lncRNA. The host genes of circRNA were mainly enriched in cellular process, single organism process. The target genes of miRNAs were mainly enriched in chromatin binding and calcium ion binding in the nucleus. The function of genes related to lncRNAs are post translation modification. The competing endogenous RNA (ceRNA) network of lncRNAs and circRNAs displays a complex interaction between ncRNA and mRNA related to skin development, such as Tcf4 , Gnas , and Gpnms related to melanocyte development. CONCLUSIONS: The ceRNA network of lncRNA and circRNA displays a complex interaction between ncRNA and mRNA related to skin development and melanocyte development. The embryonic and postnatal development of skin provide a reference for further studies on the development mechanisms of ncRNA during pigmentation.

Expression and localization of diacylglycerol kinase zeta and protein kinase C beta II in mouse back skin with different coat colors / 中国组织工程研究

BACKGROUND: In the skin and hair pigmentation mechanism, diacylglycerol kinase ζ (DGKζ) has not been reported to participate in pigmentation. OBJECTIVE: To investigate the expression and localization of DGKζ and protein kinase C βII (PKCβII) in the mouse back skin with different coat colors and their correlation with the formation of coat color. METHODS: The back skin of 2-month-old mice with different coat colors (white, gray, and black, 6 mice for each color) was taken to detect DGKζ and PKCβII mRNAs by real-time PCR, DGKζ, PKCβII and p-PKCβII proteins by western blot, and DGKζ and p-PKCβII expression by immunohistochemistry. The study protocol was approved by the Animal Ethics Committee of the Animal Experimental Center of Shanxi Medical University. RESULTS AND CONCLUSION: DGKζ and PKCβII mRNAs were both expressed in the back skin of mice with three kinds of coat colors, with its relative expression amount being: gray group > white group; black group > white group (P white group; black group > white group (P < 0.05). Immunohistochemistry staining showed that DGKζ and p-PKCβII were positively expressed in the outer root sheath of hair follicle, hair matrix cells and melanocytes in the hair matrix in the back skin of gray and black mice, while were negative in the hair follicles of white mice. According to the expression and localization of DGKζ, PKCβII in white, gray and black mouse back skin, we can speculate that DGKζ and PKCβII may participate in the formation of the coat color.

Recurrent laryngeal neuropathy secondary to nerve compression by melanomas - case report / Neuropatia laríngea recorrente secundária à compressão por melanomas - relato de caso

Recurrent laryngeal neuropathy (RLN) etiology can be acquired, iatrogenic or idiopathic. There are no previous reports of RLN caused by recurrent laryngeal nerve compression by melanomas. This report describes a horse presenting severe dyspnea and progressive weight loss. Physical exam demonstrated tachycardia, tachypnea, inspiratory dyspnea at rest, neck extension and mydriasis. Temporary tracheotomy was performed and videoendoscopic examination diagnosed grade IV laryngeal paralysis. The animal came suddenly to death by suppurative bacterial pneumonia. At necropsy, it was possible to observe multiple melanotic epithelioid melanoma nodules compressing the recurrent laryngeal nerve, alongside with lung and parotid metastasis. This finding emphasizes the importance of establishing a differential diagnosis for tumor mass compression in the etiology of RLN, especially melanomas in gray horses, with or without cutaneous manifestations of masses.(AU)

A neuropatia laríngea recorrente (NLR) pode apresentar etiologia adquirida, iatrogênica ou idiopática. Não há relatos prévios da ocorrência da NLR causada pela compressão do nervo laríngeo recorrente por melanomas. Este relato descreve um equino apresentando dispneia grave e perda de peso progressiva. O exame físico demonstrou taquicardia, taquipneia, dispneia inspiratória em repouso, extensão do pescoço e midríase. Foi realizada traqueotomia temporária e exame videoendoscópico, mediante o qual se diagnosticou paralisia laríngea grau IV. O animal veio a óbito por pneumonia bacteriana supurativa. Na necropsia, foi possível observar múltiplos nódulos de melanoma epitelioide amelanótico comprimindo o nervo laríngeo recorrente, juntamente com metástases pulmonares e parotídeas. Este achado enfatiza a importância de estabelecer um diagnóstico diferencial nos casos de NLR, pensando-se na compressão nervosa por massas tumorais, especialmente melanomas em cavalos tordilhos, com ou sem manifestações cutâneas de massas.(AU)

Intraepidermal injection of autologous non-cultured epidermal cell suspension in lesions of stable vitiligo: A novel method of repigmenting vitiligo

Background: Transplantation of autologous non-cultured epidermal cell suspension containing melanocytes (ANEM) is one of the well-known surgical options for repigmenting stable vitiligo lesions. The recipient site for transplantation has traditionally been prepared by dermabrasion, liquid N2, or laser resurfacing, which is costly, cumbersome and has risk of scarring. Objectives: The objectives of this study were to experiment a novel method of repigmenting stable vitiligo lesions by intraepidermal injection of ANEM in the vitiligo lesions. Materials and Methods: A total of 50 stable vitiligo lesions in 50 patients were included in the study. The prepared ANEM was inoculated intraepidermally in the lesions. Patients were given PUVASOL therapy in post-operative period and followed up 4 weekly for 24 weeks to see repigmentation. Results: At 24 weeks, pigmentation was seen in 31 (62%) lesions of 50 lesions. It was excellent in 6 (12%), good in 10 (20%), satisfactory in 8 (16%), and poor in 7 (14%) patients. Adverse events were mild and insignificant. Conclusion: Intraepidermal ANEM inoculation in stable vitiligo lesions is an effective, safe, and cheap dermatosurgical procedure.

Autologous noncultured melanocyte-keratinocyte transplantation in stable vitiligo: A randomized comparative study of recipient site preparation by two techniques

Background: Accurate preparation of recipient area is a critical step in melanocyte-keratinocyte transplantation procedure for vitiligo. It is an important potential step for adaptation in the quest to achieve better results and ablative lasers potentially offer excellent precision over margin and depth control in achieving that. Objective: To compare between the two techniques used for recipient site preparation: Er:YAG laser ablation and mechanical dermabrasion for melanocyte-keratinocyte transplantation procedure in terms of re-pigmentation achieved and adverse effects seen. Methods: A randomized comparative trial was performed among 32 patients of stable vitiligo undergoing melanocyte-keratinocyte transplantation procedure. In Group A (n = 15), recipient site preparation was done with Er:YAG laser, and in Group B (n = 17), it was done with a motorized dermabrader. Patients of both groups were objectively assessed for re-pigmentation at 1, 3 and 6 months. Results: A total of 253.696 cm2 of depigmented surface was operated upon and re-pigmentation of 125.359 cm2 (49.4%) was achieved. On comparison between two groups, no statistical difference was found with respect to total re-pigmentation achieved (Group A: 54.67% vs Group B: 48.841%, P = 0.663) and grades of re-pigmentation achieved (P = 0.796). Occurrence of adverse events was also statistically similar in both the groups. Conclusion: This study did not reveal any statistically different outcome (in terms of re-pigmentation and adverse effects) between the two methods of recipient site preparation – motorized dermabrasion and Er:YAG ablation. Limitations: This study is small and larger studies are needed to ascertain the benefit of Er:YAG for recipient site preparation. Future studies may also ascertain variables such as time taken to prepare the recipient area, nature of bleeding, postoperative healing, difficulties in specific area, cost of the procedure, patient comfort and ease of the surgeon, rather than comparing the re-pigmentation alone.

Anti-melanogenic effects of Hordeum vulgare L. barely sprout extract in murine B16F10 melanoma cells / 한국영양학회지

PURPOSE: Barely sprout is a well-known oriental herbal medicine with a wide range of health benefits. Recent studies have provided scientific evidence of its therapeutic effects with expanded application. This study investigated anti-melanogenic effect of barley sprout water extract (BSE) in murine melanocyte B16F10. METHODS: Various concentrations (0, 50, 125, and 250 µg/mL) of BSE and arbutin (150 ppm) were applied to B16F10 stimulated with or without alpha-melanocyte stimulating hormone (100 nM) for 72 hours. The whitening potency of BSE was determined altered cellular melanin contents. Activity and expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were also assayed. RESULTS: Experimental results revealed that treatment with BSE reduced cellular melanin production by approximately 40% compared to the control. Molecular findings supported that suppressed activity and expression of tyrosinase and MITF proteins by BSE were associated with declined cellular melanogenesis. Furthermore, anti-melanogenic effect of BSE (250 µg/mL) was similar to that of arbutin, a commonly used whitening agent. Lastly, polyphenols including p-coumaric, ferulic, and vanillic acids were identified in BSE using HPLC analyses. They might be potential active ingredients showing such melanogenesis-reducing effect. CONCLUSION: BSE was evident to possess favorable anti-melanogenic potency in an in vitro model. As a natural food sourced material, BSE could be an effective depigmentation agent with potential application in pharmaceutical and cosmetic industries.

Differentially expressed genes analysis of retinal vascular endothelial cells under hyperglycemia and hyperlipidemia induced by α-melanocyte-stimulating hormone / 中华实验眼科杂志

Objective@#To investigate the effect of α-melanocyte-stimulating hormone(α-MSH) on the expression of mRNA and long noncoding RNA (lncRNA) in retinal vascular endothelial cells stimulated by hyperglycemia and hyperlipidemia.@*Methods@#The simian retinal vascular endothelial cells (RF/6A)were cultured and divided into normal control group, model control group, 0.1 μmol/L α-MSH group, 0.5 μmol/L α-MSH group and 1.0 μmol/L α-MSH group.The cells were stained with CM-H2DCFDA to detect cell antioxidant capacity.The optimal concentration of α-MSH was screened.The cells from normal control group, model control group and α-MSH treatment group were collected at 24 hours after treatment, the total RNA was extracted, the cDNA library was constructed, and the high throughput RNA sequencing (RNA-seq) was carried out with bioinformatics analysis to analyze the expression profiling of mRNA and lncRNA.@*Results@#The fluorescence intensity of cells in 0.5 μmol/L α-MSH group was significantly lower than that in model control group (P<0.05). α-MSH of 0.5 μmol/L was chosen as the optimal concentration for subsequent experiments.Compared with the model control group, 243 mRNAs were significantly down-regulated, while 81 mRNAs were up-regulated in the α-MSH treatment group; 53 lncRNAs were markedly up-regulated and 6 lncRNAs were down-regulated in the α-MSH treatment group.Bioinformatics analysis showed that the major enrichment pathways of the down-regulated genes were transforming growth factor-β(TGF-β) signaling pathway, focal adhesion signaling pathway and extracellular matrix (ECM) receptor interactions pathways, and the main biological process involved was the regulation of small GTPase-mediated signal transduction.The co-expression gene enrichment pathways of differentially expressed lncRNA included ECM receptor interaction and hypoxia inducible factor-1(HIF-1) pathway, et al.These pathways were mainly involved in the biological processes, such as axon guidance and positive regulation of transcription from RNA polymerase Ⅱ promoter.@*Conclusions@#Under hyperglycemia and hyperlipidemia, the influence of α-MSH on the transcriptome of the retinal vascular endothelial cells manifests the downregulation of mRNA and upregulation of lncRNA.α-MSH may upregulate the lncRNA expression, which downregulates the downstream mRNA expression.

Differentially expressed genes analysis of retinal vascular endothelial cells under hyperglycemia and hyperlipidemia induced by α-melanocyte-stimulating hormone / 中华实验眼科杂志

Objective To investigate the effect of α-melanocyte-stimulating hormone (α-MSH ) on the expression of mRNA and long noncoding RNA ( lncRNA ) in retinal vascular endothelial cells stimulated by hyperglycemia and hyperlipidemia. Methods The simian retinal vascular endothelial cells (RF/6A)were cultured and divided into normal control group,model control group,0. 1μmol/Lα-MSH group,0. 5μmol/Lα-MSH group and 1. 0μmol/L α-MSH group. The cells were stained with CM-H2 DCFDA to detect cell antioxidant capacity. The optimal concentration of α-MSH was screened. The cells from normal control group,model control group andα-MSH treatment group were collected at 24 hours after treatment,the total RNA was extracted,the cDNA library was constructed,and the high throughput RNA sequencing ( RNA-seq ) was carried out with bioinformatics analysis to analyze the expression profiling of mRNA and lncRNA. Results The fluorescence intensity of cells in 0. 5 μmol/L α-MSH group was significantly lower than that in model control group ( P<0. 05 ) .α-MSH of 0. 5μmol/L was chosen as the optimal concentration for subsequent experiments. Compared with the model control group, 243 mRNAs were significantly down-regulated,while 81 mRNAs were up-regulated in the α-MSH treatment group;53 lncRNAs were markedly up-regulated and 6 lncRNAs were down-regulated in the α-MSH treatment group. Bioinformatics analysis showed that the major enrichment pathways of the down-regulated genes were transforming growth factor-β( TGF-β) signaling pathway,focal adhesion signaling pathway and extracellular matrix ( ECM) receptor interactions pathways, and the main biological process involved was the regulation of small GTPase-mediated signal transduction. The co-expression gene enrichment pathways of differentially expressed lncRNA included ECM receptor interaction and hypoxia inducible factor-1(HIF-1) pathway,et al. These pathways were mainly involved in the biological processes, such as axon guidance and positive regulation of transcription from RNA polymerase Ⅱ promoter. Conclusions Under hyperglycemia and hyperlipidemia, the influence of α-MSH on the transcriptome of the retinal vascular endothelial cells manifests the downregulation of mRNA and upregulation of lncRNA. α-MSH may upregulate the lncRNA expression,which downregulates the downstream mRNA expression.

Comparative Study Between Follicular Unit Extraction (FUE) And Non Cultured Melanocyte Transfer (NCMT) In Stable Vitiligo Patients

Background: Vitiligo is an acquired, hypomelanotic disorder characterized by circumscribed depigmented macules in the skin resulting from the loss of functional melanocytes from the cutaneous epidermis. It also causes significant psychological and social distress. Aims and Objectives: To compare the efficacy of follicular unit extraction and non cultured melanocyte transfer in patients of stable vitiligo with respect to repigmentation, vitiligo noticeability and global treatment success. Material and Methods: A total of 15 patients with stable vitiligo (as per IADVL guidelines) were enrolled in the study. In the same patient follicular unit extraction (FUE) was done in the vitiliginous lesions and the hair was transplanted approximately 3-5 mm apart on the left side of the body, while another vitiliginous lesion in the same patient was selected for non cultured melanocyte transfer (NCMT) which was done on the dermabraded area on the right side of the body. These patients were followed-up for a period of 6 months, initially at every 2 weeks or till first signs of repigmentation, then monthly follow-ups for two times and then followed-up in every 2 months. Visual analogue scale was used for assessment of repigmentation, VNS scale was used to evaluate vitiligo noticeability and global treatment success was calculated. Results: There were 2 (13.3%) females and 13 (86.7%) males in our study, showing a male preponderance. Majority of the patients were in the age group 21-40 years (66.7%). There was statistically significant increase in the mean pigmentation at each follow-up in comparison to the earlier follow-up in both the groups (p<0.05). The mean pigmentation and mean pigmentation difference, between the two groups was also comparable (p>0.05). Excellent pigmentation was seen in 60% patients of FUE and 73.3% patients of the NCMT group. Vitiligo was ‘not noticeable’in 33.3% patients of FUE and 40.0% patients of NCMT group. Global treatment success was 80% in both the groups. Bony prominence, greying and loss of follicles in FUE group; and graft displacement and herpes zoster in NCMTgroup were the factors responsible for low pigmentation. Conclusion: From the above study, we conclude that repigmentation was seen in both the groups, with equal efficacy seen between the two methodologies. Thus, any method can be applied for repigmentation with due considerations to complications of each method used.

Association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism with vitiligo susceptibility in Gujarat population

Background: Vitiligo is a multifactorial, polygenic, autoimmune skin disorder caused by selective destruction of melanocytes. Interleukin 1 receptor antagonist intron 2 polymorphism was found to be associated with various autoimmune disorders. Aims: We aimed to investigate the association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism (rs2234663) with vitiligo to assess interleukin 1 receptor antagonist transcript levels and to perform possible genotype–phenotype correlation. Methods: Three hundred and seven vitiligo patients and 316 controls were enrolled in the study, genotyping of interleukin 1 receptor antagonist rs2234663 was performed by polymerase chain reaction, and relative gene expression of interleukin 1 receptor antagonist was carried out in peripheral blood mononuclear cells from patients (n = 36) and controls (n = 36) by real-time-PCR. Results: A significant difference was observed in the frequency of interleukin 1 receptor antagonist *A (1/2) genotype among patients with active and stable vitiligo (P = 0.0172). Interleukin 1 receptor antagonist*A (2/2) genotype and allele frequencies were significantly different between SV patients and controls (P = 0.0246 and P = 0.0046, respectively). Significant difference was also observed for interleukin 1 receptor antagonist*A2 (allele) in active and stable vitiligo patients (P = 0.0060). However, other comparisons did not show any significant difference in genotype and allele frequencies. Moreover, interleukin 1 receptor antagonist*A (3/2) genotype was observed only in patients whereas interleukin 1 receptor antagonist*A (5/2) was observed only in controls. Gene expression analysis showed no significant difference in interleukin 1 receptor antagonist transcript levels in patients compared to controls (P = 0.5962). Interestingly, genotype–phenotype correlation analysis revealed that individuals with IL1RN*A (2/2) exhibited higher interleukin 1 receptor antagonist expression compared to other major genotypes interleukin 1 receptor antagonist*A (1/2) (P = 0.01) and interleukin 1 receptor antagonist*A (1/1) (P = 0.03). Limitations: More case-control studies on interleukin 1 receptor antagonist rs2234663 polymorphism and gene expression from different ethnic populations are required to explore the impact of interleukin 1 receptor antagonist in vitiligo susceptibility. Conclusion: Interleukin 1 receptor antagonist*A2 might be a risk factor for progressive vitiligo.

Plasma & urinary catecholamines & urinary vanillylmandelic acid levels in patients with generalized vitiligo

Background & objectives: Vitiligo is an acquired skin disease characterized by depigmented areas of the skin. Increased release of catecholamines from autonomic nerve endings in microenvironment of melanocytes in affected skin might be involved in the aetiopathogenesis of vitiligo. Levels of catecholamines are considered as being related to onset or worsening of the disease. Therefore, in this study, the role of catecholamines was evaluated in mapping disease stability and outcome of vitiligo patients undergoing melanocyte transfer. Methods: In this study, circulatory and urinary levels of catecholamine (CA) and vanillylmandelic acid (VMA) were determined in 45 individuals (30 vitiligo patients and 15 healthy controls) using ELISA. Results: A significant increase for plasma and urinary catecholamines along with VMA was observed as compared to healthy controls. When the pre- and post-intervention levels were analyzed in responders and non-responders, respectively, only dopamine showed significant decline in urine, rest of the molecules in plasma as well as urine showed non-significant decline except VMA which showed insignificant increase. Interpretation & conclusions: Levels of plasma/urinary epinephrine, and plasma dopamine, could not be established as biomarkers for disease stability or successful outcome of autologous melanocyte transfer in generalized vitiligo patients. However, dopamine (urine) might be of help in determining the stability in patients with generalized vitiligo undergoing melanocyte transfer. Further studies need to be done on a large sample of patients to confirm our findings.

Three Streams for the Mechanism of Hair Graying

Hair graying is an obvious sign of human aging. Although graying has been investigated extensively, the mechanism remains unclear. Here, we reviewed previous studies on the mechanism of graying and seek to offer some new insights. The traditional view is that hair graying is caused by exhaustion of the pigmentary potential of the melanocytes of hair bulbs. Melanocyte dysfunction may be attributable to the effects of toxic reactive oxygen species on melanocyte nuclei and mitochondria. A recent study suggests that bulge melanocyte stem cells (MSCs) are the key cells in play. Graying may be caused by defective MSC self-maintenance, not by any deficiency in bulbar melanocytes. Our previous study suggested that graying may be principally attributable to active hair growth. Active hair growth may produce oxidative or genotoxic stress in hair bulge. These internal stress may cause eventually depletion of MSC in the hair follicles. Taken together, hair graying may be caused by MSC depletion by genotoxic stress in the hair bulge. Hair graying may also be sometimes caused by dysfunction of the melanocytes by oxidative stress in the hair bulb. In addition, hair graying may be attributable to MSC depletion by active hair growth.

Differential expression of miR-146a-5p in giant congenital melanocytic nevi, medium-sized congenital melanocytic nevi and normal skin / 中华整形外科杂志

Objective@#To investigate the differences in miRNA expression levels between giant congenital melanocytic nevi, medium-sized congenital melanocytic nevi and normal skin.@*Methods@#The experiment was divided into three groups: giant congenital melanocytic nevi group, medium-sized congenital melanocytic nevi group and normal skin group, with ten samples in each group. Firstly, 3 samples of each group were detected by Agilent miRN Amicroarray to screen the different miRNAs between different groups. 5 differential miRNAs related to MAPK, Wnt, NF-kB signaling pathways were selected for further verification: miR-146a-5p, miR-140-5p, miR-106b-5p, miR-17-5p, and miR-483-5p. miRNA expression levels were measured using real-time quantitative PCR (Taqman) in ten clinical samples from each group. .Experimental data were analyzed using SPSS 22.0.@*Results@#A total of 23 differential miRNAs between congenital melanocytic nevi and normal skin were found by miRNA microarray detection. The results of real-time PCR showed that miR-146a-5p expression was significantly different between the three groups: giant congenital melanocytic nevi VS medium-sized congenital melanocytic nevi (P=0.003); giant congenital melanocytic nevi VS normal skin (P=0.000); medium-sized congenital melanocytic nevi VS normal skin (P=0.013). There was no statistically significant difference in the expression of the other four miRNAs between the 3 groups.@*Conclusions@#The expression of miR-146a-5p is increased in congenital melanocytic nevi, especially in giant congenital melanocytic nevi, which may be related to the proliferation and senescence of melanocytes in different tissues.